bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Oxidative Stress Biomarkers, Pro-Inflammatory Cytokines, and Histological Changes in Experimental Hypertension, Dyslipidemia, and Type 1 Diabetes Mellitus
Authors: Boarescu Paul-Mihai , Boarescu Ioana , Pop Raluca Maria , Roşian Ştefan Horia , Bocșan Ioana Corina , Rus Vasile , Mada Răzvan Olimpiu , Popa Iulia Diana , Neagu Nicholas , Bulboacă Adriana Elena , Buzoianu Anca Dana , Bolboacă Sorana D.
Published: January 2022

The present study aims to compare the oxidative stress biomarkers, pro-inflammatory cytokines, and histological changes induced by three cardiovascular risk factors, namely, hypertension, dyslipidemia, and type 1 diabetes mellitus. Hypertension was induced with 40 mg/kg body weight (b.w.) of N omega-nitro-L-arginine-methyl (L-NAME) administered orally. Dyslipidemia was induced by the administration of a diet with a high cholesterol (2%) content. Diabetes mellitus was induced by intraperitoneal administration of a single dose of streptozocin (65 mg/kg). Malondialdehyde (MDA) and total oxidative status (TOS) are increased by all three cardiovascular risk factors (up to 207%). The indirect assessment of NO synthesis (NOx) is observed to be reduced after L-NAME administration (43%), and dyslipidemia induction (16%), while type 1 diabetes mellitus is associated with the highest levels of NOx (increased 112%). Hypertension, dyslipidemia, and type 1 diabetes reduced the total antioxidative capacity (TAC) and total thiol (SH) levels (up to 57%). The values of evaluated pro-inflammatory cytokines, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), assessed from the ascending aorta were elevated by all three cardiovascular risk factors, with the highest levels induced by type 1 diabetes mellitus (up to 259%). The histopathological examination of the ascending and descending aorta revealed reversible pro-atherogenic changes consisting of the accumulation of lipid droplets in the subendothelial connective tissue on rats with hypertension and dyslipidemia. Irreversible pro-atherogenic changes consisting of a reduction of the specific elasticity of the arteries were observed in rats with type 1 diabetes mellitus. Type 1 diabetes mellitus demonstrates an alteration of the oxidative stress parameters, the elevation of tissue levels of the pro-inflammatory cytokines and causing irreversible pro-atherogenic changes on the aortic wall.
Role of Somatostatin Signalling in Neuroendocrine Tumours
Authors: Rogoza Olesja , Megnis Kaspars , Kudrjavceva Marija , Gerina-Berzina Aija , Rovite Vita
Published: January 2022

Somatostatin (SST) is a small peptide that exerts inhibitory effects on a wide range of neuroendocrine cells. Due to the fact that somatostatin regulates cell growth and hormone secretion, somatostatin receptors (SSTRs) have become valuable targets for the treatment of different types of neuroendocrine tumours (NETs). NETs are a heterogeneous group of tumours that can develop in various parts of the body, including the digestive system, lungs, and pituitary. NETs are usually slow growing, but they are often diagnosed in advanced stages and can display aggressive behaviour. The mortality rate of NETs is not outstandingly increased compared to other malignant tumours, even in the metastatic setting. One of the intrinsic properties of NETs is the expression of SSTRs that serve as drug targets for SST analogues (SSAs), which can delay tumour progression and downregulate hormone overproduction. Additionally, in many NETs, it has been demonstrated that the SSTR expression level provides a prognostic value in predicting a therapeutic response. Furthermore, higher a SSTR expression correlates with a better survival rate in NET patients. In recent studies, other epigenetic regulators affecting SST signalling or SSA–mTOR inhibitor combination therapy in NETs have been considered as novel strategies for tumour control. In conclusion, SST signalling is a relevant regulator of NET functionality. Alongside classical SSA treatment regimens, future advanced therapies and treatment modalities are expected to improve the disease outcomes and overall health of NET patients.
Allosterism in the PDZ Family
Authors: Stevens Amy O. , He Yi
Published: January 2022

Dynamic allosterism allows the propagation of signal throughout a protein. The PDZ (PSD-95/Dlg1/ZO-1) family has been named as a classic example of dynamic allostery in small modular domains. While the PDZ family consists of more than 200 domains, previous efforts have primarily focused on a few well-studied PDZ domains, including PTP-BL PDZ2, PSD-95 PDZ3, and Par6 PDZ. Taken together, experimental and computational studies have identified regions of these domains that are dynamically coupled to ligand binding. These regions include the αA helix, the αB lower-loop, and the αC helix. In this review, we summarize the specific residues on the αA helix, the αB lower-loop, and the αC helix of PTP-BL PDZ2, PSD-95 PDZ3, and Par6 PDZ that have been identified as participants in dynamic allostery by either experimental or computational approaches. This review can serve as an index for researchers to look back on the previously identified allostery in the PDZ family. Interestingly, our summary of previous work reveals clear consistencies between the domains. While the PDZ family has a low sequence identity, we show that some of the most consistently identified allosteric residues within PTP-BL PDZ2 and PSD-95 PDZ3 domains are evolutionarily conserved. These residues include A46/A347, V61/V362, and L66/L367 on PTP-BL PDZ2 and PSD-95 PDZ3, respectively. Finally, we expose a need for future work to explore dynamic allostery within (1) PDZ domains with multiple binding partners and (2) multidomain constructs containing a PDZ domain.
Synthesis Mechanisms, Structural Models, and Photothermal Therapy Applications of Top-Down Carbon Dots from Carbon Powder, Graphite, Graphene, and Carbon Nanotubes
Authors: Shi Wenquan , Han Qiurui , Wu Jiajia , Ji Chunyu , Zhou Yiqun , Li Shanghao , Gao Lipeng , Leblanc Roger M. , Peng Zhili
Published: January 2022

In this study, top-down syntheses of carbon dots (CDs) from four different carbon precursors, namely, carbon nano powders, graphite, graphene, and carbon nanotubes, were carried out. Systematic study demonstrated that the optical properties and surface functionalities of the CDs were quite similar and mainly influenced by the synthesis method, while the sizes, morphologies, chemical compositions, and core structures of the CDs were heavily influenced by the carbon precursors. On the basis of these studies, the formation processes and structural models of these four top-down CDs were proposed. The cell cytotoxicity and photothermal conversion efficiency of these CDs were also carefully evaluated, demonstrating their potential applications in photothermal therapy.
Mucoadhesive Electrospun Nanofiber-Based Hybrid System with Controlled and Unidirectional Release of Desmopressin
Authors: Stie Mai Bay , Gätke Johan Ring , Chronakis Ioannis S. , Jacobsen Jette , Nielsen Hanne Mørck
Published: January 2022

The sublingual mucosa is an attractive route for drug delivery, although challenged by a continuous flow of saliva that leads to a loss of drug by swallowing. It is of great benefit that drugs absorbed across the sublingual mucosa avoid exposure to the harsh environment of the gastro-intestinal lumen; this is especially beneficial for drugs of low physicochemical stability such as therapeutic peptides. In this study, a two-layered hybrid drug delivery system was developed for the sublingual delivery of the therapeutic peptide desmopressin. It consisted of peptide-loaded mucoadhesive electrospun chitosan/polyethylene oxide-based nanofibers (mean diameter of 183 ± 20 nm) and a saliva-repelling backing film to promote unidirectional release towards the mucosa. Desmopressin was released from the nanofiber-based hybrid system (approximately 80% of the loaded peptide was released within 45 min) in a unidirectional manner in vitro. Importantly, the nanofiber–film hybrid system protected the peptide from wash-out, as demonstrated in an ex vivo flow retention model with porcine sublingual mucosal tissue. Approximately 90% of the loaded desmopressin was retained at the surface of the ex vivo porcine sublingual mucosa after 15 min of exposure to flow rates representing salivary flow.
Tumor-Derived Exosomes in Tumor-Induced Immune Suppression
Authors: Hao Qiongyu , Wu Yong , Wu Yanyuan , Wang Piwen , Vadgama Jaydutt V.
Published: January 2022

Exosomes are a class of small membrane-bound extracellular vesicles released by almost all cell types and present in all body fluids. Based on the studies of exosome content and their interactions with recipient cells, exosomes are now thought to mediate “targeted” information transfer. Tumor-derived exosomes (TEX) carry a cargo of molecules different from that of normal cell-derived exosomes. TEX functions to mediate distinct biological effects such as receptor discharge and intercellular cross-talk. The immune system defenses, which may initially restrict tumor progression, are progressively blunted by the broad array of TEX molecules that activate suppressive pathways in different immune cells. Herein, we provide a review of the latest research progress on TEX in the context of tumor-mediated immune suppression and discuss the potential as well as challenges of TEX as a target of immunotherapy.
Oxidative Stress Modulation by Carnosine in Scaffold Free Human Dermis Spheroids Model: A Proteomic Study
Authors: Aiello Gilda , Rescigno Francesca , Meloni Marisa , Baron Giovanna , Aldini Giancarlo , Carini Marina , D’Amato Alfonsina
Published: January 2022

Carnosine is an endogenous β-alanyl-L-histidine dipeptide endowed with antioxidant and carbonyl scavenger properties, which is able to significantly prevent the visible signs of aging and photoaging. To investigate the mechanism of action of carnosine on human skin proteome, a 3D scaffold-free spheroid model of primary dermal fibroblasts from a 50-year-old donor was adopted in combination with quantitative proteomics for the first time. The label free proteomics approach based on high-resolution mass spectrometry, integrated with network analyses, provided a highly sensitive and selective method to describe the human dermis spheroid model during long-term culture and upon carnosine treatment. Overall, 2171 quantified proteins allowed the in-depth characterization of the 3D dermis phenotype during growth and differentiation, at 14 versus 7 days of culture. A total of 485 proteins were differentially regulated by carnosine at 7 days, an intermediate time of culture. Of the several modulated pathways, most are involved in mitochondrial functionality, such as oxidative phosphorylation, TCA cycle, extracellular matrix reorganization and apoptosis. In long-term culture, functional modules related to oxidative stress were upregulated, inducing the aging process of dermis spheroids, while carnosine treatment prevented this by the downregulation of the same functional modules. The application of quantitative proteomics, coupled to advanced and relevant in vitro scaffold free spheroids, represents a new concrete application for personalized therapies and a novel care approach.
ARPC1B Is Associated with Lethal Prostate Cancer and Its Inhibition Decreases Cell Invasion and Migration In Vitro
Authors: Gamallat Yaser , Zaaluk Hend , Kish Ealia Khosh , Abdelsalam Ramy , Liosis Konstantinos , Ghosh Sunita , Bismar Tarek A.
Published: January 2022

ARPC1B (Actin Related Protein 2/3 Complex Subunit 1B) has been found to be involved in platelet abnormalities of immune-mediated inflammatory disease and eosinophilia. However, its role in prostate cancer (PCa) has not been established. We characterized the role of ARPC1B in PCa invasion and metastasis and investigated its prognosis using in vitro cellular models and PCa clinical data. Higher immunohistochemistry (IHC) expressions of ARPC1B were observed in localized and castrate resistant PCa (CRPC) vs. benign prostate tissue (p < 0.01). Additionally, 47% of patients with grade group 5 (GG) showed high ARPC1B expression vs. other GG patients. Assessing ARPC1B expression in association with two of the common genetic aberrations in PCa (ERG and PTEN) showed significant association to overall and cause-specific survival for combined assessment of ARPC1B and PTEN, and ARPC1B and ERG. Knockdown of ARPC1B impaired the migration and invasion of PC3 and DU145 PCa cells via downregulation of Aurora A kinase (AURKA) and resulted in the arrest of the cells in the G2/M checkpoint of the cell cycle. Additionally, higher ARPC1B expression was observed in stable PC3-ERG cells compared to normal PC3, supporting the association between ERG and ARPC1B. Our findings implicate the role of ARPC1B in PCa invasion and metastasis in association with ERG and further support its prognostic value as a biomarker in association with ERG and PTEN in identifying aggressive phenotypes of PCa cancer.
Regulation of the Bud Dormancy Development and Release in Micropropagated Rhubarb ‘Malinowy’
Authors: Wojtania Agnieszka , Markiewicz Monika , Waligórski Piotr
Published: January 2022

Culinary rhubarb is a vegetable crop, valued for its stalks, very rich in different natural bioactive ingredients. In commercial rhubarb stalk production, the bud dormancy development and release are crucial processes that determine the yields and quality of stalks. To date, reports on rhubarb bud dormancy regulation, however, are lacking. It is known that dormancy status depends on cultivars. The study aimed to determine the dormancy regulation in a valuable selection of rhubarb ‘Malinowy’. Changes in carbohydrate, total phenolic, endogenous hormone levels, and gene expression levels during dormancy development and release were studied in micropropagated rhubarb plantlets. Dormancy developed at high temperature (25.5 °C), and long day. Leaf senescence and dying were consistent with a significant increase in starch, total phenolics, ABA, IAA and SA levels. Five weeks of cooling at 4 °C were sufficient to break dormancy, but rhizomes stored for a longer duration showed faster and more uniformity leaf growing, and higher stalk length. No growth response was observed for non-cooled rhizomes. The low temperature activated carbohydrate and hormone metabolism and signalling in the buds. The increased expression of AMY3, BMY3, SUS3, BGLU17, GAMYB genes were consistent with a decrease in starch and increase in soluble sugars levels during dormancy release. Moreover, some genes (ZEP, ABF2, GASA4, GA2OX8) related to ABA and GA metabolism and signal transduction were activated. The relationship between auxin (IAA, IBA, 5-Cl-IAA), and phenolic, including SA levels and dormancy status was also observed.
Nanoplastics Increase Fish Susceptibility to Nodavirus Infection and Reduce Antiviral Immune Responses
Authors: González-Fernández Carmen , Cuesta Alberto
Published: January 2022

Nanoplastics (NPs) might cause different negative effects on aquatic organisms at different biological levels, ranging from single cells to whole organisms, including cytotoxicity, reproduction, behavior or oxidative stress. However, the impact of NPs on disease resistance is almost unknown. The objective of this study was to assess whether exposure to 50 nm functionalized polystyrene NPs impacts fish susceptibility to viral diseases both in vitro and in vivo. In particular, we focused on the nervous necrosis virus (NNV), which affects many fish species, producing viral encephalopathy and retinopathy (VER), and causes great economic losses in marine aquaculture. In vitro and in vivo approaches were used. A brain cell line (SaB-1) was exposed to 1 μg mL−1 of functionalized polystyrene NPs (PS-NH2, PS-COOH) and then infected with NNV. Viral titers were increased in NP-exposed cells whilst the transcription of inflammatory and antiviral markers was lowered when compared to those cells only infected with NNV. In addition, European sea bass (Dicentrarchus labrax) juveniles were intraperitoneally injected with the same NPs and then challenged with NNV. Our results indicated that NPs increased the viral replication and clinical signs under which the fish died although the cumulate mortality was unaltered. Again, exposure to NPs produced a lowered inflammatory and antiviral response. Our results highlight that the presence of NPs might impact the infection process of NNV and fish resistance to the disease, posing an additional risk to marine organisms.
Protein Kinase B2 (PKB2/AKT2) Is Essential for Host Protection in CVB3-Induced Acute Viral Myocarditis
Authors: Kim So-Hee , Shin Ha-Hyeon , Kim Jin-Ho , Park Jung-Ho , Jeon Eun-Seok , Lim Byung-Kwan
Published: January 2022

Protein kinase B2 (AKT2) is involved in various cardiomyocyte signaling processes, including those important for survival and metabolism. Coxsackievirus B3 (CVB3) is one of the most common pathogens that cause myocarditis in humans. The role of AKT2 in CVB3 infection is not yet well understood. We used a cardiac-specific AKT2 knockout (KO) mouse to determine the role of AKT2 in CVB3-mediated myocarditis. CVB3 was injected intraperitoneally into wild-type (WT) and KO mice. The mice’s survival rate was recorded: survival in KO mice was significantly decreased compared with WT mice (WT vs. KO: 73.3 vs. 27.1%). Myocardial damage and inflammation were significantly increased in the hearts of KO mice compared with those of WT mice. Moreover, from surface ECG, AKT2 KO mice showed a prolonged atria and ventricle conduction time (PR interval, WT vs. KO: 47.27 ± 1.17 vs. 64.79 ± 7.17 ms). AKT2 deletion induced severe myocarditis and cardiac dysfunction due to CVB3 infection. According to real-time PCR, the mRNA level of IL-1, IL-6, and TNF-α decreased significantly in KO mice compared with WT mice on Days 5 after infection. In addition, innate immune response antiviral effectors, Type I interferon (interferon-α and β), and p62, were dramatically suppressed in the heart of KO mice. In particular, the adult cardiac myocytes isolated from the heart showed high induction of TLR4 protein in KO mice in comparison with WT. AKT2 deletion suppressed the activation of Type I interferon and p62 transcription in CVB3 infection. In cardiac myocytes, AKT2 is a key signaling molecule for the heart from damage through the activation of innate immunity during acute myocarditis.
Metallothionein1A Regulates Rhizobial Infection and Nodulation in Phaseolus vulgaris
Authors: Fonseca-García Citlali , López-García Claudia Marina , Pacheco Ronal , Armada Elisabeth , Nava Noreide , Pérez-Aguilar Rocío , Solis-Miranda Jorge , Quinto Carmen
Published: January 2022

Metallothioneins (MTs) constitute a heterogeneous family of ubiquitous metal ion-binding proteins. In plants, MTs participate in the regulation of cell growth and proliferation, protection against heavy metal stress, oxidative stress responses, and responses to pathogen attack. Despite their wide variety of functions, the role of MTs in symbiotic associations, specifically nodule-fabacean symbiosis, is poorly understood. Here, we analyzed the role of the PvMT1A gene in Phaseolus vulgaris-Rhizobium tropici symbiosis using bioinformatics and reverse genetics approaches. Using in silico analysis, we identified six genes encoding MTs in P. vulgaris, which were clustered into three of the four classes described in plants. PvMT1A transcript levels were significantly higher in roots inoculated with R. tropici at 7 and 30 days post inoculation (dpi) than in non-inoculated roots. Functional analysis showed that downregulating PvMT1A by RNA interference (RNAi) reduced the number of infection events at 7 and 10 dpi and the number of nodules at 14 and 21 dpi. In addition, nodule development was negatively affected in PvMT1A:RNAi transgenic roots, and these nodules displayed a reduced nitrogen fixation rate at 21 dpi. These results strongly suggest that PvMT1A plays an important role in the infection process and nodule development in P. vulgaris during rhizobial symbiosis.
Incorporation of a FRET Pair into a Riboswitch RNA to Measure Mg2+ Concentration and RNA Conformational Change in Cell
Authors: Xue Yanyan , Liu Yu
Published: January 2022

Riboswitches are natural biosensors that can regulate gene expression by sensing small molecules. Knowledge of the structural dynamics of riboswitches is crucial to elucidate their regulatory mechanism and develop RNA biosensors. In this work, we incorporated the fluorophore, Cy3, and its quencher, TQ3, into a full-length adenine riboswitch RNA and its isolated aptamer domain to monitor the dynamics of the RNAs in vitro and in cell. The adenine riboswitch was sensitive to Mg2+ concentrations and could be used as a biosensor to measure cellular Mg2+ concentrations. Additionally, the TQ3/Cy3-labeled adenine riboswitch yielded a Mg2+ concentration that was similar to that measured using a commercial assay kit. Furthermore, the fluorescence response to the adenine of the TQ3/Cy3-labeled riboswitch RNA was applied to determine the proportions of multiple RNA conformational changes in cells. The strategy developed in this work can be used to probe the dynamics of other RNAs in cells and may facilitate the developments of RNA biosensors, drugs and engineering.
Analysis of Driver’s Socioeconomic Characteristics Relating to Speeding Behavior and Crash Involvement: A Case Study in Lahore
Authors: Javid Muhammad Ashraf , Ali Nazam , Abdullah Muhammad , Campisi Tiziana , Shah Syed Arif Hussain , Suparp Suniti
Published: January 2022

Speeding is one of the risky behaviors which results in accident involvement causing fatalities and severe injuries. This paper aimed to identify the significant socio-economic characteristics of drivers concerning their speeding behavior and crash involvement. A questionnaire was designed consisting of driver’s demographic features, involvement in an accident, penalty on speed violations, and statements on speeding behavior in terms of exceeding the speed limits by 10 km/h or more on roads with different speed limits of 60, 80, 100, and 120 km/h per standard operating speeds on various road types in Pakistan. This survey was conducted in Lahore city and a total of 551 usable samples were obtained. A latent variable of drivers’ speeding behavior was introduced; factor loadings were estimated, and an observed variable of drivers’ crash experience was defined as the drivers’ crash involvement. Ordered regression analysis using the probit function was conducted on speeding behavior and crash involvement. The ordinal analysis revealed that the drivers’ age, gender, marital status, employment, vehicle engine size, type of vehicle they drive, and driving frequency per day are good predictors of speeding behavior. Similarly, male drivers’ age, vehicle engine size, and type of vehicle they drive were significant predictors of their likelihood to be involved in an accident. The young, single, and male drivers and drivers of cars with an engine capacity above 1.5 L were more likely to speed and be involved in crashes. These findings provide a clear understanding of a specific group of drivers who have a higher probability of speeding and crash involvement. There is a need to focus on specific demographic factors in the formulation of traffic safety policies and managing speedy drivers’ behaviors.
Cryoprotective Response as Part of the Adaptive Strategy of the Red Palm Weevil, Rhynchophorus ferrugineus, against Low Temperatures
Authors: León-Quinto Trinidad , Serna Arturo
Published: January 2022

The red palm weevil (RPW), Rhynchophorus ferrugineus, is one of the worst palm pests worldwide. In this work, we studied the physiological basis underlying its adaptive strategy against low temperatures. Specifically, we analyzed the main low-molecular-weight biochemical substances acting as possible endogenous cryoprotectants, as well as their efficiency in reducing cold injury by preserving K+/Na+ homeostasis. Wild pre-pupae were cold-treated (5.0 ± 0.5 °C) or non-treated (23 ± 1 °C) for 7 days. We then determined the levels of: (a) glucose, trehalose and glycerol, spectrophotometrically, (b) amino acids, by liquid chromatography and (c) potassium and sodium, by inductively coupled plasma mass-spectrometry. Cold-treated larvae increased their potassium level, suggesting some degree of chill injury. However, part of the cold-exposed animals was able to develop an efficient overall cryoprotective response which primarily includes glucose, as well as glycerol and several amino acids (mainly alanine). Our study shows for the first time that RPW is capable of deploying effective physiological mechanisms for a rapid response to cold, which could be relevant to improving predictive models of geographic distribution, especially in a context of climate change. The knowledge of the specific molecules involved would allow future studies to try to prevent its adaptive strategy, either by natural or chemical methods.
Sarcomere Disassembly and Transfection Efficiency in Proliferating Human iPSC-Derived Cardiomyocytes
Authors: Yuan Qianliang , Maas Renee G. C. , Brouwer Ellen C. J. , Pei Jiayi , Blok Christian Snijders , Popovic Marko A. , Paauw Nanne J. , Bovenschen Niels , Hjortnaes Jesper , Harakalova Magdalena , Doevendans Pieter A. , Sluijter Joost P. G. , van der Velden Jolanda , Buikema Jan W.
Published: January 2022

Contractility of the adult heart relates to the architectural degree of sarcomeres in individual cardiomyocytes (CMs) and appears to be inversely correlated with the ability to regenerate. In this study we utilized multiple imaging techniques to follow the sequence of sarcomere disassembly during mitosis resulting in cellular or nuclear division in a source of proliferating human pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). We observed that both mono- and binuclear hiPSC-CMs give rise to mononuclear daughter cells or binuclear progeny. Within this source of highly proliferative hiPSC-CMs, treated with the CHIR99021 small molecule, we found that Wnt and Hippo signaling was more present when compared to metabolic matured non-proliferative hiPSC-CMs and adult human heart tissue. Furthermore, we found that CHIR99021 increased the efficiency of non-viral vector incorporation in high-proliferative hiPSC-CMs, in which fluorescent transgene expression became present after the chromosomal segregation (M phase). This study provides a tool for gene manipulation studies in hiPSC-CMs and engineered cardiac tissue. Moreover, our data illustrate that there is a complex biology behind the cellular and nuclear division of mono- and binuclear CMs, with a shared-phenomenon of sarcomere disassembly during mitosis.
Seronegative Infection with Toxoplasma gondii in Asymptomatic Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Patients and in Blood Donors
Authors: Pawełczyk Agnieszka , Bednarska Małgorzata , Caraballo Cortés Kamila , Glamkowska-Sady Marianna , Kowalska Justyna , Uszyńska-Kałuża Beata , Radkowski Marek , Welc-Falęciak Renata
Published: January 2022

Background: Toxoplasmosis is a common opportunistic infection in AIDS patients. The routine diagnostics is based on serologic testing and IgG avidity index, but it may have limited utility in immunodeficient patients; thus, it is recommendable to detect T. gondii DNA in subjects with advanced HIV disease. The results of the studies published so far focused on patients with clinical symptoms of toxoplasmosis. Our study encompassed a group of HIV-infected subjects on cART therapy, without immunological disturbances and clinical symptoms of T. gondii infection. Methods: The study was retrospective, and samples were collected between 2013 and 2016. We evaluate the prevalence of serological (IgM, IgG, and avidity IgG) and molecular (DNA) T. gondii infection markers in asymptomatic HIV-infected patients and the control group using serologic (ELISA) and quantitative (real-time PCR) molecular testing. Results: Of 152 HIV-infected in routine follow-up tested for T. gondii IgM and IgG, 6 (3.9%) and 50 (32.9%) were positive, respectively. Of 168 serum samples from blood donors, 1 (0.6%) and 49 (29.2%) were IgM+ and IgG+ positive, respectively. IgM seroprevalence in HIV-infected patients was significantly higher than in blood donors. T. gondii DNA (genotype II) was identified in 47 (30.9%) HIV-infected patients, with 13 (8.6%) IgM−IgG− samples. In blood donors, T. gondii DNA was present in 15 (8.9%) IgM−IgG−. Conclusions: In both groups, T. gondii DNA was detectable in seronegative subjects, implying the need to supplement the routine serological testing via the molecular method. It can help the accurate monitoring of the reactivation of infection in asymptomatic HIV-infected persons, and the quick introduction of specific therapy, in blood donors, would be of high importance for safe blood donations.
Real-World Use and Adverse Events of SARS-CoV-2 Vaccination in Greek Patients with Inflammatory Bowel Disease
Authors: Orfanoudaki Eleni , Zacharopoulou Eirini , Kitsou Vassiliki , Karmiris Konstantinos , Theodoropoulou Angeliki , Mantzaris Gerassimos J. , Tzouvala Maria , Michopoulos Spyridon , Zampeli Evanthia , Michalopoulos Georgios , Karatzas Pantelis , Viazis Nikos , Liatsos Christos , Bamias Giorgos , Koutroubakis Ioannis E. ,   on behalf of the Hellenic Group for the Study of IBD
Published: January 2022

Since inflammatory bowel disease (IBD) patients were excluded from vaccine authorization studies, limited knowledge exists regarding perceptions and unfavorable effects of COVID-19 vaccination in this group. We aimed to investigate the real-world use and adverse events (AEs) of COVID-19 vaccines in Greek IBD patients. Fully vaccinated IBD patients followed in Greek centers were invited to participate. All patients filled out an anonymous online survey concerning the vaccination program, which included information regarding demographics, clinical characteristics, treatment, vaccination perceptions and potential AEs. Overall, 1007 IBD patients were included. Vaccine hesitancy was reported by 49%. Total AEs to vaccination were reported by 81% after dose 1 (D1) and 76% after dose 2 (D2), including isolated injection site reactions (36% and 24% respectively). Systemic AEs were more common after D2 (51%, D2 vs. 44%, D1, p < 0.0001). Very few patients reported new onset abdominal symptoms (abdominal pain 4% (D1), 6% (D2) and diarrhea 5% (D1), 7% (D2)). There were no serious AEs leading to emergency room visit or hospitalization. In multivariate analysis, AEs occurrence was positively associated with young age and female gender (p < 0.0005 for both doses), whereas inactive disease was negatively associated with AE in D1 (p = 0.044). SARS-CoV-2 vaccination in Greek IBD patients demonstrated a favorable and reassuring safety profile.
Intestinal Inflammation and Alterations in the Gut Microbiota in Cystic Fibrosis: A Review of the Current Evidence, Pathophysiology and Future Directions
Authors: Tam Rachel Y. , van Dorst Josie M. , McKay Isabelle , Coffey Michael , Ooi Chee Y.
Published: January 2022

Cystic fibrosis (CF) is a life-limiting autosomal recessive multisystem disease. While its burden of morbidity and mortality is classically associated with pulmonary disease, CF also profoundly affects the gastrointestinal (GI) tract. Chronic low-grade inflammation and alterations to the gut microbiota are hallmarks of the CF intestine. The etiology of these manifestations is likely multifactorial, resulting from cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction, a high-fat CF diet, and the use of antibiotics. There may also be a bidirectional pathophysiological link between intestinal inflammation and changes to the gut microbiome. Additionally, a growing body of evidence suggests that these GI manifestations may have significant clinical associations with growth and nutrition, quality of life, and respiratory function in CF. As such, the potential utility of GI therapies and long-term GI outcomes are areas of interest in CF. Further research involving microbial modulation and multi-omics techniques may reveal novel insights. This article provides an overview of the current evidence, pathophysiology, and future research and therapeutic considerations pertaining to intestinal inflammation and alterations in the gut microbiota in CF.
Diet/Nutrition: Ready to Transition from a Cancer Recurrence/Prevention Strategy to a Chronic Pain Management Modality for Cancer Survivors?
Authors: Tümkaya Yılmaz Sevilay , Malfliet Anneleen , Elma Ömer , Deliens Tom , Nijs Jo , Clarys Peter , De Groef An , Coppieters Iris
Published: January 2022

Evidence for the relationship between chronic pain and nutrition is mounting, and chronic pain following cancer is gaining recognition as a significant area for improving health care in the cancer survivorship population. This review explains why nutrition should be considered to be an important component in chronic pain management in cancer survivors by exploring relevant evidence from the literature and how to translate this knowledge into clinical practice. This review was built on relevant evidence from both human and pre-clinical studies identified in PubMed, Web of Science and Embase databases. Given the relationship between chronic pain, inflammation, and metabolism found in the literature, it is advised to look for a strategic dietary intervention in cancer survivors. Dietary interventions may result in weight loss, a healthy body weight, good diet quality, systemic inflammation, and immune system regulations, and a healthy gut microbiota environment, all of which may alter the pain-related pathways and mechanisms. In addition to being a cancer recurrence or prevention strategy, nutrition may become a chronic pain management modality for cancer survivors. Although additional research is needed before implementing nutrition as an evidence-based management modality for chronic pain in cancer survivors, it is already critical to counsel and inform this patient population about the importance of a healthy diet based on the data available so far.
The Hamburg Spondylodiscitis Assessment Score (HSAS) for Immediate Evaluation of Mortality Risk on Hospital Admission
Authors: Heuer Annika , Strahl André , Viezens Lennart , Koepke Leon-Gordian , Stangenberg Martin , Dreimann Marc
Published: January 2022

(1) Background: Patients with spondylodiscitis often present with unspecific and heterogeneous symptoms that delay diagnosis and inevitable therapeutic steps leading to increased mortality rates of up to 27%. A rapid initial triage is essential to identify patients at risk for a complicative disease course. We therefore aimed to develop a risk assessment score using fast available parameters to predict in-hospital mortality of patients admitted with spondylodiscitis. (2) Methods: A retrospective data analysis of 307 patients with spondylodiscitis recruited from 2013 to 2020 was carried out. Patients were grouped according to all-cause mortality. Via logistic regression, individual patient and clinical characteristics predictive of mortality were identified. A weighted sum score to estimate a patient’s risk of mortality was developed and validated in a randomly selected subgroup of spondylodiscitis patients. (3) Results: 14% of patients with spondylodiscitis died during their in-hospital stay at a tertiary center for spinal surgery. Univariate and logistic regression analyses of parameters recorded at hospital admission showed that age older than 72.5 years, rheumatoid arthritis, creatinine > 1.29 mg/dL and CRP > 140.5 mg/L increased the risk of mortality 3.9-fold, 9.4-fold, 4.3-fold and 4.1-fold, respectively. S. aureus detection increased the risk of mortality by 2.3-fold. (4) Conclusions: The novel Hamburg Spondylodiscitis Assessment Score (HSAS) shows a good fit identifying patients at low-, moderate-, high- and very high risk for in hospital mortality on admission (AUC: 0.795; p < 0.001). The implementation of the HSAS into clinical practice could ease identification of high-risk patients using readily available parameters alone, improving the patient’s safety and outcome.
Influence of Cytokines on Inflammatory Eye Diseases: A Citation Network Study
Authors: Gálvez Beatriz G. , Martinez-Perez Clara , Villa-Collar Cesar , Alvarez-Peregrina Cristina , Sánchez-Tena Miguel Ángel
Published: January 2022

Background: The main objective of this study was to use citation networks to analyze the relationship between different publications on the impact of cytokines at an ocular level and their authors. Furthermore, the different research areas will be identified, and the most cited publications determined. Methods: A search was performed in the Web of Science (WoS) database using the following keywords: “cytokine”, “inflammatory”, and “eye disease” for the period from 1990 to October 2021. The Citation Network Explorer and the CiteSpace software were then used to analyze the different publications. Results: 3127 publications with 8955 citations generated on the web were found. The largest number of publications on this topic emerged in 2018 and the authors with the largest number of publications addressing this area of research were Peizeng Yang (1.4%), Aize Kijlstra (1.3%), and Stephen C. Pflugfelder (1.2%). Conclusions: the citation network has provided a comprehensive and objective analysis of the main studies on the influence of cytokines in ocular inflammatory diseases.
The Impact of Pancreatic Head Resection on Blood Glucose Homeostasis in Patients with Chronic Pancreatitis
Authors: Hempel Sebastian , Oehme Florian , Ehehalt Florian , Solimena Michele , Kolbinger Fiona , Bogner Andreas , Welsch Thilo , Weitz Jürgen , Distler Marius
Published: January 2022

Background: Chronic pancreatitis (CP) often leads to recurrent pain as well as exocrine and/or endocrine pancreatic insufficiency. This study aimed to investigate the effect of pancreatic head resections on glucose metabolism in patients with CP. Methods: Patients who underwent pylorus-preserving pancreaticoduodenectomy (PPPD), Whipple procedure (cPD), or duodenum-preserving pancreatic head resection (DPPHR) for CP between January 2011 and December 2020 were retrospectively analyzed with regard to markers of pancreatic endocrine function including steady-state beta cell function (%B), insulin resistance (IR), and insulin sensitivity (%S) according to the updated Homeostasis Model Assessment (HOMA2). Results: Out of 141 pancreatic resections for CP, 43 cases including 31 PPPD, 2 cPD and 10 DPPHR, met the inclusion criteria. Preoperatively, six patients (14%) were normoglycemic (NG), 10 patients (23.2%) had impaired glucose tolerance (IGT) and 27 patients (62.8%) had diabetes mellitus (DM). In each subgroup, no significant changes were observed for HOMA2-%B (NG: p = 0.57; IGT: p = 0.38; DM: p = 0.1), HOMA2-IR (NG: p = 0.41; IGT: p = 0.61; DM: p = 0.18) or HOMA2-%S (NG: p = 0.44; IGT: p = 0.52; DM: p = 0.51) 3 and 12 months after surgery, respectively. Conclusion: Pancreatic head resections for CP, including DPPHR and pancreatoduodenectomies, do not significantly affect glucose metabolism within a follow-up period of 12 months.
Flexibility to Change the Solution: An Indicator of Problem Solving That Predicted 9th Grade Students’ Academic Achievement during Distance Learning, in Parallel to Reasoning Abilities and Parental Education
Authors: Hacatrjana Liena
Published: January 2022

The relation between academic achievement and various measurements of cognitive abilities, problem-solving skills and self-managed learning has been established in the research before the COVID-19 pandemic and distance learning. The aim of the current research was to analyze the extent to which these aspects predicted the educational achievement of 9th grade students (mean age 15.4 years) during distance learning, when students had to do relatively more tasks independently, organize their daily learning and deal with problems on their own. Relations between self-assessed problem-solving skills, self-management skills, tests of reasoning abilities and the results of diagnostic tests in Mathematics and Latvian were analyzed for n = 256 and n = 244 students, respectively. The results show that: (1) diagnostic test results in Mathematics are best predicted by the parental education level, fluid nonverbal reasoning and verbal reasoning; (2) the best predictors for the results in the diagnostic test in Latvian are parental education, flexibility to change the solution, fluid nonverbal reasoning and verbal reasoning; (3) self-management cannot significantly predict the results of either of the two tests, although it correlates to the results of the tests in both Mathematics and Latvian; (4) only one of the aspects of problem-solving, flexibility to change the solution, can significantly predict results in diagnostic tests. The results confirm the significance of cognitive abilities as an important predictor of academic achievement, as well as the role of parents’ education level. The results also suggest that the flexibility to change the solution, an aspect of problem-solving, might play a role in students’ success in academic tests.
A Review of Computational Simulation Methods for a Ship Advancing in Broken Ice
Authors: Li Fang , Huang Luofeng
Published: January 2022

Apart from breaking level ice, polar ships can interact with broken ice in various scenarios. In recent years, computational simulation models have increasingly been used for the evaluation of ship operability under broken ice conditions, presenting some challenging issues. This paper reviews existing simulation methods used to estimate ship performance and ice loads for ships advancing continuously in broken ice fields. Models for different types of broken ice, including ice floes, ice ridges, brash ice, and sliding ice pieces, are reviewed separately. A ship’s response in broken ice is divided into two categories: resistance, which relates to the overall ship performance, and local loads, which relates to structural safety. This review shows that most existing models are proposed for unbreakable ice particles, which are only applicable to broken ice of small size; most models treat fluid flow with extensive simplification, which does not reflect the influence of a ship’s wake or bow waves, and most models are aimed at resistance estimation, adopting elastic or viscoelastic contact models which do not include ice crushing. As for future work, it is suggested that more effort should be assigned to simulating a ship’s interaction with ice ridges and sliding ice pieces, the modelling of breakable ice floes, and the coupling of the Discrete Element Method (DEM) and Computational Fluid Dynamics (CFD). More attention to the local ice load estimation is also encouraged.
Chaetomugilins and Chaetoviridins—Promising Natural Metabolites: Structures, Separation, Characterization, Biosynthesis, Bioactivities, Molecular Docking, and Molecular Dynamics
Authors: Omar Abdelsattar M. , Mohamed Gamal A. , Ibrahim Sabrin R. M.
Published: January 2022

Fungi are recognized as luxuriant metabolic artists that generate propitious biometabolites. Historically, fungal metabolites have largely been investigated as leads for various therapeutic agents. Chaetomugilins and the closely related chaetoviridins are fungal metabolites, and each has an oxygenated bicyclic pyranoquinone core. They are mainly produced by various Chaetomaceae species. These metabolites display unique chemical features and diversified bioactivities. The current review gives an overview of research about fungal chaetomugilins and chaetoviridins regarding their structures, separation, characterization, biosynthesis, and bioactivities. Additionally, their antiviral potential towards the SARS-CoV-2 protease was evaluated using docking studies and molecular dynamics (MD) simulations. We report on the docking and predictive binding energy estimations using reported crystal structures of the main protease (PDB ID: 6M2N, 6W81, and 7K0f) at variable resolutions—i.e., 2.20, 1.55, and 1.65 Å, respectively. Chaetovirdin D (43) exhibited highly negative docking scores of −7.944, −8.141, and −6.615 kcal/mol, when complexed with 6M2N, 6W81, and 7K0f, respectively. The reference inhibitors exhibited the following scores: −5.377, −6.995, and −8.159 kcal/mol, when complexed with 6M2N, 6W81, and 7K0f, respectively. By using molecular dynamics simulations, chaetovirdin D’s stability in complexes with the viral protease was analyzed, and it was found to be stable over the course of 100 ns.
PCSK9 Promotes Cardiovascular Diseases: Recent Evidence about Its Association with Platelet Activation-Induced Myocardial Infarction
Authors: Puteri Meidi Utami , Azmi Nuriza Ulul , Kato Mitsuyasu , Saputri Fadlina Chany
Published: January 2022

Cardiovascular diseases are the leading cause of death worldwide, with the majority of the cases being heart failure due to myocardial infarction. Research on cardiovascular diseases is currently underway, particularly on atherosclerosis prevention, to reduce the risk of myocardial infarction. Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been reported to play a role in lipid metabolism, by enhancing low-density lipoprotein (LDL) receptor degradation. Therefore, PCSK9 inhibitors have been developed and found to successfully decrease LDL plasma levels. Recent experimental studies have also implicated PCSK9 in platelet activation, having a key role during atherosclerosis progression. Although numerous studies have addressed the role of PCSK9 role in controlling hypercholesterolemia, studies and discussions exploring its involvement in platelet activation are still limited. Hence, here, we address our current understanding of the pathophysiological process involved in atherosclerosis-induced myocardial infarction (MI) through platelet activation and highlight the molecular mechanisms used by PCSK9 in regulating platelet activation. Undoubtedly, a deeper understanding of the relationship between platelet activation and the underlying molecular mechanisms of PCSK9 in the context of MI progression will provide a new strategy for developing drugs that selectively inhibit the most relevant pathways in cardiovascular disease progression.
2-Nitro-1-vinyl-1H-imidazole
Authors: Velez Afonso Santine M. M. , de Souza Gabriela Alves , Pitasse-Santos Paulo , de Alcântara Pinto Douglas Chaves , Decote-Ricardo Debora , de Lima Marco Edilson Freire
Published: January 2022

Nitroimidazoles are pharmacophoric groups responsible for important antiparasitic activity against several infectious diseases. 2-Nitroimidazoles are found in some antiparasitic drugs and are one of the main moieties responsible for the biological activities exhibited. As an example, we can mention the drug benznidazole, the only drug available in Brazil for the treatment of Chagas disease. This work describes an efficient methodology for the synthesis of 2-nitro-1-vinyl-1H-imidazole through a simple and direct approach, as well as its full characterization and biological assessment. The antiparasitic evaluation of 2-nitro-1-vinyl-1H-imidazole against Trypanosoma cruzi (Tulahuen C2C4-LacZ strain) showed IC50 = 4.8 μM on amastigotes and low cytotoxicity against LLC-MK2 cells (IC50 > 500 μM), validating 2-nitro-1-vinyl-1H-imidazole as a biologically active structural subunit for anti-T. cruzi activity. The results presented herein demonstrate that 2-nitro-1-vinyl-1H-imidazole can be easily obtained, possessing great potential for use in the design of new antichagasic drugs through a molecular hybridization strategy using known coupling reactions.