bluuebunny/crossref_metadata_2025 huggingface dataset:
Flazin as a Lipid Droplet Regulator against Lipid Disorders
Authors: Wu Xunzhi , Chen Zhen , Wu Yue , Chen Yifan , Jia Jiaping , Shen Nianqiu , Chiba Hitoshi , Hui Shu-Ping
Published: April 2022

Lipid disorders are closely related to numerous metabolic diseases, and lipid droplets (LDs) have been considered as a new target for regulating lipid metabolism. Dietary intervention and nutraceuticals provide safe and long-term beneficial effects for treating metabolic diseases. Flazin is a diet-derived bioactive constituent mainly existing in fermented foods, of which the lipid metabolism improvement function has not been studied. In this study, the effect of flazin on lipid regulation at both cell level and organelle level was investigated. Lipidomic profiling showed that flazin significantly decreased cellular triglyceride (TG) by 12.0–22.4% compared with modeling groups and improved the TG and free fatty acid profile. LD staining revealed that flazin efficiently reduced both cellular neutral lipid content by 17.4–53.9% and LD size by 10.0–35.3%. Furthermore, nanoelectrospray ionization mass spectrometry analysis proved that flazin exhibited a preferential suppression of LD TG and regulated LD morphology, including a size decrease and surface property improvement. An evaluation of related gene expression suggested the mechanism to be lipolysis promotion and lipogenesis inhibition. These findings indicated that flazin might be an LD regulator for reversing lipid metabolism disturbance. Moreover, the strategy proposed in this study may contribute to developing other nutraceuticals for treating lipid disorder-related metabolic diseases.
Food Neophobia, Familiarity with French Cuisine, Body Mass, and Restaurant Food Choices in a Sample of Polish Women
Authors: Guzek Dominika , Głąbska Dominika
Published: April 2022

Food neophobia, a condition characterized by a reluctance or avoidance of unknown foods and meals, may influence food choice, and is also associated with body mass and familiarity with food items. This study aimed to analyze the associations between food neophobia, familiarity with French cuisine, body mass, and French restaurant menu food choices in a sample of 203 young Polish women. The Computer-Assisted Web Interview (CAWI) method was used in the study. The food choice questionnaire used for assessment was based on a model French restaurant menu, with dishes planned using a 2 × 2 factorial design for the components of neophobic potential (unfamiliar to Polish consumers) and animal-based components. Food neophobia, familiarity with French cuisine, and body mass were considered independent variables. The food neophobia scale (FNS) developed by Pliner and Hobden was used to assess food neophobia among respondents. The results showed an association between food neophobia and familiarity with French cuisine and French restaurant menu food choices (p ≤ 0.05), but no association with body mass was observed (p > 0.05). The respondents with a high level of food neophobia chose dishes with neophobic components (for soups and desserts) less often compared to those with a low neophobia level, and in the absence of such an association, they chose dishes with animal-based components (for starters and main courses) less often (p ≤ 0.05). The respondents who declared that they were familiar with French cuisine chose dishes with animal-based components (for starters and desserts) more often than those with no familiarity, but a reverse association was observed for soups (p ≤ 0.05). Based on the findings of the study, it may be concluded that food neophobia and familiarity with French cuisine may be important determinants of food choice within a French restaurant menu. The study did not show any association between body mass and the choice of dishes from the model French restaurant menu. The findings suggest that the presence of unfamiliar and animal-based ingredients may reduce the frequency of choosing specific dishes within a French restaurant menu, which may reduce the diversity of individuals’ diets.
Bacteria Associated with the Parasitic Nematode Haemonchus contortus and Its Control Using Antibiotics
Authors: Bouchet Charlotte , Deng Qing , Umair Saleh
Published: April 2022

Internal parasitism, a significant cause of production losses in sheep, is routinely controlled by anthelmintic drenches. A better understanding and alternative control strategies are needed to combat the increasing resistance. This study investigated the presence of resident bacteria in the field strain of Haemonchus contortus. Adult female worms were collected from the abomasa of sheep. DNA was extracted from adult female worms and parasite eggs laid in vitro using long or shorter enzymatic incubation methods. Polymerase Chain Reaction (PCR) was performed using universal bacterial and phylum Firmicutes-specific primers; PCR products were cloned and sequenced. The analysis of the sequences shows a majority of the sequences belong to rumen bacteria, mainly Ruminococcus. Streptococcus was detected in four eggs, and adult worm samples and the sequences had a very high homology to the Streptococcus sequences in the database. Clostridium was detected only in the adult samples, whereas Nevskia and Pseudomonas were detected only in the egg samples. Three antibiotics, Ampicillin (Amp), Gentamycin (Gen) and Tetracycline (Tet), individually or combination, were tested to establish proof of concept that abomasal nematode parasites can be controlled by killing the resident bacteria. A larval migration inhibition assay was used to test the hypothesis. Tet (10 and 20 mM) resulted in around 30% mortality in larvae. Amp and Gen did not result in significant levels of larval mortality but, when given in combination, resulted in significant mortality of the larvae, suggesting the role of antibiotics in controlling the parasites by targeting the resident bacteria.
The History of Live Attenuated Centrin Gene-Deleted Leishmania Vaccine Candidates
Authors: Volpedo Greta , Bhattacharya Parna , Gannavaram Sreenivas , Pacheco-Fernandez Thalia , Oljuskin Timur , Dey Ranadhir , Satoskar Abhay R. , Nakhasi Hira L.
Published: April 2022

Leishmaniasis, caused by an infection of the Leishmania protozoa, is a neglected tropical disease and a major health problem in tropical and subtropical regions of the world, with approximately 350 million people worldwide at risk and 2 million new cases occurring annually. Current treatments for leishmaniasis are not highly efficacious and are associated with high costs, especially in low- and middle-income endemic countries, and high toxicity. Due to a surge in the incidence of leishmaniases worldwide, the development of new strategies such as a prophylactic vaccine has become a high priority. However, the ability of Leishmania to undermine immune recognition has limited our efforts to design safe and efficacious vaccines against leishmaniasis. Numerous antileishmanial vaccine preparations based on DNA, subunit, and heat-killed parasites with or without adjuvants have been tried in several animal models but very few have progressed beyond the experimental stage. However, it is known that people who recover from Leishmania infection can be protected lifelong against future infection, suggesting that a successful vaccine requires a controlled infection to develop immunologic memory and subsequent long-term immunity. Live attenuated Leishmania parasites that are non-pathogenic and provide a complete range of antigens similarly to their wild-type counterparts could evoke such memory and, thus, would be effective vaccine candidates. Our laboratory has developed several live attenuated Leishmania vaccines by targeted centrin gene disruptions either by homologous recombination or, more recently, by using genome editing technologies involving CRISPR-Cas9. In this review, we focused on the sequential history of centrin gene-deleted Leishmania vaccine development, along with the characterization of its safety and efficacy. Further, we discussed other major considerations regarding the transition of dermotropic live attenuated centrin gene-deleted parasites from the laboratory to human clinical trials.
Pathogenic and Endosymbiotic Bacteria and Their Associated Antibiotic Resistance Biomarkers in Amblyomma and Hyalomma Ticks Infesting Nguni Cattle (Bos spp.)
Authors: Chigwada Aubrey Dickson , Mapholi Ntanganedzeni Olivia , Ogola Henry Joseph Oduor , Mbizeni Sikhumbuzo , Masebe Tracy Madimabi
Published: April 2022

Deciphering the interactions between ticks and their microbiome is key to revealing new insights on tick biology and pathogen transmission. However, knowledge on tick-borne microbiome diversity and their contribution to drug resistance is scarce in sub–Saharan Africa (SSA), despite endemism of ticks. In this study, high-throughput 16S rRNA amplicon sequencing and PICRUSt predictive function profiling were used to characterize the bacterial community structure and associated antibiotic resistance markers in Amblyomma variegatum, A. hebraeum, and Hyalomma truncatum ticks infesting Nguni cattle (Bos spp.). Twenty-one (seven families and fourteen genera) potentially pathogenic and endosymbiotic bacterial taxa were differentially enriched in two tick genera. In H. truncatum ticks, a higher abundance of Corynebacterium (35.6%), Porphyromonas (14.4%), Anaerococcus (11.1%), Trueperella (3.7%), and Helcococcus (4.7%) was detected. However, Rickettsia (38.6%), Escherichia (7%), and Coxiellaceae (2%) were the major differentially abundant taxa in A. variegatum and A. hebraeum. Further, an abundance of 50 distinct antibiotic resistance biomarkers relating to multidrug resistance (MDR) efflux pumps, drug detoxification enzymes, ribosomal protection proteins, and secretion systems, were inferred in the microbiome. This study provides theoretical insights on the microbiome and associated antibiotic resistance markers, important for the design of effective therapeutic and control decisions for tick-borne diseases in the SSA region.
Outbreak of Alimentary Tick-Borne Encephalitis in Eastern Slovakia: An Analysis of Affected Patients and Long-Term Outcomes
Authors: Paraličová Zuzana , Sekula Jakub , Jarčuška Pavol , Novotný Martin , Rovňáková Alena , Hockicko Ján , Hockicková Ivana
Published: April 2022

Objective: Tick-borne encephalitis (TBE) is an endemic zoonotic viral disease in many European countries and in the central and eastern parts of Asia. Slovakia reports the highest occurrence of alimentary tick-borne encephalitis in Europe, after the consumption of unpasteurized milk and cheese from domestic ruminants. In May 2016, an outbreak of tick-borne encephalitis that emerged after the consumption of sheep cheese occurred in eastern Slovakia. In total, 44 people were ill and 36 were hospitalized. Methods: Data from the 36 hospitalized patients at the Department of Infectology and Travel Medicine in Košice with TBE were retrospectively analysed from the medical documentation. The patients were contacted 3 years after discharge. Results: Twenty of the hospitalized patients had meningoencephalitis and 16 had meningitis. The main symptoms that occurred in all patients were fever and headache. Nuchal rigidity was seen in 50% of the patients. Three patients developed late systemic complications and another six patients had psychiatric complications. None of the patients died. Three years after the disease onset, 52% of contacted patients reported persistent discomfort. Conclusions: TBE is an infection with a wide range of clinical courses. Our findings suggest that alimentary-acquired TBE lead to severe disease and persistent discomfort.
Paramyxovirus Diversity within One Population of Miniopterus fuliginosus Bats in Sri Lanka
Authors: Muzeniek Therese , Perera Thejanee , Siriwardana Sahan , Bayram Fatimanur , Bas Dilara , Öruc Mizgin , Becker-Ziaja Beate , Perera Inoka , Weerasena Jagathpriya , Handunnetti Shiroma , Schwarz Franziska , Premawansa Gayani , Premawansa Sunil , Yapa Wipula , Nitsche Andreas , Kohl Claudia
Published: April 2022

Bats are known as typical reservoirs for a number of viruses, including viruses of the family Paramyxoviridae. Representatives of the subfamily Orthoparamyxovirinae are distributed worldwide and can cause mild to fatal diseases when infecting humans. The research on Paramyxoviruses (PMVs) from different bat hosts all over the world aims to understand the diversity, evolution and distribution of these viruses and to assess their zoonotic potential. A high number of yet unclassified PMVs from bats are recorded. In our study, we investigated bat species from the families Rhinolophidae, Hipposiderae, Pteropodidae and Miniopteridae that are roosting sympatrically in the Wavul Galge cave (Koslanda, Sri Lanka). The sampling at three time points (March and July 2018; January 2019) and screening for PMVs with a generic PCR show the presence of different novel PMVs in 10 urine samples collected from Miniopterus fuliginosus. Sequence analysis revealed a high similarity of the novel strains among each other and to other unclassified PMVs collected from Miniopterus bats. In this study, we present the first detection of PMVs in Sri Lanka and the presence of PMVs in the bat species M. fuliginosus for the first time.
A Three-Case Series of Thrombotic Deaths in Patients over 50 with Comorbidities Temporally after modRNA COVID-19 Vaccination
Authors: Roncati Luca , Manenti Antonio , Corsi Lorenzo
Published: April 2022

Coronavirus disease 2019 (COVID-19) is the most dramatic pandemic of the new millennium; to counteract it, specific vaccines have been launched in record time under emergency use authorization or conditional marketing authorization by virtue of a favorable risk/benefit balance. Among the various technological platforms, there is that exploiting a nucleoside-modified messenger RNA (modRNA), such as Comirnaty®, and that which is adenoviral vector-based. In the ongoing pharmacovigilance, the product information of the latter has been updated about the risk of thrombotic thrombocytopenia, venous thromboembolism without thrombocytopenia and immune thrombocytopenia without thrombosis. However, from an in-depth literature review, the same adverse events can rarely occur with modRNA vaccines too. In support of this, we here report a three-case series of thrombotic deaths in patients over 50 with comorbidities temporally after Comirnaty®, investigated by means of post-mortem histopathology and immunohistochemistry. In two out of three cases, the cause of death is traced back to pulmonary microthromboses rich in activated platelets, quite similar morphologically to those described in patients who died from severe COVID-19. Even if remote in the face of millions of administered doses, clinicians should be aware of the possible thrombotic risk also after Comirnaty®, in order to avoid a misdiagnosis with potentially lethal consequences. Since COVID-19 vaccines are inoculated in subjects to be protected, maximum attention must be paid to their safety, and prophylactic measures to increase it are always welcome. In light of the evidence, the product information of modRNA COVID-19 vaccines should be updated about the thrombotic risk, as happened for adenoviral vector-based vaccines.
A Case of Focal Segmental Glomerulosclerosis in a Young Girl with a Very Low Birth Weight
Authors: Kashiwagi Yasuyo , Agata Kazushi , Yamanaka Gaku , Kawashima Hisashi
Published: April 2022

In Japan, the prevalence of low birth weight (LBW) has been estimated to be approximately 10%, which is the highest among developed countries. This high prevalence might affect the occurrence of LBW-associated diseases in the adult population of Japan. LBW has been recognized as a contributing factor to post-adaptive focal segmental glomerulosclerosis (FSGS) in adulthood; however, few reports to date have evaluated the clinical and pathological characteristics of post-adaptive FSGS. A 13-year-old girl was referred to our hospital owing to mild proteinuria, which was detected at a school urinary screening. She was born at a gestational age of 23 weeks, with a very LBW of 630 g. Dipstick urinalysis revealed grade (2+) proteinuria. Her serum creatinine level was 1.02 mg/dL, and she was diagnosed as having stage 2 chronic kidney disease (CKD). Her serum uric acid level was 7 mg/dL. Furthermore, her mother and 16-year old brother had hyperuricemia. A percutaneous renal biopsy leads to a diagnosis of FSGS. After 3 years of treatment with an angiotensin receptor blocker, her proteinuria decreased. However, her serum creatinine level was 1.07 mg/dL, and she still had stage 2 CKD. We considered that in this patient, the first hit was her LBW, and the second hit was hyperuricemia. The second hit might be associated with the development of CKD. The birth history of patients is not usually confirmed by nephrologists. Our case demonstrates that obtaining information regarding the preterm birth and LBW of patients is important in the diagnosis of noncommunicable diseases because school urinary screening is not routinely performed in countries other than Japan.
A Clinical Perspective of the Multifaceted Mechanism of Metformin in Diabetes, Infections, Cognitive Dysfunction, and Cancer
Authors: Chow Elaine , Yang Aimin , Chung Colin H. L. , Chan Juliana C. N.
Published: April 2022

In type 2 diabetes, ecological and lifecourse factors may interact with the host microbiota to influence expression of his/her genomes causing perturbation of interconnecting biological pathways with diverse clinical course. Metformin is a plant-based or plant-derived medicinal product used for the treatment of type 2 diabetes for over 60 years and is an essential drug listed by the World Health Organization. By reducing mitochondrial oxidative phosphorylation and adenosine triphosphate (ATP) production, metformin increased AMP (adenosine monophosphate)-activated protein kinase (AMPK) activity and altered cellular redox state with reduced glucagon activity, endogenous glucose production, lipogenesis, and protein synthesis. Metformin modulated immune response by directly reducing neutrophil to lymphocyte ratio and improving the phagocytic function of immune cells. By increasing the relative abundance of mucin-producing and short-chain-fatty-acid-producing gut microbes, metformin further improved the host inflammatory and metabolic milieu. Experimentally, metformin promoted apoptosis and reduced proliferation of cancer cells by reducing their oxygen consumption and modulating the microenvironment. Both clinical and mechanistic studies support the pluripotent effects of metformin on reducing cardiovascular–renal events, infection, cancer, cognitive dysfunction, and all-cause death in type 2 diabetes, making this low-cost medication a fundamental therapy for individualization of other glucose-lowering drugs in type 2 diabetes. Further research into the effects of metformin on cognitive function, infection and cancer, especially in people without diabetes, will provide new insights into the therapeutic value of metformin in our pursuit of prevention and treatment of ageing-related as well as acute and chronic diseases beyond diabetes.
Isolation and Characterisation of Bacteriophage Selective for Key Acinetobacter baumannii Capsule Chemotypes
Authors: Soontarach Rosesathorn , Srimanote Potjanee , Enright Mark C. , Blundell-Hunter George , Dorman Matthew J. , Thomson Nicholas R. , Taylor Peter W. , Voravuthikunchai Supayang P.
Published: April 2022

Nineteen bacteriophages against five main capsular types of multidrug-resistant Acinetobacter baumannii were isolated from tertiary care hospital sewage. Eight representative phages from each capsular type were characterized and tested for their biological properties. The biological features revealed that phages T1245, T444, and T515 had a large burst size of more than 420 pfu/mL, together with a short latent period lasting less than 6 min, and were readily adsorbed to a bacterial host within 10 min. Moreover, these phages demonstrated host specificity and stability over a broad range of temperatures (−20 to 60 °C) and pH (5.0–9.0). A whole-genome analysis of six lytic and two temperate phages revealed high genomic similarity with double-stranded DNA between 40 and 50 kb and G + C content of 38–39%. The protein compositions disclosed the absence of toxin-coding genes. The phylogenic results, together with morphological micrographs, confirmed that three selected phages (T1245, T444, and T515) belong to the Podoviridae family within the order Caudovirales. The biological data and bioinformatics analysis indicated that these novel A. baumannii phages possess important enzymes, including depolymerase and endolysin, which could be further developed as promising alternative antibacterial agents to control A. baumannii infections.
Synthetic Design and Biological Evaluation of New p53-MDM2 Interaction Inhibitors Based on Imidazoline Core
Authors: Bazanov Daniil R. , Pervushin Nikolay V. , Savin Egor V. , Tsymliakov Michael D. , Maksutova Anita I. , Savitskaya Victoria Yu. , Sosonyuk Sergey E. , Gracheva Yulia A. , Seliverstov Michael Yu. , Lozinskaya Natalia A. , Kopeina Gelina S.
Published: April 2022

The use of p53-MDM2 inhibitors is a prospective strategy in anti-cancer therapy for tumors expressing wild type p53 protein. In this study, we have applied a simple approach of two-step synthesis of imidazoline-based alkoxyaryl compounds, which are able to efficiently inhibit p53-MDM2 protein–protein interactions, promote accumulation of p53 and p53-inducible proteins in various cancer cell lines. Compounds 2l and 2k cause significant upregulation of p53 and p53-inducible proteins in five human cancer cell lines, one of which possesses overexpression of MDM2.
Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants
Authors: Delandre Océane , Gendrot Mathieu , Jardot Priscilla , Le Bideau Marion , Boxberger Manon , Boschi Céline , Fonta Isabelle , Mosnier Joel , Hutter Sébastien , Levasseur Anthony , La Scola Bernard , Pradines Bruno
Published: April 2022

Over the past two years, several variants of SARS-CoV-2 have emerged and spread all over the world. However, infectivity, clinical severity, re-infection, virulence, transmissibility, vaccine responses and escape, and epidemiological aspects have differed between SARS-CoV-2 variants. Currently, very few treatments are recommended against SARS-CoV-2. Identification of effective drugs among repurposing FDA-approved drugs is a rapid, efficient and low-cost strategy against SARS-CoV-2. One of those drugs is ivermectin. Ivermectin is an antihelminthic agent that previously showed in vitro effects against a SARS-CoV-2 isolate (Australia/VI01/2020 isolate) with an IC50 of around 2 µM. We evaluated the in vitro activity of ivermectin on Vero E6 cells infected with 30 clinically isolated SARS-CoV-2 strains belonging to 14 different variants, and particularly 17 strains belonging to six variants of concern (VOC) (variants related to Wuhan, alpha, beta, gamma, delta and omicron). The in vitro activity of ivermectin was compared to those of chloroquine and remdesivir. Unlike chloroquine (EC50 from 4.3 ± 2.5 to 29.3 ± 5.2 µM) or remdesivir (EC50 from 0.4 ± 0.3 to 25.2 ± 9.4 µM), ivermectin showed a relatively homogeneous in vitro activity against SARS-CoV-2 regardless of the strains or variants (EC50 from 5.1 ± 0.5 to 6.7 ± 0.4 µM), except for one omicron strain (EC50 = 1.3 ± 0.5 µM). Ivermectin (No. EC50 = 219, mean EC50 = 5.7 ± 1.0 µM) was, overall, more potent in vitro than chloroquine (No. EC50 = 214, mean EC50 = 16.1 ± 9.0 µM) (p = 1.3 × 10−34) and remdesivir (No. EC50 = 201, mean EC50 = 11.9 ± 10.0 µM) (p = 1.6 × 10−13). These results should be interpreted with caution regarding the potential use of ivermectin in SARS-CoV-2-infected patients: it is difficult to translate in vitro study results into actual clinical treatment in patients.
Beneficial Effects of Polydeoxyribonucleotide (PDRN) in an In Vitro Model of Fuchs Endothelial Corneal Dystrophy
Authors: Ceravolo Ida , Mannino Federica , Irrera Natasha , Minutoli Letteria , Arcoraci Vincenzo , Altavilla Domenica , Cavallini Gian Maria , Guarini Salvatore , Squadrito Francesco , Pallio Giovanni
Published: April 2022

Fuchs endothelial corneal dystrophy (FECD) is a bilateral, hereditary syndrome characterized by progressive irreversible injury in the corneal endothelium; it is the most frequent cause for corneal transplantation worldwide. Oxidative stress induces the apoptosis of corneal endothelial cells (CECs), and has a crucial function in FECD pathogenesis. The stimulation of the adenosine A2A receptor (A2Ar) inhibits oxidative stress, reduces inflammation and modulates apoptosis. Polydeoxyribonucleotide (PDRN) is a registered drug that acts through adenosine A2Ar. Thus, the goal of this study was to assess the effect of PDRN in an in vitro FECD model. Human Corneal Endothelial Cells (IHCE) were challenged with H2O2 (200 μM) alone or in combination with PDRN (100 μg/mL), PDRN plus ZM241385 (1 μM) as an A2Ar antagonist, and CGS21680 (1 μM) as a well-known A2Ar agonist. H2O2 reduced the cells’ viability and increased the expression of the pro-inflammatory markers NF-κB, IL-6, IL-1β, and TNF-α; by contrast, it decreased the expression of the anti-inflammatory IL-10. Moreover, the pro-apoptotic genes Bax, Caspase-3 and Caspase-8 were concurrently upregulated with a decrease of Bcl-2 expression. PDRN and CGS21680 reverted the negative effects of H2O2. Co-incubation with ZM241385 abolished the effects of PDRN, indicating that A2Ar is involved in the mode of action of PDRN. These data suggest that PDRN defends IHCE cells against H2O2-induced damage, potentially as a result of its antioxidant, anti-inflammatory and antiapoptotic properties, suggesting that PDRN could be used as an FECD therapy.
Antispasmodic Effect of Bergamot Essential Oil on Rat Isolated Gut Tissues
Authors: Rombolà Laura , Straface Marilisa , Scuteri Damiana , Sakurada Tsukasa , Sakurada Shinobu , Corasaniti Maria Tiziana , Bagetta Giacinto , Morrone Luigi Antonio
Published: April 2022

Preclinical data indicate that bergamot essential oil (BEO) can modulate the synaptic functions within the central nervous system (CNS). Particularly, several data shows that essential oil is endowed with reproducible analgesic and anxiolytic effects that may derived from the ability to modulate the excitatory and inhibitory neurotransmission in the CNS. Although there are differences in the functional complexity of the enteric nervous system (ENS), it is likely that the phytocomplex has biological properties in gut superimposable to those showed in the CNS. Accordingly, the aim of this study was to investigate ex-vivo the effect of bergamot essential oil and its main constituents on the contractile activity of rat isolated colon, jejunum and ileum induced by different muscle stimulants such as acetylcholine (10−6 M) and potassium chloride (80 mM). Our present data demonstrate that BEO inhibits cholinergically- and non cholinergically-mediated contractions in rat isolated gut and that linalool is the most active component. These results suggest that the phytocomplex might be useful in the treatment of spastic disorders in ENS mainly characterized by the presence of pain; incidentally, irritable bowel syndrome (IBS) is a painful condition in which a role for neurotransmitter dysfunction has been envisaged. More investigation is required for clinical translation of the present data.
Pharmacogenetics of Osteoporosis: A Pathway Analysis of the Genetic Influence on the Effects of Antiresorptive Drugs
Authors: del Real Álvaro , Valero Carmen , Olmos José M. , Hernández Jose L. , Riancho José A.
Published: April 2022

Osteoporosis is a skeletal disorder defined by a decreased bone mineral density (BMD) and an increased susceptibility to fractures. Bisphosphonates and selective oestrogen receptor modulators (SERM) are among the most widely used drugs. They inhibit bone resorption by targeting the mevalonate and oestrogen pathways, respectively. The aim of this study was to determine if common variants of genes in those pathways influence drug responses. We studied 192 women treated with oral aminobisphosphonates and 51 with SERMs. Genotypes at 154 SNPs of the mevalonate pathway and 806 in the oestrogen pathway were analyzed. Several SNPs located in genes FDPS and FNTA were associated with the bisphosphonate-induced changes in hip bone mineral density (BMD), whereas polymorphisms of the PDSS1, CYP19A1, CYP1A1, and CYP1A2 genes were associated with SERM-induced changes in spine BMD. After multivariate analyses, genotypes combining genes FDPS and FNTA showed a stronger association with bisphosphonate response (r = 0.34; p = 0.00009), whereas the combination of CYP19A1 and PDSS1 genotypes was associated with the response to SERMs (r = 0.62, p = 0.0003). These results suggest that genotyping genes in these pathways may help predict the response to antiresorptive drugs and hence make personalized therapeutic choices.
Polymer-Modified Liposomes for Drug Delivery: From Fundamentals to Applications
Authors: Cao Yifeng , Dong Xinyan , Chen Xuepeng
Published: April 2022

Liposomes are highly advantageous platforms for drug delivery. To improve the colloidal stability and avoid rapid uptake by the mononuclear phagocytic system of conventional liposomes while controlling the release of encapsulated agents, modification of liposomes with well-designed polymers to modulate the physiological, particularly the interfacial properties of the drug carriers, has been intensively investigated. Briefly, polymers are incorporated into liposomes mainly using “grafting” or “coating”, defined according to the configuration of polymers at the surface. Polymer-modified liposomes preserve the advantages of liposomes as drug-delivery carriers and possess specific functionality from the polymers, such as long circulation, precise targeting, and stimulus-responsiveness, thereby resulting in improved pharmacokinetics, biodistribution, toxicity, and therapeutic efficacy. In this review, we summarize the progress in polymer-modified liposomes for drug delivery, focusing on the change in physiological properties of liposomes and factors influencing the overall therapeutic efficacy.
In Vivo Investigation of (2-Hydroxypropyl)-β-cyclodextrin-Based Formulation of Spironolactone in Aqueous Solution for Paediatric Use
Authors: Lopalco Antonio , Manni Annachiara , Keeley Alexander , Haider Shozeb , Li Wenliang , Lopedota Angela , Altomare Cosimo Damiano , Denora Nunzio , Tuleu Catherine
Published: April 2022

Spironolactone (SPL), a potent anti-aldosterone steroidal drug used to treat several diseases in paediatric patients (e.g., hypertension, primary aldosteronism, Bartter’s syndrome, and congestive heart failure), is not available in child-friendly dosage forms, and spironolactone liquids have been reported to be unpalatable. Aiming to enhance SPL solubility in aqueous solution and overcome palatability, herein, the effects of (2-hydroxypropyl)-β-cyclodextrin (HP-β-CyD) were thoroughly investigated on solubilisation in water and on masking the unpleasant taste of SPL in vivo. Although the complexation of SPL with HP-β-CyD was demonstrated through phase solubility studies, Job’s plot, NMR and computational docking studies, our in vivo tests did not show significant effects on taste aversion. Our findings, on the one hand, suggest that the formation of an inclusion complex of SPL with HP-β-CyD itself is not necessarily a good indicator for an acceptable degree of palatability, whereas, on the other hand, they constitute the basis for investigating other cyclodextrin-based formulations of the poorly water-soluble steroidal drug, including solid dosage forms, such as spray-dried powders and orodispersible tablets.
Carbon Nanotubes-Based Assays for Cancer Detection and Screening
Authors: Bura Cristina , Mocan Teodora , Grapa Cristiana , Mocan Lucian
Published: April 2022

Carbon nanotubes (CNTs) were considered a potential cargo for cancer therapy and diagnosis following researchers’ shared goal of finding a new delivery system to enhance the pharmacological performance of the administered drugs. To date, several excellent reviews have focused on the role of CNTs as drug delivery systems, although there is currently no existing study that gathers all the advances in research-connected carbon nanotubes-based assay development for the early detection of cancer. In this review article, we will focus on the emerging role of CNTs as anticancer detection agents.
Formulation and Evaluation of Novel Film Wound Dressing Based on Collagen/Microfibrillated Carboxymethylcellulose Blend
Authors: Tenorová Kateřina , Masteiková Ruta , Pavloková Sylvie , Kostelanská Klára , Bernatonienė Jurga , Vetchý David
Published: April 2022

Collagen is essential as a physiological material in wound healing, so it is often used in wound management, mainly as a lyophilisate. Collagen also has excellent film-forming properties; unfortunately, however, its utilisation as a film wound dressing is limited because of its weak mechanical properties, especially in its wet state. For this reason, modifications or combinations with different materials are investigated. The combination of collagen with partially modified microfibrillar carboxymethylcellulose (CMC), which has not previously been described, provided a new possibility for strengthening collagen films and was the aim of this work. The collagen–CMC films based on three types of collagens, two plasticizers and two collagen. Plasticiser ratios were prepared using the solvent casting method; partially modified CMC served here as both a film-forming agent and a filler, without compromising the transparency of the films. The presence of microfibrils was confirmed microscopically by SEM. Organoleptic and physicochemical evaluation, especially in terms of practical application on wounds, demonstrated that all the samples had satisfactory properties for this purpose even after wetting. All the films retained acidic pH values even after 24 h, with a maximum of 6.27 ± 0.17, and showed a mild degree of swelling, with a maximum of about 6 after 24 h.
Bacteria as Nanoparticle Carriers for Immunotherapy in Oncology
Authors: Moreno Víctor M. , Baeza Alejandro
Published: April 2022

The use of nanocarriers to deliver antitumor agents to solid tumors must overcome biological barriers in order to provide effective clinical responses. Once within the tumor, a nanocarrier should navigate into a dense extracellular matrix, overcoming intratumoral pressure to push it out of the diseased tissue. In recent years, a paradigm change has been proposed, shifting the target of nanomedicine from the tumoral cells to the immune system, in order to exploit the natural ability of this system to capture and interact with nanometric moieties. Thus, nanocarriers have been engineered to interact with immune cells, with the aim of triggering specific antitumor responses. The use of bacteria as nanoparticle carriers has been proposed as a valuable strategy to improve both the accumulation of nanomedicines in solid tumors and their penetration into the malignancy. These microorganisms are capable of propelling themselves into biological environments and navigating through the tumor, guided by the presence of specific molecules secreted by the diseased tissue. These capacities, in addition to the natural immunogenic nature of bacteria, can be exploited to design more effective immunotherapies that yield potent synergistic effects to induce efficient and selective immune responses that lead to the complete eradication of the tumor.
Development of Self-Administered Formulation to Improve the Bioavailability of Leuprorelin Acetate
Authors: Okada Akie , Niki Rina , Inoue Yutaka , Tomita Junki , Todo Hiroaki , Itakura Shoko , Sugibayashi Kenji
Published: April 2022

In recent years, the development of self-injectable formulations has attracted much attention, and the development of formulations to control pharmacokinetics, as well as drug release and migration in the skin, has become an active research area. In the present study, the development of a lipid-based depot formulation containing leuprorelin acetate (LA) as an easily metabolizable drug in the skin was prepared with a novel non-lamellar liquid-crystal-forming lipid of mono-O-(5,9,13-trimethyl-4-tetradecenyl) glycerol ester (MGE). Small-angle X-ray scattering, cryo-transmission electron microscopy, and nuclear magnetic resonance observations showed that the MGE-containing formulations had a face-centered cubic packed micellar structure. In addition, the bioavailability (BA) of LA after subcutaneous injection was significantly improved with the MGE-containing formulation compared with the administration of LA solution. Notably, higher Cmax and faster Tmax were obtained with the MGE-containing formulation, and the BA increased with increasing MGE content in the formulation, suggesting that LA migration into the systemic circulation and its stability might be enhanced by MGE. These results may support the development of self-administered formulations of peptide drugs as well as nucleic acids, which are easily metabolized in the skin.
Naturalizing Morality to Unveil the Status of Violence: Coalition Enforcement, Cognitive Moral Niches, and Moral Bubbles in an Evolutionary Perspective
Authors: Magnani Lorenzo
Published: April 2022

I propose that the relationship between moral and violent behavior is overlooked in current philosophical, epistemological, and cognitive studies. To the aim of clarifying the complex dynamics of this interplay, I will describe, adopting an evolutionary perspective, the concepts of coalition enforcement, cognitive moral niche, and of what I call moral bubbles. Showing the interesting relationships between these three basic concepts, I will explain the role of morality in causing and justifying violence. The main theoretical merit of the concept of coalition enforcement is that it permits the naturalization of morality that is the only conceptual means to unveil, in a naturalized way, the status of violence beyond the constraints generated by the so-called moral bubbles that prevent agents from seeing the potential violence generated by their own moral acts.
Analyzing the Effects of a Basin on Atmospheric Environment Relevant to Optical Turbulence
Authors: Xu Manman , Zhou Liangping , Shao Shiyong , Weng Ningquan , Liu Qing
Published: April 2022

The performance of adaptive optics (AO) systems are highly dependent upon optical turbulence. Thus, it is necessary to have the appropriate knowledge of the spatiotemporal characteristics of optical turbulence strength. In this paper, the spatiotemporal distribution of meteorological parameters (wind and temperature) and optical turbulence parameters (turbulence strength, temperature gradient, and wind shear) derived from pulsed coherent Doppler lidar, a microwave radiometer, and ERA5 reanalysis data are investigated, and the results show that the meteorological parameters in a basin develop independently, while the external influence will increase above the basin. By fitting radiosonde data, an existing parameterized model was improved to be more in line with the evolutionary properties of local optical turbulence. The development of temperature gradient and wind shear is influenced by the basin, which ultimately leads to an optical turbulence vertical profile that is discrepant at different altitude layers. The results indicate that temperature gradient plays a dominant role in turbulence generation below 2 km, and wind shear increases its impact significantly above 2 km. Furthermore, the optical turbulence parameters (outer scale, turbulence diffusion coefficient, and turbulence energy dissipation rate) and optical turbulence strength have good consistency, which might be derived from the combined effect of terrain and complex environment. Finally, the integrated parameters for astronomy and optical telecommunication were derived from optical turbulence strength profiles. An appropriate knowledge of optical turbulence is essential for improving the performance of adaptive optics systems and astronomical site selection.
High Linearity Microwave Photonic Up-Conversion System Based on Parallel Dual-Drive Mach–Zehnder Modulators
Authors: Wang Weiheng , Bai Yu , Fu Shuanglin , Su Xinxin , Gu Yiying , Chi Hao , Zhao Mingshan , Han Xiuyou
Published: April 2022

A large dynamic frequency up-conversion scheme based on parallel dual-drive Mach–Zehnder modulators (DD-MZM) and balance detection is proposed and demonstrated experimentally. By optimizing the distribution ratio of the optical carrier power and the IF signal power between the two DD-MZMs, the third-order intermodulation components in two sub-links cancel each other upon the balanced photodetector. The measured results show that the large spurious-free dynamic range of 112.3 dB·Hz4/5 is obtained for an intermediate frequency signal of 2 GHz up-converted to 18 GHz, which is a 14.8 dB enhancement compared with the traditional carrier suppression double-sideband modulation mixer. The frequency up-conversion performance of the established system for the broadband signal is measured with the results demonstrating the feasibility of the proposed optimization scheme.
Deformation Measurement of Scaling and Rotation Objects Based on Digital Image Correlation Method with Color Information
Authors: Wang Lianpo
Published: April 2022

The digital image correlation (DIC) method is widely used in deformation measurement due to the advantages of being non-contact, high precision, full field measurement, and requiring simple experimental equipment. Traditionally, the grayscale speckle patterns captured by a monochromatic camera are used in the DIC method. With the growing development of consumer color cameras, there is a great potential for developing color information in the DIC method. This paper proposes a scaling- and rotation-invariant DIC (SRI-DIC) method based on the color speckle patterns. For the integer-pixel matching stage, the scaling- and rotation-invariant color histogram feature is used to estimate the initial value of the deformation parameters. For the sub-pixel matching stage, a new error function using the three-channel information of color camera is proposed to avoid the influence of illumination changes. In addition, this paper proposes a reverse retrieve strategy instead of the forward search to reduce the search time. Experiments show that the proposed SRI-DIC algorithm not only has scaling and rotation invariance, robustness, and high efficiency, but also that the average accuracy of the strain result can reach 0.1%.
Problems of Red Blood Cell Aggregation and Deformation Assessed by Laser Tweezers, Diffuse Light Scattering and Laser Diffractometry
Authors: Semenov Alexey , Lugovtsov Andrei , Ermolinskiy Petr , Lee Kisung , Priezzhev Alexander
Published: April 2022

This study aims to highlight the problems with implementing optical techniques (laser tweezers, diffuse light scattering and laser diffractometry) in clinical hemorheological practice. We provide the feasibility of these techniques to assess microrheological effects of various molecular mechanisms affecting RBC aggregation and deformability. In particular, we show that they allow assessment of changes in RBC aggregation in whole blood samples both on the level of single cells and on the level of large ensembles of cells. Application of these methods allows for studying the mechanisms of RBC aggregation because they are sensitive to changes in the medium which surrounds the RBC (i.e., blood plasma, serum or model solutions of blood plasma proteins) and to changes in the cellular properties of RBCs (i.e., effects on the cell membrane due to glycoprotein inhibition).
Topology-Abstraction-Based Protection Scheme in Quantum Key Distribution Networks with Partially Trusted Relays
Authors: Zhang Qin , Liu Yikai , Yu Xiaosong , Zhao Yongli , Zhang Jie
Published: April 2022

Quantum key distribution (QKD) can protect the exchange process of confidential information between communicating parties. By using the basic principles of quantum mechanics and combined with “one-time pad” cipher encryption, information can be unconditionally secure. The BB84 protocol first describes the method of transmitting information by photon polarization state, and it expounds the transmission process of services between trusted relays. However, due to the defects of real experimental devices, there are security vulnerabilities in QKD in a real system. The birth of measurement-device-independent quantum key distribution (MDI-QKD) protocol solves the problem, providing immunity to hacker attacks at the end of the detector. It can enable both sides of the transmission service to establish a connection and generate secret keys through an untrusted relay node to ensure information security. However, the types and properties of link nodes in quantum key distribution network (QKDN) based on partially trusted relay are more complex, which can easily result in network fault. Therefore, how to prevent the impact of failure on QKDN has become an urgent problem. In this paper, we propose a protection scheme for QKDN with partially trusted relays. The method deals with trusted and untrusted relays differently and constructs the working and protection paths of the secret key for each service. It reduces resource conflict between the protection and working paths by establishing a key protection threshold, which realizes the resource trade-off between the two factors. Simulation results show that the scheme provides effective protection to the services, and it improves the stability and reliability of QKDN based on partially trusted relay.
Many Body Current Density from Foldy–Wouthuysen Transformation of the Dirac–Coulomb Hamiltonian
Authors: Summa Francesco Ferdinando , Citro Roberta
Published: April 2022

This paper analyzes how special relativity changes the equation for the many-body-induced current density starting from the Foldy–Wouthuysen diagonalization of the Dirac–Coulomb Hamiltonian. This current density differs from that obtained with the Gordon decomposition due to the presence of a spin-orbit coupling contribution not considered before for many-body molecular systems. This contribution diverges on atomic nuclei due to the nature of the point charges considered in the nonrelativistic approach, demonstrating that conventionally used nonrelativistic methods are not suitable for dealing with spin effects such as spin-orbit coupling or effects smaller than α2, with α the fine structure constant, and that a fully relativistic approach with a finite charge should be used. Despite the singularity, the spin-orbit coupling current becomes an important contribution to the total current in open-shell systems with high-spin multiplicity and a high atomic number in the nuclear proximity. On long ranges, this contribution is overcome by the Coulomb potential and the derived electric field which decays very quickly for small distances from nuclear charges. An evaluation of this spin-orbit current has been performed in the linear response approach at the HF/DFT level of theory.