bluuebunny/crossref_metadata_2025 huggingface dataset:
The Divergent Effects of Ovarian Steroid Hormones in the MCF-7 Model for Luminal A Breast Cancer: Mechanistic Leads for Therapy
Authors: Telang Nitin T.
Published: April 2022

The growth modulating effects of the ovarian steroid hormones 17β-estradiol (E2) and progesterone (PRG) on endocrine-responsive target tissues are well established. In hormone-receptor-positive breast cancer, E2 functions as a potent growth promoter, while the function of PRG is less defined. In the hormone-receptor-positive Luminal A and Luminal B molecular subtypes of clinical breast cancer, conventional endocrine therapy predominantly targets estrogen receptor function and estrogen biosynthesis and/or growth factor receptors. These therapeutic options are associated with systemic toxicity, acquired tumor resistance, and the emergence of drug-resistant cancer stem cells, facilitating the progression of therapy-resistant disease. The limitations of targeted endocrine therapy emphasize the identification of nontoxic testable alternatives. In the human breast, carcinoma-derived hormone-receptor-positive MCF-7 model treatment with E2 within the physiological concentration range of 1 nM to 20 nM induces progressive growth, upregulated cell cycle progression, and downregulated cellular apoptosis. In contrast, treatment with PRG at the equimolar concentration range exhibits dose-dependent growth inhibition, downregulated cell-cycle progression, and upregulated cellular apoptosis. Nontoxic nutritional herbs at their respective maximum cytostatic concentrations (IC90) effectively increase the E2 metabolite ratio in favor of the anti-proliferative metabolite. The long-term exposure to the selective estrogen-receptor modulator tamoxifen selects a drug-resistant phenotype, exhibiting increased expressions of stem cell markers. The present review discusses the published evidence relevant to hormone metabolism, growth modulation by hormone metabolites, drug-resistant stem cells, and growth-inhibitory efficacy of nutritional herbs. Collectively, this evidence provides proof of the concept for future research directions that are focused on novel therapeutic options for endocrine therapy-resistant breast cancer that may operate via E2- and/or PRG-mediated growth regulation.
Application of Droplet Digital PCR Technology in Muscular Dystrophies Research
Authors: Lambrescu Ioana , Popa Alexandra , Manole Emilia , Ceafalan Laura Cristina , Gaina Gisela
Published: April 2022

Although they are considered rare disorders, muscular dystrophies have a strong impact on people’s health. Increased disease severity with age, frequently accompanied by the loss of ability to walk in some people, and the lack of treatment, have directed the researchers towards the development of more effective therapeutic strategies aimed to improve the quality of life and life expectancy, slow down the progression, and delay the onset or convert a severe phenotype into a milder one. Improved understanding of the complex pathology of these diseases together with the tremendous advances in molecular biology technologies has led to personalized therapeutic procedures. Different approaches that are currently under extensive investigation require more efficient, sensitive, and less invasive methods. Due to its remarkable analytical sensitivity, droplet digital PCR has become a promising tool for accurate measurement of biomarkers that monitor disease progression and quantification of various therapeutic efficiency and can be considered a tool for non-invasive prenatal diagnosis and newborn screening. Here, we summarize the recent applications of droplet digital PCR in muscular dystrophy research and discuss the factors that should be considered to get the best performance with this technology.
Novel Chemicals Derived from Tadalafil Exhibit PRMT5 Inhibition and Promising Activities against Breast Cancer
Authors: Yang Ziyan , Xiao Tian , Li Zezhi , Zhang Jian , Chen Suning
Published: April 2022

Breast cancer seriously endangers women’s health worldwide. Protein arginine methyltransferase 5 (PRMT5) is highly expressed in breast cancer and represents a potential druggable target for breast cancer treatment. However, because the currently available clinical PRMT5 inhibitors are relatively limited, there is an urgent need to develop new PRMT5 inhibitors. Our team previously found that the FDA-approved drug tadalafil can act as a PRMT5 inhibitor and enhance the sensitivity of breast cancer patients to doxorubicin treatment. To further improve the binding specificity of tadalafil to PRMT5, we chemically modified tadalafil, and designed three compounds, A, B, and C, based on the PRMT5 protein structure. These three compounds could bind to PRMT5 through different binding modes and inhibit histone arginine methylation. They arrested the proliferation and triggered the apoptosis of breast cancer cells in vitro and also promoted the antitumor effects of the chemotherapy drugs cisplatin, doxorubicin, and olaparib in combination regimens. Among them, compound A possessed the highest potency. Finally, the anti-breast cancer effects of PRMT5 inhibitor A and its ability to enhance chemosensitivity were further verified in a xenograft mouse model. These results indicate that the new PRMT5 inhibitors A, B, and C may be potential candidates for breast cancer treatment.
Plant Responses and Tolerance to Salt Stress: Physiological and Molecular Interventions
Authors: Hasanuzzaman Mirza , Fujita Masayuki
Published: April 2022

Salinity is considered one of the most devastating environmental stresses that drastically curtails the productivity and quality of crops across the world [...]
Overexpression of Human Estrogen Biosynthetic Enzyme Hydroxysteroid (17beta) Dehydrogenase Type 1 Induces Adenomyosis-like Phenotype in Transgenic Mice
Authors: Heinosalo Taija , Rytkönen Kalle T. , Saarinen Niina , Järvensivu Päivi , Damdimopoulou Pauliina , Strauss Leena , Orasniemi Satu , Horshauge Petricia , Gabriel Michael , Koskimies Pasi , Ohlsson Claes , Kronqvist Pauliina , Poutanen Matti
Published: April 2022

Hydroxysteroid (17beta) dehydrogenase type 1 (HSD17B1) is an enzyme that converts estrone to estradiol, while adenomyosis is an estrogen-dependent disease with poorly understood pathophysiology. In the present study, we show that mice universally over-expressing human estrogen biosynthetic enzyme HSD17B1 (HSD17B1TG mice) present with adenomyosis phenotype, characterized by histological and molecular evaluation. The first adenomyotic changes with endometrial glands partially or fully infiltrated into the myometrium appeared at the age of 5.5 months in HSD17B1TG females and became more prominent with increasing age. Preceding the phenotype, increased myometrial smooth muscle actin positivity and increased amount of glandular myofibroblast cells were observed in HSD17B1TG uteri. This was accompanied by transcriptomic upregulation of inflammatory and estrogen signaling pathways. Further, the genes upregulated in the HSD17B1TG uterus were enriched with genes previously observed to be induced in the human adenomyotic uterus, including several genes of the NFKB pathway. A 6-week-long HSD17B1 inhibitor treatment reduced the occurrence of the adenomyotic changes by 5-fold, whereas no effect was observed in the vehicle-treated HSD17B1TG mice, suggesting that estrogen is the main upstream regulator of adenomyosis-induced uterine signaling pathways. HSD17B1 is considered as a promising drug target to inhibit estrogen-dependent growth of endometrial disorders. The present data indicate that HSD17B1 over-expression in TG mice results in adenomyotic changes reversed by HSD17B1 inhibitor treatment and HSD17B1 is, thus, a potential novel drug target for adenomyosis.
The Role of H2S Regulating NLRP3 Inflammasome in Diabetes
Authors: Zhao Huijie , Liu Huiyang , Yang Yihan , Wang Honggang
Published: April 2022

Nucleotide-binding oligomeric domain (NOD)-like receptor protein 3 (NLRP3) is a recently discovered cytoplasmic multiprotein complex involved in inflammation. The NLRP3 inflammasome contains NLRP3, apoptosis-related specific protein (ASC) and precursor caspase-1. The NLRP3 inflammasome is involved in many diseases, including diabetes. H2S is a harmful gas with a rotten egg smell. Recently, it has been identified as the third gas signal molecule after nitric oxide and carbon monoxide. It has many biological functions and plays an important role in many diseases, including diabetes. In recent years, it has been reported that H2S regulation of the NLRP3 inflammasome contributes to a variety of diseases. However, the mechanism has not been fully understood. In this review, we summarized the recent role and mechanism of H2S in regulating the NLRP3 inflammasome in diabetes, in order to provide a theoretical basis for future research.
Whole Genome Amplification in Preimplantation Genetic Testing in the Era of Massively Parallel Sequencing
Authors: Volozonoka Ludmila , Miskova Anna , Gailite Linda
Published: April 2022

Successful whole genome amplification (WGA) is a cornerstone of contemporary preimplantation genetic testing (PGT). Choosing the most suitable WGA technique for PGT can be particularly challenging because each WGA technique performs differently in combination with different downstream processing and detection methods. The aim of this review is to provide insight into the performance and drawbacks of DOP-PCR, MDA and MALBAC, as well as the hybrid WGA techniques most widely used in PGT. As the field of PGT is moving towards a wide adaptation of comprehensive massively parallel sequencing (MPS)-based approaches, we especially focus our review on MPS parameters and detection opportunities of WGA-amplified material, i.e., mappability of reads, uniformity of coverage and its influence on copy number variation analysis, and genomic coverage and its influence on single nucleotide variation calling. The ability of MDA-based WGA solutions to better cover the targeted genome and the ability of PCR-based solutions to provide better uniformity of coverage are highlighted. While numerous comprehensive PGT solutions exploiting different WGA types and adjusted bioinformatic pipelines to detect copy number and single nucleotide changes are available, the ones exploiting MDA appear more advantageous. The opportunity to fully analyse the targeted genome is influenced by the MPS parameters themselves rather than the solely chosen WGA.
The Mighty Mitochondria Are Unifying Organelles and Metabolic Hubs in Multiple Organs of Obesity, Insulin Resistance, Metabolic Syndrome, and Type 2 Diabetes: An Observational Ultrastructure Study
Authors: Hayden Melvin R.
Published: April 2022

Mitochondria (Mt) are essential cellular organelles for the production of energy and thermogenesis. Mt also serve a host of functions in addition to energy production, which include cell signaling, metabolism, cell death, and aging. Due to the central role of Mt in metabolism as metabolic hubs, there has been renewed interest in how Mt impact metabolic pathways and multiple pathologies. This review shares multiple observational ultrastructural findings in multiple cells and organs to depict aberrant mitochondrial (aMt) remodeling in pre-clinical rodent models. Further, it is intended to show how remodeling of Mt are associated with obesity, insulin resistance, metabolic syndrome (MetS), and type 2 diabetes mellitus (T2DM). Specifically, Mt remodeling in hypertensive and insulin-resistant lean models (Ren2 rat models), lean mice with streptozotocin-induced diabetes, obesity models including diet-induced obesity, genetic leptin-deficient ob/ob, and leptin receptor-deficient db/db diabetic mice are examined. Indeed, aMt dysfunction and damage have been implicated in multiple pathogenic diseases. Manipulation of Mt such as the induction of Mt biogenesis coupled with improvement of mitophagy machinery may be helpful to remove leaky damaged aMt in order to prevent the complications associated with the generation of superoxide-derived reactive oxygen species and the subsequent reactive species interactome. A better understanding of Mt remodeling may help to unlock many of the mysteries in obesity, insulin resistance, MetS, T2DM, and the associated complications of diabetic end-organ disease.
Kinetics of Reordering in Quenched Ni2Mn0.8Cu0.2Ga Ferromagnetic Shape Memory Alloys
Authors: Seguí Concepció
Published: April 2022

Quenched Ni2Mn1−xCuxGa ferromagnetic shape memory alloys undergo two consecutive post-quench ordering processes. The kinetics of order recovery has been analysed in detail for Ni2Mn0.8Cu0.2Ga, based on the calorimetric curves obtained during post-quench heating at constant rates. Isoconversional methods have been used to determine the activation energy, the pre-exponential factor, and the reaction model that best fits the two reordering processes. The kinetic analysis has been extended to samples quenched from different temperatures. The kinetic study shows that order improvement processes in quenched Ni2Mn0.8Cu0.2Ga alloys can be described by a first order reaction model, consistent with site-saturation nucleation and homogeneous diffusion-controlled growth, with apparent activation energies around 1.1 eV. The pre-exponential factors, especially those obtained for samples quenched from different temperatures, highlight the crucial role of the vacancies retained by high temperature quenching on the atomic reordering underlying the observed processes.
Metabolomics Reveals 5-Aminolevulinic Acid Improved the Ability of Tea Leaves (Camellia sinensis L.) against Cold Stress
Authors: Yan Fei , Qu Dong , Chen Xiaohua , Zeng Haitao , Li Xinsheng , Hu Ching Yuan
Published: April 2022

Tea is an important woody crop whose cultivation is severely limited by cold stress. Although 5-aminolevulinic acid (ALA) is known to be effective in alleviating abiotic stresses in plants, knowledge of the detailed metabolic response of tea plants to exogenous ALA-induced cold resistance is still limited—a lack which restricts our ability to protect tea plants from cold stress. In the present study, we performed an in-depth metabolomics analysis to elucidate the metabolic responses of tea plants to cold stress and explore the role of ALA in improving tea plants’ cold-resistance capability. Metabolic profiles showed that cold stress altered various metabolisms in tea plants, especially galactose composition and flavonoid contents. Furthermore, exogenous ALA application altered a series of metabolisms associated with cold stress. Importantly, increases in metabolites, including catechin, 3,4-dihydroxyphenylacetic acid and procyanidin B2, involved in the mechanisms of ALA improved tea plants’ cold resistance. Overall, our study deciphered detailed metabolic responses of tea plants to cold stress and elucidated the mechanisms of ALA in enhancing cold resistance through rebuilding compositions of soluble carbohydrates and flavonoids. Therefore, we have provided a basis for exogenous usage of ALA to protect tea plants from cold stress.
Geochemistry and Mineralogy of Ferromanganese Crusts from the Western Cocos-Nazca Spreading Centre, Pacific
Authors: Zawadzki Dominik , Maciąg Łukasz , Blasco Iker , González Francisco Javier , Wernette Benjamin , Marino Egidio , Kozub-Budzyń Gabriela A. , Piestrzyński Adam , Wróbel Rafał J. , McCartney Kevin
Published: April 2022

Late Pleistocene–Holocene rocks from the western part of Cocos-Nazca Spreading Centre (C-NSC) include ferromanganese crusts that elucidate the geochemistry and mineralogy of a deep-sea geological setting. Six representative Fe-Mn crust samples were studied using petrological methods, such as optical transmitted light microscopy, energy dispersive X-ray fluorescence spectrometry, inductively coupled plasma mass spectrometry, bulk X-ray diffraction, scanning electron microscopy and electron probe microanalysis. Geochemical, mineralogical and petrological signatures indicate complex formation influenced by mild hydrothermal processes. These crusts consist mostly of mixed birnessite, todorokite-buserite, and Mn-(Fe) vernadite with traces of diagenetic manganates (asbolane), Fe-oxides and oxyhydroxides or hydrothermally associated and relatively pure Mn-oxyhydroxides (manganite). The average Mn/Fe ratio is 2.7, which suggests predominant mixed hydrogenous-early diagenetic crusts with hydrothermal influences. The mean concentrations of three prospective metals (Ni, Cu and Co) are low: 0.17, 0.08 and 0.025 wt %, respectively. The total content of ΣREY is also low, and ranges from 81 to 741 mg/kg (mean 339 mg/kg). We interpret the complex geochemical and mineralogical data to reflect mixed origin of the crusts, initially related with formation of hydrothermal plume over the region. This process occurred during further interactions with seawater from which additional diagenetic and hydrogenetic elemental signatures were acquired.
Plant Polysaccharides Modulate Immune Function via the Gut Microbiome and May Have Potential in COVID-19 Therapy
Authors: Tang Mengsheng , Cheng Lu , Liu Yanan , Wu Zufang , Zhang Xin , Luo Songmei
Published: April 2022

Plant polysaccharides can increase the number and variety of beneficial bacteria in the gut and produce a variety of active substances, including short-chain fatty acids (SCFAs). Gut microbes and their specific metabolites have the effects of promoting anti-inflammatory activity, enhancing the intestinal barrier, and activating and regulating immune cells, which are beneficial for improving immunity. A strong immune system reduces inflammation caused by external viruses and other pathogens. Coronavirus disease 2019 (COVID-19) is still spreading globally, and patients with COVID-19 often have intestinal disease and weakened immune systems. This article mainly evaluates how polysaccharides in plants can improve the immune system barrier by improving the intestinal microecological balance, which may have potential in the prevention and treatment of COVID-19.
Lycopodium Mitigates Oxidative Stress and Inflammation in the Colonic Mucosa of Acetic Acid-Induced Colitis in Rats
Authors: Bastaki Salim M. A. , Amir Naheed , Adeghate Ernest , Ojha Shreesh
Published: April 2022

Inflammatory bowel diseases (IBDs) such as ulcerative colitis (UC) and Crohn’s disease (CD) are diseases of the gastrointestinal system involving genetic and environmental factors attributed to oxidative stress and inflammation. Targeting oxidative stress and inflammation by novel dietary compounds of natural origin convincingly appears to be one of the important therapeutic strategies to keep the disease in remission. As there is no permanent cure for IBD except for chronic long-term treatment or surgery, it is therefore imperative to investigate plant-based agents that are receiving attention for their therapeutic benefits to overcome the debilitating clinical conditions of IBD. Lycopodium (LYCO), a plant of tropical and subtropical origin and known by numerous names such as ground pine, club moss, or devil’s claw, has been popularly used for centuries in traditional medicine including Chinese and Indian medicines. In the present study, the effect of LYCO has been investigated in an acetic acid (AA)-induced colitis model in Wistar rats. LYCO was orally administered at the dose of 50 mg/kg/day either 3 days before or 30 min after the induction of IBD and continued for 7 days by intrarectal administration of AA. The changes in body weight and macroscopic and microscopic analysis of the colon of rats of different experimental groups were observed on days 0, 2, 4, and 7. The levels of myeloperoxidase (MPO), reduced glutathione (GSH), and malondialdehyde (MDA) were measured. AA caused a significant reduction in body weight and increased macroscopic and microscopic ulcer scores along with a significant decline in antioxidant enzymes, superoxide dismutase (SOD), and catalase and antioxidant substrate, glutathione (GSH). There was a concomitant increased formation of malondialdehyde (MDA), a marker of lipid peroxidation, and raised myeloperoxidase (MPO) activity, a marker of neutrophil activation. Treatment with LYCO significantly improved IBD-induced reduction in body weight, improved histology, inhibited MDA formation, and restored antioxidants along with reduced MPO activity. AA also caused the release of proinflammatory cytokines such as interleukin-1β (IL-1β) and interleukin-23 (IL-23). Furthermore, AA also increased the levels of calprotectin, a protein released by neutrophils under inflammatory conditions of the gastrointestinal tract. LYCO treatment significantly reduced the release of calprotectin and proinflammatory cytokines. The results demonstrate that LYCO treatment has the potential to improve disease activity by inhibiting oxidative stress, lipid peroxidation, and inflammation along with histological preservation of colonic tissues.
Microwave-Assisted Synthesis of N/TiO2 Nanoparticles for Photocatalysis under Different Irradiation Spectra
Authors: Sanchez Tobon Camilo , Ljubas Davor , Mandić Vilko , Panžić Ivana , Matijašić Gordana , Ćurković Lidija
Published: April 2022

Nitrogen-doped TiO2 (N/TiO2) photocatalyst nanoparticles were derived by the environmentally friendly and cost-effective microwave-assisted synthesis method. The samples were prepared at different reaction parameters (temperature and time) and precursor ratio (amount of nitrogen source; urea). The obtained materials were characterized by X-ray diffraction (XRD), photoelectron spectroscopy (XPS), Raman spectroscopy (RS), infrared spectroscopy (FTIR), diffuse reflectance spectroscopy (DRS), electron microscopy (SEM-EDS), and nitrogen adsorption/desorption isotherms. Two cycles of optimizations were conducted to determine the best reaction temperature and time, as well as N content. The phase composition for all N/TiO2 nanomaterials was identified as photoactive anatase. The reaction temperature was found to be the most relevant parameter for the course of the structural evolution of the samples. The nitrogen content was the least relevant for the development of the particle morphology, but it was important for photocatalytic performance. The photocatalytic activity of N/TiO2 nanoparticle aqueous suspensions was evaluated by the degradation of antibiotic ciprofloxacin (CIP) under different irradiation spectra: ultraviolet A light (UVA), simulated solar light, and visible light. As expected, all prepared samples demonstrated efficient CIP degradation. For all irradiation sources, increasing synthesis temperature and increasing nitrogen content further improved the degradation efficiencies.
Recent Advances in Electrochemical Sensing of Hydrogen Peroxide (H2O2) Released from Cancer Cells
Authors: Ahmad Touqeer , Iqbal Ayesha , Halim Sobia Ahsan , Uddin Jalal , Khan Ajmal , El Deeb Sami , Al-Harrasi Ahmed
Published: April 2022

Cancer is by far the most common cause of death worldwide. There are more than 200 types of cancer known hitherto depending upon the origin and type. Early diagnosis of cancer provides better disease prognosis and the best chance for a cure. This fact prompts world-leading scientists and clinicians to develop techniques for the early detection of cancer. Thus, less morbidity and lower mortality rates are envisioned. The latest advancements in the diagnosis of cancer utilizing nanotechnology have manifested encouraging results. Cancerous cells are well known for their substantial amounts of hydrogen peroxide (H2O2). The common methods for the detection of H2O2 include colorimetry, titration, chromatography, spectrophotometry, fluorimetry, and chemiluminescence. These methods commonly lack selectivity, sensitivity, and reproducibility and have prolonged analytical time. New biosensors are reported to circumvent these obstacles. The production of detectable amounts of H2O2 by cancerous cells has promoted the use of bio- and electrochemical sensors because of their high sensitivity, selectivity, robustness, and miniaturized point-of-care cancer diagnostics. Thus, this review will emphasize the principles, analytical parameters, advantages, and disadvantages of the latest electrochemical biosensors in the detection of H2O2. It will provide a summary of the latest technological advancements of biosensors based on potentiometric, impedimetric, amperometric, and voltammetric H2O2 detection. Moreover, it will critically describe the classification of biosensors based on the material, nature, conjugation, and carbon-nanocomposite electrodes for rapid and effective detection of H2O2, which can be useful in the early detection of cancerous cells.
SARS-CoV-2 Omicron Variant in Croatia—Rapid Detection of the First Case and Cross-Border Spread
Authors: Ferenčak Ivana , Obrovac Mihaela , Žmak Ljiljana , Kuzle Josipa , Petrović Goranka , Vilibić-Čavlek Tatjana , Jurić Dragan , Jurić Anita , Hruškar Željka , Capak Krunoslav , Stevanović Vladimir , Milanović Maja , Govedarica Marija , Vujošević Danijela , Tabain Irena
Published: April 2022

Background: Due to rapid spread, the Omicron variant has become the dominant SARS-CoV-2 variant responsible for infections worldwide. We present the first detection of the Omicron variant in Croatia which resulted in rapid cross-border spreading. Methods: Whole-genome sequencing was performed using the Illumina MiniSeq sequencing system. SARS-CoV-2 lineages were identified using the PANGOLIN and GISAID databases. Results: The first case of the Omicron variant (BA.1.17) emerged in Croatia after a workshop held in Zagreb in November 2021. The patient reported a history of previous COVID-19 and received two doses of an mRNA vaccine. Three additional cases were detected among Croatian participants of the workshop. At the beginning of December, SARS-CoV-2 infection was confirmed in one participant from Montenegro and her husband. Phylogenetic analysis showed that the detected Omicron variants were closely related to the first Croatian case, confirming the connection with the workshop outbreak and rapid cross-border spreading. Subsequent analyses of SARS-CoV-2 positive samples in Croatia showed the rapid introduction of the Omicron variant and depletion of the Delta variant resulting in the fifth pandemic wave. Conclusions: Genomic monitoring and early detection of novel SARS-CoV-2 variants are essential to implement timely epidemiological interventions and reduce further transmission in the population.
Immune Responses Regulated by Key Periodontal Bacteria in Germ-Free Mice
Authors: Shen Xin , Yang Yutao , Li Jian , Zhang Bo , Wei Wei , Lu Changqing , Yan Caixia , Wei Hong , Li Yan
Published: April 2022

The immune dysregulation induced by periodontal bacteria has important roles in the development of periodontitis. However, the role of key periodontal bacteria in local and systemic immunity has not been comprehensively studied. Herein, to explore immunoregulation maps of key periodontal bacteria, a mono-colonized germ-free mice model with P. gingivalis, F. nucleatum, and T. denticola for two weeks was designed in this study. The alveolar bone loss was determined by micro-CT. A total of 14 types of innate and adaptive immune cells of the gingiva, spleen, and colon were detected by multi-color flow cytometry. P. gingivalis induced the strongest innate immune response in gingiva and mononuclear phagocytes (MNPs) changed most significantly, compared to F. nucleatum and T. denticola. Immune dysregulation of the colon was widely induced by F. nucleatum. T. denticola mainly induced immune disorder in spleen. ILC3s, Tregs, CD11B+ dendritic cells s, MNPs, macrophages, and plasmacytoid dendritic cells were the main types in response to key periodontal bacteria. However, the alveolar bone loss was not induced by key periodontal bacteria. In conclusion, the overall immunoregulation of monomicrobial stimuli to decipher the complexities of periodontitis was provided in this study. P. gingivalis, F. nucleatum, and T. denticola have different effects on local and systemic immunity in gingiva, colon, and spleen of germ-free mice.
SARS-CoV-2 Delta VOC in a Paucisymptomatic Dog, Italy
Authors: Pascucci Ilaria , Paniccià Marta , Giammarioli Monica , Biagetti Massimo , Duranti Anna , Campomori Pamela , Smilari Valerio , Ancora Massimo , Scialabba Silvia , Secondini Barbara , Cammà Cesare , Lorusso Alessio
Published: April 2022

Since the very beginning of the COVID-19 pandemic, SARS-CoV-2 detection has been described in several animal species. A total of 625 outbreaks in animals have been reported globally, affecting 17 species in 32 countries and the human source of infection has been recognized including pet owners, zookeepers, and farmers. In this report, we describe the case of a paucisymptomatic dog in Italy infected with SARS-CoV-2 from a household with three confirmed human cases of COVID-19 living in Pesaro (Marche region, Italy). The dog showed high viral RNA titers in the nasal and oropharyngeal swabs. In the nasal swab, SARS-CoV-2 RNA lasted for a least a week. By sequencing, the strain was assigned to the AY.23 lineage (PANGO), one of the sub-lineages of the major SARS-CoV-2 Delta variant of concern (VOC). Although we did not process the swabs of the three human cases, we strongly suspect a human origin for the dog infection. In this regard, AY.23 sequences, although never released thus far in the Marche region, were detected in the neighboring regions. Our findings highlight once more the need for a One Health approach for SARS-CoV-2 surveillance, management, and control, thus preventing viral spillover from animals to humans.
SARS-CoV-2: An Overview of the Genetic Profile and Vaccine Effectiveness of the Five Variants of Concern
Authors: Dumache Raluca , Enache Alexandra , Macasoi Ioana , Dehelean Cristina Adriana , Dumitrascu Victor , Mihailescu Alexandra , Popescu Roxana , Vlad Daliborca , Vlad Cristian Sebastian , Muresan Camelia
Published: April 2022

With the onset of the COVID-19 pandemic, enormous efforts have been made to understand the genus SARS-CoV-2. Due to the high rate of global transmission, mutations in the viral genome were inevitable. A full understanding of the viral genome and its possible changes represents one of the crucial aspects of pandemic management. Structural protein S plays an important role in the pathogenicity of SARS-CoV-2, mutations occurring at this level leading to viral forms with increased affinity for ACE2 receptors, higher transmissibility and infectivity, resistance to neutralizing antibodies and immune escape, increasing the risk of infection and disease severity. Thus, five variants of concern are currently being discussed, Alpha, Beta, Gamma, Delta and Omicron. In the present review, a comprehensive summary of the following critical aspects regarding SARS-CoV-2 has been made: (i) the genomic characteristics of SARS-CoV-2; (ii) the pathological mechanism of transmission, penetration into the cell and action on specific receptors; (iii) mutations in the SARS-CoV-2 genome; and (iv) possible implications of mutations in diagnosis, treatment, and vaccination.
Cobalt Bis-Dicarbollide Enhances Antibiotics Action towards Staphylococcus epidermidis Planktonic Growth Due to Cell Envelopes Disruption
Authors: Vaňková Eva , Lokočová Kristýna , Kašparová Petra , Hadravová Romana , Křížová Ivana , Maťátková Olga , Masák Jan , Šícha Václav
Published: April 2022

The emergence of antibiotic resistance in opportunistic pathogens represents a huge problem, the solution for which may be a treatment with a combination of multiple antimicrobial agents. Sodium salt of cobalt bis-dicarbollide (COSAN.Na) is one of the very stable, low-toxic, amphiphilic boron-rich sandwich complex heteroboranes. This compound has a wide range of potential applications in the biological sciences due to its antitumor, anti-HIV-1, antimicrobial and antibiofilm activity. Our study confirmed the ability of COSAN.Na (in the concentration range 0.2–2.48 µg/mL) to enhance tetracycline, erythromycin, and vancomycin action towards Staphylococcus epidermidis planktonic growth with an additive or synergistic effect (e.g., the combination of 1.24 µg/mL COSAN.Na and 6.5 µg/mL TET). The effective inhibitory concentration of antibiotics was reduced up to tenfold most efficiently in the case of tetracycline (from 65 to 6.5 µg/mL). In addition, strong effect of COSAN.Na on disruption of the cell envelopes was determined using propidium iodide uptake measurement and further confirmed by transmission electron microscopy. The combination of amphiphilic COSAN.Na with antibiotics can therefore be considered a promising way to overcome antibiotic resistance in Gram-positive cocci.
Growth of MIN-6 Cells on Salmon Fibrinogen Scaffold Improves Insulin Secretion
Authors: Laidmäe Ivo , Aints Alar , Uibo Raivo
Published: April 2022

The incidence of type I diabetes has been increasing worldwide at an annual rate of approximately 3%. One of the strategies to treat type I diabetes is islet transplantation, in which damaged β-cells are replaced with new islets. To improve β-cells’ expansion and pseudoislet formation, studies are focusing on using extracellular-matrix-resembling substrates. We evaluated the potential of salmon fibrinogen and chitosan electrospun scaffold as cell substrate for cultivating MIN-6 cells. The morphology of cells, insulin secretion and gene expression was evaluated and compared with other substrates (nanofibrous scaffold, microporous scaffold and tissue culture polystyrene). We found that all tested 3D conditions favored the pseudoislet formation of MIN-6 cells. The insulin secretion of MIN-6 cells after stimulation with high-glucose media shows approximately a 9-fold increase compared to the control group when a fibrinogen/chitosan-based electrospun scaffold was used for cultivation. The differences in insulin secretion were corroborated by differences in gene expression. The differences in insulin secretion could probably be attributed to the differences in the mechanical and/or chemical nature of the tested substrates.
Chitosan-Hyaluronan Nanoparticles for Vinblastine Sulfate Delivery: Characterization and Internalization Studies on K-562 Cells
Authors: Cannavà Carmela , De Gaetano Federica , Stancanelli Rosanna , Venuti Valentina , Paladini Giuseppe , Caridi Francesco , Ghica Corneliu , Crupi Vincenza , Majolino Domenico , Ferlazzo Guido , Tommasini Silvana , Ventura Cinzia Anna
Published: April 2022

In the present study, we developed chitosan/hyaluronan nanoparticles (CS/HY NPs) for tumor targeting with vinblastine sulfate (VBL), that can be directed to the CD44 transmembrane receptor, over-expressed in cancer cells. NPs were prepared by coating with HY-preformed chitosan/tripolyphosphate (CS/TPP) NPs, or by polyelectrolyte complexation of CS with HY. NPs with a mean hydrodynamic radius (RH) of 110 nm, 12% polydispersity index and negative zeta potential values were obtained by a direct complexation process. Transmission Electron Microscopy (TEM) images showed spherical NPs with a non-homogeneous matrix, probably due to a random localization of CS and HY interacting chains. The intermolecular interactions occurring between CS and HY upon NPs formation were experimentally evidenced by micro-Raman (µ-Raman) spectroscopy, through the analysis of the spectral changes of characteristic vibrational bands of HY during NP formation, in order to reveal the involvement of specific chemical groups in the process. Optimized NP formulation efficiently encapsulated VBL, producing a drug sustained release for 20 h. In vitro studies demonstrated a fast internalization of labeled CS/HY NPs (within 6 h) on K-562 human myeloid leukemia cells. Pre-saturation of CD44 by free HY produced a slowing-down of NP uptake over 24 h, demonstrating the need of CD44 for the internalization of HY-based NPs.
Drug-Induced Immune Thrombocytopenia Toxicity Prediction Based on Machine Learning
Authors: Wang Binyou , Tan Xiaoqiu , Guo Jianmin , Xiao Ting , Jiao Yan , Zhao Junlin , Wu Jianming , Wang Yiwei
Published: April 2022

Drug-induced immune thrombocytopenia (DITP) often occurs in patients receiving many drug treatments simultaneously. However, clinicians usually fail to accurately distinguish which drugs can be plausible culprits. Despite significant advances in laboratory-based DITP testing, in vitro experimental assays have been expensive and, in certain cases, cannot provide a timely diagnosis to patients. To address these shortcomings, this paper proposes an efficient machine learning-based method for DITP toxicity prediction. A small dataset consisting of 225 molecules was constructed. The molecules were represented by six fingerprints, three descriptors, and their combinations. Seven classical machine learning-based models were examined to determine an optimal model. The results show that the RDMD + PubChem-k-NN model provides the best prediction performance among all the models, achieving an area under the curve of 76.9% and overall accuracy of 75.6% on the external validation set. The application domain (AD) analysis demonstrates the prediction reliability of the RDMD + PubChem-k-NN model. Five structural fragments related to the DITP toxicity are identified through information gain (IG) method along with fragment frequency analysis. Overall, as far as known, it is the first machine learning-based classification model for recognizing chemicals with DITP toxicity and can be used as an efficient tool in drug design and clinical therapy.
Transcriptomic Analysis Elaborates the Resistance Mechanism of Grapevine Rootstocks against Salt Stress
Authors: Zhao Fanggui , Zheng Ting , Liu Zhongjie , Fu Weihong , Fang Jinggui
Published: April 2022

Grapes are subject to a wide range of climatic conditions during their life cycle, but the use of rootstocks can effectively ameliorate the effects of abiotic stress. However, the tolerance mechanism of different grape rootstock varieties varies under various stresses, and systematic research on this aspect is limited. On the basis of previous research, transcriptome sequencing was performed on three tolerant grape rootstock varieties (3309C, 520A, 1103P) and three intolerant grape rootstock varieties (5BB, 101–14, Beta). In total, 56,478,468 clean reads were obtained. One hundred and ten genes only existed in all combinations during P1 with a downregulated trend, and 178 genes existed only in P1 of tolerant grape rootstock varieties. Salt treatment firstly affected the photosynthesis of leaves, and tolerant varieties weakened or even eliminated this effect through their own mechanisms in the later stage. Tolerant varieties mobilized a large number of MFs during the P2 stage, such as hydrolase activity, carboxypeptidase activity, and dioxygenase activity. Carbon metabolism was significantly enriched in P1, while circadian rhythm and flavonoid biosynthesis were only enriched in tolerant varieties. In the intolerant varieties, photosynthesis-related pathways were always the most significantly enriched. There were large differences in the gene expression of the main signal pathways related to salt stress in different varieties. Salt stress affected the expression of genes related to plant abiotic stress, biotic stress, transcription factors, hormones, and secondary metabolism. Tolerant varieties mobilized more bHLH, WRKY, and MYB transcription factors to respond to salt stress than intolerant varieties. In the tolerant rootstocks, SOS was co-expressed. Among these, SOS1 and SOS2 were upregulated, and the SOS3 and SOS5 components were downregulated. The genes of heat shock proteins and the phenylalanine pathway were upregulated in the tolerant varieties. These findings outline a tolerance mechanism model for rootstocks for coping with osmotic stress, providing important information for improving the resistance of grapes under global climate change.
Morphological and Molecular Characterization of Some Alternaria Species Isolated from Tomato Fruits Concerning Mycotoxin Production and Polyketide Synthase Genes
Authors: Saleem Abdelrahman , El-Shahir Amany A.
Published: April 2022

Tomatoes (Lycopersicon esculentum) are one of the main crops grown in Egypt. The fungal black spot illness of fruits is usually associated with the secretion of mycotoxin by Alternaria toxigenic species. Twenty Alternaria isolates were isolated from infected tomatoes fruits by baiting technique, morphologically identified to species level, and confirmed using Internal Transcribed Spacer (ITS) gene sequencing. ITS gene sequencing of fragments obtained 547, 547, 542, 554, and 547 bp for A. alternata, A. brassicicola, A. citri, A. radicina, and A. tenuissima, respectively. Alternaria species were investigated for mycotoxin production using the high-performance liquid chromatography (HPLC) technique. The data from the HPLC analysis showed that the mycotoxins were determined in four out of five Alternaria species, with the incidence ranging from 0.89–9.85 µg/mL of fungal extract at different retention times. Alternaria alternata was the most active species and produced three types of toxins. Polyketide synthase genes (pksH and pksJ) which are involved in the Alternaria toxin’s biosynthesis were also amplified from the DNA of Alternaria species.
Exploration of the Genetic Diversity of Solina Wheat and Its Implication for Grain Quality
Authors: De Flaviis Riccardo , Tumino Giorgio , Terzi Valeria , Morcia Caterina , Santarelli Veronica , Sacchetti Giampiero , Mastrocola Dino
Published: April 2022

Different Solina wheat accessions (n = 24) collected in the Abruzzo region (Italy) were studied using 45,000 SNP markers generated from the DarTseq platform. The structure of genetic data was analyzed by Principal Component Analysis and Hierarchical Cluster analysis that revealed the existence of two main clusters (Clu1 and Clu2) characterized by samples with different geographical origin. The Solina genetic dataset was further merged and analyzed with a public genetic one provided by CIMMYT containing 25,963 genotypes from all over the world. The Solina accessions occupied a vast space, thus confirming a high heterogeneity of this landrace that, nevertheless, is considerably unique and placed quite far from other clusters. Clu1 and Clu2 divergence were clearly visible. Solina clusters were genetically closer to landraces from Turkey and the central fertile crescent than to the Italian genotypes present in the dataset. Selected commercial quality traits of accessions of the two Solina clusters were analyzed (yield, thousand kernel weight, test weight, and protein content), and significant differences were found between clusters. The results of this investigation did not highlight any relationships of Solina with Italian genotypes, and confirmed its wide genetic diversity by permitting to identify two genetic groups with distinct origin and quality traits.
3D Natural Mesoporous Biosilica-Embedded Polysulfone Made Ultrafiltration Membranes for Application in Separation Technology
Authors: Paidi Murali Krishna , Polisetti Veerababu , Damarla Krishnaiah , Singh Puyam Sobhindro , Mandal Subir Kumar , Ray Paramita
Published: April 2022

Diatoms are the most abundant photosynthetic microalgae found in all aquatic habitats. In the extant study, the spent biomass (after lipid extraction) of the centric marine diatom Thalassiosira lundiana CSIRCSMCRI 001 was subjected to acid digestion for the extraction of micro composite inorganic biosilica. Then, the resulting three-dimensional mesoporous biosilica material (diatomite) was used as a filler in polysulfone (PSF) membrane preparation by phase inversion. The fabricated PSF/diatomite composite membranes were characterized by SEM-EDX, TGA, and ATR-IR, and their performances were evaluated. The number of pores and pore size were increased on the membrane surface with increased diatomite in the composite membranes as compared to the control. The diatomite composite membranes had high hydrophilicity and thermal stability, lower surface roughness, and excellent water permeability. Membranes with high % diatomite, i.e., PSF/Dia0.5, had a maximum water flux of 806.8 LMH (Liter/m2/h) at 20 psi operating pressure. High-diatomite content membranes also exhibited the highest rejection of BSA protein (98.5%) and rhodamine 6G (94.8%). Similarly, in biomedical rejection tests, the PSF/Dia0.5 membrane exhibited a maximum rejection of ampicillin (75.84%) and neomycin (85.88%) at 20 Psi pressure. In conclusion, the mesoporous inorganic biosilica material was extracted from spent biomass of diatom and successfully used in filtration techniques. The results of this study could enhance the application of natural biogenic porous silica materials in wastewater treatment for water recycling.
Synthesis and In Vitro Characterization of Ascorbyl Palmitate-Loaded Solid Lipid Nanoparticles
Authors: Ledinski Maja , Marić Ivan , Peharec Štefanić Petra , Ladan Iva , Caput Mihalić Katarina , Jurkin Tanja , Gotić Marijan , Urlić Inga
Published: April 2022

Antitumor applications of ascorbic acid (AA) and its oxidized form dehydroascorbic acid (DHA) can be quite challenging due to their instability and sensitivity to degradation in aqueous media. To overcome this obstacle, we have synthesized solid lipid nanoparticles loaded with ascorbyl palmitate (SLN-AP) with variations in proportions of the polymer Pluronic F-68. SLNs were synthesized using the hot homogenization method, characterized by measuring the particle size, polydispersity, zeta potential and visualized by TEM. To investigate the cellular uptake of the SLN, we have incorporated coumarin-6 into the same SLN formulation and followed their successful uptake for 48 h. We have tested the cytotoxicity of the SLN formulations and free ascorbate forms, AA and DHA, on HEK 293 and U2OS cell lines by MTT assay. The SLN-AP in both formulations have a cytotoxic effect at lower concentrations when compared to ascorbate applied the form of AA or DHA. Better selectivity for targeting tumor cell line was observed with 3% Pluronic F-68. The antioxidative effect of the SLN-AP was observed as early as 1 h after the treatment with a small dose of ascorbate applied (5 µM). SLN-AP formulation with 3% Pluronic F-68 needs to be further optimized as an ascorbate carrier due to its intrinsic cytotoxicity.
Effect of Addition of Polyurea as an Aggregate in Mortars: Analysis of Microstructure and Strength
Authors: Chacon Hernan , Cano Heidis , Fernández Joaquin Hernández , Guerra Yoleima , Puello-Polo Esneyder , Ríos-Rojas John Fredy , Ruiz Yolima
Published: April 2022

The addition of polymers in construction is a new tendency and an important step toward the production of structures with better functional properties. This work investigates the addition of polyurea (PU) as a polymeric material in mortars. Polymer mortars were manufactured with the addition of polyurea retained in different sieves (T50 and T100) and different concentrations (2% and 5%). The characterization of the, polyurea (PU)control mortar (PU0%) and manufactured polyurea mortars (PU2%T50, PU5%T50, PU2%T100, and PU5%T100) was conducted by means of morphological analysis, SEM, XRF, TGA, and a compressive strength test of hydraulic mortars. The results show that mortars with polyurea retained in sieve 100 with a particle size of 150 μm exhibit better thermal behavior and a greater resistance to compression with a concentration of 5% polyurea with respect to the other samples. The present work reveals that polyurea retained in sieve 100 can be considered as a polymeric additive for mortars, indicating that it could be a candidate for applications such as construction.