bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of High-Risk Extramedullary Relapse Factors in Newly Diagnosed MM Patients
Authors: Yue Xiaoyan , He Donghua , Zheng Gaofeng , Yang Yang , Han Xiaoyan , Li Yi , Zhao Yi , Wu Wenjun , Chen Qingxiao , Zhang Enfang , Cai Zhen , He Jingsong
Published: December 2022

Extramedullary relapse of multiple myeloma (MM) is often resistant to existing treatments, and has an extremely poor prognosis, but our understanding of extramedullary relapse is still limited. The incidence, clinical characteristics, impact on the prognosis of extramedullary relapse, and the risk factors for extramedullary relapse in NDMM patients were analyzed. Among the 471 NDMM patients, a total of 267 patients had disease relapse during follow-up, including 64 (24.0%) patients with extramedullary relapse. Extramedullary relapse was more common in patients with younger age, IgD subtype, elevated LDH, extensive osteolytic lesions, extramedullary involvement, and spleen enlargement at the time of MM diagnosis. Survival analysis showed that extramedullary relapse patients had significantly worse median OS than patients with relapse but without extramedullary involvement (30.8 months vs. 53.6 months, p = 0.012). Multivariate analysis confirmed that elevated LDH (OR = 2.09, p = 0.023), >2 osteolytic lesions (OR = 3.70, p < 0.001), extramedullary involvement (OR = 3.48, p < 0.001) and spleen enlargement (OR = 2.27, p = 0.011) at the time of MM diagnosis were independent risk factors for extramedullary relapse in NDMM patients. Each of the above four factors was assigned a value of 1 to form the extramedullary relapse prediction score, and the 3-year extramedullary relapse rates of patients in the 0–2 and 3–4 score groups were 9.0 % and 76.7 %, respectively. This study suggested that extramedullary relapse was associated with poor clinical characteristics and poor prognosis in NDMM patients. The extramedullary relapse prediction score model composed of LDH, osteolytic lesions, extramedullary involvement and spleen enlargement has a better ability to predict extramedullary relapse than the existing ISS and R-ISS stages.
Intra-Tumoral Secondary Follicle-like Tertiary Lymphoid Structures Are Associated with a Superior Prognosis of Overall Survival of Perihilar Cholangiocarcinoma
Authors: Zhang Fa-Peng , Zhu Ke , Zhu Tai-Feng , Liu Chao-Qun , Zhang Hong-Hua , Xu Lei-Bo , Xiao Gang , Liu Chao
Published: December 2022

Ectopic lymphoid structures termed tertiary lymphoid structures (TLSs) have an immunomodulatory function and positively affect prognosis in certain cancers. However, their clinical relevance and prognostic utility in perihilar cholangiocarcinoma (pCCA) are unknown. Therefore, determining the involvement and prognostic utility of TLSs in pCCA is the aim of this study. Ninety-three patients with surgically resected pCCA were included retrospectively. Hematoxylin and eosin and immunohistochemical staining identified and classified the TLSs, and multiplex immunofluorescence determined the TLS composition in the pCCA sample. The correlations between clinical features and TLSs were analyzed using either Fisher’s exact test or the Chi-squared test. Recurrence-free survival (RFS) and overall survival (OS) correlations with TLSs were analyzed using Cox regression and Kaplan–Meier analyses. We identified TLSs in 86% of patients with pCCA, including lymphoid aggregates (6.45%), primary (13.98%) and secondary follicles (65.59%). Patients with intra-tumoral secondary follicle-like TLSs (S-TLSs) had better OS (p = 0.003) and RFS (p = 0.0313). The multivariate analysis identified the presence of S-TLSs as a good independent prognostic indicator for OS but not for RFS. Interestingly, the presence of S-TLS only indicated better 5-year OS in 54 patients without lymph node metastasis (LNM−, p = 0.0232) but not in the 39 patients with lymph node metastasis (LNM+, p = 0.1244). Intra-tumoral S-TLSs predicted longer OS in patients with surgically resected pCCA, suggesting intra-tumoral S-TLSs’ contribution to effective antitumor immunity and that S-TLSs hold promise for diagnostic and therapeutic development in pCCA.
Imidazolium-Modified Silica Gel for Highly Selective Preconcentration of Ag(I) from the Nitric Acid Medium
Authors: Konshina Dzhamilay N. , Lupanova Ida A. , Konshin Valery V.
Published: December 2022

The ion-exchange behavior of an organomineral material with an imidazolium (1-methyl-3-(prop-2-yn-1-yl)-1H-imidazol-3-ium bromide)-modified silica gel was studied for the extraction of Ag(I) from nitric acid media. The extraction from multicomponent systems containing Fe(III), Co(II), Ni(II), Cu(II), Pb(II), and Mn(II) in 100- and 1000-fold molar excesses with respect to Ag(I) was shown to occur with high selectivity. Based on the data of X-ray diffraction and X-ray fluorescence spectroscopy for samples of modified silica gel, a mixed ion exchange–adsorption mechanism for the extraction of Ag(I) was proposed. The effect of the phase contact time and the concentration of nitric acid on the distribution coefficient of Ag(I) was studied. The selectivity factors of the extraction of Ag(I) from multicomponent systems containing foreign cations in 100- and 1000-fold molar excesses under steady-state and dynamic concentration conditions were calculated.
Adaptive List Flip Decoder for Polar Codes with High-Order Error Correction Capability and a Simplified Flip Metric
Authors: Lv Yansong , Yin Hang , Yang Zhanxin , Wang Yuhuan , Dai Jingxin
Published: December 2022

Designing an efficient decoder is an effective way to improve the performance of polar codes with limited code length. List flip decoders have received attention due to their good performance trade-off between list decoders and flip decoders. In particular, the newly proposed dynamic successive cancellation list flip (D-SCLF) decoder employs a new flip metric to effectively correct high-order errors and thus enhances the performance potential of present list flip decoders. However, this flip metric introduces extra exponential and logarithmic operations, and the number of these operations rises exponentially with the increase in the order of error correction and the number of information bits, which then limits its application value. Therefore, we designed an adaptive list flip (ALF) decoder with a new heuristic simplified flip metric, which replaces these extra nonlinear operations in the original flip metric with linear operations. Simulation results show that the simplified flip metric does not reduce the performance of the D-SCLF decoder. Moreover, based on the in-depth theoretical analyses of the combination of the adaptive list and the list flip decoders, the ALF decoder adopts the adaptive list to further reduce the average complexity.
Circular Economy Models in Industry: Developing a Conceptual Framework
Authors: Marinina Oksana , Kirsanova Natalia , Nevskaya Marina
Published: December 2022

One of the trends in sustainable economic development is the transition to circular business models, which aim to optimize goods and material flows by taking into account their cyclical nature at all production stages. Adapting circular business models to mining and mineral processing operations can serve as an impetus for mining companies to upgrade and move to a new level of technological sophistication. This article attempts to develop a conceptual framework for circular business models factoring in the nature of production chains in coal mining, power generation, and metal production to reduce production costs, expand the product range, improve sustainable development indicators, and deliver growth in company value. This article is based on desk studies that were aimed at analyzing the efficiency of circular models, organizing data on experience in rational resource use in the mining industry, and transforming basic circular models into adapted ones for the environment in which coal companies operate. This study developed a conceptual framework of options for the implementation and evaluation of circular business models using an interdisciplinary approach and taking into account the specific features of coal companies and the principle of a resource being valuable throughout its whole life cycle. The proposed conceptual framework of circular business models can be used by Russian coal companies to design corporate strategies and long-term development plans.
Growth Hormone-Releasing Hormone Antagonist JV-1-36 Suppresses Reactive Oxygen Species Generation in A549 Lung Cancer Cells
Authors: Kubra Khadeja-Tul , Akhter Mohammad S. , Apperley Kaitlyn , Barabutis Nektarios
Published: December 2022

Growth hormone-releasing hormone (GHRH) and its receptors are expressed in a variety of human cancers, and have been involved in malignancies. GHRH antagonists (GHRHAnt) were developed to suppress tumor progression and metastasis. Previous studies demonstrate the involvement of reactive oxygen species (ROS) in cancer progression. Herein, we investigate the effect of a commercially available GHRH antagonist, namely JV-1-36, in the redox status of the A549 human cancer cell line. Our results suggest that this peptide significantly reduces ROS production in those cells in a time-dependent manner and counteracts H2O2-induced ROS. Our study supports the anti-oxidative effects of JV-1-36 and contributes in our knowledge towards the in vitro effects of GHRHAnt in cancers.
An Irish Multi-Centre Study of Behaviours, Attitudes and Barriers to Exercise in Inflammatory Bowel Disease, a Survey from the Patient’s Perspective
Authors: Gettigan Mc N. , Allen K. , Foley C. , Bennett S. , Lardner C. , Lukose T. , Kelly O. , O’Toole A. , Boland K.
Published: December 2022

Background: Physical activity (PA) in inflammatory bowel disease (IBD) has many potential favourable outcomes including anti-inflammatory effects, improvement in quality of life and improvements in patient body composition. It is recognised that patients with IBD have a significantly decreased exercise tolerance. Aim: 1. To assess physical activity levels, behaviours and barriers to PA in IBD. 2. To assess the likelihood of patients with IBD to engage in a community-based exercise programme. 3. To examine the presence of body image concerns in IBD. Method: Patient surveys were distributed in Beaumont and Connolly Hospitals between October and December 2021. Descriptive statistics, Chi-squared testing and Pearson’s correlations were completed using Minitab. p < 0.05 denoted statistical significance. Results: Data were recorded for a total of 203 patients. Out of all patients, 62% (n = 126) had Crohn’s disease (CD). Over half of the cohort were male (n = 115). Mean weight among females was 75 kg and 83 kg among males. Exercise behaviours: Out of all patients, 71% exercise regularly, on average for 59 min, 3.2 days/week. Walking was the most common form of PA (74%). A post-diagnosis change in exercise behaviour was found in 66% with three-quarters exercising less. The primary barrier to exercise was fatigue (54%). Female gender (p = 0.007) and age < 45 years (p = 0.02) were associated with body image dissatisfaction reported in 62% of patients. Conclusion: These data demonstrate the patient-reported impact of IBD on patient participation in PA. Concerns regarding body image were common and associated with gender and age. A feasibility study of a physician-derived exercise programme in patients with active IBD is underway in Beaumont Hospital to determine the effect on patient response to therapy, inflammation and body composition outcomes (NCT05174754).
Underneath the Purple Stain
Authors: Pinheiro Catarina , Miller Ana Zélia , Vaz Patrícia , Caldeira Ana Teresa , Casanova Conceição
Published: December 2022

The Alcobacenses are one of the most important Portuguese collections of Monastic codices. During a campaign study to further advance our knowledge on this important legacy and its state of conservation, a heavily deteriorated codex (ALC.338) stood out due to the presence of purple stains on the lower margins on virtually all folios. In some of them, the purple stains are accompanied by yellow and brown patches as well. Also noticed was the presence of these purple spots on the white tawed leather covering the codex. The codex was analyzed macro and microscopically, chemically and biologically using state-of-the-art technology such as next-generation sequencing. The biological deterioration associated with the appearance of these purple spots arises from the inside out and reveals significant abundance of the bacterial genus Saccharopolyspora sp., which accounted for 86% of the bacterial genera identified. For the fungal population, the most common genus was Malassezia sp. Visual inspection of the sample confirmed the presence of fungal and bacterial biofilms. Pressing questions, comparison to similar studies and future perspectives are also given.
Does a Little Difference Make a Big Difference? Bovine β-Casein A1 and A2 Variants and Human Health—An Update
Authors: Cieślińska Anna , Fiedorowicz Ewa , Rozmus Dominika , Sienkiewicz-Szłapka Edyta , Jarmołowska Beata , Kamiński Stanisław
Published: December 2022

For over 20 years, bovine beta-casein has been a subject of increasing scientific interest because its genetic A1 variant during gastrointestinal digestion releases opioid-like peptide β-casomorphin-7 (β-CM-7). Since β-CM-7 is involved in the dysregulation of many physiological processes, there is a growing discussion of whether the consumption of the β-casein A1 variant has an influence on human health. In the last decade, the number of papers dealing with this problem has substantially increased. The newest clinical studies on humans showed a negative effect of variant A1 on serum glutathione level, digestive well-being, cognitive performance score in children, and mood score in women. Scientific reports in this field can affect the policies of dairy cattle breeders and the milk industry, leading to the elimination of allele A1 in dairy cattle populations and promoting milk products based on milk from cows with the A2A2 genotype. More scientific proof, especially in well-designed clinical studies, is necessary to determine whether a little difference in the β-casein amino acid sequence negatively affects the health of milk consumers.
Annulation of Perimidines with 5-Alkynylpyrimidines en Route to 7-Formyl-1,3-Diazopyrenes
Authors: Shcherbakov Stanislav V. , Aksenov Alexander V. , Vendin Maksim V. , Shcherbakova Viktoria Yu. , Ivanova Anna Yu. , Shcheglov Maksim O. , Ovcharov Sergei N. , Rubin Michael
Published: December 2022

Unusual rearrangements were shown to accompany Brønsted acid-assisted peri-annulations of 1H-perimidines with 5-alkynylpyrimidines. These transformations take different routes depending on the nature of acetylene precursor, and lead to the formation of 7-formyl-1,3-diazopyrenes.
Quasispecies Analysis of SARS-CoV-2 of 15 Different Lineages during the First Year of the Pandemic Prompts Scratching under the Surface of Consensus Genome Sequences
Authors: Bader Wahiba , Delerce Jeremy , Aherfi Sarah , La Scola Bernard , Colson Philippe
Published: December 2022

The tremendous majority of SARS-CoV-2 genomic data so far neglected intra-host genetic diversity. Here, we studied SARS-CoV-2 quasispecies based on data generated by next-generation sequencing (NGS) of complete genomes. SARS-CoV-2 raw NGS data had been generated for nasopharyngeal samples collected between March 2020 and February 2021 by the Illumina technology on a MiSeq instrument, without prior PCR amplification. To analyze viral quasispecies, we designed and implemented an in-house Excel file (“QuasiS”) that can characterize intra-sample nucleotide diversity along the genomes using data of the mapping of NGS reads. We compared intra-sample genetic diversity and global genetic diversity available from Nextstrain. Hierarchical clustering of all samples based on the intra-sample genetic diversity was performed and visualized with the Morpheus web application. NGS mapping data from 110 SARS-CoV-2-positive respiratory samples characterized by a mean depth of 169 NGS reads/nucleotide position and for which consensus genomes that had been obtained were classified into 15 viral lineages were analyzed. Mean intra-sample nucleotide diversity was 0.21 ± 0.65%, and 5357 positions (17.9%) exhibited significant (>4%) diversity, in ≥2 genomes for 1730 (5.8%) of them. ORF10, spike, and N genes had the highest number of positions exhibiting diversity (0.56%, 0.34%, and 0.24%, respectively). Nine hot spots of intra-sample diversity were identified in the SARS-CoV-2 NSP6, NSP12, ORF8, and N genes. Hierarchical clustering delineated a set of six genomes of different lineages characterized by 920 positions exhibiting intra-sample diversity. In addition, 118 nucleotide positions (0.4%) exhibited diversity at both intra- and inter-patient levels. Overall, the present study illustrates that the SARS-CoV-2 consensus genome sequences are only an incomplete and imperfect representation of the entire viral population infecting a patient, and that quasispecies analysis may allow deciphering more accurately the viral evolutionary pathways.
Deciphering the Role of miR-200c-3p in Type 1 Diabetes (Subclinical Cardiovascular Disease) and Its Correlation with Inflammation and Vascular Health
Authors: Bakhashab Sherin , Yuen Yeoh Megan Li , Coulson David J. , Steel Samuel Christian , Ray Sabina L. , Weaver Jolanta U.
Published: December 2022

Uncomplicated type 1 diabetes (T1DM) displays all features of subclinical cardiovascular disease (CVD) as is associated with inflammation, endothelial dysfunction and low endothelial progenitor cells. MiR-200c-3p has been shown in animal tissues to be pro-atherogenic. We aimed to explore the role of miR-200c-3p in T1DM, a model of subclinical CVD. 19 samples from T1DM patients and 20 from matched controls (HC) were analyzed. MiR-200c in plasma and peripheral blood mononuclear cells (PBMCs) was measured by real-time quantitative polymerase chain reaction. The results were compared with the following indices of vascular health: circulating endothelial progenitor cells, (CD45dimCD34+VEGFR-2+ or CD45dimCD34+CD133+) and proangiogenic cells (PACs). MiR-200c-3p was significantly downregulated in PBMCs but not in plasma in T1DM. There was a significant negative correlation between the expression of miR-200c-3p and HbA1c, interleukin-7 (IL-7), vascular endothelial growth factor-C (VEGF-C), and soluble vascular cell adhesion molecule-1, and a positive correlation with CD45dimCD34+VEGFR-2+, CD45dimCD34+CD133+ and PACs. Receiver operating curve analyses showed miR-200c-3p as a biomarker for T1DM with significant downregulation of miR-200c-3p, possibly defining subclinical CVD at HbA1c > 44.8 mmol/mol (6.2%). In conclusion, downregulated miR-200c-3p in T1DM correlated with diabetic control, VEGF signaling, inflammation, vascular health and targeting VEGF signaling, and may define subclinical CVD. Further prospective studies are necessary to validate our findings in a larger group of patients.
Novel Antitumor Agents Based on Fluorescent Benzofurazan Derivatives and Mesoporous Silica
Authors: Tudose Madalina , Culita Daniela C. , Baratoiu-Carpen Rodica D. , Mitran Raul-Augustin , Kuncser Andrei , Romanitan Cosmin , Popescu Roxana Cristina , Savu Diana Iulia
Published: December 2022

Two novel fluorescent mesoporous silica-based hybrid materials were obtained through the covalent grafting of [4-hydrazinyl-7-nitrobenz-[2,1,3-d]-oxadiazole (NBDH) and N1-(7-nitrobenzo[c][1,2,5]-oxadiazol-4-yl) benzene-1,2-diamine (NBD-PD), respectively, inside the channels of mesoporous silica SBA-15. The presence of fluorescent organic compounds (nitrobenzofurazan derivatives) was confirmed by infrared spectroscopy (IR), X-ray photoelectron spectroscopy (XPS), thermal analysis (TG), and fluorescence spectroscopy. The nitrogen physisorption analysis showed that the nitrobenzofurazan derivatives were distributed uniformly on the internal surface of SBA-15, the immobilization process having a negligible effect on the structure of the support. Their antioxidant activity was studied by measuring the ability to reduce free radicals DPPH (free radical scavenging activity), in order to formulate potential applications of the materials obtained. Cytotoxicity of the newly synthesized materials, SBA-NBDH and SBA-NBD-PD, was evaluated on human B16 melanoma cells. The morphology of these cells, internalization and localization of the investigated materials in melanoma and fibroblast cells were examined through fluorescence imaging. The viability of B16 (3D) spheroids after treatment with SBA-NBDH and SBA-NBD-PD was evaluated using MTS assay. The results showed that both materials induced a selective antiproliferative effect, reducing to various degrees the viability of melanoma cells. The observed effect was enhanced with increasing concentration. SBA-NBD-PD exhibited a higher antitumor effect compared to SBA-NBDH starting with a concentration of 125 µg/mL. In both cases, a significantly more pronounced antiproliferative effect on tumor cells compared to normal cells was observed. The viability of B16 spheroids dropped by 40% after treatment with SBA-NBDH and SBA-NBD-PD at 500 µg/mL concentration, indicating a clear cytotoxic effect of the tested compounds. These results suggest that both newly synthesized biomaterials could be promising antitumor agents for applications in cancer therapy.
Lung Organoids for Hazard Assessment of Nanomaterials
Authors: Kastlmeier Miriam T. , Guenther Eva M. , Stoeger Tobias , Voss Carola
Published: December 2022

Lung epithelial organoids for the hazard assessment of inhaled nanomaterials offer a promising improvement to in vitro culture systems used so far. Organoids grow in three-dimensional (3D) spheres and can be derived from either induced pluripotent stem cells (iPSC) or primary lung tissue stem cells from either human or mouse. In this perspective we will highlight advantages and disadvantages of traditional culture systems frequently used for testing nanomaterials and compare them to lung epithelial organoids. We also discuss the differences between tissue and iPSC-derived organoids and give an outlook in which direction the whole field could possibly go with these versatile tools.
The Combination of Panobinostat and Melphalan for the Treatment of Patients with Multiple Myeloma
Authors: Gkotzamanidou Maria , Terpos Evangelos , Dimopoulos Meletios A. , Souliotis Vassilis L.
Published: December 2022

Histone deacetylase inhibitors show synergy with several genotoxic drugs. Herein, we investigated the biological impact of the combined treatment of panobinostat and melphalan in multiple myeloma (MM). DNA damage response (DDR) parameters and the expression of DDR-associated genes were analyzed in bone marrow plasma cells (BMPCs) and peripheral blood mononuclear cells (PBMCs) from 26 newly diagnosed MM patients. PBMCs from 25 healthy controls (HC) were examined in parallel. Compared with the ex vivo melphalan-only treatment, combined treatment with panobinostat and melphalan significantly reduced the efficiency of nucleotide excision repair (NER) and double-strand-break repair (DSB/R), enhanced the accumulation of DNA lesions (monoadducts and DSBs), and increased the apoptosis rate only in patients’ BMPCs (all p < 0.001); marginal changes were observed in PBMCs from the same patients or HC. Accordingly, panobinostat pre-treatment decreased the expression levels of critical NER (DDB2, XPC) and DSB/R (MRE11A, PRKDC/DNAPKc, RAD50, XRCC6/Ku70) genes only in patients’ BMPCs; no significant changes were observed in PBMCs from patients or HC. Together, our findings demonstrate that panobinostat significantly increased the melphalan sensitivity of malignant BMPCs without increasing the melphalan sensitivity of PBMCs from the same patients, thus paving the way for combination therapies in MM with improved anti-myeloma efficacy and lower side effects.
Degradation of the Selected Antibiotic in an Aqueous Solution by the Fenton Process: Kinetics, Products and Ecotoxicity
Authors: Adamek Ewa , Masternak Ewa , Sapińska Dominika , Baran Wojciech
Published: December 2022

Sulfonamides used in veterinary medicine can be degraded via the Fenton processes. In the premise, the process should also remove the antimicrobial activity of wastewater containing antibiotics. The kinetics of sulfathiazole degradation and identification of the degradation products were investigated in the experiments. In addition, their toxicity against Vibrio fischeri, the MARA® assay, and unselected microorganisms from a wastewater treatment plant and the river was evaluated. It was found that in the Fenton process, the sulfathiazole degradation was described by the following kinetic equation: r0 = k CSTZ−1 or 0 CFe(II)3 CH2O20 or 1 CTOC−2, where r0 is the initial reaction rate, k is the reaction rate constant, C is the concentration of sulfathiazole, Fe(II) ions, hydrogen peroxide and total organic carbon, respectively. The reaction efficiency and the useful pH range (up to pH 5) could be increased by UVa irradiation of the reaction mixture. Eighteen organic degradation products of sulfathiazole were detected and identified, and a possible degradation mechanism was proposed. An increase in the H2O2 dose, to obtain a high degree of mineralization of sulfonamide, resulted in an increase in the ecotoxicity of the post-reaction mixture.
Glucocorticoid Effects on Proteoglycans and Glycosaminoglycans
Authors: Strokotova Anastasia V. , Grigorieva Elvira V.
Published: December 2022

Glucocorticoids are steroid hormones that play diverse roles in numerous normal and pathological processes. They are actively used to treat a wide variety of diseases, including neurodegenerative and inflammatory diseases, cancers, and COVID-19, among others. However, the long-term use of glucocorticoids is associated with numerous side effects. Molecular mechanisms of these negative side effects are not completely understood. Recently, arguments have been made that one such mechanisms may be related to the influence of glucocorticoids on O-glycosylated components of the cell surface and extracellular matrix, in particular on proteoglycans and glycosaminoglycans. The potential toxic effects of glucocorticoids on these glycosylated macromolecules are particularly meaningful for brain physiology because proteoglycans/glycosaminoglycans are the main extracellular components of brain tissue. Here, we aim to review the known effects of glucocorticoids on proteoglycan expression and glycosaminoglycan content in different tissues, with a specific focus on the brain.
A Mini-Review on Reflectins, from Biochemical Properties to Bio-Inspired Applications
Authors: Song Junyi , Li Baoshan , Zeng Ling , Ye Zonghuang , Wu Wenjian , Hu Biru
Published: December 2022

Some cephalopods (squids, octopuses, and cuttlefishes) produce dynamic structural colors, for camouflage or communication. The key to this remarkable capability is one group of specialized cells called iridocytes, which contain aligned membrane-enclosed platelets of high-reflective reflectins and work as intracellular Bragg reflectors. These reflectins have unusual amino acid compositions and sequential properties, which endows them with functional characteristics: an extremely high reflective index among natural proteins and the ability to answer various environmental stimuli. Based on their unique material composition and responsive self-organization properties, the material community has developed an impressive array of reflectin- or iridocyte-inspired optical systems with distinct tunable reflectance according to a series of internal and external factors. More recently, scientists have made creative attempts to engineer mammalian cells to explore the function potentials of reflectin proteins as well as their working mechanism in the cellular environment. Progress in wide scientific areas (biophysics, genomics, gene editing, etc.) brings in new opportunities to better understand reflectins and new approaches to fully utilize them. The work introduced the composition features, biochemical properties, the latest developments, future considerations of reflectins, and their inspiration applications to give newcomers a comprehensive understanding and mutually exchanged knowledge from different communities (e.g., biology and material).
Opposing Actions of TLR2 and TLR4 in Adipocyte Differentiation and Mature-Onset Obesity
Authors: Cuesta Natalia , Fernández-Veledo Sonia , Punzón Carmen , Moreno Cristóbal , Barrocal Beatriz , Sreeramkumar Vinatha , Desco Manuel , Fresno Manuel
Published: December 2022

Understanding the signaling cascades that govern adipocyte metabolism and differentiation is necessary for the development of therapies for obesity. Toll-like receptors (TLRs) are key mediators in adipogenesis, but their specific role is not completely understood. In this study, siRNA knockdown of Tlr2 in 3T3-L1 cells allowed them to differentiate more efficiently into adipocytes, whereas the opposite was observed for the knockdown of Tlr4. At the same time, we show that TLR2 knock-out mice spontaneously developed mature-onset obesity and insulin resistance. Besides a higher incidence of hyperplasia and hypertrophy in white adipose tissue (WAT), we found a significantly increased number of adipocyte precursor cells in TLR2−/− mice compared to TLR4−/− mice. Interestingly, genetic inactivation of Tlr4 in TLR2−/− mice reverted their increased adiposity, insulin resistance, and restored normal levels of adipocyte precursor cells. These findings provide evidence that TLR2 and TLR4 play opposing roles in WAT homeostasis and point to the existence of cross-regulation among TLR2 and TLR4 during adipocyte differentiation both in vitro and in vivo.
The Role of Apoptosis and Autophagy in the Hypothalamic-Pituitary-Adrenal (HPA) Axis after Traumatic Brain Injury (TBI)
Authors: Taheri Serpil , Karaca Züleyha , Mehmetbeyoglu Ecmel , Hamurcu Zuhal , Yilmaz Zeynep , Dal Fatma , Çınar Venhar , Ulutabanca Halil , Tanriverdi Fatih , Unluhizarci Kursad , Rassoulzadegan Minoo , Kelestimur Fahrettin
Published: December 2022

Traumatic brain injury (TBI) is a major health problem affecting millions of people worldwide and leading to death or permanent damage. TBI affects the hypothalamic–pituitary–adrenal (HPA) axis either by primary injury to the hypothalamic–hypophyseal region or by secondary vascular damage, brain, and/or pituitary edema, vasospasm, and inflammation. Neuroendocrine dysfunctions after TBI have been clinically described in all hypothalamic–pituitary axes. We established a mild TBI (mTBI) in rats by using the controlled cortical impact (CCI) model. The hypothalamus, pituitary, and adrenals were collected in the acute (24 h) and chronic (30 days) groups after TBI, and we investigated transcripts and protein-related autophagy (Lc3, Bcln1, P150, Ulk, and Atg5) and apoptosis (pro-caspase-3, cleaved caspase-3). Transcripts related to autophagy were reduced in the hypothalamus, pituitary, and adrenals after TBI, however, this was not reflected in autophagy-related protein levels. In contrast, protein markers related to apoptosis increased in the adrenals during the acute phase and in the pituitary during the chronic phase. TBI stresses induce a variation of autophagy-related transcripts without modifying the levels of their proteins in the HPA axis. In contrast, protein markers related to apoptosis are increased in the acute phase in the adrenals, which could lead to impaired communication via the hypothalamus, pituitary, and adrenals. This may then explain the permanent pituitary damage with increased apoptosis and inflammation in the chronic phase. These results contribute to the elucidation of the mechanisms underlying endocrine dysfunctions such as pituitary and adrenal insufficiency that occur after TBI. Although the adrenals are not directly affected by TBI, we suggest that the role of the adrenals along with the hypothalamus and pituitary should not be ignored in the acute phase after TBI.
The Role of Ectodysplasin A on the Ocular Surface Homeostasis
Authors: Ou Shangkun , Jeyalatha Mani Vimalin , Mao Yi , Wang Junqi , Chen Chao , Zhang Minjie , Liu Xiaodong , Liang Minghui , Lin Sijie , Wu Yiming , Li Yixuan , Li Wei
Published: December 2022

Ectodysplasin A (EDA), a ligand of the TNF family, plays an important role in maintaining the homeostasis of the ocular surface. EDA is necessary for the development of the meibomian gland, the lacrimal gland, as well as the proliferation and barrier function of the corneal epithelium. The mutation of EDA can induce the destruction of the ocular surface resulting in keratopathy, abnormality of the meibomian gland and maturation of the lacrimal gland. Experimental animal studies showed that a prenatal ultrasound-guided intra-amniotic injection or postnatal intravenous administration of soluble recombinant EDA protein can efficiently prevent the development of ocular surface abnormalities in EDA mutant animals. Furthermore, local application of EDA could restore the damaged ocular surface to some extent. Hence, a recombinant EDA-based therapy may serve as a novel paradigm to treat ocular surface disorders, such as meibomian gland dysfunction and corneal epithelium abnormalities.
Fluid Shear Stress Regulates Osteogenic Differentiation via AnnexinA6-Mediated Autophagy in MC3T3-E1 Cells
Authors: Pei Tong , Su Guanyue , Yang Jie , Gao Wenbo , Yang Xinrui , Zhang Yaojia , Ren Jie , Shen Yang , Liu Xiaoheng
Published: December 2022

Fluid shear stress (FSS) facilitates bone remodeling by regulating osteogenic differentiation, and extracellular matrix maturation and mineralization. However, the underlying molecular mechanisms of how mechanical stimuli from FSS are converted into osteogenesis remain largely unexplored. Here, we exposed MC3T3-E1 cells to FSS with different intensities (1 h FSS with 0, 5, 10, and 20 dyn/cm2 intensities) and treatment durations (10 dyn/cm2 FSS with 0, 0.5, 1, 2 and 4 h treatment). The results demonstrate that the 1 h of 10 dyn/cm2 FSS treatment greatly upregulated the expression of osteogenic markers (Runx2, ALP, Col I), accompanied by AnxA6 activation. The genetic ablation of AnxA6 suppressed the autophagic process, demonstrating lowered autophagy markers (Beclin1, ATG5, ATG7, LC3) and decreased autophagosome formation, and strongly reduced osteogenic differentiation induced by FSS. Furthermore, the addition of autophagic activator rapamycin to AnxA6 knockdown cells stimulated autophagy process, and coincided with more expressions of osteogenic proteins ALP and Col I under both static and FSS conditions. In conclusion, the findings in this study reveal a hitherto unidentified relationship between FSS-induced osteogenic differentiation and autophagy, and point to AnxA6 as a key mediator of autophagy in response to FSS, which may provide a new target for the treatment of osteoporosis and other diseases.
AICAR Improves Outcomes of Metabolic Syndrome and Type 2 Diabetes Induced by High-Fat Diet in C57Bl/6 Male Mice
Authors: Tukhovskaya Elena A. , Shaykhutdinova Elvira R. , Pakhomova Irina A. , Slashcheva Gulsara A. , Goryacheva Natalya A. , Sadovnikova Elena S. , Rasskazova Ekaterina A. , Kazakov Vitaly A. , Dyachenko Igor A. , Frolova Alina A. , Brovkin Alexey N. , Kaluzhsky Vasiliy E. , Beburov Mikhail Yu. , Murashev Arkady N.
Published: December 2022

The aim of the study was to investigate the effect of AMP-activated protein kinase activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) on the consequences of metabolic syndrome and type 2 diabetes induced by the consumption of a high-fat diet (HFD) in male C57Bl/6 mice. Additionally, the animals from group 6 were administered Methotrexate (MTX) at a dose of 1 mg/kg in parallel with AICAR, which slows down the metabolism of AICAR. The animals were recorded with signs of metabolic syndrome and type 2 diabetes mellitus by recording their body weights, glucose and insulin levels, and the calculating HOMA-IRs. At the end of the study, at the end of the 13th week, during necropsy, the internal organs were assessed, the masses of the organs were recorded, and special attention was paid to visceral fat, assessing its amount and the mass of the fat surrounding epididymis. The biochemical parameters and histology of the internal organs and tissues were assessed. The animals showed signs of metabolic syndrome and type 2 diabetes, namely, weight gain, hyperglycemia, hyperinsulinemia, an increase in the amount and mass of abdominal fat, and metabolic disorders, all expressed in a pathological change in biochemical parameters and pathological changes in internal organs. The AICAR treatment led to a decrease in body weight, a decrease in the amount and mass of abdominal fat, and an improvement in the pathomorphological picture of internal organs. However, some hepatotoxic effects were observed when the animals, on a received standard diet (STD), were treated with AICAR starting from the first day of the study. The additional administration of MTX, an AICAR metabolic inhibitor, did not improve its efficacy. Thus, AICAR has therapeutic potential for the treatment of metabolic syndrome and type 2 diabetes.
Endothelial Dysfunction and Chronic Inflammation: The Cornerstones of Vascular Alterations in Age-Related Diseases
Authors: Pacinella Gaetano , Ciaccio Anna Maria , Tuttolomondo Antonino
Published: December 2022

Vascular diseases of the elderly are a topic of enormous interest in clinical practice, as they have great epidemiological significance and lead to ever-increasing healthcare expenditures. The mechanisms underlying these pathologies have been increasingly characterized over the years. It has emerged that endothelial dysfunction and chronic inflammation play a diriment role among the most relevant pathophysiological mechanisms. As one can easily imagine, various processes occur during aging, and several pathways undergo irreversible alterations that can promote the decline and aberrations that trigger the diseases above. Endothelial dysfunction and aging of circulating and resident cells are the main characteristics of the aged organism; they represent the framework within which an enormous array of molecular abnormalities occur and contribute to accelerating and perpetuating the decline of organs and tissues. Recognizing and detailing each of these dysfunctional pathways is helpful for therapeutic purposes, as it allows one to hypothesize the possibility of tailoring interventions to the damaged mechanism and hypothetically limiting the cascade of events that drive the onset of these diseases. With this paper, we have reviewed the scientific literature, analysing the pathophysiological basis of the vascular diseases of the elderly and pausing to reflect on attempts to interrupt the vicious cycle that connotes the diseases of aging, laying the groundwork for therapeutic reasoning and expanding the field of scientific research by moving from a solid foundation.
Pancreatic Secretory Trypsin Inhibitor (SPINK1) Gene Mutation in Patients with Acute Alcohol Pancreatitis (AAP) Compared to Healthy Controls and Heavy Alcohol Users without Pancreatitis
Authors: Nikkola Anssi , Mäkelä Kari , Herzig Karl-Heinz , Mutt Shivaprakash , Prasannan Aishwarya , Seppänen Hanna , Lehtimäki Terho , Kähönen Mika , Raitakari Olli , Seppälä Ilkka , Pakkanen Pihla , Nordback Isto , Sand Juhani , Laukkarinen Johanna
Published: December 2022

Only 3–5% of heavy alcohol users develop acute alcohol pancreatitis (AAP). This suggests that additional triggers are required to initiate the inflammatory process. Genetic susceptibility contributes to the development of AAP, and SPINK1 mutation is a documented risk factor. We investigated the prevalence of the SPINK1(N34S) mutation in patients with AAP compared to heavy alcohol users who had never suffered an episode of pancreatitis. Blood samples for the mutational analysis from patients with first episode (n = 60) and recurrent AAP (n = 43) and from heavy alcohol users without a history of AAP (n = 98) as well as from a control population (n = 1914) were obtained. SPINK1 mutation was found in 8.7% of the patients with AAP. The prevalence was significantly lower in healthy controls (3.4%, OR 2.72; 1.32–5.64) and very low in alcoholics without pancreatitis (1.0%, OR 9.29; 1.15–74.74). In a comparison adjusted for potential cofounders between AAP patients and alcoholics, SPINK1 was found to be an independent marker for AAP. The prevalence of the SPINK1 mutation is overrepresented in AAP patients and very low in alcoholics without pancreatitis. This finding may play a role in understanding the variable susceptibility to AAP found in heavy alcohol users.
Genome-Wide Identification and Expression Analysis of the Aux/IAA Gene Family of the Drumstick Tree (Moringa oleifera Lam.) Reveals Regulatory Effects on Shoot Regeneration
Authors: Yang Endian , Yang Heyue , Li Chunmei , Zheng Mingyang , Song Huiyun , Zou Xuan , Chen Xiaoyang , Zhang Junjie
Published: December 2022

Auxin plays a critical role in organogenesis in plants. The classical auxin signaling pathway holds that auxin initiates downstream signal transduction by degrading Aux/IAA transcription repressors that interact with ARF transcription factors. In this study, 23 MoIAA genes were identified in the drumstick tree genome. All MoIAA genes were located within five subfamilies based on phylogenetic evolution analysis; the gene characteristics and promoter cis-elements were also analyzed. The protein interaction network between the MoIAAs with MoARFs was complex. The MoIAA gene family responded positively to NAA treatment, exhibiting different patterns and degrees, notably for MoIAA1, MoIAA7 and MoIAA13. The three genes expressed and functioned in the nucleus; only the intact encoding protein of MoIAA13 exhibited transcriptional activation activity. The shoot regeneration capacity in the 35S::MoIAA13-OE transgenic line was considerably lower than in the wild type. These results establish a foundation for further research on MoIAA gene function and provide useful information for improved tissue culture efficiency and molecular breeding of M. oleifera.
Host–Guest Complexes
Authors: Mejuto Juan C. , Simal-Gandara Jesus
Published: December 2022

Host–guest complexes, also known as inclusion complexes, are supramolecular structures [...]
Comprehensive Genome Analysis of Neisseria meningitidis from South America Reveals a Distinctive Pathogenicity-Related Prophage Repertoire
Authors: Madariaga-Troncoso David , Leyton-Carcaman Benjamin , Garcia Matias , Kawai Mikihiko , Abanto Marin Michel
Published: December 2022

Neisseria meningitidis, a bacterium that colonizes in the human nasopharynx, occasionally causes invasive meningococcal disease leading to meningitis or septicemia. Different serogroups and lineages (clonal complexes) are related to the occurrence and epidemiology of N. meningitidis. Despite vaccines for most serogroups, N. meningitidis lineages causing unusual clinical manifestations and a higher fatality rate compared to other lineages have been reported in South America. The present study focused on exploring the diversity of N. meningitidis prophages from South America and their relationship with the epidemiological variables of these strains. We found a high diversity of prophages among the different clonal complexes. By comparing them with previously described N. meningitidis phages and prophages, we revealed groups of prophages sharing similar compositions, which could be useful for prophage comparison in N. meningitidis. Furthermore, we observed a high correlation between the prophage content and epidemiological features, e.g., pathogenicity or clonal complex. Additionally, a distinctive filamentous prophage named here as IMSAR-11 (Invasive Meningococci from South America Related to cc11) was identified. Interestingly, two versions of IMSAR-11, circular and chromosomally integrated, were found. Overall, this study reinforces the importance of the genomic characterization of circulating N. meningitidis lineages to generate new targets for lineage monitoring, diagnosis, or appropriateness of vaccine development. Further studies are necessary to understand the role of these prophages in the persistence, dispersal, and virulence of N. meningitidis in the world.
Biominerals Added Bioresorbable Calcium Phosphate Loaded Biopolymer Composites
Authors: Furko Monika , Horváth Zsolt E. , Czömpöly Ottó , Balázsi Katalin , Balázsi Csaba
Published: December 2022

Nanocrystalline calcium phosphate (CP) bioceramic coatings and their combination with biopolymers are innovative types of resorbable coatings for load-bearing implants that can promote the integration of metallic implants into human bodies. The nanocrystalline, amorphous CP particles are an advantageous form of the various calcium phosphate phases since they have a faster dissolution rate than that of crystalline hydroxyapatite. Owing to the biomineral additions (Mg, Zn, Sr) in optimized concentrations, the base CP particles became more similar to the mineral phase in human bones (dCP). The effect of biomineral addition into the CaP phases was thoroughly studied. The results showed that the shape, morphology, and amorphous characteristic slightly changed in the case of biomineral addition in low concentrations. The optimized dCP particles were then incorporated into a chosen polycaprolactone (PCL) biopolymer matrix. Very thin, non-continuous, rough layers were formed on the surface of implant substrates via the spin coating method. The SEM elemental mapping proved the perfect incorporation and distribution of dCP particles into the polymer matrix. The bioresorption rate of thin films was followed by corrosion measurements over a long period of time. The corrosion results indicated a faster dissolution rate for the dCP-PCL composite compared to the dCP and CP powder layers.
Chrysin Induces Apoptosis via the MAPK Pathway and Regulates ERK/mTOR-Mediated Autophagy in MC-3 Cells
Authors: Jung Gi-Hwan , Lee Jae-Han , Han So-Hee , Woo Joong-Seok , Choi Eun-Young , Jeon Su-Ji , Han Eun-Ji , Jung Soo-Hyun , Park Young-Seok , Park Byung-Kwon , Kim Byeong-Soo , Kim Sang-Ki , Jung Ji-Youn
Published: December 2022

Chrysin is a flavonoid found abundantly in substances, such as honey and phytochemicals, and is known to exhibit anticancer effects against various cancer cells. Nevertheless, the anticancer effect of chrysin against oral cancer has not yet been verified. Furthermore, the mechanism underlying autophagy is yet to be clearly elucidated. Thus, this study investigated chrysin-mediated apoptosis and autophagy in human mucoepidermoid carcinoma (MC-3) cells. The change in MC-3 cell viability was examined using a 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide cell viability assay, as well as 40,6-diamidino-2-phenylindole, annexin V, and propidium iodide staining. Western blotting was used to analyze the proteins related to apoptosis and the mitogen-activated protein kinase (MAPK) pathway. In addition, the presence or absence of autophagy and changes in the expression of related proteins were investigated using acridine orange staining and Western blot. The results suggested that chrysin induced apoptosis and autophagy in MC-3 oral cancer cells via the MAPK/extracellular signal-regulated kinase pathway. Moreover, the induced autophagy exerted a cytoprotective effect against apoptosis. Thus, the further reduced cell viability due to autophagy as well as apoptosis induction highlight therapeutic potential of chrysin for oral cancer.