bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in Carbon Sequestration Ability of Diverse Tartary Buckwheat Genotypes in Barren Soil Caused by Microbial Action
Authors: Chen Wei , Zhang Zhiwei , Sun Congjian
Published: January 2023

Planting plants to increase soil carbon input has been widely used to achieve carbon neutrality goals. Tartary buckwheat not only has good barren tolerance but is also rich in nutrients and very suitable for planting in barren areas. However, the effects of different genotypes of Tartary buckwheat roots and rhizosphere microorganisms on soil carbon input are still unclear. In this study, ozone sterilization was used to distinguish the sources of soil organic acids and C-transforming enzymes, and the contribution of root and rhizosphere microorganisms to soil carbon storage during the growth period of two genotypes of tartary buckwheat was studied separately to screen suitable varieties. Through the analysis of the experimental results, the conclusions are as follows: (1) The roots of Diqing tartary buckwheat have stronger carbon sequestration ability in a barren environment than Heifeng, and the microorganisms in Diqing tartary buckwheat soil will also increase soil carbon input. Therefore, Diqing tartary buckwheat is more suitable for carbon sequestration than Heifeng tartary buckwheat in barren soil areas. (2) In the absence of microorganisms, the rhizosphere soil of tartary buckwheat can regulate the storage of soil organic carbon by secreting extracellular enzymes and organic acids. (3) The structural equation model showed that to promote carbon sequestration, Heifeng tartary buckwheat needed to inhibit microbial action when planted in the barren area of Loess Plateau, while Diqing tartary buckwheat needed to use microbial-promoting agents. Adaptive strategies should focus more on cultivar selection to retain carbon in soil and to assure the tolerance of fineness in the future.
Quality of Sexuality during Pregnancy, We Must Do Something—Survey Study
Authors: García-Duarte Sonia , Nievas-Soriano Bruno José , Fischer-Suárez Natalia , Castro-Luna Gracia , Parrón-Carreño Tesifón , Aguilera-Manrique Gabriel
Published: January 2023

Background: The main aim of this study was to describe the changes in sexual desire in pregnant women during the gestation period. We also sought to analyze their sexual habits, how they perceive their partners’ attitudes, and determine if they know the importance of sex education during pregnancy. Methods: A cross-sectional descriptive observational study was conducted using an existing 32-item questionnaire among pregnant women attending the Fetal Welfare Clinic of a reference hospital. Univariate and bivariate analyses were performed. Results: One hundred seventeen women participated. 50.4% stated that their sexual interest decreased. Aspects like the number of coitus, feeling orgasm with penetration or with masturbation, or the frequency of oral sex, were significantly reduced during pregnancy. 90.6% of the women stated that they would like to receive more sex education during pregnancy. There were no differences according to their education level, their partners’ education level, or whether they believed that sexual intercourse could harm the baby. Conclusions: Several advances have been achieved in the healthcare that physicians and midwives provide pregnant women. However, the quality of women’s sex lives still declines during pregnancy. Healthcare providers should assume a proactive role, essential in helping future parents to enjoy their sexuality and dispel myths about sexuality, regardless of their education level.
From Sarcopenia to Depressive Symptoms in Elderly: A Path Analysis
Authors: Ustevic Cedomir , Rajovic Nina , Stanisavljevic Dejana , Tiosavljevic Danijela , Pavlovic Andrija , Tasic Radica , Rajovic Tatjana , Grupkovic Jovana , Pilipovic Filip , Pejin Vedrana , Milcanovic Petar , Mazic Sanja , Milic Natasa
Published: January 2023

Background: Sarcopenia is an age-related progressive, generalized skeletal muscle disorder involving the accelerated loss of muscle function and muscle mass. The aim of this study was to assess the complex relationship between sarcopenia, malnutrition, cognitive impairment, physical activity, and depression in the elderly, with the potential role of quality of life as a mediator in these associations. Methods: A cross-sectional study was conducted on a sample (n = 298) of elderly patients admitted to Special Hospital for Rehabilitation “Termal”, Vrdnik, Serbia. Sarcopenia, the risk for malnutrition, cognitive impairment, physical activity, quality of life, and depressive symptoms were measured by standardized instruments. Additional data included sociodemographic characteristics. Simultaneous assessment of the direct and indirect relationships of all determinants was performed by path analysis. Results: A total of 40% (n = 120) of the elderly were diagnosed with sarcopenia, and 42.6% had depression symptoms. The risk of malnutrition was present in 23.5%, cognitive impairment in 5.4%, and a low level of physical activity was reported in 26.2% of elderly participants. The mean reported quality of life measured by Sarcopenia and Quality of Life Questionnaire was 60 (on the scale ranging from 0 to 100; where a higher score reflects a higher quality of life). The best-fitted model (χ2/DF = 1.885, NFI = 0.987, CFI = 0.993, GFI = 0.997, RMSEA = 0.055) highlighted the mediating effect of quality of life between sarcopenia, malnutrition, cognitive impairment, lower level of physical activities and depression. According to the model, quality of life was a direct negative predictor of depressive symptoms in the elderly, while malnutrition positively affected depression. Conclusions: The presented path model may assist rehabilitation centers in developing strategies to screen for sarcopenia and risk of malnutrition, and promote physical activity in elderly, aiming to prevent their negative effects on mental health. For the elderly currently affected by sarcopenia, we consider regenerative medicine and stem cell therapy, which, in view of their etiology, could be a potential therapeutic strategy for sarcopenia.
Physical Fitness as a Predictor of Performance during Competition in Professional Women’s Basketball Players
Authors: Ibáñez Sergio J. , Piñar María Isabel , García David , Mancha-Triguero David
Published: January 2023

The evaluation of physical fitness in team sports is enjoying greater importance in the training of professional teams. The objectives of this research were to characterize physical fitness and game indicators based on the game position. This is an empirical study, with a quantitative, descriptive and cross-sectional methodology. In addition, different relationships between the level of physical fitness and the game indicators during the competition were determined. Finally, a predictive analysis of the selected variables was carried out in order to know the importance of the variables in the performance and at what time of the season they had the greatest impact. For this, a professional female basketball team (n = 12) with a mean age of 25.25 ± 7.617 years, height 178.25 ± 9.206 cm and a body mass of 72.33 ± 11.657 kg was analyzed. Each player was equipped with a WIMUPRO inertial device, and all competition statistics were analyzed. The results obtained show that there were no differences among all the skills evaluated and game indicators depending on the game position. Likewise, a relationship was determined between the level of physical fitness and the technical–tactical contribution, being different between different times of the season. Moreover, physical fitness only predicted the player’s final performance in the competition for female player centers in the first and second rounds of the championship, and for forwards in the first round. Four physical-physiological profiles with contributions to the different ones during the competition were also determined. Finally, three groups of female players by playing position were identified according to their sport performance, namely PIR, high, medium and low ratings, associated with physical performances. In all groups, there were significant differences between playing positions, PIR and physical performances.
Experimental and Bioinformatic Insights into the Effects of Epileptogenic Variants on the Function and Trafficking of the GABA Transporter GAT-1
Authors: Piniella Dolores , Canseco Ania , Vidal Silvia , Xiol Clara , Díaz de Bustamante Aránzazu , Martí-Carrera Itxaso , Armstrong Judith , Bastolla Ugo , Zafra Francisco
Published: January 2023

In this article, we identified a novel epileptogenic variant (G307R) of the gene SLC6A1, which encodes the GABA transporter GAT-1. Our main goal was to investigate the pathogenic mechanisms of this variant, located near the neurotransmitter permeation pathway, and compare it with other variants located either in the permeation pathway or close to the lipid bilayer. The mutants G307R and A334P, close to the gates of the transporter, could be glycosylated with variable efficiency and reached the membrane, albeit inactive. Mutants located in the center of the permeation pathway (G297R) or close to the lipid bilayer (A128V, G550R) were retained in the endoplasmic reticulum. Applying an Elastic Network Model, to these and to other previously characterized variants, we found that G307R and A334P significantly perturb the structure and dynamics of the intracellular gate, which can explain their reduced activity, while for A228V and G362R, the reduced translocation to the membrane quantitatively accounts for the reduced activity. The addition of a chemical chaperone (4-phenylbutyric acid, PBA), which improves protein folding, increased the activity of GAT-1WT, as well as most of the assayed variants, including G307R, suggesting that PBA might also assist the conformational changes occurring during the alternative access transport cycle.
Structural Dynamics of the Bacillus subtilis MntR Transcription Factor Is Locked by Mn2+ Binding
Authors: Jelić Matošević Zoe , Radman Katarina , Loubser Jolene , Crnolatac Ivo , Piantanida Ivo , Cukrowski Ignacy , Ašler Ivana Leščić , Bertoša Branimir
Published: January 2023

Manganese (II) ions are essential for a variety of bacterial cellular processes. The transcription factor MntR is a metallosensor that regulates Mn2+ ion homeostasis in the bacterium Bacillus subtilis. Its DNA-binding affinity is increased by Mn2+ ion binding, allowing it to act as a transcriptional repressor of manganese import systems. Although experimentally well-researched, the molecular mechanism that regulates this process is still a puzzle. Computational simulations supported by circular dichroism (CD), differential scanning calorimetry (DSC) and native gel electrophoresis (native-PAGE) experiments were employed to study MntR structural and dynamical properties in the presence and absence of Mn2+ ions. The results of molecular dynamics (MD) simulations revealed that Mn2+ ion binding reduces the structural dynamics of the MntR protein and shifts the dynamic equilibrium towards the conformations adequate for DNA binding. Results of CD and DSC measurements support the computational results showing the change in helical content and stability of the MntR protein upon Mn2+ ion binding. Further, MD simulations show that Mn2+ binding induces polarization of the protein electrostatic potential, increasing the positive electrostatic potential of the DNA-binding helices in particular. In order to provide a deeper understanding of the changes in protein structure and dynamics due to Mn2+ binding, a mutant in which Mn2+ binding is mimicked by a cysteine bridge was constructed and also studied computationally and experimentally.
Posttranscriptional Regulation of the Plasminogen Activation System by Non-Coding RNA in Cancer
Authors: Alfieri Mariaevelina , Meo Luigia , Ragno Pia
Published: January 2023

Various species of non-coding RNAs (ncRNAs) may act as functional molecules regulating diverse biological processes. In cancer cell biology, ncRNAs include RNAs that regulate the expression of oncogenes and tumor suppressor genes through various mechanisms. The urokinase (uPA)-mediated plasminogen activation system (PAS) includes uPA, its inhibitors PAI-1 and PAI-2 and its specific cellular receptor uPAR; their increased expression represents a negative prognostic factor in several cancers. Here, we will briefly describe the main uPA-mediated PAS components and ncRNA species; then, we will review more recent evidence of the roles that ncRNAs may play in regulating the expression and functions of uPA-mediated PAS components in cancer.
The Roles of miRNAs in Predicting Bladder Cancer Recurrence and Resistance to Treatment
Authors: Das Sanjna , Hayden Joshua , Sullivan Travis , Rieger-Christ Kimberly
Published: January 2023

Bladder cancer (BCa) is associated with significant morbidity, with development linked to environmental, lifestyle, and genetic causes. Recurrence presents a significant issue and is managed in the clinical setting with intravesical chemotherapy or immunotherapy. In order to address challenges such as a limited supply of BCG and identifying cases likely to recur, it would be advantageous to use molecular biomarkers to determine likelihood of recurrence and treatment response. Here, we review microRNAs (miRNAs) that have shown promise as predictors of BCa recurrence. MiRNAs are also discussed in the context of predicting resistance or susceptibility to BCa treatment.
Fine Mapping and Cloning of a qRA2 Affect the Ratooning Ability in Rice (Oryza sativa L.)
Authors: He Niqing , Huang Fenghuang , Yang Dewei
Published: January 2023

Ratooning ability is a key factor that influences the ratoon rice yield in areas where light and temperature are not sufficient for second-season rice. Near-isogenic lines (NILs) are the most powerful tools for the detection and precise mapping of quantitative trait loci (QTLs). In this study, using 176 NILs, we identified a novel QTL for ratooning ability in NIL128. First, we mapped the QTL between the markers Indel12-29 and Indel12-31, which encompass a region of 233 kb. The rice genome annotation indicated the existence of three candidate genes in this region that may be related to ratooning ability. Through gene prediction and cDNA sequencing, we speculated that the target gene of ratooning ability is LOC_Os02g51930 which encodes cytokinin glucosyl transferases (CGTs), hereafter named qRA2. Further analysis showed that qra2 was a 1-bp substitution in the first exon in NIL128, which resulted in the premature termination of qRA2. The results of the knockdown experiment showed that the Jiafuzhan knockdown mutants exhibited the ratooning ability phenotype of NIL128. Interestingly, the qRA2 gene was found to improve ratooning ability without affecting major agronomic traits. These results will help us better understand the genetic basis of rice ratooning ability and provide a valuable gene resource for breeding strong ratoon rice varieties.
Pharmacological Activation of YAP/TAZ by Targeting LATS1/2 Enhances Periodontal Tissue Regeneration in a Murine Model
Authors: Sato Akiko , Suzuki Shigeki , Yuan Hang , Fahreza Rahmad Rifqi , Wang Xiuting , Nemoto Eiji , Saito Masahiro , Yamada Satoru
Published: January 2023

Due to their multi-differentiation potential, periodontal ligament fibroblasts (PDLF) play pivotal roles in periodontal tissue regeneration in vivo. Several in vitro studies have suggested that PDLFs can transmit mechanical stress into favorable basic cellular functions. However, the application of mechanical force for periodontal regeneration therapy is not expected to exhibit an effective prognosis since mechanical forces, such as traumatic occlusion, also exacerbate periodontal tissue degeneration and loss. Herein, we established a standardized murine periodontal regeneration model and evaluated the regeneration process associated with cementum remodeling. By administering a kinase inhibitor of YAP/TAZ suppressor molecules, such as large tumor suppressor homolog 1/2 (LATS1/2), we found that the activation of YAP/TAZ, a key downstream effector of mechanical signals, accelerated periodontal tissue regeneration due to the activation of PDLF cell proliferation. Mechanistically, among six kinds of MAP4Ks previously reported as upstream kinases that suppressed YAP/TAZ transcriptional activity through LATS1/2 in various types of cells, MAP4K4 was identified as the predominant MAP4K in PDLF and contributed to cell proliferation and differentiation depending on its kinase activity. Ultimately, pharmacological activation of YAP/TAZ by inhibiting upstream inhibitory kinase in PDLFs is a valuable strategy for improving the clinical outcomes of periodontal regeneration therapies.
Recombinant Human Clusterin Seals Damage to the Ocular Surface Barrier in a Mouse Model of Ophthalmic Preservative-Induced Epitheliopathy
Authors: Chintala Shravan K. , Pan Jinhong , Satapathy Sandeep , Condruti Rebecca , Hao Zixuan , Liu Pei-wen , O’Conner Christian F. , Barr Joseph T. , Wilson Mark R. , Jeong Shinwu , Fini M. Elizabeth
Published: January 2023

There is a significant unmet need for therapeutics to treat ocular surface barrier damage, also called epitheliopathy, due to dry eye and related diseases. We recently reported that the natural tear glycoprotein CLU (clusterin), a molecular chaperone and matrix metalloproteinase inhibitor, seals and heals epitheliopathy in mice subjected to desiccating stress in a model of aqueous-deficient/evaporative dry eye. Here we investigated CLU sealing using a second model with features of ophthalmic preservative-induced dry eye. The ocular surface was stressed by topical application of the ophthalmic preservative benzalkonium chloride (BAC). Then eyes were treated with CLU and sealing was evaluated immediately by quantification of clinical dye uptake. A commercial recombinant form of human CLU (rhCLU), as well as an rhCLU form produced in our laboratory, designed to be compatible with U.S. Food and Drug Administration guidelines on current Good Manufacturing Practices (cGMP), were as effective as natural plasma-derived human CLU (pCLU) in sealing the damaged ocular surface barrier. In contrast, two other proteins found in tears: TIMP1 and LCN1 (tear lipocalin), exhibited no sealing activity. The efficacy and selectivity of rhCLU for sealing of the damaged ocular surface epithelial barrier suggests that it could be of therapeutic value in treating BAC-induced epitheliopathy and related diseases.
JUL1, Ring-Type E3 Ubiquitin Ligase, Is Involved in Transcriptional Reprogramming for ERF15-Mediated Gene Regulation
Authors: Kawaguchi Junna , Hayashi Kaito , Desaki Yoshitake , Ramadan Abdelaziz , Nozawa Akira , Nemoto Keiichirou , Sawasaki Tatsuya , Arimura Gen-ichiro
Published: January 2023

JAV1-associated ubiquitin ligase 1 (JUL1) is a RING-type E3 ubiquitin ligase that catalyzes ubiquitination of JAV1, a jasmonate signaling repressor, in Arabidopsis thaliana in response to herbivore attack. Here we present a new insight into the nature of JUL1 as a multi-targeting enzyme for not only JAV1 but also transcription factors (TFs) screened using in vitro and in vivo protein interaction assays. Reporter assays using protoplasts showed that the JUL1-interacting TFs (JiTFs), including ERF15, bZIP53 and ORA59, were involved in transcriptional activation of jasmonate-responsive PDF1.2 and abscisic acid-responsive GEA6. Likewise, assays using mutant plants suggested that the 3 JiTFs were indeed responsible for transcriptional regulation of PDF1.2 and/or GEA6, and ERF15 and ORA59 were substantially responsible for the anti-herbivore trait. In vitro protein ubiqutination assays showed that JUL1 catalyzed ubiqutination of JAV1 but not any of the TFs. This was in accord with the finding that JUL1 abolished JAV1′s interference with ERF15 function, according to the reporter assay. Moreover, of great interest is our finding that ERF15 but not bZIP53 or ORA59 serves as a scaffold for the JAV1/JUL1 system, indicating that there is narrow selectivity of the transcriptional reprogramming by the JAV1/JUL1 system.
Recent Advances of Microfluidic Platform for Cell Based Non-Invasive Prenatal Diagnosis
Authors: Jou Hei-Jen , Lo Pei-Hsuan , Ling Pei-Ying
Published: January 2023

The purpose of the present review is to try to highlight recent advances in the application of microfluidic technology on non-invasive prenatal diagnosis (NIPD). The immunoaffinity based microfluidic technology is the most common approach for NIPD, followed by size-based microfluidic methods. Immunoaffinity microfluidic methods can enrich and isolate circulating fetal extravillous trophoblasts (fEVTs) or fetal nucleated red blood cells (fnRBCs) for NIPD by using specific antibodies, but size-based microfluidic systems are only applied to isolate fEVTs. Most studies based on the immunoaffinity microfluidic system gave good results. Enough fetal cells were obtained for chromosomal and/or genetic analysis in all blood samples. However, the results from studies using size-based microfluidic systems for NIPD are less than ideal. In conclusion, recent advances in microfluidic devices make the immunoaffinity based microfluidic system potentially a powerful tool for cell-based NIPD. However, more clinical validation is needed.
The Role of Fecal Microbiota Transplantation in the Treatment of Neurodegenerative Diseases: A Review
Authors: Matheson Julie-Anne T. , Holsinger R. M. Damian
Published: January 2023

Neurodegenerative diseases are highly prevalent but poorly understood, and with few treatment options despite decades of intense research, attention has recently shifted toward other mediators of neurological disease that may present future targets for therapeutic research. One such mediator is the gut microbiome, which communicates with the brain through the gut–brain axis and has been implicated in various neurological disorders. Alterations in the gut microbiome have been associated with numerous neurological and other diseases, and restoration of the dysbiotic gut has been shown to improve disease conditions. One method of restoring a dysbiotic gut is via fecal microbiota transplantation (FMT), recolonizing the “diseased” gut with normal microbiome. Fecal microbiota transplantation is a treatment method traditionally used for Clostridium difficile infections, but it has recently been used in neurodegenerative disease research as a potential treatment method. This review aims to present a summary of neurodegenerative research that has used FMT, whether as a treatment or to investigate how the microbiome influences pathogenesis.
An Automated High-Throughput Screening (HTS) Spotter for 3D Tumor Spheroid Formation
Authors: Jeong Mi-Hyeon , Kim Inhee , Park Kyunghyun , Ku Bosung , Lee Dong Woo , Park Kyoung Ryeol , Jeon Sang Youl , Kim Jung Eun
Published: January 2023

Three-dimensional (3D) culture platforms have been adopted in a high-throughput screening (HTS) system to mimic in vivo physiological microenvironments. The automated dispenser has been established commercially to enable spotting or distributing non-viscous or viscous biomaterials onto microplates. However, there are still challenges to the precise and accurate dispensation of cells embedded in hydrogels such as Alginate- and Matrigel-extracellular matrices. We developed and improved an automated contact-free dispensing machine, the ASFA SPOTTER (V5 and V6), which is compatible with 96- and 384-pillar/well plates and 330- and 532-micropillar/well chips for the support of 3D spheroid/organoid models using bioprinting techniques. This enables the distribution of non-viscous and viscous biosamples, including chemical drugs and cancer cells, for large-scale drug screening at high speed and small volumes (20 to 4000 nanoliters) with no damage to cells. The ASFA SPOTTER (V5 and V6) utilizes a contact-free method that minimizes cross-contamination for the dispensation of encapsulated tissue cells with highly viscous scaffolds (over 70%). In particular, the SPOTTER V6 does not require a washing process and offers the advantage of almost no dead volume (defined as additional required sample volume, including a pre-shot and flushing shot for dispensing). It can be successfully applied for the achievement of an organoid culture in automation, with rapid and easy operation, as well as miniaturization for high-throughput screening. In this study, we report the advantages of the ASFA SPOTTER, which distributes standard-sized cell spots with hydrogels onto a 384-pillar/well plate with a fast dispensing speed, small-scale volume, accuracy, and precision.
Photoperiodic Remodeling of Adiposity and Energy Metabolism in Non-Human Mammals
Authors: Navarro-Masip Èlia , Caron Alexandre , Mulero Miquel , Arola Lluís , Aragonès Gerard
Published: January 2023

Energy homeostasis and metabolism in mammals are strongly influenced by seasonal changes. Variations in photoperiod patterns drive adaptations in body weight and adiposity, reflecting changes in the regulation of food intake and energy expenditure. Humans also show distinct patterns of energy balance depending on the season, being more susceptible to gaining weight during a specific time of the year. Changes in body weight are mainly reflected by the adipose tissue, which is a key metabolic tissue and is highly affected by circannual rhythms. Mostly, in summer-like (long-active) photoperiod, adipocytes adopt a rather anabolic profile, more predisposed to store energy, while food intake increases and energy expenditure is reduced. These metabolic adaptations involve molecular modifications, some of which have been studied during the last years and are summarized in this review. In addition, there is a bidirectional relation between obesity and the seasonal responses, with obesity disrupting some of the seasonal responses observed in healthy mammals, and altered seasonality being highly associated with increased risk of developing obesity. This suggests that changes in photoperiod produce important metabolic alterations in healthy organisms. Biological rhythms impact the regulation of metabolism to different extents, some of which are already known, but further research is needed to fully understand the relationship between energy balance and seasonality.
Blue Light Regulates Cell Wall Structure and Carbohydrate Metabolism of Soybean Hypocotyl
Authors: Wang Chang , Chen Yu , Cui Can , Shan Fuxin , Zhang Rui , Lyu Xiaochen , Lyu Lin , Chang Hanwen , Yan Chao , Ma Chunmei
Published: January 2023

Soybean stem elongation and thickening are related to cell wall composition. Plant morphogenesis can be influenced by blue light, which can regulate cell wall structure and composition, and affect stem growth and development. Here, using proteomics and metabolomics, differentially expressed proteins and metabolites of hypocotyls grown in the dark and under blue light were studied to clarify the effects of blue light on the cell wall structure and carbohydrate metabolism pathway of soybean hypocotyls. Results showed that 1120 differential proteins were upregulated and 797 differential proteins were downregulated under blue light treatment, while 63 differential metabolites were upregulated and 36 differential metabolites were downregulated. Blue light promoted the establishment of cell wall structure and composition by regulating the expression of both the enzymes and metabolites related to cell wall structural composition and nonstructural carbohydrates. Thus, under blue light, the cross-sectional area of the hypocotyl and xylem were larger, the longitudinal length of pith cells was smaller, elongation of the soybean hypocotyl was inhibited, and diameter was increased.
Determination of the Predictive Roles and Potentially Pathogenic Antigen Epitopes of α-Enolase Related to the Development of Miscarriage in Females with Autoimmune Thyroiditis
Authors: Guo Jiahui , Lu Yihan , He Xiaoqing , Li Jiashu , Fan Chenling , Zhang Hongmei , Teng Weiping , Shan Zhongyan , Li Jing
Published: January 2023

Autoimmune thyroiditis (AIT) is a common endocrine disease which causes a significantly increased risk of miscarriage. Our recent study has shown that the increased ENO1 autoantibody (ENO1Ab) expression in an experimental AIT mouse model was induced by thyroglobulin (Tg) immunization only. In this study, we explored the potential roles of ENO1Ab in miscarriage occurrence among AIT women, and the specific epitopes of ENO1 targeted by ENO1Ab. A total of 432 euthyroid pregnant participants were selected from the project of Subclinical Hypothyroid during Early Pregnancy, including 48 women with AIT and miscarriage, 96 with miscarriage but no AIT, 96 with AIT but no miscarriage, and 192 without either AIT or miscarriage. The enzyme-linked immunosorbent assay was used to determine the serum levels of total IgG against ENO1 and 18 predicted antigen epitopes of ENO1. The results showed that women with AIT and miscarriage had the highest serum levels of ENO1Ab compared to the other groups. Logistic regression analysis showed that the serum ENO1Ab was an independent risk factor for miscarriage, especially among AIT females. The serum level of total IgG against the predicted epitope peptide 6 (i.e., P6 and aa168-183) of ENO1 was significantly increased in women with AIT and miscarriage when compared with those of both the AIT non-miscarriage group and non-AIT miscarriage group. This pilot study suggests that serum ENO1Ab may have a fair predictive value for AIT-related miscarriage, and the autoantibody specific to P6 epitope may especially be more specifically related to this disorder.
Janus Kinase Inhibitors: A New Tool for the Treatment of Axial Spondyloarthritis
Authors: Paroli Marino , Caccavale Rosalba , Paroli Maria Pia , Spadea Luca , Accapezzato Daniele
Published: January 2023

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease involving the spine, peripheral joints, and entheses. This condition causes stiffness, pain, and significant limitation of movement. In recent years, several effective therapies have become available based on the use of biologics that selectively block cytokines involved in the pathogenesis of the disease, such as tumor necrosis factor-α (TNFα), interleukin (IL)-17, and IL-23. However, a significant number of patients show an inadequate response to treatment. Over 10 years ago, small synthetic molecules capable of blocking the activity of Janus kinases (JAK) were introduced in the therapy of rheumatoid arthritis. Subsequently, their indication extended to the treatment of other inflammatory rheumatic diseases. The purpose of this review is to discuss the efficacy and safety of these molecules in axSpA therapy.
Rs11726196 Single-Nucleotide Polymorphism of the Transient Receptor Potential Canonical 3 (TRPC3) Gene Is Associated with Chronic Pain
Authors: Aoki Yoshinori , Nishizawa Daisuke , Ohka Seii , Kasai Shinya , Arita Hideko , Hanaoka Kazuo , Yajima Choku , Iseki Masako , Kato Jitsu , Ogawa Setsuro , Hiranuma Ayako , Hasegawa Junko , Nakayama Kyoko , Ebata Yuko , Ichinohe Tatsuya , Hayashida Masakazu , Fukuda Ken-ichi , Ikeda Kazutaka
Published: January 2023

Chronic pain is reportedly associated with the transient receptor potential canonical 3 (TRPC3) gene. The present study examined the genetic associations between the single-nucleotide polymorphisms (SNPs) of the TRPC3 gene and chronic pain. The genomic samples from 194 patients underwent linkage disequilibrium (LD) analyses of 29 SNPs within and around the vicinity of the TRPC3 gene. We examined the associations between the SNPs and the susceptibility to chronic pain by comparing the genotype distribution of 194 patients with 282 control subjects. All SNP genotype data were extracted from our previous whole-genome genotyping results. Twenty-nine SNPs were extracted, and a total of four LD blocks with 15 tag SNPs were observed within and around the TRPC3 gene. We further analyzed the associations between these tag SNPs and chronic pain. The rs11726196 SNP genotype distribution of patients was significantly different from the control subjects even after multiple-testing correction with the number of SNPs. The TT + TG genotype of rs11726196 is often carried by chronic pain patients, suggesting a causal role for the T allele. These results contribute to our understanding of the genetic risk factors for chronic pain.
Equine Muscle Derived Mesenchymal Stem Cells Loaded with Water-Soluble Curcumin: Modulation of Neutrophil Activation and Enhanced Protection against Intracellular Oxidative Attack
Authors: Franck Thierry , Ceusters Justine , Graide Hélène , Niesten Ariane , Duysens Julien , Mickalad Ange Mouithys , Serteyn Didier
Published: January 2023

We investigated the antioxidant potential of equine mesenchymal stem cells derived from muscle microbiopsies (mdMSCs), loaded by a water-soluble curcumin lysinate incorporated into hydroxypropyl-β-cyclodextrin (NDS27). The cell loading was rapid and dependent on NDS27 dosage (14, 7, 3.5 and 1 µM). The immunomodulatory capacity of loaded mdMSCs was evaluated by ROS production, on active and total myeloperoxidase (MPO) degranulation and neutrophil extracellular trap (NET) formation after neutrophil stimulation. The intracellular protection of loaded cells was tested by an oxidative stress induced by cumene hydroperoxide. Results showed that 10 min of mdMSC loading with NDS27 did not affect their viability while reducing their metabolism. NDS27 loaded cells in presence of 14, 7 µM NDS27 inhibited more intensively the ROS production, the activity of the MPO released and bound to the NET after neutrophil stimulation. Furthermore, loaded cells powerfully inhibited intracellular ROS production induced by cumene as compared to control cells or cyclodextrin-loaded cells. Our results showed that the loading of mdMSCs with NDS27 significantly improved their antioxidant potential against the oxidative burst of neutrophil and protected them against intracellular ROS production. The improved antioxidant protective capacity of loaded mdMSCs could be applied to target inflammatory foci involving neutrophils.
The Advancement of Biodegradable Polyesters as Delivery Systems for Camptothecin and Its Analogues—A Status Report
Authors: Strzelecka Katarzyna , Piotrowska Urszula , Sobczak Marcin , Oledzka Ewa
Published: January 2023

Camptothecin (CPT) has demonstrated antitumor activity in lung, ovarian, breast, pancreas, and stomach cancers. However, this drug, like many other potent anticancer agents, is extremely water-insoluble. Furthermore, pharmacology studies have revealed that prolonged schedules must be administered continuously. For these reasons, several of its water-soluble analogues, prodrugs, and macromolecular conjugates have been synthesized, and various formulation approaches have been investigated. Biodegradable polyesters have gained popularity in cancer treatment in recent years. A number of biodegradable polymeric drug delivery systems (DDSs), designed for localized and systemic administration of therapeutic agents, as well as tumor-targeting macromolecules, have entered clinical trials, demonstrating the importance of biodegradable polyesters in cancer therapy. Biodegradable polyester-based DDSs have the potential to deliver the payload to the target while also increasing drug availability at intended site. The systemic toxicity and serious side-effects associated with conventional cancer therapies can be significantly reduced with targeted polymeric systems. This review elaborates on the use of biodegradable polyesters in the delivery of CPT and its analogues. The design of various DDSs based on biodegradable polyesters has been described, with the drug either adsorbed on the polymer’s surface or encapsulated within its macrostructure, as well as those in which a hydrolyzed chemical bond is formed between the active substance and the polymer chain. The data related to the type of DDSs, the kind of linkage, and the details of in vitro and in vivo studies are included.
The Impact of Recirculation on Extracorporeal Gas Exchange and Patient Oxygenation during Veno-Venous Extracorporeal Membrane Oxygenation—Results of an Observational Clinical Trial
Authors: Gehron Johannes , Bandorski Dirk , Mayer Konstantin , Böning Andreas
Published: January 2023

Background: Recirculation during veno-venous extracorporeal membrane oxygenation reduces extracorporeal oxygen exchange and patient oxygenation. To minimize recirculation and maximize oxygen delivery (DO2) the interaction of cannulation, ECMO flow and cardiac output requires careful consideration. We investigated this interaction in an observational trial. Methods: In 19 patients with acute respiratory distress syndrome and ECMO, we measured recirculation with the ultrasound dilution technique and calculated extracorporeal oxygen transfer (VO2), extracorporeal oxygen delivery (DO2) and patient oxygenation. To assess the impact of cardiac output (CO), we included CO measurement through pulse contour analysis. Results: In all patients, there was a median recirculation rate of approximately 14–16%, with a maximum rate of 58%. Recirculation rates >35% occurred in 13–14% of all cases. In contrast to decreasing extracorporeal gas exchange with increasing ECMO flow and recirculation, patient oxygenation increased with greater ECMO flows. High CO diminished recirculation by between 5–20%. Conclusions: Extracorporeal gas exchange masks the importance of DO2 and its effects on patients. We assume that increasing DO2 is more important than reduced VO2. A negative correlation of recirculation to CO adds to the complexity of this phenomenon. Patient oxygenation may be optimized with the direct measurement of recirculation.
Effects of Multidisciplinary Rehabilitation Program in Patients with Long COVID-19: Post-COVID-19 Rehabilitation (PCR SIRIO 8) Study
Authors: Ostrowska Małgorzata , Rzepka-Cholasińska Alicja , Pietrzykowski Łukasz , Michalski Piotr , Kosobucka-Ozdoba Agata , Jasiewicz Małgorzata , Kasprzak Michał , Kryś Jacek , Kubica Aldona
Published: January 2023

Up to 80% of COVID-19 survivors experience prolonged symptoms known as long COVID-19. The aim of this study was to evaluate the effects of a multidisciplinary rehabilitation program in patients with long COVID-19. The rehabilitation program was composed of physical training (aerobic, resistance, and breathing exercises), education, and group psychotherapy. After 6 weeks of rehabilitation in 97 patients with long COVID-19, body composition analysis revealed a significant decrease of abdominal fatty tissue (from 2.75 kg to 2.5 kg; p = 0.0086) with concomitant increase in skeletal muscle mass (from 23.2 kg to 24.2 kg; p = 0.0104). Almost 80% of participants reported dyspnea improvement assessed with the modified Medical Research Council scale. Patients’ physical capacity assessed with the 6 Minute Walking Test increased from 320 to 382.5 m (p < 0.0001), the number of repetitions in the 30 s Chair Stand Test improved from 13 to 16 (p < 0.0001), as well as physical fitness in the Short Physical Performance Battery Test from 14 to 16 (p < 0.0001). The impact of fatigue on everyday functioning was reduced in the Modified Fatigue Impact Scale from 37 to 27 (p < 0.0001). Cardiopulmonary exercise test did not show any change. The multidisciplinary rehabilitation program has improved body composition, dyspnea, fatigue and physical capacity in long COVID-19 patients.
Tocilizumab Evaluation in HLA-Desensitization before Kidney Transplantation as an Add-On Therapy to Apheresis: The TETRA Study
Authors: Jouve Thomas , Daligault Mélanie , Noble Johan , Terrec Florian , Imerzoukene Farida , Dard Céline , Bardy Béatrice , Malvezzi Paolo , Rostaing Lionel
Published: January 2023

Background: Desensitization strategies improve access to transplantation in highly sensitized kidney transplant candidates. Tocilizumab could be a valuable addition to more traditional desensitization regimens. We investigated the effect of tocilizumab as an add-on therapy to our standard of care (SoC) desensitization strategy based on rituximab and apheresis. Methods: In this study, we prospectively included highly sensitized patients to receive monthly tocilizumab infusions for 6 months before our SoC regimen (Toci + SoC group). We compared the reductions in the mean fluorescent intensity (MFI) rebound at post-transplantation and kidney function at 1-year post-transplantation to patients treated by SoC (based on apheresis and two doses of rituximab). Results: Twenty-six patients were included in the SoC group; seven in the Toci + SoC group. Reductions in pre-transplantation MFI were similar between groups. At 1-year post-transplantation, there was no absolute difference in overall MFI rebounds, including donor-specific antibodies. Toci + SoC helped lower the rebound of antibodies with more elevated baseline MFIs. Graft function and survival rates were similar at one-year post-transplantation (median eGFR 62.8 vs. 65.6 mL/min/1.73 m2 for SoC and Toci + SoC, respectively). Conclusions: Tocilizumab as an add-on to SoC desensitization may help control the post-transplantation rebound of antibodies with elevated baseline MFIs. However, reductions in pre-transplantation MFIs were similar with or without tocilizumab. Further studies are needed to validate this pilot study.
Do Sensory Impairments Portend Cognitive Decline in Older Chinese Adults? Longitudinal Evidence from a Nationally Representative Survey, 2011–2018
Authors: Zhou Yifan , Wei Jin , Sun Qinglei , Liu Haiyun , Liu Ye , Luo Jianfeng , Zhou Minwen
Published: January 2023

Previous studies on longitudinal sensory-cognition association are limited and have yielded inconsistent conclusions in western and developed countries. The present study obtained data from the China Health and Retirement Longitudinal Survey (CHARLS, 2011–2018) and aimed to investigate the longitudinal effects of sensory impairments including single vision impairment (SVI), single hearing impairment (SHI), and dual sensory impairment (DSI) on cognitive decline in middle-aged and older Chinese population. In total, 11,122 participants accomplished all 4 interviews over 8 years and were included. Cognitive performances were assessed using Mini-Mental Status Examination (MMSE) and self-reported sensory status were accepted as well. Confounding variables included age, sex, educational level, marital status, medical, and lifestyle related information. The impact of sensory impairment on cognitive decline over time was assessed using linear mixed-effects models (LMM). After being adjusted for multiple confounders, SVI/SHI/DSI were all shown to be significantly associated with executive functions, episodic memory impairment, and global cognitive decline over 8 years (all p < 0.05). Such associations become less significant among female and relatively younger populations (45–59 years old). Single vision and hearing impairments, along with dual sensory impairment, are all independently associated with subsequent cognitive decline among middle-aged and older Chinese populations over 8 years of longitudinal observation.
A Novel Reperfusion Strategy for Primary Percutaneous Coronary Intervention in Patients with Acute ST-Segment Elevation Myocardial Infarction: A Prospective Case Series
Authors: He Ji-Fang , Yang Yi-Xing , Li Jiang-Yuan , Liang Lu , Xu Li , Liu Yu , Guo Zong-Sheng , Yang Qi , Jiang Tao , Lin Xiang-Min , Yang Xin-Chun , Chen Mu-Lei , Su Pi-Xiong , Zhong Jiu-Chang , Wang Le-Feng
Published: January 2023

Background: Ischemia reperfusion injury (IRI) remains a major problem in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). We have developed a novel reperfusion strategy for PCI and named it “volume-controlled reperfusion (VCR)”. The aim of the current study was to assess the safety and feasibility of VCR in patients with STEMI. Methods: Consecutive patients admitted to Beijing Chaoyang Hospital with STEMI were prospectively enrolled. The feasibility endpoint was procedural success. The safety endpoints included death from all causes, major vascular complications, and major adverse cardiac event (MACE), i.e., a composite of cardiac death, myocardial reinfarction, target vessel revascularization (TVR), and heart failure. Results: A total of 30 patients were finally included. Procedural success was achieved in 28 (93.3%) patients. No patients died during the study and no major vascular complications or MACE occurred during hospitalization. With the exception of one patient (3.3%) who underwent TVR three months after discharge, no patient encountered death (0.0%), major vascular complications (0.0%), or and other MACEs (0.0%) during the median follow-up of 16 months. Conclusion: The findings of the pilot study suggest that VCR has favorable feasibility and safety in patients with STEMI. Further larger randomized trials are required to evaluate the effectiveness of VCR in STEMI patients.
An Approach toward Automatic Specifics Diagnosis of Breast Cancer Based on an Immunohistochemical Image
Authors: Berezsky Oleh , Pitsun Oleh , Melnyk Grygoriy , Datsko Tamara , Izonin Ivan , Derysh Bohdan
Published: January 2023

The paper explored the problem of automatic diagnosis based on immunohistochemical image analysis. The issue of automated diagnosis is a preliminary and advisory statement for a diagnostician. The authors studied breast cancer histological and immunohistochemical images using the following biomarkers progesterone, estrogen, oncoprotein, and a cell proliferation biomarker. The authors developed a breast cancer diagnosis method based on immunohistochemical image analysis. The proposed method consists of algorithms for image preprocessing, segmentation, and the determination of informative indicators (relative area and intensity of cells) and an algorithm for determining the molecular genetic breast cancer subtype. An adaptive algorithm for image preprocessing was developed to improve the quality of the images. It includes median filtering and image brightness equalization techniques. In addition, the authors developed a software module part of the HIAMS software package based on the Java programming language and the OpenCV computer vision library. Four molecular genetic breast cancer subtypes could be identified using this solution: subtype Luminal A, subtype Luminal B, subtype HER2/neu amplified, and basalt-like subtype. The developed algorithm for the quantitative characteristics of the immunohistochemical images showed sufficient accuracy in determining the cancer subtype “Luminal A”. It was experimentally established that the relative area of the nuclei of cells covered with biomarkers of progesterone, estrogen, and oncoprotein was more than 85%. The given approach allows for automating and accelerating the process of diagnosis. Developed algorithms for calculating the quantitative characteristics of cells on immunohistochemical images can increase the accuracy of diagnosis.
Riverine Litter Flux to the Northeastern Part of the Black Sea
Authors: Pogojeva Maria , Korshenko Evgeniya , Osadchiev Alexander
Published: January 2023

Rivers are among the main sources of marine litter, especially for semi-isolated sea areas with high populations and intense economic activity. The semi-isolated Black Sea located in the Eastern Europe is an example of such an area, whose watershed basin is under high anthropogenic pressure. In this study, we report the results of the first long-term monitoring program of floating litter at several rivers inflowing to the northeastern part of the Black Sea. We describe the main characteristics of registered marine litter, including the distribution of its type and size. Based on the obtained results, we reveal the relation between river discharge rate and the litter flux for the considered rivers. Using this relation extended to all rivers of the study area, we assess the total annual flux of riverine litter to the northeastern part of the Black Sea.