Miracle-dz/UniFAR-FTUs huggingface dataset:
Membranous Nephropathy: From Research Bench to Personalized Care

Membranous nephropathy is a glomerulopathy that causes nephrotic syndrome and, in at least a third of cases, lasting end-stage kidney disease (ESKD). It is also a rare case of revolutionary changes in our understanding of the disease, that translates from scientific findings to real diagnosis and treatment recommendations in less than ten years. In this review we present: (1) a short history and traditional approach to patients with membranous nephropathy, (2) current recommendations and treatment options that have emerged in recent years, (3) findings of new studies, with a particular focus on serological/immunological methods, genomic and proteomic studies, still requiring validation. With further development in this field, membranous nephropathy may become one of the first nephrological conditions that apply a truly personalized approach with the omission of invasive measures such as kidney biopsy.
Cadmium (II)-Induced Oxidative Stress Results in Replication Stress and Epigenetic Modifications in Root Meristem Cell Nuclei of Vicia faba

Among heavy metals, cadmium is considered one of the most toxic and dangerous environmental factors, contributing to stress by disturbing the delicate balance between production and scavenging of reactive oxygen species (ROS). To explore possible relationships and linkages between Cd(II)-induced oxidative stress and the consequent damage at the genomic level (followed by DNA replication stress), root apical meristem (RAM) cells in broad bean (V. faba) seedlings exposed to CdCl2 treatment and to post-cadmium recovery water incubations were tested with respect to H2O2 production, DNA double-strand breaks (γ-phosphorylation of H2AX histones), chromatin morphology, histone H3S10 phosphorylation on serine (a marker of chromatin condensation), mitotic activity, and EdU staining (to quantify cells typical of different stages of nuclear DNA replication). In order to evaluate Cd(II)-mediated epigenetic changes involved in transcription and in the assembly of nucleosomes during the S-phase of the cell cycle, the acetylation of histone H3 on lysine 5 (H3K56Ac) was investigated by immunofluorescence. Cellular responses to cadmium (II) toxicity seem to be composed of a series of interlinked biochemical reactions, which, via generation of ROS and DNA damage-induced replication stress, ultimately activate signal factors engaged in cell cycle control pathways, DNA repair systems, and epigenetic adaptations.
Roles of Plant Growth-Promoting Rhizobacteria (PGPR) in Stimulating Salinity Stress Defense in Plants: A Review

To date, soil salinity becomes a huge obstacle for food production worldwide since salt stress is one of the major factors limiting agricultural productivity. It is estimated that a significant loss of crops (20–50%) would be due to drought and salinity. To embark upon this harsh situation, numerous strategies such as plant breeding, plant genetic engineering, and a large variety of agricultural practices including the applications of plant growth-promoting rhizobacteria (PGPR) and seed biopriming technique have been developed to improve plant defense system against salt stress, resulting in higher crop yields to meet human’s increasing food demand in the future. In the present review, we update and discuss the advantageous roles of beneficial PGPR as green bioinoculants in mitigating the burden of high saline conditions on morphological parameters and on physio-biochemical attributes of plant crops via diverse mechanisms. In addition, the applications of PGPR as a useful tool in seed biopriming technique are also updated and discussed since this approach exhibits promising potentials in improving seed vigor, rapid seed germination, and seedling growth uniformity. Furthermore, the controversial findings regarding the fluctuation of antioxidants and osmolytes in PGPR-treated plants are also pointed out and discussed.
Dietary Antioxidants in the Treatment of Male Infertility: Counteracting Oxidative Stress

Simple Summary The present review is a comprehensive description of reactive oxygen species (ROS’s) different sources, the re-productive consequences of excessive ROS and oxidative stress, and the possible treatments of ROS imbalances through antioxidant intake, foods, and dietary patterns to im-prove male infertility. In summary here we describe that some antioxidants, especially selenium and zinc, ω-3 fatty acids, CoQ10 and carnitines, have been positively related to sperm quality and therefore can help improving male sperm quality and fertility. However, excessive use of antioxidants may be detrimental to the spermatic function and many of the over-the-counter supplements are not scientifically proven to improve fertility. A long term and innocuous solution could be a balanced diet, as it takes advantage of the synergy of multiple antioxidants. Abstract Infertility affects about 15% of the population and male factors only are responsible for ~25–30% of cases of infertility. Currently, the etiology of suboptimal semen quality is poorly understood, and many environmental and genetic factors, including oxidative stress, have been implicated. Oxidative stress is an imbalance between the production of free radicals, or reactive oxygen species (ROS), and the capacity of the body to counteract their harmful effects through neutralization by antioxidants. The purpose of this review, by employing the joint expertise of international researchers specialized in nutrition and male fertility areas, is to update the knowledge about the reproductive consequences of excessive ROS concentrations and oxidative stress on the semen quality and Assisted Reproduction Techniques (ART) clinical outcomes, to discuss the role of antioxidants in fertility outcomes, and finally to discuss why foods and dietary patterns are more innocuous long term solution for ameliorating oxidative stress and therefore semen quality results and ART fertility outcomes. Since this is a narrative review and not a systematic/meta-analysis, the summarized information in the present study should be considered cautiously.
Evaluation of Antibiotic Dissemination into the Environment and Untreated Animals, by Analysis of Oxytetracycline in Poultry Droppings and Litter

Simple Summary Oxytetracycline (OTC) is an antibiotic used mainly in feed and drinking water. OTC is poorly absorbed in the gastrointestinal tract of poultry; making droppings a potential route of dissemination of this antibiotic. The aim of this study was to evaluate the dissemination of oxytetracycline excreted from treated birds to the environment and other untreated animals (sentinels), through the analysis of their droppings and litter by HPLC-MS/MS following the end of treatment. In treated bird droppings, the average concentration of OTC+4-epi-OTC ranged from 347.63 to 2244.66 µg kg−1. OTC+4-epi-OTC in litter reached concentrations of 22,741.68 µg kg−1. Traces of OTC+4-epi-OTC were detected in the droppings and litter from sentinels. Therefore, OTC+4-epi-OTC can persist in the litter of treated animals at high concentrations and can be transferred to untreated birds that share the same environment. This exposure has the potential to increase the likelihood of selection of resistant bacteria in the environment. Abstract Oxytetracycline (OTC) is widely used in broiler chickens. During and after treatment a fraction of OTC is excreted in its original form and as its epimer, 4-epi-OTC in droppings. To address the transfer of OTC into the environment, we evaluated the dissemination of OTC and 4-epi-OTC from treated birds to the environment and sentinels, through the simultaneous analysis of broiler droppings and litter. Male broiler chickens were bred in controlled conditions. One group was treated by orogastric tube with 80 mg kg−1 of OTC and two groups received no treatment (sentinels). OTC+4-epi-OTC were analyzed and detected by a HPLC-MS/MS post the end of treatment. The highest concentrations of OTC+4-epi-OTC were detected in the droppings of treated birds 14-days following the end of treatment (2244.66 µg kg−1), and one day following the end of treatment in the litter (22,741.68 µg kg−1). Traces of OTC+4-epi-OTC were detected in the sentinels’ droppings and litter (<12.2 µg kg−1). OTC+4-epi-OTC can be transferred from treated birds to the environment and to other untreated birds. The presence and persistence of OTC+4-epi-OTC in litter could contribute to the selection of resistant bacteria in the environment, increasing the potential hazard to public and animal health.
12-Week Inspiratory Muscle Training Improves Respiratory Muscle Strength in Adult Patients with Stable Asthma: A Randomized Controlled Trial

This study aims to investigate and compare the effects of conventional breathing exercises and an inspiratory muscle training intervention on clinical symptoms in asthma patients. Sixty asthma patients (40–65 years old) were randomly assigned to either the conventional breathing exercises (BTE) or inspiratory muscle training (IMT) group for a 12-week intervention period. Outcome measurements were performed before and after the intervention, including the spirometry data, maximal inspiratory and expiratory pressures (PImax and PEmax), asthma control test, asthma control questionnaire, six-minute walk test, and three-day physical activity log, were recorded. PImax expressed as % of predicted value controlled for age and gender in healthy subjects (% predicted) increased by 16.92% (82.45% to 99.38%, p < 0.05) in the BTE group and by 29.84% (71.19% to 101.03%, p < 0.05) in the IMT group. Except for forced vital capacity, which was reduced in the BTE group, all other measured variables improved in both groups, and no statistically significant between-group differences were found. IMT appears to be more effective than breathing exercise intervention in promoting improvements in respiratory muscle strength. IMT may act as an alternative to conventional breathing exercises for middle-aged and elderly asthma patients.
Baicalin Represses Type Three Secretion System of Pseudomonas aeruginosa through PQS System

Therapeutics that target the virulence of pathogens rather than their viability offer a promising alternative for treating infectious diseases and circumventing antibiotic resistance. In this study, we searched for anti-virulence compounds against Pseudomonas aeruginosa from Chinese herbs and investigated baicalin from Scutellariae radix as such an active anti-virulence compound. The effect of baicalin on a range of important virulence factors in P. aeruginosa was assessed using luxCDABE-based reporters and by phenotypical assays. The molecular mechanism of the virulence inhibition by baicalin was investigated using genetic approaches. The impact of baicalin on P. aeruginosa pathogenicity was evaluated by both in vitro assays and in vivo animal models. The results show that baicalin diminished a plenty of important virulence factors in P. aeruginosa, including the Type III secretion system (T3SS). Baicalin treatment reduced the cellular toxicity of P. aeruginosa on the mammalian cells and attenuated in vivo pathogenicity in a Drosophila melanogaster infection model. In a rat pulmonary infection model, baicalin significantly reduced the severity of lung pathology and accelerated lung bacterial clearance. The PqsR of the Pseudomonas quinolone signal (PQS) system was found to be required for baicalin’s impact on T3SS. These findings indicate that baicalin is a promising therapeutic candidate for treating P. aeruginosa infections.
Comparison of Polysaccharides Extracted from Cultivated Mycelium of Inonotus obliquus with Polysaccharide Fractions Obtained from Sterile Conk (Chaga) and Birch Heart Rot

The polysaccharides of the sterile conk of Inonotus obliquus (Chaga) have demonstrated multiple bioactivities. The mycelium of this basidiomycete, obtained after submerged cultivation, has been considered a feasible alternative to the sterile conk for the production of polysaccharides. However, previous research has paid little attention to the differences in the structures of polymers obtained from the different resources. Moreover, the birch wood colonized by I. obliquus has never been investigated as a source of bioactive polysaccharides. In the present study, polysaccharide fractions produced from cultivated mycelium, sterile conks of different geographical origins, and birch heart rot were investigated. High amounts of phenolic compounds, possibly lignans, were bound to the sterile conk polysaccharides. Mycelial polysaccharides were rich in α- and β-glucans and had high (105 Da) and low (104 Da) molecular weight populations. On the other hand, sterile conk polysaccharides were mainly β-glucan of lower and monodispersed molecular weight (103 Da). Heart rot polysaccharides were comprised mainly of low molecular weight (103 Da) hemicelluloses. Nevertheless, fungal polysaccharides were identified in the extracts. The differences in structure and molecular properties among the polysaccharide fractions of mycelium, heart rot, and sterile conk are likely associated with differences in bioactivities and, therefore, in nutraceutical potential.
Oxidative Stress and Vascular Damage in the Context of Obesity: The Hidden Guest

The vascular system plays a central role in the transport of cells, oxygen and nutrients between different regions of the body, depending on the needs, as well as of metabolic waste products for their elimination. While the structure of different components of the vascular system varies, these structures, especially those of main arteries and arterioles, can be affected by the presence of different cardiovascular risk factors, including obesity. This vascular remodeling is mainly characterized by a thickening of the media layer as a consequence of changes in smooth muscle cells or excessive fibrosis accumulation. These vascular changes associated with obesity can trigger functional alterations, with endothelial dysfunction and vascular stiffness being especially common features of obese vessels. These changes can also lead to impaired tissue perfusion that may affect multiple tissues and organs. In this review, we focus on the role played by perivascular adipose tissue, the activation of the renin-angiotensin-aldosterone system and endoplasmic reticulum stress in the vascular dysfunction associated with obesity. In addition, the participation of oxidative stress in this vascular damage, which can be produced in the perivascular adipose tissue as well as in other components of the vascular wall, is updated.
Ischemic Stroke Risk Factors in Patients with Atrial Fibrillation Treated with New Oral Anticoagulants

The most commonly used therapeutic option for the prevention of ischemic stroke in patients with atrial fibrillation is new- or old-generation oral anticoagulants. New oral anticoagulants are at least as effective as old-generation oral anticoagulants in the prevention of ischemic stroke, with a reduced risk of life-threatening hemorrhage. Moreover, the constant monitoring of these drugs in the patient’s blood is not required during routine use. However, ischemic stroke can still occur in these patients. Therefore, the aim of this study was to investigate the pattern of risk factors for ischemic stroke in patients with atrial fibrillation treated with new oral anticoagulants. Our multicenter retrospective study involved 2032 patients with acute ischemic stroke. The experimental group consisted of 256 patients with acute ischemic stroke and nonvalvular atrial fibrillation, who were treated with new oral anticoagulants. The control group consisted of 1776 ischemic stroke patients without coexisting atrial fibrillation. The results of our study show that patients with atrial fibrillation treated with new oral anticoagulants are more likely to display thrombotic, proatherogenic, and proinflammatory factors in addition to the embolic factors associated with atrial fibrillation. Therefore, solely taking new oral anticoagulants is insufficient in protecting this group of patients from ischemic stroke.
Fungicidal Activity of a Safe 1,3,4-Oxadiazole Derivative Against Candida albicans

Candida albicans is the most common species isolated from nosocomial bloodstream infections. Due to limited therapeutic arsenal and increase of drug resistance, there is an urgent need for new antifungals. Therefore, the antifungal activity against C. albicans and in vivo toxicity of a 1,3,4-oxadiazole compound (LMM6) was evaluated. This compound was selected by in silico approach based on chemical similarity. LMM6 was highly effective against several clinical C. albicans isolates, with minimum inhibitory concentration values ranging from 8 to 32 µg/mL. This compound also showed synergic effect with amphotericin B and caspofungin. In addition, quantitative assay showed that LMM6 exhibited a fungicidal profile and a promising anti-biofilm activity, pointing to its therapeutic potential. The evaluation of acute toxicity indicated that LMM6 is safe for preclinical trials. No mortality and no alterations in the investigated parameters were observed. In addition, no substantial alteration was found in Hippocratic screening, biochemical or hematological analyzes. LMM6 (5 mg/kg twice a day) was able to reduce both spleen and kidneys fungal burden and further, promoted the suppresses of inflammatory cytokines, resulting in infection control. These preclinical findings support future application of LMM6 as potential antifungal in the treatment of invasive candidiasis.
Dietary Fibre Intake Is Associated with Serum Levels of Uraemic Toxins in Children with Chronic Kidney Disease

Imbalanced colonic microbial metabolism plays a pivotal role in generating protein-bound uraemic toxins (PBUTs), which accumulate with deteriorating kidney function and contribute to the uraemic burden of children with chronic kidney disease (CKD). Dietary choices impact the gut microbiome and metabolism. The aim of this study was to investigate the relation between dietary fibre and gut-derived PBUTs in paediatric CKD. Sixty-one (44 male) CKD children (9 ± 5 years) were prospectively followed for two years. Dietary fibre intake was evaluated by either 24-h recalls (73%) or 3-day food records (27%) at the same time of blood sampling for assessment of total and free serum levels of different PBUTs using liquid chromatography. We used linear mixed models to assess associations between fibre intake and PBUT levels. We found an inverse association between increase in fibre consumption (g/day) and serum concentrations of free indoxyl sulfate (−3.1% (−5.9%; −0.3%) (p = 0.035)), free p-cresyl sulfate (−2.5% (−4.7%; −0.3%) (p = 0.034)), total indole acetic acid (IAA) (−1.6% (−3.0%; −0.3%) (p = 0.020)), free IAA (−6.6% (−9.3%; −3.7%) (p < 0.001)), total serum p-cresyl glucuronide (pCG) (−3.0% (−5.6%; −0.5%) (p = 0.021)) and free pCG levels (−3.3% (−5.8%; −0.8%) (p = 0.010)). The observed associations between dietary fibre intake and the investigated PBUTs highlight potential benefits of fibre intake for the paediatric CKD population. The present observational findings should inform and guide adaptations of dietary prescriptions in children with CKD.
Sex Differences in Dysfunctional Movements and Asymmetries in Young Normal Weight, Overweight, and Obese Children

This study evaluated overall performance on the functional movement screen (FMS), prevalence of asymmetries and dysfunctional movements, and the relationship between measures of adiposity and the FMS score. Methods: Ninety-four (53 boys; 41 girls) 10–12-year-old children in Hungary and Germany who were participating in daily physical education performed the FMS. The mean FMS score in girls (14.1) was significantly higher than in boys (12.9). Individual test item scores were similar, except girls scored higher on the straight-leg raise. Most children (55% of boys, 68% of girls) presented with at least one asymmetry and 72% of boys and 76% of girls had at least one dysfunctional score. Measures of adiposity were negatively correlated to performance on all test items. Underweight and normal weight children performed significantly better on the FMS than overweight and obese children. Sex differences and the high prevalence of asymmetries and dysfunctional scores should be interpreted with caution since they may be due to dynamic changes in strength, proprioception, balance, and motor control that occur as part of growth and involvement in activities. Nevertheless, the high prevalence of asymmetries and dysfunctional scores indicate that most children have movement limitations.
EPIP-Evoked Modifications of Redox, Lipid, and Pectin Homeostasis in the Abscission Zone of Lupine Flowers

Yellow lupine is a great model for abscission-related research given that excessive flower abortion reduces its yield. It has been previously shown that the EPIP peptide, a fragment of LlIDL (INFLORESCENCE DEFICIENT IN ABSCISSION) amino-acid sequence, is a sufficient molecule to induce flower abortion, however, the question remains: What are the exact changes evoked by this peptide locally in abscission zone (AZ) cells? Therefore, we used EPIP peptide to monitor specific modifications accompanied by early steps of flower abscission directly in the AZ. EPIP stimulates the downstream elements of the pathway—HAESA and MITOGEN-ACTIVATED PROTEIN KINASE6 and induces cellular symptoms indicating AZ activation. The EPIP treatment disrupts redox homeostasis, involving the accumulation of H2O2 and upregulation of the enzymatic antioxidant system including superoxide dismutase, catalase, and ascorbate peroxidase. A weakening of the cell wall structure in response to EPIP is reflected by pectin demethylation, while a changing pattern of fatty acids and acyl lipids composition suggests a modification of lipid metabolism. Notably, the formation of a signaling molecule—phosphatidic acid is induced locally in EPIP-treated AZ. Collectively, all these changes indicate the switching of several metabolic and signaling pathways directly in the AZ in response to EPIP, which inevitably leads to flower abscission.
Stretching of Bombyx mori Silk Protein in Flow

The flow-induced self-assembly of entangled Bombyx mori silk proteins is hypothesised to be aided by the ‘registration’ of aligned protein chains using intermolecularly interacting ‘sticky’ patches. This suggests that upon chain alignment, a hierarchical network forms that collectively stretches and induces nucleation in a precisely controlled way. Through the lens of polymer physics, we argue that if all chains would stretch to a similar extent, a clear correlation length of the stickers in the direction of the flow emerges, which may indeed favour such a registration effect. Through simulations in both extensional flow and shear, we show that there is, on the other hand, a very broad distribution of protein–chain stretch, which suggests the registration of proteins is not directly coupled to the applied strain, but may be a slow statistical process. This qualitative prediction seems to be consistent with the large strains (i.e., at long time scales) required to induce gelation in our rheological measurements under constant shear. We discuss our perspective of how the flow-induced self-assembly of silk may be addressed by new experiments and model development.