Miracle-dz/UniFAR-FTUs huggingface dataset:
Trace Element and Mineral Levels in Serum, Hair, and Urine of Obese Women in Relation to Body Composition, Blood Pressure, Lipid Profile, and Insulin Resistance

The objective of this study was to evaluate serum, hair, and urinary trace element and mineral content in normal-weight and obese women in relation to metabolic risk factors. A total of 80 women aged 30–70 y.o. were enrolled in the obese group (n = 40) and normal-weight group (n = 40). Serum, hair, and urinary trace element and mineral levels were assessed using inductively coupled plasma spectrometry. Body fat percentage was evaluated using bioimpedance. Obese subjects were characterized by significantly higher body fat percentage, blood pressure, serum triglyceride concentration, and insulin resistance. Serum Ca, Fe, Mg, Se, V, Zn levels, hair Fe, Mg, V content, and urinary Se and V concentrations were found to be lower in obese subjects as compared to lean controls. In turn, serum Cu and urinary Fe levels in obese women were characterized by a significant increase. In multiple regression models serum Cu, Se, and Zn levels were significantly associated with BMI even after adjustment for blood biochemistry, body composition, and blood pressure. Serum trace element and mineral levels also significantly contributed to group discrimination. These findings allow to propose that obesity-associated disturbances in trace element and mineral status may at least partially contribute to metabolic risk in obese subjects.
Probiotic-Based Vaccines May Provide Effective Protection against COVID-19 Acute Respiratory Disease

Severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) infection, the causative agent of COVID-19, now represents the sixth Public Health Emergency of International Concern (PHEIC)—as declared by the World Health Organization (WHO) since 2009. Considering that SARS-CoV-2 is mainly transmitted via the mucosal route, a therapy administered by this same route may represent a desirable approach to fight SARS-CoV-2 infection. It is now widely accepted that genetically modified microorganisms, including probiotics, represent attractive vehicles for oral or nasal mucosal delivery of therapeutic molecules. Previous studies have shown that the mucosal administration of therapeutic molecules is able to induce an immune response mediated by specific serum IgG and mucosal IgA antibodies along with mucosal cell-mediated immune responses, which effectively concur to neutralize and eradicate infections. Therefore, advances in the modulation of mucosal immune responses, and in particular the use of probiotics as live delivery vectors, may encourage prospective studies to assess the effectiveness of genetically modified probiotics for SARS-CoV-2 infection. Emerging trends in the ever-progressing field of vaccine development re-emphasize the contribution of adjuvants, along with optimization of codon usage (when designing a synthetic gene), expression level, and inoculation dose to elicit specific and potent protective immune responses. In this review, we will highlight the existing pre-clinical and clinical information on the use of genetically modified microorganisms in control strategies against respiratory and non-respiratory viruses. In addition, we will discuss some controversial aspects of the use of genetically modified probiotics in modulating the cross-talk between mucosal delivery of therapeutics and immune system modulation.
Detection and Differentiation of SARS-CoV-2, Influenza, and Respiratory Syncytial Viruses by CRISPR

SARS-CoV-2, influenza, and respiratory syncytial viruses (RSVs) cause acute respiratory infections with similar symptoms. Since the treatments and outcomes of these infections are different, the early detection and accurate differentiation of the viruses are clinically important for the prevention and treatment of the diseases. We previously demonstrated that clustered regularly interspaced short palindromic repeats (CRISPR) could rapidly and precisely detect SARS-CoV-2. The objective of this study was to develop CRISPR as a test for simultaneously detecting and accurately distinguishing the viruses. The CRISPR assay with an RNA guide against each virus was performed in the reference standards of SARS-CoV-2, influenza A and B, and RSV. The CRISPR assay had a limit of detection of 1–100 copies/µL for specifically detecting SARS-CoV-2, influenza A and B, and RSV without cross-reaction with other respiratory viruses. The validation of the test in nasopharyngeal specimens showed that it had a 90–100% sensitivity and 100% specificity for the detection of SARS-CoV-2, influenza A and B, and RSV. The CRISPR assay could potentially be used for sensitive detection and specific differentiation of the respiratory viruses.
Chromothripsis—Explosion in Genetic Science

Chromothripsis has been defined as complex patterns of alternating genes copy number changes (normal, gain or loss) along the length of a chromosome or chromosome segment (International System for Human Cytogenomic Nomenclature 2020). The phenomenon of chromothripsis was discovered in 2011 and changed the concept of genome variability, mechanisms of oncogenic transformation, and hereditary diseases. This review describes the phenomenon of chromothripsis, its prevalence in genomes, the mechanisms underlying this phenomenon, and methods of its detection. Due to the fact that most often the phenomenon of chromothripsis occurs in cancer cells, in this review, we will separately discuss the issue of the contribution of chromothripsis to the process of oncogenesis.
Plant Preparations and Compounds with Activities against Biofilms Formed by Candida spp.

Fungi from the genus Candida are very important human and animal pathogens. Many strains can produce biofilms, which inhibit the activity of antifungal drugs and increase the tolerance or resistance to them as well. Clinically, this process leads to persistent infections and increased mortality. Today, many Candida species are resistant to drugs, including C. auris, which is a multiresistant pathogen. Natural compounds may potentially be used to combat multiresistant and biofilm-forming strains. The aim of this review was to present plant-derived preparations and compounds that inhibit Candida biofilm formation by at least 50%. A total of 29 essential oils and 16 plant extracts demonstrate activity against Candida biofilms, with the following families predominating: Lamiaceae, Myrtaceae, Asteraceae, Fabaceae, and Apiacae. Lavandula dentata (0.045–0.07 mg/L), Satureja macrosiphon (0.06–8 mg/L), and Ziziphora tenuior (2.5 mg/L) have the best antifungal activity. High efficacy has also been observed with Artemisia judaica, Lawsonia inermis, and Thymus vulgaris. Moreover, 69 plant compounds demonstrate activity against Candida biofilms. Activity in concentrations below 16 mg/L was observed with phenolic compounds (thymol, pterostilbene, and eugenol), sesquiterpene derivatives (warburganal, polygodial, and ivalin), chalconoid (lichochalcone A), steroidal saponin (dioscin), flavonoid (baicalein), alkaloids (waltheriones), macrocyclic bisbibenzyl (riccardin D), and cannabinoid (cannabidiol). The above compounds act on biofilm formation and/or mature biofilms. In summary, plant preparations and compounds exhibit anti-biofilm activity against Candida. Given this, they may be a promising alternative to antifungal drugs.
Regulation of Vitamin C Accumulation for Improved Tomato Fruit Quality and Alleviation of Abiotic Stress

Ascorbic acid (AsA) is an essential multifaceted phytonutrient for both the human diet and plant growth. Optimum levels of AsA accumulation combined with balanced redox homeostasis are required for normal plant development and defense response to adverse environmental stimuli. Notwithstanding its moderate AsA levels, tomatoes constitute a good source of vitamin C in the human diet. Therefore, the enhancement of AsA levels in tomato fruit attracts considerable attention, not only to improve its nutritional value but also to stimulate stress tolerance. Genetic regulation of AsA concentrations in plants can be achieved through the fine-tuning of biosynthetic, recycling, and transport mechanisms; it is also linked to changes in the whole fruit metabolism. Emerging evidence suggests that tomato synthesizes AsA mainly through the l-galactose pathway, but alternative pathways through d-galacturonate or myo-inositol, or seemingly unrelated transcription and regulatory factors, can be also relevant in certain developmental stages or in response to abiotic factors. Considering the recent advances in our understanding of AsA regulation in model and other non-model species, this review attempts to link the current consensus with novel technologies to provide a comprehensive strategy for AsA enhancement in tomatoes, without any detrimental effect on plant growth or fruit development.
Differential Effects of Angiotensin-II Compared to Phenylephrine on Arterial Stiffness and Hemodynamics: A Placebo-Controlled Study in Healthy Humans

The α1-adrenoceptor agonist phenylephrine (PE) and Angiotensin II (Ang II) are both potent vasoconstrictors at peripheral resistance arteries. PE has pure vasoconstrictive properties. Ang II, additionally, modulates central nervous blood pressure (BP) control via sympathetic baroreflex resetting. However, it is unknown whether Ang II vs. PE mediated vasoconstriction at equipressor dose uniformly or specifically modifies arterial stiffness. We conducted a three-arm randomized placebo-controlled cross-over trial in 30 healthy volunteers (15 female) investigating the effects of Ang II compared to PE at equal systolic pressor dose on pulse wave velocity (PWV), pulse wave reflection (augmentation index normalized to heart rate 75/min, AIx) and non-invasive hemodynamics by Mobil-O-Graph™ and circulating core markers of endothelial (dys-)function. PE but not Ang II-mediated hypertension induced a strong reflex-decrease in cardiac output. Increases in PWV, AIx, total peripheral resistance and pulse pressure, in contrast, were stronger during PE compared to Ang II at equal mean aortic BP. This was accompanied by minute changes in circulating markers of endothelial function. Moreover, we observed differential hemodynamic changes after stopping either vasoactive infusion. Ang II- and PE-mediated BP increase specifically modifies arterial stiffness and hemodynamics with aftereffects lasting beyond mere vasoconstriction. This appears attributable in part to different interactions with central nervous BP control including modified baroreflex function.
Effects of Medicinal Plants and Organic Selenium against Ovine Haemonchosis

Simple Summary Maintaining high productivity in small ruminants is hindered by infection with the parasitic gastrointestinal nematode (GIN) Haemonchus contortus. There is an increasing interest to find alternative treatments for controlling GINs due to the rapid development of resistance to synthetic anthelmintics. Supplementary feeding of plant nutraceuticals or mineral supplements may contribute to improving the resilience of lambs. The trace element selenium and vitamin E act synergistically as antioxidants in circulation, but the natural occurrence of selenium is very low in the soil, grain, and roughage. The aim of this study was therefore to determine the long-term effects of medicinal plants and organic selenium in lambs experimentally infected with H. contortus. The results indicated that both supplements favorably affected the infected lambs and may provide a new approach to controlling haemonchosis in small ruminants. Abstract The objective of this study was to determine the effect of traditional medicinal plants typical to Central Europe as well as organic selenium on increasing the resistance of lambs to gastrointestinal nematode (GIN) infection with Haemonchus contortus. 21 female lambs were infected with third-stage larvae of H. contortus on the day (D) 0 and re-infected on D49 and D77. The animals were divided into three groups based on a treatment diet: a basal diet (control), a diet enriched with dry plants (Herbmix), and a diet enriched with selenized yeast (Selplex). The number of eggs per gram (EPG) of feces was quantified on D21, D28, D35, D42, D49, D56, D63, D70, D77, D84, D91, D98, D105, D112, and D119. The mean reductions in EPG on D28 were 43.4 and 28.6% for Selplex and Herbmix, respectively. The reduction in egg output was nearly uniform throughout the experiment for Selplex. However, for Herbmix the mean reduction was only 19.8% up to D91 and 46.1% after D91. Glutathione peroxidase activity in the blood from D35 to D98 was two to three-fold higher for Selplex than the other groups. Both supplements slowed the dynamics of GIN infection and gradually increased the resistance of lambs against ovine haemonchosis.
Transcriptome Analysis of Light-Regulated Monoterpenes Biosynthesis in Leaves of Mentha canadensis L.

Light is a key environmental aspect that regulates secondary metabolic synthesis. The essential oil produced in mint (Mentha canadensis L.) leaves is used widely in the aromatics industry and in medicine. Under low-light treatment, significant reductions in peltate glandular trichome densities were observed. GC-MS analysis showed dramatically reduced essential oil and menthol contents. Light affected the peltate glandular trichomes’ development and essential oil yield production. However, the underlying mechanisms of this regulation were elusive. To identify the critical genes during light-regulated changes in oil content, following a 24 h darkness treatment and a 24 h recovery light treatment, leaves were collected for transcriptome analysis. A total of 95,579 unigenes were obtained, with an average length of 754 bp. About 56.58% of the unigenes were annotated using four public protein databases: 10,977 differentially expressed genes (DEGs) were found to be involved in the light signaling pathway and monoterpene synthesis pathway. Most of the TPs showed a similar expression pattern: downregulation after darkness treatment and upregulation after the return of light. In addition, the genes involved in the light signal transduction pathway were analyzed. A series of responsive transcription factors (TFs) were identified and could be used in metabolic engineering as an effective strategy for increasing essential oil yields.
Genetic Alterations and Therapeutic Targeting of Philadelphia-Like Acute Lymphoblastic Leukemia

Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a subgroup of B-cell precursor ALL which by gene expression analysis clusters with Philadelphia-positive ALL although lacking the pathognomonic BCR-ABL1 oncoprotein. Its prevalence increases with age and similar to BCR-ABL1-positive ALL, Ph-like ALL is characterized by IKZF1 or other B-lymphoid transcription factor gene deletions and by poor outcome to conventional therapeutic approaches. Genetic alterations are highly heterogenous across patients and include gene fusions, sequence mutations, DNA copy number changes and cryptic rearrangements. These lesions drive constitutively active cytokine receptor and kinase signaling pathways which deregulate ABL1 or JAK signaling and more rarely other kinase-driven pathways. The presence of activated kinase alterations and cytokine receptors has led to the incorporation of targeted therapy to the chemotherapy backbone which has improved treatment outcome for this high-risk subtype. More recently, retrospective studies have shown the efficacy of immunotherapies including both antibody drug-conjugates and chimeric antigen receptor T cell therapy and as they are not dependent on a specific genetic alteration, it is likely their use will increase in prospective clinical trials. This review summarizes the genomic landscape, clinical features, diagnostic assays, and novel therapeutic approaches for patients with Ph-like ALL.
Peste des Petits Ruminants Virus Infection at the Wildlife–Livestock Interface in the Greater Serengeti Ecosystem, 2015–2019

Peste des petits ruminants (PPR) is a viral disease of goats and sheep that occurs in Africa, the Middle East and Asia with a severe impact on livelihoods and livestock trade. Many wild artiodactyls are susceptible to PPR virus (PPRV) infection, and some outbreaks have threatened endangered wild populations. The role of wild species in PPRV epidemiology is unclear, which is a knowledge gap for the Global Strategy for the Control and Eradication of PPR. These studies aimed to investigate PPRV infection in wild artiodactyls in the Greater Serengeti and Amboseli ecosystems of Kenya and Tanzania. Out of 132 animals purposively sampled in 2015–2016, 19.7% were PPRV seropositive by ID Screen PPR competition enzyme-linked immunosorbent assay (cELISA; IDvet, France) from the following species: African buffalo, wildebeest, topi, kongoni, Grant’s gazelle, impala, Thomson’s gazelle, warthog and gerenuk, while waterbuck and lesser kudu were seronegative. In 2018–2019, a cross-sectional survey of randomly selected African buffalo and Grant’s gazelle herds was conducted. The weighted estimate of PPRV seroprevalence was 12.0% out of 191 African buffalo and 1.1% out of 139 Grant’s gazelles. All ocular and nasal swabs and faeces were negative by PPRV real-time reverse transcription-polymerase chain reaction (RT-qPCR). Investigations of a PPR-like disease in sheep and goats confirmed PPRV circulation in the area by rapid detection test and/or RT-qPCR. These results demonstrated serological evidence of PPRV infection in wild artiodactyl species at the wildlife–livestock interface in this ecosystem where PPRV is endemic in domestic small ruminants. Exposure to PPRV could be via spillover from infected small ruminants or from transmission between wild animals, while the relatively low seroprevalence suggests that sustained transmission is unlikely. Further studies of other major wild artiodactyls in this ecosystem are required, such as impala, Thomson’s gazelle and wildebeest.
Fibrotic Events in the Progression of Cholestatic Liver Disease

Cholestatic liver diseases including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are associated with active hepatic fibrogenesis, which can ultimately lead to the development of cirrhosis. However, the exact relationship between the development of liver fibrosis and the progression of cholestatic liver disease remains elusive. Periductular fibroblasts located around the bile ducts seem biologically different from hepatic stellate cells (HSCs). The fibrotic events in these clinical conditions appear to be related to complex crosstalk between immune/inflammatory mechanisms, cytokine signalling, and perturbed homeostasis between cholangiocytes and mesenchymal cells. Several animal models including bile duct ligation (BDL) and the Mdr2-knockout mice have improved our understanding of mechanisms underlying chronic cholestasis. In the present review, we aim to elucidate the mechanisms of fibrosis in order to help to identify potential diagnostic and therapeutic targets.
Genomic Imprinting at the Porcine DIRAS3 Locus

Simple Summary DNA methylation associated with one of the two alleles from parents is an important mechanism that causes a silencing of that allele, leading to expression of another allele only. There has been a lack of detailed studies on DNA methylation and expression patterns that are related to the DIRAS3 gene in pigs. The objective of this study was to provide a comprehensive overview of DNA methylation and expression associated with the DIRAS3 gene in pigs by generating an embryonic pig model and analyzing next-generation sequencing using pig embryos and adult pigs. Our results clearly showed the presence of DNA methylation near the DIRAS3 gene in pigs and high expression of DIRAS3 in the hypothalamus from adult pigs and expression of only one allele in all the tested tissues including the hypothalamus. In summary, our findings suggested DNA methylation might be related to those unique gene expression patterns during the development of pigs. Abstract The epigenetic mechanisms underlying genomic imprinting include DNA methylation and monoallelic expression of genes in close proximity. Although genes imprinted in humans and mice have been widely characterized, there is a lack of detailed and comprehensive studies in livestock species including pigs. The purpose of this study was to investigate a detailed methylation status and parent-of-origin-specific gene expression within the genomic region containing an underexamined porcine DIRAS3 locus. Through whole-genome bisulfite sequencing (WGBS) and RNA sequencing (RNA-seq) of porcine parthenogenetic embryos and analyses of public RNA-seq data from adult pigs, DNA methylation and monoallelic expression pattern were investigated. As a result, maternal hypermethylation at the DIRAS3 locus and hypothalamus-specific and monoallelic expression of the DIRAS3 gene were found in pigs. In conclusion, the findings from this study suggest that the presence of maternal hypermethylation, or imprints, might be maintained and related to monoallelic expression of DIRAS3 during pig development.
Ribosome-Inactivating Proteins of Bougainvillea glabra Uncovered Polymorphism and Active Site Divergence

Ribosome-inactivating proteins (RIPs) are toxic proteins that can inhibit protein synthesis. RIPs purified from Bougainvillea have low nonspecific toxicity, showing promise for processing applications in the agricultural and medical fields. However, systematic research on the polymorphism of Bougainvillea RIPs is lacking, and it is worth exploring whether different isoforms differ in their active characteristics. The transcriptional and translational expression of type I RIPs in Bougainvillea glabra leaves was investigated in this study. Seven RIPs exhibited seasonal variation at both the mRNA and protein levels. The isoforms BI4 and BI6 showed the highest transcriptional expression in both the summer and autumn samples. Interestingly, BI6 was not detected in the protein level in any of the samples. However, the bioinformatics analysis showed that RIPs derived from the same species were gathered in a different cluster, and that the active sites changed among the isoforms during evolution. The significant discrepancy in Bougainvillea RIPs mainly locates at both termini of the amino acid sequence, particularly at the C terminus. Post-translational modifications may also exist in Bougainvillea RIPs. It is concluded that the reason for the polymorphism of Bougainvillea RIPs may be that these proteins are encoded by multiple genes due to genetic processes such as gene duplication and mutation. According to the results of sequence analysis, the possible functional differences of B. glabra RIP isoforms are discussed with regard to the observed discrepancy in both active sites and structures.