Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-Term Exposure of Cultured Astrocytes to High Glucose Impact on Their LPS-Induced Activation

Diabetes mellitus is associated with various complications, mainly caused by the chronic exposure of the cells to high glucose (HG) concentrations. The effects of long-term HG exposure in vitro accompanied by lipopolysaccharide (LPS) application on astrocytes are relatively unknown. We used cell medium with normal (NG, 5.5 mM) or high glucose (HG, 25 mM) for rat astrocyte cultures and measured the release of NO, IL-6, β-hexosaminidase and cell survival in response to LPS. We first demonstrated that HG long-term incubation of astrocytes increased the release of β-hexosaminidase without decreasing MTT-detected cell survival, suggesting that there is no cell membrane damage or astrocyte death but could be lysosome exocytosis. Different from what was observed for NG, all LPS concentrations tested at HG resulted in an increase in IL-6, and this was detected for both 6 h and 48 h treatments. Interestingly, β-hexosaminidase level increased after 48 h of LPS and only at HG. The NO release from astrocytes also increased with LPS application at HG but was less significant. These data endorsed the original hypothesis that long-term hyperglycemia increases proinflammatory activation of astrocytes, and β-hexosaminidase could be a specific marker of excessive activation of astrocytes associated with exocytosis.
Hypoxia Modulates Radiosensitivity and Response to Different Radiation Qualities in A549 Non-Small Cell Lung Cancer (NSCLC) Cells

Hypoxia-induced radioresistance reduces the efficacy of radiotherapy for solid malignancies, including non-small cell lung cancer (NSCLC). Cellular hypoxia can confer radioresistance through cellular and tumor micro-environment adaptations. Until recently, studies evaluating radioresistance secondary to hypoxia were designed to maintain cellular hypoxia only before and during irradiation, while any handling of post-irradiated cells was carried out in standard oxic conditions due to the unavailability of hypoxia workstations. This limited the possibility of simulating in vivo or clinical conditions in vitro. The presence of molecular oxygen is more important for the radiotoxicity of low-linear energy transfer (LET) radiation (e.g., X-rays) than that of high-LET carbon (12C) ions. The mechanisms responsible for 12C ions’ potential to overcome hypoxia-induced radioresistance are currently not fully understood. Therefore, the radioresistance of hypoxic A549 NSCLC cells following exposure to X-rays or 12C ions was investigated along with cell cycle progression and gene expression by maintaining hypoxia before, during and after irradiation. A549 cells were incubated under normoxia (20% O2) or hypoxia (1% O2) for 48 h and then irradiated with X-rays (200 kV) or 12C ions (35 MeV/n, LET ~75 keV/µm). Cell survival was evaluated using colony-forming ability (CFA) assays immediately or 24 h after irradiation (late plating). DNA double-strand breaks (DSBs) were analyzed using γH2AX immunofluorescence microscopy. Cell cycle progression was determined by flow cytometry of 4′,6-diamidino-2-phenylindole-stained cells. The global transcription profile post-irradiation was evaluated by RNA sequencing. When hypoxia was maintained before, during and after irradiation, hypoxia-induced radioresistance was observed only in late plating CFA experiments. The killing efficiency of 12C ions was much higher than that of X-rays. Cell survival under hypoxia was affected more strongly by the timepoint of plating in the case of X-rays compared to 12C ions. Cell cycle arrest following irradiation under hypoxia was less pronounced but more prolonged. DSB induction and resolution following irradiation were not significantly different under normoxia and hypoxia. Gene expression response to irradiation primarily comprised cell cycle regulation for both radiation qualities and oxygen conditions. Several PI3K target genes involved in cell migration and cell motility were differentially upregulated in hypoxic cells. Hypoxia-induced radioresistance may be linked to altered cell cycle response to irradiation and PI3K-mediated changes in cell motility and migration in A549 cells rather than less DNA damage or faster repair.
Lactiplantibacillus plantarum Induces Apoptosis in Melanoma and Breast Cancer Cells

Despite the notable advancements witnessed in the past decade in medical and health research domain, cancer remains a prominent global cause of mortality. Moreover, the conventional treatments employed to combat this disease have been found to considerably compromise the quality of life experienced by patients due to its severe side effects. Recent in vitro studies revealed encouraging findings on the potential beneficial effects of probiotics as adjuvants of anticancer therapy, and even as possible agents for the prevention and treatment of various types of malignancies. From this standpoint, the primary objective of this work was to investigate the anticancer properties of Lactiplantibacillus plantarum (LP) and elucidate its underlying mechanism of action. In order to investigate this matter, several doses of LP (ranging from 105 to 1010 CFU/mL) were examined in relation to melanoma cancer cell lines (A375) and breast cancer cell line (MCF-7). The cell viability findings, which were substantiated by morphological investigations and annexin V/PI assay, indicated that LP exerted inhibitory effects on cellular activity and triggered apoptosis. Additionally, upon further investigation into its mechanism, it was observed through the apoptosis assay and Western blot analysis that the administration of LP resulted in an elevation of pro-apoptotic BAX protein levels and an upregulation of cleaved poly-ADP-ribose polymerase (PARP) protein expression. Conversely, the levels of anti-apoptotic Bcl-2 protein were found to decrease in the A375 and MCF-7 cell lines. These findings provide insight into the pro-apoptotic mechanism of action of LP in these specific cell lines.
Effect of Protein Content on Heat Stability of Reconstituted Milk Protein Concentrate under Controlled Shearing

Milk protein concentrates (MPCs) possess significant potential for diverse applications in the food industry. However, their heat stability may be a limitation to achieving optimal functional performance. Shearing, an inherent process in food manufacturing, can also influence the functionality of proteins. The aim of this research was to examine the heat stability of reconstituted MPCs prepared at two protein concentrations (4% and 8% w/w protein) when subjected to varying levels of shearing (100, 1000, or 1500 s−1) during heating at 90 °C for 5 min or 121 °C for 2.6 min. While the impact of shear was relatively minor at 4% protein, it was more pronounced in 8% protein MPC suspensions, leading to a considerable decline in heat stability. An increase in protein concentration to 8% amplified protein interactions, intensified by shearing. This, in turn, resulted in comparatively higher aggregation at elevated temperatures and subsequently reduced the heat stability of the reconstituted MPCs.
Do patients benefit from omega-3 fatty acids?

Abstract Omega-3 fatty acids (O3FAs) possess beneficial properties for cardiovascular (CV) health and elevated O3FA levels are associated with lower incident risk for CV disease (CVD.) Yet, treatment of at-risk patients with various O3FA formulations has produced disparate results in large, well-controlled and well-conducted clinical trials. Prescription formulations and fish oil supplements containing low-dose mixtures of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have routinely failed to prevent CV events in primary and secondary prevention settings when added to contemporary care, as shown most recently in the STRENGTH and OMEMI trials. However, as observed in JELIS, REDUCE-IT, and RESPECT-EPA, EPA-only formulations significantly reduce CVD events in high-risk patients. The CV mechanism of action of EPA, while certainly multifaceted, does not depend solely on reductions of circulating lipids, including triglycerides (TG) and LDL, and event reduction appears related to achieved EPA levels suggesting that the particular chemical and biological properties of EPA, as compared to DHA and other O3FAs, may contribute to its distinct clinical efficacy. In vitro and in vivo studies have shown different effects of EPA compared with DHA alone or EPA/DHA combination treatments, on atherosclerotic plaque morphology, LDL and membrane oxidation, cholesterol distribution, membrane lipid dynamics, glucose homeostasis, endothelial function, and downstream lipid metabolite function. These findings indicate that prescription-grade, EPA-only formulations provide greater benefit than other O3FAs formulations tested. This review summarizes the clinical findings associated with various O3FA formulations, their efficacy in treating CV disease, and their underlying mechanisms of action.
Association of the rs1126616 and rs9138 Variants in the SPP1 Gene among Mexican Patients with Systemic Lupus Erythematosus and Lupus Nephritis

Systemic lupus erythematosus (SLE) is a multisystem disease considered a prototype of the main autoimmune disease and presents serious complications, such as lupus nephritis (LN), which generates a significant impact on morbidity and mortality. The SPP1 gene encodes the osteopontin (OPN) protein, which plays a crucial role in the regulation of inflammation and immunity. The variants rs1126616 and rs9138 of this gene have been associated with the inflammatory response. The study aims to analyze the association of the rs1126616 and rs9138 variants of the SPP1 gene in SLE Mexican-Mestizo patients without LN (SLE-LN). In this cross-sectional study, a total of 171 genomic DNA samples from SLE patients were clinically confirmed, of which 111 were SLE without LN, 60 were SLE with LN, and 100 healthy individuals were included as reference group. The rs1126616 variant was genotyped using PCR-RFLPs, and the rs9138 variant was genotyped using qPCR TaqMan. The TT genotype, the recessive model [OR 2.76 (95% CI 1.31–5.82), p = 0.011], and the T allele [OR 2.0 (95% CI 1.26–3.16), p = 0.003] of the rs1126616 variant are risk factors for SLE with LN. By contrast, the rs9138 variant did not show statistically significant differences among SLE patients stratified by LN. In our study of SLE Mexican-Mestizo patients with and without NL, demographic and clinical characteristics do not differ from other SLE populations, and the TT genotype of the rs1126616 variant of the SPP1 gene confers a risk factor for the presentation of LN. Otherwise, the rs9138 variant did not show association with NL.
Regular and Irregular Use and Reasons for Discontinuation of Solifenacin Therapy in Patients with Overactive Bladder Managed by Urologists

Solifenacin, a selective muscarinic receptor antagonist, is one of the best-tolerated and most effective medicines that relieve storage symptoms in patients with an overactive bladder (OAB). However, the persistence of solifenacin in daily clinical practice remains far below that reported in clinical trials. This study aimed to analyze the adherence of patients to the therapy and the reasons for solifenacin discontinuation and non-regular use in OAB patients managed by urologists. Data concerning non-compliance and the discontinuation of solifenacin, along with the reasons, were collected during two consecutive visits for 64,049 OAB outpatients. Over the two visits, 81.6% of the patients continued therapy, and 88.6% were taking solifenacin regularly. An age ≥ 75 yrs. , the male sex, a rural or small-city dwelling, and a prescription of ≥10 mg predicted therapy continuation. The female sex, a higher education, a short or long duration of an OAB, and a non-idiopathic OAB predicted regular use. The persistence of nycturia and urinary incontinence during therapy predicted both discontinuation and non-regular use. Dissatisfaction with therapy was the most frequent reason for discontinuation. In conclusion, an initial prescription of solifenacin at a low dose reduces the chance of OAB symptom improvement and results in more frequent discontinuation. A high rate of discontinuation related to dissatisfaction suggests unrealistic expectations for OAB patients and insufficient education by urologists.
Isolation and Molecular Identification of New Benzene Degrading Lysinibacillus Strains from Gasoline Contaminated Soil

The aim of this study was to isolate and identify aerobic benzene-degrading bacteria from soil sample contaminated with gasoline. Soil samples were collected from gasoline-contaminated sites located around gas stations in the Al-Mafraq city of Jordan. Ten grams of soil were transferred to Stanier's medium supplemented with 1% benzene and aerobically incubate at 30°C for 72 h. Five morphologically different bacterial isolates were recovered from soil samples and designated as 1J1, 2J2, DJ2, 3J4 and 1J1-2. These isolates were subjected to analyses for identification and characterization. All isolates were Gram positive, endospore-forming, motile, mesophilic and rod-shaped aerobic bacteria. Biochemically, all were catalase and oxidase positive except DJ2, which was negative for oxidase. Based on their 16S rDNA sequences, they appear to be closely related to the genus Lysinibacillus (L). Isolate 1J1 revealed 91% homology with L. fusiformis, suggesting a member of a new genus with some similarity to the genus Lysinibacillus. Isolates 2J2, DJ2, 3J4 and 1J1-2 exhibited more than 97% sequence identity to L. xylanilyticus, L. odeysseyi, L. macrolides and L. boronitolerans, respectively. The 16S rDNA sequences of these isolates were deposited in GenBank database. All isolates grew best in Stanier's medium when the optimal growth conditions were 1% benzene, 30°C and pH 6.8. In conclusion, five novel bacterial isolates with similarity to the genus Lysinibacillus that utilize benzene as the sole carbon and energy source were isolated and characterized from soil samples contaminated by gasoline. These five isolates can be considered as ideal candidates for bioremediation of benzene from soils.
Rehabilitation and recovery for ethnic minority patients with severe mental illness

There is growing evidence to support recovery and rehabilitation services and interventions for people with severe mental illness (SMI). However, those from ethnic minority communities face inequitable outcomes and access to mental health services and poorer functional outcomes. This article reviews the evidence and discusses facilitators and barriers in the recovery journey of people with SMI from ethnic minority groups. Although there is limited evidence for specific interventions for ethnic minority patients, areas for future study and action are discussed.After reading this article you will be able to:•understand the scope of rehabilitation practices and interventions and evidence for use with ethnic minority patients with severe mental illness•describe differences and similarities in the conceptualisation of recovery by majority and minority ethnic communities•appreciate facilitators and barriers to rehabilitation and recovery for ethnic minority patients with SMI.None.
Integration of social and IoT technologies: architectural framework for digital transformation and cyber security challenges

ABSTRACT Growing synergies between the Internet of Things (IoT) and Social technologies are contributing to the advances in Cyber Physical Social Systems. Integration of new technologies is facing key challenges related to information security and privacy. This paper explores the interplay and synergetic relationships among these technologies, identifying relevant interactions, key challenges primarily focusing on cybersecurity and privacy. Specific contributions include (1) concise description of digital transformation based on the literature and resulting potential business impact (2) identification of opportunities related to the integration of social and IoT technologies and (3) challenges in technology convergence with a focus on cybersecurity challenges.
Upregulation of Anti-Angiogenic miR-106b-3p Correlates Negatively with IGF-1 and Vascular Health Parameters in a Model of Subclinical Cardiovascular Disease: Study with Metformin Therapy

Well-controlled type 1 diabetes mellitus (T1DM) is regarded as a model of subclinical cardiovascular disease (CVD), characterized by inflammation and adverse vascular health. However, the underlying mechanisms are not fully understood. We investigated insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) levels, their correlation to miR-106b-3p expression in a subclinical CVD model, and the cardioprotective effect of metformin. A total of 20 controls and 29 well-controlled T1DM subjects were studied. Plasma IGF-1, IGFBP-3 levels, and miR-106b-3p expression in colony-forming unit-Hills were analyzed and compared with vascular markers. miR-106b-3p was upregulated in T1DM (p < 0.05) and negatively correlated with pro-angiogenic markers CD34+/100-lymphocytes (p < 0.05) and IGF-1 (p < 0.05). IGF-1 was downregulated in T1DM (p < 0.01), which was associated with increased inflammatory markers TNF-α, CRP, and IL-10 and reduced CD34+/100-lymphocytes. IGFBP-3 had no significant results. Metformin had no effect on IGF-1 but significantly reduced miR-106b-3p (p < 0.0001). An Ingenuity Pathway analysis predicted miR-106b-3p to inhibit PDGFA, PIK3CG, GDNF, and ADAMTS13, which activated CVD. Metformin was predicted to be cardioprotective by inhibiting miR-106b-3p. In conclusion: Subclinical CVD is characterized by a cardio-adverse profile of low IGF-1 and upregulated miR-106b-3p. We demonstrated that the cardioprotective effect of metformin may be via downregulation of upregulated miR-106b-3p and its effect on downstream targets.
Influence of Combinations of Lipophilic and Phosphate Backbone Modifications on Cellular Uptake of Modified Oligonucleotides

Numerous types of oligonucleotide modifications have been developed since automated synthesis of DNA/RNA became a common instrument in the creation of synthetic oligonucleotides. Despite the growing number of types of oligonucleotide modifications under development, only a few of them and, moreover, their combinations have been studied widely enough in terms of their influence on the properties of corresponding NA constructions. In the present study, a number of oligonucleotides with combinations of 3′-end lipophilic (a single cholesteryl or a pair of dodecyl residues) and phosphate backbone modifications were synthesized. The influence of the combination of used lipophilic groups with phosphate modifications of various natures and different positions on the efficiency of cell penetration was evaluated. The obtained results indicate that even a couple of phosphate modifications are able to affect a set of oligonucleotide properties in a complex manner and can remarkably change cellular uptake. These data clearly show that the strategy of using different patterns of modification combinations has great potential for the rational design of oligonucleotide structures with desired predefined properties.
River gauging at global scale using optical and passive microwave remote sensing

Recent discharge observations are lacking for most rivers globally. Discharge can be estimated from remotely sensed floodplain and channel inundation area, but there is currently no method that can be automatically extended to many rivers. We examined whether automated monitoring is feasible by statistically relating inundation estimates from moderate to coarse (>0.05°) resolution remote sensing to monthly station discharge records. Inundation extents were derived from optical MODIS data and passive microwave sensors, and compared to monthly discharge records from over 8000 gauging stations and satellite altimetry observations for 442 reaches of large rivers. An automated statistical method selected grid cells to construct “satellite gauging reaches” (SGRs). MODIS SGRs were generally more accurate than passive microwave SGRs, but there were complementary strengths. The rivers widely varied in size, regime, and morphology. As expected performance was low (R < 0.7) for many (86%), often small or regulated, rivers, but 1263 successful SGRs remained. High monthly discharge variability enhanced performance: a standard deviation of 100–1000 m3 s−1 yielded ca. 50% chance of R > 0.6. The best results (R > 0.9) were obtained for large unregulated lowland rivers, particularly in tropical and boreal regions. Relatively poor results were obtained in arid regions, where flow pulses are few and recede rapidly, and in temperate regions, where many rivers are modified and contained. Provided discharge variations produce clear changes in inundated area and gauge records are available for part of the satellite record, SGRs can retrieve monthly river discharge values back to around 1998 and up to present.
A systematic literature review on factors of socio-environmental vulnerability associated with water-borne diseases.

INTRODUCTION Diarrhoeas, acute gastroenteritis with moderate dehydration, malaria and cholera are water-borne diseases with a high incidence in childhood and are one of the principal causes of morbidity and mortality in children under the age of 5 years, and predominantly so in developing countries. Various factors influence the population's vulnerability to these diseases. The objective of this work was to identify the factors of socio-environmental vulnerability associated with the occurrence of water-borne diseases (diarrhoeas, acute gastroenteritis with moderate dehydration, malaria and cholera). METHODOLOGY A systematic review of the literature was performed, with the databases PubMed, Scopus, B-On and Scielo to identify studies published between 2010 and 2021. RESULTS AND CONCLUSIONS The results showed that the most significant factors related to vulnerability to water-borne diseases have to do with sanitation and the availability of clean drinking water; however, temperature and precipitation were also found to exert considerable influence, together with the demographic factor.
Cytokine Profiling of Plasma and Atherosclerotic Plaques in Patients Undergoing Carotid Endarterectomy

Atherosclerotic plaques are sites of chronic inflammation with diverse cell contents and complex immune signaling. Plaque progression and destabilization are driven by the infiltration of immune cells and the cytokines that mediate their interactions. Here, we attempted to compare the systemic cytokine profiles in the blood plasma of patients with atherosclerosis and the local cytokine production, using ex vivo plaque explants from the same patients. The developed method of 41-plex xMAP data normalization allowed us to differentiate twenty-two cytokines produced by the plaque that were not readily detectable in free circulation and six cytokines elevated in blood plasma that may have other sources than atherosclerotic plaque. To verify the xMAP data on the putative atherogenesis-driving chemokines MCP-1 (CCL2), MIP-1α (CCL3), MIP-1β (CCL4), RANTES (CCL5), and fractalkine (CX3CL1), qPCR was performed. The MIP1A (CCL3), MIP1B (CCL4), FKN (CX3CL1), and MCP1 (CCL2) genes were expressed at high levels in the plaques, whereas RANTES (CCL5) was almost absent. The expression patterns of the chemokines were restricted to the plaque cell types: the MCP1 (CCL2) gene was predominantly expressed in endothelial cells and monocytes/macrophages, MIP1A (CCL3) in monocytes/macrophages, and MIP1B (CCL4) in monocytes/macrophages and T cells. RANTES (CCL5) was restricted to T cells, while FKN (CX3CL1) was not differentially expressed. Taken together, our data indicate a plaque-specific cytokine production profile that may be a useful tool in atherosclerosis studies.