Miracle-dz/UniFAR-FTUs huggingface dataset:
EGCG Inhibits Adipose-Derived Mesenchymal Stem Cells Differentiation into Adipocytes and Prevents a STAT3-Mediated Paracrine Oncogenic Control of Triple-Negative Breast Cancer Cell Invasive Phenotype

Obese subjects have an increased risk of developing triple-negative breast cancer (TNBC), in part associated with the chronic low-grade inflammation state. On the other hand, epidemiological data indicates that increased consumption of polyphenol-rich fruits and vegetables plays a key role in reducing incidence of some cancer types. Here, we tested whether green tea-derived epigallocatechin-3-gallate (EGCG) could alter adipose-derived mesenchymal stem cell differentiation into adipocytes, and how this impacts the secretome profile and paracrine regulation of the TNBC invasive phenotype. Here, cell differentiation was performed and conditioned media (CM) from preadipocytes and mature adipocytes harvested. Human TNBC-derived MDA-MB-231 real-time cell migration was performed using the exCELLigence system. Differential gene arrays and RT-qPCR were used to assess gene expression levels. Western blotting was used to assess protein expression and phosphorylation status levels. In vitro vasculogenic mimicry (VM) was assessed with Matrigel. EGCG was found to inhibit the induction of key adipogenic biomarkers, including lipoprotein lipase, adiponectin, leptin, fatty acid synthase, and fatty acid binding protein 4. Increased TNBC-derived MDA-MB-231 cell chemotaxis and vasculogenic mimicry were observed in response to mature adipocytes secretome, and this was correlated with increased STAT3 phosphorylation status. This invasive phenotype was prevented by EGCG, the JAK/STAT inhibitors Tofacitinib and AG490, as well as upon STAT3 gene silencing. In conclusion, dietary catechin-mediated interventions could, in part through the inhibition of adipogenesis and modulation of adipocytes secretome profile, prevent the onset of an obesogenic environment that favors TNBC development.
Characterization of CRISPR Spacer and Protospacer Sequences in Paenibacillus larvae and Its Bacteriophages

The bacterium Paenibacillus larvae is the causative agent of American foulbrood, the most devastating bacterial disease of honeybees. Because P. larvae is antibiotic resistant, phages that infect it are currently used as alternative treatments. However, the acquisition by P. larvae of CRISPR spacer sequences from the phages could be an obstacle to treatment efforts. We searched nine complete genomes of P. larvae strains and identified 714 CRISPR spacer sequences, of which 384 are unique. Of the four epidemiologically important P. larvae strains, three of these have fewer than 20 spacers, while one strain has over 150 spacers. Of the 384 unique spacers, 18 are found as protospacers in the genomes of 49 currently sequenced P. larvae phages. One P. larvae strain does not have any protospacers found in phages, while another has eight. Protospacer distribution in the phages is uneven, with two phages having up to four protospacers, while a third of phages have none. Some phages lack protospacers found in closely related phages due to point mutations, indicating a possible escape mechanism. This study serve a point of reference for future studies on the CRISPR-Cas system in P. larvae as well as for comparative studies of other phage–host systems.
Three-Dimensional Evaluation of Soft Tissue Malar Modifications after Zygomatic Valgization Osteotomy via Geometrical Descriptors

Patients with severe facial deformities present serious dysfunctionalities along with an unsatisfactory aesthetic facial appearance. Several methods have been proposed to specifically plan the interventions on the patient’s needs, but none of these seem to achieve a sufficient level of accuracy in predicting the resulting facial appearance. In this context, a deep knowledge of what occurs in the face after bony movements in specific surgeries would give the possibility to develop more reliable systems. This study aims to propose a novel 3D approach for the evaluation of soft tissue zygomatic modifications after zygomatic osteotomy; geometrical descriptors usually involved in face analysis tasks, i.e., face recognition and facial expression recognition, are here applied to soft tissue malar region to detect changes in surface shape. As ground truth for zygomatic changes, a zygomatic openness angular measure is adopted. The results show a high sensibility of geometrical descriptors in detecting shape modification of the facial surface, outperforming the results obtained from the angular evaluation.
Functional Characterization of Mung Bean Meal Protein-Derived Antioxidant Peptides

The aim of this work was to characterize the antioxidant properties of some of the peptides present in bromelain mung bean meal protein hydrolysate (MMPH). The MMPH was subjected to two rounds of bioassay-guided reversed-phase HPLC separation followed by peptide identification in the most potent fractions using tandem mass spectrometry. Twelve antioxidant peptides, namely, HC, CGN, LAN, CTN, LAF, CSGD, MMGW, QFAAD, ERF, EYW, FLQL, and QFAW were identified and assayed for antioxidant properties. CTN, HC, CGN, and CSGD were the most potent (p < 0.05) DPPH radical scavengers with EC50 values of 0.30, 0.29, 0.28, and 0.30 mg/mL, respectively, which are lower than the 0.03 mg/mL obtained for reduced glutathione (GSH). CTN, HC, CGN, and CSGD exhibited the most potent (p < 0.05) scavenging activities against hydroxyl and superoxide radicals with EC50 values that are similar to those of GSH. The cysteine-containing peptides also had stronger ferric reducing antioxidant power and metal chelation activity than peptides devoid of cysteine. In contrast, MMGW, ERF, and EYW had poor radical scavenging and metal chelation activities. We conclude that the availability of the sulfhydryl group may have enhanced antioxidant potency while the presence of bulky groups such phenylalanine and tryptophan had an opposite effect.
Characterization of Chitosan Film Incorporated with Curcumin Extract

Curcumin is a phenolic compound derived from turmeric roots (Curcuma longa L.). This research studied the effects of curcumin extract on the properties of chitosan films. The film characteristics measured included mechanical properties, visual aspects, color parameters, light transmission, moisture content, water solubility, water vapor permeability, infrared spectroscopy, and antioxidant activity. The results suggest that adding curcumin to chitosan-based films increases yellowness and light barriers. Infrared spectroscopy analysis showed interactions between the phenolic compounds of the extract and the chitosan, which may have improved the mechanical properties and reduced the moisture content, water solubility, and water vapor permeability of the films. The antioxidant activity of the films increased with increasing concentrations of the curcumin extract. This study shows the potential benefits of incorporating curcumin extract into chitosan films used as active packaging.
The Esterase PfeE, the Achilles’ Heel in the Battle for Iron between Pseudomonas aeruginosa and Escherichia coli

Bacteria access iron, a key nutrient, by producing siderophores or using siderophores produced by other microorganisms. The pathogen Pseudomonas aeruginosa produces two siderophores but is also able to pirate enterobactin (ENT), the siderophore produced by Escherichia coli. ENT-Fe complexes are imported across the outer membrane of P. aeruginosa by the two outer membrane transporters PfeA and PirA. Iron is released from ENT in the P. aeruginosa periplasm by hydrolysis of ENT by the esterase PfeE. We show here that pfeE gene deletion renders P. aeruginosa unable to grow in the presence of ENT because it is unable to access iron via this siderophore. Two-species co-cultures under iron-restricted conditions show that P. aeruginosa strongly represses the growth of E. coli as long it is able to produce its own siderophores. Both strains are present in similar proportions in the culture as long as the siderophore-deficient P. aeruginosa strain is able to use ENT produced by E. coli to access iron. If pfeE is deleted, E. coli has the upper hand in the culture and P. aeruginosa growth is repressed. Overall, these data show that PfeE is the Achilles’ heel of P. aeruginosa in communities with bacteria producing ENT.
Current Status of the Self-Expandable Metal Stent as a Bridge to Surgery Versus Emergency Surgery in Colorectal Cancer: Results from an Updated Systematic Review and Meta-Analysis of the Literature

Background: The current use of endoscopic stenting as a bridge to surgery is not always accepted in standard clinical practice to treat neoplastic colonic obstructions. Objectives: The role of colonic self-expandable metal stent (SEMS) positioning as a bridge to resective surgery versus emergency surgery (ES) for malignant obstruction, using all new data and available variables, was studied and we focused on short- and long-term results. Materials and Methods: A systematic review with meta-analysis was performed. PubMed, SCOPUS and Web of Science databases were included. The search comprised only randomized controlled trials (RCTs) investigating the interventions that included SEMS positioning versus ES. The primary outcomes were the rates of overall postoperative mortality, clinical and technical success. The secondary outcomes were the short- and long-term results. Results: A total of 12 studies were eligible for further analyses. A laparoscopic colectomy was the most common operation performed in the SEMS group, whereas the traditional open approach was commonly used in the ES group. Intraoperative colonic lavage was seldomly performed during ES. There were no differences in mortality rates between the two groups (RR 1.06, 95% CI 0.55 to 2.04; I2 = 0%). In the SEMS group, the rate of successful primary anastomosis was significantly higher in of SEMS (69.75%) than in the ES (55.07%) (RR 1.26, 95% 245 CI 1.01 to 1.57; I2 = 86%). Conversely, the upfront Hartmann procedure was performed more frequently in the ES (39.1%) as compared to the SEMS group (23.4%) (RR 0.61, 95% CI 0.45 to 0.85; I2 = 23%). The overall postoperative complications rate was significantly lower in the SEMS group (32.74%) than in the ES group (48.25%) (RR 0.61, 95% CI 0.41 to 0.91; I2 = 65%). Conclusions: In the presence of malignant colorectal obstruction, SEMS is safe and associated with the same mortality and significantly lower morbidity than the ES group. The rate of successful primary anastomosis was significantly higher than the ES group. Nevertheless, recurrence and survival outcomes are not significantly different between the two groups. The analysis of short- and long-term results can suggest the use of SEMS as a bridge to resective surgery when it is performed by an endoscopist with adequate expertise in both colonoscopy and fluoroscopic techniques and who performed commonly colonic stenting.
Assessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea Pigs

Treatment to ameliorate the symptoms of infection with herpes simplex virus 2 (HSV-2) and to suppress reactivation has been available for decades. However, a safe and effective preventative or therapeutic vaccine has eluded development. Two novel live-attenuated HSV-2 vaccine candidates (RVx201 and RVx202) have been tested preclinically for safety. Hartley guinea pigs were inoculated vaginally (n = 3) or intradermally (n = 16) with either vaccine candidate (2 × 107 PFU) and observed for disease for 28 days. All animals survived to study end without developing HSV-2-associated disease. Neither vaccine candidate established latency in dorsal root or sacral sympathetic ganglia, as determined by viral DNA quantification, LAT expression, or explant reactivation. Infectious virus was shed in vaginal secretions for three days following vaginal inoculation with RVx202, but not RVx201, although active or latent HSV-2 was not detected at study end. In contrast, guinea pigs inoculated with wild-type HSV-2 MS (2 × 105 PFU) vaginally (n = 5) or intradermally (n = 16) developed acute disease, neurological signs, shed virus in vaginal secretions, experienced periodic recurrences throughout the study period, and had latent HSV-2 in their dorsal root and sacral sympathetic ganglia at study end. Both vaccine candidates generated neutralizing antibody. Taken together, these findings suggest that these novel vaccine candidates are safe in guinea pigs and should be tested for efficacy as preventative and/or therapeutic anti-HSV-2 vaccines.
Virulence and Antifungal Susceptibility of Microsporum canis Strains from Animals and Humans

The enzymatic and antifungal profiles of dermatophytes play an important role in causing infections in humans and animals. This study aimed to assess the virulence factors produced by Microsporum canis strains, in vitro antifungal profile and the relationship between virulence, antifungal profile and occurrence of lesions in animals and humans. A total of 100 M. canis strains from humans with tinea corporis (n = 10) and from animals presenting (n = 64) or not (n = 26) skin lesions was employed to evaluate phospholipase (Pz), hemolytic (Hz), lipase (Lz), catalase (Ca), and thermotolerance (GI) activities. In addition, in vitro antifungal profile was conducted using the CLSI broth microdilution method. A statistically significant difference (p < 0.05) in Lz and Ca values was revealed among strains from hosts with and without lesions. Voriconazole, terbinafine, and posaconazole were the most active drugs followed by ketoconazole, griseofulvin, itraconazole, and fluconazole in decreasing activity order. The significant positive correlation between azole susceptibility profile of M. canis and virulence factors (i.e., hemolysin and catalase) suggest that both enzyme patterns and antifungal susceptibility play a role in the appearance of skin lesions in animals and humans.
Differential Methylation in the GSTT1 Regulatory Region in Sudden Unexplained Death and Sudden Unexpected Death in Epilepsy

Sudden cardiac death (SCD) is a diagnostic challenge in forensic medicine. In a relatively large proportion of the SCDs, the deaths remain unexplained after autopsy. This challenge is likely caused by unknown disease mechanisms. Changes in DNA methylation have been associated with several heart diseases, but the role of DNA methylation in SCD is unknown. In this study, we investigated DNA methylation in two SCD subtypes, sudden unexplained death (SUD) and sudden unexpected death in epilepsy (SUDEP). We assessed DNA methylation of more than 850,000 positions in cardiac tissue from nine SUD and 14 SUDEP cases using the Illumina Infinium MethylationEPIC BeadChip. In total, six differently methylated regions (DMRs) between the SUD and SUDEP cases were identified. The DMRs were located in proximity to or overlapping genes encoding proteins that are a part of the glutathione S-transferase (GST) superfamily. Whole genome sequencing (WGS) showed that the DNA methylation alterations were not caused by genetic changes, while whole transcriptome sequencing (WTS) showed that DNA methylation was associated with expression levels of the GSTT1 gene. In conclusion, our results indicate that cardiac DNA methylation is similar in SUD and SUDEP, but with regional differential methylation in proximity to GST genes.
Neurodegeneration, Neuroprotection and Regeneration in the Zebrafish Retina

Neurodegenerative retinal diseases, such as glaucoma and diabetic retinopathy, involve a gradual loss of neurons in the retina as the disease progresses. Central nervous system neurons are not able to regenerate in mammals, therefore, an often sought after course of treatment for neuronal loss follows a neuroprotective or regenerative strategy. Neuroprotection is the process of preserving the structure and function of the neurons that have survived a harmful insult; while regenerative approaches aim to replace or rewire the neurons and synaptic connections that were lost, or induce regrowth of damaged axons or dendrites. In order to test the neuroprotective effectiveness or the regenerative capacity of a particular agent, a robust experimental model of retinal neuronal damage is essential. Zebrafish are being used more often in this type of study because their eye structure and development is well-conserved between zebrafish and mammals. Zebrafish are robust genetic tools and are relatively inexpensive to maintain. The large array of functional and behavioral tests available in zebrafish makes them an attractive model for neuroprotection studies. Some common insults used to model retinal disease and study neuroprotection in zebrafish include intense light, chemical toxicity and mechanical damage. This review covers the existing retinal neuroprotection and regeneration literature in the zebrafish and highlights their potential for future studies.
Early Colorectal Responses to HIV-1 and Modulation by Antiretroviral Drugs

Innate responses during acute HIV infection correlate with disease progression and pathogenesis. However, limited information is available about the events occurring during the first hours of infection in the mucosal sites of transmission. With an ex vivo HIV-1 challenge model of human colorectal tissue we assessed the mucosal responses induced by R5- and X4-tropic HIV-1 isolates in the first 24 h of exposure. Microscopy studies demonstrated virus penetration of up to 39 μm into the lamina propia within 6 h of inoculation. A rapid, 6 h post-challenge, increase in the level of secretion of inflammatory cytokines, chemokines, interferon- γ (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) was observed following exposure to R5- or X4-tropic isolates. This profile persisted at the later time point measured of 24 h. However, exposure to the X4-tropic isolate tested induced greater changes at the proteomic and transcriptomic levels than the R5-tropic. The X4-isolate induced greater levels of CCR5 ligands (RANTES, MIP-1α and MIP-1β) secretion than R5-HIV-1. Potential drugs candidates for colorectal microbicides, including entry, fusion or reverse transcriptase inhibitors demonstrated differential capacity to modulate these responses. Our findings indicate that in colorectal tissue, inflammatory responses and a Th1 cytokine profile are induced in the first 24 h following viral exposure.
Salt Replacement Changed the Bacterial Community Composition and Physicochemical Characteristics of Sodium-Reduced Fermented Sausages during Fermentation and Ripening

The impact on fermented sausages with 25% replacement of the sodium chloride content by 14% potassium chloride, 10% calcium ascorbate and 1% calcium glutamate during fermentation and ripening was evaluated based on the bacterial community composition and physicochemical and sensory characteristic analysis. Our results showed that the use of salt replacement varied the composition of the bacterial community and reduced the diversity of that in sodium-reduced fermented sausages. Moreover, the decrease in pH and the moisture content of fermented sausages with salt replacement accelerated the drying and ripening processes. The texture profile and color analysis did not reveal marked differences between normal fermented sausages and sodium-reduced products with salt replacement; however, salt replacement reduced resilience and lightness of fermented sausages. In addition, as shown in the principal component analysis, the comprehensive parameters of the fermented sausages with salt replacement were similar to those of normal salt products. These results indicate that the complex blends of salt replacement have great potential to be used to produce sodium-reduced fermented sausages.
Green Synthesis of Nickel Oxide Nanoparticles from Berberis balochistanica Stem for Investigating Bioactivities

Green synthesis of nanomaterials is advancing due to its ease of synthesis, inexpensiveness, nontoxicity and renewability. In the present study, an eco-friendly biogenic method was developed for the green synthesis of nickel oxide nanoparticles (NiONPs) using phytochemically rich Berberis balochistanica stem (BBS) extract. The BBS extract was rich in phenolics, flavonoids and berberine. These phytochemicals successfully reduced and stabilised the NiNO3 (green) into NiONPs (greenish-gray). BBS-NiONPs were confirmed by using UV-visible spectroscopy (peak at 305 nm), X-ray diffraction (size of 31.44 nm), Fourier transform infrared spectroscopy (identified -OH group and Ni-O formation), energy dispersive spectroscopy (showed specified elemental nature) and scanning electron microscopy (showed rhombohedral agglomerated shape). BBS-NiONPs were exposed to multiple in vitro bioactivities to ascertain their beneficial biological applications. They exhibited strong antioxidant activities: total antioxidant capacity (64.77%) and 2, 2-diphenyl-1-picrylhydrazyl (71.48%); and cytotoxic potential: Brine shrimp cytotoxicity assay with IC50 (10.40 µg/mL). BBS-NiONPs restricted the bacterial and fungal pathogenic growths at 1000, 500 and 100 µg/mL. Additionally, BBS-NiONPs showed stimulatory efficacy by enhancing seed germination rate and seedling growth at 31.25 and 62.5 µg/mL. In aggregate, BBS extract has a potent antioxidant activity which makes the green biosynthesis of NiONPs easy, economical and safe. The biochemical potential of BBS-NiONPs can be useful in various biomedical and agricultural fields.
Marine-Derived Natural Products as ATP-Competitive mTOR Kinase Inhibitors for Cancer Therapeutics

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase portraying a quintessential role in cellular proliferation and survival. Aberrations in the mTOR signaling pathway have been reported in numerous cancers including thyroid, lung, gastric and ovarian cancer, thus making it a therapeutic target. To attain this objective, an in silico investigation was designed, employing a pharmacophore modeling approach. A structure-based pharmacophore (SBP) model exploiting the key features of a selective mTOR inhibitor, Torkinib directed at the ATP-binding pocket was generated. A Marine Natural Products (MNP) library was screened using SBP model as a query. The retrieved compounds after consequent drug-likeness filtration were subjected to molecular docking with mTOR, thus revealing four MNPs with better scores than Torkinib. Successive refinement via molecular dynamics simulations demonstrated that the hits formed crucial interactions with key residues of the pocket. Furthermore, the four identified hits exhibited good binding free energy scores through MM-PBSA calculations and the subsequent in silico toxicity assessments displayed three hits deemed essentially non-carcinogenic and non-mutagenic. The hits presented in this investigation could act as potent ATP-competitive mTOR inhibitors, representing a platform for the future discovery of drugs from marine natural origin.