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Zika virus (ZIKV) has spread all over the world since its major outbreak in 2015. This infection has been recognized as a major global health issue due to the neurological complications related to ZIKV infection, such as Guillain–Barré Syndrome and Zika virus Congenital Syndrome. Currently, there are no vaccines or specific treatments for ZIKV infection, which makes the development of specific therapies for its treatment very important. Several studies have been developed to analyze the potential of compounds against ZIKV, with the aim of finding new promising treatments. Herein, we evaluate the ability of a copaiba ( Copaifera officinalis ) oil nanoemulsion (CNE) to inhibit ZIKV. First, the highest non-cytotoxic concentration of 180 μg/mL was chosen since this concentration maintains 80% cell viability up to 96h after treatment with CNE in VERO cells resulted from MTT assay. The intracellular uptake assay was performed, and confirmed the internalization of the nanoemulsion in cells at all times analyzed. VERO cells were infected with ZIKV and simultaneously treated with CNE and the nanoformulation without oil (ENE) at the highest non-toxic concentration. The results evaluated by plaque assay revealed a viral inhibition of 80% for CNE and 70% for ENE. A dose-dependence assay revealed that the CNE treatment demonstrated a dose-dependent response in the viral RNA levels, whereas all ENE tested concentrations exhibited a similar degree of reduction. Taken together, our results suggest CNE as a promising nano-sized platform to be further studied for antiviral treatments.

Non-invasive approaches for cell-free DNA (cfDNA) assessment provide an opportunity for cancer detection and intervention. Here, we use a machine learning model for detecting tumor-derived cfDNA through genome-wide analyses of cfDNA fragmentation in a prospective study of 365 individuals at risk for lung cancer. We validate the cancer detection model using an independent cohort of 385 non-cancer individuals and 46 lung cancer patients. Combining fragmentation features, clinical risk factors, and CEA levels, followed by CT imaging, detected 94% of patients with cancer across stages and subtypes, including 91% of stage I/II and 96% of stage III/IV, at 80% specificity. Genome-wide fragmentation profiles across ~13,000 ASCL1 transcription factor binding sites distinguished individuals with small cell lung cancer from those with non-small cell lung cancer with high accuracy (AUC = 0.98). A higher fragmentation score represented an independent prognostic indicator of survival. This approach provides a facile avenue for non-invasive detection of lung cancer. DNA from tumour cells can be detected in the blood of cancer patients. Here, the authors show that cell free DNA fragmentation patterns can identify lung cancer patients and when this information is further interrogated it can be used to predict lung cancer histological subtype.

The reconstruction of craniomaxillofacial bone defects remains clinically challenging. To date, autogenous grafts are considered the gold standard but present critical drawbacks. These shortcomings have driven recent research on craniomaxillofacial bone reconstruction to focus on synthetic grafts with distinct materials and fabrication techniques. Among the various fabrication methods, additive manufacturing (AM) has shown significant clinical potential. AM technologies build three-dimensional (3D) objects with personalized geometry customizable from a computer-aided design. These layer-by-layer 3D biomaterial structures can support bone formation by guiding cell migration/proliferation, osteogenesis, and angiogenesis. Additionally, these structures can be engineered to degrade concomitantly with the new bone tissue formation, making them ideal as synthetic grafts. This review delves into the key advances of bioceramic grafts/scaffolds obtained by 3D printing for personalized craniomaxillofacial bone reconstruction. In this regard, clinically relevant topics such as ceramic-based biomaterials, graft/scaffold characteristics (macro/micro-features), material extrusion-based 3D printing, and the step-by-step workflow to engineer personalized bioceramic grafts are discussed. Importantly, in vitro models are highlighted in conjunction with a thorough examination of the signaling pathways reported when investigating these bioceramics and their effect on cellular response/behavior. Lastly, we summarize the clinical potential and translation opportunities of personalized bioceramics for craniomaxillofacial bone regeneration.

The effects of β-mannanase supplementation in metabolizable energy (ME)-reduced diets containing xylanase-phytase were investigated on growth performance, fecal score, ultra-sounded backfat thickness and loin depth, blood profile, apparent total tract digestibility (ATTD), digesta passage rate, and fecal microbiome in grower pigs (n = 40, 26.09 ± 0.96 kg) randomly assigned within 4 treatments: a control diet containing isolated phytase and xylanase valued at 40 kcal of ME/kg (CD0), CD0 + β-mannanase (0.3 g/kg valued at 30 kcal of ME/kg) (CD70), CD0 + β-mannanase (0.3 g/kg valued at 45 kcal of ME/kg) (CD85), and CD0 + β-mannanase (0.3 g/kg valued at 60 kcal of ME/kg) (CD100). Growth performance was not affected in pigs fed ME-reduced diets containing β-mannanase. Pigs with CD100 had lower serum IL-1β concentration, and higher IL-10 was observed in pigs on CD0 than those fed β-mannanase. Coefficients of ATTD, and ATTD of DM and CP were higher in animals fed CD85 or CD100. Pigs with CD85 had higher alpha diversity richness but lower Firmicutes:Bacteroidota ratio. Acidaminococcaceae and Ruminococcaceae were more abundant in pigs fed CD0, but lower for Christensenellaceae NSJ-63 and NSJ-63 sp014384805 . Pigs in CD85 showed higher Bacteroidaceae and Prevotella abundance, and lower for Streptococcaceae and Streptococcus . In conclusion, supplementation of β-mannanase in diets containing xylanase-phytase saved 85 to 100 kcal of ME/kg by supporting growth performance and improving nutrient digestibility in grower pigs.

•The prevalence of obesity in patients with SLE is aching rates ranging between 29% and 50%.•The excess of adipose tissue triggers the production of pro-inflammatory cytokines and adipokines such as leptin that could be central to connecting obesity and autoimmunity.•Obesity may negatively impact treatment response, disease progression, and patient prognosis.•Obesity associated to SLE Patients may as increase symptom severity, the risk of cardiovascular and renal complications. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect various organs and systems. Symptoms of SLE can vary widely from person to person and over time, including fatigue, joint pain, skin rashes, fever, and inflammation of multiple organs. The association between SLE and excess body weight has been the subject of study, with evidence suggesting that overweight and obesity can worsen the disease´s clinical presentation. Obesity is linked to a state of low-grade chronic inflammation, which can exacerbate the inflammation present in SLE. Additionally, obesity may negatively impact treatment response, disease progression, and patient prognosis. Patients with SLE and obesity may face additional challenges in managing the disease, such as increased symptom severity, higher risk of cardiovascular and renal complications, and a reduced response to conventional treatments. Obesity can also influence the quality of life of patients with SLE, making a holistic approach that considers the individual's nutritional status essential. Therefore, understanding the relationship between obesity and SLE is crucial for optimizing treatment, improving clinical outcomes, and enhancing patients' quality of life. Further research is needed to elucidate the underlying pathophysiological mechanisms, develop more precise and personalized management strategies, and identify biomarkers that can predict disease prognosis and treatment response.

Obesity is a complex and multifactorial condition strongly associated with metabolic burdens and cardiovascular diseases. This review focuses on precision nutrition as a strategy for obesity management, exploring how personalized interventions can modulate the composition and functionality of the gut microbiome to promote weight loss and improve metabolic health. A growing body of evidence suggests that imbalances in gut microbiota composition directly impact lipid metabolism, immune and inflammatory pathways, and appetite regulation mechanisms. Furthermore, the review discusses the relationship between gut microbiota and dietary factors, highlighting how certain types of diets (such as the Mediterranean diet and fiber-rich diets) can promote the production of short-chain fatty acids (SCFAs) and the growth of beneficial bacteria associated with weight regulation and reduced inflammation. While diet is the primary factor modulating the gut microbiota, factors such as genetics and epigenetic characteristics, body composition, maternal nutritional, type of birth delivery, physical activity and even drug use also play significant roles in this modulation. Although the use of precision nutrition approaches still faces challenges, such as cost and variability in individual response, the integration of omics technologies, artificial intelligence, and machine learning appear to offer great potential as tools to identify specific microbial and genetic profiles that allow for the personalization of nutritional interventions. These technologies enable large-scale analysis of dietary, genomic, and microbial factors to create dietary strategies to prevent or treat obesity that meet the specific metabolic needs of each individual. Thus, the application of these tools in clinical settings could transform obesity management, creating data-driven interventions that enhance treatment effectiveness. [Display omitted] •Precision nutrition personalizes obesity management by considering microbiome profiles.•Gut microbiota impacts lipid metabolism, immune function, inflammation, and appetite.•Fiber-rich and Mediterranean diets support beneficial gut bacteria and SCFA production.•Omics, AI, and ML tools enhance microbial and genetic profiling for tailored obesity treatments.

Many antidepressants, atomoxetine, and several antipsychotics are metabolized by the cytochrome P450 enzymes CYP2D6 and CYP2C19, and guidelines for prescribers based on genetic variants exist. Although some laboratories offer such testing, there is no consensus regarding validated methodology for clinical genotyping of CYP2D6 and CYP2C19. The aim of this paper was to cross-validate multiple technologies for genotyping CYP2D6 and CYP2C19 against each other, and to contribute to feasibility for clinical implementation by providing an enhanced range of assay options, customizable automated translation of data into haplotypes, and a workflow algorithm. AmpliChip CYP450 and some TaqMan single nucleotide variant (SNV) and copy number variant (CNV) data in the Genome-based therapeutic drugs for depression (GENDEP) study were used to select 95 samples (out of 853) to represent as broad a range of CYP2D6 and CYP2C19 genotypes as possible. These 95 included a larger range of CYP2D6 hybrid configurations than have previously been reported using inter-technology data. Genotyping techniques employed were: further TaqMan CNV and SNV assays, xTAGv3 Luminex CYP2D6 and CYP2C19, PharmacoScan, the Ion AmpliSeq Pharmacogenomics Panel, and, for samples with CYP2D6 hybrid configurations, long-range polymerase chain reactions (L-PCRs) with Sanger sequencing and Luminex. Agena MassARRAY was also used for CYP2C19. This study has led to the development of a broader range of TaqMan SNV assays, haplotype phasing methodology with TaqMan adaptable for other technologies, a multiplex genotyping method for efficient identification of some hybrid haplotypes, a customizable automated translation of SNV and CNV data into haplotypes, and a clinical workflow algorithm.

This study aimed to evaluate if single-nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene are associated with gene expression in human periodontal ligament (hPDL) fibroblasts under simulated orthodontic compressive force. hPDL samples from 57 patients were used. A physiological compressive strain was performed to simulate orthodontic tooth movement in pressure areas under cell culture conditions. The RNA from hPDL fibroblasts was isolated to determine the relative gene expression (mRNA) of the VDR. The DNA was also isolated for the genotyping analysis of five SNPs in the VDR gene: BglI (rs739837, G/T), BsmI (rs1544410, T/C), ApaI (rs7975232, A/C), FokI (rs2228570, A/G), and TaqI (rs731236, A/G). Real-time polymerase chain reaction was used for both analyses. Kruskal–Wallis tests were used to compare VDR expression among genotypes of each SNP. A linear regression analysis was performed to evaluate SNP–SNP interaction. An established alpha of 5% was used. The relative mRNA VDR expression according to the genotypes in the SNPs BglI, BsmI, ApaI, FokI, and TaqI was not statistically significantly different (p > 0.05). The SNP–SNP interaction evaluated by regression analysis did not demonstrate any statistically significant association. No association was observed (p > 0.05). In conclusion, the SNPs BglI (rs739837), BsmI (rs1544410), ApaI (rs7975232), FokI (rs2228570), and TaqI (rs731236) did not show an impact on VDR gene expression in hPDL fibroblasts under simulated orthodontic compressive force.

Salicylic acid (SA) is an important plant regulator reported as a mitigator of water deficit in plants, however without a recommendation for use in field conditions. Thus, this research aims to validate the use of SA under field conditions in regions with low water availability. For that, we evaluated CO2 assimilation (A), stomatal conductance (gs), transpiration (E), water use efficiency (WUE), and carboxylation efficiency (A/Ci) at 15, 30, and 45 days of continuous stress water deficit, as well as the application of salicylic acid (0.0; 0.5; 1.0; 1.5; 2.0 mM) in tomato plants subjected to continuous water deficit (45 days), in two years (2019 and 2020). The water deficit reduced the A, gs, E and A/Ci, while the foliar application of SA increased these parameters in all evaluated times, resulting in similar or even higher values than in plants without water deficit. Water deficit caused floral abortion in tomato plants, without the application of SA, reducing the number of fruit production. In contrast, plants that received about 1.3 mM of SA increased A and A/Ci and translocated the photo-assimilates, mainly to flowers and fruits, reducing floral abortion and increasing fruit production. Thus, foliar application of SA was efficient in mitigating the deleterious effects of water deficit in tomato plants regarding the gas exchange and fruit production.

Ruthenium(II) arene complexes exhibit promising chemotherapeutic properties. In this study, the effect of the counter anion in Ru(II) complexes was evaluated by analyzing the biological effect of two Ru(II) p-cymene derivatives with the 1,10-phenanthroline-5,6-dione ligand of general-formula [(η6-arene)Ru(L)Cl][X] X = CF3SO3 (JHOR10) and PF6 (JHOR11). The biological activity of JHOR10 and JHOR11 was examined in the ovarian carcinoma cell line A2780, colorectal carcinoma cell line HCT116, doxorubicin-resistant HCT116 (HCT116-Dox) and in normal human dermal fibroblasts. Both complexes JHOR10 and JHOR11 displayed an antiproliferative effect on A2780 and HCT116 cell lines, and low cytotoxicity in fibroblasts. Interestingly, JHOR11 also showed antiproliferative activity in the HCT116-Dox cancer cell line, while JHOR10 was inactive. Studies in A2780 cells showed that JHOR11 induced the production of reactive oxygen species (ROS) that trigger autophagy and cellular senescence, but no apoptosis induction. Further analysis showed that JHOR11 presented no tumorigenicity, with no effect in the cellular mobility, as evaluated by thye wound scratch assay, and no anti- or pro-angiogenic effect, as evaluated by the ex-ovo chorioallantoic membrane (CAM) assay. Importantly, JHOR11 presented no toxicity in chicken and zebrafish embryos and reduced in vivo the proliferation of HCT116 injected into zebrafish embryos. These results show that these are suitable complexes for clinical applications with improved tumor cell cytotoxicity and low toxicity, and that counter-anion alteration might be a viable clinical strategy for improving chemotherapy outcomes in multidrug-resistant (MDR) tumors.