Search Results (808)

Background/Objectives: Histone acetylation regulates gene expression and plays a key role in cancer pathophysiology. Nanotherapeutics are known to modulate histone acetylation and influence cancer progression. This systematic scoping review examines the effects of nanotherapeutics on histone acetylation enrichment across multiple cancers. Methods: A systematic search of Embase, PubMed/MEDLINE, Scopus, and Web of Science was conducted in accordance with the PRISMA 2020 statement. A total of 13 studies were included. Data were analyzed and visualized in R, and risk of bias was assessed with ToxRTool (OSF Registration: 10.17605/OSF.IO/E643S). Results: Nanotherapeutics were most commonly evaluated against breast (21.4%), prostate (21.4%), pancreatic (14.3%), and bladder (14.3%) cancers. Primary nanomaterials used in the synthesis of nanotherapeutics included poly(lactic-co-glycolic acid) (25.0%), gold (21.4%) and arsenic oxide (21.4%) nanoparticles. Studied histone acetylation marks included H3K9ac, H3K14ac, H3K27ac and H4K16ac. Treatment with nanotherapeutics increased histone H3 and H4 acetylation enrichment, particularly H3K14ac in colorectal and prostate cancers and H4K16ac in ovarian cancer. Conversely, gold-based nanotherapeutics decreased H3K9ac and H3K14ac enrichment in breast cancer. The optimal concentration for most nanotherapeutics was ≤25 µM, with PpIX-FFYSV showing the strongest anticancer effect (viability <25%). Across four preclinical studies (n = 58), treatment with the nanotherapeutics reduced tumor size to less than 50% of control in 64% of animals (95% CI: 21–92%, I² = 63.8%). Altered histone acetylation was associated with differential expression of CDKN1A, HSPA1, SREBF2 and TGFB. Conclusions: The evidence demonstrates that nanotherapeutics can alter histone acetylation patterns by modulating EP300/CBP, GCN5 and HDAC, preventing cancer progression and invasion. Full article

Exopolysaccharides (EPSs) are important extracellular metabolites secreted by microorganisms. Klebsiella pneumoniae is an opportunistic pathogen widely distributed in the environment, host mucosal and intestinal surfaces, and EPS from Klebsiella pneumoniae are of significant interest. Conventional studies have mainly focused on hypervirulent strains, whereas comprehensive investigations of non-hypervirulent strains and their EPS functionalities remain limited. This study employed ST678-type Klebsiella pneumoniae CGMCC 31459 as the model to investigate genomic characteristics, EPS structural features, and biological activities. Its genome comprises one chromosome and four plasmids, functionally enriched in carbohydrate metabolism genes, including abundant glycoside hydrolases and glycosyltransferases essential for EPS biosynthesis. Virulence and antimicrobial resistance assessments confirmed the absence of typical hypervirulence loci, indicating genetic stability with low pathogenic and resistance potential. EPS-KP is a weakly acidic, branched heteropolysaccharide composed of glucose, galactose, mannose, and glucuronic acid. EPS-KP exhibited significant antioxidant and anti-aging activities, with a 77.47% (5 mg/mL) superoxide anion scavenging rate and a 30.9% (200 μg/mL) lifespan extension in Caenorhabditis elegans, accompanied by enhanced SOD/CAT enzyme activity and reduced lipofuscin accumulation. This integrated genomic and biochemical analysis provides new insights into the safe, non-hypervirulent Klebsiella pneumoniae strain and its functional EPS, highlighting its potential for biotechnological applications. Full article

Torrefaction, a mild thermochemical pretreatment process, generates the fuel-torrefied biomass along with non-condensable and condensable gases. The latter can be condensed to yield a dark, viscous liquid called torrefaction condensate (TC). In this study, we investigated the effect of TC on growth and exopolysaccharide (EPS) production by the green microalgae Chlamydomonas reinhardtii, a well-known model organism. Aspen wood pellets were torrefied at different temperatures, and the condensate formed at each temperature was analyzed. Based on the GC-MS analysis, 225 °C TC was selected and used for the cultivation of C. reinhardtii. Results show that at 2 mL/L and 2.5 mL/L concentrations, TC negatively impacts growth, EPS production, as well as the composition of amino acids, lipids, and fatty acids n of C. reinhardtii. However, C. reinhardtii gradually adapted to TC and attained the growth patterns comparable to the control, showing the resilience of the culture. The biochemical and antioxidant properties of the EPS showed significant differences to that of the control. Therefore, cultivating these microalgae in TC suggests a new microalgal biorefinery approach through the utilization of low-value TC for the production of value-added products, such as EPS. Full article

Biomolecules of microbial origin are gaining attention for their use in various industries, including cosmetics, due to their broad bioactivities, peculiar properties, and sustainability. This study aimed to develop a novel, eco-friendly nanoemulsion from fungal chitosan hydrochloride (ChC), Pseudomonas aeruginosa biosurfactant (PaB), and grape seed oil (GSO), and to assess its antimicrobial action, biofilm control, and biocompatibility. High-energy emulsification was performed to produce the nanoemulsion (CCh-PaB-GSO), which was characterized by FTIR. Its stability was monitored for 30 days via DLS, zeta potential (ZP), and PDI. The minimum inhibitory concentration (MIC) for cariogenic Streptococcus species, inhibitory fraction concentration (FIC), influence on exopolysaccharide (EPS) quantification produced by bacteria, bacteria’s cell wall hydrophobicity, and biofilm control were determined. Biocompatibility was assessed using the HET-CAM technique by determining the irritation potential. FTIR analysis confirmed the formation the interaction between the substances that compound the nanoemulsion. The CCh-PaB-GSO had nanometric micelles (169.5–203.4 nm), PDI (0.241–0.271), and a positive ZP (+20.25 to +31.94 mV). It showed a consistent MIC (2.0 mg/mL CCh, 0.1 mg/mL PaB, and 3.2 mg/mL GSO) for all tested Streptococcus species and an indifferent interaction effect, FIC (1.32). At sub-MIC, the CCh-PaB-GSO effectively reduced EPS and microbial cell wall hydrophobicity, inhibiting biofilm adhesion. The CCh-PaB-GSO demonstrated biocompatibility with no signs of irritation. In conclusion, the ChC-PaB-GSO system forms an effective and stable nanoemulsion with potential for application as an eco-sustainable and biocompatible product for caries control. Full article

Beyond mechanical performance and aesthetics, the susceptibility of 3D-printed resins to microbial colonization and biofilm formation represent an important factor influencing dentures’ longevity. Therefore, this study evaluated Candida albicans colonization and mature biofilm formation on three different 3D-printed denture base resins (Bio Denture—BD; Denture Base Cosmos—CD; Smart Print Bio Denture—SP) and compared them to heat-curing resin (HC). Before the microbiological evaluation, the surface roughness (Sa) was assessed. Biofilm viability was determined through colony-forming units per milliliter (CFU/mL) and biofilm morphology was qualitatively examined using a scanning electron microscope (SEM). The composition of the extracellular polymeric substance (EPS) was investigated by measuring the amounts of carbohydrates (µg/mL), proteins (ng/mL), and extracellular DNA (eDNA) (fluorescence unit). One-way ANOVA was performed for eDNA and Sa and Kruskal–Wallis for the other properties (α = 0.05). Higher surface roughness mean values (standard deviation) (p < 0.05) were observed in CD [0.111 (0.013)] compared to HC [0.084 (0.018) and BD [0.078 (0.015)]. For wettability, BD [63.2 (5.2)] and SP [65.2 (3.1)] resins showed a greater wettability (p < 0.05) than HC resin [73.0 (3.5)], while SP showed lower (p < 0.01) protein levels (425 ng/mL) compared to HC (568.6 ng/mL) and BD (554.8 ng/mL) in the EPS. Despite these differences, the 3D-printed denture base resins exhibited microbial load (CFU/mL), EPS composition (carbohydrates and eDNA), and morphological features of C. albicans biofilm comparable to those of conventional heat-cured PMMA. These findings suggest that, despite resin-specific variations, 3D-printed denture base materials exhibit a similar susceptibility to C. albicans colonization and biofilm formation as conventional denture bases, thereby directing future research towards developing new 3D-printed resins with enhanced antimicrobial properties to improve clinical outcomes. Full article

Background: Spontaneous regression of testicular cancer with retroperitoneal metastasis is a rare phenomenon and poses challenges in its diagnosis. Methods: A 33-year-old male patient presented with severe lower back pain (10/10) of 4 months’ duration, radiating to the left lower limb, refractory to NSAIDs, and significantly impaired ambulation, accompanied by nausea and vomiting. In addition to difficulty initiating urination and defecation, with weight loss of 30 kg, he was referred to the urology service of our hospital. Results: On physical examination, the left testicle showed signs of varicocele without pain. Therefore, laboratory and imaging studies were requested, highlighting elevated β-hCG (156.4 mIU/mL) and LDH (850 IU/L). Testicular ultrasound confirmed the diagnosis of left varicocele, while computed tomography of the abdomen and pelvis with contrast revealed a conglomerated retroperitoneal mass of more than 5 cm, located in the paravertebral, retrocural, paraaortic, and intercavoaortic regions. Based on these findings, primary treatment with left radical orchiectomy was chosen, which showed regression of the seminomatous tumor. Histopathological examination revealed a seminomatous germ cell tumor (pT0, pN3, M0), clinical stage IIC, with a good prognosis. Therefore, chemotherapy was initiated with four cycles of EP (etoposide 170 mg and cisplatin 35 mg). However, despite standard chemotherapy, the disease progressed until the patient died. Conclusions: Cases of testicular tumor with retroperitoneal metastasis are rare and infrequently present with clinical, testicular, and imaging findings. Therefore, histopathology, accompanied by the intentional identification of mutations associated with the TP53 gene when therapeutic failure exists. Full article

Background/Objectives: African Swine Fever (ASF), caused by the African Swine Fever Virus (ASFV), is a highly contagious and lethal disease in pigs, for which no recognized safe and effective vaccine is currently available. The ASFV EP153R gene, expressed during both early and late infection stages, exhibits strong protective potential. Utilizing advances in genetic engineering, recombinant PRRSV vector vaccines carrying ASFV exogenous genes were constructed. This study aims to prepare pEP153R-based polyclonal antibodies and an iELISA detection method using the constructed rPRRSV-EP153R as a specific target to verify the iELISA’s specificity and effectiveness. Methods: A prokaryotic plasmid, pCold-TF-EP153R, was constructed to express protein in BL21 (DE3). The purified soluble protein (2 mg/mL) was used to generate a murine polyclonal antibody and establish an indirect ELISA. The EP153R gene was inserted between ORF1b and ORF2a of PRRSV via reverse genetics, yielding recombinant rPRRSV-EP153R. Its biological properties were assessed in vitro and in vivo. Results: The pEP153R was specifically detected by both anti-His antibody and generated polyclonal antibodies. An established iELISA showed high specificity, sensitivity, and 98.18% accuracy. The antibodies specifically recognized pEP153R expressed in recombinant virus and eukaryotic systems. Additionally, the recombinant virus stably maintained EP153R without changes in virological characteristics relative to vHuN4-F112. In vaccinated piglets, the rPRRSV-EP153R induced a specific, consistent, and detectable immune response. Conclusions: The established iELISA, characterized by high specificity, sensitivity, and accuracy, furnishes reliable technical support for the serological diagnosis of ASFV. Meanwhile, the recombinant virus rPRRSV-EP153R demonstrates potential as a novel live vectored vaccine candidate, with the capability to induce specific immunity against both ASFV and PRRSV. Full article

In saline soil, legumes are restricted in their growth potential by osmotic stress, ion toxicity, and oxidative damage. We evaluated five halotolerant plant growth-promoting bacteria and selected Pseudomonas putida RT12 for its exceptional EPS production, tolerance to 600 mM NaCl, strong biofilm development, and plant growth-promoting traits (ACC-deaminase 2.86 µM·mg⁻¹; IAA 144 µM·mL⁻¹). RT12 was evaluated on two varieties of peas (peas2009 and 9800-10) with and without inoculation at 0, 75, and 150 mM NaCl concentrations. RT12 markedly protected growth under severe salinity: at 150 mM, shoot length rose to 23.13 cm (peas2009) and 17.44 cm (9800-10), in contrast to 11.18 cm and 12.32 cm in uninoculated specimens; root length and dry weight demonstrated comparable recovery (root length increased from 11.00 to 22.25 cm; dry weight of peas2009 from 0.15 to 0.17 and 0.41 to 0.71 g). RT12 sustained photosynthesis (total chlorophyll increased from 43.5 to 54.5), enhanced relative water content (to 94.1% and 97.2%), elevated osmolytes (total soluble proteins rose from 7.34 to 18.12 µg·g⁻¹ FW; total soluble sugars increased from 19.1 to 41.3 mg·g⁻¹ FW), and augmented antioxidant activities (catalase increased from 2.11 to 4.70; superoxide dismutase rose from 1.20 to 4.83; peroxidase increased from 0.08 to 0.18), while reducing malondialdehyde/hydrogen peroxide levels. RT12 was significant as it inhibited the accumulation of Na⁺ (from 23.95 to 16.32 mg·g⁻¹ DW), elevated K⁺ levels (from 17.76 to 29.12 mg·g⁻¹ DW), and restored the K⁺/Na⁺ ratio to normal (from 0.74 to 1.59) in inoculated plants compared to non-inoculated ones. A multivariate analysis linked growth protection to ionic homeostasis, osmotic control, and the detoxification of reactive oxygen species (ROS). RT12 is a promising bioinoculant for cultivating peas in saline-affected soils. Full article

The financial feasibility of microbial carotenoid synthesis can be markedly improved by using widely available and renewable carbon sources. In this study, different carbon sources including molasses, were tested as carbon sources for Rhodococcus corynebacteioides TAO1. The effect of different molasses concentrations (50–250 mL/L) on bacterial growth, carotenoid synthesis, and exopolysaccharide production was determined during a 30-day period. The results demonstrated an upward trend between molasses concentration and bacterial dry weight up to 200 mL/L, with the highest dry weight measured as 0.656 ± 0.049 g. Bacterial growth was decreased at 250 mL/L molasses concentration due to possible carbon-source inhibition. However, carotenoid production exhibited a negative interaction with a maximum yield of 1.572 ± 0.108 mg/g in basal medium, while the lowest carotenoid production was determined as 0.84 ± 0.007 mg/g at 250 mL/L molasses concentration, showing that increased carbon availability might inhibit pigment biosynthesis. FTIR analysis indicated significant functional groups, such as C=O, O-H, C=C, and =CH, with significant peaks at 1713, 1655, and 1459 cm⁻¹, indicating the presence of carotenoid intermediates. The data highlight the interaction between carbon source concentration and microbial metabolism, emphasizing the importance of optimal nutrient factors for improving both carotenoid and EPS production. This research presents significant insights into economical biotechnological methods for the production of microbial pigments and biopolymers from industrial by-products. Full article

New brain imaging modalities and neuropsychological testing tools are used to study neuronal changes in brain injuries such as mild traumatic brain injury (mTBI). Here we utilized diffusion tensor imaging (DTI) parameters and Wisconsin Card Sorting Test (WCST) variables to investigate patients with chronic mTBI. Neuropsychological assessments for mTBI evaluate impairments across a broad spectrum of executive functions. Our study aims to examine the relationship between fractional anisotropy (FA) and WCST covariates in patients with chronic mTBI. We hypothesize that patients who suffered chronic mTBI have significantly reduced FA in frontal white matter regions in association with significant deviation from standard percentile scores in WSCT. Utilizing multi-linear regression models alongside analyzing DTI scans, WCST covariates were linearly regressed to produce positive and negative contrasts to identify specific regions of interest (ROIs) with reduced FA. Results show that WCST covariates (such as percentile perseverative responses (Ep), non-perseverative responses (Enp), and conceptual response (CResp)) significantly deviate beyond standard percentile scores and correlate with lower FA in white matter regions in the frontal cortex, demonstrating executive function deficits. These frontal regions include the inferior frontal, superior frontal, and corpus callosum (CC), correlated with greater errors in WCST percentile scores. This study investigates the correlation between WCST covariates and DTI parameters as valuable tools in the diagnosis and prognosis of persistent cognitive impairment for patients with a history of chronic traumatic brain injury. Full article

Investigating immunological and viral reservoir dynamics in blood and GALT during acute HIV phase advances understanding of HIV persistence. Dynamics of T cells and HIV reservoirs immediately after early ART require further investigation. We evaluated the ART impact at 12 (M12) and 24 months (M24) on immunological, virological and reservoir markers of 24 participants starting ART at Fiebig ≤ V (Baseline = D0) in a Brazilian cohort. We measured the frequency of T cell activation, exhaustion, memory subsets, Th17 and pTfh cells by flow cytometry and quantified total HIV DNA by qPCR in PBMC and GALT. Most participants were cisgender MSM (95.9%), with a median age of 27 years (IQR 25–36). At enrollment (D0), four participants used triple ART as PEP, and two were under oral PrEP and they exhibited higher CD4/CD8 ratios. Higher CD4/CD8 ratios were also observed in participants classified as Fiebig I to III. A total of 92% achieved viral suppression at M12 and 96% at M24. CD4 counts rose from 646 to 861 cells/mm³, and the CD4/CD8 ratio improved from 0.76 to 1.24 (p < 0.01). HIV DNA in PBMCs decreased 4-fold by M12 and 61-fold by M24, with 50% of participants reaching undetectable levels by M24 (p < 0.01). In GALT, undetectable HIV DNA increased from 27% at D0 to 75% at M12. HIV DNA in PBMCs and GALT correlated with plasma VL, while the CD4/CD8 ratio was inversely linked to PBMC reservoirs (rho = −0.66; p < 0.05). Early ART reduced activated CD8⁺ T cells (p < 0.05) but had minimal effects on CD4⁺ T cells or exhaustion markers. By M24, CD8⁺ TCM increased, and CD8⁺ TEF decreased (p < 0.01), while Th17 and pTfh levels remained stable. Early ART led to viral suppression and immune restoration, and influenced reservoir dynamics. The CD4/CD8 ratio was shown to be a key marker of early treatment success. Since a quarter of the participants were identified while initiating PrEP/PEP, it is important to consider the acute phase window according to vulnerability. Recent PEP/PrEP use often excludes participants from clinical trials on bNAbs and therapeutic vaccines targeting viral reservoirs during the acute phase of HIV. Since these are the populations that may benefit from these strategies, larger studies including those people are needed. Full article

Background/Objectives: Neurodegenerative diseases (NDs) such as Alzheimer’s (AD), Parkinson’s (PD), Huntington’s (HD), and Amyotrophic Lateral Sclerosis (ALS) are clinically distinct but share overlapping molecular mechanisms. Methods: To identify conserved systemic signatures, we analyzed blood RNA-Seq datasets using Weighted Gene Co-Expression Network Analysis (WGCNA), differential expression, pathway enrichment, and miRNA–mRNA network mapping. Results: Two modules, the red and turquoise, showed strong preservation across diseases. The red module was enriched for cytoskeletal and metabolic regulation, while the turquoise module involved immune, stress-response, and proteostatic pathways. Discussion: Key hub genes, such as HMGCR, ACTR2, MYD88, PTEN, EP300, and regulatory miRNAs like miR-29, miR-132, and miR-146a, formed interconnected networks reflecting shared molecular vulnerabilities. The absence of classical heat shock proteins in preserved blood modules highlights tissue-specific expression differences between blood and neural systems. Several hub genes overlap with known pharmacological targets, suggesting potential in translational relevance. Conclusions: Together, these findings reveal conserved blood-based transcriptional modules that suggest parallel central neurodegenerative processes and may support future biomarker development and possible therapeutic exploration. Full article

Background/Objectives: Citrus × paradisi Macfad., Rutaceae. peel is a rich source of naringin (NR), but its poor solubility and low bioavailability limit applications. This study aimed to improve NR delivery by comparing microencapsulation, liposomal microencapsulation, and buccal films containing either pure NR or grapefruit peel extract. Methods: Four spray-dried powder formulations—spray-dried NR (NS), liposomal NR (NLS), spray-dried extract (ES), and liposomal extract (ELS)—were produced using maltodextrin, β-cyclodextrin, and HPMC as wall materials. Buccal films (EP1, EP2, NP1, NP2) were prepared via solvent casting with HPMC, alginate (ALG), or polyvinyl alcohol (PVA). All samples were evaluated for solubility, moisture content, mucoadhesion, and in vitro release under simulated gastric, intestinal, and salivary conditions. Results: NR powders had the highest absolute solubility (306.42 ± 10.34 µg/mL), whereas ELS showed the lowest due to low loading. However, relative to theoretical NR content, ELS achieved the highest dissolution efficiency (55.3%), followed by NLS (42.7%), outperforming NS (5.6%) and ES (91.8%) in sustained release potential. Dual encapsulation (NLS, ELS) slowed gastric release and maintained intestinal delivery, while non-liposomal powders released rapidly. In buccal films, NP2 (NR + PVA) showed the highest release (69.97 ± 3.01 µg/mL; 40.9% efficiency) and strongest mucoadhesion (0.47 N·s). Extract-based films had lower absolute NR release but higher relative efficiency to content, likely due to co-extracted compounds enhancing wettability and matrix erosion. Conclusions: Liposomal microencapsulation improves relative dissolution efficiency and sustains intestinal release, while PVA-based buccal films enhance both release and mucoadhesion. Polymer choice and active ingredient composition are critical for optimising oral delivery of NR. These results demonstrate the potential of the proposed systems in the pharmaceutical or dietary supplement field, especially in improving the oral delivery of poorly soluble flavonoids. A graphical summary is included, visually summarising the main formulation strategies and results. Full article

Background: The detection of circulating tumor cells (CTCs) holds significant promise for the diagnosis and monitoring of lung cancer (LC). However, the clinical utility of CTCs is limited by the heterogeneity of their phenotypes and the shortcomings of existing detection methods, which often rely on epithelial markers like EpCAM. DNA aptamers offer a promising alternative due to their high affinity, stability, and ability to recognize diverse cancer-specific biomarkers. Methods: This study utilized DNA aptamers LC-17 and LC-18, previously selected against primary lung tumor tissue, to isolate and detect CTCs in the peripheral blood of 43 non-small cell lung cancer (NSCLC) patients. Mass spectrometry (LC-MS/MS) was employed to identify the target proteins of aptamer LC-17. CTCs from patients’ blood and healthy donors were isolated via filtration after erythrocyte and lymphocyte lysis and stained with FAM-labeled LC-17 and LC-18 aptamers for detection using fluorescence and light microscopy. Results: Mass spectrometry identified neutrophil defensin 1 (DEFA1) and peroxiredoxin-2 (PRDX2) as the primary protein targets of aptamer LC-17 in CTCs, both of which were absent in healthy donor samples. CTC enumeration revealed statistically significant correlations between elevated CTC counts (>3 cells/4 mL blood) and advanced primary tumor size (T4 vs. T1–T3, p = 0.012), extensive regional lymph node metastasis (N3 vs. N1–N2, p = 0.014), and shorter overall survival (median 24 vs. 32 months, p < 0.05). Conclusions: The developed aptamer-based liquid biopsy method effectively captures heterogeneous CTC populations independent of EpCAM expression. The strong correlation of CTC counts with disease progression and survival underscores their clinical relevance as a prognostic biomarker in NSCLC. This approach presents a viable, non-invasive tool for disease monitoring and stratification of NSCLC patients, with potential for integration into clinical practice. Full article

The epoxy monomer N,1-bis(4-(2-oxiranemethoxy)phenyl)methylamine (HBAP-EP) was synthesized through the Schiff base reaction and epichlorohydrin method, and the HBAP-EP monomer was cured using p-aminobenzene sulfonamide (SAA). Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and polarizing optical microscopy (POM) demonstrated that the epoxy monomer exhibits reversible liquid crystal properties, and the liquid crystal fraction of the monomer can reach 14.4% after curing at 120 °C. The fracture toughness of the resin cured at 120 °C can reach 0.93 KJ·m⁻², and its thermal conductivity is 0.3229 W·(m·K)⁻¹, both of which are higher than those of ordinary epoxy resin. Full article