Green synthesized extracts/Au complex of Phyllospongia lamellosa: Unrevealing the anti-cancer and anti-bacterial potentialities, supported by metabolomics and molecular modeling.

The anti-cancer and anti-bacterial potential of the Red Sea sponge Phyllospongia lamellosa in its bulk (crude extracts) and gold nanostructure (loaded on gold nanaoparticles) were investigated. Metabolomics analysis was conducted, and subsequently, molecular modeling studies were conducted to explore and anticipate the P. lamellosa secondary metabolites and their potential target for their various bioactivities. The chloroformic extract (CE) and ethyl acetate extract (EE) of the P. lamellosa predicted to include bioactive lipophilic and moderately polar metabolites, respectively, were used to synthesize gold nanoparticles (AuNPs). The prepared AuNPs were characterized through transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), and UV-vis spectrophotometric analyses. The cytotoxic activities were tested against MCF-7, MDB-231, and MCF-10A. Moreover, the anti-bacterial, antifungal, and anti-biofilm activity were assessed. Definite classes of metabolites were identified in CE (terpenoids) and EE (brominated phenyl ethers and sulfated fatty amides). Molecular modeling involving docking and molecular dynamics identified Protein-tyrosine phosphatase 1B (PTP1B) as a potential target for the anti-cancer activities of terpenoids. Moreover, CE exhibited the most powerful activity against breast cancer cell lines, matching our molecular modeling study. On the other hand, only EE was demonstrated to possess powerful anti-bacterial and anti-biofilm activity against Escherichia coli. In conclusion, depending on their bioactive metabolites, P. lamellosa-derived extracts, after being loaded on AuNPs, could be considered anti-cancer, anti-bacterial, and anti-biofilm bioactive products. Future work should be completed to produce drug leads.

A Probiotic Amylase Blend Positively Impacts Gut Microbiota Modulation in a Randomized, Placebo-Controlled, Double-Blind Study.

The present study was performed to determine if ingesting a blend of probiotics plus amylase would alter the abundance and diversity of gut microbiota in subjects consuming the blend over a 6-week period. 16S and ITS ribosomal RNA (rRNA) sequencing was performed on fecal samples provided by subjects who participated in a clinical study where they consumed either a probiotic amylase blend (Bifidobacterium breve 19bx, Lactobacillus acidophilus 16axg, Lacticaseibacillus rhamnosus 18fx, and Saccharomyces boulardii 16mxg, alpha amylase (500 SKB (Alpha-amylase-Dextrinizing Units)) or a placebo consisting of rice oligodextrin. The abundance and diversity of both bacterial and fungal organisms was assessed at baseline and following 6 weeks of probiotic amylase blend or placebo consumption. In the subjects consuming the probiotic blend, the abundance of Saccharomyces cerevisiae increased 200-fold, and its prevalence increased (~20% to ~60%) (p ≤ 0.05), whereas the potential pathogens Bacillus thuringiensis and Macrococcus caseolyticus decreased more than 150- and 175-fold, respectively, after probiotic-amylase blend consumption. We also evaluated the correlation between change in microbiota and clinical features reported following probiotic amylase consumption. Nine (9) species (seven bacterial and two fungal) were significantly (negatively or positively) associated with the change in 32 clinical features that were originally evaluated in the clinical study. Oral supplementation with the probiotic-amylase blend caused a marked increase in abundance of the beneficial yeast S. cerevisiae and concomitant modulation of gut-dwelling commensal bacterial organisms, providing the proof of concept that a beneficial commensal organism can re-align the gut microbiota.

Uncovering SIRT3 and SHMT2-dependent pathways as novel targets for apigenin in modulating colorectal cancer: In vitro and in vivo studies.

Despite significant advances in the treatment of colorectal cancer (CRC), identification of novel targets and treatment options are imperative for improving its prognosis and survival rates. The mitochondrial SIRT3 and SHMT2 have key roles in metabolic reprogramming and cell proliferation. This study investigated the potential use of the natural product apigenin in CRC treatment employing both in vivo and in vitro models and explored the role of SIRT3 and SHMT2 in apigenin-induced CRC apoptosis. The role of SHMT2 in CRC patients' survival was verified using TCGA database. In vivo, apigenin treatment restored the normal colon appearance. On the molecular level, apigenin augmented the immunohistochemical expression of cleaved caspase-3 and attenuated SIRT3 and SHMT2 mRNA expression CRC patients with decreased SHMT2 expression had improved overall and disease-free survival rates. In vitro, apigenin reduced the cell viability in a time-dependent manner, induced G0/G1 cell cycle arrest, and increased the apoptotic cell population compared to the untreated control. Mechanistically, apigenin treatment mitigated the expression of SHMT2, SIRT3, and its upstream long intergenic noncoding RNA LINC01234 in CRC cells. Conclusively, apigenin induces caspase-3-dependent apoptosis in CRC through modulation of SIRT3-triggered mitochondrial pathway suggesting it as a promising therapeutic agent to improve patient outcomes.

Dietary nanocomposite of vitamin C and vitamin E enhanced the performance of Nile tilapia.

Nowadays, nanomaterials enter high numbers of daily used products and drug manufacture. A nanocomposite of vitamins C (VC) and vitamin E (VE) with chitosan as a vehicle and protector was used in a comparative eight-week feeding study, Nile tilapia weighing 31.2 ± 0.36 g distributed in seven groups and fed (G1) basal diet, (G2) bulk VC, (G3) VC- nanoparticles (NPs), (G4) bulk VE, (G5) VE-NPs, bulk VCE (G6), and (G7) VC plus VE (VCE)-NPs, respectively. The Nile tilapia-fed nanocomposite vitamins had significantly higher growth performance compared to the control; VCE-NPs had the superiority among tested supplementations where total weight gain (63.6 g), daily weight gain (1.13 g), relative growth rate (206.1%) with lower feed conversion rate (1.6) and insignificant feed intake (101.5 g). Overall, the level of liver enzymes was significantly decreased in fish serum after eight-week nanocomposite supplementation, and dietary VCE-NPs caused a significant reduction of serum AST (18.45 IU/L) and ALT (14.77 IU/L) compared to the control 25.5 IU/L and 17.6 IU/L, respectively. Fish fed dietary VCE-NPs, VC-NPs, and VE-NPs had significant enhancement of RBCs 4.2 × 106/µL, 3.8 × 106/µL, and 3.55 × 106/µL; WBCs 46.15 × 103, 42.9 × 103, and 44 × 103/µL, respectively, Also TP was significantly higher 6.38 g/dL in VCE-NPs group compared to the control and the other treatments. Over all, the dietary nanocomposite vitamins boost the innate immunity of the experimental Nile tilapia, the oxidative burst activity (OBA), phagocytic activity (PA), phagocytic index (PI), and serum antibacterial (SAA) were significantly increased compared to those received bulk vitamins and the control. The activity of antioxidant biomarkers in fish serum including glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), glutathione reductase (GR), and myeloperoxidase (MPO) showed a rise in the serum of Nile tilapia received nano- and bulk-form of VC and VCE compared to the control and both forms of VE. Furthermore, the level of malondialdehyde (MDA), reduced glutathione (GSH), and oxidized glutathione (GSSG) were significantly increased in the fish serum following the trend of antioxidants enzymes. In conclusion, a dietary nanocomposite of vitamin C and vitamin E enhanced Nile tilapia's growth performance and feed utilization. It could also improve health status and immune response. The values of antioxidant biomarkers indicated that the nanocomposite could help the fish body scavenge the generated reactive oxidative species (ROS).

Arctigenin from Burdock Root Exhibits Potent Antibacterial and Anti-Virulence Properties against Pseudomonas aeruginosa.

Arctium lappa (Burdock) root is used in various culinary applications especially in Asian Cuisine. Arctigenin (ARC) is a polyphenolic compound abundant in the roots of the burdock plant from which it derives its name. The emergence of bacterial resistance is a growing global worry, specifically due to the declining availability of new antibiotics. Screening for the antibacterial candidates among the safe natural products is a promising approach. The present study was aimed to assess the antibacterial activity of ARC against Pseudomonas aeruginosa exploring its effect on the bacterial cell membrane. Furthermore, the anti-virulence activities and anti-quorum sensing (QS) activities of ARC were in vitro, in vivo and in silico assessed against P. aeruginosa. The current results showed the ARC antibacterial activity was owed to its disruption effect of the cell membrane. ARC at sub-MIC significantly decreased the formation of biofilm, motility, production of extracellular enzymes and in vivo protected mice against P. aeruginosa. These anti-virulence activities of ARC are owed to its interference with bacterial QS and its expression. Furthermore, ARC showed mild effect on mammalian erythrocytes, low probability to induce resistance and synergistically combined with antibiotics. In summary, the promising anti-virulence properties of ARC indicate its potential as an effective supplement to conventional antibiotics for treating severe P. aeruginosa infections.

Rapid eco-friendly selective dye removal using modified chitosan-based sponges: Synthesis, characterization, and application.

The ongoing challenge of water scarcity persists alongside a concerning rise in water pollution driven by population expansion and industrial development. As a result, urgent measures are imperative to address the pressing need for a clean and sustainable water supply. In this study, a sustainable and green approach was utilized to prepare four chitosan-based sponges from a chemically modified chitosan with different alkyl chains in aqueous medium and at room temperature. The resulting sponges displayed excellent stability in water with outstanding dye removal efficiency. The adsorption capacity was associated with the alkyl chain length incorporated to the polymer backbone. All sponges displayed a high adsorption capacity of methyl orange (MO) ranges between 238 and 380 mg g-1, while a low capacity were obtained for methylene blue (MB) and Rhodamine B (RB). Competitive adsorption experiments were conducted on binary and ternary mixtures to assess the selective removal of MO from a mixture of dyes in which the separation factor was found to be ranging between 1.6 and 32. The adsorption kinetics isotherms of all sponges followed the pseudo-second-order, and the Langmuir model was found to be more suitable than the Freundlich for the adsorption of MO on the sponges. The chitosan-based sponges showed stable performance, robustness and reusability over 5 adsorption-desorption cycles, indicating their great potential for water treatment applications.

Anti-tumor withanolides as signal transducers and activators of transcription 3 (STAT3)-inhibition from Withania obtusifolia.

The Solanaceae family and the Withania genus specifically are rich sources of medicinal plants. Liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS/MS) revealed a predominance of withanolides from an organic extract of Withania obtusifolia. A constructed molecular network uncovered the presence of potentially novel withanolides. A series of withanolides were then isolated and structurally characterized from the extract including two new withanolides (withafolia A and withafolia B) and seven previously reported metabolites. Of the isolated compounds, cytotoxicity of withanolide J, physaperuvin G, and a commercial STAT3 inhibitor (S3I-201) were assessed against a human leukemia HL-60 cell line resulting in IC50 values of 26, 29, and 120 µM, respectively. In silico molecular docking simulations indicate that withanolide J and physaperuvin G can bind as an inhibitor in the active site of STAT3 with docking scores comparable to the selective STAT3 inhibitor, S3I-201.

The metabolic benefits of thermogenic stimulation are preserved in aging.

Adipose thermogenesis has been actively investigated as a therapeutic target for improving metabolic dysfunction in obesity. However, its applicability to middle-aged and older populations, which bear the highest obesity prevalence in the US (approximately 40%), remains uncertain due to age-related decline in thermogenic responses. In this study, we investigated the effects of chronic thermogenic stimulation using the ß3-adrenergic (AR) agonist CL316,243 (CL) on systemic metabolism and adipose function in aged (18-month-old) C57BL/6JN mice. Sustained ß3-AR treatment resulted in reduced fat mass, increased energy expenditure, increased fatty acid oxidation and mitochondrial activity in adipose depots, improved glucose homeostasis, and a favorable adipokine profile. At the cellular level, CL treatment increased uncoupling protein 1 (UCP1)-dependent thermogenesis in brown adipose tissue (BAT). However, in white adipose tissue (WAT) depots, CL treatment increased glycerol and lipid de novo lipogenesis (DNL) and turnover suggesting the activation of the futile substrate cycle of lipolysis and reesterification in a UCP1-independent manner. Increased lipid turnover was also associated with the simultaneous upregulation of proteins involved in glycerol metabolism, fatty acid oxidation, and reesterification in WAT. Further, a dose-dependent impact of CL treatment on inflammation was observed, particularly in subcutaneous WAT, suggesting a potential mismatch between fatty acid supply and oxidation. These findings indicate that chronic ß3-AR stimulation activates distinct cellular mechanisms that increase energy expenditure in BAT and WAT to improve systemic metabolism in aged mice. Our study provides foundational evidence for targeting adipose thermogenesis to improve age-related metabolic dysfunction.

Smart Chemometric­Assisted Spectrophotometric Approaches for Simultaneous Quantification of Tertiary Combination Recommended for COVID-19 Supportive Treatments with Their Greenness Assessment.

BACKGROUND: There is an increasing interest of scientific community in developing innovative methodologies for their analysis needs within green analytical chemistry framework. UV spectrophotometry is one of the most promising eco-friendly methods, which is integrated with advanced chemometric tools to enhance the selectivity of the analysis of complex mixtures with severe overlapped signals. OBJECTIVES: Simultaneous determination of a triple-combination of pseudoephedrine hydrochloride (PSE), carbinoxamine maleate (CRX), and paracetamol (PAR) using an artificial intelligence system and multivariate calibration methods. This combination is recently recommended for COVID-19 home-treated patients as part of a symptomatic treatment. METHODS: Namely, the suggested models are: Artificial Neural Networks, Partial Least Squares, and Principal Component Regression. The proposed algorithms were optimized and developed with the aid of a five-level, three-factor experimental design. RESULTS: The investigated methods were applied over the concentration range of 100-180 µg/mL, 18-16 µg/mL, and 4-12 µg/mL for PSE, CRX, and PAR, respectively. The models validation results demonstrated excellent recoveries (around 98 to 102%), signaling the approaches outstanding resolution capacity for the cited compounds in the presence of common excipients. The outcomes of the studied methods were statistically compared to the official approaches, and no significant difference was found. CONCLUSION: The suggested models were efficiently employed to determine the selected drugs in their combined tablets without any initial separation steps. The impact of these methods on the environment was evaluated via greenness tools, namely; National Environmental Method Index, Raynie and Driver's green assessment method, analytical Eco-Scale, Green Analytical Procedure Index, and Analytical Greenness Metric. HIGHLIGHTS: Green chemometric quality assessment of PSE, CRX, and PAR in their pure and pharmaceutical dosage forms. The established approaches are innovative, sustainable, smart, fast, selective, and cost-effective. These models are potential green nominees for routine analysis of the investigated mixture in quality control laboratories.

Modulation of aryl hydrocarbon receptor activity by tyrosine kinase inhibitors (ponatinib and tofacitinib).

Ponatinib and tofacitinib, established kinase inhibitors and FDA-approved for chronic myeloid leukemia and rheumatoid arthritis, are recently undergoing investigation in diverse clinical trials for potential repurposing. The aryl hydrocarbon receptor (AhR), a transcription factor influencing a spectrum of physiological and pathophysiological activities, stands as a therapeutic target for numerous diseases. This study employs molecular modelling tools and in vitro assays to identify ponatinib and tofacitinib as AhR ligands, elucidating their binding and molecular interactions in the AhR PAS-B domain. Molecular docking analyses revealed that ponatinib and tofacitinib occupy the central pocket within the primary cavity, similar to AhR agonists 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and (benzo[a]pyrene) B[a]P. Our simulations also showed that these compounds exhibit good stability, stabilizing many hot spots within the PAS-B domain, including the Dα-Eα loop, which serves as a regulatory element for the binding pocket. Binding energy calculations highlighted ponatinib's superior predicted affinity, revealing F295 as a crucial residue in maintaining strong interaction with the two compounds. Our in vitro data suggest that ponatinib functions as an AhR antagonist, blocking the downstream signaling of AhR pathway induced by TCDD and B[a]P. Additionally, both tofacitinib and ponatinib cause impairment in AhR-regulated CYP1A1 enzyme activity induced by potent AhR agonists. This study unveils ponatinib and tofacitinib as potential modulators of AhR, providing valuable insights into their therapeutic roles in AhR-associated diseases and enhancing our understanding of the intricate relationship between kinase inhibitors and AhR.

Sustained corneal nerve loss predicts the development of diabetic neuropathy in type 2 diabetes.

Introduction: This study was undertaken to investigate whether sustained rather than a single measure of corneal nerve loss was associated with the onset of diabetic peripheral neuropathy (DPN) and the progression of neuropathic symptoms and deficits in individuals with type 2 diabetes (T2D). Methods: Participants underwent clinical, metabolic testing and assessment of neuropathic symptoms, vibration perception threshold (VPT), sudomotor function, and corneal confocal microscopy (CCM) at baseline, 1, 2, and 4-7 years. Sustained corneal nerve loss was defined as abnormal corneal nerve fiber density (CNFD, <24 fibers/mm2), corneal nerve branch density (CNBD, <21 branches/mm2), and corneal nerve fiber length (CNFL, <16 mm/mm2) persisting for ≥50% of the study duration. Results: A total of 107 participants with a mean duration of T2D of 13.3 ± 7.3 years, aged 54.8 ± 8.5 years, underwent baseline and follow-up assessments over a median duration of 4 years, ranging from 1 to 7 years. The DPN prevalence at baseline was 18/107 (16.8%), and of the 89 participants without DPN at baseline, 13 (14.6%) developed DPN during follow-up. Approximately half of the cohort had sustained corneal nerve damage, and corneal nerve measures were significantly lower in this group than those without sustained damage (p < 0.0001). Sustained corneal nerve damage was associated with the development of DPN (p < 0.0001), a progressive loss of vibration perception (p ≤ 0.05), an increased incidence of burning pain, numbness, or a combination of both (p = 0.01-0.001), and a borderline association with progressive sudomotor dysfunction (p = 0.07). Sustained abnormal CNFL effectively distinguished between participants who developed DPN and those who did not (AUC: 76.3, 95% CI: 65.9-86.8%, p < 0.0001), while baseline and other sustained measures did not predict DPN onset. Conclusion: Sustained abnormal CCM is associated with more severe corneal nerve damage, DPN development, and the progression of neuropathic symptoms and deficits. Regular CCM monitoring may enable the identification of those at greater risk of developing and worsening DPN who may benefit from more aggressive risk factor reduction.

Carboxymethylcellulose encapsulated fingolimod, siRNA@ZnO hybrid nanocomposite as a new anti-Alzheimer's material.

Alzheimer's disease (AD) is a fatal neurological disorder that causes cognitive and memory function to deteriorate. A critical pathogenic event that speeds up the development of AD is the interaction between dysfunctional microglia and amyloid-ß (Aß). We have developed a hybrid nanocomposite material to treat AD by normalizing the dysfunctional microglia. The material is based on carboxymethylcellulose (CMC) encapsulated fingolimod, siRNA, and zinc oxide (ZnO) with variable loading (CMC-Fi-siRNA@ZnO a-d ). The material was characterized using different techniques including FTIR, XRD, thermal analysis, SEM with EDX, and TEM micrographs. The chemical structure was confirmed by FTIR and XRD analyses, which indicated the successful integration of ZnO nanoparticles (NPs) into the polymer matrix, signifying a well-formed composite structure. The thermal stability order at 10% weight loss was CMC-Fi-siRNA@ZnO c > CMC-Fi-siRNA@ZnO b > CMC-Fi-siRNA@ZnO d > CMC-Fi-siRNA@ZnO a . The CMC-Fi-siRNA@ZnO d dramatically alleviates the priming of microglia by lowering the level of proinflammatory mediators and increasing the secretion of BDNF. This considerably improves the phagocytosis of Aß. In the cell viability test in immortalized microglia cells (IMG), the hybrid nanocomposite (NP) exhibited no significant effect on cell survival after 48 hours of incubation. The NP also decreased the cytotoxicity caused by Aß. Therefore, the CMC-hybrid NP has high potential as a drug delivery system in the development of therapeutic strategies for AD.

Anticoagulation activity of sulfated carboxymethyl cellulose/Azadirachta indica leaf powder-based bio-composite.

Polymeric bio-composites synthesized via a green approach using natural herbs have fascinating anticoagulant activity due to their eco-friendly and non-toxic behavior towards various physical and chemical actions. Herein, we introduce a simple and eco-friendly approach for the fabrication of a new hybrid type of bio-composite based on sulfated carboxymethyl cellulose (S-CMC) and Azadirachta indica leaf powder (S-CMC/NLP). First, a non-toxic sulfating agent called N(SO3Na)3 was used to modify carboxymethyl cellulose into S-CMC. With an ion exchange capacity of 0.25 meq. g-1, the level of sulfation (%) of S-CMC (modified polysaccharide) was measured to be 12.01%. Three types of S-CMC/NLP bio-composites were developed by varying the concentration of NLP. FE-SEM, EDX, and XRD were used to characterize the structural features of S-CMC/NLP bio-composites. FTIR spectroscopy indicated that the S-CMC/NLP bio-composite possesses COO-, -OH and SO3- groups, suggesting the structural similarity to heparin. In addition, the anticoagulant effect of the S-CMC/NLP bio-composite was investigated using PT and APTT assays. The APTT investigation confirmed that following the intrinsic pathway of the coagulation system, 2-NLP/S-CMC bio-composite dose-dependently (0.045-0.28 mg mL-1) prolonged the time of blood coagulation compared to control (pure plasma). The S-CMC/NLP bio-composite showed its potential as a new, safe, and effective candidate for anticoagulant activity.

Effect of web-based health education on nursing students' knowledge, adaptive healthy measures and attitudes regarding polycystic ovary syndrome: a randomized controlled trial.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting women of reproductive age, and it has emerged as a significant global public health issue. This study aimed to investigate the effects of web-based health education on nursing students' knowledge, adaptive healthy measures, and attitudes toward PCOS. METHODS: A two-group randomized controlled trial (RCT) with pre-test and immediate post-test assessments was conducted. Study participants were recruited using a simple random sampling method from the Faculty of Nursing, Mansoura University, Egypt. A questionnaire consisting of six sections was developed to collect data, which was analyzed with the SPSS 23.0 using Student's t-test, Pearson's correlation test, and chi-square test analysis of variance. RESULTS: The analysis revealed a significant increase in knowledge scores post-intervention, with the web-based learning groups (32.2 ± 10.5) outperforming the traditional learning group (22.1 ± 10.2), with (p < 0.05). Similarly, there was a notable improvement in adaptive healthy measures scores post-intervention, with the web-based learning group (8.9 ± 2.4) showing better results than the traditional group (6.5 ± 2.9), with (p < 0.05). In terms of attitudes toward PCOS, the web-based group (18.2 ± 4.9) displayed a significant improvement compared to the traditional group (11.7 ± 5.2), with (p < 0.05). CONCLUSIONS: The findings suggest that web-based learning is more effective than traditional methods in enhancing nursing students' knowledge, adaptive healthy measures, and attitudes toward PCOS. TRIAL REGISTRATION: This study was registered by Clinical Trials.gov Identifier: (NCT06192381|| https://www. CLINICALTRIALS: gov/ ) on 5-1-2024.

Efficacy and Safety of Autologous Nanofat Injection in the Treatment of Postburn Scars Using Optical Skin Imaging Analysis.

BACKGROUND: Burn scars are considered one of the challenging issues that can affect the quality of life by causing aesthetic and functional problems. Injecting nanofat particles, which are considered a source of stem cells, into the dermis and/or subcutis of the burned area is considered a promising procedure for the treatment of scars and the correction of volume shortage and skin renewal. OBJECTIVE: To assess the safety and effectiveness of using autologous nanofat injections to treat burn scars. METHODS: Thirty patients with postburn scars participated in the trial. Each patient received one session of liposuction, which was then converted into nanofat and injected back into the scar tissue. Four months after the session, the evaluation was conducted both objectively using the Antera camera 3D imaging and subjectively using the Vancouver scar scale (VSS). RESULTS: Because there were statistically significant improvements in the treated scars' height, color, vascularity, and pliability, the total VSS scores differed significantly before and after treatment. Furthermore, the Antera 3D imaging revealed a statistically significant variation in the treated scars' indentations, erythema, and pigmentation scores. CONCLUSION: The study findings demonstrated that nanofat is a successful postburn scar treatment option that improves patients' quality of life.

Huntingtin is an RNA binding protein and participates in NEAT1-mediated paraspeckles.

Huntingtin protein, mutated in Huntington's disease, is implicated in nucleic acid-mediated processes, yet the evidence for direct huntingtin-nucleic acid interaction is limited. Here, we show wild-type and mutant huntingtin copurify with nucleic acids, primarily RNA, and interact directly with G-rich RNAs in in vitro assays. Huntingtin RNA-immunoprecipitation sequencing from patient-derived fibroblasts and neuronal progenitor cells expressing wild-type and mutant huntingtin revealed long noncoding RNA NEAT1 as a significantly enriched transcript. Altered NEAT1 levels were evident in Huntington's disease cells and postmortem brain tissues, and huntingtin knockdown decreased NEAT1 levels. Huntingtin colocalized with NEAT1 in paraspeckles, and we identified a high-affinity RNA motif preferred by huntingtin. This study highlights NEAT1 as a huntingtin interactor, demonstrating huntingtin's involvement in RNA-mediated functions and paraspeckle regulation.

Unravelling the Phytochemical Composition and Antioxidant Potential of Different Parts of Rumex vesicarius L.: A RP-HPLC-MS-MS/MS, Chemometrics, and Molecular Docking-Based Comparative Study.

Rumex vesicarius L. Polygonaceae is a wildly grown plant in Egypt, North Africa, and Asia with wide traditional uses. Several studies reported its biological activities and richness in phytochemicals. This research addresses a comprehensive metabolic profiling of the flowers, leaves, stems, and roots via RP-HPLC-QTOF-MS and MS/MS with chemometrics. A total of 60 metabolites were observed and grouped into phenolic acids, flavonoids, phenols, terpenes, amino acids, fatty acids, organic acids, and sugars. Principal component analysis and hierarchal cluster analysis showed the segregation of different parts. Moreover, the antioxidant capacity was determined via several methods and agreed with the previous results. Additionally, an in silico approach of molecular docking of the predominant bioactive metabolites was employed against two antioxidant targets, NADPH oxidase and human peroxiredoxin 5 enzyme (PDB ID: 2CDU and 1HD2) receptors, alongside ADME predictions. The molecular modelling revealed that most of the approached molecules were specifically binding with the tested enzymes, achieving high binding affinities. The results confirmed that R. vesicarius stems and roots are rich sources of bioactive antioxidant components. To our knowledge, this is the first comprehensive metabolic profiling of R. vesicarius giving a prospect of its relevance in the development of new naturally based antioxidants.

σ-Hole, lone-pair-hole, and π-hole site-based interactions in aerogen-comprising complexes: a comparative study.

Herein, the potential of ZO3 and ZF2 aerogen-comprising molecules (where Z = Ar, Kr, and Xe) to engage in σ-, lp-, and π-hole site-based interactions was comparatively studied using various ab initio computations. For the first time, a premier in-depth elucidation of the external electric field (EEF) influence on the strength of the σ-, lp-, and π-hole site-based interactions within the ZO3/ZF2⋯NH3 and ⋯NCH complexes was addressed using oriented EEF with disparate magnitude. Upon the energetic features, σ-hole site-based interactions were noticed with the most prominent preferability in comparison to lp- and π-hole analogs. This finding was ensured by the negative interaction energy values of -11.65, -3.50, and -2.74 kcal mol-1 in the case of σ-, lp-, and π-hole site-based interactions within the XeO3⋯ and XeF2⋯NH3 complexes, respectively. Detailedly, the strength of the σ- and lp-hole site-based interactions directly correlated with the atomic size of the aerogen atoms and the magnitude of the positively oriented EEF. Unexpectedly, an irregular correlation was noticed for the interaction energies of the π-hole site-based interactions with the size of the π-hole. Interestingly, the π-hole site-based interactions within Kr-comprising complexes exhibited higher negative interaction energies than the Ar- and Xe-comprising counterparts. Notwithstanding, a direct proportion between the interaction energies of the π-hole site-based interactions and π-hole size was obtained by employing EEF along the positive orientation with high strength. The present outcomes would be a fundamental basis for forthcoming progress in studying the σ-, lp-, and π-hole site-based interactions within aerogen-comprising complexes and their pertinent applications in materials science and crystal engineering.

CELF4 (rs1786814) gene polymorphism and speckle-tracking Echocardiography for cardiovascular complications in childhood cancer survivors.

BACKGROUND: Despite a well-known dose-dependent association between the risk of cardiac dysfunction and anthracycline, the risk of cardiac dysfunction for any given anthracycline dose varies between patients. So, we assessed CELF4 (rs1786814) gene polymorphism on anthracycline-related cardiotoxicity in childhood cancer survivors (CCS). METHODS: This comparative cross-sectional study included 53 CCS who had regular follow-up visits at the Pediatric Oncology Unit, Menoufia University Hospital. CELF4 (rs1786814) gene polymorphism and conventional and speckle-tracking Echocardiography were done for all survivors. RESULTS: Regarding CELF4 (rs1786814) genotypes, significant differences existed between the studied groups with a predominance of GG homozygous mutation. For Echocardiographic findings, the ejection fraction and end-systolic diameter compared to the control group, were significantly lower in the survivors group. Speckle- tracking Echocardiography showed a significant difference regarding (GLPS-A4C) and (GLPS-LAX), with no significant difference regarding (GLPS-A2C), (GLPS-Avg) and left atrium between the studied groups. Multivariate logistic regression analysis illustrated a statistically significant relation between cumulative anthracycline dose >300 mg/m2 and CLEF4 (rs1786814) genotypes (GG and GA) and the risk of cardiotoxicity with more significance in GG mutation. CONCLUSION: Early detection of ventricular dysfunction in CCS with subclinical cardiotoxicity with regular follow-up is promising before the development of life-threatening complications. IMPACT: Early detection of anthracycline-related cardiotoxicity in childhood cancer survivors (CCS) after finishing chemotherapy. CLEF4 (rs1786814) GG variant is more significant in CCS exposed to high-dose anthracycline. GLPS holds promise as an early predictor of late left ventricular dysfunction and subclinical cardiotoxicity in CCS.