Potential Role Research Articles

Investigation into the DNA's conformations and their conversions from the phase transition theory

The functions and transformation mechanisms of nucleic acids in their various states are of great importance in physiology and pathology. Based on the Landau model, this study reveals the mechanism of the existence of chirality and the transformation rules between different chiral conformations by studying the Duffing oscillation response of the local gauge potential on the DNA chain. The research results show that normal chiral DNA and DNA configuration transition behaviors exhibit regular nonlinear periodic oscillations. Moreover, the gauge potential value approaches zero at the B-Z junction site, which may add a criterion for detecting Z-forming sites. In addition, external force and damping play a key role in the chiral gauge potential of nucleic acids, and they can influence, regulate and even control the configuration transition of nucleic acids. Finally, we verified the rationality of our theory by combining x-ray crystal diffraction data of multiple configurations of DNA. This study provides new insights into the behavior and function of chiral DNA in organisms, and provides new possibilities for regulating DNA conformational transition in the future.

The fractional multi-dimensional Bessel transform and its role in anisotropic Riesz-Bessel potential

This paper introduces an innovative fractional multidimensional Bessel transform, enhanced by a novel convolution structure. This integral transform parallels the established roles of the Fourier and multidimensional Bessel transforms, establishing a unique position in the field of fractional calculus. Its most notable feature is the seamless integration with a new class of anisotropic Riesz-Bessel potentials.

The Structure of Carbon Dioxide at the Air-Water Interface and its Chemical Implications.

The efficient reduction of CO2 into valuable products is a challenging task in an international context marked by the climate change crisis and the need to move away from fossil fuels. Recently, the use of water microdroplets has emerged as an interesting reaction media where many redox processes which do not occur in conventional solutions take place spontaneously. Indeed, several experimental studies in microdroplets have already been devoted to study the reduction of CO2 with promising results. The increased reactivity in microdroplets is thought to be linked to unique electrostatic solvation effects at the air-water interface. In the present work, we report a theoretical investigation on this issue for CO2 using first-principles molecular dynamics simulations. We show that CO2 is stabilized at the interface, where it can accumulate, and that compared to bulk water solution, its electron capture ability is larger. Our results suggest that reduction of CO2 might be easier in interface-rich systems such as water microdroplets, which is in line with early experimental data and indicate directions for future laboratory studies. The effect of other relevant factors which could play a role in CO2 reduction potential is discussed.

Therapeutic Potential of Myricetin in the Treatment of Neurological, Neuropsychiatric, and Neurodegenerative Disorders.

Myricetin (MC), 3,5,7,3',4',5'-hexahydroxyflavone, chemically belongs to a flavonoid category known to confer antioxidant, antimicrobial, antidiabetic, and neuroprotective effects. MC is known to suppress the generation of Reactive Oxygen Species (ROS), lipid peroxidation (MDA), and inflammatory markers. It has been reported to improve insulin function in the human brain and periphery. Besides this, it modulates several neurochemicals including glutamate, GABA, serotonin, etc. MC has been shown to reduce the expression of the enzyme Mono Amine Oxidase (MAO), which is responsible for the metabolism of monoamines. MC treatment reduces levels of plasma corticosterone and restores hippocampal BDNF (full form) protein in stressed animals. Further, MC has shown its protective effect against amyloid-beta, MPTP, rotenone, 6-OHDA, etc. suggesting its potential role against neurodegenerative disorders. The aim of the present review is to highlight the therapeutic potential of MC in the treatment of several neurological, neuropsychiatric, and neurodegenerative disorders.

Exploring the Therapeutic Potential of Chalcones in Oncology: A Comprehensive Review

Abstract:: Chalcone is a bioactive flavonoid contained in various plants such as Angelica archangelica, Pueraria lobata, and Glycyrrhiza glabra. It has been studied extensively in the field of pharmaceutical sciences due to its significant role in therapeutic potential including antibacterial, antiinflammatory, analgesic, cytotoxic, and anti-tumour properties. A plenty of study indicated numerous chalcone derivatives exhibit enhanced potency and reduced toxicity as compared to natural analogues. In this review, we introduce chalcone and its various derivatives including 1- naphthylacetophenone, 2-benzimidazolyl, 2-furoyloxy, 3-(furan-2-yl)pyrazol-4-yl, 4'-alkoxy, 4- anilinoquinolinyl, 4-aryloxyquinazolines, acridine, benzamide, benzenesulfonamide, bischalcone, cinnamoylthiazoles, D-glucosyl azides, dialkylamino, dihydropyrimidinone, indole, isoquinoline, ligustrazine, morpholinothiazole, naphthalene, quinoline, sulphonamide, thiazoleimidazopyridine, thienyl, thiophene, triazines, triazole-benzimidazole, tri-methoxyphenyl, and α- trifluoromethyl hybrids and display their promising activity against various cancer cell lines, such as breast cancer, prostate cancer, colon cancer, lung cancer, cervical cancer, and liver cancer.

Signalling Pathways Involved in Microglial Activation in Alzheimer's Disease and Potential Neuroprotective Role of Phytoconstituents.

Alzheimer's disease (AD) is a commonly reported neurodegenerative disorder associated with dementia and cognitive impairment. The pathophysiology of AD comprises Aβ, hyperphosphorylated tau protein formation, abrupt cholinergic cascade, oxidative stress, neuronal apoptosis, and neuroinflammation. Recent findings have established the profound role of immunological dysfunction and microglial activation in the pathogenesis of AD. Microglial activation is a multifactorial cascade encompassing various signalling molecules and pathways such as Nrf2/NLRP3/NF-kB/p38 MAPKs/ GSK-3β. Additionally, deposited Aβ or tau protein triggers microglial activation and accelerates its pathogenesis. Currently, the FDA-approved therapeutic regimens are based on the modulation of the cholinergic system, and recently, one more drug, aducanumab, has been approved by the FDA. On the one hand, these drugs only offer symptomatic relief and not a cure for AD. Additionally, no targeted-based microglial medicines are available for treating and managing AD. On the other hand, various natural products have been explored for the possible anti-Alzheimer effect via targeting microglial activation or different targets of microglial activation. Therefore, the present review focuses on exploring the mechanism and associated signalling related to microglial activation and a detailed description of various natural products that have previously been reported with anti-Alzheimer's effect via mitigation of microglial activation. Additionally, we have discussed the various patents and clinical trials related to managing and treating AD.

The Use of Nanocarriers to Enhance the Anti-neuroinflammatory Potential of Dietary Flavonoids in Animal Models of Neurodegenerative Diseases: A Systematic Review.

Neurodegenerative diseases (NDs) have become a common and growing cause of mortality and morbidity worldwide, especially in older adults. The natural flavonoids found in fruits and vegetables have been shown to have therapeutic effects against many diseases, including NDs; however, in general, flavonoids have limited bioavailability to the target cells. One promising strategy to increase bioavailability is to entrap them in nanocarriers. This article aims to review the potential role of nanocarriers in enhancing the anti-neuroinflammatory efficacy of flavonoids in experimentally induced ND. A literature search was conducted in the scientific databases using the keywords "neurodegenerative", "anti-neuroinflammatory", "dietary flavonoids," "nanoparticles", and "therapeutic mechanisms". A total of 289 articles were initially identified, of which 45 articles reported on flavonoids. After completion of the selection process, five articles that met the criteria of the review were selected for analysis. Preclinical studies identified in this review showed that nanoencapsulated flavonoids attenuated cognitive impairment and seizure, improved behavioral patterns, and reduced levels of astrocytes. Importantly, they exhibited strong antioxidant properties, increasing the levels of antioxidant enzymes and reducing oxidative stress (OS) biomarkers. Moreover, nanocarrier-complexed flavonoids decreased the levels of the pro-inflammatory cytokines, interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nod-like receptor protein 3 inflammasome activation (NLRP3). They also had remarkable effects on important ND-related neurotransmitters, improved cognitive function via cholinergic neurotransmission, and increased prefrontal cortical and hippocampal norepinephrine (NE) and 5-hydroxytryptamine (5-HT). Nanoencapsulated flavonoids should, therefore, be considered a novel therapeutic approach for the treatment of NDs.

Casein kinase 2 affects epilepsy by regulating ion channels: a potential mechanism.

Epilepsy, characterized by recurrent seizures and abnormal brain discharges, is the third most common chronic disorder of the Central Nervous System (CNS). Although significant progress has been made in the research on antiepileptic drugs (AEDs), approximately one-third of patients with epilepsy are refractory to these drugs. Thus, research on the pathogenesis of epilepsy is ongoing to find more effective treatments. Many pathological mechanisms are involved in epilepsy, including neuronal apoptosis, mossy fiber sprouting, neuroinflammation, and dysfunction of neuronal ion channels, leading to abnormal neuronal excitatory networks in the brain. CK2 (Casein kinase 2), which plays a critical role in modulating neuronal excitability and synaptic transmission, has been shown to be associated with epilepsy. However, there is limited research on the mechanisms involved. Recent studies have suggested that CK2 is involved in regulating the function of neuronal ion channels by directly phosphorylating them or their binding partners. Therefore, in this review, we will summarize recent research advances regarding the potential role of CK2 regulating ion channels in epilepsy, aiming to provide more evidence for future studies.

Study of The Effect of Boswellia Leaf Extract on The Activity of Cardiac Enzymes (ALP, AST, ALT, LDH) Using Spectroscopic Methods

This study investigates the impact of Boswellia carterii leaf extracts on serum enzyme activity in myocardial infarction (MI) patients. Employing a comparative analysis between 60 healthy individuals and 40 cardiac patients, we measured the serum activity of ALP, AST, ALT, and LDH enzymes. Our findings reveal elevated enzyme activity in MI patients. We explored the inhibitory effects of aqueous, alcoholic, and ethyl acetate extracts of Boswellia carterii on these enzymes, demonstrating non-competitive inhibition. The inhibition ratio of ALT, ALP, and AST post-treatment was quantitatively assessed. Statistical analysis was conducted using SPSS-26 with independent t-tests. This research highlights the potential therapeutic role of Boswellia carterii in modulating enzyme activity associated with cardiac events, suggesting avenues for novel treatments in cardiac care.

Coupling motor evoked potentials and brain [18F]FDG-PET in Amyotrophic Lateral Sclerosis: preliminary findings on disease severity

BackgroundThe diagnosis of amyotrophic lateral sclerosis (ALS) is primarily clinical, supported by the electromyographic examination to reveal signs of lower motor neuron damage. Identifying reliable markers of upper motor neuron (UMN) involvement is challenging. On this regard, the role of transcranial magnetic stimulation-induced motor-evoked potentials (TMS-MEPs), and its relationship with UMN burden, is still under investigation. ObjectiveTo evaluate the ability of TMS-MEPs in delineating the neurophysiological UMN damage, and to determine the relationship between TMS-MEPs and [18F]FDG-PET measures of neural dysfunction. MethodsWe retrospectively selected 13 ALS patients who underwent, during the diagnostic process, the TMS-MEPs and [18F]FDG-PET scans. Demographic and clinical data were collected. For the MEP evaluation, we considered normal MEP, absent MEP, or significantly increased central-motor-conduction-time. For [18F]FDG-PET, we conducted voxel-wise analyses, both at single-subject and group levels, exploring hypometabolism and hypermetabolism patterns in comparison with a large dataset of healthy controls (HC). ResultsBased on TMS-MEPs, we identified 4/13 patients with normal MEP in all limbs (GROUP-NO), while 9/13 had an abnormal MEP in at least one limb (GROUP-AB). Despite the [18F]FDG-PET single-subject analysis revealed heterogenous expression of regional hypo- and hyper-metabolism patterns in the patients, the group-level analysis revealed a common hypometabolism, involving the precentral gyrus and the supplementary motor area, the paracentral lobule and the anterior cingulate cortex in the GROUP-AB. Moreover, exclusively for the GROUP-AB compared with HC, a relative hypermetabolism was observed in the right cerebellum, right inferior and middle temporal gyrus. The GROUP-NO showed no specific cluster of hypo- and hyper-metabolism compared to HC. ConclusionThis study showed altered brain metabolism only in the ALS group with abnormal MEPs, suggesting an association between the two biomarkers in defining the UMN damage.

Ras-dependent activation of BMAL2 regulates hypoxic metabolism in pancreatic cancer.

To identify drivers of malignancy in human pancreatic ductal adenocarcinoma (PDAC), we performed regulatory network analysis on a large collection of expression profiles from laser capture microdissected samples of PDAC and benign precursors. We discovered that BMAL2 plays a role in the initiation, progression, post resection survival, and KRAS activity in PDAC. Functional analysis of BMAL2 target genes led us to hypothesize that it plays a role in regulating the response to hypoxia, a critical but poorly understood feature of PDAC physiology. Knockout of BMAL2 in multiple human PDAC cell lines revealed effects on viability and invasion, particularly under hypoxic conditions. Loss of BMAL2 also affected glycolysis and other metabolic processes. We found that BMAL2 directly regulates hypoxia-responsive target genes. We also found that BMAL2 is necessary for the stabilization of HIF1A upon exposure to hypoxia, but destabilizes HIF2A under hypoxia. These data demonstrate that BMAL2 is a master transcriptional regulator of hypoxia responses in PDAC and may serve as a long-sought molecular switch that distinguishes HIF1A- and HIF2A-dependent modes of hypoxic metabolism.

Exploring the immune landscape and drug prediction of an M2 tumor-associated macrophage-related gene signature in EGFR-negative lung adenocarcinoma.

Improving immunotherapy efficacy for EGFR-negative lung adenocarcinoma (LUAD) patients remains a critical challenge, and the therapeutic effect of immunotherapy is largely determined by the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are the top-ranked immune infiltrating cells in the TME, and M2-TAMs exert potent roles in tumor promotion and chemotherapy resistance. An M2-TAM-based prognostic signature was constructed by integrative analysis of single-cell RNA-seq (scRNA-seq) and bulk RNA-seq data to reveal the immune landscape and select drugs in EGFR-negative LUAD. M2-TAM-based biomarkers were obtained from the intersection of bulk RNA-seq data and scRNA-seq data. After consensus clustering of EGFR-negative LUAD into different clusters based on M2-TAM-based genes, we compared the prognosis, clinical features, estimate scores, immune infiltration, and checkpoint genes among the clusters. Next, we combined univariate Cox and LASSO regression analyses to establish an M2-TAM-based prognostic signature. CCL20, HLA-DMA, HLA-DRB5, KLF4, and TMSB4X were verified as prognostic M2-like TAM-related genes by univariate Cox and LASSO regression analyses. IPS and TMB analyses revealed that the high-risk group responded better to common immunotherapy. The study shows the potential of the M2-like TAM-related gene signature in EGFR-negative LUAD, explores the immune landscape based on M2-like TAM-related genes, and predict immunotherapy response of patients with EGFR-negative LUAD, providing a new insight for individualized treatment.

Structure of the human systemic RNAi defective transmembrane protein 1 (hSIDT1) reveals the conformational flexibility of its lipid binding domain.

In C. elegans , inter-cellular transport of the small non-coding RNA causing systemic RNA interference (RNAi) is mediated by the transmembrane protein SID1, encoded by the sid1 gene in the systemic RNA interference-defective ( sid ) loci. SID1 shares structural and sequence similarity with cholesterol uptake protein 1 (CHUP1) and is classified as a member of the cholesterol uptake family (ChUP). Although systemic RNAi is not an evolutionarily conserved process, the sid gene products are found across the animal kingdom, suggesting the existence of other novel gene regulatory mechanisms mediated by small non-coding RNAs. Human homologs of sid gene products - hSIDT1 and hSIDT2 - mediate contact-dependent lipophilic small non-coding dsRNA transport. Here, we report the structure of recombinant human SIDT1. We find that the extra- cytosolic domain (ECD) of hSIDT1 adopts a double jelly roll fold, and the transmembrane domain (TMD) exists as two modules - a flexible lipid binding domain (LBD) and a rigid TMD core. Our structural analyses provide insights into the inherent conformational dynamics within the lipid binding domain in cholesterol uptake (ChUP) family members.

Environment-Driven Variability in Absolute Band Edge Positions and Work Functions of Reduced Ceria.

The absolute band edge positions and work function (Φ) are the key electronic properties of metal oxides that determine their performance in electronic devices and photocatalysis. However, experimental measurements of these properties often show notable variations, and the mechanisms underlying these discrepancies remain inadequately understood. In this work, we focus on ceria (CeO2), a material renowned for its outstanding oxygen storage capacity, and combine theoretical and experimental techniques to demonstrate environmental modifications of its ionization potential (IP) and Φ. Under O-deficient conditions, reduced ceria exhibits a decreased IP and Φ with significant sensitivity to defect distributions. In contrast, the IP and Φ are elevated in O-rich conditions due to the formation of surface peroxide species. Surface adsorbates and impurities can further augment these variabilities under realistic conditions. We rationalize the shifts in energy levels by separating the individual contributions from bulk and surface factors, using hybrid quantum mechanical/molecular mechanical (QM/MM) embedded-cluster and periodic density functional theory (DFT) calculations supported by interatomic-potential-based electrostatic analyses. Our results highlight the critical role of on-site electrostatic potentials in determining the absolute energy levels in metal oxides, implying a dynamic evolution of band edges under catalytic conditions.

Long non-coding RNA BRE-AS1 inhibits proliferation, migration and invasion of clear cell renal cell carcinoma by downregulating miR-106b-5p.

The objective of this study was to investigate the involvement of the long non-coding RNA (lncRNA) BRE-AS1 in clear cell renal cell carcinoma (ccRCC) and to explore its potential therapeutic role. The expression of BRE-AS1 and miR-106b-5p was determined by qRT-PCR. Overexpression of BRE-AS1 and miR-106b-5p were performed to study their relationship. Transwell assays were used to evaluate cell movement. Methylation-specific PCR (MSP) was performed to explore the role of BRE-AS1 in the methylation of the miR-106b-5p gene. The results showed that the expression levels of BRE-AS1 were decreased, while those of miR-106b-5p were increased in ccRCC tissues. BRE-AS1 was found to be closely associated with the prognosis of patients with ccRCC. The expression of BRE-AS1 was inversely correlated with that of miR-106b-5p in tumor tissues. Overexpression of BRE-AS1 led to decreased expression levels of miR-106b-5p and increased methylation of the miR-106b-5p gene, whereas miR-106b-5p did not affect the expression of BRE-AS1. BRE-AS1 inhibited the movement and proliferation of ccRCC cell lines, while miR-106b-5p suppressed the role of BRE-AS1. BRE-AS1 may suppress ccRCC by downregulating the expression of miR-106b-5p.

Bioinformatic Analysis to Identify and Cellular Experiments to Validate Autophagy-related Genes in Psoriasis.

To explore differentially expressed genes (DEGs) associated with autophagy in psoriasis using bioinformatics analysis and verify them in an M5-induced psoriatic cell model. We obtained gene expression microarray data from patients with psoriasis and normal skin tissues from the dataset GSE78097 of the NCBI Gene Expression Omnibus (GEO) database. R software was used to identify DEGs associated with autophagy in psoriasis. Proteinprotein interaction (PPI) and correlation analyses were used to show interactions between certain genes. Their potential biological roles were determined using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, all the DEGs associated with autophagy in psoriasis were validated in a psoriatic cell model by RT-qPCR. 28 DEGs associated with autophagy were identified. These genes were linked to one another, and the most connected hub gene was VEGFA, according to PPI analysis. GO and KEGG enrichment analyses revealed various biological pathways associated with autophagy. The RT-qPCR findings of the expression of 18 genes in the psoriatic cell model confirmed the bioinformatics analysis results. The five genes with the most significant differences were IL24, CCL2, NAMPT, PPP1R15A, and SPHK1. We identified DEGs associated with autophagy in patients with psoriasis. IL24, CCL2, NAMPT, PPP1R15A, and SPHK1 were identified as important genes that may influence psoriasis development through the regulation of autophagy.

Subcortico-Cortical Dysconnectivity in ADHD: A Voxel-Wise Mega-Analysis Across Multiple Cohorts.

A large body of functional MRI research has examined a potential role for subcortico-cortical loops in the pathogenesis of attention deficit hyperactivity disorder (ADHD), but has produced inconsistent findings. The authors performed a mega-analysis of six neuroimaging data sets to examine associations between ADHD diagnosis and traits and subcortico-cortical connectivity. Group differences were examined in the functional connectivity of four subcortical seeds in 1,696 youths with ADHD diagnoses (66.39% males; mean age, 10.83 years [SD=2.17]) and 6,737 unaffected control subjects (47.05% males; mean age, 10.33 years [SD=1.30]). The authors examined associations between functional connectivity and ADHD traits (total N=9,890; 50.3% males; mean age, 10.77 years [SD=1.96]). Sensitivity analyses were used to examine specificity relative to commonly comorbid internalizing and non-ADHD externalizing problems. The authors further examined results within motion-matched subsamples, and after adjusting for estimated intelligence. In the group comparison, youths with ADHD showed greater connectivity between striatal seeds and temporal, fronto-insular, and supplementary motor regions, as well as between the amygdala and dorsal anterior cingulate cortex, compared with control subjects. Similar findings emerged when ADHD traits were considered and when alternative seed definitions were adopted. Dominant associations centered on the connectivity of the caudate bilaterally. Findings were not driven by in-scanner motion and were not shared with commonly comorbid internalizing and externalizing problems. Effect sizes were small (largest peak d, 0.15). The findings from this large-scale mega-analysis support established links with subcortico-cortical circuits, which were robust to potential confounders. However, effect sizes were small, and it seems likely that resting-state subcortico-cortical connectivity can capture only a fraction of the complex pathophysiology of ADHD.

Potential Role of Hydrogels in Stem Cell Culture and Hepatocyte Differentiation

Potential Role of Hydrogels in Stem Cell Culture and Hepatocyte Differentiation

BMSC-derived exosomes attenuate persistent corneal epithelial injury by affecting retinal neural-like cells

Persistent corneal epithelial defect (PED) is a challenge to human which is difficultly cured, normally requiring long-term follow-up. Herein, this study explored the potential role of bone marrow mesenchymal stem cell-derived exosomes (BMSC-exos) in persistent corneal epithelial injury and the underlying mechanism. After characterization of BMSC-exos, RGC-5 cell viability was determined and surface markers of BMSCs were analyzed. Additionally, RT-qPCR and Western blot measured miR-150-5p, Brn3, Islet-1, and PCNA expression. Dual luciferase assays were conducted to evaluate the targeting relationship between long non-coding Ribonucleic Acid (lncRNA) MIAT and miR-150-5p. Presented in ellipsoidal or cup shape, BMSC-exos were positive to BMSC-specific markers CD29 and CD90, and cell surface markers CD9 and CD63 were detected on exosomes. Importantly, treatment with BMSC-exos significantly promoted proliferation of retinal ganglion cells (RGCs) and hindered cell differentiation. Interestingly, down-regulating lncRNA MIAT exerted the same effect as BMSC-exos, increasing cell viability and decreasing the expression of differentiation-related proteins Brn3 and ISL1. Bioinformatics software predicted miR-150-5P as target of lncRNA MIAT, and the relative luciferase activity of miR-150-5P+MIAT-WT co-transfection group was lower. Conclusively, BMSC-exos can improve PED by targeting and regulating miR-150-5p expression through lncRNA MIAT, which can up-regulate PCNA in RGC-5 cells and down-regulate Brn3 and ISL1.

Mechanistic Insights into Bisphenol A-Mediated Male Infertility: Potential Role of Panax Ginseng Extract.

. The escalating prevalence of male infertility in the contemporary era across the globe can be largely attributed to environmental pollution, which is the common etiological factor due to the ubiquitous presence of the environmental contaminants. Bisphenol A is recognized as an endocrine-disrupting chemical that has adverse effects on both male and female reproductive systems. On the other hand, numerous studies have demonstrated that Panax ginseng possessed the potential to improve male infertility parameters; promote spermatogenesis, recover the quality and motility of sperm and enhance testicular functions as it acted as a natural androgen supplement. The objective of this review is to offer a summary of the findings obtained from the current research data on the insult of bisphenol A (BPA) on male infertility and its supposed mode of action, as well as shed light on the potent ameliorative role of Panax ginseng extract, with a special focus on the mechanism behind its action. This review delivers a clear understanding of BPA mechanism of action on male infertility and the presumed risks deriving from its exposure. Also, this review provides evidence for the functional role of Panax ginseng extract in restoring male fertility.