Cellular Functions Research Articles

Low Magnetic Field Exposure Alters Prostate Cancer Cell Properties

Prostate cancer is the second most common neoplasia and fifth-leading cause of cancer death in men worldwide. Electromagnetic and magnetic fields have been classified as possible human carcinogens, but current understanding of molecular and cellular pathways involved is very limited. Effects due to extremely low magnetic/hypomagnetic fields (LMF) are furthermore poorly understood. Extracellular vesicles (EVs) are crucial mediators of cellular communication with multifaceted roles in cancer progression, including via transport and uptake of various protein and microRNA (miRNA) EV-cargoes. miRNAs regulate gene expression and are implicated in cancer-related processes such as proliferation, metastasis, and chemoresistance. This study investigated the effects of LMF exposure (20 nT) by magnetic shielding on the prostate cancer cell line PC3 compared to the prostate epithelial cell line PNT2 under short-term (4 h) conditions. We examined EV profiles following a 4 h LMF exposure alongside associated functional enrichment KEGG and GO pathways for the EV proteomes. The 4 h LMF exposure significantly reduced cellular EV release and modified PC3 EV cargoes to a more inflammatory and metastatic profile, with 16 Disease Pathways and 95 Human Phenotypes associated specifically with the LMF-treated PC3 EV proteomes. These included cancerous, metabolic, blood, skin, cardiac and skeletal Disease Pathways, as well as pain and developmental disorders. In the normal PNT2 cells, less EV protein cargo was observed following LMF exposure compared with cells not exposed to LMF, and fewer associated functional enrichment pathways were identified. This pointed to some differences in various cellular functions, ageing, defence responses, oxidative stress, and disease phenotypes, including respiratory, digestive, immune, and developmental pathways. Furthermore, we analysed alterations in matrix metalloproteinases (MMPs) and miRNAs linked to metastasis, as this is crucial in cancer aggressiveness. The 4 h LMF exposure caused a significant increase in MMP2 and MMP9, as well as in onco-miRs miR-155, miR-210, miR-21, but a significant reduction in tumour-suppressor miRs (miR-200c and miR-126) in the metastatic PC3 cells, compared with normal PNT2 cells. In addition, 4 h LMF exposure significantly induced cellular invasion of PC3 cells. Overall, our findings suggest that changes in magnetic field exposures modulate EV-mediated and miR-regulatory processes in PCa metastasis, providing a basis for exploring novel therapeutic strategies.

Organ crosstalk and dysfunction in sepsis

AbstractSepsis is a dysregulated immune response to an infection that leads to organ dysfunction. Sepsis-associated organ dysfunction involves multiple inflammatory mechanisms and complex metabolic reprogramming of cellular function. These mechanisms cooperate through multiple organs and systems according to a complex set of long-distance communications mediated by cellular pathways, solutes, and neurohormonal actions. In sepsis, the concept of organ crosstalk involves the dysregulation of one system, which triggers compensatory mechanisms in other systems that can induce further damage. Despite the abundance of studies published on ​​organ crosstalk in the last decade, there is a need to formulate a more comprehensive framework involving all organs to create a more detailed picture of sepsis. In this paper, we review the literature published on organ crosstalk in the last 10 years and explore how these relationships affect the progression of organ failure in patients with septic shock. We explored these relationships in terms of the heart–kidney–lung, gut-microbiome–liver–brain, and adipose tissue–muscle–bone crosstalk in sepsis patients. A deep connection exists among these organs based on crosstalk. We also review how multiple therapeutic interventions administered in intensive care units, such as mechanical ventilation, antibiotics, anesthesia, nutrition, and proton pump inhibitors, affect these systems and must be carefully considered when managing septic patients. The progression to multiple organ dysfunction syndrome in sepsis patients is still one of the most frequent causes of death in critically ill patients. A better understanding and monitoring of the mechanics of organ crosstalk will enable the anticipation of organ damage and the development of individualized therapeutic strategies.

De Novo Synthesis of Perdeuterated Phosphoinositide by Installing a Non-native Phospholipid Biopathway in E. coli.

Phosphatidylinositol (PI) and its phosphorylated derivatives are of paramount importance in cellular functions and diseases. Understanding their diverse roles is, however, challenged by difficulties in synthesis and labeling techniques. In this proof-of-concept study, we demonstrate that PI can be straightforwardly de novo-synthesized and deuterium (2H)-labeled in Escherichia coli by genomic insertion of PI synthase from Trypanosoma brucei under constitutive synthetic promoter proD. Insertion into loci atpi-gidB and ybb revealed PI accumulation of 41% and 34% (mol/mol), respectively, when cultivated with glycerol as the sole carbon source. Growth of the atpi-gidB-PIS strain in deuterium-labeled (2H) substrates D2O, D8-glycerol, and D6-myo-inositol achieved PI deuteration of 90%, PE deuteration of 95%, and total fatty acids|fatty acid (FA) deuteration of 97%. This study offers an alternative convenient route to chemical and enzymatic labeling synthesis of PI; more excitingly, this work also, in principle, opens a door for tailoring the FA profile of deuterated PI/PE for task-specific application by repurposing FA biosynthesis pathways.

M6Am Methyltransferase PCIF1 Regulates Periodontal Inflammation.

N6,2'-O-dimethyladenosine (m6Am), a common mRNA modification in eukaryotic capped mRNAs, plays a pivotal role in cellular functions and disease progression. However, its involvement in host inflammation remains elusive. Here, we demonstrate that loss of m6Am methyltransferase phosphorylated CTD interacting factor 1 (PCIF1) attenuates periodontal inflammation in whole-body and myeloid lineage-specific knockout mouse models. Pcif1 deletion inhibits macrophage phagocytosis and migration through m6Am-Csf1r signaling. In addition, colony-stimulating factor-1 receptor (CSF1R) is identified as a potential target for the treatment of periodontitis. We thus reveal a previously unrecognized role for PCIF1-mediated m6Am modification in governing macrophage responses and periodontal inflammation.

Epigenetic Landscapes of Endometriosis: From Pathogenesis to Precision Medicine

Endometriosis, a challenging gynecological disorder characterized by the ectopic presence of endometrial-like tissue, presents significant diagnostic and therapeutic hurdles due to its complex etiology and diverse clinical manifestations. Recent advancements in understanding its pathogenesis have underscored the pivotal role of epigenetic alterations, offering new insights into disease mechanisms and therapeutic targets. Epigenetic changes in endometrial cells significantly contribute to endometriosis pathogenesis, disrupting normal physiology and hormone responsiveness, particularly to progesterone. Dysregulation of histone modifications, DNA methylation, and non-coding RNA expression disrupts cellular homeostasis and promotes disease progression. Histone modifications, notably methylation and acetylation, influence chromatin structure and gene expression, affecting progesterone responsiveness and disease progression. Epigenetic regulators such as Cfp1 modulate progesterone receptor expression and downstream signalling pathways, presenting potential therapeutic targets. Non-coding RNAs, including miRNAs and lncRNAs, exert regulatory effects on gene expression and are implicated in endometriosis pathogenesis. Dysregulated expression disrupts cellular homeostasis and promotes disease progression. Biomarker studies have identified specific miRNAs and lncRNAs associated with endometriosis, offering avenues for non-invasive diagnosis and targeted therapies. siRNA-based therapies targeting key genes involved in endometriosis pathogenesis show promise as novel treatment modalities. By modulating gene expression and cellular functions, siRNA-based therapies offer a targeted approach to mitigate pathological processes. In this review, we summarize recent findings in the molecular mechanisms and regulatory pathways of endometriosis, offering valuable insights into pathology and therapeutic interventions. Future research efforts aimed at elucidating the complex interplay between epigenetic regulators and disease pathways hold promise for innovative diagnostic tools and targeted therapies.

Virtual Screening and Molecular Dynamics Simulation to Identify Inhibitors of the m6A-RNA Reader Protein YTHDC1

YTHDC1 (YTH domain containing 1), a crucial reader protein of N6-methyladenosine (m6A) mRNA, plays a critical role in various cellular functions and is considered a promising target for therapeutic intervention in acute myeloid leukemia and other cancers. In this study, we identified orthosteric small-molecule ligands for YTHDC1. Using a molecular docking approach, we screened the eMolecules database and recognized 15 top-ranked ligands. Subsequently, molecular dynamics simulations and MM/PBSA analysis were used to assess the stability and binding free energy of these potential hit compounds in complex with YTHDC1. Notably, five compounds with IDs of ZINC82121447, ZINC02170552, ZINC65274016, ZINC10763862, and ZINC02412146 exhibited high binding affinities and favorable binding free energies. The results also showed that these compounds formed strong hydrogen bonds with residues SER378, ASN363, and ASN367 and interacted with the aromatic cage of the YTHDC1 reader protein through TRP377, TRP428, and hydrophobic residue LEU439. To assess their viability as lead compounds, we conducted absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies to reveal promising features for these identified small molecules, shedding light on their pharmacokinetic and safety profiles.

Nuclear expansion and chromatin structure remodeling in mouse aging neurons

Abstract Aging, particularly in the brain, involves impairments in multiple cellular functions, many regulated at the nucleus. Chromatin structure plays a critical role in regulating gene expression and the maintenance of genomic stability. During differentiation, each cell type acquire their unique topology, this should be kept for a lifetime, but may deteriorate as we age. However, the effects of aging on the chromatin 3D structure of neurons remain largely unknown and much has been inferred from senescent cells. By combining chromosome conformation capture and microscopy techniques, we investigated cortical neurons of young and aged mice and discovered signs of neuronal nuclear expansion during neuronal aging, leading to increased distances between chromosomes. This expansion alters the topology of compartments, topologically associating domains (TADs) and chromatin loops. While larger TADs tend to dissociate, smaller TADs and loops exhibit strengthened interactions of chromatin in aged neurons. These topological changes impact the borders of TADs, resulting in weakening, this is parallel to Lamin-B weakening and nuclear envelope alterations. We attribute these alterations to changes in physical forces of an expanding nucleus, driving the distancing of chromosomes filling a growing nuclear area, affecting gene expression and topology, contributing to the functional declines observed during aging.

Childhood Multiple Endocrine Neoplasia (MEN) Syndromes: Genetics, Clinical Heterogeneity and Modifying Genes

Multiple endocrine neoplasia (MEN) syndromes are part of a spectrum of clinically well-defined tumor syndromes ultimately characterized by histologically similar tumors arising in patients and families with mutations in one of the following four genes: MEN1, RET, CDKN1B, and MAX. The high level of genetic and phenotypic heterogeneity has been linked to phenocopies and modifying genes, as well as unknown mechanisms that might be investigated in the future based on preclinical and translational considerations. MEN1, also known as Wermer’s syndrome (OMIM *131100), is an autosomal dominant syndrome codifying for the most frequent MEN syndrome showing high penetrance due to mutations in the MEN1 gene; nevertheless, clinical manifestations vary among patients in terms of tumor localization, age of onset, and clinical aggressiveness/severity, even within the same families. This has been linked to the effect of modifying genes, as described in the review. MEN 2-2b-4 and 5 also show remarkable clinical heterogeneity. The traditional view of genetically predisposing monogenic or multifactorial disorders is no longer valid, and mandates a change in scientific focus. Phenotypes are indeed rarely consistent across genetic backgrounds and environments. In the future, understanding factors and genetic variants that control cellular functions and the expression of disease genes should provide insights into fundamental disease processes, providing implications for counseling and therapeutic and prophylactic possibilities.

The p53 target DRAM1 modulates calcium homeostasis and ER stress by promoting contact between lysosomes and the ER through STIM1

It is well established that DNA Damage Regulated Autophagy Modulator 1 (DRAM1), a lysosomal protein and a target of p53, participates in autophagy. The cellular functions of DRAM1 beyond autophagy remain elusive. Here, we show p53-dependent upregulation of DRAM1 in mitochondrial damage-induced Parkinson's disease (PD) models and exacerbation of disease phenotypes by DRAM1. We find that the lysosomal location of DRAM1 relies on its intact structure including the cytosol-facing C-terminal domain. Excess DRAM1 disrupts endoplasmic reticulum (ER) structure, triggers ER stress, and induces protective ER-phagy. Mechanistically, DRAM1 interacts with stromal interacting molecule 1 (STIM1) to tether lysosomes to the ER and perturb STIM1 function in maintaining intracellular calcium homeostasis. STIM1 overexpression promotes cellular health by restoring calcium homeostasis, ER stress response, ER-phagy, and AMP-activated protein kinase (AMPK)-Unc-51 like autophagy activating kinase 1 (ULK1) signaling in cells with excess DRAM1. Thus, by promoting organelle contact between lysosomes and the ER, DRAM1 modulates ER structure and function and cell survival under stress. Our results suggest that DRAM1 as a lysosomal protein performs diverse roles in cellular homeostasis and stress response. These findings may have significant implications for our understanding of the role of the p53/DRAM1 axis in human diseases, from cancer to neurodegenerative diseases.

Development of a sensor to detect methylmercury toxicity

Methylmercury (MeHg) is a well-known neurotoxicant that induces various cellular functions depending on cellular- and developmental-specific vulnerabilities. MeHg has a high affinity for selenol and thiol groups, thus impairing the antioxidant system. Such affinity characteristics of MeHg led us to develop sensor vectors to assess MeHg toxicity. In this study, MeHg-mediated defects in selenocysteine (Sec) incorporation were demonstrated using thioredoxin reductase 1 cDNA fused with the hemagglutinin tag sequence at the C-terminus. Taking advantage of such MeHg-mediated defects in Sec incorporation, a cDNA encoding luciferase with a Sec substituted for cysteine-491 was constructed. This construct showed MeHg-induced decreases in signaling in a dose-dependent manner. To directly detect truncated luciferase under MeHg exposure, we further constructed a new sensor vector fused with a target for proteasomal degradation. However, this construct was inadequate because of the low rate of Sec insertion, even in the absence of MeHg. Finally, a Krab transcriptional suppressor fused with Sec was constructed and assessed to demonstrate MeHg-dependent increases in signal intensity. We confirmed that the vector responded specifically and in a dose-dependent manner to MeHg in cultured cerebellar granule cells. This vector is expected to allow monitoring of MeHg-specific toxicity via spatial and temporal imaging.

ANXA2 promotes osteogenic differentiation and inhibits cellular senescence of periodontal ligament cells (PDLCs) in high glucose conditions

Background Periodontal ligament cells (PDLCs) are a major component of the periodontal ligament and have an important role in the regeneration of periodontal tissue and maintenance of homeostasis. High glucose can affect the activity and function of PDLCs in a variety of ways; therefore, it is particularly important to find ways to alleviate the effects of high glucose on PDLCs. Annexin A2 (ANXA2) is a calcium- and phospholipid-binding protein involved in a variety of cellular functions and processes, including cellular cytokinesis, cytophagy, migration, and proliferation. Aim The aim of this study was to exploring whether ANXA2 attenuates the deleterious effects of high glucose on PDLCs and promotes osteogenic differentiation capacity. Methods and results Osteogenic differentiation potential, cellular senescence, oxidative stress, and cellular autophagy were detected. Culturing PDLCs with medium containing different glucose concentrations (CTRL, 8 mM, 10 mM, 25 mM, and 40 mM) revealed that high glucose decreased the protein expression of ANXA2 (p < 0.0001). In addition, high glucose decreased the osteogenic differentiation potential of PDLCs as evidenced by decreased calcium deposition (p = 0.0003), lowered ALP activity (p = 0.0010), and a decline in the expression of osteogenesis-related genes (p = 0.0008). Moreover, β-Galactosidase staining and expression of p16, p21 and p53 genes showed that it increased cellular senescence in PDLCs (p < 0.0001). Meanwhile high glucose increased oxidative stress in PDLCs as shown by ROS (p < 0.0001). However, these damages caused by high glucose were inhibited after the addition of 1 µM recombinant ANXA2 (rANXA2), and we found that rANXA2 enhanced autophagy in PDLCs under high glucose conditions. Conclusions and discussion Therefore, our present study demonstrates that alterations in ANXA2 under high glucose conditions may be a factor in the decreased osteogenic differentiation potential of PDLCs. Meanwhile, ANXA2 is associated with autophagy, oxidative stress, and cellular senescence under high glucose conditions.

Dual optical elastography detects -induced alterations in the biomechanical properties of skin scaffolds.

The skin's mechanical properties are tightly regulated. Various pathologies can affect skin stiffness, and understanding these changes is a focus in tissue engineering. Ex vivo skin scaffolds are a robust platform for evaluating the effects of various genetic and molecular interactions on the skin. Transforming growth factor-beta ( ) is a critical signaling molecule in the skin that can regulate the amount of collagen and elastin in the skin and, consequently, its mechanical properties. This study investigates the biomechanical properties of bio-engineered skin scaffolds, focusing on the influence of , a signaling molecule with diverse cellular functions. The receptor I inhibitor, galunisertib, was employed to assess the mechanical changes resulting from dysregulation of . Skin scaffold samples, grouped into three categories (control, -treated, and + galunisertib-treated), were prepared in two distinct culture media-one with aprotinin (AP) and another without. Two optical elastography techniques, namely wave-based optical coherence elastography (OCE) and Brillouin microscopy, were utilized to quantify the biomechanical properties of the tissues. Results showed significantly higher wave speed (with AP, ; without AP, ) and Brillouin frequency shift (with AP, ; without AP, ) in -treated group compared with the control group. The difference in wave speed between the control and + galunisertib with ( ) and without AP ( ) was not significant. Moreover, the + galunisertib-treated group exhibited lower wave speed without and with AP and reduced Brillouin frequency shift than the -treated group without AP, further strengthening the potential role of in regulating the mechanical properties of the samples. These findings offer valuable insights into -induced biomechanical alterations in bio-engineered skin scaffolds, highlighting the potential of OCE and Brillouin microscopy in the development of targeted therapies in conditions involving abnormal tissue remodeling and fibrosis.

Endometrial Cell-Type Specific Regulation of the Endocannabinoids System and the Impact of Menstrual Cycle and Endometriosis.

Introduction: Anandamide (AEA) and 2-arachidonoylglycerol are endogenous agonists of the cannabinoid receptors and regulate and control many cellular functions. Their activities are governed by enzymes and proteins that regulate their synthesis, receptor binding, transport, and degradation, which are known as the endocannabinoid system (ECS). The aim of this study was to investigate the regulation of endocannabinoid activity in the endometrium by studying the RNA and protein expression of the ECS within endometrial cell types and during different menstrual cycle stages and the impact of endometriosis. Materials and Methods: The RNA expression of 70 ECS genes was assessed using RNA sequencing of isolated endometrial epithelial and stromal cells. Subsequent immunofluorescence-stained endometrial samples on ECS components of interest were objectively analyzed via an agnostic and automated image analysis pipeline to extract quantitative information. Differential gene and protein expression was investigated between the two cell types, menstrual cycle phases, and endometriosis cases and controls. Results: Sufficient RNA expression was detected for 45 genes, and 17 (38%) genes were significantly different between epithelial and stromal cells. FAAH RNA was significantly higher in epithelial cells compared with stromal cells. Protein expression analysis of the main synthesizing (NAPE-PLD) and catabolizing (FAAH and NAAA) enzymes of AEA revealed a significantly stronger epithelial expression compared to stromal cells. The RNA and protein expression of CB1 receptors was very low with no significant difference between epithelial and stromal cells. Eleven ECS genes were regulated across the menstrual cycle, and there was no gene with significant difference between endometriosis cases and controls in epithelial cells. Discussion: Differential expression of ECS genes supports a cell type-specific endocannabinoid activity in the endometrium. As endocannabinoids are short-lived signaling molecules, higher RNA and protein expression of FAAH in the epithelial cells suggests an active regulation of endocannabinoid activity in epithelial cells within the endometrium.

Tyrosinase-Woven Melanin Nets for Melanoma Therapy through Targeted Mitochondrial Tethering and Enhanced Photothermal Treatment.

Manipulating intracellular biological processes and organelles has emerged as a pivotal strategy to influence cellular physiological functions. Mitochondria, recognized as the powerhouse of cells, play a crucial role in tumorigenesis and progression. Inspired by the Nature's tyrosinase-catalyzed melanin formation within melanoma cells, here an approach is developed using a polysaccharide dually-functionalized with tyrosine and triphenylphosphine (TPP) for targeted mitochondria cross-linking in melanoma cells. This technique intricately weaves melanin nets within the cells, serving as a tether for the mitochondria and effectively decelerating tumor metabolism through nanoparticle-net transformation. Tyrosinase acts as the "needle", while the functionalized polysaccharide serves as the "string" successfully constructing nets within the cell. Furthermore, the tyrosinase-catalyzed cross-linking of tyrosine not only facilitates the production of artificial melanin but also enhances the photothermal conversion efficiency of melanoma cells, leading to decrease of the tumor growth. This study unveils a non-drug method for regulating organelle physiological activity and introduces photothermal treatment. This work not only sheds light on the manipulation of cellular functions but also holds promise for advancing cancer therapeutic strategies.

Repurposing auranofin and meclofenamic acid as energy-metabolism inhibitors and anti-cancer drugs.

Cytotoxicity of the antirheumatic drug auranofin (Aur) and the non-steroidal anti-inflammatory drug meclofenamic acid (MA) on several cancer cell lines and isolated mitochondria was examined to assess whether these drugs behave as oxidative phosphorylation inhibitors. The effect of Aur or MA for 24 h was assayed on metastatic cancer and non-cancer cell proliferation, energy metabolism, mitophagy and metastasis; as well as on oxygen consumption rates of cancer and non-cancer mitochondria. Aur doses in the low micromolar range were required to decrease proliferation of metastatic HeLa and MDA-MB-231 cells, whereas one or two orders of magnitude higher levels were required to affect proliferation of non-cancer cells. MA doses required to affect cancer cell growth were one order of magnitude higher than those of Aur. At the same doses, Aur impaired oxidative phosphorylation in isolated mitochondria and intact cells through mitophagy induction, as well as glycolysis. Consequently, cell migration and invasiveness were severely affected. The combination of Aur with very low cisplatin concentrations promoted that the effects on cellular functions were potentiated. Aur surges as a highly promising anticancer drug, suggesting that efforts to establish this drug in the clinical treatment protocols are warranted and worthy to undertake.

Identifying immune checkpoints on dysregulated T-cells as prognostic biomarkers for multiple myeloma patients with COVID-19

BackgroundBroad T cell phenotypic alterations and potential dysfunctions were prominent in COVID-19. There are few and inconclusive data about the role of immune checkpoints for T cell exhaustion/activation during SARS-CoV-2 infection in multiple myeloma (MM) patients.MethodsWe tested T cell subsets and immune checkpoints in 177 MM patients with COVID-19, as well as in 32 healthy infected controls and 42 uninfected MM patients. The percentage of CD4+ and CD8+ subpopulation and immune checkpoints (PD-1, TIGIT, TIM-3, LAG-3, CTLA-4, OX40, and 4-1BB) were evaluated by flow cytometry.ResultsWe have found that pronounced lymphopenia and inverted CD4/CD8 ratio in severe COVID-19 patients were especially developed within the first month after infection. And T cell subset dysregulation was persistent in severe patients recovering from SARS-CoV-2 infection. Immune checkpoints on CD4+ T cells were variable and uncorrelated with the level of adaptive immunity, while the proportion of CD4+ T cells was positively correlated with humoral immune response. PD-1 and TIGIT on CD8+ T cells were significantly elevated in severe patients and sustained for more than 2 months, which was associated with impaired cellular immune function. Moreover, exhausted molecules PD-1 and TIGIT on T cells were reduced in immunotherapy patients.ConclusionThe prolonged T cell dysregulation after severe SARS-CoV-2 infection highlights the close surveillance from reinfection in MM patients even during convalescence. PD-1 and TIGIT on CD8+ T cells could be important prognostic factors to stratify prognosis in MM patients with COVID-19. Moreover, immunotherapy may downregulate the expression of exhausted checkpoints PD-1 and TIGIT, leading to T cell overactivation and severe COVID-19.

Radial Egg White Hydrogel Releasing Extracellular Vesicles for Cell Fate Guidance and Accelerated Diabetic Skin Regeneration.

Topology and bioactive molecules are crucial for stimulating cellular and tissue functions. To regulate the chronic wound microenvironment, mono-assembly technology is employed to fabricate a radial egg white hydrogel loaded with lyophilized adipose tissue-extracellular vesicles (radial EWH@L-EVs). The radial architecture not only significantly modified the gene expression of functional cells, but also achieved directional and controlled release kinetics of L-EVs. Through the synergy of topographical and inherent bioactive cues, radial EWH@L-EVs effectively reduced intracellular oxidative stressand promoted the polarization of macrophages toward an anti-inflammatory phenotype during the inflammatory phase. Afterward, radial EWH@L-EVs facilitated the centripetal migration and proliferation of fibroblasts and endothelial cells as the wound transitioned to the proliferative phase. During the latter remodeling phase, radial EWH@L-EVs accelerated the regeneration of granulation tissue, angiogenesis, and collagen deposition, thereby promoting the reorganization chronic wound. Compared with the gold standard collagen scaffold, radial EWH@L-EVs actively accommodated the microenvironment via various functions throughout all stages of diabetic wound healing. This can be attributed to the orientation of topological structures and bioactive molecules, which should be considered of utmost importance in tissue engineering.

Association between dietary inflammatory index and phase angle in university employees: a cross-sectional study

Phase angle (PhA), measured by bioelectrical impedance analysis, indicates cellular health, integrity, and function. As inflammation can damage cells, phase angle may be useful in detecting inflammatory status early. The relationship between dietary inflammatory index (DII) and PhA has not been studied yet. Therefore, we aimed to examine this association in Iranian adults. This cross-sectional study included 206 university employees. Dietary intakes were assessed by using a validated 86-item food frequency questionnaire (FFQ). Anthropometric indices and blood pressure were measured. A short form of the validated International Physical Activity Questionnaire (IPAQ) was used for evaluating physical activity. The PhA was measured by the Body Composition Analyzer Mc780 MA device. The mean age of participants was 43.50 ± 8.82 years and the range of DII score was − 4.66 to 0 among them. The highest tertile of DII compared to the lowest tertile, showed greater weight, WC, HC, basal metabolic rate (BMR), and diastolic blood pressure. We found no significant association between DII and PhA (crude model: OR: 0.68; 95% CI 0.34, 1.33, fully-adjusted model: OR: 0.65; 95% CI 0.26, 1.64). Also, after BMI stratification this association remained (fully-adjusted: normal weight: OR: 0.61; 95% CI 0.11, 3.27; Overweight and obese: OR: 0.57; 95% CI 0.16, 1.98). Having a higher DII score was not associated with a lower PhA. Further well-controlled prospective studies are warranted.

The role of circular RNA targeting IGF2BPs in cancer-a potential target for cancer therapy.

Circular RNAs (circRNAs) are an interesting class of conserved single-stranded RNA molecules derived from exon or intron sequences produced by the reverse splicing of precursor mRNA. CircRNAs play important roles as microRNA sponges, gene splicing and transcriptional regulators, RNA-binding protein sponges, and protein/peptide translation factors. Abnormal functions of circRNAs and RBPs in tumor progression have been widely reported. Insulin-like growth factor-2 mRNA-binding proteins (IGF2BPs) are a highly conserved family of RBPs identified in humans that function as post-transcriptional fine-tuners of target transcripts. Emerging evidence suggests that IGF2BPs regulate the processing and metabolism of RNA, including its stability, translation, and localization, and participate in a variety of cellular functions and pathophysiology. In this review, we have summarized the roles and molecular mechanisms of circRNAs and IGF2BPs in cancer development and progression. In addition, we briefly introduce the role of other RNAs and IGF2BPs in cancer, discuss the current clinical applications and challenges faced by circRNAs and IGF2BPs, and propose future directions for this promising research field.

A Multi-Omics, Machine Learning-Aware, Genome-Wide Metabolic Model of Bacillus Subtilis Refines the Gene Expression and Cell Growth Prediction.

Given the extensive heterogeneity and variability, understanding cellular functions and regulatory mechanisms through the analysis of multi-omics datasets becomes extremely challenging. Here, a comprehensive modeling framework of multi-omics machine learning and metabolic network models are proposed that covers various cellular biological processes across multiple scales. This model on an extensive normalized compendium of Bacillus subtilis is validated, which encompasses gene expression data from environmental perturbations, transcriptional regulation, signal transduction, protein translation, and growth measurements. Comparison with high-throughput experimental data shows that EM_iBsu1209-ME, constructed on this basis, can accurately predict the expression of 605 genes and the synthesis of 23 metabolites under different conditions. This study paves the way for the construction of comprehensive biological databases and high-performance multi-omics metabolic models to achieve accurate predictive analysis in exploring complex mechanisms of cell genotypes and phenotypes.