As tiny extracellular vesicles ranging 30-150 nm in size, exosomes are crucial for cell-to-cell communication and show great promise in therapeutic applications. All cell types release lipid bilayer-enclosed vesicles tha...As tiny extracellular vesicles ranging 30-150 nm in size, exosomes are crucial for cell-to-cell communication and show great promise in therapeutic applications. All cell types release lipid bilayer-enclosed vesicles that carry bioactive molecules such as proteins, lipids, and nucleic acids, which reveal the health conditions of their originating cells. Exosome-based therapeutics have developed rapidly over the past decade due to their natural biocompatibility and minimal immune response, with the added benefit of traversing biological barriers such as the blood-brain barrier. This review presents a thorough critical synthesis of current developments in the development and use of therapies based on exosomes. This article explores basic exosome biology alongside methods for their isolation and characterization, as well as describes bioengineering approaches used to enhance their therapeutic capabilities. This review highlights their clinical applications, specifically in oncological treatments and therapies targeting neurodegenerative conditions, cardiovascular disorders, and regenerative medicine procedures. This review explores current clinical trials of exosome-based therapies and discusses manufacturing obstacles and regulatory frameworks, along with ethical issues that influence the development of exosome- based treatments. This chapter concludes by examining the future prospects of synthetic exosome mimetics and artificial exosome engineering, which will transform exosomes into the leading edge of next-generation nanomedicine.
INTRODUCTION: The increase of Multidrug-Resistant (MDR) bacteria continues to complicate antimicrobial therapy and motivates and investigates alternative bioactive sources. Moringa peregrina and Moringa oleifera contain...INTRODUCTION: The increase of Multidrug-Resistant (MDR) bacteria continues to complicate antimicrobial therapy and motivates and investigates alternative bioactive sources. Moringa peregrina and Moringa oleifera contain diverse phytochemicals associated with antimicrobial activity and therefore represent candidates for experimental evaluation. METHODS: Ethanol and aqueous leaf extracts were characterized using Fourier Transform Infrared Spectroscopy (FTIR) and Gas Chromatography-Mass Spectrometry (GC-MS). These were evaluated against Methicillin-Resistant Staphylococcus aureus (MRSA), Vancomycin-Resistant Enterococcus (VRE), Carbapenemresistant K. pneumoniae (CRKP), and Carbapenem-resistant Pseudomonas aeruginosa (CRPA) using agar well diffusion, Minimum Inhibitory Concentration (MIC), and Minimum Bactericidal Concentration (MBC) assays. Ultrastructural changes were examined by Scanning Electron Microscope (SEM) and Transmission Electron Microscope (TEM). RESULTS: FTIR showed the presence of hydroxyl, carbonyl, and aromatic groups. GC-MS found sterols, fatty acids, terpenoids, and glycosides as the main parts. The ethanol extract of M. peregrina was the best at killing bacteria, especially MRSA and CRKP. It had a Zone of Inhibition (ZI) up to 10 mm, a Minimum Inhibitory Concentration (MIC) of 0.5-1.4 mg/mL, and a Minimum Bactericidal Concentration (MBC) of 1.4-2.1 mg/mL. The water extract of M. oleifera worked best against CRKP and VRE, with a ZI of 11.5 mm, MIC of 0.9 mg/mL, and MBC of 1.8 mg/mL. The electron microscope revealed structural alteration following the treatment. SEM analysis demonstrated bacterial surface deformation, while TEM observation indicated membrane disruption accompanied by cytoplasmic disorganization; these findings indicate cellular damage associated with extracted exposure. DISCUSSION: Phytochemical polarity has a significant impact on antimicrobial potency, as seen by the varying antibacterial responses seen in solvent extracts. The potent effect of M. peregrina ethanol extract on MRSA and CRKP indicates that terpenoids, fatty acids, and lipid-soluble sterols may cause membranetargeted disruption. On the other hand, the wider inhibitory spectrum of M. oleifera aqueous extract against VRE and CRKP suggests that polar glycosides, phenolics, and cardenolide-type substances aid in the disruption of cell walls. SEM and TEM imaging confirmed that extract exposure leads to profound ultrastructural collapse, including membrane rupture, cytoplasmic leakage, and loss of intracellular organization, supporting a mechanism of direct structural assault rather than metabolic inhibition. As a whole, the observations support continued investigation of Moringa-derived phytochemicals as experimentally relevant antimicrobial sources and provide methodical insight for future validation studies. CONCLUSION: M. peregrina and M. oleifera extracts demonstrate selective antibacterial activity against MDR pathogens, with ethanol extracts favoring Gram-positive and aqueous extracts showing broader activity. These findings highlight Moringa phytochemicals as promising complementary agents in the fight against antibiotic resistance, warranting further in vivo and synergistic studies.
Aptamers are short single-stranded DNA (ssDNA) or RNA (ssRNA) molecules that bind cancer-associated targets with high specificity and low immunogenicity. Their small size and structural flexibility make them an attractiv...Aptamers are short single-stranded DNA (ssDNA) or RNA (ssRNA) molecules that bind cancer-associated targets with high specificity and low immunogenicity. Their small size and structural flexibility make them an attractive alternative to antibodies for diagnosing and treating cancer. The way in which the aptamer Selection Method (SELEX) is performed plays a key role in determining whether aptamers will be successful in oncology. The way the selection strategy mimics the tumour's biological environment and the clinical intent behind the selection of the aptamer determine the likelihood of finding useful aptamers using the SELEX technique. This review discusses how various SELEX formats have been used in cancer research, including protein, cell, tissue, serum, magnetic bead, microfluidic, in vivo, and hybrid-based SELEX approaches. These formats are examined as separate methods, with a focus on comparing and evaluating their efficacy against a wide range of cancer targets and biological environments. Examples of studies utilising SELEX-derived aptamers in diagnostic imaging, histopathology, and targeted drug delivery are provided. Roadblocks to drug development, including the decreasing biological relevance of models, potential selection bias, and tumor variability, are also discussed. In addition, areas in which emerging technologies-such as patient-derived selection systems, advances in microfluidic processes, and the maximum achievable resolution of single-cell experiments- can improve the environment for drug selection and development are highlighted. The authors provide a framework for applying SELEX as a context-based selection tool for developers, enabling the development of equally effective clinical trial designs that are more aligned with precision oncology.
Pulmonary delivery of nanosuspensions has emerged as a transformative strategy to enhance the bioavailability of hydrophobic natural products (HNPs) in the treatment of pulmonary infections and systemic diseases. However...Pulmonary delivery of nanosuspensions has emerged as a transformative strategy to enhance the bioavailability of hydrophobic natural products (HNPs) in the treatment of pulmonary infections and systemic diseases. However, challenges remain in balancing the safety and efficacy of nanosuspension-based inhalable formulations, particularly regarding formulation stability and lung deposition efficiency. This review systematically evaluates recent advancements in inhalable nanosuspension technologies, with a focus on dry powder inhaler (DPI) formulations tailored for HNPs (e.g., curcumin, resveratrol, breviscapine, paclitaxel). Key factors influencing formulation performance, including human lung anatomy, inflammatory microenvironments, fine particle index (FPI ≥ 50%), and physicochemical stability, are critically discussed. In vitro characterization (e.g., particle size of 1-5 μm, aerosolization efficiency >60%) and in vivo studies demonstrate that optimized nanosuspensions achieve 2-3-fold higher lung retention compared to conventional formulations, along with improved permeability across inflamed alveolar epithelia. Despite these advancements, challenges such as protein corona formation, batch-to-batch variability, and long-term storage stability call for further interdisciplinary innovation. This review highlights nanosuspensions as a transformative platform for the precision pulmonary delivery of HNPs, emphasizing the need for standardized characterization and translational validation to bridge the bench-to-bedside gap.
INTRODUCTION: Diabetic wounds are a type of chronic wound characterized by delayed and difficult healing. In recent years, the use of bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exo) in wound treatment has s...INTRODUCTION: Diabetic wounds are a type of chronic wound characterized by delayed and difficult healing. In recent years, the use of bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exo) in wound treatment has shown promising progress. This research aims to investigate whether BMSC-Exo can promote the healing of diabetic wounds and to explore the underlying mechanisms. METHODS: 1. Exosome extraction and identification; 2. Animal experiments: 54 male SD rats were randomly divided into 3 groups: Normal control (Control) group, diabetes model + normal saline (DM+NS) group, and diabetes model + exosome (DM+Exo) group. After successful modeling of diabetes, 2 cm × 2 cm wounds were created on the backs of rats in each group. Normal saline was injected into the wounds of the control group and DM+NS group, and exosomes were injected into the wounds of the DM+Exo group. The wound-healing rate in each group was measured, and the levels of NLRP3, IL-18, IL-1β, caspase-1, and GSDMD protein were assessed by Western Blot. 3. Cell experiment: Fibroblasts were divided into 3 groups: fibroblasts (Control) group, fibroblasts + hyperglycemia (Hy) group, and fibroblasts + hyperglycemia + exosomes (Hy+Exo) group. Cells in each group were detected by CCK-8, Annexin V/PI staining, and scratch assay. The levels of NLRP3, IL-18, IL-1β, caspase-1, and GSDMD protein were detected by Western Blot in each group. RESULTS: The findings demonstrated that BMSC-Exo significantly enhanced wound healing in diabetic rats and promoted the proliferation and migration of fibroblasts under high-glucose conditions. BMSC-derived exosomes enhanced the wound healing rate by an average of 21.3% in diabetic rat models. Pyroptosis was markedly increased in the wounds of diabetic rats and in fibroblasts exposed to high glucose; however, BMSC-Exo significantly inhibited pyroptosis in both contexts. DISCUSSION: The poor healing of diabetic wounds is closely associated with hyperglycemiainduced pyroptosis and chronic inflammation; pyroptosis mediated by the NLRP3/caspase1/GSDMD pathway exacerbates inflammation and inhibits fibroblast function. This study is the first to confirm that BMSC-Exo can target this pathway to inhibit pyroptosis, thereby promoting wound healing and expanding the therapeutic mechanism of MSC-derived exosomes. However, the key functional molecules in BMSC-Exo remain unclear, and their long-term efficacy and clinical translation require further verification. CONCLUSION: These results suggest that BMSC-Exo promotes wound healing in diabetic rats by inhibiting cell pyroptosis via the NLRP3/caspase-1/GSDMD signaling pathway in both in vivo and in vitro settings.
Introduction Cyperotundone (CYT), a vital component of Cyperus rotundus L., is known to suppress tumor growth effectively. This investigation was performed to reveal the antibreast cancer(BC) effect of CYT and its mechan...Introduction Cyperotundone (CYT), a vital component of Cyperus rotundus L., is known to suppress tumor growth effectively. This investigation was performed to reveal the antibreast cancer(BC) effect of CYT and its mechanism. Methods CCK-8 assay, colony formation, cell cycle/apoptosis assays, and subcutaneous tumor model were used to investigate the anticancer effects of CYT. RNA sequencing was used to predict the targets of CYT, which were then verified by drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), and molecular docking. The pan-cancer analysis on PLK1 was excavated by the comprehensive use of datasets from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Project (GTEx). Western blotting, immunohistochemical staining (IHC), and RT-qPCR were used to determine protein and gene levels. Pyruvate and lactate production assays were used to represent the glycolysis level. Results In vitro, CYT inhibited the proliferation of BC cells, as well as causing apoptosis and blocking the cell cycle. In vivo, CYT decreased tumor regression without obvious toxicity. PLK1 was identified as a key target of CYT. High PLK1 expression was associated with early diagnostic value and poor survival of BC. Of note, PLK1 is positively correlated with glycolysis. CYT can inhibit the key proteins of glycolysis and production of metabolites through the PTEN/AKT pathway in BC cells. In the rescue experiments, CYT significantly inhibited the overexpression of PLK1-induced elevation of glycolysis levels. Discussion This is the first study to reveal the correlation between PLK1 and glycolysis and the regulation of glycolysis by PLK1 in TNBC cells. Although PLK1 was identified as a target of CYT, the research on how CYT exerts its anti-BC effect through PLK1 is still insufficient. Other molecular pathways involved in CYT action, how disruption of glycolytic pathways contributes to its anticancer effects, and its potential compensatory mechanisms in cancer cells are needed to explore. Conclusion CYT is a potent PLK1 inhibitor that has an anticancer effect in BC cells by decreasing glycolytic function.
INTRODUCTION: The mortality risk factors in intensive care unit (ICU) patients with liver necrosis (LN) remain unclear. This study aimed to develop a prediction model for mortality risk in LN patients to assist clinical...INTRODUCTION: The mortality risk factors in intensive care unit (ICU) patients with liver necrosis (LN) remain unclear. This study aimed to develop a prediction model for mortality risk in LN patients to assist clinical practice. METHODS: We enrolled 1153 acute and subacute LN patients from the MIMIC-III database, randomly divided into training and validation cohorts. LASSO regression was used to screen risk factors. A multiple logistic regression model and nomogram were established for 28-day mortality prediction. The model was assessed by AUC, calibration curves, and DCA. RESULTS: LASSO regression identified age, gender, ethnicity, marital status, bicarbonate, bilirubin, hemoglobin, electrolytes, heart rate, temperature, and SpO₂as independent risk factors. DISCUSSION: Although there is currently no suitable model for predicting patients with sepsis, the model we have constructed includes some factors that were previously considered independent but were not as significant. This time, we have highlighted the more important positions. Our model will provide ideas for predicting liver necrosis insepsis. CONCLUSION: Our model integrates previously underappreciated predictors and emphasizes their clinical significance, providing novel insights for predicting LN in patients with sepsis.
INTRODUCTION: The application of nanotechnology to drug delivery has the potential to improve drug therapeutic efficacy. Jambolan (Syzygium cumini Linn.) is a natural source that provides several pharmacological activiti...INTRODUCTION: The application of nanotechnology to drug delivery has the potential to improve drug therapeutic efficacy. Jambolan (Syzygium cumini Linn.) is a natural source that provides several pharmacological activities, including antioxidant, antidiabetic, and anticancer properties. However, the use of Jambolan seeds remains limited due to the lack of delivery systems. Therefore, this study aimed to develop a nanocarrier, Nanostructured Lipid Carrier (NLC), containing Jambolan Seed Extract (JSE) incorporated into a patch. METHODS: Three formulations with various surfactant concentrations of Cremophor RH 40 and Span 80 were prepared, followed by characterization, including particle size, Polydispersity Index (PI), and zeta potential. The selected formulation was evaluated for its morphology and antioxidant activity. Moreover, the NLC-JSE patch was prepared, and the physical properties, weight uniformity, thickness, folding endurance, and stability were evaluated. RESULTS: The selected NLC-JSE formulation showed particle sizes of 183.10 ± 12.97 nm, PI of 0.58 ± 0.06, and zeta potential of -31.41 ± 1.20 mV. The IC50 of NLC-JSE (3.10 + 0.12 mg/L) was significantly less than that of ascorbic acid as a standard (12.52 + 0.69 mg/L). The patch produced the required properties. DISCUSSION: A desirable NLC-JSE patch was produced. NLC-JSE with a 3:3 ratio of Cremophor RH 40 and Span 80 met the required characteristics. NLC-JSE provided a higher potential antioxidant than the standard. CONCLUSION: The resulting NLC-JSE patch exhibited the required properties and was physically and chemically stable during storage.
INTRODUCTION: Nicotine dependence remains a major global public health challenge, with relapse remaining high despite the availability of conventional cessation therapies. In traditional medicine, lemongrass (Cymbopogon...INTRODUCTION: Nicotine dependence remains a major global public health challenge, with relapse remaining high despite the availability of conventional cessation therapies. In traditional medicine, lemongrass (Cymbopogon citratus) has been widely used for calming, respiratory, and stress-related conditions, and modern evidence suggests that citral, its primary phytochemical, may modulate nicotinic acetylcholine receptors (nAChRs) involved in nicotine addiction. These properties provide a biological and traditional rationale for investigating lemongrass inhalation as a supportive intervention to reduce dependence. This study aims to evaluate the efficacy of a 3% lemongrass essential oil inhaler in reducing nicotine dependence through modulation of nAChRs. METHODS: A randomized, pretest-posttest controlled group design was conducted involving 100 adult smokers (aged 18-30 years) with moderate-to-high nicotine dependence (FTND ≥ 5). Participants were allocated to receive either a 3% lemongrass inhaler or a placebo, administered four times daily for eight weeks. The primary outcomes were changes in FTND scores and serum nAChRs levels measured using ELISA. ANCOVA was used to assess treatment effects while controlling for demographic covariates. RESULTS: The lemongrass group demonstrated significantly greater reductions in FTND scores (mean difference = 2.3; p < 0.001) and serum nAChRs levels (mean difference = 0.6 ng/mL; p = 0.003) compared with placebo. After adjustment for baseline FTND and demographic covariates, ANCOVA confirmed a large treatment effect (partial η² = 0.390). Multivariable logistic regression further demonstrated that participants receiving lemongrass inhalation had significantly lower adjusted odds of remaining highly nicotine-dependent after the intervention. DISCUSSION: These findings show that lemongrass inhalation significantly reduces both subjective dependence levels and biological markers associated with nicotine addiction, consistent with traditional medicinal uses and mechanistic evidence for the interaction of citral with nAChRs. CONCLUSION: This natural and accessible intervention may serve as an effective adjunct to smoking- cessation strategies and warrants further long-term evaluation.
INTRODUCTION: Acute lung injury (ALI) is the initial complication in the pathogenesis of sepsis and a leading cause of mortality in patients with sepsis. Adiponectin (APN), an important downstream effector of fibroblast...INTRODUCTION: Acute lung injury (ALI) is the initial complication in the pathogenesis of sepsis and a leading cause of mortality in patients with sepsis. Adiponectin (APN), an important downstream effector of fibroblast growth factor 21 (FGF21), exerts metabolic regulatory effects; however, the specific role of FGF21 in alleviating sepsis-induced ALI through APN remains to be fully elucidated. METHODS: The present study established a sepsis-induced ALI model in C57BL/6J mice via intraperitoneal injection of lipopolysaccharide (LPS, 15.0 mg/kg). Three FGF21 treatment groups were set up (intraperitoneal injection of 0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg FGF21 6 hours after LPS administration) to explore the optimal usage concentration of FGF21 in this study. Additionally, adeno-associated virus (AAV)-mediated APN overexpression and knockdown were performed to verify the mediating role of APN. RESULTS: LPS-induced sepsis significantly increased FGF21 levels in mouse serum (p < 0.05) and lung tissues (p < 0.01), while reducing APN expression (p < 0.01), increasing percent weight loss (%WL ≈ 15%), elevating lung wet-to-dry (W/D) ratio by ~125%, upregulating mRNA levels of inflammatory factors (IL-1β, IL-6, TNF-α; p < 0.001), and promoting pulmonary fibrosis (increased α-SMA and TGF-β1 expression; p < 0.05 or p < 0.01). Among the FGF21 treatment groups, the medium dose (1.0 mg/kg) exhibited the most potent therapeutic effects: it reduced %WL by approximately 40%, decreased lung W/D ratio by approximately 30%, significantly downregulated the expression of inflammatory factors, and attenuated pulmonary fibrosis. APN overexpression mimicked the protective effects of FGF21, whereas APN knockdown partially abolished FGF21's therapeutic benefits. Mechanistically, FGF21 administration significantly reversed the sepsis-induced decrease in APN expression, inhibited pulmonary collagen deposition, and reversed the dysregulated Nrf2-Keap1-HO-1 pathway (upregulating Nrf2 and HO-1, downregulating Keap1; p < 0.05 or p < 0.01), which in turn restored redox homeostasis by increasing serum levels of catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD) (p < 0.05 or p < 0.001). DISCUSSION: The present study revealed that APN mediates FGF21 to alleviate sepsis-induced ALI in mice, and its mechanism of action may be related to the alleviation of pulmonary fibrosis, the improvement of redox imbalance, and the down-regulation of inflammatory factor expression. This discovery provides a new strategy for the treatment of ALI. CONCLUSION: APN mediates FGF21's protective effects against sepsis-induced ALI in mice. The underlying mechanism involves reversing the sepsis-induced decrease in APN expression, inhibiting pulmonary fibrosis, downregulating inflammatory factor expression, and restoring redox homeostasis via the Nrf2-Keap1-HO-1 pathway. This discovery provides a novel therapeutic strategy for the treatment of sepsis-induced ALI.
INTRODUCTION: Sponge-associated bacteria are recognized as prolific sources of bioactive metabolites. Although members of the promising phylum Bacillota are commonly found in marine sponges, their genomic potential remai...INTRODUCTION: Sponge-associated bacteria are recognized as prolific sources of bioactive metabolites. Although members of the promising phylum Bacillota are commonly found in marine sponges, their genomic potential remains largely unexplored. This study aims to investigate the Bacillus stercoris 84-5 strain isolated from the sponge Darwinella sp. and evaluate its biosynthetic and enzymatic potential. METHODS: Whole-genome sequencing and comparative analyses of biosynthetic gene clusters (BGCs) were conducted. In parallel, in vitro assays were performed to evaluate biosurfactant activity (emulsification and surface tension) and enzymatic profiles. RESULTS: The 84-5 genome (4.12 Mbp) encodes at least 11 potential BGCs. In particular, a nonribosomal peptide synthetase (NRPS) cluster showed 82% similarity to a surfactin gene cluster from Bacillus velezensis FZB42, and a corresponding surface tension of 27.44 ± 0.33 mN/m. Genes related to the production of carbohydrate-active enzymes (CAZymes) were also detected. In vitro assays confirmed the production of agarase, alginate lyase, and peptidase, with an enzymatic index (EI) > 3.5 for agarase and peptidase. Comparative analyses revealed shared BGC families among sponge-associated Bacillota genomes. DISCUSSION: The high diversity of putative bioactive BGCs found, including many shared among sponge-associated Bacillota, suggests biosynthetic pathways that are likely to play important ecological roles within the sponge holobiome. Additionally, the abundance of enzymes probably reflects the metabolic versatility required for life in marine niches. CONCLUSION: The marine B. stercoris 84-5 exploration thus reveals a promising candidate for exploiting both biosurfactant and enzymatic capabilities, shedding light on the understudied potential of sponge-associated Bacillota.
INTRODUCTION: Lung Adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality worldwide, with a limited understanding of cytokine-mediated molecular mechanisms driving its progression. Interleukin-22 (IL-2...INTRODUCTION: Lung Adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality worldwide, with a limited understanding of cytokine-mediated molecular mechanisms driving its progression. Interleukin-22 (IL-22), a cytokine involved in inflammation and tissue regeneration, has been implicated in several malignancies, but its role in LUAD is unclear. This study aimed to investigate IL-22 expression, regulation, and its functional impact on LUAD progression via the PI3K/AKT signaling pathway. METHODS: IL-22 expression was analyzed in six LUAD and four normal bronchial epithelial cell lines using RT-qPCR and ELISA. Validation across TCGA and GSCA datasets assessed transcriptional levels, promoter methylation, and pathway enrichment. Functional assays, including CCK-8, colony formation, Transwell invasion, and wound-healing assays, were performed with recombinant IL-22 (0-100 ng/mL) in A549 and H1299 cells, with or without the PI3K inhibitor LY294002. Western blot analysis determined pathway activation, and luciferase assays verified miRNA regulation of IL-22. RESULTS: IL-22 was significantly upregulated in LUAD at both mRNA and protein levels, correlated with promoter hypomethylation, and was associated with poor prognosis. Functional studies demonstrated that IL-22 enhanced proliferation, clonogenicity, invasion, and migration in a dose-dependent manner via PI3K/AKT phosphorylation. LY294002 co-treatment reversed these effects. Moreover, hsa-miR-21-5p directly targeted IL-22 3'UTR and was significantly downregulated in LUAD, indicating a regulatory role in IL-22 overexpression. DISCUSSION: This study identifies IL-22 as a cytokine that promotes malignant phenotypes in LUAD cells through activation of the PI3K/AKT signaling pathway. The integration of functional assays with multi-omics analyses suggests that IL-22 overexpression is driven by promoter hypomethylation and reduced hsa-miR-21-5p-mediated post-transcriptional regulation. While these findings support a mechanistic role for IL-22 in LUAD progression, further in vivo and clinical studies are required to validate the relevance of the IL-22/PI3K/AKT axis within the tumor microenvironment and its translational potential. CONCLUSION: IL-22 promotes LUAD progression by activating the PI3K/AKT signaling pathway and inducing EMT, while its upregulation is modulated by promoter hypomethylation and miR- 21-5p suppression. The IL-22/PI3K/AKT axis represents a potential therapeutic target for LUAD management.
Corn silk (Zea mays L.), a resource traditionally regarded as an agricultural byproduct, has emerged in recent years as a focal point in natural product research. This review systematically outlines the chemical composit...Corn silk (Zea mays L.), a resource traditionally regarded as an agricultural byproduct, has emerged in recent years as a focal point in natural product research. This review systematically outlines the chemical composition spectrum of corn silk, focusing on its diverse bioactive constituents, including flavonoids, polysaccharides, sterols, terpenoids, saponins, and organic acids. It further explores its multifaceted pharmacological value and therapeutic potential. These compounds exert multiple effects, including antioxidant, anti-inflammatory, hypoglycaemic, hypolipidaemic, and antihypertensive actions through key signalling pathways such as NF-κB, Nrf2, PI3K/Akt, and FoxO1. Molecular docking and metabolomics studies have further elucidated the interactions between bioactive compounds in corn silk and disease-related targets. This evidence indicates that corn silk represents a promising natural therapeutic resource and a candidate for biotechnology applications in drug development. This review aims to provide a scientific foundation for future preclinical and translational research into corn silkbased therapeutic agents.
Traumatic brain injury (TBI) is a globally prevalent neurological disorder, with longterm deteriorating neurological deficits (especially learning and memory impairments). Classified into primary and secondary injuries,...Traumatic brain injury (TBI) is a globally prevalent neurological disorder, with longterm deteriorating neurological deficits (especially learning and memory impairments). Classified into primary and secondary injuries, TBI's secondary phase is characterized by inflammation and apoptosis-key pathological processes driving further neurological dysfunction with complex bidirectional regulation. This study systematically elaborates the core mechanisms: glial cells act as central "regulatory hubs" that modulate their phenotype via proinflammatory factor release and key signaling pathway activation, directly or indirectly inducing neuronal apoptosis; non-coding RNAs [Long Non-coding RNAs (lncRNAs), MicroRNAs (miRNAs)] function as "molecular bridges" by targeting glial activation, inflammatory factor secretion, and apoptosis-related pathways [e.g., LINC00707/miR-30a-5p, miR-21-5p/ phosphatase and tensin homologue (PTEN)]. Additionally, diverse therapeutic strategies are summarized: pharmacological agents (e.g., minocycline, dexmedetomidine) inhibit inflammatory pathways and reduce apoptosis-related proteins; mesenchymal stem cell therapy exerts immunomodulatory and neuroregenerative effects; nanoparticles enable precise drug delivery; hyperbaric oxygen therapy blocks the vicious cycle by improving oxygenation; gut microbiota interventions restore homeostasis via metabolic and immune modulation. In conclusion, in-depth analysis of glial cells and non-coding RNAs in TBI-induced inflammation and apoptosis provides a theoretical basis for developing targeted therapies, holding great significance for improving TBI patient prognosis.
INTRODUCTION: Propofol has reported to have anti-inflammatory effects and has been suggested to reduce TLR4 membrane expression via Rab5a. We aimed to characterize, at atomic resolution, propofol's binding mode to Rab5a...INTRODUCTION: Propofol has reported to have anti-inflammatory effects and has been suggested to reduce TLR4 membrane expression via Rab5a. We aimed to characterize, at atomic resolution, propofol's binding mode to Rab5a and its effect on Rab5a dynamics using in-silico methods. METHODS: We performed molecular docking, 300-ns molecular dynamics (MD) simulations of apo-Rab5a and Rab5a-propofol complex, MM/GBSA binding free energy calculations, perresidue energy decomposition, RMSD/RMSF/RoG/SASA analyses, and principal component analysis (PCA). RESULTS: We show that propofol adopts a stable binding pose, with an MM/GBSA ΔG!"#$, -21.72 kcal/mol, and that propofol binding reduces Rab5a flexibility, increases compactness, and shifts principal component motions toward correlated, lower-amplitude dynamics. Key interacting residues include Glu36, Ala42, and Asp61. DISCUSSION: The results provide atomistic evidence supporting the hypothesis that propofol stabilizes Rab5a in a conformational state that may limit TLR4 trafficking to the plasma membrane. These findings align with prior cellular observations and generate residue-specific hypotheses testable experimentally. Study limitations include reliance on computational methods, a single ligand-binding mode, and the absence of entropy contributions. Experimental validation is required to confirm physiological relevance. CONCLUSION: Our in-silico results provide mechanistic hypotheses (binding site, residue hotspots, and dynamic stabilization) that are consistent with previous cellular work and warrant biochemical validation.
INTRODUCTION: The red andong (Cordyline fruticosa (L) A. Chev.) plant, known for its potent anti-diarrheal properties and abundant anthocyanin pigments, has attracted significant research interest because of its strong a...INTRODUCTION: The red andong (Cordyline fruticosa (L) A. Chev.) plant, known for its potent anti-diarrheal properties and abundant anthocyanin pigments, has attracted significant research interest because of its strong antioxidant activity. This study aims to explore the biotechnological enhancement of red andong leaves through fermentation with Bacillus subtilis. METHODS: This investigation examines incubation periods of 24, 48, and 72 hours to analyze the subsequent effects on total polyphenol content and antioxidant efficacy. Leaf extracts were prepared by maceration in 70% ethanol, and total polyphenol concentrations were quantified using the Folin-Ciocalteu assay, expressed as mg gallic acid equivalents per gram (mg GAE/g). Antioxidant capacity was assessed via IC50 values using DPPH radical scavenging and the Ferric Reducing Antioxidant Power (FRAP) assay. In silico studies were conducted to predict the potential molecular mechanisms of these effects. RESULTS: Statistically significant increases in polyphenolic content were observed post-fermentation; Non-Fermented Extracts (NFE) contained 29.11 ± 0.90 mg GAE/g, while extracts fermented for 24 (EF24 - 63.03 ± 0.90 mg GAE/g), 48 (EF48 - 73.54 ± 0.98 mg GAE/g), and 72 hours (EF72 - 38.56 ± 0.82 mg GAE/g) showed notable increases. Concomitantly, antioxidant activities demonstrated marked improvements; the NFE exhibited an IC50 value of 39.297 μg/mL, vs. 13.159 μg/mL for EF24, 10.488 μg/mL for EF48, and 37.872 μg/mL for EF72. An in silico study revealed that fermentation-derived compounds (phytol and α-tocopherol) may contribute to antioxidant pathways by modulating CDK6, AR, and PKM. DISCUSSION: The FRAP results confirmed an increase in reducing power throughout the fermentation period, underscoring EF48's superior profile. CONCLUSION: Thus, the study confirms that fermentation substantially enhances the bioactive properties of red Andong leaves, meriting additional mechanistic research and scalability assessments for applications in functional foods and therapeutics.
INTRODUCTION: The rising global incidence of diabetes mellitus underscores the pressing necessity for safer and more efficacious therapy approaches. Medicinal herbs remain a significant source of bioactive compounds with...INTRODUCTION: The rising global incidence of diabetes mellitus underscores the pressing necessity for safer and more efficacious therapy approaches. Medicinal herbs remain a significant source of bioactive compounds with potential antidiabetic effects. Achyranthes aspera has historically been utilized in traditional medicine for the treatment of metabolic disorders; however, its mechanisms of action remain poorly elucidated. This work sought to assess the antidiabetic efficacy of A. aspera using a combined experimental and computational approach, emphasizing its capacity to inhibit key carbohydrate-digesting enzymes and enhance cellular glucose uptake. METHODS: An aqueous extract derived from the leaves of A. aspera was examined for its phytochemical constituents and antioxidant efficacy. In vitro studies were conducted to evaluate its inhibitory effects on α- amylase, α-glucosidase, and Dipeptidase-4 (DPP-4), as well as its cytotoxicity and glucose absorption activity in L6 myotube cells. The extract's chemical profile was characterized by Liquid Chromatography-Mass Spectrometry (LC-MS). Molecular docking and 100-nanosecond molecular dynamics simulations were performed to assess the interactions and stability of the discovered compounds within the active sites of the target enzymes. RESULTS: The extract exhibited significant levels of phenolic compounds (2.4 ± 0.32 mg GAE/g) and flavonoids (1.18 ± 0.12 mg QE/g), which correlated with robust antioxidant activity. The extract exhibited strong inhibitory effects on α-amylase, α-glucosidase, and DPP-4, with some samples demonstrating activity equal to or exceeding that of conventional reference medications. The extract exhibited no cytotoxicity in L6 myotubes and dramatically increased glucose absorption in a dose-dependent manner. LC-MS analysis identified multiple bioactive constituents, while computational studies validated their stable binding interactions with critical enzymatic targets, corroborating the observed biological effects. The results demonstrate that A. aspera has antidiabetic properties via multiple mechanisms, including the inhibition of carbohydrate-metabolizing enzymes and the enhancement of cellular glucose uptake. These findings corroborate its historical use in diabetes therapy and suggest that it may serve as a viable source of antidiabetic phytochemicals. The computer research provided mechanistic insight into the molecular connections underlying these effects. Nonetheless, the current work is confined to in vitro and in silico analyses. Subsequent research should focus on isolating specific active molecules and verifying their efficacy and safety in in vivo models to ascertain their medicinal potential. DISCUSSION: The study demonstrates that Achyranthes aspera exhibits multi-target antidiabetic activity through enzyme inhibition, DPP-4 modulation, and enhanced glucose uptake. These effects are supported by its phenolic-rich composition and validated by in silico binding interactions. However, further in vivo studies are required to confirm its therapeutic potential. CONCLUSION: These results confirm that Achyranthes aspera is a potent, multifunctional agent for glycaemic regulation, warranting further investigation for its development into functional food products or as an adjunctive diabetic therapy.
INTRODUCTION/OBJECTIVE: This study aimed to evaluate the in vitro and in vivo antihypertensive effects of red tilapia (Oreochromis spp.) viscera hydrolysate and its fractions. METHODS: The viscera were hydrolyzed by Alca...INTRODUCTION/OBJECTIVE: This study aimed to evaluate the in vitro and in vivo antihypertensive effects of red tilapia (Oreochromis spp.) viscera hydrolysate and its fractions. METHODS: The viscera were hydrolyzed by Alcalase® 2.4L, and their fractions were separated in a ceramic tubular membranes system with an MWCO of 3 kDa, obtaining >3 kDa and <3 kDa fractions. Both hydrolysate and fractions were evaluated for vasodilatory effect in rat aorta rings and in an acute test involving normotensive rats. In addition, the chronic antihypertensive effect of the fraction <3 kDa was evaluated in hypertensive rats for 35 days, using doses of 75 and 150 mg/kg, respectively. RESULTS: The hydrolysate induced vasodilation in rat aorta rings through an endotheliumdependent nitric oxide (NO) pathway. In the acute in vivo test, hydrolysates and fractions significantly decreased rat systolic pressure, with the <3 kDa fraction showing the most potent effect. DISCUSSION: Meanwhile, in the chronic antihypertensive study with rats, a blood pressure drop was observed over time, reducing systolic blood pressure to 122.7 mmHg on day 29 of the study, using the fraction <3 kDa. CONCLUSION: The results suggested the hydrolysate and fractions under study contain bioactive peptides with potential for the development of antihypertensive drugs.
INTRODUCTION/BACKGROUND: Leukemia progression is strongly influenced by the immune microenvironment, yet the regulatory gene networks that coordinate immune activity in leukemia remain incompletely defined. Identifying i...INTRODUCTION/BACKGROUND: Leukemia progression is strongly influenced by the immune microenvironment, yet the regulatory gene networks that coordinate immune activity in leukemia remain incompletely defined. Identifying immune-associated hub genes with diagnostic, prognostic, and functional relevance may improve biological understanding and guide biomarker development. METHODS: GEO datasets (GSE9476, GSE12417, GSE13159) were analyzed by WGCNA to identify immune-related hub genes. Expression, diagnostic, and prognostic value were validated in independent AML cohorts (GSE37642, GSE6891, TCGA-LAML). Genomic alterations and miRNA regulators were assessed bioinformatically and confirmed by luciferase assays. Functional effects were examined via gene knockdown/overexpression and functional assays. RESULTS: WGCNA identified an immune-associated module significantly correlated with leukemia and immune infiltration, from which CXCR4, LCP2, ITGAM, and HLA-DRA emerged as hub genes. All four genes were significantly upregulated in leukemia and demonstrated strong diagnostic performance (AUC 0.78-0.85). The four-gene prognostic model stratified survival consistently across three independent cohorts. Mutational and copy number profiling revealed low but functionally relevant genomic alterations. miR-27a-3p and miR-185-5p were identified and experimentally validated as shared upstream regulators. Knockdown of hub genes reduced proliferation, clonogenicity, and migration in leukemia cells, whereas overexpression enhanced these malignant phenotypes. DISCUSSION: In this study, we identified a robust immune-associated gene module in leukemia and demonstrated that CXCR4, LCP2, ITGAM, and HLA-DRA function as central hubs with consistent diagnostic and prognostic value across multiple independent cohorts. Integrated transcriptomic, genomic, and experimental analyses revealed that these genes are coordinately regulated by shared miRNAs and actively promote leukemic proliferation, clonogenicity, and migration. Our findings highlight the importance of immune-tumor interactions in leukemia progression and suggest that this four-gene signature may serve as a promising biomarker set and therapeutic target for immune-informed leukemia management. CONCLUSION: This integrative multi-omic and functional study identifies a four-gene immuneassociated module with diagnostic, prognostic, and biological significance in leukemia. The coordinated regulation of hub genes by shared miRNAs and their functional impact on leukemic behavior highlight potential avenues for biomarker development and therapeutic targeting.
INTRODUCTION: Nanoparticles have attracted significant interest due to their potential in various applications, including food fortification. However, their behavior during the digestive process has not yet been studied...INTRODUCTION: Nanoparticles have attracted significant interest due to their potential in various applications, including food fortification. However, their behavior during the digestive process has not yet been studied in depth. This study aimed to evaluate the bioaccessibility of high doses of CaCO3 using in vitro simulated gastrointestinal digestion and to investigate the behavior of this material in relation to in vitro cytotoxicity and in vivo acute toxicity in mice. METHODS: Calcium Carbonate Nanoparticles (Ca-NPs) were obtained from eggshells. Bioaccessibility and cytotoxicity were evaluated using concentrations of 6, 12, and 25 mg·mL-1 (≈60-250 mM Ca2+), compared with commercial CaCO3 (Ca-Ccial). An acute oral toxicity study was conducted in mice with 2000 mg/kg of Ca-NPs administered. RESULTS: During the gastric phase, Ca-NPs exhibited 18% higher calcium bioaccessibility than CaCcial (p < 0.05). However, bioaccessibility decreased in the intestinal phase for both calcium sources due to pH-induced precipitation. Cytotoxicity assays showed that both calcium sources were non-toxic at concentrations up to 250 mM Ca2+ (p > 0.05). Acute toxicity tests in mice with 2000 mg/kg of CaCO3 confirmed the absence of adverse effects (p > 0.05). DISCUSSION: Nanoscale surface and porosity of Ca-NPs provoked superior gastric dissolution and bioaccessibility compared to commercial CaCO3. The decline in intestinal solubility reflected pHinduced reprecipitation of Ca species. In vitro and in vivo assays confirmed biocompatibility without cytotoxicity. These findings elucidate the relationship between nanoparticle physicochemistry, solubility dynamics, and short-term biological safety. CONCLUSION: These findings support the use of Ca-NPs as safe, bioaccessible, and potentially functional components for foods and pharmaceutical applications.