Search Results (704)

Cinnamic acid, an organic acid naturally occurring in plants of the Cinnamomum genus, has been highly valued for its medicinal properties in numerous ancient Chinese texts. This article reviews the chemical composition, pharmacological effects, and various applications of cinnamic acid and its derivatives reported in publications from 2016 to 2025, and anticipates their potential in medical and industrial fields. This review evaluates studies in major scientific databases, including Web of Science, PubMed, and ScienceDirect, to ensure a comprehensive analysis of the therapeutic potential of cinnamic acid. Through systematic integration of existing knowledge, it has been revealed that cinnamic acid has a wide range of pharmacological activities, including anti-tumor, antibacterial, anti-inflammatory, antidepressant and hypoglycemic effects. Additionally, it has been shown to be effective against a variety of pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, and foodborne Pseudomonas. Cinnamic acid acts by disrupting cell membranes, inhibiting ATPase activity, and preventing biofilm formation, thereby demonstrating its ability to act as a natural antimicrobial agent. Its anti-inflammatory properties are demonstrated by improving oxidative stress and reducing inflammatory cell infiltration. Furthermore, cinnamic acid enhances metabolic health by improving glucose uptake and insulin sensitivity, showing promising results in improving metabolic health in patients with diabetes and its complications. This systematic approach highlights the need for further investigation of the mechanisms and safety of cinnamic acid to substantiate its use as a basis for new drug development. Particularly in the context of increasing antibiotic resistance and the search for sustainable, effective medical treatments, the study of cinnamic acid is notably significant and innovative. Full article

Background: Aicardi-Goutières Syndrome (AGS) is a rare neuroinflammatory condition characterized by early-onset symptoms that extend outside the nervous system. Due to the rarity of the disease, the pathogenesis is not well understood, and its diagnosis and treatment remain elusive. We recently demonstrated mitochondrial abnormalities and increased reactive oxygen species (ROS) levels in lymphoblastoid cell lines (LCLs) derived from RNASEH2B- and RNASEH2A-mutated AGS patients. On this background, we turned our attention to metformin, the first-choice drug for type 2 diabetes, as a possible treatment acting on oxidative stress in RNASEH2-mutant AGS cells. Methods and Results: By means of flow cytometry, we found that metformin treatment significantly decreases ROS production in RNASEH2B- and RNASEH2A-mutated AGS LCLs. Of note, metformin treatment reduces the green JC-1 monomeric signal and, concurrently, increases the red JC-1 signal in both mutated LCLs, accounting for restoration of the mitochondrial membrane potential. Immunofluorescence staining shows a decrease in 8-oxoG levels only in RNASEH2B- mutated AGS LCLs. Finally, the significant upregulation of Forkhead Box O3 (FOXO3), cytochrome C somatic (CYCS), and superoxide dismutase 2 (SOD2) mRNA levels in RNASEH2B-mutated AGS LCLs after metformin treatment points to FOXO3 signaling as a possible mechanism to reduce oxidative stress. Conclusions: In conclusion, even if these pilot results need to be confirmed on a larger cohort, we shed light on metformin treatment as a valid approach to ameliorate oxidative stress-related inflammation in AGS patients. Full article

The vast majority of viruses causing human and animal diseases are enveloped—their virions contain an outer lipid bilayer originating from a host cell. Small molecule antivirals targeting the lipid bilayer cover the broadest spectrum of viruses. In this context, we consider the chemical nature and mechanisms of action of membrane-targeting antivirals. They can affect virions by (1) physically modulating membrane properties to inhibit fusion of the viral envelope with the cell membrane, (2) physically affecting envelope lipids and proteins leading to membrane damage, pore formation and lysis, (3) causing photochemical damage of unsaturated membrane lipids resulting in integrity loss and fusion arrest. Other membrane-active compounds can target host cell membranes involved in virion’s maturation, coating, and egress (endoplasmic reticulum, Golgi apparatus, and outer membrane) affecting these last stages of viral reproduction. Both virion- and host-targeting membrane-active molecules are promising concepts for broad-spectrum antivirals. A panel of approved antivirals would be a superior weapon to respond to and control emerging disease outbreaks caused by new viral strains and variants. Full article

Choline has been recognized as an essential nutrient involved in various physiological functions critical to human health. Adequate daily intake of choline has been established by the US National Academy of Medicine in 1998, considering choline requirements for different ages, sex differences and physiological states (e.g., pregnancy). By serving as a precursor for acetylcholine and phospholipids, choline is important for cholinergic transmission and the structural integrity of cell membranes. In addition, choline is involved in lipid and cholesterol transport and serves as a methyl donor after oxidation to betaine. Extracellular choline is transported across the cell membrane via various transport systems (high-affinity and low-affinity choline transporters) with distinct features and roles. An adequate dietary intake of choline during pregnancy supports proper fetal development, and throughout life supports brain, liver, and muscle functions, while choline deficiency is linked to disease states like fatty liver. Choline has important roles in neurodevelopment, cognition, liver function, lipid metabolism, and cardiovascular health. While its signaling role has been considered mostly indirect via acetylcholine and phosphatidylcholine which are synthesized from choline, emerging evidence supports a role for choline as an intracellular messenger acting on Sigma-1R, a non-opioid intracellular receptor. These new findings expand the cell signaling repertoire and increase the current understanding of the role of choline while warranting more research to uncover the molecular mechanisms and significance in the context of GPCR signaling, the relevance for physiology and disease states. Full article

Sugars Will Eventually Be Exported Transporters (SWEETs) are involved in plant growth and development, particularly in resistance to adverse environments. Achnatherum splendens (Trin.) Nevski exhibits rhizosheath formation and demonstrates notable salt and drought tolerance. We identified 31 sugar transporter family genes (AsSWEETs) from the Achnatherum splendens genome in the NCBI database and performed bioinformatics analyses, including gene structure, subcellular localization, conserved sequences, promoter cis-acting elements, phylogenetic relationships, and chromosomal localization. The 31 AsSWEET genes are distributed across 13 chromosomes, encoding peptides ranging from 375 to 1353 amino acids. Their predicted molecular weights range from 31,499.38 to 109,286.91 Da, with isoelectric points (pI) between 4.78 and 5.21. The aliphatic index values range from 13.59 to 24.19, and the grand average of hydropathicity (GRAVY) values range from 0.663 to 1.664. An analysis of promoter cis-acting elements reveals that all 31 AsSWEET genes contain multiple elements related to light, stress, and hormone responses. Subcellular localization predictions indicate that most genes in this family are localized to the plasma membrane or tonoplast, with AsSWEET12-2 and AsSWEET3b localized in chloroplasts and AsSWEET2b-2 in the nucleus. qRT-PCR results show that AsSWEET13-1, AsSWEET13-3, and AsSWEET1a exhibit upregulated expression in response to salt and drought stress in the roots of Achnatherum splendens. These genes may serve as candidate genes for investigating the stress resistance mechanisms of Achnatherum splendens. The findings provide a theoretical basis for further research on stress resistance mechanisms and candidate gene identification under salt and drought stress in Achnatherum splendens. Full article

Background: The late embryogenesis abundant (LEA) gene family plays a critical role in abiotic stress tolerance during plant growth and development. Myricaria laxiflora, as a key pioneer species in the extreme hydrological fluctuation zone of the Yangtze River, has evolved unique adaptation mechanisms potentially linked to gene family evolution. However, the molecular mechanisms underlying how the LEA gene family responds to alternating flooding–drought cycles remain unclear. Methods and Results: In this study, we identified 31 LEA genes through whole-genome and transcriptome analyses using bioinformatics approaches, and classified them into nine subfamilies based on protein sequence similarity. These genes were distributed across 12 chromosomes. Our analysis revealed that LEA promoters contain cis-acting elements associated with anaerobic induction, abscisic acid (ABA) response, and combined low-temperature/light stress, suggesting their role in a multi-tiered environmental signal integration network. Spatio-temporal expression profiling further indicated that root-specific LEA genes maintain cellular integrity via membrane lipid binding, while leaf-predominant members cooperate with the antioxidant system to mitigate photoinhibition damage. Conclusions: This study elucidates the dynamic regulatory mechanisms of the LEA gene family during flooding-drought adaptation in M. laxiflora, providing molecular targets for ecological restoration in the Yangtze River Basin. Full article

Klebsiella pneumoniae can acquire resistance mechanisms to colistin and present a pan-resistant phenotype. Therefore, new alternative agents are imperative to control this pathogen, and the peptide Jelleine-I stands out as a promising prototype. Here, the antibacterial activity of Jelleine-I against clinical isolates of colistin-resistant K. pneumoniae (CRKP) was investigated. Antimicrobial activity was assessed by determining the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time kill-curve assay. The release of 260 nm-absorbing materials (DNA/RNA) and the release of proteins were used in the lysis assay. Anti-biofilm activity was studied in microplates. In vivo activity was determined by the lethality assay using Tenebrio molitor larvae. The results show that the MIC of Jelleine-I ranged from 16 to 128 µM and the MBC was on average 128 µM. Jelleine-I at 200 µM killed all CRKP cells in suspension (10⁶ colony-forming units (CFU)/mL) after 150 min of incubation. Jelleine-I acts on the CRKP cell membrane inducing lysis. Biomass and viability of CRKP-induced biofilms are reduced after treatment with Jelleine-I, and the use of this peptide in T. molitor larvae infected with CRKP reduces lethality and improves overall larval health. In conclusion, Jelleine-I is a potential prototype for the development of new antimicrobial agents. Full article

Background: Cell-penetrating peptides cross cell membrane barriers while carrying cargoes in a functional form. Our work identified two novel lung-targeting peptides, S7A and R11A. Here, we present studies on biodistribution, the cell types targeted, and an in vitro proof of application. Methods: Studies were performed in human bronchial epithelial cells (HBECs) with and without various endocytic inhibitors, and coincubation with fluorescently labeled transferrin or endocytic markers. Cyclic R11A (cR11A) was conjugated to siRNA duplexes and anti-viral activity against SARS-CoV-2 was tested. Biodistribution studies were performed by injecting wild-type mice with fluorescently labeled peptides, and various circulation times were allowed for, as well as cross-staining of lung sections or isolated single cells with various cellular markers, followed by fluorescence-activated cell sorting or confocal microscopy. Results: cR11A showed peak uptake in 15 min, with the highest uptake in airway epithelial type II (ATII) cells, followed by p63+ basal cells and ionocytes. Cyclization increased transduction efficiencies ~100-fold. Endocytosis studies showed a decrease in peptide uptake by pre-treatment with Pitstop2 but not Amiloride or Nystatin. Endocytic marker Lamp1 showed colocalization at the earliest time point, with the escape of the peptide from endocytic vesicles later. cR11A conjugated to ant-spike and anti-envelop proteins showed anti-viral effects with an EC₉₀ of 0.6 μM and 1.0 µM, respectively. Conclusions: We have identified a novel peptide, cR11A, that targets ATII, basal cells, and ionocytes, the cyclization of which increased transduction efficiency in vitro and in vivo. The uptake mechanism appears to be via clathrin-mediated endocytosis with escape from endocytic vesicles. cR11A can act as a vector to deliver anti-viral siRNA to epithelial cells. Full article

Background: Dithiolopyrrolones (DTPs), such as holomycin and thiolutin, exhibit potent antibacterial activities. DTPs contain a disulfide within a unique bicyclic scaffold, which may chelate metal ions and disrupt metal-dependent cellular processes once the disulfide is reductively transformed to thiols. However, the contribution of the intrinsic redox mechanism of DTPs to their antibacterial activity remains unclear. Herein we used pyrroloformamide (Pyf) A, a DTP with a unique formyl substituent, as a prototype to study the antibacterial potential and mechanism against ESKAPE pathogens, in particular carbapenem-resistant Klebsiella pneumoniae (CRKP). Methods: The antibacterial and anti-biofilm activities of Pyf A were mainly assessed against clinical CRKP isolates. Propidium iodide staining, scanning electron microscopy, glutathione (GSH) quantification, and reactive oxygen species (ROS) analysis were utilized to infer its anti-CRKP mechanism. The synergistic antibacterial effects of Pyf A and AgNO₃ were evaluated through checkerboard and time-kill assays, as well as in vivo murine wound and catheter biofilm infection models. Results: Pyf A exhibited broad-spectrum antibacterial activity against ESKAPE pathogens with minimum inhibitory concentrations ranging from 0.25 to 4 μg/mL. It also showed potent anti-biofilm effects against CRKP. Pyf A disrupted the cell membranes of CRKP and markedly depleted intracellular GSH without triggering ROS accumulation. Pyf A and AgNO₃ showed synergistic anti-CRKP activities in vitro and in vivo, by disrupting both GSH- and thioredoxin-mediated redox homeostasis. Conclusions: Pyf A acts as a GSH-depleting agent and, when combined with AgNO₃, achieves dual-targeted disruption of bacterial thiol redox systems. This dual-targeting strategy enhances antibacterial efficacy of Pyf A and represents a promising therapeutic approach to combat CRKP infections. Full article

Microorganisms play a dual role in human health, serving as both essential allies and serious threats. Their association with infections led to the development of antimicrobials like penicillin, which revolutionized medicine. However, the emergence of antimicrobial resistance (AMR) has created a global health crisis, rendering many treatments ineffective due to pathogen mutations and acquired resistance mechanisms, particularly among ESKAPE pathogens. This resistance increases morbidity, mortality, and healthcare costs, exacerbated by antibiotic overuse and globalization. Biofilms and sepsis further complicate treatment. Addressing AMR requires new therapies, rational antibiotic use, and innovative approaches for drug discovery. Coordinated global action is essential to ensure future access to effective treatments. Antimicrobial peptides (AMPs) derived from Boana species (Anura, Hylidae) represent a promising alternative in the fight against AMR. These peptides exhibit activity against multidrug-resistant pathogens. Unlike conventional antibiotics, Boana peptides act through a broad mechanism that limits resistance development. Their ability to disrupt bacterial membranes and modulate immune responses makes them ideal candidates for the development of new treatments. These peptides may offer valuable alternatives for treating resistant infections and addressing the global AMR crisis. Full article

Membrane tubes, a class of soft biological confinement for ubiquitous transport intermediates, are essential for cell trafficking and intercellular communication. However, the confinement interaction and directional migration of diffusive nanoparticles (NPs) are widely dismissed as improbable due to the surrounding environment compressive force. Here, combined with the mechanics analysis of nanoparticles (such as extracellular vesicles, EVs) to study their interaction in confinement, we perform dissipative particle dynamics (DPD) simulations to construct a model that is as large as possible to clarify the submissive behavior of NPs. Both molecular simulations and mechanical analysis revealed that the interactions between NPs are controlled by confinement deformation and the centroid distance of the NPs. When the centroid distance exceeds a threshold value, the degree of crowding variation becomes invalid for NPs motion. The above conclusions are further supported by the observed dynamics of multiple NPs under confinement. These findings provide new insights into the physical mechanism, revealing that the confinement squeeze generated by asymmetric deformation serves as the key factor governing the directional movement of the NPs. Therefore, the constraints acting on NPs differ between rigid confinement and soft confinement environments, with NPs maintaining relative stillness in rigid confinement. Full article

Long-range intercellular communication is essential for multicellular biological systems to regulate multiscale cell–cell interactions and maintain life. Growing evidence suggests that intercellular calcium waves (ICWs) act as a class of long-range signals that influence a broad spectrum of cellular functions and behaviors. Importantly, mechanical signals, ranging from single-molecule-scale to tissue-scale in vivo, can initiate and modulate ICWs in addition to relatively well-appreciated biochemical and bioelectrical signals. Despite these recent conceptual and experimental advances, the full nature of underpinning mechanotransduction mechanisms by which cells convert mechanical signals into ICW dynamics remains poorly understood. This review provides a systematic analysis of quantitative ICW dynamics around three main stages: initiation, propagation, and regeneration/relay. We highlight the landscape of upstream molecules and organelles that sense and respond to mechanical stimuli, including mechanosensitive membrane proteins and cytoskeletal machinery. We clarify the roles of downstream molecular networks that mediate signal release, spread, and amplification, including adenosine triphosphate (ATP) release, purinergic receptor activation, and gap junction (GJ) communication. Furthermore, we discuss the broad pathophysiological implications of ICWs, covering pathophysiological processes such as cancer metastasis, tissue repair, and developmental patterning. Finally, we summarize recent advances in optical imaging and artificial intelligence (AI)/machine learning (ML) technologies that reveal the precise spatial-temporal-functional dynamics of ICWs and ATP waves. By synthesizing these insights, we offer a comprehensive framework of ICW mechanobiology and propose new directions for mechano-therapeutic strategies in disease diagnosis, cancer immunotherapies, and drug discovery. Full article

Hyperosmolality-gated calcium-permeable cation channel protein denoted as OSCA, which are mechanosensitive pore-forming ion channels, play a pivotal role in plants’ responses to abiotic stressors. Notopterygium franchetii, an endemic perennial plant species distributed in the Qinghai–Tibetan Plateau and its adjacent high-altitude regions, is likely to have undergone adaptive evolution in response to extreme abiotic stress conditions. The current study was conducted to characterize the genome-wide characteristics and phylogenetic evolution of the OSCA gene family in N. franchetii and identify its response patterns to drought and high-temperature stresses. We examined the gene family’s structural features, phylogenetic relationships, and response to abiotic stresses. The N. franchetii genome had 29 OSCA gene family members on 11 chromosomes. Subcellular localization showed they were mainly in the cell membrane, and a promoter cis-acting element study found that the OSCA gene family contained methyl jasmonate, abscisic acid, and various adversity and hormone response components. Under drought stress, most of the NofOSCAs genes showed a tendency to increase over time in the roots of N. franchetii, while in the aboveground parts, most of the NofOSCAs genes showed a tendency to increase and then decrease. The expression of different NofOSCAs genes in N. franchetii also showed alternating changes under high-temperature stress. Nine members of NofOSCAs were found to be linked to the PPI network, and these members were involved in membrane structure, transmembrane transport, and ion channel function. Our analysis of differential expression revealed that the expression of OSCA genes differed among the different N. franchetii tissues, with the roots exhibiting the highest average expression level, and many genes displayed tissue-specific high expression patterns. These results provided novel insights into the phylogenetic evolution and abiotic stress response mechanisms in the high-altitude medicinal herb N. franchetii. Full article

The auxin efflux transporter PIN protein plays a crucial role in the asymmetric distribution of auxin on the plasma membrane, influencing the growth and development of plant organs. In this study, we identified nine members of the PIN gene family in the cucumber genome, which could be classified into five phylogenetic groups. These genes have diverse structures but conserved transmembrane domains. Analysis of cis-acting elements in the promoters revealed that CsPINs contain 48 types of cis-acting elements, predominantly light-responsive elements and plant hormone response elements. In addition, PIN proteins may interact with a variety of auxin-related proteins (including auxin response factor, auxin binding protein, mitogen-activated protein kinase PINOID, etc.) to jointly regulate the auxin synthesis and metabolic pathways. We analyzed the expression profiles of PIN genes in 23 tissues of cucumber using the CuGenDB database, and further investigated the expression levels of PIN genes in leaves and roots in response to different abiotic stresses and hormone treatments by qRT-PCR. This study provides a theoretical basis for clarifying the regulatory mechanism of the cucumber PIN gene family during environmental stress processes. Full article

Autophagy and apoptosis are two essential mechanisms regulating cell fate. Although distinct, their signaling pathways are closely interconnected through various crosstalk mechanisms. Lipid rafts are described to act as both physical and functional platforms during the early stages of autophagic and apoptotic processes. Only recently has a role for lipid raft-associated molecules in regulating EV biogenesis and release begun to emerge. In particular, lipids of EV membranes are essential components in conferring stability to these vesicles in different extracellular environments and/or to facilitate binding or uptake into recipient cells. In this review we highlight these aspects, focusing on the role of lipid molecules during apoptosis and secretory autophagy pathways. We describe the molecular machinery that connects autophagy and apoptosis with vesicular trafficking and lipid metabolism during the release of EVs, and how their alterations contribute to the development of various diseases, including autoimmune disorders and cancer. Overall, these findings emphasize the complexity of autophagy/apoptosis crosstalk and its key role in cellular dynamics, supporting the role of lipid rafts as new therapeutic targets. Full article