Membrane Disruption Research Articles

Synergistic Inhibition of Colorectal Cancer Cells by Autocrine Motility Factor Peptide and Glycyrrhetinic Acid.

Anti-cancer peptides are a powerful drug concept that induces cancer cell death through growth inhibition and membrane disruption, providing broad efficacy. The autocrine motility factor (AMF) interacts with the AMF receptor, regulating cancer cell motility, proliferation, metastasis, and angiogenesis through autocrine and paracrine pathways. However, studies verifying the synergistic effect of the combined use of anti-cancer drugs extracted from plants and AMF treatment are insufficient. The effects of AMF-derived peptide sequences were evaluated in HT29 and SW620 colorectal cancer (CRC) cell lines. The study assessed the impact of AMF peptides on cell proliferation, colony formation, the Nicotinamide Adenine Dinucleotide Phosphate/Reduced Nicotinamide Adenine Dinucleotide Phosphate (NADP+/NADPH) ratio, and reactive oxygen species (ROS) generation in these CRC cells. Additionally, the combined effect of AMF peptides and glycyrrhetinic acid (GA), a compound derived from licorice plants, was investigated by analyzing cell proliferation, colony formation, ROS production, and cell cycle progression in CRC cells. AMF peptides significantly inhibited CRC cell growth (p < 0.05), decreased colony formation (p < 0.05), and increased the NADP+/NADPH ratio (p < 0.05) and ROS production (p < 0.001). When combined with GA, AMF peptides enhanced GA's effects on CRC cells, further suppressing cell growth (p < 0.05) and colony formation (p < 0.05) while increasing ROS generation (p < 0.05). The synergy between AMF peptides and GA, derived from licorice plants, suggests the potential for combined peptide-phytochemical therapy for treating CRC.

Synergistic effect of acetic acid and chitosan against Aspergillus flavus

The mycotoxin-producing fungi contamination of foodstuffs and agricultural commodities is a serious problem. In this study, the efficacy of acetic acid (AcA), chitosan (CS), and CS with extra AcA (CS/extra AcA) against Aspergillus flavus (A. flavus) in vitro and in vivo were investigated. Results showed that CS/extra AcA strongly inhibited the mycelial growth and aflatoxins production of A. flavus at lower concentrations than CS (MIC >16.0 mg/mL) or AcA (MIC: 0.31 %). Significant inhibition was achieved in the presence of 4.0/0.12 and 8.0/0.08 CS (mg/mL)/extra AcA (%). CS/extra AcA exhibited remarkable antifungal activities based on the results of spore germination inhibition, abnormalities of spore morphology, disruption of cell membrane, mitochondrial dysfunction, and induction of apoptosis of hyphae. Moreover, pathogenicity test in peanut kernels showed that 8.0/0.16 CS (mg/mL)/extra AcA (%) could effectively inhibit the fungal infection and aflatoxin B1 production. The efficacy of CS/extra AcA is possibly due to the synergy of the antifungal property of CS, and undissociated AcA. The findings referred that CS/extra AcA is safe, efficient, and economical, and it could be used as a promising way to control A. flavus contamination in agro-foods preservation.

Bioinorganic Chemistry Meets Microbiology: Copper(II) and Zinc(II) Complexes Doing the Cha-Cha with the C-t-CCL-28 Peptide, Dancing till the End of Microbes.

The necessity to move away from conventional antibiotic therapy has sparked interest in antimicrobial peptides (AMPs). One fascinating example is human CCL-28 chemokine produced by acinar epithelial cells in the salivary glands. It can also be released into the oral cavity with saliva, playing a crucial role in oral protection. The C-terminal domain of CCL-28 possesses antifungal and antibacterial properties, which are likely linked to membrane disruption and enzyme leakage. Studies suggest that AMPs can become more potent after they have bound Cu(II) or Zn(II). In many cases, these ions are essential for maximizing effectiveness by altering the peptides' physicochemical properties, such as their local charge or structure. The examined peptide binds Cu(II) and Zn(II) ions very effectively, forming equimolar complexes. Metal ion binding affinity, coordination mode, and antimicrobial activity strongly depend on the pH of the environment. Coordination modes have been proposed based on the results of potentiometric titrations, spectroscopic studies (UV-visible, electron paramagnetic resonance and circular dichroism at different path lengths), and mass spectrometry. The antimicrobial properties of the Cu(II) and Zn(II) complexes with the C-terminal fragment of CCL-28 chemokine have been assessed against fungal and bacterial strains, demonstrating exceptional activity against Candida albicans at pH 5.4. Moreover, the complex with Zn(II) ions shows the same activity against theStreptococcus mutans bacterium as chloramphenicol, a commonly used antibiotic. Cyclic voltammetry proposed a probable antimicrobial mechanism of the studied Cu(II) complex through the formation of reactive oxygen species, which was also confirmed by tests with ascorbic acid in UV-vis and fluorescence spectroscopic studies.

Targeting the phosphatidylglycerol lipid: An amphiphilic dendrimer as a promising antibacterial candidate.

The rapid emergence and spread of multidrug-resistant bacterial pathogens require the development of antibacterial agents that are robustly effective while inducing no toxicity or resistance development. In this context, we designed and synthesized amphiphilic dendrimers as antibacterial candidates. We report the promising potent antibacterial activity shown by the amphiphilic dendrimer AD1b, composed of a long hydrophobic alkyl chain and a tertiary amine-terminated poly(amidoamine) dendron, against a panel of Gram-negative bacteria, including multidrug-resistant Escherichia coli and Acinetobacter baumannii. AD1b exhibited effective activity against drug-resistant bacterial infections in vivo. Mechanistic studies revealed that AD1b targeted the membrane phospholipids phosphatidylglycerol (PG) and cardiolipin (CL), leading to the disruption of the bacterial membrane and proton motive force, metabolic disturbance, leakage of cellular components, and, ultimately, cell death. Together, AD1b that specifically interacts with PG/CL in bacterial membranes supports the use of small amphiphilic dendrimers as a promising strategy to target drug-resistant bacterial pathogens and addresses the global antibiotic crisis.

Association between phase angle and inflammatory blood biomarkers in community-dwelling older adults: Itabashi Longitudinal Study on Aging

Background & AimBioelectrical impedance analysis–derived phase angle (PhA) reflects the disruption of the cell membrane and intra- and extracellular fluid imbalances caused by chronic inflammation. This study examined the association between PhA and inflammatory markers in community-dwelling older adults. MethodsA sex-stratified logistic regression analysis was conducted, with elevated C-reactive protein (CRP; ≥3.0 mg/L) and interleukin-6 (IL-6; >4.0 pg/mL) levels as the outcomes and whole-body and local PhAs as the exposures. The same analysis was conducted with further stratification for age, overweight status, history of inflammation-related non-communicable diseases, and dietary inflammatory index. The ability to identify inflammation in whole-body and local PhAs was assessed using a receiver operating characteristic (ROC) curve. ResultsThis study included 1,664 participants (age: 76 [73–80] years; 855 women). In men, significant odds ratios (ORs) at the 95% confidence interval (95% CI) were observed for abnormal CRP and IL-6 levels for both whole-body and leg PhAs in the third quartile compared with the lowest quartile (OR [95% CI] for abnormal CRP levels: 0.36 [0.18, 0.68] for whole-body PhA, 0.51 [0.27, 0.95] for leg PhA; OR [95% CI] for abnormal IL-6 levels: 0.36 [0.15, 0.81] for whole-body PhA, 0.33 [0.12, 0.78] for leg PhA). The areas under the ROC curves (95% CI) for identifying abnormal IL-6 were mild in men (0.62 [0.54, 0.70] for whole-body PhA and 0.62 [0.55, 0.70] for leg PhA). In men without a history of inflammation-related non-communicable diseases, it was 0.72 (0.59, 0.85) for whole-body PhA and 0.68 (0.54, 0.81) for leg PhA. In women, the PhA was not significantly associated with inflammatory markers. ConclusionPhA is associated with inflammation in community-dwelling older men, but may need to be combined with other information to identify inflammation.

Underlying mechanism of the microwave non-thermal effect as additional microbial inactivation on Clostridium sporogenes at pasteurization temperature level

Microwave processing can induce non-thermal effects that can inactivate additional levels of microorganisms at pasteurization temperature level (80–100 °C). The objective of this study was to investigate the mechanism behind the non-thermal effects of microwaves on vegetative cells of Clostridium sporogenes. Cell membrane damage were assessed through nuclear fluorescent dyes and by measuring nuclear acid and protein leakage. The results showed that microwave non-thermal effects and conventional water bath treatment resulted in similar nuclear acid leakage. However, microwave non-thermal effects inflicted more severe damage to the cell membranes of Clostridium sporogenes, resulting in increased protein leakage from both the inner of the cell and the cell membrane (A260 = 0.25 vs. 0.18). Consequently, it can be inferred that the inactivation of additional Clostridium sporogenes by microwave non-thermal effects is primarily attributed to the disruption of cell membranes induced by alternating electromagnetic fields, and this phenomenon is further potentiated at elevated temperatures.

Synergistic antimicrobial action of chlorogenic acid and ultraviolet-A (365 nm) irradiation; mechanisms and effects on DNA integrity

Chlorogenic acid (CGA) is abundant in various plants and notably in coffee beans. This study investigated the bactericidal activity of CGA combined with ultraviolet-A light (UVA, 365 nm) (CGA + UVA) against Escherichia coli DH5α, with the aim of developing novel strategies for food preservation and healthcare. CGA + UVA treatment was superiorin reducing bacterial survival than either treatment alone. At 20 J/cm2 and pH 7, CGA (0.3%) + UVA treatment resulted in only about a 3-log reduction in bacterial survival, whereas at 15 J/cm2 and pH 3, no surviving bacteria could be detected, demostrating that the treatment was more effective at acidic pH. CGA + UVA treatment was also bactericidal in green plum juice, confirming that its low pH-dependent property could be effective in acidic food products. To elucidate the bactericidal mechanism of CGA + UVA treatment, its effects on reactive oxygen species (ROS) generation, membrane integrity, and enzyme activity were measured. ROS generated via the type-1 reaction, such as hydrogen peroxide (H2O2) and hydroxyl radicals (·OH), were mainly detected. CGA + UVA disrupted the bacterial cell membrane, causing the leakage of cellular components, particularly proteins. CGA + UVA treatment also led to deoxyribonucleic acid (DNA) degradation and reduced succinate-coenzyme Q reductase activity by approximately 72 %. Furthermore, CGA + UVA treatment decreased β-lactamase activity and plasmid transforming efficacy with maximal reductions of 68 % and 98 %, respectively, highlighting its potential for increasing antibiotic susceptibility and preventing the spread of antimicrobial resistance. The results demonstrate that CGA + UVA treatment could be used to effectively combat antibiotic-resistant bacteria and prevent the spoilage of preserved foods or food poisoning.

Effects of Secondary Amine and Molecular Weight on the Biological Activities of Cationic Amphipathic Antimicrobial Macromolecules.

Cationic amphipathic antimicrobial agents inspired by antimicrobial peptides (AMPs) have shown potential in combating multidrug-resistant bacteria because of minimal resistance development. Here, this study focuses on the development of novel cationic amphipathic macromolecules in the form of dendrons and polymers with different molecular weights that employ secondary amine piperidine derivative as the cationic moiety. Generally, secondary amine compounds, especially at low molecular weights, have stronger bacteriostatic, bactericidal, and inner membrane disruption abilities than those of their primary amine counterparts. Low molecular weight D2 dendrons with two cationic centers and one hydrophobic dodecyl chain produce outstanding synergistic activity with the antibiotic rifampicin against Escherichia coli, where one-eighth of the standalone dose of D2 dendrons could reduce the concentration of rifampicin required by up to 4000-fold. The low molecular weight compounds are also less toxic and therefore have higher therapeutic index values compared to compounds with larger molecular weights. This study thus reveals key information that may inform the design of future synthetic AMPs and mimics, specifically, the design of low-molecular-weight compounds with secondary amine as the cationic center to achieve high antimicrobial potency and biocompatibility.

Comparative Analyses of Muscle Quality in Hooked, Trawl-Net, and Radar-Net Hairtail (Trichiurus haumela) during Thermal Processing.

To investigate and compare the changes in muscle quality of hooked, trawl-net, and radar-net hairtail (Trichiurus haumela, HH, TH, and RH) during thermal processing, the physicochemical properties of three kinds of hairtail were determined under heating at 30, 50, 70 and 90 °C for 10 min. Additionally, the muscle tissues were observed via Oil Red O (ORO) staining, Masson staining, and scanning electron microscopy (SEM). The results showed that with increased heating temperature, pH, L*, b*, chewiness, and gumminess in hairtail muscle increased, while a* and shearing force decreased. The springiness, relative contents of hydrophobic and disulfide bonds, myosin surface hydrophobicity, and TCA-soluble peptide content increased first and then decreased. However, the relative contents of ionic and hydrogen bonds showed an opposite trend. Histological observations revealed that heating disrupted hairtail muscle tissue, manifested by the blurriness and disorder of myofibrils and breakage of myofibrillar bundle membranes. The RH muscle exhibited the highest chewiness, gumminess, and chemical force levels, accompanied by the lowest content of TCA-soluble peptide. Furthermore, the RH muscle presented the greatest fat droplet content, diffusivity, and integrity of collagen and myofibers. Correlation analysis revealed a close correlation between muscle quality and protein function in HH, TH, and RH. This study provides a theoretical basis for the difference in muscle quality in three different types of hairtail.

Antimicrobial properties of essential oil extracted from Schizonepeta annua against methicillin-resistant Staphylococcus aureus via membrane disruption

Schizonepeta annua (Pall.) Schischk. has long been traditionally employed in China for its anti-inflammatory, antimicrobial, and soothing properties. This study evaluates the antibacterial properties of essential oil extracted from Schizonepeta annua (SEO) and oregano (OEO) against methicillin-resistant Staphylococcus aureus (MRSA). SEO and OEO demonstrated substantial antibacterial efficacy, with SEO exhibiting significantly enhanced antibacterial activity due to its complex composition. Mechanistic investigations revealed that both essential oils disrupt bacterial membrane integrity and biosynthetic pathways, leading to the extrusion of intracellular contents. Metabolomic analyses using GC-Q-TOF-MS highlighted SEO's selective targeting of bacterial membranes, while non-targeted metabolomics indicated significant effects on MRSA's amino acid metabolism and aminoacyl-tRNA biosynthesis. These findings suggest that SEO causes considerable damage to MRSA cell membranes and affects amino acid metabolism, supporting its traditional use and highlighting its potential in treating infections. Our results offer robust theoretical support for SEO's role as an antimicrobial agent and establish a solid foundation for its practical application in combating multidrug-resistant infections.

Alkyl Pyridinol Compounds Exhibit Antimicrobial Effects against Gram-Positive Bacteria.

Background/Objectives. The rise of antibiotic-resistant pathogens represents a significant global challenge in infectious disease control, which is amplified by the decline in the discovery of novel antibiotics. Staphylococcus aureus continues to be a highly significant pathogen, causing infections in multiple organs and tissues in both healthcare institutions and community settings. The bacterium has become increasingly resistant to all available antibiotics. Consequently, there is an urgent need for novel small molecules that inhibit the growth or impair the survival of bacterial pathogens. Given their large structural and chemical diversity, as well as often unique mechanisms of action, natural products represent an excellent avenue for the discovery and development of novel antimicrobial treatments. Anaephene A and B are two such naturally occurring compounds with significant antimicrobial activity against Gram-positive bacteria. Here, we report the rapid syntheses and biological characterization of five novel anaephene derivatives, which display low cytotoxicity against mammalian cells but potent antibacterial activity against various S. aureus strains, including methicillin-resistant S. aureus (MRSA) and the multi-drug-resistant community-acquired strain USA300LAC. Methods. A Sonogashira cross-coupling reaction served as the key step for the synthesis of the alkyl pyridinol products. Results/Conclusions. Using the compound JC-01-074, which displays bactericidal activity already at low concentrations (MIC: 16 μg/mL), we provide evidence that alkyl pyridinols target actively growing and biofilm-forming cells and show that these compounds cause disruption and deformation of the staphylococcal membrane, indicating a membrane-associated mechanism of action.

Glutathione peroxidase 3 is essential for countering senescence in adipose remodelling by maintaining mitochondrial homeostasis

Adipose tissue senescence is a precursor to organismal aging and understanding adipose remodelling contributes to discovering novel anti-aging targets. Glutathione peroxidase 3 (GPx3), a critical endogenous antioxidant enzyme, is diminished in the subcutaneous adipose tissue (sWAT) with white adipose expansion. Based on the active role of the antioxidant system in counteracting aging, we investigated the involvement of GPx3 in adipose senescence. We determined that knockdown of GPx3 in adipose tissue by adeno-associated viruses impaired mitochondrial function in mice, increased susceptibility to obesity, and exacerbated adipose tissue senescence. Impairment of GPx3 may cause mitochondrial dysfunction through inner mitochondrial membrane disruption. Adipose reshaping management (cold stimulation and intermittent diet) counteracted the aging of tissues, with an increase in GPx3 expression. Overall metabolic improvement induced by cold stimulation was partially attenuated when GPx3 was depleted. GPx3 may be involved in adipose browning by interacting with UCP1, and GPx3 may be a limiting factor for intracellular reactive oxygen species (ROS) accumulation during stem cell browning. Collectively, these findings emphasise the importance of restoring the imbalanced redox state in adipose tissue to counteract aging and that GPx3 may be a potential target for maintaining mitochondrial homeostasis and longevity.

Strongly ROS-Correlated, Time-Dependent, and Selective Antiproliferative Effects of Synthesized Nano Vesicles on BRAF Mutant Melanoma Cells and Their Hyaluronic Acid-Based Hydrogel Formulation.

Cutaneous metastatic melanoma (CMM) is the most aggressive form of skin cancer with a poor prognosis. Drug-induced secondary tumorigenesis and the emergency of drug resistance worsen an already worrying scenario, thus rendering urgent the development of new treatments not dealing with mutable cellular processes. Triphenyl phosphonium salts (TPPSs), in addiction to acting as cytoplasmic membrane disruptors, are reported to be mitochondria-targeting compounds, exerting anticancer effects mainly by damaging their membranes and causing depolarization, impairing mitochondria functions and their DNA, triggering oxidative stress (OS), and priming primarily apoptotic cell death. TPP-based bola amphiphiles are capable of self-forming nanoparticles (NPs) with enhanced biological properties, as commonly observed for nanomaterials. Already employed in several other biomedical applications, the per se selective potent antibacterial effects of a TPP bola amphiphile have only recently been demonstrated on 50 multidrug resistant (MDR) clinical superbugs, as well as its exceptional and selective anticancer properties on sensitive and MDR neuroblastoma cells. Here, aiming at finding new molecules possibly developable as new treatments for counteracting CMM, the effects of this TPP-based bola amphiphile (BPPB) have been investigated against two BRAF mutants CMM cell lines (MeOV and MeTRAV) with excellent results (even IC50 = 49 nM on MeOV after 72 h treatment). With these findings and considering the low cytotoxicity of BPPB against different mammalian non-tumoral cell lines and red blood cells (RBCs, selectivity indexes up to 299 on MeOV after 72 h treatment), the possible future development of BPPB as topical treatment for CMM lesions was presumed. With this aim, a biodegradable hyaluronic acid (HA)-based hydrogel formulation (HA-BPPB-HG) was prepared without using any potentially toxic crosslinking agents simply by dispersing suitable amounts of the two ingredients in water and sonicating under gentle heating. HA-BPPB-HA was completely characterized, with promising outcomes such as high swelling capability, high porosity, and viscous elastic rheological behavior.

Probing the relevance of synergistic lipid membrane disruption to the eye irritation of binary mixed nonionic surfactants

Nonionic surfactant aerosols play a crucial role in many industries, but they can cause acute irritation to users’ eyes during spraying. This cytotoxic process is associated with corneal cell necrosis causing cell membrane disruption. Industrial grade surfactants are typically polydisperse mixtures described by their nominal chemical structure but how the polydispersity affects their interactions with cell membrane, remains largely unexplored. A better understanding could benefit product formulations to maximise their efficiency whilst minimising their toxicity to the users. In this study, poly-oxyethylene glycol monododecyl ethers (C12E4, C12E23) were used to form ideal binary surfactant mixtures. The cytotoxicities of mono and polydispersed surfactants towards human corneal epithelial cells were examined, followed by a series of biophysical characterisations of interactions between surfactants and model cell membranes. Notably, to probe the journey of individual C12E4 and C12E23 surfactant molecules across the cell membrane from a binary surfactant mixture, “two-colour” neutron reflection measurements were achieved via Hydrogen/Deuterium substitution. The relative distributions of C12E4 and C12E23 across cell membranes and their nanostructural conformations revealed a synergistic membrane-lytic ability initiated by surfactant mixing, with the more hydrophobic C12E4 exhibiting stronger membrane binding potency than the hydrophilic C12E23. The exact molar ratio of C12E4 against C12E23 in the mixture determined how the mixed surfactant interacted with the cell membrane, and how the process directly impacted cytotoxicity and eye irritation. Thus, the cytotoxicity of polydisperse surfactants is not the same as monodisperse surfactant of the same average structure. This work provides a useful basis for the assessment of surfactant mixing by balancing their efficiency and toxicity.

Antimicrobial Peptides with Spermicidal Activity as New Contraceptive Agents: Killing Two Birds with One Stone

Abstract: Antimicrobial peptides (AMPs) have emerged as promising candidates for dual-action contraceptive agents, offering both spermicidal and antimicrobial properties. This perspective explores the potential of AMPs in developing novel contraceptive technologies, focusing on their application in condom coatings and vaginal formulations. AMPs exert their effects through membrane disruption mechanisms, targeting both microbial pathogens and sperm cells. Their broad-spectrum activity against various microorganisms, coupled with spermicidal effects, makes them ideal for multipurpose prevention technologies. The incorporation of AMPs into condoms could enhance barrier protection, while vaginal applications offer non-hormonal, on-demand contraceptive options. However, challenges, such as potential vaginal irritation, microbiome disruption, and the need for long-term safety studies, must be addressed. Future research should focus on optimizing AMP selectivity, developing stable formulations, and conducting comprehensive efficacy and safety trials. The dual-action nature of AMPs aligns with the growing demand for integrated approaches to sexual and reproductive health, potentially revolutionizing contraception and STI prevention. By addressing current challenges and leveraging the unique properties of AMPs, researchers can develop a new generation of contraceptive products that offer improved efficacy, safety, and user acceptability.

Metallic and metallic oxide nanoparticles toxicity primarily targets the mitochondria of hepatocytes and renal cells.

Nanoparticles (NPs) are utilized in various applications, posing potential risks to human health, tissues, cells, and macromolecules. This study aimed to investigate the ultrastructural alterations in hepatocytes and renal tubular cells induced by metallic and metal oxide NPs. Adult healthy male Wistar albino rats (Rattus norvegicus) were divided into 6 (n = 7) control and 6 treated groups (n = 7). The rats in the treated groups exposed daily to silver NPs, gold NPs, zinc oxide NPs, silicon dioxide NPs, copper oxide NPs, and ferric oxide NPs for 35 days. The members of the control group for each corresponding NPs received the respective vehicle. Liver and kidney tissue blocks from all rats were processed for Transmission Electron Microscopy (TEM) examinations. The hepatocytes and renal tubular cells of all NPs-treated rats demonstrated mitochondrial ultrastructural alterations mainly cristolysis, swelling, membrane disruption, lucent matrices, matrices lysis, and electron-dense deposits. However, other organelles demonstrated injury but to a lesser extent in the form of shrunken nuclei, nuclear membrane indentation, endoplasmic reticulum fragmentation, cellular membranes enfolding, brush border microvilli disruption, lysosomal hyperplasia, ribosomes dropping, and peroxisome formation. One may conclude from the findings that the hepatocytes and the renal tubular cells mitochondria are the main targets for nanoparticles toxicity ending in mitochondrial disruption and cell injury. Further studies taking into account the relation of mitochondrial ultrastructural damage with a weakened antioxidant defense system induced by chronic exposure to nanomaterials are needed.

Antifungal effect of cinnamon essential oil against Penicillium oxalicum on rice noodles.

Plant essential oils have been extensively investigated for their application in food industry due to their broad antimicrobial spectrum and safety. However, rare studies investigated their application in decontaminating rice noodles from fungal contamination. In this study, the cinnamon essential oil was screened out among 12 species of plant essential oils, and its antifungal activity against Penicillium oxalicum isolated from rice noodles was investigated. Our study revealed that cinnamon essential oil inhibited the spore germination in a concentration-dependent manner, and a dosage of 0.025% (v/v) could entirely disable the spore germination. The disruption of the fungal plasma membrane was evidenced by the change of plasma membrane permeability and the leakage of cellular components. The cinnamon essential oil in vapor phase (0.00625% [v/v]) could totally inhibit the growth of fungi inoculated on rice noodles. In addition to the potential application in inactivating fungi germination on rice noodles, this study also demonstrated the feasibility of cinnamon essential as an environmental disinfectant. This study is the first report that cinnamon essential oil has been studied for decontaminating rice noodles from fungal contamination with P. oxalicum, which not only broadens the application field of plant essential oil but also provides an alternative approach for rice noodle preservation.

Isobavachalcone enhances sensitivity of colistin-resistant Klebsiella pneumoniae: In vitro and in vivo proof-of-concept studies

ObjectiveAntibiotic resistance poses a considerable worldwide concern, particularly in clinical environments where drug-resistant Gram-negative bacteria like Klebsiella pneumoniae (K. pneumoniae) present a major challenge. The objective of this research was to investigate the mechanisms by which isobavachalcone (IBC) restores the sensitivity of K. pneumoniae to colistin in vitro and to validate the synergistic therapeutic effect in vivo. ResultsThe results indicate that the combined administration of colistin and IBC exhibits a potent antibacterial effect both in vitro and in vivo. The in vitro concurrent administration of colistin and IBC resulted in increased membrane permeability, compromised cell integrity, diminished membrane fluidity, and disrupted membrane homeostasis. Additionally, this combination reduced biofilm production, inhibited the synthesis of the autoinducer factor, altered membrane potential, and affected levels of reactive oxygen species and adenosine triphosphate synthesis, ultimately leading to bacterial death. In vivo experiments on Galleria mellonella and mice demonstrated that the co-administration of colistin and IBC increased the survival rate and significantly reduced pathological damage compared to colistin alone. ConclusionThese results suggested that IBC effectively restores the sensitivity of colistin by inducing physical disruption of bacterial membranes and oxidative stress. The combination therapy of colistin and IBC presents a viable and safe strategy to combat drug-resistant K. pneumoniae-associated infections.

Osteocyte Sptbn1 Deficiency Alters Cell Survival and Mechanotransduction Following Formation of Plasma Membrane Disruptions (PMD) from Mechanical Loading.

We and others have shown that application of high-level mechanical loading promotes the formation of transient plasma membrane disruptions (PMD) which initiate mechanotransduction. We hypothesized that increasing osteocyte cell membrane fragility, by disrupting the cytoskeleton-associated protein β2-spectrin (Sptbn1), could alter osteocytic responses and bone adaptation to loading in a PMD-related fashion. In MLO-Y4 cells, treatment with the spectrin-disrupting agent diamide or knockdown of Sptbn1 via siRNA increased the number of PMD formed by fluid shear stress. Primary osteocytes from an osteocyte-targeted DMP1-Cre Sptbn1 conditional knockout (CKO) model mimicked trends seen with diamide and siRNA treatment and suggested the creation of larger PMD, which repaired more slowly, for a given level of stimulus. Post-wounding cell survival was impaired in all three models, and calcium signaling responses from the wounded osteocyte were mildly altered in Sptbn1 CKO cultures. Although Sptbn1 CKO mice did not demonstrate an altered skeletal phenotype as compared to WT littermates under baseline conditions, they showed a blunted increase in cortical thickness when subjected to an osteogenic tibial loading protocol as well as evidence of increased osteocyte death (increased lacunar vacancy) in the loaded limb after 2weeks of loading. The impaired post-wounding cell viability and impaired bone adaptation seen with Sptbn1 disruption support the existence of an important role for Sptbn1, and PMD formation, in osteocyte mechanotransduction and bone adaptation to mechanical loading.

Expanding the horizons of photodynamic therapy: Indium metalated pyridinyl-based trans-A2B2 porphyrin as novel anti-biofilm agents

Modern medicine is exploring new approaches to combat bacterial infections associated with antibiotic-resistant bacteria and biofilms. Among these, antimicrobial photodynamic therapy (aPDT) stands out for its ability to target pathogenic microbes effectively. In this study, we investigated the antimicrobial potential of the newly synthesized indium metalated pyridinyl-based trans-A2B2 porphyrin complexes, 1a,b and 2a,b. The dicationic porphyrins, 1b and 2b, exhibited remarkable aPDT efficacy against both S. aureus and E. coli planktonic forms. Further investigation into the antimicrobial effects of the cationic porphyrins against E. coli and S. aureus biofilms revealed that both complexes (1b and 2b) exhibited high efficacy in aPDT attributed to tert-butyl and thiophene groups that enhance photo-physicochemical properties and bacterial membrane accumulation. Scanning electron microscopy (SEM) showed disruption of cell membranes following light exposure. Our work highlights the potential of aPDT as an effective strategy for managing biofilms. By harnessing the power of these innovative compounds, we contribute to the ongoing battle against microbial threats.