Cdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila.

Cdk8 in Drosophila is the orthologue of vertebrate CDK8 and CDK19. These proteins have been shown to modulate transcriptional control by RNA polymerase II. We found that neuronal loss of Cdk8 severely reduces fly lifespan and causes bang sensitivity. Remarkably, these defects can be rescued by expression of human CDK19, found in the cytoplasm of neurons, suggesting a non-nuclear function of CDK19/Cdk8. Here we show that Cdk8 plays a critical role in the cytoplasm, with its loss causing elongated mitochondria in both muscles and neurons. We find that endogenous GFP-tagged Cdk8 can be found in both the cytoplasm and nucleus. We show that Cdk8 promotes the phosphorylation of Drp1 at S616, a protein required for mitochondrial fission. Interestingly, Pink1, a mitochondrial kinase implicated in Parkinson's disease, also phosphorylates Drp1 at the same residue. Indeed, overexpression of Cdk8 significantly suppresses the phenotypes observed in flies with low levels of Pink1, including elevated levels of ROS, mitochondrial dysmorphology, and behavioral defects. In summary, we propose that Pink1 and Cdk8 perform similar functions to promote Drp1-mediated fission.

Whole organism snRNA-seq reveals systemic peripheral changes in Alzheimer's Disease fly models.

Peripheral tissues become disrupted in Alzheimer's Disease (AD). However, a comprehensive understanding of how the expression of AD-associated toxic proteins, Aß42 and Tau, in neurons impacts the periphery is lacking. Using Drosophila, a prime model organism for studying aging and neurodegeneration, we generated the Alzheimer's Disease Fly Cell Atlas (AD-FCA): whole-organism single-nucleus transcriptomes of 219 cell types from adult flies neuronally expressing human Aß42 or Tau. In-depth analyses and functional data reveal impacts on peripheral sensory neurons by Aß42 and on various non-neuronal peripheral tissues by Tau, including the gut, fat body, and reproductive system. This novel AD atlas provides valuable insights into potential biomarkers and the intricate interplay between the nervous system and peripheral tissues in response to AD-associated proteins.

Comparative exploration of mammalian deafness gene homologues in the Drosophila auditory organ shows genetic correlation between insect and vertebrate hearing.

Johnston's organ, the Drosophila auditory organ, is anatomically very different from the mammalian organ of Corti. However, recent evidence indicates significant cellular and molecular similarities exist between vertebrate and invertebrate hearing, suggesting that Drosophila may be a useful platform to determine the function of the many mammalian deafness genes whose underlying biological mechanisms are poorly characterized. Our goal was a comprehensive screen of all known orthologues of mammalian deafness genes in the fruit fly to better understand conservation of hearing mechanisms between the insect and the fly and ultimately gain insight into human hereditary deafness. We used bioinformatic comparisons to screen previously reported human and mouse deafness genes and found that 156 of them have orthologues in Drosophila melanogaster. We used fluorescent imaging of T2A-GAL4 gene trap and GFP or YFP fluorescent protein trap lines for 54 of the Drosophila genes and found 38 to be expressed in different cell types in Johnston's organ. We phenotypically characterized the function of strong loss-of-function mutants in three genes expressed in Johnston's organ (Cad99C, Msp-300, and Koi) using a courtship assay and electrophysiological recordings of sound-evoked potentials. Cad99C and Koi were found to have significant courtship defects. However, when we tested these genes for electrophysiological defects in hearing response, we did not see a significant difference suggesting the courtship defects were not caused by hearing deficiencies. Furthermore, we used a UAS/RNAi approach to test the function of seven genes and found two additional genes, CG5921 and Myo10a, that gave a statistically significant delay in courtship but not in sound-evoked potentials. Our results suggest that many mammalian deafness genes have Drosophila homologues expressed in the Johnston's organ, but that their requirement for hearing may not necessarily be the same as in mammals.

Inactivation of Salmonella Typhimurium and Listeria monocytogenes on buckwheat seeds through combination treatment with plasma, vacuum packaging, and hot water.

AIMS: The objectives of this study were to evaluate the effect of combination treatment with cold plasma (CP), vacuum packaging (VP), and hot water (HW) on the inactivation of foodborne pathogens on buckwheat seeds, and determined the germination rates of seeds and the quality of sprouts following combination treatment. METHODS AND RESULTS: Buckwheat seeds inoculated with Salmonella Typhimurium and Listeria monocytogenes were treated with CP, HW, CP + HW, VP + HW, or CP + VP + HW. The germination rates of the HW-, CP + HW-, VP + HW-, and CP + VP + HW-treated seeds and the antioxidant activities and rutin contents of the CP + HW- and CP + VP + HW-treated sprouts were determined. HW, CP + HW, and CP + VP + HW were found to reduce the levels of the two pathogens to below the detection limit (1.0 log CFU g-1) at 70°C. However, HW and CP + HW significantly reduced the germination rate of buckwheat seeds. CP + VP + HW did not affect the germination rate of seeds nor the antioxidant activities and rutin content of buckwheat sprouts. CONCLUSIONS: These results indicate that CP + VP + HW can be used as a novel control method to reduce foodborne pathogens in seeds without causing quality deterioration.

Effects of Mitochondrial Transplantation on Transcriptomics in a Polymicrobial Sepsis Model.

Previously, we demonstrated that mitochondrial transplantation has beneficial effects in a polymicrobial sepsis model. However, the mechanism has not been fully investigated. Mitochondria have their own genes, and genomic changes in sepsis are an important issue in terms of pathophysiology, biomarkers, and therapeutic targets. To investigate the changes in transcriptomic features after mitochondrial transplantation in a polymicrobial sepsis model, we used a rat model of fecal slurry polymicrobial sepsis. Total RNA from splenocytes of sham-operated (SHAM, n = 10), sepsis-induced (SEPSIS, n = 7), and sepsis receiving mitochondrial transplantation (SEPSIS + MT, n = 8) samples was extracted and we conducted a comparative transcriptome-wide analysis between three groups. We also confirmed these results with qPCR. In terms of percentage of mitochondrial mapped reads, the SEPSIS + MT group had a significantly higher mapping ratio than the others. RT1-M2 and Cbln2 were identified as highly expressed in SEPSIS + MT compared with SEPSIS. Using SHAM expression levels as another control variable, we further identified six genes (Fxyd4, Apex2l1, Kctd4, 7SK, SNORD94, and SNORA53) that were highly expressed after sepsis induction and observed that their expression levels were attenuated by mitochondrial transplantation. Changes in transcriptomic features were identified after mitochondrial transplantation in sepsis. This might provide a hint for exploring the mechanism of mitochondrial transplantation in sepsis.

Continuous synthesis of artificial speech sounds from human cortical surface recordings during silent speech production.

Objective. Brain-computer interfaces can restore various forms of communication in paralyzed patients who have lost their ability to articulate intelligible speech. This study aimed to demonstrate the feasibility of closed-loop synthesis of artificial speech sounds from human cortical surface recordings during silent speech production.Approach. Ten participants with intractable epilepsy were temporarily implanted with intracranial electrode arrays over cortical surfaces. A decoding model that predicted audible outputs directly from patient-specific neural feature inputs was trained during overt word reading and immediately tested with overt, mimed and imagined word reading. Predicted outputs were later assessed objectively against corresponding voice recordings and subjectively through human perceptual judgments.Main results. Artificial speech sounds were successfully synthesized during overt and mimed utterances by two participants with some coverage of the precentral gyrus. About a third of these sounds were correctly identified by naïve listeners in two-alternative forced-choice tasks. A similar outcome could not be achieved during imagined utterances by any of the participants. However, neural feature contribution analyses suggested the presence of exploitable activation patterns during imagined speech in the postcentral gyrus and the superior temporal gyrus. In future work, a more comprehensive coverage of cortical surfaces, including posterior parts of the middle frontal gyrus and the inferior frontal gyrus, could improve synthesis performance during imagined speech.Significance.As the field of speech neuroprostheses is rapidly moving toward clinical trials, this study addressed important considerations about task instructions and brain coverage when conducting research on silent speech with non-target participants.

Aging Fly Cell Atlas identifies exhaustive aging features at cellular resolution.

Aging is characterized by a decline in tissue function, but the underlying changes at cellular resolution across the organism remain unclear. Here, we present the Aging Fly Cell Atlas, a single-nucleus transcriptomic map of the whole aging Drosophila. We characterized 163 distinct cell types and performed an in-depth analysis of changes in tissue cell composition, gene expression, and cell identities. We further developed aging clock models to predict fly age and show that ribosomal gene expression is a conserved predictive factor for age. Combining all aging features, we find distinctive cell type-specific aging patterns. This atlas provides a valuable resource for studying fundamental principles of aging in complex organisms.

The Effects of Mitochondrial Transplantation on Sepsis Depend on the Type of Cell from Which They Are Isolated.

Previously, we have shown that mitochondrial transplantation in the sepsis model has immune modulatory effects. The mitochondrial function could have different characteristics dependent on cell types. Here, we investigated whether the effects of mitochondrial transplantation on the sepsis model could be different depending on the cell type, from which mitochondria were isolated. We isolated mitochondria from L6 muscle cells, clone 9 liver cells and mesenchymal stem cells (MSC). We tested the effects of mitochondrial transplantation using in vitro and in vivo sepsis models. We used the LPS stimulation of THP-1 cell, a monocyte cell line, as an in vitro model. First, we observed changes in mitochondrial function in the mitochondria-transplanted cells. Second, we compared the anti-inflammatory effects of mitochondrial transplantation. Third, we investigated the immune-enhancing effects using the endotoxin tolerance model. In the in vivo polymicrobial fecal slurry sepsis model, we examined the survival and biochemical effects of each type of mitochondrial transplantation. In the in vitro LPS model, mitochondrial transplantation with each cell type improved mitochondrial function, as measured by oxygen consumption. Among the three cell types, L6-mitochondrial transplantation significantly enhanced mitochondrial function. Mitochondrial transplantation with each cell type reduced hyper-inflammation in the acute phase of in vitro LPS model. It also enhanced immune function during the late immune suppression phase, as shown by endotoxin tolerance. These functions were not significantly different between the three cell types of origin for mitochondrial transplantation. However, only L6-mitochondrial transplantation significantly improved survival compared to the control in the polymicrobial intraabdominal sepsis model. The effects of mitochondria transplantation on both in vitro and in vivo sepsis models differed depending on the cell types of origin for mitochondria. L6-mitochondrial transplantation might be more beneficial in the sepsis model.

Very-long-chain fatty acids induce glial-derived sphingosine-1-phosphate synthesis, secretion, and neuroinflammation.

VLCFAs (very-long-chain fatty acids) are the most abundant fatty acids in myelin. Hence, during demyelination or aging, glia are exposed to higher levels of VLCFA than normal. We report that glia convert these VLCFA into sphingosine-1-phosphate (S1P) via a glial-specific S1P pathway. Excess S1P causes neuroinflammation, NF-κB activation, and macrophage infiltration into the CNS. Suppressing the function of S1P in fly glia or neurons, or administration of Fingolimod, an S1P receptor antagonist, strongly attenuates the phenotypes caused by excess VLCFAs. In contrast, elevating the VLCFA levels in glia and immune cells exacerbates these phenotypes. Elevated VLCFA and S1P are also toxic in vertebrates based on a mouse model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). Indeed, reducing VLCFA with bezafibrate ameliorates the phenotypes. Moreover, simultaneous use of bezafibrate and fingolimod synergizes to improve EAE, suggesting that lowering VLCFA and S1P is a treatment avenue for MS.

Process Controlled Ruthenium on 2D Engineered V-MXene via Atomic Layer Deposition for Human Healthcare Monitoring.

In searching for unique and unexplored 2D materials, the authors try to investigate for the very first time the use of delaminated V-MXene coupled with precious metal ruthenium (Ru) through atomic layer deposition (ALD) for various contact and noncontact mode of real-time temperature sensing applications at the human-machine interface. The novel delaminated V-MXene (DM-V2 CTx ) engineered ruthenium-ALD (Ru-ALD) temperature sensor demonstrates a competitive sensing performance of 1.11% °C-1 as of only V-MXene of 0.42% °C-1 . A nearly threefold increase in sensing and reversibility performance linked to the highly ordered few-layered V-MXene and selective, well-controlled Ru atomic doping by ALD for the successful formation of Ru@DM-V2 CTX heterostructure. The advanced heterostructure formation, the mechanism, and the role of Ru have been comprehensively investigated by ultra-high-resolution transmission/scanning transmission electron microscopies coupled with next-generation spherical aberration correction technology and fast, accurate elemental mapping quantifications, also by ultraviolet photoelectron spectroscopy. To the knowledge, this work is the first to use the novel, optimally processed V-MXene over conventionally used Ti-MXene and its surface-internal structure engineering by Ru-ALD process-based temperature-sensing devices function and operational demonstrations. The current work could potentially motivate the development of multifunctional, future, next-generation, safe, personal healthcare electronic devices by the industrially scalable ALD technique.

Serial Change of Endotoxin Tolerance in a Polymicrobial Sepsis Model.

Immune suppression is known to occur during sepsis. Endotoxin tolerance is considered a mechanism of immune suppression in sepsis. However, the timing and serial changes in endotoxin tolerance have not been fully investigated. In this study, we investigated serial changes in endotoxin tolerance in a polymicrobial sepsis model. Herein, we used a rat model of fecal slurry polymicrobial sepsis. After induction of sepsis, endotoxin tolerance of peripheral blood mononuclear cells (PBMCs) and splenocytes was measured at various time points (6 h, 12 h, 24 h, 48 h, 72 h, 5 days, and 7 days), through the measurement of TNF-α production after stimulation with lipopolysaccharide (LPS) in an ex vivo model. At each time point, we checked for plasma tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 levels. Moreover, we analyzed reactive oxygen species (ROS) as measured by 2',7'-dichlorodihydrofluorescein, plasma lactate, serum alanine aminotransferase (ALT), and creatinine levels. Nuclear factor (NF)-κB, IL-1 receptor-associated kinase (IRAK)-M, and cleaved caspase 3 levels were measured in the spleen. Endotoxin tolerance, measured by TNF-α production stimulated through LPS in PBMCs and splenocytes, was induced early in the sepsis model, starting from 6 h after sepsis. It reached a nadir at 24 to 48 h after sepsis, and then started to recover. Endotoxin tolerance was more prominent in the severe sepsis model. Plasma cytokines peaked at time points ranging from 6 to 12 h after sepsis. ROS levels peaked at 12 h and then decreased. Lactate, ALT, and serum creatinine levels increased up to 24 to 48 h, and then decreased. Phosphorylated p65 and IRAK-M levels of spleen increased up to 12 to 24 h and then decreased. Apoptosis was prominent 48 h after sepsis, and then recovered. In the rat model of polymicrobial sepsis, endotoxin tolerance occurred earlier and started to recover from 24 to 48 h after sepsis.

A simple and novel equation to estimate the degree of bleeding in haemorrhagic shock: mathematical derivation and preliminary in vivo validation.

Determining blood loss [100% - RBV (%)] is challenging in the management of haemorrhagic shock. We derived an equation estimating RBV (%) via serial haematocrits (Hct1, Hct2) by fixing infused crystalloid fluid volume (N) as [0.015 × body weight (g)]. Then, we validated it in vivo. Mathematically, the following estimation equation was derived: RBV (%) = 24k / [(Hct1 / Hct2) - 1]. For validation, nonongoing haemorrhagic shock was induced in Sprague-Dawley rats by withdrawing 20.0%-60.0% of their total blood volume (TBV) in 5.0% intervals (n = 9). Hct1 was checked after 10 min and normal saline N cc was infused over 10 min. Hct2 was checked five minutes later. We applied a linear equation to explain RBV (%) with 1 / [(Hct1 / Hct2) - 1]. Seven rats losing 30.0%-60.0% of their TBV suffered shock persistently. For them, RBV (%) was updated as 5.67 / [(Hct1 / Hct2) - 1] + 32.8 (95% confidence interval [CI] of the slope: 3.14-8.21, p = 0.002, R2 = 0.87). On a Bland-Altman plot, the difference between the estimated and actual RBV was 0.00 ± 4.03%; the 95% CIs of the limits of agreements were included within the pre-determined criterion of validation (< 20%). For rats suffering from persistent, non-ongoing haemorrhagic shock, we derived and validated a simple equation estimating RBV (%). This enables the calculation of blood loss via information on serial haematocrits under a fixed N. Clinical validation is required before utilisation for emergency care of haemorrhagic shock.

Effects of Glucocorticoid Therapy on Sepsis Depend Both on the Dose of Steroids and on the Severity and Phase of the Animal Sepsis Model.

Steroids are currently being used in sepsis, particularly in septic shock. However, clinical trials to date have shown contradictory results. This could be attributed to the different patient endotypes and steroid doses, which have also contributed to the inconclusive results. We investigated the effects of glucocorticoid therapy on sepsis in a polymicrobial sepsis model in a variety of settings, such as steroid dose, severity, and sepsis phase. We used a rat model of fecal slurry polymicrobial sepsis. First, we investigated the optimum dose of steroids in a sepsis model. We administered different doses of dexamethasone after sepsis induction (0.1DEX; 0.1 mg/kg, 0.2DEX; 0.2 mg/kg, 5DEX; 5 mg/kg). Second, we used two different severities of the fecal slurry polymicrobial sepsis rat model to examine the effects of the steroids. A moderate or severe model was defined as a survival rate of approximately 70% and 30%, respectively. Third, we administered steroids in an early (1 h after sepsis induction) or late phase (25 h after sepsis). In all the experiments, we investigated the survival rates. In the determined optimal model and settings, we measured serum lactate, alanine transferase (ALT), creatinine, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-10, and arterial blood gas. We evaluated the bacterial burden in the blood and spleen. Endotoxin tolerance of peripheral blood mononuclear cells (PBMCs) and splenocytes was also investigated to determine the level of immune suppression 24 h after sepsis by measuring TNF-α production after stimulation with lipopolysaccharide (LPS) in an ex vivo model. Early treatment of 0.2 mg/kg dexamethasone in a severe sepsis model showed the best beneficial effects. In moderate- or late-phase sepsis, there was no survival gain with steroid treatment. DEX0.2 group showed less acute kidney injury manifested by serum creatinine and blood urea nitrogen. DEX decreased the levels of cytokines, including IL-6, IL-10, and TNF-α. Colony-forming units were significantly decreased in the blood when administered with dexamethasone. Endotoxin tolerance was not significantly different between the DEX0.2 and control groups. In conclusion, early treatment of 0.2 mg/kg dexamethasone improved the outcomes of rats in a severe sepsis model.

Effect of Surrounding Solvents on Interfacial Behavior of Gallium-Based Liquid Metal Droplets.

Gallium-based liquid metal (GaLM) alloys have been extensively used in applications ranging from electronics to drug delivery systems. To broaden the understanding and applications of GaLMs, this paper discusses the interfacial behavior of eutectic gallium-indium liquid metal (EGaIn) droplets in various solvents. No significant difference in contact angles of EGaIn is observed regardless of the solvent types. However, the presence or absence of a conical tip on EGaIn droplets after dispensing could indirectly support that the interfacial energy of EGaIn is relatively low in non-polar solvents. Furthermore, in the impact experiments, the EGaIn droplet bounces off in the polar solvents of water and dimethyl sulfoxide (DMSO), whereas it spreads and adheres to the substrate in the non-polar solvents of hexane and benzene. Based on the dimensionless We number, it can be stated that the different impact behavior depending on the solvent types is closely related to the interfacial energy of EGaIn in each solvent. Finally, the contact angles and shapes of EGaIn droplets in aqueous buffer solutions with different pH values (4, 7, and 10) are compared. In the pH 10 buffer solution, the EGaIn droplet forms a spherical shape without the conical tip, representing the high surface energy. This is associated with the dissolution of the "interfacial energy-reducing" surface layer on EGaIn, which is supported by the enhanced concentration of gallium ion released from EGaIn in the buffer solution.

Pulsed Electrical Stimulation Enhances Consistency of Directional Migration of Adipose-Derived Stem Cells.

Electrical stimulation is a well-known strategy for regulating cell behavior, both in pathological and physiological processes such as wound healing, tissue regeneration, and embryonic development. Electrotaxis is the directional migration of cells toward the cathode or anode when subjected to electrical stimulation. In this study, we investigated the conditions for enhanced directional migration of electrically stimulated adipose-derived stem cells (ADSCs) during prolonged culture, using a customized agar-salt electrotaxis chamber. Exposure of ADSCs to a 1200 µA electric current for 3 h, followed by cessation of stimulation for 6 h and resumed stimulation for a further 3 h, increased directional cell migration toward the anode without inducing cell death. Moreover, Golgi polarization maintained the direction of polarity parallel to the direction of cell movement. Herein, we demonstrated that a pulsed electric current is sufficient to trigger directional migration of ADSCs in long-term culture while maintaining cell viability.

A collagen-AS/εPLL bilayered artificial substitute regulates anti-inflammation and infection for initial inflamed wound healing.

Despite the development of advanced tissue engineering substitutes, inflammation is still a significant problem that can arise from inflamed burn injuries, chronic wounds, or microbial diseases. Although topical wound dressing accelerates healing by minimizing or preventing the consequences of skin inflammation, there remains a need for the development of a novel substitute scaffold that can effectively eliminate immoderate inflammation and infection in the initial phase of the healing meachanism. In this study, an artificial skin substitute scaffold fabricated with asiaticoside (AS) and epsilon-poly-L-lysine (εPLL) was prepared. Upon the release of these bioactive compounds, they accelerate wound healing and inhibit any bacterial infection at the wound site. We determined whether AS and εPLL exhibit anti-inflammatory and bactericidal effects through different mechanisms. Collectively, the collagen-AS/εPLL artificial skin substitute could be a significant therapeutic agent for scar-less rapid wound healing (without infection and inflammation) of initially-inflamed full-thickness wounds.

Sterilization of sealed PVDF pouches containing decellularized scaffold by electrical stimulation.

A terminal sterilization process for tissue engineering products, such as allografts and biomaterials is necessary to ensure complete removal of pathogenic microorganisms such as the bacteria, fungi, and viruses. However, it can be difficult to sterilize allografts and artificial tissue models packaged in wet conditions without deformation. In this study, we investigated the sterilization effects of electrical stimulation (ES) and assessed its suitability by evaluating sterility assurance levels in pouches at a constant current. Stability of polyvinylidene fluoride pouches was determined by a sterility test performed after exposure to five microorganisms (Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans) for 5 days; the sterility test was also performed with decellularized human dermal tissues inoculated with the five microorganisms. Sterilization using ES inactivated microorganisms both inside and outside of sealed pouches and caused no damage to the packaged tissue. Our results support the development of a novel system that involves ES sterilization for packaging of implantable biomaterials and human derived materials.

Phosphatidylserine synthase plays an essential role in glia and affects development, as well as the maintenance of neuronal function.

Phosphatidylserine (PS) is an integral component of eukaryotic cell membranes and organelles. The Drosophila genome contains a single PS synthase (PSS)-encoding gene (Pss) homologous to mammalian PSSs. Flies with Pss loss-of-function alleles show a reduced life span, increased bang sensitivity, locomotor defects, and vacuolated brain, which are the signs associated with neurodegeneration. We observed defective mitochondria in mutant adult brain, as well as elevated production of reactive oxygen species, and an increase in autophagy and apoptotic cell death. Intriguingly, glial-specific knockdown or overexpression of Pss alters synaptogenesis and axonal growth in the larval stage, causes developmental arrest in pupal stages, and neurodegeneration in adults. This is not observed with pan-neuronal up- or down-regulation. These findings suggest that precisely regulated expression of Pss in glia is essential for the development and maintenance of brain function. We propose a mechanism that underlies these neurodegenerative phenotypes triggered by defective PS metabolism.

An effective method to generate controllable levels of ROS for the enhancement of HUVEC proliferation using a chlorin e6-immobilized PET film as a photo-functional biomaterial.

Reactive oxygen species (ROS) are byproducts of cellular metabolism; they play a significant role as secondary messengers in cell signaling. In cells, high concentrations of ROS induce apoptosis, senescence, and contact inhibition, while low concentrations of ROS result in angiogenesis, proliferation, and cytoskeleton remodeling. Thus, controlling ROS generation is an important factor in cell biology. We designed a chlorin e6 (Ce6)-immobilized polyethylene terephthalate (PET) film (Ce6-PET) to produce extracellular ROS under red-light irradiation. The application of Ce6-PET films can regulate the generation of ROS by altering the intensity of light-emitting diode sources. We confirmed that the Ce6-PET film could effectively promote cell growth under irradiation at 500 µW/cm2 for 30 min in human umbilical vein endothelial cells. We also found that the Ce6-PET film is more efficient in generating ROS than a Ce6-incorporated polyurethane film under the same conditions. Ce6-PET fabrication shows promise for improving the localized delivery of extracellular ROS and regulating ROS formation through the optimization of irradiation intensity.

Asiaticoside and polylysine-releasing collagen complex for effectively reducing initial inflammatory response using inflamed induced in vitro model.

Inflammation is a significant clinical problem that can arise from full-thickness wounds or burn injuries or microbial disease. Although topical wound healing substances could promote rapid wound healing by preventing or reducing the consequences of inflammation, there still remains a need for the development of novel substances that can effectively reduce infection and inflammation in initial wound healing phase. In this study, collagen was combined with asiaticoside (AS) and ε-poly-l-lysine (εPLL). This complex was then applied to in vitro models of infection and inflammation. Collagen-AS coatings inhibited the initial inflammatory response to LPS through a sustained release of AS, and a bilayer coating-εPLL showed a notable antimicrobial effect using microbial infection test. In this study, we determined whether asiaticoside and εPLL have anti-inflammatory and antibacterial effects through different mechanisms. Collectively, the collagen-AS/εPLL complex indicated great therapeutic potentials for accelerate wound healing and the complex may be considered as a artificial scaffold substitute product to full-thickness wound healing.