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Nature Communications May 2024The major ampullate Spidroin 1 (MaSp1) is the main protein of the dragline spider silk. The C-terminal (CT) domain of MaSp1 is crucial for the self-assembly into fibers...
The major ampullate Spidroin 1 (MaSp1) is the main protein of the dragline spider silk. The C-terminal (CT) domain of MaSp1 is crucial for the self-assembly into fibers but the details of how it contributes to the fiber formation remain unsolved. Here we exploit the fact that the CT domain can form silk-like fibers by itself to gain knowledge about this transition. Structural investigations of fibers from recombinantly produced CT domain from E. australis MaSp1 reveal an α-helix to β-sheet transition upon fiber formation and highlight the helix N4 segment as most likely to initiate the structural conversion. This prediction is corroborated by the finding that a peptide corresponding to helix N4 has the ability of pH-induced conversion into β-sheets and self-assembly into nanofibrils. Our results provide structural information about the CT domain in fiber form and clues about its role in triggering the structural conversion of spidroins during fiber assembly.
Topics: Fibroins; Animals; Spiders; Silk; Protein Domains; Amino Acid Sequence; Protein Conformation, beta-Strand; Recombinant Proteins; Hydrogen-Ion Concentration; Protein Conformation, alpha-Helical; Protein Structure, Secondary
PubMed: 38821983
DOI: 10.1038/s41467-024-49111-5 -
NanoImpact May 2024Nanoplastics are anticipated to be ubiquitous in various environmental compartments. However, challenges in analytical methods hinder our understanding of risks related...
Nanoplastics are anticipated to be ubiquitous in various environmental compartments. However, challenges in analytical methods hinder our understanding of risks related to specific nanplastics characteristics such as size and chemical compositions, and interactions between nanoplastics and microorganisms. In this study, we applied fit-for-purpose analytical methods and techniques to understand how nanoplastic chemical composition influences their interaction with bacteria collected from activated sludge. When exposed to polystyrene (PS) and polyvinyl chloride (PVC) nanoplastics for 5 days, the nanoplastics attached to the bacteria. Specifically, on day 1, there was a significant predominance of PS nanoplastics over PVC ones of similar size and shape, possibly due to differences in their chemical composition. After 5 days, there is a substantial decrease in nanoplastics attached to bacteria, suggesting bacterial defence mechanisms may reduce particles attachment over time. The overall bacterial community structure demonstrated a high degree of resilience. This resilience highlights the ability of microbial communities to maintain their structure despite nanoplastic stressors, as evidenced by consistent alpha diversity, PCoA, and PERMANOVA results. Understanding these mechanisms is crucial for assessing nanoplastic fate and thus environmental impacts.
PubMed: 38821169
DOI: 10.1016/j.impact.2024.100514 -
RSC Advances May 2024The synthesis techniques used for metal oxide semiconductors strongly influence their chemical, physical and gas sensing characteristics. In this context, hematite...
The synthesis techniques used for metal oxide semiconductors strongly influence their chemical, physical and gas sensing characteristics. In this context, hematite (α-FeO) nanoparticles (NPs) were synthesized using two different techniques, namely, sol-gel (named H) and Pechini sol-gel (named H). The average crystallite size and surface area were 15 nm and 76 m g and 20 nm and 57 m g for H and H, respectively. Morphological studies showed that the H material was composed of ellipsoid-shaped particles, while the H material had peanut-shaped particles with open pores and channels. The comparison between the sensing performances of H and H toward ethanol indicated H to be a better sensing material for ethanol detection. The H sensor exhibited a response of 12 toward 500 ppm ethanol at 250 °C, a fast response time of 5 s and excellent selectivity. The enhanced characteristics were mainly related to the peculiar morphology with a porous nature, which led to more gas adsorption and diffusion. In addition to shape influence, the size of NPs also has an effect on the gas sensing performance. In fact, a decrease in the crystallite size led to an increase in the surface area of the material where the gas molecule-sensing layer interaction took place. The increase in the surface area created more interaction sites, and thus the sensitivity was improved. From these results, the H sensor can be regarded as a promising candidate for ethanol detection.
PubMed: 38818359
DOI: 10.1039/d4ra02338b -
World Journal of Stem Cells May 2024Atherosclerosis (AS), a chronic inflammatory disease of blood vessels, is a major contributor to cardiovascular disease. Dental pulp stem cells (DPSCs) are capable of...
BACKGROUND
Atherosclerosis (AS), a chronic inflammatory disease of blood vessels, is a major contributor to cardiovascular disease. Dental pulp stem cells (DPSCs) are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflammation-related diseases. Hepatocyte growth factor (HGF) is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases.
AIM
To modify DPSCs with HGF (DPSC-HGF) and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout (ApoE) mouse model and an cellular model.
METHODS
ApoE mice were fed with a high-fat diet (HFD) for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs (DPSC-Null) through tail vein at weeks 4, 7, and 11, respectively, and the therapeutic efficacy and mechanisms were analyzed by histopathology, flow cytometry, lipid and glucose measurements, real-time reverse transcription polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay at the different time points of the experiment. An inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells (HAOECs), and indirect co-cultured with supernatant of DPSC-Null (DPSC-Null-CM) or DPSC-HGF-CM, and the effect and mechanisms were analyzed by flow cytometry, RT-PCR and western blot. Nuclear factor-κB (NF-κB) activators and inhibitors were also used to validate the related signaling pathways.
RESULTS
DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors, and the percentage of macrophages in the aorta, and DPSC-HGF treatment had more pronounced effects. DPSCs treatment had no effect on serum lipoprotein levels. The FACS results showed that DPSCs treatment reduced the percentages of monocytes, neutrophils, and M1 macrophages in the peripheral blood and spleen. DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-α stimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway.
CONCLUSION
This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE mice on a HFD, and could be of greater value in stem cell-based treatments for AS.
PubMed: 38817328
DOI: 10.4252/wjsc.v16.i5.575 -
PLoS Neglected Tropical Diseases May 2024Photobiomodulation has exhibited promise in mitigating the local effects induced by Bothrops snakebite envenoming; however, the mechanisms underlying this protection are...
BACKGROUND
Photobiomodulation has exhibited promise in mitigating the local effects induced by Bothrops snakebite envenoming; however, the mechanisms underlying this protection are not yet fully understood. Herein, the effectiveness of photobiomodulation effects on regenerative response of C2C12 myoblast cells following exposure to Bothrops jararacussu venom (BjsuV), as well as the mechanisms involved was investigated.
METHODOLOGY/PRINCIPAL FINDINGS
C2C12 myoblast cells were exposed to BjsuV (12.5 μg/mL) and irradiated once for 10 seconds with laser light of 660 nm (14.08 mW; 0.04 cm2; 352 mW/cm2) or 780 nm (17.6 mW; 0.04 cm2; 440 mW/ cm2) to provide energy densities of 3.52 and 4.4 J/cm2, and total energies of 0.1408 and 0.176 J, respectively. Cell migration was assessed through a wound-healing assay. The expression of MAPK p38-α, NF-Кβ, Myf5, Pax-7, MyoD, and myogenin proteins were assessed by western blotting analysis. In addition, interleukin IL1-β, IL-6, TNF-alfa and IL-10 levels were measured in the supernatant by ELISA. The PBM applied to C2C12 cells exposed to BjsuV promoted cell migration, increase the expression of myogenic factors (Pax7, MyF5, MyoD and myogenin), reduced the levels of proinflammatory cytokines, IL1-β, IL-6, TNF-alfa, and increased the levels of anti-inflammatory cytokine IL-10. In addition, PBM downregulates the expression of NF-kB, and had no effect on p38 MAKP.
CONCLUSION/SIGNIFICANCE
These data demonstrated that protection of the muscle cell by PBM seems to be related to the increase of myogenic factors as well as the modulation of inflammatory mediators. PBM therapy may offer a new therapeutic strategy to address the local effects of snakebite envenoming by promoting muscle regeneration and reducing the inflammatory process.
Topics: Animals; Bothrops; Myoblasts; Mice; Low-Level Light Therapy; Cytokines; Cell Line; Crotalid Venoms; Myogenin; PAX7 Transcription Factor; NF-kappa B; MyoD Protein; Cell Movement; Myogenic Regulatory Factor 5; p38 Mitogen-Activated Protein Kinases; Snake Bites; Venomous Snakes
PubMed: 38814992
DOI: 10.1371/journal.pntd.0012227 -
Cell Death & Disease May 2024The targeted elimination of radio- or chemotherapy-induced senescent cells by so-called senolytic substances represents a promising approach to reduce tumor relapse as...
The targeted elimination of radio- or chemotherapy-induced senescent cells by so-called senolytic substances represents a promising approach to reduce tumor relapse as well as therapeutic side effects such as fibrosis. We screened an in-house library of 178 substances derived from marine sponges, endophytic fungi, and higher plants, and determined their senolytic activities towards DNA damage-induced senescent HCT116 colon carcinoma cells. The Pan-PI3K-inhibitor wortmannin and its clinical derivative, PX-866, were identified to act as senolytics. PX-866 potently induced apoptotic cell death in senescent HCT116, MCF-7 mammary carcinoma, and A549 lung carcinoma cells, independently of whether senescence was induced by ionizing radiation or by chemotherapeutics, but not in proliferating cells. Other Pan-PI3K inhibitors, such as the FDA-approved drug BAY80-6946 (Copanlisib, Aliqopa®), also efficiently and specifically eliminated senescent cells. Interestingly, only the simultaneous inhibition of both PI3K class I alpha (with BYL-719 (Alpelisib, Piqray®)) and delta (with CAL-101 (Idelalisib, Zydelig®)) isoforms was sufficient to induce senolysis, whereas single application of these inhibitors had no effect. On the molecular level, inhibition of PI3Ks resulted in an increased proteasomal degradation of the CDK inhibitor p21 in all tumor cell lines analyzed. This led to a timely induction of apoptosis in senescent tumor cells. Taken together, the senolytic properties of PI3K-inhibitors reveal a novel dimension of these promising compounds, which holds particular potential when employed alongside DNA damaging agents in combination tumor therapies.
Topics: Humans; Cellular Senescence; Cyclin-Dependent Kinase Inhibitor p21; HCT116 Cells; Proteasome Endopeptidase Complex; Apoptosis; Phosphoinositide-3 Kinase Inhibitors; MCF-7 Cells; Proteolysis; A549 Cells; Wortmannin; Senotherapeutics; Class I Phosphatidylinositol 3-Kinases; DNA Damage; Pyrimidines; Quinazolines
PubMed: 38811535
DOI: 10.1038/s41419-024-06755-x -
Pharmacological Research Jul 2024Coronavirus disease 2019 (COVID-19) affected people worldwide, and fever is one of the major symptoms of this disease. Although Acetaminophen (APAP) is a common...
Coronavirus disease 2019 (COVID-19) affected people worldwide, and fever is one of the major symptoms of this disease. Although Acetaminophen (APAP) is a common fever-reducing medication, it can also mediate liver injury. However, the role of PGC-1α in regulating mitochondrial quality control by lactate dehydrogenase B (LDHB), a vital enzyme catalyzing the conversion of lactate to pyruvate, in APAP-induced hepatotoxicity, is unclear. Here, gene expression omnibus data of patients with APAP-induced liver injury were used to explore gene expression profiles. AML12 cells and C57/BL6 mice were used to establish models of APAP-induced acute liver injury. SIRT1 and PGC-1α were overexpressed in vitro via lentiviral transfection to establish stable cell lines. The results showed that APAP treatment decreased SIRT1/PGC-1α/LDHB expression and increased protein lactylation, mitochondrial lactate levels, and pathological damage in liver mitochondria. PGC-1α upregulation or activation ameliorated APAP-induced damage in the cells and liver. Furthermore, PGC-1α overexpression increased LDHB synthesis, reduced lactylation, and induced a switch from lactate to pyruvate production. These results suggest that PGC-1α and LDHB play a role in APAP-induced liver injury by regulating mitochondrial quality control and lactate metabolic reprogramming. Therefore, the PGC-1α/LDHB axis is a potential therapeutic target for APAP-induced liver injury.
Topics: Animals; Acetaminophen; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Chemical and Drug Induced Liver Injury; Mice, Inbred C57BL; Mice; Humans; Male; L-Lactate Dehydrogenase; Lactic Acid; Mitochondrial Proteins; Cell Line; Mitochondria, Liver; Sirtuin 1; Isoenzymes
PubMed: 38810904
DOI: 10.1016/j.phrs.2024.107228 -
Physics and Imaging in Radiation... Apr 2024Dynamic trajectory radiotherapy (DTRT) has been shown to improve healthy tissue sparing compared to volumetric arc therapy (VMAT). This study aimed to assess and compare...
BACKGROUND AND PURPOSE
Dynamic trajectory radiotherapy (DTRT) has been shown to improve healthy tissue sparing compared to volumetric arc therapy (VMAT). This study aimed to assess and compare the robustness of DTRT and VMAT treatment-plans for head and neck (H&N) cancer to patient-setup (PS) and machine-positioning uncertainties.
MATERIALS AND METHODS
The robustness of DTRT and VMAT plans previously created for 46 H&N cases, prescribed 50-70 Gy to 95 % of the planning-target-volume, was assessed. For this purpose, dose distributions were recalculated using Monte Carlo, including uncertainties in PS (translation and rotation) and machine-positioning (gantry-, table-, collimator-rotation and multi-leaf collimator (MLC)). Plan robustness was evaluated by the uncertainties' impact on normal tissue complication probabilities (NTCP) for xerostomia and dysphagia and on dose-volume endpoints. Differences between DTRT and VMAT plan robustness were compared using Wilcoxon matched-pair signed-rank test ( = 5 %).
RESULTS
Average NTCP for moderate-to-severe xerostomia and grade ≥ II dysphagia was lower for DTRT than VMAT in the nominal scenario (0.5 %, p = 0.01; 2.1 %, p < 0.01) and for all investigated uncertainties, except MLC positioning, where the difference was not significant. Average differences compared to the nominal scenario were 3.5 Gy for rotational PS ( 3°) and machine-positioning ( 2°) uncertainties, <7 Gy for translational PS uncertainties ( 5 mm) and < 20 Gy for MLC-positioning uncertainties ( 5 mm).
CONCLUSIONS
DTRT and VMAT plan robustness to the investigated uncertainties depended on uncertainty direction and location of the structure-of-interest to the target. NTCP remained on average lower for DTRT than VMAT even when considering uncertainties.
PubMed: 38808098
DOI: 10.1016/j.phro.2024.100586 -
Frontiers in Public Health 2024Treatments that currently exist in the strategic national stockpile for acute radiation syndrome (ARS) focus on the hematopoietic subsyndrome, with no treatments on...
INTRODUCTION
Treatments that currently exist in the strategic national stockpile for acute radiation syndrome (ARS) focus on the hematopoietic subsyndrome, with no treatments on gastrointestinal (GI)-ARS. While the gut microbiota helps maintain host homeostasis by mediating GI epithelial and mucosal integrity, radiation exposure can alter gut commensal microbiota which may leave the host susceptible to opportunistic pathogens and serious sequelae such as sepsis. To mitigate the effects of hematopoietic ARS irradiation, currently approved treatments exist in the form of colony stimulating factors and antibiotics: however, there are few studies examining how these therapeutics affect GI-ARS and the gut microbiota. The aim of our study was to examine the longitudinal effects of Neulasta and/or ciprofloxacin treatment on the gut microbiota after exposure to 9.5 Gy Co gamma-radiation in mice.
METHODS
The gut microbiota of vehicle and drug-treated mice exposed to sham or gamma-radiation was characterized by shotgun sequencing with alpha diversity, beta diversity, and taxonomy analyzed on days 2, 4, 9, and 15 post-irradiation.
RESULTS
No significant alpha diversity differences were observed following radiation, while beta diversity shifts and taxonomic profiles revealed significant alterations in , , and . Ciprofloxacin generally led to lower Shannon diversity and prevalence with increases in and compared to vehicle treated and irradiated mice. While Neulasta increased Shannon diversity and by day 9 had more similar taxonomic profiles to sham than ciprofloxacin-or vehicle-treated irradiated animals. Combined therapy of Neulasta and ciprofloxacin induced a decrease in Shannon diversity and resulted in unique taxonomic profiles early post-irradiation, returning closer to vehicle-treated levels over time, but persistent increases in and compared to Neulasta alone.
DISCUSSION
This study provides a framework for the identification of microbial elements that may influence radiosensitivity, biodosimetry and the efficacy of potential therapeutics. Moreover, increased survival from H-ARS using these therapeutics may affect the symptoms and appearance of what may have been subclinical GI-ARS.
Topics: Animals; Ciprofloxacin; Gastrointestinal Microbiome; Mice; Anti-Bacterial Agents; Acute Radiation Syndrome; Gamma Rays; Male; Female
PubMed: 38807988
DOI: 10.3389/fpubh.2024.1365161 -
Dental Research Journal 2024The presence of treatment-resistant microorganisms is known as the main cause of pulpectomy failure in the endodontic treatment of deciduous teeth. The usage of lasers...
BACKGROUND
The presence of treatment-resistant microorganisms is known as the main cause of pulpectomy failure in the endodontic treatment of deciduous teeth. The usage of lasers can contribute to reducing these microorganisms. This study aimed to compare the effect of three disinfection methods for deciduous teeth canals using laser diode 810 nm, photodynamic therapy with laser 660 nm and methylene blue, and sodium hypochlorite.
MATERIALS AND METHODS
In this experimental study, 58 single-root deciduous teeth with no root resorption were investigated in four groups, including one control group of 10 and three intervention groups of 16. Preparation of the samples was done using manual files up to three numbers after the initial file. After sterilizing the samples in an autoclave, bacteria were cultured in the canals. In the first group, irrigating with hypochlorite 2.5% was done; in the second group, photodynamic therapy was performed using a laser diode and 0.1 mg/mL methylene solution; and in the third group, high-intensity laser 810 nm direct radiation was done into the canal. Next, samples were taken from all canals. The colony formation unit (CFU) of the bacteria was counted in the blood agar culture medium. The data were analyzed using Kruskal-Wallis and negative binomial regression test (α =0.05).
RESULTS
The mean CFU differed significantly between the four groups. The rate of incidence of colonies showed a reduction in all three intervention groups compared to the negative control. In the high-intensity laser 810 nm group, there was 68.4%; in the photodynamic therapy with diode 660 nm and methylene blue, there was 88%; and in the hypochlorite group, 98.3% reduction was observed compared to the negative control group.
CONCLUSION
Based on the results of this study, to compare three disinfection methods of the deciduous teeth canals without preparation of canals, sodium hypochlorite had greater efficiency. All three groups of laser, photodynamic therapy, and sodium hypochlorite showed reductions of bacterial colony compared to the control group. The reductive effects of CFU were greater in the hypochlorite sodium group, followed by photodynamic and direct laser radiation groups.
PubMed: 38807661
DOI: No ID Found