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PloS One 2024This study aimed to develop a novel Gelatin silver oxide material for releasing nitric oxide bionanocomposite wound dressing with enhanced mechanical, chemical, and...
This study aimed to develop a novel Gelatin silver oxide material for releasing nitric oxide bionanocomposite wound dressing with enhanced mechanical, chemical, and antibacterial properties for the treatment of diabetic wounds. The gelatin- silver oxide nanoparticles (Ag2O-NP) bio nanocomposite was prepared using chitosan and gelatin polymers incorporated with silver oxide nanoparticles through the freeze-drying method. The samples were characterized using scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis. Results showed that the Ag2O-NP nanoparticles increased porosity, decreased pore size, and improved elastic modulus. The Ag2O-NP wound dressing exhibited the most effective antibacterial properties against Staphylococcus aureus and Escherichia coli. Among the samples, the wound dressing containing silver oxide nanoparticles demonstrated superior physical and mechanical properties, with 48% porosity, a tensile strength of 3.2 MPa, and an elastic modulus of 51.7 MPa. The fabricated wound dressings had a volume ratio of empty space to total volume ranging from 40% to 60%. In parallel, considering the complications of diabetes and its impact on the vascular system, another aspect of the research focused on developing a per2mediated wound dressing capable of releasing nitric oxide gas to regenerate damaged vessels and accelerate diabetic wound healing. Chitosan, a biocompatible and biodegradable polymer, was selected as the substrate for the wound dressing, and beta-glycerophosphate (GPβ), tripolyphosphate (TPP), and per2mediated alginate (AL) were used as crosslinkers. The chitosan-alginate (CS-AL) wound dressing exhibited optimal characteristics in terms of hole count and uniformity in the scanning electron microscope test. It also demonstrated superior water absorption (3854%) and minimal air permeability. Furthermore, the CS-AL sample exhibited an 80% degradation rate after 14 days, indicating its suitability as a wound dressing. The wound dressing was loaded with S-nitrosoglutathione (GSNO) powder, and the successful release of nitric oxide gas was confirmed through the grease test, showing a peak at a wavelength of 540 nm. Subsequent investigations revealed that the treatment of human umbilical vein endothelial cells (HUVECs) with high glucose led to a decrease in the expression of PER2 and SIRT1, while the expression of PER2 increased, which may subsequently enhance the expression of SIRT1 and promote cell proliferation activity. However, upon treatment of the cells with the modified materials, an increase in the expression of PER2 and SIRT1 was observed, resulting in a partial restoration of cell proliferative activity. This comprehensive study successfully developed per2-mediated bio-nanocomposite wound dressings with improved physical, mechanical, chemical, and antibacterial properties. The incorporation of silver oxide nanoparticles enhanced the antimicrobial activity, while the released nitric oxide gas from the dressing demonstrated the ability to mitigate vascular endothelial cell damage induced by high glucose levels. These advancements show promising potential for facilitating the healing process of diabetic wounds by addressing complications associated with diabetes and enhancing overall wound healing.
Topics: Gelatin; Wound Healing; Nitric Oxide; Bandages; Silver Compounds; Humans; Escherichia coli; Anti-Bacterial Agents; Staphylococcus aureus; Chitosan; Metal Nanoparticles; Porosity; Diabetic Foot; Nanoparticles; Oxides
PubMed: 38885218
DOI: 10.1371/journal.pone.0298124 -
The Israel Medical Association Journal... Jun 2024Although minimally invasive surgery for Crohn's disease has been validated in previous studies, most of those reports have referred to laparoscopic-assisted procedures... (Comparative Study)
Comparative Study
BACKGROUND
Although minimally invasive surgery for Crohn's disease has been validated in previous studies, most of those reports have referred to laparoscopic-assisted procedures with an extra-corporeal anastomosis.
OBJECTIVES
To evaluate the short- and long-term outcomes of total laparoscopic ileocolic resection with an intracorporeal anastomosis for Crohn's disease patients.
METHODS
We conducted a single-center retrospective review of all patients who underwent primary ileocolic resection for Crohn's disease between 2010 and 2021. Group A included 34 patients who underwent total laparoscopic ileocolic resection with intracorporeal anastomosis. Group B comprised 144 patients who underwent an open or laparoscopic-assisted procedure.
RESULTS
No differences were noted in operative time (mean 167 minutes vs. 152 minutes, P = 0.122), length of stay (median 6.4 days vs. 7.5 days, P = 0.135), readmission rates (11.8% vs. 13.2%, P = 1), and microscopic involvement of surgical margins (7.7% vs. 18.5%, P = 0.249). Group A had significantly fewer postoperative surgical site infections (2.9% vs. 22.2% respectively, P = 0.013), with no differences in other complications prevalence. After a median follow-up of 46 months, there were similar rates of endoscopic recurrence (47.1% vs. 51.4%, P = 0.72), clinical recurrence (35.3% vs. 47.9%, P = 0.253), and surgical recurrence (2.9% vs. 4.9%, P = 0.722).
CONCLUSIONS
Total laparoscopic ileocolic resection with intracorporeal anastomosis for Crohn's disease is safe and resulted in favorable outcomes in terms of postoperative wound healing. The long-term disease recurrence rates were like those of laparoscopic-assisted and open ileocolic resection.
Topics: Humans; Crohn Disease; Laparoscopy; Anastomosis, Surgical; Male; Female; Retrospective Studies; Adult; Ileum; Length of Stay; Operative Time; Colon; Treatment Outcome; Middle Aged; Colectomy; Postoperative Complications
PubMed: 38884309
DOI: No ID Found -
F1000Research 2022Malaria in pregnancy leads to placental malaria. The primary pathogenesis of the complex fetal implications in placental malaria is tissue hypoxia due to sequestrations...
BACKGROUND
Malaria in pregnancy leads to placental malaria. The primary pathogenesis of the complex fetal implications in placental malaria is tissue hypoxia due to sequestrations of -infected erythrocytes in the placenta. However, the pathomechanism of placental infection has not been thoroughly investigated. Hypoxia-inducible factor-1α (HIF-1α) is a key transcriptional mediator of the response to hypoxic conditions, which interacts with the change and imbalances of many chemical mediators, including angiogenic factors, leading to fetal growth abnormality.
METHODS
This study was conducted cross-sectionally in Maumere, Sikka Regency, East Nusa Tenggara Province, previously known as one of the malaria endemic areas with a high incidence of low birth weight (LBW) cases. This study collected peripheral and umbilical blood samples and placental tissues from mothers who delivered their babies with LBW at the TC Hiller Regional Hospital. All of the blood samples were examined for parasites by microscopic and PCR techniques, while the plasma levels of VEGF, PlGF, VEGFR-1, VEGFR-2, and HIF-1α were determined using ELISA. The sequestration of infected erythrocytes and hemozoin was determined from placental histological slides, and the expression of placenta angiogenic factors was observed using the immunofluorescent technique.
RESULTS
In this study, 33 cases had complete data to be analyzed. Of them, 19 samples were diagnosed as vivax malaria and none of falciparum malaria. There were significant differences in Δ 10th percentile growth curve of baby's body weights and also all angiogenic factors in placental tissues {VEGF, PlGF, and VEGFR-1, VEGFR-2, and HIF-1α} between those infected and not infected cases (p<0.05), but not for VEGF and VEGFR-2 in the plasma.
CONCLUSION
This study indicated that sequestration may promote LBW through alterations and imbalances in angiogenic factors led by HIF-1α.
Topics: Humans; Female; Hypoxia-Inducible Factor 1, alpha Subunit; Malaria, Vivax; Pregnancy; Infant, Low Birth Weight; Placenta; Adult; Plasmodium vivax; Infant, Newborn; Angiogenesis Inducing Agents; Vascular Endothelial Growth Factor A; Pregnancy Complications, Parasitic; Cross-Sectional Studies; Vascular Endothelial Growth Factor Receptor-1
PubMed: 38884107
DOI: 10.12688/f1000research.73820.3 -
Factors associated with incomplete resection for large, locally invasive non-small cell lung cancer.Journal of Thoracic Disease May 2024Large, node-negative but locally invasive non-small cell lung cancer (NSCLC) is associated with increased perioperative risk but improved survival if a complete...
BACKGROUND
Large, node-negative but locally invasive non-small cell lung cancer (NSCLC) is associated with increased perioperative risk but improved survival if a complete resection is obtained. Factors associated with positive margins in this population are not well-studied.
METHODS
We performed a retrospective cohort study using National Cancer Database (NCDB) for adult patients with >5 cm, clinically node-negative NSCLC with evidence of invasion of nearby structures [2006-2015]. Patients were classified as having major structure involvement (azygous vein, pulmonary artery/vein, vena cava, carina/trachea, esophagus, recurrent laryngeal/vagus nerve, heart, aorta, vertebrae) or chest wall invasion (rib pleura, chest wall, diaphragm). Our primary outcome was to evaluate factors associated with incomplete resection (microscopic: R1, macroscopic: R2). Kaplan-Meier analysis and cox multivariable regression models were used to evaluate overall survival (OS), 90-day mortality, and factors associated with positive margins.
RESULTS
Among 2,368 patients identified, the median follow-up was 33.8 months [interquartile range (IQR), 12.6-66.5 months]. Most patients were white (86.9%) with squamous cell histology (47.3%). Major structures were involved in 26.4% of patients and chest wall invasion was seen in 73.6%. Four hundred and seventy-eight patients (20.2%) had an incomplete resection. Multivariable analysis revealed that black race [hazard ratio (HR) 1.568, 95% confidence interval (CI): 1.109-2.218] and major structure involvement (HR 1.412, 95% CI: 1.091-1.827) was associated with increased risk of incomplete resection and surgery at an academic hospitals (HR 0.773, 95% CI: 0.607-0.984), adenocarcinoma histology (HR 0.672, 95% CI: 0.514-0.878), and neoadjuvant chemotherapy (HR 0.431, 95% CI: 0.316-0.587) were associated with decreased risk of incomplete resection. The 5-year OS was 43.7% in the entire cohort and 28.8% in patients with positive margins and 47.5% in patients with an R0 resection. Positive margin was also associated with a significantly higher 90-day mortality rate (9.9% versus 6.7%).
CONCLUSIONS
For patients with large, node-negative NSCLC invading nearby structures, R0 resection portends better survival. Treatment at academic centers, adenocarcinoma histology, and receipt of neoadjuvant chemotherapy are associated with R0 resection in this high-risk cohort.
PubMed: 38883676
DOI: 10.21037/jtd-23-989 -
International Journal of Biomedical... 2024Surgical resection is the only curative option for pancreatic carcinoma, but disease-free and overall survival times after surgery are limited due to early tumor...
PURPOSE
Surgical resection is the only curative option for pancreatic carcinoma, but disease-free and overall survival times after surgery are limited due to early tumor recurrence, most often originating from local microscopic tumor residues (R1 resection). The intraoperative identification of microscopic tumor residues within the resection margin could improve surgical performance. The aim of this study was to evaluate the effectiveness of fiber-optic microscopy for detecting microscopic residues in vital pancreatic cancer tissues. . Fresh whole-mount human pancreatic tissues, histological tissue slides, cell culture, and chorioallantoic membrane xenografts were analyzed. Specimens were stained with selected fluorophore-conjugated antibodies and studied using conventional wide-field and self-designed multicolor fiber-optic fluorescence microscopy instruments.
RESULTS
Whole-mount vital human tissues and xenografts were stained and imaged using an immunofluorescence protocol. Fiber-optic microscopy enabled the detection of epitope-based fluorescence in vital whole-mount tissue using fluorophore-conjugated antibodies and enabled visualization of microvascular, epithelial, and malignant tumor cells. Among the selected antigen-antibody pairs, antibody clones WM59, AY13, and 9C4 were the most promising for fiber-optic imaging in human tissue samples and for endothelial, tumor and epithelial cell detection.
CONCLUSIONS
Fresh dissected whole-mount tissue can be stained using direct exposure to selected antibody clones. Several antibody clones were identified that provided excellent immunofluorescence imaging of labeled structures, such as endothelial, epithelial, or EGFR-expressing cells. The combination of immunofluorescence staining and fiber-optic microscopy visualizes structures in vital tissues and could be proposed as an useful tool for the identification of residual tumor mass in patients with a high operative risk for incomplete resection.
PubMed: 38883274
DOI: 10.1155/2024/1397875 -
International Journal of Nanomedicine 2024Rheumatoid Arthritis (RA) involves prolonged inflammation of the synovium, damaging joints and causing stiffness and deformity. Celastrol (Cel), derived from the Chinese...
BACKGROUND
Rheumatoid Arthritis (RA) involves prolonged inflammation of the synovium, damaging joints and causing stiffness and deformity. Celastrol (Cel), derived from the Chinese herbal medicine Hook F, offers immunosuppressive effects for RA treatment but is limited by poor solubility and bioavailability.
PURPOSE
In this study, long-circulating Cel-loaded liposomes (Cel-LPs) were used to increase the pharmacokinetics of Cel, thereby improving drug delivery and efficacy for the treatment of RA.
METHODS
Cel-LPs were prepared and administered orally and intravenously to compare the elimination half-life of drugs and bioavailability of Cel. Cel-LPs were prepared using the lipid thin-layer-hydration-extrusion method. Human rheumatoid arthritis synovial (MH7A) cells were used to investigate the compatibility of Cel-LPs. The pharmacokinetic studies were performed on male Sprague-Dawley (SD) rats.
RESULTS
The Cel-LPs had an average size of 72.20 ± 27.99 nm, a PDI of 0.267, a zeta potential of -31.60 ± 6.81 mV, 78.77 ± 5.69% drug entrapment efficiency and sustained release (5.83 ± 0.42% drug loading). The cytotoxicity test showed that liposomes had excellent biocompatibility and the fluorescence microscope diagram indicated that liposome entrapment increased intracellular accumulation of Rhodamine B by MH7A cells. Furthermore, the results exhibited that Cel-LPs improved the pharmacokinetics of Cel by increasing the elimination half-life (t) to 11.71 hr, mean residence time (MRT) to 7.98 hr and apparent volume of distribution (Vz/F) to 44.63 L/kg in rats, compared to the Cel solution.
CONCLUSION
In this study, liposomes were demonstrated to be effective in optimizing the delivery of Cel, enabling the formulation of Cel-LPs with prolonged blood circulation and sustained release characteristics. This formulation enhanced the intravenous solubility and bioavailability of Cel, developing a foundation for its clinical application in RA and providing insights on poorly soluble drug management.
Topics: Pentacyclic Triterpenes; Animals; Liposomes; Triterpenes; Male; Rats, Sprague-Dawley; Humans; Administration, Intravenous; Rats; Biological Availability; Cell Line; Arthritis, Rheumatoid; Particle Size; Cell Survival; Drug Delivery Systems
PubMed: 38882540
DOI: 10.2147/IJN.S461624 -
Frontiers in Cellular and Infection... 2024Nocardiosis demonstrates a temporal categorization that includes acute, subacute, and chronic stages alongside distinct typical localizations such as pulmonary,...
Nocardiosis demonstrates a temporal categorization that includes acute, subacute, and chronic stages alongside distinct typical localizations such as pulmonary, cutaneous, and disseminated forms. Disseminated nocardiosis, commonly caused by , , and , continues to result in substantial morbidity and mortality. Herein, we report a life-threatening disseminated nocardiosis caused by in a patient with minimal change disease. This study emphasizes the difficulty in the diagnosis and treatment of unknown infections in clinical settings and highlights the important role played by laboratories in solving infectious diseases caused by rare pathogens.
Topics: Nocardia Infections; Humans; Nocardia; Anti-Bacterial Agents; Male; Treatment Outcome; Middle Aged
PubMed: 38881735
DOI: 10.3389/fcimb.2024.1397847 -
Neurophotonics Jul 2024Widefield microscopy of the entire dorsal part of mouse cerebral cortex enables large-scale ("mesoscopic") imaging of different aspects of neuronal activity with...
SIGNIFICANCE
Widefield microscopy of the entire dorsal part of mouse cerebral cortex enables large-scale ("mesoscopic") imaging of different aspects of neuronal activity with spectrally compatible fluorescent indicators as well as hemodynamics via oxy- and deoxyhemoglobin absorption. Versatile and cost-effective imaging systems are needed for large-scale, color-multiplexed imaging of multiple fluorescent and intrinsic contrasts.
AIM
We aim to develop a system for mesoscopic imaging of two fluorescent and two reflectance channels.
APPROACH
Excitation of red and green fluorescence is achieved through epi-illumination. Hemoglobin absorption imaging is achieved using 525- and 625-nm light-emitting diodes positioned around the objective lens. An aluminum hemisphere placed between objective and cranial window provides diffuse illumination of the brain. Signals are recorded sequentially by a single sCMOS detector.
RESULTS
We demonstrate the performance of our imaging system by recording large-scale spontaneous and stimulus-evoked neuronal, cholinergic, and hemodynamic activity in awake, head-fixed mice with a curved "crystal skull" window expressing the red calcium indicator jRGECO1a and the green acetylcholine sensor . Shielding of illumination light through the aluminum hemisphere enables concurrent recording of pupil diameter changes.
CONCLUSIONS
Our widefield microscope design with a single camera can be used to acquire multiple aspects of brain physiology and is compatible with behavioral readouts of pupil diameter.
PubMed: 38881627
DOI: 10.1117/1.NPh.11.3.034310 -
Journal of Experimental & Clinical... Jun 2024Cancer is characterized by dysregulated cellular metabolism. Thus, understanding the mechanisms underlying these metabolic alterations is important for developing...
BACKGROUND
Cancer is characterized by dysregulated cellular metabolism. Thus, understanding the mechanisms underlying these metabolic alterations is important for developing targeted therapies. In this study, we investigated the pro-tumoral effect of PDZ and LIM domain 2 (PDLIM2) downregulation in lung cancer growth and its association with the accumulation of mitochondrial ROS, oncometabolites and the activation of hypoxia-inducible factor-1 (HIF-1) α in the process.
METHODS
Databases and human cancer tissue samples were analyzed to investigate the roles of PDLIM2 and HIF-1α in cancer growth. DNA microarray and gene ontology enrichment analyses were performed to determine the cellular functions of PDLIM2. Seahorse assay, flow cytometric analysis, and confocal microscopic analysis were employed to study mitochondrial functions. Oncometabolites were analyzed using liquid chromatography-mass spectrometry (LC-MS). A Lewis lung carcinoma (LLC) mouse model was established to assess the in vivo function of PDLIM2 and HIF-1α.
RESULTS
The expression of PDLIM2 was downregulated in lung cancer, and this downregulation correlated with poor prognosis in patients. PDLIM2 highly regulated genes associated with mitochondrial functions. Mechanistically, PDLIM2 downregulation resulted in NF-κB activation, impaired expression of tricarboxylic acid (TCA) cycle genes particularly the succinate dehydrogenase (SDH) genes, and mitochondrial dysfunction. This disturbance contributed to the accumulation of succinate and other oncometabolites, as well as the buildup of mitochondrial reactive oxygen species (mtROS), leading to the activation of hypoxia-inducible factor 1α (HIF-1α). Furthermore, the expression of HIF-1α was increased in all stages of lung cancer. The expression of PDLIM2 and HIF-1α was reversely correlated in lung cancer patients. In the animal study, the orally administered HIF-1α inhibitor, PX-478, significantly reduces PDLIM2 knockdown-promoted tumor growth.
CONCLUSION
These findings shed light on the complex action of PDLIM2 on mitochondria and HIF-1α activities in lung cancer, emphasizing the role of HIF-1α in the tumor-promoting effect of PDLIM2 downregulation. Additionally, they provide new insights into a strategy for precise targeted treatment by suggesting that HIF-1α inhibitors may serve as therapy for lung cancer patients with PDLIM2 downregulation.
Topics: Humans; LIM Domain Proteins; Animals; Hypoxia-Inducible Factor 1, alpha Subunit; Mice; Mitochondria; Reactive Oxygen Species; Down-Regulation; Lung Neoplasms; Cell Line, Tumor; Microfilament Proteins; Carcinoma, Lewis Lung; Gene Expression Regulation, Neoplastic; Female; Male
PubMed: 38880883
DOI: 10.1186/s13046-024-03094-9 -
Microbial Pathogenesis Jun 2024Arcobacter butzleri is a foodborne pathogen that mainly causes enteritis in humans, but the number of cases of bacteraemia has increased in recent years. However, there...
Arcobacter butzleri is a foodborne pathogen that mainly causes enteritis in humans, but the number of cases of bacteraemia has increased in recent years. However, there is still limited knowledge on the pathogenic mechanisms of this bacterium. To investigate how A. butzleri causes disease, single knockout mutants were constructed in the cadF, ABU_RS00335, ciaB, and flaAB genes, which might be involved in adhesion and invasion properties. These mutants and the isogenic wild-type (WT) were then tested for their ability to adhere and invade human Caco-2 and HT29-MTX cells. The adhesion and invasion of A. butzleri RM4018 strain was also visualized by a Leica CTR 6500 confocal microscope. The adhesion and invasion abilities of mutants lacking the invasion antigen CiaB or a functional flagellum were lower than those of the WTs. However, the extent of the decrease varied depending on the strain and/or cell line. Mutants lacking the fibronectin (FN)-binding protein CadF consistently exhibited reduced abilities, while the inactivation of the other studied FN-binding protein, ABU_RS00335, led to a reduction in only one of the two strains tested. Therefore, the ciaB and flaAB genes appear to be important for A. butzleri adhesion and invasion properties, while cadF appears to be indispensable.
PubMed: 38880315
DOI: 10.1016/j.micpath.2024.106752