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Journal of Nanobiotechnology Jul 2024Diabetic wounds present significant challenges, specifically in terms of bacterial infection and delayed healing. Therefore, it is crucial to address local bacterial...
BACKGROUND
Diabetic wounds present significant challenges, specifically in terms of bacterial infection and delayed healing. Therefore, it is crucial to address local bacterial issues and promote accelerated wound healing. In this investigation, we utilized electrospinning to fabricate microgel/nanofiber membranes encapsulating MXene-encapsulated microgels and chitosan/gelatin polymers.
RESULTS
The film dressing facilitates programmed photothermal therapy (PPT) and mild photothermal therapy (MPTT) under near-infrared (NIR), showcasing swift and extensive antibacterial and biofilm-disrupting capabilities. The PPT effect achieves prompt sterilization within 5 min at 52 °C and disperses mature biofilm within 10 min. Concurrently, by adjusting the NIR power to induce local mild heating (42 °C), the dressing stimulates fibroblast proliferation and migration, significantly enhancing vascularization. Moreover, in vivo experimentation successfully validates the film dressing, underscoring its immense potential in addressing the intricacies of diabetic wounds.
CONCLUSIONS
The MXene microgel-loaded nanofiber dressing employs temperature-coordinated photothermal therapy, effectively amalgamating the advantageous features of high-temperature sterilization and low-temperature promotion of wound healing. It exhibits rapid, broad-spectrum antibacterial and biofilm-disrupting capabilities, exceptional biocompatibility, and noteworthy effects on promoting cell proliferation and vascularization. These results affirm the efficacy of our nanofiber dressing, highlighting its significant potential in addressing the challenge of diabetic wounds struggling to heal due to infection.
Topics: Wound Healing; Nanofibers; Photothermal Therapy; Animals; Bandages; Anti-Bacterial Agents; Mice; Biofilms; Chitosan; Male; Diabetes Mellitus, Experimental; Temperature; Rats; Infrared Rays; Cell Proliferation; Rats, Sprague-Dawley; Humans; Wound Infection
PubMed: 38951903
DOI: 10.1186/s12951-024-02621-2 -
Journal of Cardiothoracic Surgery Jun 2024The outcomes of Thoracic Endovascular Aortic Repair (TEVAR) vary depending on thoracic aortic pathologies, comorbidities. This study presents our comprehensive...
BACKGROUND
The outcomes of Thoracic Endovascular Aortic Repair (TEVAR) vary depending on thoracic aortic pathologies, comorbidities. This study presents our comprehensive endovascular experience, focusing on exploring the outcome in long term follow-up.
METHODS
From 2006 to 2018, we conducted TEVAR on 97 patients presenting with various aortic pathologies. This retrospective cohort study was designed primarily to assess graft durability and secondarily to evaluate mortality causes, complications, reinterventions, and the impact of comorbidities on survival using Kaplan-Meier and Cox regression analyses.
RESULTS
The most common indication was thoracic aortic aneurysm (n = 52). Ten patients had aortic arch variations and anomalies, and the bovine arch was observed in eight patients. Endoleaks were the main complications encountered, and 10 of 15 endoleaks were type I endoleaks. There were 18 reinterventions; the most of which was TEVAR (n = 5). The overall mortality was 20 patients, with TEVAR-related causes accounting for 12 of these deaths, including intracranial bleeding in three patients. Multivariant Cox regression revealed chronic renal diseases (OR = 11.73; 95% CI: 2.04-67.2; p = 0.006), previous cardiac operation (OR = 14.26; 95% CI: 1.59-127.36; p = 0.01), and chronic obstructive pulmonary diseases (OR = 7.82; 95% CI: 1.43-42.78; p = 0.001) to be independent risk factors for 10-year survival. There was no significant difference in the survival curves of the various aortic pathologies. In the follow-up period, two non-symptomatic intragraft thromboses and one graft infection were found.
CONCLUSION
Comorbidities can increase the risk of TEVAR-related mortality without significantly impacting endoleak rates. TEVAR is effective for severe aortic pathologies, though long-term graft durability may be compromised by its thrombosis and infection.
Topics: Humans; Retrospective Studies; Male; Female; Middle Aged; Endovascular Procedures; Aorta, Thoracic; Aged; Blood Vessel Prosthesis Implantation; Treatment Outcome; Aortic Diseases; Postoperative Complications; Adult; Aortic Aneurysm, Thoracic; Follow-Up Studies; Time Factors; Endovascular Aneurysm Repair
PubMed: 38951901
DOI: 10.1186/s13019-024-02886-6 -
Journal of Cardiothoracic Surgery Jul 2024Right heart failure is a common complication after cardiac surgery, and its mortality remains high. The medical management and veno-arterial extracorporeal membrane...
Right heart failure is a common complication after cardiac surgery, and its mortality remains high. The medical management and veno-arterial extracorporeal membrane oxygenation has shown significant improvement in the majority of cases. However, a minority of patients may still require long-term mechanical circulatory support or heart transplantation. Balloon atrial septostomy is a new method for the prevention and treatment of right heart failure, which may avoid the patient's dependence on mechanical circulatory support. We used this method to try to treat patients with right heart failure after cardiac surgery, and all received good benefits. Therefore, we selected several representative cases to report, in order to guide other qualified cardiac surgeons to carry out relevant clinical practice.
Topics: Humans; Heart Failure; Male; Cardiac Surgical Procedures; Female; Postoperative Complications; Middle Aged; Atrial Septum; Aged; Adult; Catheterization; Heart Atria
PubMed: 38951889
DOI: 10.1186/s13019-024-02884-8 -
Journal of Nanobiotechnology Jul 2024The characteristic features of the rheumatoid arthritis (RA) microenvironment are synovial inflammation and hyperplasia. Therefore, there is a growing interest in...
Graphene oxide quantum dots-loaded sinomenine hydrochloride nanocomplexes for effective treatment of rheumatoid arthritis via inducing macrophage repolarization and arresting abnormal proliferation of fibroblast-like synoviocytes.
The characteristic features of the rheumatoid arthritis (RA) microenvironment are synovial inflammation and hyperplasia. Therefore, there is a growing interest in developing a suitable therapeutic strategy for RA that targets the synovial macrophages and fibroblast-like synoviocytes (FLSs). In this study, we used graphene oxide quantum dots (GOQDs) for loading anti-arthritic sinomenine hydrochloride (SIN). By combining with hyaluronic acid (HA)-inserted hybrid membrane (RFM), we successfully constructed a new nanodrug system named HA@RFM@GP@SIN NPs for target therapy of inflammatory articular lesions. Mechanistic studies showed that this nanomedicine system was effective against RA by facilitating the transition of M1 to M2 macrophages and inhibiting the abnormal proliferation of FLSs in vitro. In vivo therapeutic potential investigation demonstrated its effects on macrophage polarization and synovial hyperplasia, ultimately preventing cartilage destruction and bone erosion in the preclinical models of adjuvant-induced arthritis and collagen-induced arthritis in rats. Metabolomics indicated that the anti-arthritic effects of HA@RFM@GP@SIN NPs were mainly associated with the regulation of steroid hormone biosynthesis, ovarian steroidogenesis, tryptophan metabolism, and tyrosine metabolism. More notably, transcriptomic analyses revealed that HA@RFM@GP@SIN NPs suppressed the cell cycle pathway while inducing the cell apoptosis pathway. Furthermore, protein validation revealed that HA@RFM@GP@SIN NPs disrupted the excessive growth of RAFLS by interfering with the PI3K/Akt/SGK/FoxO signaling cascade, resulting in a decline in cyclin B1 expression and the arrest of the G2 phase. Additionally, considering the favorable biocompatibility and biosafety, these multifunctional nanoparticles offer a promising therapeutic approach for patients with RA.
Topics: Morphinans; Animals; Quantum Dots; Arthritis, Rheumatoid; Synoviocytes; Graphite; Cell Proliferation; Rats; Macrophages; Fibroblasts; Male; Arthritis, Experimental; Rats, Sprague-Dawley; Mice; Humans; RAW 264.7 Cells; Hyaluronic Acid
PubMed: 38951875
DOI: 10.1186/s12951-024-02645-8 -
Journal of Nanobiotechnology Jul 2024Reperfusion therapy is critical for saving heart muscle after myocardial infarction, but the process of restoring blood flow can itself exacerbate injury to the...
Targeting delivery of miR-146a via IMTP modified milk exosomes exerted cardioprotective effects by inhibiting NF-κB signaling pathway after myocardial ischemia-reperfusion injury.
Reperfusion therapy is critical for saving heart muscle after myocardial infarction, but the process of restoring blood flow can itself exacerbate injury to the myocardium. This phenomenon is known as myocardial ischemia-reperfusion injury (MIRI), which includes oxidative stress, inflammation, and further cell death. microRNA-146a (miR-146a) is known to play a significant role in regulating the immune response and inflammation, and has been studied for its potential impact on the improvement of heart function after myocardial injury. However, the delivery of miR-146a to the heart in a specific and efficient manner remains a challenge as extracellular RNAs are unstable and rapidly degraded. Milk exosomes (MEs) have been proposed as ideal delivery platform for miRNA-based therapy as they can protect miRNAs from RNase degradation. In this study, the effects of miR-146a containing MEs (MEs-miR-146a) on improvement of cardiac function were examined in a rat model of MIRI. To enhance the targeting delivery of MEs-miR-146a to the site of myocardial injury, the ischemic myocardium-targeted peptide IMTP was modified onto the surfaces, and whether the modified MEs-miR-146a could exert a better therapeutic role was examined by echocardiography, myocardial injury indicators and the levels of inflammatory factors. Furthermore, the expressions of miR-146a mediated NF-κB signaling pathway-related proteins were detected by western blotting and qRT-PCR to further elucidate its mechanisms. MiR-146 mimics were successfully loaded into the MEs by electroporation at a square wave 1000 V voltage and 0.1 ms pulse duration. MEs-miR-146a can be up-taken by cardiomyocytes and protected the cells from oxygen glucose deprivation/reperfusion induced damage in vitro. Oral administration of MEs-miR-146a decreased myocardial tissue apoptosis and the expression of inflammatory factors and improved cardiac function after MIRI. The miR-146a level in myocardium tissues was significantly increased after the administration IMTP modified MEs-miR-146a, which was higher than that of the MEs-miR-146a group. In addition, intravenous injection of IMTP modified MEs-miR-146a enhanced the targeting to heart, improved cardiac function, reduced myocardial tissue apoptosis and suppressed inflammation after MIRI, which was more effective than the MEs-miR-146a treatment. Moreover, IMTP modified MEs-miR-146a reduced the protein levels of IRAK1, TRAF6 and p-p65. Therefore, IMTP modified MEs-miR-146a exerted their anti-inflammatory effect by inhibiting the IRAK1/TRAF6/NF-κB signaling pathway. Taken together, our findings suggested miR-146a containing MEs may be a promising strategy for the treatment of MIRI with better outcome after modification with ischemic myocardium-targeted peptide, which was expected to be applied in clinical practice in future.
Topics: Animals; MicroRNAs; Myocardial Reperfusion Injury; Exosomes; NF-kappa B; Signal Transduction; Rats; Rats, Sprague-Dawley; Male; Milk; Myocardium; Cardiotonic Agents; Myocytes, Cardiac
PubMed: 38951872
DOI: 10.1186/s12951-024-02631-0 -
BMC Veterinary Research Jun 2024The aim of this research was to estimate the immunopotentiation effect of brown algae Padina boergesenii water extract on Nile tilapia, Oreochromis niloticus through...
The aim of this research was to estimate the immunopotentiation effect of brown algae Padina boergesenii water extract on Nile tilapia, Oreochromis niloticus through resistance to Pseudomonas putida infection. Gas Chromatography Mass Spectrometry was utilized to characterize the seaweed phytoconstituents. One hundred and twenty-six fish were divided in triplicates into two equal groups corresponding to two diet variants that used to feed Nile tilapia for 20 successive days: a basal (control), and P. boergesenii water extract supplemented group. Fish samples were collected at 10-days intervals throughout the experiment. Serum biochemical constituents, total antioxidant capacity (TAC), and some immune related genes expression of the spleen and intestinal tissues of experimental fish were studied, as well as histological examination of fish immune tissues. Moreover, following 20 days of feeding, the susceptibility of Nile tilapia to P. putida infection was evaluated to assess the protective effect of the used extract. The findings indicated that the studied parameters were significantly increased, and the best immune response profiles were observed in fish fed P. boergesenii water extract for 20 successive days. A bacterial challenge experiment using P. putida resulted in higher survival within the supplemented fish group than the control. Thus, the lowered post-challenge mortality of the fish may be related to the protection provided by the stimulation of the innate immune system, reduced oxidative stress by higher activity of TAC, and elevated levels of expression of iterleukin-1beta (IL-1β), beta-defensin (β-defensin), and natural killer-lysin (NKl). Moreover, the constituents of the extract used showed potential protective activity for histological features of the supplemented fish group when compared to the control. Collectively, this study presents a great insight on the protective role of P. boergesenii water extract as an additive in Nile tilapia feed which suggests its potential for improving the immune response against P. putida infection.
Topics: Animals; Pseudomonas putida; Fish Diseases; Cichlids; Animal Feed; Pseudomonas Infections; Dietary Supplements; Phaeophyceae; Diet; Disease Resistance; Plant Extracts
PubMed: 38951863
DOI: 10.1186/s12917-024-04115-7 -
BMC Musculoskeletal Disorders Jul 2024This study aimed to compare the clinical effect of modified anterolateral and traditional acromioplasty in arthroscopic rotator cuff repair. (Comparative Study)
Comparative Study
BACKGROUND
This study aimed to compare the clinical effect of modified anterolateral and traditional acromioplasty in arthroscopic rotator cuff repair.
METHODS
The clinical data of 92 patients with total rotator cuff tears admitted to the Department of Joint Surgery of Jinhua Central Hospital from January 2016 to December 2019 were retrospectively analyzed. Among them, 42 patients underwent traditional acromioplasty during arthroscopic rotator cuff repair, and 50 underwent modified anterolateral acromioplasty. Patients were evaluated for preoperative and postoperative shoulder function, pain and critical shoulder angle, and incidence of rotator cuff re-tear at 12 months postoperatively.
RESULTS
The preoperative general data of patients in the classic and modified anterolateral acromioplasty groups did not differ significantly (P > 0.05) and were comparable. The UCLA, ASES, and Constant shoulder joint scores were significantly improved in both groups. The VAS score was significantly decreased at 12 months postoperative than preoperative, with a statistically significant difference (P ≤ 0.05). Shoulder function and pain scores did not differ significantly between the two groups at 12 months postoperatively (P > 0.05). The CSA did not differ significantly between preoperative and postoperative 12 months in the traditional acromioplasty group (P > 0.05). However, 12 months postoperative CSA in the modified anterolateral acromioplasty group was significantly smaller than the preoperative CSA, with a statistically significant difference (P ≤ 0.05). The rates of rotator cuff re-tears were 16.67% (7/42) and 4% (2/50) in the two groups at 12 months postoperatively, respectively, with statistically significant differences (P ≤ 0.05).
CONCLUSIONS
Traditional and modified anterolateral acromioplasty while treating total rotator cuff tears using arthroscopic rotator cuff repair significantly improves shoulder joint function. However, modified anterolateral acromioplasty significantly reduced the CSA value and decreased the incidence of rotator cuff re-tears.
Topics: Humans; Rotator Cuff Injuries; Male; Female; Retrospective Studies; Middle Aged; Arthroscopy; Acromion; Aged; Treatment Outcome; Rotator Cuff; Arthroplasty; Range of Motion, Articular; Shoulder Joint
PubMed: 38951861
DOI: 10.1186/s12891-024-07619-3 -
Journal of Experimental & Clinical... Jun 2024During targeted treatment, HER2-positive breast cancers invariably lose HER2 DNA amplification. In contrast, and interestingly, HER2 proteins may be either lost or...
BACKGROUND
During targeted treatment, HER2-positive breast cancers invariably lose HER2 DNA amplification. In contrast, and interestingly, HER2 proteins may be either lost or gained. To longitudinally and systematically appreciate complex/discordant changes in HER2 DNA/protein stoichiometry, HER2 DNA copy numbers and soluble blood proteins (aHER2/sHER2) were tested in parallel, non-invasively (by liquid biopsy), and in two-dimensions, hence HER2-2D.
METHODS
aHER2 and sHER2 were assessed by digital PCR and ELISA before and after standard-of-care treatment of advanced HER2-positive breast cancer patients (n=37) with the antibody-drug conjugate (ADC) Trastuzumab-emtansine (T-DM1).
RESULTS
As expected, aHER2 was invariably suppressed by T-DM1, but this loss was surprisingly mirrored by sHER2 gain, sometimes of considerable entity, in most (30/37; 81%) patients. This unorthodox split in HER2 oncogenic dosage was supported by reciprocal aHER2/sHER2 kinetics in two representative cases, and an immunohistochemistry-high status despite copy-number-neutrality in 4/5 available post-T-DM1 tumor re-biopsies from sHER2-gain patients. Moreover, sHER2 was preferentially released by dying breast cancer cell lines treated in vitro by T-DM1. Finally, sHER2 gain was associated with a longer PFS than sHER2 loss (mean PFS 282 vs 133 days, 95% CI [210-354] vs [56-209], log-rank test p=0.047), particularly when cases (n=11) developing circulating HER2-bypass alterations during T-DM1 treatment were excluded (mean PFS 349 vs 139 days, 95% CI [255-444] vs [45-232], log-rank test p=0.009).
CONCLUSIONS
HER2 gain is adaptively selected in tumor tissues and recapitulated in blood by sHER2 gain. Possibly, an increased oncogenic dosage is beneficial to the tumor during anti-HER2 treatment with naked antibodies, but favorable to the host during treatment with a strongly cytotoxic ADC such as T-DM1. In the latter case, HER2-gain tumors may be kept transiently in check until alternative oncogenic drivers, revealed by liquid biopsy, bypass HER2. Whichever the interpretation, HER2-2D might help to tailor/prioritize anti-HER2 treatments, particularly ADCs active on aHER2-low/sHER2-low tumors.
TRIAL REGISTRATION
NCT05735392 retrospectively registered on January 31, 2023 https://www.
CLINICALTRIALS
gov/search?term=NCT05735392.
Topics: Humans; Female; Breast Neoplasms; Receptor, ErbB-2; Liquid Biopsy; Middle Aged; Ado-Trastuzumab Emtansine; Aged; Trastuzumab; Adult; Biomarkers, Tumor
PubMed: 38951853
DOI: 10.1186/s13046-024-03105-9 -
BMC Infectious Diseases Jun 2024Vaccination against COVID-19 was integral to controlling the pandemic that persisted with the continuous emergence of SARS-CoV-2 variants. Using a mathematical model...
Vaccination against COVID-19 was integral to controlling the pandemic that persisted with the continuous emergence of SARS-CoV-2 variants. Using a mathematical model describing SARS-CoV-2 within-host infection dynamics, we estimate differences in virus and immunity due to factors of infecting variant, age, and vaccination history (vaccination brand, number of doses and time since vaccination). We fit our model in a Bayesian framework to upper respiratory tract viral load measurements obtained from cases of Delta and Omicron infections in Singapore, of whom the majority only had one nasopharyngeal swab measurement. With this dataset, we are able to recreate similar trends in URT virus dynamics observed in past within-host modelling studies fitted to longitudinal patient data.We found that Omicron had higher R values than Delta, indicating greater initial cell-to-cell spread of infection within the host. Moreover, heterogeneities in infection dynamics across patient subgroups could be recreated by fitting immunity-related parameters as vaccination history-specific, with or without age modification. Our model results are consistent with the notion of immunosenescence in SARS-CoV-2 infection in elderly individuals, and the issue of waning immunity with increased time since last vaccination. Lastly, vaccination was not found to subdue virus dynamics in Omicron infections as well as it had for Delta infections.This study provides insight into the influence of vaccine-elicited immunity on SARS-CoV-2 within-host dynamics, and the interplay between age and vaccination history. Furthermore, it demonstrates the need to disentangle host factors and changes in pathogen to discern factors influencing virus dynamics. Finally, this work demonstrates a way forward in the study of within-host virus dynamics, by use of viral load datasets including a large number of patients without repeated measurements.
Topics: Humans; COVID-19; SARS-CoV-2; COVID-19 Vaccines; Middle Aged; Aged; Vaccination; Adult; Singapore; Age Factors; Viral Load; Young Adult; Bayes Theorem; Models, Theoretical; Male; Aged, 80 and over; Female; Adolescent
PubMed: 38951848
DOI: 10.1186/s12879-024-09572-x -
BMC Medicine Jul 2024Benzodiazepine use is common, particularly in older adults. Benzodiazepines have well-established acute adverse effects on cognition, but long-term effects on...
BACKGROUND
Benzodiazepine use is common, particularly in older adults. Benzodiazepines have well-established acute adverse effects on cognition, but long-term effects on neurodegeneration and dementia risk remain uncertain.
METHODS
We included 5443 cognitively healthy (MMSE ≥ 26) participants from the population-based Rotterdam Study (57.4% women, mean age 70.6 years). Benzodiazepine use from 1991 until baseline (2005-2008) was derived from pharmacy dispensing records, from which we determined drug type and cumulative dose. Benzodiazepine use was defined as prescription of anxiolytics (ATC-code: N05BA) or sedative-hypnotics (ATC-code: N05CD) between inception of pharmacy records and study baseline. Cumulative dose was calculated as the sum of the defined daily doses for all prescriptions. We determined the association with dementia risk until 2020 using Cox regression. Among 4836 participants with repeated brain MRI, we further determined the association of benzodiazepine use with changes in neuroimaging markers using linear mixed models.
RESULTS
Of all 5443 participants, 2697 (49.5%) had used benzodiazepines at any time in the 15 years preceding baseline, of whom 1263 (46.8%) used anxiolytics, 530 (19.7%) sedative-hypnotics, and 904 (33.5%) used both; 345 (12.8%) participants were still using at baseline assessment. During a mean follow-up of 11.2 years, 726 participants (13.3%) developed dementia. Overall, use of benzodiazepines was not associated with dementia risk compared to never use (HR [95% CI]: 1.06 [0.90-1.25]), irrespective of cumulative dose. Risk estimates were somewhat higher for any use of anxiolytics than for sedative-hypnotics (HR 1.17 [0.96-1.41] vs 0.92 [0.70-1.21]), with strongest associations for high cumulative dose of anxiolytics (HR [95% CI] 1.33 [1.04-1.71]). In imaging analyses, current use of benzodiazepine was associated cross-sectionally with lower brain volumes of the hippocampus, amygdala, and thalamus and longitudinally with accelerated volume loss of the hippocampus and to a lesser extent amygdala. However, imaging findings did not differ by type of benzodiazepines or cumulative dose.
CONCLUSIONS
In this population-based sample of cognitively healthy adults, overall use of benzodiazepines was not associated with increased dementia risk, but potential class-dependent adverse effects and associations with subclinical markers of neurodegeneration may warrant further investigation.
Topics: Humans; Female; Dementia; Male; Aged; Benzodiazepines; Middle Aged; Magnetic Resonance Imaging; Netherlands; Aged, 80 and over; Neuroimaging; Brain; Prospective Studies; Neurodegenerative Diseases; Hypnotics and Sedatives; Risk Factors
PubMed: 38951846
DOI: 10.1186/s12916-024-03437-5