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Scientific Reports Jul 2024Rapamycin slows cystogenesis in murine models of polycystic kidney disease (PKD) but failed in clinical trials, potentially due to insufficient drug dosing. To improve...
Rapamycin slows cystogenesis in murine models of polycystic kidney disease (PKD) but failed in clinical trials, potentially due to insufficient drug dosing. To improve drug efficiency without increasing dose, kidney-specific drug delivery may be used. Mesoscale nanoparticles (MNP) selectively target the proximal tubules in rodents. We explored whether MNPs can target cystic kidney tubules and whether rapamycin-encapsulated-MNPs (RapaMNPs) can slow cyst growth in Pkd1 knockout (KO) mice. MNP was intravenously administered in adult Pkd1KO mice. Serum and organs were harvested after 8, 24, 48 or 72 h to measure MNP localization, mTOR levels, and rapamycin concentration. Pkd1KO mice were then injected bi-weekly for 6 weeks with RapaMNP, rapamycin, or vehicle to determine drug efficacy on kidney cyst growth. Single MNP injections lead to kidney-preferential accumulation over other organs, specifically in tubules and cysts. Likewise, one RapaMNP injection resulted in higher drug delivery to the kidney compared to the liver, and displayed sustained mTOR inhibition. Bi-weekly injections with RapaMNP, rapamycin or vehicle for 6 weeks resulted in inconsistent mTOR inhibition and little change in cyst index, however. MNPs serve as an effective short-term, kidney-specific delivery system, but long-term RapaMNP failed to slow cyst progression in Pkd1KO mice.
Topics: Animals; Sirolimus; Mice; Polycystic Kidney Diseases; Mice, Knockout; Nanoparticles; Disease Models, Animal; TOR Serine-Threonine Kinases; TRPP Cation Channels; Kidney; Drug Delivery Systems; Male
PubMed: 38956234
DOI: 10.1038/s41598-024-65830-7 -
Scientific Reports Jul 2024Adjuvant oxaliplatin plus S-1 (SOX) chemotherapy for gastric cancer (GC) after D2 gastrectomy has been proven effective. There has yet to be a study that evaluates...
Adjuvant oxaliplatin plus S-1 (SOX) chemotherapy for gastric cancer (GC) after D2 gastrectomy has been proven effective. There has yet to be a study that evaluates adjuvant nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus S-1. In this single-center, retrospective study, GC patients after D2 gastrectomy received either nab-paclitaxel plus S-1 (AS group) or SOX group were recruited between January 2018 and December 2020 in The First Affiliated Hospital of Zhejiang University. Intravenous nab-paclitaxel 120 mg/m or 260 mg/m and oxaliplatin 130 mg/m were administered as eight 3 week cycle, especially in the AS and SOX group. Patients received S-1 twice daily with a dose of 40 mg/m in the two groups on days 1-14 of each cycle. The end points were disease-free survival (DFS) rate at 3 years and adverse events (AEs). There were 56 eligible patients, 28 in the AS group and 35 in the SOX group. The 3 year DFS rate was 78.0% in AS group versus 70.7% in SOX group (p = 0.46). Subgroup analysis showed that the patients with signet-ring positive in the AS group had a prolonged DFS compared with the SOX group (40.0 vs. 13.8 m, p = 0.02). The diffuse-type GC or low differentiation in the AS group was associated with numerically prolonged DFS compared with the SOX group, but the association was not statistically significant (p = 0.27 and p = 0.15 especially). Leukopenia (14.3%) were the most prevalent AEs in the AS group, while thrombocytopenia (28.5%) in the SOX group. Neutropenia (7.1% in AS group) and thrombocytopenia (22.8% in SOX group) were the most common grade 3 or 4 AEs. In this study analyzing past data, a tendency towards a greater 3 year DFS was observed when using AS regimen in signet-ring positive patients. AS group had fewer thrombocytopenia compared to SOX group. More studies should be conducted with larger sample sizes.
Topics: Humans; Stomach Neoplasms; Male; Female; Tegafur; Middle Aged; Oxaliplatin; Retrospective Studies; Gastrectomy; Drug Combinations; Oxonic Acid; Antineoplastic Combined Chemotherapy Protocols; Aged; Chemotherapy, Adjuvant; Albumin-Bound Paclitaxel; Adult; Disease-Free Survival; Paclitaxel; Albumins
PubMed: 38956232
DOI: 10.1038/s41598-024-65724-8 -
Scientific Reports Jul 2024To treat hypovolemic shock, fluid infusion or blood transfusion is essential to address insufficient volume. Much controversy surrounds resuscitation in hypovolemic...
To treat hypovolemic shock, fluid infusion or blood transfusion is essential to address insufficient volume. Much controversy surrounds resuscitation in hypovolemic shock. We aimed to identify the ideal fluid combination for treating hypovolemic shock-induced swine model, analyzing bioelectrical impedance and hemodynamics. Fifteen female three-way crossbred pigs were divided into three different groups. The three resuscitation fluids were (1) balanced crystalloid, (2) balanced crystalloid + 5% dextrose water, and (3) balanced crystalloid + 20% albumin. The experiment was divided into three phases and conducted sequentially: (1) controlled hemorrhage (1 L bleeding, 60 min), (2) resuscitation phase 1 (1 L fluid infusion, 60 min), and (3) resuscitation phase 2 (1 L fluid infusion, 60 min). Bioelectrical impedance analysis was implemented with a segmental multifrequency bioelectrical impedance analyzer. A total of 61 impedance measurements were assessed for each pig at six different frequencies in five segments of the pig. Pulse rate (PR), mean arterial pressure (MAP), stroke volume (SV), and stroke volume variation (SVV) were measured using a minimally invasive hemodynamic monitoring device. The three-dimensional graph showed a curved pattern when infused with 1 L of balanced crystalloid + 1 L of 5% dextrose water and 1.6 L of balanced crystalloid + 400 ml of 20% albumin. The 1M impedance increased in all groups during the controlled hemorrhage, and continuously decreased from fluid infusion to the end of the experiment. Only balanced crystalloid + 20% albumin significantly restored MAP and SV to the same level as the start of the experiment after the end of fluid infusion. There were no significant differences in MAP and SV from the time of recovery to the initial value of 1M impedance to the end of fluid infusion in all groups. The change and the recovery of hemodynamic indices such as MAP and SV coincide with the change and the recovery of 1M impedance. Using balanced crystalloid mixed with 20% albumin in hypovolemic shock-induced swine model may be helpful in securing hemodynamic stability, compared with balanced crystalloid single administration.
Topics: Animals; Swine; Electric Impedance; Hemodynamics; Female; Shock; Disease Models, Animal; Fluid Therapy; Resuscitation; Crystalloid Solutions; Albumins
PubMed: 38956216
DOI: 10.1038/s41598-024-65847-y -
Scientific Reports Jul 2024This retrospective cohort study investigated patients with cytomegalovirus anterior uveitis (CMV AU) and compared treatment outcomes between regional and systemic...
This retrospective cohort study investigated patients with cytomegalovirus anterior uveitis (CMV AU) and compared treatment outcomes between regional and systemic antiviral therapies. Treatment modalities included topical (2% ganciclovir [GCV] eye drops or 0.2% GCV eye gel) and systemic (intravenous GCV or oral valganciclovir) groups. The comparison parameters included response rates, time to response, recurrence rates, time to recurrence, and complications. Forty-four patients (54.5% male) with a mean age of 56 ± 9.87 years were enrolled, with 31 eyes in the topical group and 13 eyes in the systemic group. The median response time was significantly slower in the topical group (63 days [IQR 28-112]) compared to the systemic group (28 days [IQR 24-59]) (p = 0.04). Treatment response rates were 87.1% (27/31) in the topical group and 100% (13/13) in the systemic group (p = 0.30), while recurrence rates were 37% (10/27) and 69.2% (9/13) (p = 0.056), with a median time to recurrence of 483 days [IQR 145-1388] and 392 days [IQR 203.5-1907.5] (p = 0.20), respectively. In conclusion, both topical and systemic GCV treatments demonstrated favorable outcomes for CMV AU. Systemic GCV showed rapid control of intraocular inflammation.
Topics: Humans; Male; Female; Middle Aged; Cytomegalovirus Infections; Uveitis, Anterior; Antiviral Agents; Retrospective Studies; Treatment Outcome; Ganciclovir; Aged; Cytomegalovirus; Adult; Valganciclovir; Recurrence; Ophthalmic Solutions
PubMed: 38956212
DOI: 10.1038/s41598-024-66224-5 -
Scientific Reports Jul 2024In hybrid automatic insulin delivery (HAID) systems, meal disturbance is compensated by feedforward control, which requires the announcement of the meal by the patient...
In hybrid automatic insulin delivery (HAID) systems, meal disturbance is compensated by feedforward control, which requires the announcement of the meal by the patient with type 1 diabetes (DM1) to achieve the desired glycemic control performance. The calculation of insulin bolus in the HAID system is based on the amount of carbohydrates (CHO) in the meal and patient-specific parameters, i.e. carbohydrate-to-insulin ratio (CR) and insulin sensitivity-related correction factor (CF). The estimation of CHO in a meal is prone to errors and is burdensome for patients. This study proposes a fully automatic insulin delivery (FAID) system that eliminates patient intervention by compensating for unannounced meals. This study exploits the deep reinforcement learning (DRL) algorithm to calculate insulin bolus for unannounced meals without utilizing the information on CHO content. The DRL bolus calculator is integrated with a closed-loop controller and a meal detector (both previously developed by our group) to implement the FAID system. An adult cohort of 68 virtual patients based on the modified UVa/Padova simulator was used for in-silico trials. The percentage of the overall duration spent in the target range of 70-180 mg/dL was and , mg/dL was and , and mg/dL was and , respectively, for the FAID system and HAID system utilizing a standard bolus calculator (SBC) including CHO misestimation. The proposed algorithm can be exploited to realize FAID systems in the future.
Topics: Insulin; Humans; Diabetes Mellitus, Type 1; Insulin Infusion Systems; Deep Learning; Algorithms; Blood Glucose; Adult; Hypoglycemic Agents
PubMed: 38956183
DOI: 10.1038/s41598-024-62912-4 -
Scientific Reports Jul 2024This study aimed to develop a highly efficient nanocomposite composed of magnetic chitosan/molybdenum disulfide (CS/MoS/FeO) for the removal of three polycyclic aromatic...
This study aimed to develop a highly efficient nanocomposite composed of magnetic chitosan/molybdenum disulfide (CS/MoS/FeO) for the removal of three polycyclic aromatic hydrocarbons (PAHs)-pyrene, anthracene, and phenanthrene. Novelty was introduced through the innovative synthesis procedure and the utilization of magnetic properties for enhanced adsorption capabilities. Additionally, the greenness of chitosan as a sorbent component was emphasized, highlighting its biodegradability and low environmental impact compared to traditional sorbents. Factors influencing PAH adsorption, such as nanocomposite dosage, initial PAH concentration, pH, and contact time, were systematically investigated and optimized. The results revealed that optimal removal efficiencies were attained at an initial PAH concentration of 150 mg/L, a sorbent dose of 0.045 g, pH 6.0, and a contact time of 150 min. The pseudo-second-order kinetic model exhibited superior fitting to the experimental data, indicating an equilibrium time of approximately 150 min. Moreover, the equilibrium adsorption process followed the Freundlich isotherm model, with k and n values exceeding 7.91 mg/g and 1.20, respectively. Remarkably, the maximum absorption capacities for phenanthrene, anthracene, and pyrene on the sorbent were determined as 217 mg/g, 204 mg/g, and 222 mg/g, respectively. These findings underscore the significant potential of the CS/MoS/FeO nanocomposite for efficiently removing PAHs from milk and other dairy products, thereby contributing to improved food safety and public health.
Topics: Disulfides; Nanocomposites; Chitosan; Polycyclic Aromatic Hydrocarbons; Molybdenum; Milk; Animals; Adsorption; Kinetics; Hydrogen-Ion Concentration
PubMed: 38956159
DOI: 10.1038/s41598-024-66087-w -
Scientific Reports Jul 2024Wheat straw returning is a common agronomic measure in the farmland. Understanding organic carbon transformation is of great significance for carbon budget under the...
Wheat straw returning is a common agronomic measure in the farmland. Understanding organic carbon transformation is of great significance for carbon budget under the premise of widespread distribution of cadmium (Cd) contaminated soils. An incubation experiment was conducted to assess the influence of Cd contamination on the decomposition and accumulation of total organic carbon (TOC) as well as the composition and abundance of bacterial communities in eight soil types with wheat straw addition. The results showed that inhibition of Cd contamination on microbially mediated organic carbon decomposition was affected by soil types. The lower cumulative C mineralization and higher TOC content could be observed in the acidic soils relative to that in the alkaline soils. The content of Cd in soil exhibits different effects on the inhibition in decomposition of TOC. The high dosage level of Cd had stronger inhibitory impact due to its high toxicity. The decomposition of TOC was restricted by a reduction in soil bacterial abundance and weakening of bacterial activities. Redundancy analysis (RDA) indicated that Proteobacteria and Gemmatimonadetes were abundant in alkaline Cd-contaminated soils with wheat straw addition, while Bacteroidetes dominated cumulative C mineralization in acidic Cd-contamination soils. Moreover, the abundance of predicted functional bacteria indicated that high-dose Cd-contamination and acid environment all inhibited the decomposition of TOC. The present study suggested that pH played an important role on carbon dynamics in the Cd-contaminated soils with wheat straw addition.
Topics: Cadmium; Triticum; Soil Pollutants; Soil Microbiology; Carbon; Soil; Bacteria; Biodegradation, Environmental; Hydrogen-Ion Concentration
PubMed: 38956155
DOI: 10.1038/s41598-024-64267-2 -
Scientific Reports Jul 2024This study aims to investigate the factors effective in predicting the persistence of reflux after the first subureteric transurethral injection (STING) of...
This study aims to investigate the factors effective in predicting the persistence of reflux after the first subureteric transurethral injection (STING) of dextranomer/hyaluronic acid copolymer in pediatric patients with vesicoureteral reflux. The data of patients without a previous history of surgery to treat vesicoureteral reflux and who underwent STING for the first time between September 2011 and November 2020 were investigated retrospectively. After considering exclusion criteria, of 199 patients, 127 patients and 180 renal units were suitable for inclusion. A renal unit-based evaluation was made. Age < 61 months (univariate: p = 0.001, multivariate: p = 0.015, HR: 2.352 (1.181-4.686), OR (95% CI)), moderate reflux level (grade 3) (univariate: p < 0.001, multivariate: p = 0.019, HR: 2.703 (1.177-6.209), OR (95% CI)), DRF (differential renal function) < 45 (univariate: p = 0.020, multivariate: p = 0.047, HR: 1.992 (1.009-3.935), OR (95% CI)), and UDR (ureteral diameter ratio) > 0.15 (univariate: p < 0.001, multivariate: p = 0.005, HR: 2.786 (1.368-5.672), OR (95% CI)) were found predictors of reflux persistence after STING surgery both univariate and multivariate analysis. High reflux level (grade 4-5) was statistically significant in univariate analysis (p < 0.001) but not statistically significant in multivariate analysis (p = 0.215). In our study, UDR and DRF were found to be factors affecting reflux persistence. UDR and DRF should be considered in order to predict reflux resolution in patients who will undergo STING.
Topics: Humans; Vesico-Ureteral Reflux; Hyaluronic Acid; Dextrans; Female; Male; Child, Preschool; Retrospective Studies; Infant; Child; Injections; Treatment Outcome
PubMed: 38956126
DOI: 10.1038/s41598-024-62449-6 -
Scientific Reports Jul 2024Nanogels offer hope for precise drug delivery, while addressing drug delivery hurdles is vital for effective prostate cancer (PCa) management. We developed an injectable...
Nanogels offer hope for precise drug delivery, while addressing drug delivery hurdles is vital for effective prostate cancer (PCa) management. We developed an injectable elastin nanogels (ENG) for efficient drug delivery system to overcome castration-resistant prostate cancer (CRPC) by delivering Decursin, a small molecule inhibitor that blocks Wnt/βcatenin pathways for PCa. The ENG exhibited favourable characteristics such as biocompatibility, flexibility, and low toxicity. In this study, size, shape, surface charge, chemical composition, thermal stability, and other properties of ENG were used to confirm the successful synthesis and incorporation of Decursin (DEC) into elastin nanogels (ENG) for prostate cancer therapy. In vitro studies demonstrated sustained release of DEC from the ENG over 120 h, with a pH-dependent release pattern. DU145 cell line induces moderate cytotoxicity of DEC-ENG indicates that nanomedicine has an impact on cell viability and helps strike a balance between therapeutics efficacy and safety while the EPR effect enables targeted drug delivery to prostate tumor sites compared to free DEC. Morphological analysis further supported the effectiveness of DEC-ENG in inducing cell death. Overall, these findings highlight the promising role of ENG-encapsulated decursin as a targeted drug delivery system for CRPC.
Topics: Male; Elastin; Humans; Cell Line, Tumor; Nanogels; Prostatic Neoplasms, Castration-Resistant; Drug Delivery Systems; Cell Survival; Drug Liberation; Antineoplastic Agents; Benzopyrans; Butyrates
PubMed: 38956125
DOI: 10.1038/s41598-024-65999-x -
Nature Communications Jul 2024Long-term treatment of myocardial infarction is challenging despite medical advances. Tissue engineering shows promise for MI repair, but implantation complexity and...
Long-term treatment of myocardial infarction is challenging despite medical advances. Tissue engineering shows promise for MI repair, but implantation complexity and uncertain outcomes pose obstacles. microRNAs regulate genes involved in apoptosis, angiogenesis, and myocardial contraction, making them valuable for long-term repair. In this study, we find downregulated miR-199a-5p expression in MI. Intramyocardial injection of miR-199a-5p into the infarcted region of male rats revealed its dual protective effects on the heart. Specifically, miR-199a-5p targets AGTR1, diminishing early oxidative damage post-myocardial infarction, and MARK4, which influences long-term myocardial contractility and enhances cardiac function. To deliver miR-199a-5p efficiently and specifically to ischemic myocardial tissue, we use CSTSMLKAC peptide to construct P-MSN/miR199a-5p nanoparticles. Intravenous administration of these nanoparticles reduces myocardial injury and protects cardiac function. Our findings demonstrate the effectiveness of P-MSN/miR199a-5p nanoparticles in repairing MI through enhanced contraction and anti-apoptosis. miR199a-5p holds significant therapeutic potential for long-term repair of myocardial infarction.
Topics: MicroRNAs; Animals; Myocardial Infarction; Male; Rats; Nanoparticles; Rats, Sprague-Dawley; Apoptosis; Myocardium; Disease Models, Animal; Myocardial Contraction; Administration, Intravenous; Myocardial Ischemia
PubMed: 38956062
DOI: 10.1038/s41467-024-49901-x