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International Journal of Pharmaceutics Jun 2024Uveal melanoma is one of the most common and aggressive intraocular malignancies, and, due to its great capability of metastasize, it constitutes the most incident...
Uveal melanoma is one of the most common and aggressive intraocular malignancies, and, due to its great capability of metastasize, it constitutes the most incident intraocular tumor in adults. However, to date there is no effective treatment since achieving the inner ocular tissues still constitutes one of the greatest challenges in actual medicine, because of the complex structure and barriers. Uncoated and PEGylated nanostructured lipid carriers were developed to achieve physico-chemical properties (mean particle size, homogeneity, zeta potential, pH and osmolality) compatible for the ophthalmic administration of (S)-(-)-MRJF22, a new custom-synthetized prodrug for the potential treatment of uveal melanoma. The colloidal physical stability was investigated at different temperatures by Turbiscan® Ageing Station. Morphology analysis and mucoadhesive studies highlighted the presence of small particles suitable to be topically administered on the ocular surface. In vitro release studies performed using Franz diffusion cells demonstrated that the systems were able to provide a slow and prolonged prodrug release. In vitro cytotoxicity test on Human Corneal Epithelium and Human Uveal Melanoma cell lines and Hen's egg-chorioallantoic membrane test showed a dose-dependent cytotoxic effect of the free prodrug on corneal cells, whose cytocompatibility improved when encapsulated into nanoparticles, as also confirmed by in vivo studies on New Zealand albino rabbits. Antiangiogenic capability and preventive anti-inflammatory properties were also investigated on embryonated eggs and rabbits, respectively. Furthermore, preliminary in vivo biodistribution images of fluorescent nanoparticles after topical instillation in rabbits' eyes, suggested their ability to reach the posterior segment of the eye, as a promising strategy for the treatment of choroidal uveal melanoma.
PubMed: 38851409
DOI: 10.1016/j.ijpharm.2024.124300 -
Clinical Nutrition (Edinburgh, Scotland) Jul 2024Patients with an ileostomy are at increased risk of dehydration and sodium depletion. Treatments recommended may include oral rehydration solutions (ORS). We aimed to... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIM
Patients with an ileostomy are at increased risk of dehydration and sodium depletion. Treatments recommended may include oral rehydration solutions (ORS). We aimed to investigate if protein type or protein hydrolysation affects absorption from iso-osmolar ORS in patients with an ileostomy.
METHODS
This was a randomised, double-blinded, active comparator-controlled 3 × 3 crossover intervention study. We developed three protein-based ORS with whey protein isolate, caseinate or whey protein hydrolysate. The solutions contained 40-48 g protein/L, 34-45 mmol sodium/L and had an osmolality of 248-270 mOsm/kg. The patients ingested 500 mL/d. The study consisted of three 4-week periods with a >2-week washout between each intervention. The primary outcome was wet-weight ileostomy output. Ileostomy output and urine were collected for a 24-h period before and after each intervention. Additionally, blood sampling, dietary records, muscle-strength tests, bioimpedance analyses, questionnaires and psychometric tests were conducted.
RESULTS
We included 14 patients, of whom 13 completed at least one intervention. Ten patients completed all three interventions. Wet-weight ileostomy output did not change following either of the three interventions and did not differ between interventions (p = 0.38). A cluster of statistically significant improvements related to absorption was observed following the intake of whey protein isolate ORS, including decreased faecal losses of energy (-365 kJ/d, 95% confidence interval (CI), -643 to -87, p = 0.012), potassium (-7.8 mmol/L, 95%CI, -12.0 to -3.6, p = 0.001), magnesium (-4.0 mmol/L, 95%CI, -7.4 to -0.7, p = 0.020), improved plasma aldosterone (-4674 pmol/L 95%CI, -8536 to -812, p = 0.019), estimated glomerular filtration rate (eGFR) (2.8 mL/min/1.73 m, 95%CI, 0.3 to 5.4, p = 0.03) and CO (1.7 mmol/L 95%CI, 0.1 to 3.3, p = 0.04).
CONCLUSION
Ingestion of 500 mL/d of iso-osmolar solutions containing either whey protein isolate, caseinate or whey protein hydrolysate for four weeks resulted in unchanged and comparable ileostomy outputs in patients with an ileostomy. Following whey protein isolate ORS, we observed discrete improvements in a series of absorption proxies in both faeces and blood, indicating increased absorption. The protein-based ORS were safe and well-tolerated. Treatments should be tailored to each patient, and future studies are warranted to explore treatment-effect heterogeneity and whether different compositions or doses of ORS can improve absorption and nutritional status in patients with an ileostomy.
GOV STUDY IDENTIFIER
NCT04141826.
Topics: Humans; Ileostomy; Cross-Over Studies; Double-Blind Method; Male; Female; Whey Proteins; Middle Aged; Aged; Rehydration Solutions; Fluid Therapy; Dehydration; Caseins; Protein Hydrolysates; Adult
PubMed: 38850996
DOI: 10.1016/j.clnu.2024.05.038 -
Ecotoxicology and Environmental Safety Jul 2024The widespread utilization of plastic products ineluctably leads to the ubiquity of nanoplastics (NPs), causing potential risks for aquatic environments. Interactions of...
Heteroaggregation and deposition behaviors of carboxylated nanoplastics with different types of clay minerals in aquatic environments: Important role of calcium(II) ion-assisted bridging.
The widespread utilization of plastic products ineluctably leads to the ubiquity of nanoplastics (NPs), causing potential risks for aquatic environments. Interactions of NPs with mineral surfaces may affect NPs transport, fate and ecotoxicity. This study aims to investigate systematically the deposition and aggregation behaviors of carboxylated polystyrene nanoplastics (COOH-PSNPs) by four types of clay minerals (illite, kaolinite, Na-montmorillonite, and Ca-montmorillonite) under various solution chemistry conditions (pH, temperature, ionic strength and type). Results demonstrate that the deposition process was dominated by electrostatic interactions. Divalent cations (i.e., Ca, Mg, Cd, or Pb) were more efficient for screening surface negative charges and compressing the electrical double layer (EDL). Hence, there were significant increases in deposition rates of COOH-PSNPs with clay minerals in suspension containing divalent cations, whereas only slight increases in deposition rates of COOH-PSNPs were observed in monovalent cations (Na, K). Negligible deposition occurred in the presence of anions (F, Cl, NO, CO, SO, or PO). Divalent Ca could incrementally facilitate the deposition of COOH-PSNPs through Ca-assisted bridging with increasing CaCl concentrations (0-100 mM). The weakened deposition of COOH-PSNPs with increasing pH (2.0-10.0) was primarily attributed to the reduce in positive charge density at the edges of clay minerals. In suspensions containing 2 mM CaCl, increased Na ionic strength (0-100 mM) and temperature (15-55 C) also favored the deposition of COOH-PSNPs. The ability of COOH-PSNPs deposited by four types of clay minerals followed the sequence of kaolinite > Na-montmorillonite > Ca-montmorillonite > illite, which was related to their structural and surface charge properties. This study revealed the deposition behaviors and mechanisms between NPs and clay minerals under environmentally representative conditions, which provided novel insights into the transport and fate of NPs in natural aquatic environments.
Topics: Clay; Calcium; Water Pollutants, Chemical; Osmolar Concentration; Hydrogen-Ion Concentration; Aluminum Silicates; Polystyrenes; Temperature; Minerals; Bentonite; Nanoparticles; Kaolin; Static Electricity
PubMed: 38850697
DOI: 10.1016/j.ecoenv.2024.116533 -
Biomedicine & Pharmacotherapy =... Jul 2024Polymer-cationic mediated gene delivery is a well-stablished strategy of transient gene expression (TGE) in mammalian cell cultures. Nonetheless, its industrial...
Polymer-cationic mediated gene delivery is a well-stablished strategy of transient gene expression (TGE) in mammalian cell cultures. Nonetheless, its industrial implementation is hindered by the phenomenon known as cell density effect (CDE) that limits the cell density at which cultures can be efficiently transfected. The rise in personalized medicine and multiple cell and gene therapy approaches based on TGE, make more relevant to understand how to circumvent the CDE. A rational study upon DNA/PEI complex formation, stability and delivery during transfection of HEK293 cell cultures has been conducted, providing insights on the mechanisms for polyplexes uptake at low cell density and disruption at high cell density. DNA/PEI polyplexes were physiochemically characterized by coupling X-ray spectroscopy, confocal microscopy, cryo-transmission electron microscopy (TEM) and nuclear magnetic resonance (NMR). Our results showed that the ionic strength of polyplexes significantly increased upon their addition to exhausted media. This was reverted by depleting extracellular vesicles (EVs) from the media. The increase in ionic strength led to polyplex aggregation and prevented efficient cell transfection which could be counterbalanced by implementing a simple media replacement (MR) step before transfection. Inhibiting and labeling specific cell-surface proteoglycans (PGs) species revealed different roles of PGs in polyplexes uptake. Importantly, the polyplexes uptake process seemed to be triggered by a coalescence phenomenon of HSPG like glypican-4 around polyplex entry points. Ultimately, this study provides new insights into PEI-based cell transfection methodologies, enabling to enhance transient transfection and mitigate the cell density effect (CDE).
Topics: Humans; HEK293 Cells; Transfection; Glypicans; DNA; Polyethyleneimine; Heparan Sulfate Proteoglycans; Osmolar Concentration
PubMed: 38850653
DOI: 10.1016/j.biopha.2024.116893 -
Scientific Reports Jun 2024Salinity stress significantly hinders plant growth by disrupting osmotic balance and inhibiting nutrient uptake, leading to reduced biomass and stunted development....
Salinity stress significantly hinders plant growth by disrupting osmotic balance and inhibiting nutrient uptake, leading to reduced biomass and stunted development. Using saponin (SAP) and boron (B) can effectively overcome this issue. Boron decreases salinity stress by stabilizing cell walls and membranes, regulating ion balance, activating antioxidant enzymes, and enhancing water uptake. SAP are bioactive compounds that have the potential to alleviate salinity stress by improving nutrient uptake, modulating plant hormone levels, promoting root growth, and stimulating antioxidant activity. That's why the current study was planned to use a combination of SAP and boron as amendments to mitigate salinity stress in sweet potatoes. Four levels of SAP (0%, 0.1%, 0.15%, and 0.20%) and B (control, 5, 10, and 20 mg/L B) were applied in 4 replications following a completely randomized design. Results illustrated that 0.15% SAP with 20 mg/L B caused significant enhancement in sweet potato vine length (13.12%), vine weight (12.86%), root weight (8.31%), over control under salinity stress. A significant improvement in sweet potato chlorophyll a (9.84%), chlorophyll b (20.20%), total chlorophyll (13.94%), photosynthetic rate (17.69%), transpiration rate (16.03%), and stomatal conductance (17.59%) contrast to control under salinity stress prove the effectiveness of 0.15% SAP + 20 mg/L B treatment. In conclusion, 0.15% SAP + 20 mg/L B is recommended to mitigate salinity stress in sweet potatoes.
Topics: Ipomoea batatas; Boron; Saponins; Salt Stress; Photosynthesis; Plant Roots; Chlorophyll; Drug Synergism; Salinity
PubMed: 38844823
DOI: 10.1038/s41598-024-63840-z -
BMC Plant Biology Jun 2024Lentil is a significant legume that are consumed as a staple food and have a significant economic impact around the world. The purpose of the present research on lentil...
BACKGROUND
Lentil is a significant legume that are consumed as a staple food and have a significant economic impact around the world. The purpose of the present research on lentil was to assess the hydrothermal time model's capacity to explain the dynamics of Lens culinaris L. var. Markaz-09 seed germination, as well as to ascertain the germination responses at various sub-optimal temperatures (T) and water potentials (Ψ). In order to study lentil seed germination (SG) behavior at variable water potentials (Ψs) and temperatures (Ts). A lab experiment employing the hydrothermal time model was created. Seeds were germinated at six distinct temperatures: 15 С, 20 С, 25 С, 30 С, 35 С, and 40 С, with five Ψs of 0, -0.3, -0.6, -0.9, and - 1.2 MPa in a PEG-6000 (Polyethylene glycol 6000) solution.
RESULTS
The results indicated that the agronomic parameters like Germination index (GI), Germination energy (GE), Timson germination index (TGI), were maximum in 25 C at (-0.9 MPa) and lowest at 40 C in 0 MPa. On other hand, mean germination time (MGT) value was highest at 15 C in -1.2 MPa and minimum at 40 C in (-0.6 MPa) while Mean germination rate (MGR) was maximum at 40 C in (0 MPa) and minimum at 15 C in (-0.6 MPa).
CONCLUSIONS
The HTT model eventually defined the germination response of Lens culinaris L. var. Markaz-09 (Lentil) for all Ts and Ψs, allowing it to be employed as a predictive tool in Lens culinaris L. var. Markaz-09 (Lentil) seed germination simulation models.
Topics: Germination; Seeds; Lens Plant; Temperature; Water; Models, Biological; Osmotic Pressure
PubMed: 38840053
DOI: 10.1186/s12870-024-05223-0 -
The Science of the Total Environment Sep 2024A multitude of anthropogenic stressors impact biological communities and ecosystem processes in urban streams. Prominent among them are salinization, increased...
Multiple stressors affecting microbial decomposer and litter decomposition in restored urban streams: Assessing effects of salinization, increased temperature, and reduced flow velocity in a field mesocosm experiment.
A multitude of anthropogenic stressors impact biological communities and ecosystem processes in urban streams. Prominent among them are salinization, increased temperature, and altered flow regimes, all of which can affect microbial decomposer communities and litter decomposition, a fundamental ecosystem process in streams. Impairments caused by these stressors individually or in combination and recovery of communities and ecosystem processes after release from these stressors are not well understood. To improve our understanding of multiple stressors impacts we performed an outdoor stream mesocosm experiment with 64 experimental units to assess the response of microbial litter decomposers and decomposition. The three stressors we applied in a full-factorial design were increased salinity (NaCl addition, 0.53 mS cm above ambient), elevated temperature (3.5 °C above ambient), and reduced flow velocity (3.5 vs 14.2 cm s). After two weeks of stressor exposure (first sampling) and two subsequent weeks of recovery (second sampling), we determined leaf-associated microbial respiration, fungal biomass, and the sporulation activity and community composition of aquatic hyphomycetes in addition to decomposition rates of black alder (Alnus glutinosa) leaves confined in fine-mesh litter bags. Microbial colonization of the litter was accompanied by significant mass loss in all mesocosms. However, there was little indication that mass loss, microbial respiration, fungal biomass, sporulation rate or community composition of aquatic hyphomycetes was strongly affected by either single stressors or their interactions. Two exceptions were temperature effects on sporulation and decomposition rate. Similarly, no notable differences among mesocosms were observed after the recovery phase. These results suggest that microbial decomposers and leaf litter decomposition are either barely impaired by exposure to the tested stressors at the levels applied in our experiment, or that communities in restored urban streams are well adapted to cope with these stressor levels.
Topics: Rivers; Salinity; Biodegradation, Environmental; Ecosystem; Plant Leaves; Alnus; Temperature; Environmental Monitoring
PubMed: 38839005
DOI: 10.1016/j.scitotenv.2024.173669 -
The Science of the Total Environment Sep 2024Field observations form the basis of the majority of studies on microphytobenthic algal communities in freshwater ecosystems. Controlled mesocosm experiments data are...
Field observations form the basis of the majority of studies on microphytobenthic algal communities in freshwater ecosystems. Controlled mesocosm experiments data are comparatively uncommon. The few experimental mesocosm studies that have been conducted provide valuable insights into how multiple stressors affect the community structures and photosynthesis-related traits of benthic microalgae. The recovery process after the stressors have subsided, however, has received less attention in mesocosm studies. To close this gap, here we present the results of a riparian mesocosm experiment designed to investigate the effects of reduced flow velocity, increased salinity and increased temperature on microphytobenthic communities. We used a full factorial design with a semi-randomised distribution of treatments consisting of two levels of each stressor (2 × 2 × 2 treatments), with eight replicates making a total of 64 circular mesocosms, allowing a nuanced examination of their individual and combined influences. We aimed to elucidate the responses of microalgae communities seeded from stream water to the applied environmental stressors. Our results showed significant effects of reduced flow velocity and increased temperature on microphytobenthic communities. Recovery after stressor treatment led to a convergence in community composition, with priority effects (hypothesized to reflect competition for substrate between resident and newly arriving immigrant taxa) slowing down community shifts and biomass increase. Our study contributes to the growing body of literature on the ecological dynamics of microphytobenthos and emphasises the importance of rigorous experiments to validate hypotheses. These results encourage further investigation into the nuanced interactions between microphytobenthos and their environment and shed light on the complexity of ecological responses in benthic systems.
Topics: Rivers; Microalgae; Ecosystem; Salinity; Environmental Monitoring; Stress, Physiological
PubMed: 38838995
DOI: 10.1016/j.scitotenv.2024.173670 -
Kidney Diseases (Basel, Switzerland) Jun 2024G protein-coupled bile acid receptor (TGR5), the first G protein-coupled receptor for bile acids identified, is capable of activating a variety of intracellular...
INTRODUCTION
G protein-coupled bile acid receptor (TGR5), the first G protein-coupled receptor for bile acids identified, is capable of activating a variety of intracellular signaling pathways after interacting with bile acids. TGR5 plays an important role in multiple physiological processes and is considered to be a potential target for the treatment of various metabolic diseases, including type 2 diabetes. Evidence has emerged that genetic deletion of TGR5 results in an increase in basal urine output, suggesting that it may play a critical role in renal water and salt reabsorption. The present study aims to elucidate the effect and mechanism of TGR5 activation on urine concentration.
METHODS
Mice were treated with TGR5 agonists (LCA and INT-777) for 3 days. The 24-h urine of mice was collected and analyzed for urine biochemical parameters. The mRNA expressions were detected by real-time PCR, and the protein expressions were detected by western blot. Immunohistochemistry and immunofluorescence were performed to examine the cellular location of proteins. The cultured primary medullary collecting duct cells were pretreated with H89 (a PKA inhibitor) for 1 h, followed by 12-h treatment of LCA and INT-777. Luciferase reporter assays were used to detect the effect of CREB on the gene transcription of AQPs. Gel electrophoretic mobility shift assays were used to analyze DNA-protein interactions.
RESULTS
Treatment of mice with the TGR5 agonist LCA and INT-777 markedly reduced urine output and increased urine osmolality, accompanied by a marked increase in AQP2 and AQP3 protein expression and membrane translocation. In cultured primary medullary collecting duct cells, LCA and INT-777 dose-dependently upregulated AQP2 and AQP3 expression in a cAMP/PKA-dependent manner. Mechanistically, both AQP2 and AQP3 gene promoter contains a putative CREB-binding site, which can be bound and activated by CREB as assessed by both gene promoter-driven luciferase and gel shift assays.
CONCLUSION
Collectively, our findings demonstrate that activation of TGR5 can promote urine concentration by upregulation of AQP2 and AQP3 expression in renal collecting ducts. TGR5 may represent an attractive target for the treatment of patients with urine concentration defect.
PubMed: 38835402
DOI: 10.1159/000538107 -
Scientific Reports Jun 2024Salinity stress significantly impacts crops, disrupting their water balance and nutrient uptake, reducing growth, yield, and overall plant health. High salinity in soil...
Salinity stress significantly impacts crops, disrupting their water balance and nutrient uptake, reducing growth, yield, and overall plant health. High salinity in soil can adversely affect plants by disrupting their water balance. Excessive salt levels can lead to dehydration, hinder nutrient absorption, and damage plant cells, ultimately impairing growth and reducing crop yields. Gallic acid (GA) and zinc ferrite (ZnFNP) can effectively overcome this problem. GA can promote root growth, boost photosynthesis, and help plants absorb nutrients efficiently. However, their combined application as an amendment against drought still needs scientific justification. Zinc ferrite nanoparticles possess many beneficial properties for soil remediation and medical applications. That's why the current study used a combination of GA and ZnFNP as amendments to wheat. There were 4 treatments, i.e., 0, 10 µM GA, 15 μM GA, and 20 µM GA, without and with 5 μM ZnFNP applied in 4 replications following a completely randomized design. Results exhibited that 20 µM GA + 5 μM ZnFNP caused significant improvement in wheat shoot length (28.62%), shoot fresh weight (16.52%), shoot dry weight (11.38%), root length (3.64%), root fresh weight (14.72%), and root dry weight (9.71%) in contrast to the control. Significant enrichment in wheat chlorophyll a (19.76%), chlorophyll b (25.16%), total chlorophyll (21.35%), photosynthetic rate (12.72%), transpiration rate (10.09%), and stomatal conductance (15.25%) over the control validate the potential of 20 µM GA + 5 μM ZnFNP. Furthermore, improvement in N, P, and K concentration in grain and shoot verified the effective functioning of 20 µM GA + 5 μM ZnFNP compared to control. In conclusion, 20 µM GA + 5 μM ZnFNP can potentially improve the growth, chlorophyll contents and gas exchange attributes of wheat cultivated in salinity stress. More investigations are suggested to declare 20 µM GA + 5 μM ZnFNP as the best amendment for alleviating salinity stress in different cereal crops.
Topics: Triticum; Salt Stress; Ferric Compounds; Gallic Acid; Zinc; Photosynthesis; Nanoparticles; Chlorophyll; Plant Roots; Salinity; Soil
PubMed: 38834735
DOI: 10.1038/s41598-024-63175-9