A potent formula against triple-negative breast cancer-sorafenib-carbon nanotubes-folic acid: Targeting, apoptosis triggering, and bioavailability enhancing.

Triple-negative breast cancer (TNBC) has short survival rates. This study aimed to prepare a novel formula of sorafenib, carbon nanotubes (CNTs), and folic acid to be tested as a drug delivery system targeting versus TNBC compared with free sorafenib and to evaluate the formula stability, in vitro pharmacodynamic, and in vivo pharmacokinetic properties. The formula preparation was done by the synthesis of polyethylene glycol bis amine linker, CNT PEGylation, folic acid attachment, and sorafenib loading. The prepared formula has been characterized using X-ray diffraction, Flourier-transform infrared, 1HNMR, UV, high resolution-transmission electron microscope, field emission scanning electron microscopy, and Zeta potential. In vitro studies included drug release determination, MTT assay, flow cytometry to determine the apoptotic stage with percent, cell cycle analysis, and apoptotic marker assays for caspase-3, 8, 9, cytochrome c, and BCL-2. The in vivo study was performed to determine bioavailability and half-life in rats. The in vitro MTT antiproliferative assay revealed that the formula was threefold more cytotoxic toward TNBC cells than free sorafenib, and the flow cytometry showed a significant increase in apoptosis and necrosis. The formula has a greater inhibitory effect on BCL-2 and a lessening effect on cytochrome c and caspases 3, 8, and 9 than free sorafenib. In vivo experiments proved that our novel formula was superior to free sorafenib by increasing bioavailability by eight times and prolonging the half-life by three times. These results confirmed the successful preparation of the desired formula with better pharmacodynamic and pharmacokinetic properties. These promising results may show a novel therapeutic strategy for TNBC patients.

Curcumin-loaded soluplus® based ternary solid dispersions with enhanced solubility, dissolution and antibacterial, antioxidant, anti-inflammatory activities.

Amorphous solid dispersion (ASD) has emerged to be an outstanding strategy among multiple options available for improving solubility and consequently biological activity. Interestingly several binary SD systems continue to exhibit insufficient solubility over time. Therefore, the goal of current research was to design ternary amorphous solid dispersions (ASDs) of hydrophobic model drug curcumin (CUR) to enhance the solubility and dissolution rate in turn, presenting enhanced anti-bacterial, antioxidant and anti-inflammatory activity. For this purpose several ternary solid dispersions (TSDs) consisting of Soluplus®, Syloid® XDP 3150, Syloid® 244 and Poloxamer® 188 in combination with HPMC E5 (binary carrier) were prepared using solvent evaporation method. Both solubility and dissolution testing of prepared solid dispersion were performed to determine the increase in solubility and dissolution. Solid state investigation was carried out utilizing infrared spectroscopy, also known as Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM),Differential scanning calorimetry (DSC) and X-ray diffraction (XRD).Optimized formulations were also tested for their biological effectiveness including anti-bacterial, anti-oxidant and anti-inflammatory activity. Amid all Ternary formulations F3 entailing 20 % soluplus® remarkably improved the solubility (186 µg/ml ± 3.95) and consequently dissolution (91 % ± 3.89 %) of curcumin by 3100 and 9 fold respectively. These finding were also supported by FTIR, SEM, XRD and DSC. In-vitro antibacterial investigation of F3 also demonstrated significant improvement in antibacterial activity against both gram positive (Staphylococcus aureus, Bacillus cereus) and gram negative (Pseudomonas aeruginosa, Escherichia coli) bacteria. Among all the tested strains Staphylococcus aureus was found to be most susceptible with a zone of inhibition of 24 mm ± 2.87. Antioxidant activity of F3 was also notably enhanced (93 % ± 5.30) in contrast to CUR (69 % ± 4.79). In vitro anti-inflammatory assessment also exhibited that F3 markedly protected BSA (bovine serum albumin) from denaturation with percent BSA inhibition of 80 % ± 3.16 in comparison to CUR (49 % ± 2.91). Hence, F3 could be an effective solid dispersion system for the delivery of model hydrophobic drug curcumin.

Engineering a 3D Biomimetic Peptides Functionalized-Polyethylene Glycol Hydrogel Model Cocultured with Endothelial Cells and Astrocytes: Enhancing In Vitro Blood-Brain Barrier Biomimicry.

The blood-brain barrier (BBB) poses a significant challenge for drug delivery and is linked to various neurovascular disorders. In vitro BBB models provide a tool to investigate drug permeation across the BBB and the barrier's response to external injury events. Yet, existing models lack fidelity in replicating the BBB's complexity, hindering a comprehensive understanding of its functions. This study introduces a three-dimensional (3D) model using polyethylene glycol (PEG) hydrogels modified with biomimetic peptides that represent recognition sequences of key proteins in the brain. Hydrogels were functionalized with recognition sequences for laminin (IKVAV) and fibronectin peptides (RGD) and chemically cross-linked with matrix metalloprotease-sensitive peptides (MMPs) to mimic the extracellular matrix of the BBB. Astrocytes and endothelial cells were seeded within and on the surface of the hydrogels, respectively. The barrier integrity was assessed through different tests including transendothelial electrical resistance (TEER), the permeability of sodium fluorescence (Na-F), the permeability of Evan's blue bound to albumin (EBA), and the expression of zonula occluden-1 (ZO-1) in seeded endothelial cells. Hydrogels with a combination of RGD and IKVAV peptides displayed superior performance, exhibiting significantly higher TEER values (55.33 ± 1.47 Ω·cm2) at day 5 compared to other 2D controls including HAECs-monoculture and HAECs-cocultured with NHAs seeded on well inserts and 3D controls including RGD hydrogel and RGD-IKVAV monoculture with HAECs and RGD hydrogel cocultured with HAECs and NHAs. The designed 3D system resulted in the lowest Evan's blue permeability at 120 min (0.215 ± 0.055 µg/mL) compared to controls. ZO-1 expression was significantly higher and formed a relatively larger network in the functionalized hydrogel cocultured with astrocytes and endothelial cells compared to the controls. Thus, the designed 3D model effectively recapitulates the main BBB structure and function in vitro and is expected to contribute to a deeper understanding of pathological CNS angiogenesis and the development of effective CNS medications.

siRNA-loaded folic acid-modified TPGS alleviate MASH via targeting ER stress sensor XBP1 and reprogramming macrophages.

Macrophages show high plasticity and play a vital role in the progression of metabolic dysfunction-associated steatohepatitis (MASH). X-box binding protein 1 (XBP1), a key sensor of the unfolded protein response, can modulate macrophage-mediated pro-inflammatory responses in the pathogenesis of MASH. However, how XBP1 influences macrophage plasticity and promotes MASH progression remains unclear. Herein, we formulated an Xbp1 siRNA delivery system based on folic acid modified D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles (FT@XBP1) to explore the precise role of macrophage-specific Xbp1 deficiency in the progression of MASH. FT@XBP1 was specifically internalized into hepatic macrophages and subsequently inhibited the expression of spliced XBP1 both in vitro and in vivo. It promoted M1-phenotype macrophage repolarization to M2 macrophages, reduced the release of pro-inflammatory factors, and alleviated hepatic steatosis, liver injury, and fibrosis in mice with fat-, fructose- and cholesterol-rich diet-induced MASH. Mechanistically, FT@XBP1 promoted macrophage polarization toward the M2 phenotype and enhanced the release of exosomes that could inhibit the activation of hepatic stellate cells. A promising macrophage-targeted siRNA delivery system was revealed to pave a promising strategy in the treatment of MASH.

A Phase I Dose-Escalation Study of The Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Polyethylene Glycol-Erythropoietin (PEG-EPO) in Healthy Subjects.

PURPOSE: This first-in-human trial aimed to investigate the pharmacokinetics and pharmacodynamics characteristics and safety and tolerability of single ascending doses of subcutaneous polyethylene glycol-erythropoietin (PEG-EPO) in healthy subjects. METHODS: In this phase I, randomized, double-blind, placebo-controlled, dose-escalating trial, subjects were sequentially enrolled into 7 cohorts with 12 subjects in each cohort and randomized in a 5:1 ratio to receive a single dose of 0.2, 0.4, 0.8, 1.6, 2.4, 3.6, or 4.8 µg/kg PEG-EPO or matching placebo. Safety and tolerability including dose-limiting toxicities (DLTs) were assessed. Pharmacokinetics parameters, including Cmax, AUC0-inf, Tmax, and t1/2, and pharmacodynamics parameters, including reticulocyte count and hemoglobin content, were evaluated. FINDINGS: Eighty-four subjects (median age 30.4 years and 77.4% male) were enrolled. No subjects developed DLTs. Any grade treatment-related adverse events occurred in 66.7% of the subjects, but most (92.9%) were mild. No serious adverse events and no death occurred. Forty percent of the subjects receiving PEG-EPO had iron decreased, 27.1% reported ferritin decreased, 25.7% showed unsaturated iron binding capacity increased, and 17.1% had neutrophil count decreased. Cmax exhibited a dose-disproportionate rise from a geometric mean of 525 pg/mL with 0.2 µg/kg PEG-EPO to 23196 pg/mL with 4.8 µg/kg PEG-EPO. The mean t1/2 ranged between 82.4 ± 21.3 h with 0.4 µg/kg PEG-EPO and 160.6 ± 65.7 h with 1.6 µg/kg PEG-EPO. AUC0-inf displayed a largely dose-proportional rise from 226264.5 pg*h/mL with 0.2 µg/kg PEG-EPO to 5206434.0 pg*h/mL with 4.8 µg/kg PEG-EPO. The absolute reticulocyte count increased with escalating doses of PEG-EPO, with the mean maximal change from baseline between 3.2 ± 1.5*10^10/L (Q1,Q3 1.8-3.6*10^10/L) with PEG-EPO 0.2 µg/kg and 9.3 ± 4.0*10^10/L (Q1,Q3 6.2-13.5*10^10/L) with 3.6 µg/kg PEG-EPO. The mean maximal change from baseline in the mean hemoglobin content ranged between 5.9 ± 4.4 g/L (Q1,Q3 3.5,7.0) with 0.2 µg/kg PEG-EPO and 15.4 ± 8.7 g/L (Q1,Q3 10.5,20.0) with 2.4 µg/kg PEG-EPO. IMPLICATIONS: This trial demonstrated that PEG-EPO was safe and tolerable in healthy subjects. The subcutaneous route of administration allows outpatient treatment and the pharmacokinetics characteristics of PEG-EPO support less frequent dosing regimens and effective treatment for chronic kidney disease patients with anemia. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT03657238.

Nanostructure and interfacial mechanical properties of PEG/cellulose nanocomposites studied with molecular dynamics.

Our starting hypothesis is that Polyethylene glycol (PEG) can be utilized to mix with the biopolymers for consolidating fiber-reinforced composites without deteriorating their hygro-mechanical properties. The effect of PEG on the shear strength during pull-out of crystalline cellulose (CC) fiber out of an amorphous cellulose matrix is simulated with molecular dynamics. The interfacial shear stress shows a stick-slip behavior and is weakened with increasing moisture content. Shear strength increases at low moisture content, manifesting a slight strengthening of interfacial mechanical property due to cohesive forces exerted by the water molecules. At higher moisture content, shear strength is reduced due to breakage of the hydrogen bonds between CC and matrix by water molecules. When adding PEG, amorphous cellulose around the crystalline fiber is replaced by PEG, forming a mixture with amorphous cellulose. It is found that PEG-treated CC-AC composite maintains its shear strength and the presence of PEG does not deteriorate the dependence of the shear strength on moisture content. A shear strength model based on the number of hydrogen bonds between the fiber and the matrix is developed, which validates our initial hypothesis by unraveling the fundamental mechanisms at play. The model reveals that, although the shear strength per hydrogen bond between the fiber and PEG is lower than the shear strength per hydrogen bond between the fiber and amorphous cellulose, the final shear strength is partly compensated by an increase in the total number of hydrogen bonds with increasing PEG ratio. Since PEG reduces the moisture content in the composite at low relative humidity, PEG treated wood in museum conditions will show enhanced shear strength. The framework is a basis for further investigation of realistic archaeological wood with PEG-treatment.

Oral sulfate solution versus polyethylene glycol for bowel preparation before colonoscopy, meta-analysis and trial sequential analysis of randomized clinical trials.

BACKGROUND: This study aimed to compare oral sulfate solution (OSS) with polyethylene glycol (PEG) for bowel preparation before colonoscopy. METHODS: A literature search was performed on PubMed, Ovid, and Cochrane Databases for randomized clinical trials (RCT) comparing OSS with PEG for bowel preparation before colonoscopy. The last search was performed on 22 August 2023. The primary outcome was the quality of bowel preparation. The outcomes were compared by meta-analysis and trial sequential analysis (TSA). RESULTS: A total of 14 RCTs with 4526 patients were included. OSS was comparable with PEG regarding adequate bowel preparation [P = 0.16, odds ratio (OR) = 1.19, 95% confidence interval (CI) [0.93, 1.51], I2 = 0%]. However, OSS showed obvious priority in excellent bowel preparation (P < 0.001, OR = 1.62, 95% CI [1.27, 2.05], I2 = 0%) and total Boston bowel preparation scale (BBPS) [P = 0.02, weighted mean difference (WMD) = 0.27, 95% CI [0.05, 0.50], I2 = 84%]. Additionally, the detection rate of polyps (P = 0.001, OR = 1.44, 95% CI [1.15, 1.80], I2 = 0%) and adenoma (P = 0.007, OR = 1.22, 95% CI [1.06, 1.42], I2 = 0%) was significantly higher in the OSS group. The two groups showed comparable incidence of adverse events except for a higher incidence of dizziness (P = 0.02, OR = 1.74, 95% CI [1.08, 2.83], I2 = 11%) was indicated in the OSS group. Moreover, OSS was associated with a higher satisfaction score (P = 0.02, WMD = 0.62, 95% CI [0.09, 1.15], I2 = 70%). In the TSA, the cumulative Z-curve crossed both the conventional boundary and trial sequential monitoring boundary and the required information size has been reached for excellent bowel preparation and total BBPS. CONCLUSION: The current data demonstrated that OSS was associated with better quality of bowel preparation. More clinical trials are still needed to confirm other outcomes.

Efficacy and safety of polyethylene glycol loxenatide in treating mild-to-moderate diabetic kidney disease in type 2 diabetes patients: a randomized, open-label, clinical trial.

Objective: This study aimed to evaluate the efficacy and safety of polyethylene glycol loxenatide (PEG-Loxe) compared to those of dapagliflozin in patients with mild-to-moderate diabetic kidney disease (DKD), a prevalent microvascular complication of type 2 diabetes mellitus (T2DM). The study is set against the backdrop of increasing global diabetes incidence and the need for effective DKD management. Methods: This study constituted a single-center, randomized, open-label, clinical trial. The trial included patients with mild-to-moderate DKD and suboptimal glycemic control. Eligible participants were randomly allocated to one of the two groups for treatment with either PEG-Loxe or dapagliflozin. The primary endpoint was the change in UACR from baseline at 24 weeks. Results: Overall, 106 patients were randomized and 80 patients completed the study. Following 24 weeks of treatment, the PEG-Loxe group exhibited a mean percent change in baseline UACR of -29.3% (95% confidence interval [CI]: -34.8, -23.7), compared to that of -31.8% in the dapagliflozin group (95% CI: -34.8, -23.7). Both PEG-Loxe and dapagliflozin showed similar efficacy in reducing UACR, with no significant difference between the groups (p = 0.336). The HbA1c levels decreased by -1.30% (95% CI: -1.43, -1.18) in the PEG-Loxe group and by -1.29% (95% CI: -1.42, -1.17) in the dapagliflozin group (p = 0.905). The TG levels decreased by -0.56 mmol/L (95% CI: -0.71, -0.42) in the PEG-Loxe group and -0.33 mmol/L (95% CI: -0.48, -0.19) in the dapagliflozin group (p = 0.023). Differences in TC, HDL-C, LDL-C, SBP, and DBP levels between the groups were not statistically significant (all p > 0.05). Safety profiles were consistent with previous findings, with gastrointestinal adverse events being more common in the PEG-Loxe group. Conclusions: PEG-Loxe is as effective as dapagliflozin in improving urine protein levels in patients with mild-to-moderate DKD and offers superior benefits in improving lipid profiles. These findings support the use of PEG-Loxe in DKD management, contributing to evidence-based treatment options. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2300070919.

Analysis of Freeze-Thaw Damage of Cement Mortars Doped with Polyethylene Glycol-Based Form Stable Phase Change Materials.

The development of construction materials with the integration of phase change materials (PCMs) has been a topic of wide interest in the scientific community, especially in recent years, due to its positive impact on temperature regulation inside buildings. However, little is known about the behavior of materials doped with PCMs when exposed to accidental or severe environments. Currently, a large area of the planet experiences seasonal freeze-thaw effects, which impact the durability and performance of construction materials. Accordingly, the main objective of this study was to evaluate the damage caused by cyclic freeze-thaw actions on the behavior of a cement mortar, including a PEG-based form-stable PCM. An experimental methodology was developed based on the physical and mechanical characterization of mortars under normal operating conditions and after being subjected to freeze-thaw cycles. The results indicated that, under normal exposure conditions, the incorporation of aggregate functionalized with PCM led to a decrease in the mortar's water absorption capacity, compressive strength, and adhesion. However, its applicability has not been compromised. Exposure to freeze-thaw cycles caused a loss of mass in the specimens and a decrease in the compressive strength and adhesion capability of the mortar.

The Effect of Polyethylene Glycol on the Non-Isothermal Crystallization of Poly(L-lactide) and Poly(D-lactide) Blends.

The formation of polylactide stereocomplex (sc-PLA), involving the blending of poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA), enhances PLA materials by making them stronger and more heat-resistant. This study investigated the competitive crystallization behavior of homocrystals (HCs) and stereocomplex crystals (SCs) in a 50/50 PLLA/PDLA blend with added polyethylene glycol (PEG). PEG, with molecular weights of 400 g/mol and 35,000 g/mol, was incorporated at concentrations ranging from 5% to 20% by weight. Differential scanning calorimetry (DSC) analysis revealed that PEG increased the crystallization temperature, promoted SC formation, and inhibited HC formation. PEG also acted as a plasticizer, lowering both melting and crystallization temperatures. The second heating DSC curve showed that the pure PLLA/PDLA blend had a 57.1% fraction of SC while adding 5% PEG with a molecular weight of 400 g/mol resulted in complete SC formation. In contrast, PEG with a molecular weight of 35,000 g/mol was less effective, allowing some HC formation. Additionally, PEG consistently promoted SC formation across various cooling rates (2, 5, 10, or 20 °C/min), demonstrating a robust influence under different conditions.

Anti-Cancer Properties of Two Intravenously Administrable Curcumin Formulations as Evaluated in the 3D Patient-Derived Cancer Spheroid Model.

Curcumin (Cur) is a heavily used complementary derived drug from cancer patients. Spheroid samples derived from 82 patients were prepared and treated after 48 h with two Cur formulations (CurA, CurB) in mono- and combination therapy. After 72 h, cell viability and morphology were assessed. The Cur formulations had significant inhibitory effects of -8.47% (p < 0.001), CurA of -10.01% (-50.14-23.11%, p = 0.001) and CurB of -6.30% (-33.50-19.30%, p = 0.006), compared to their solvent controls Polyethylene-glycol, ß-Cyclodextrin (CurA) and Kolliphor-ELP, Citrate (CurB). Cur formulations were more effective in prostate cancer (-19.54%) and less effective in gynecological non-breast cancers (0.30%). CurA showed better responses in samples of patients <40 (-13.81%) and >70 years of age (-17.74%). CurB had stronger effects in metastasized and heavily pretreated tumors. Combinations of Cur formulations and standard therapies were superior in 20/47 samples (42.55%) and inferior in 7/47 (14.89%). CurB stimulated chemo-doublets more strongly than monotherapies (-0.53% vs. -6.51%, p = 0.022) and more effectively than CurA (-6.51% vs. 3.33%, p = 0.005). Combinations of Cur formulations with Artesunate, Resveratrol and vitamin C were superior in 35/70 (50.00%) and inferior in 16/70 (22.86%) of samples. Cur formulations were significantly enhanced by combination with Artesunate (p = 0.020). Cur formulations showed a high variance in their anti-cancer effects, suggesting a need for individual testing before administration.

Acute Gastropathy Associated with Bowel Preparation for Colonoscopy.

Background/Aims: Utilization of low-volume preparation agents is crucial to improve patient willingness to undergo repeat colonoscopies. However, gastric safety data on preparation agents are limited. This study evaluated the acute gastropathy associated with bowel preparation agents. Methods: This retrospective study enrolled healthy subjects who underwent both esophagogastroduodenoscopy and colonoscopy screening. Baseline patient characteristics, bowel preparation success, acute gastropathy, and polyp and adenoma detection rates were evaluated for 1 L polyethylene glycol with ascorbic acid (1 L PEG/Asc) and oral sulfate tablet (OST) groups. Results: Comparison of the OST group (n=2,463) with the 1 L PEG/Asc group (n=2,060) revealed that the rates of successful cleansing and high-quality cleansing were similar between the two groups. Polyp and adenoma detection rates were significantly higher in the OST group than in the 1 L PEG/Asc group (p<0.001 and p=0.013), while the incidence of acute gastric mucosal lesion-like blood stain/clot, erosions at greater curvature side of antrum/body, multiple erosions, and overlying mucosal erythema or edema were all significantly higher in the OST group than in the 1 L PEG/Asc group (all p<0.001). Additionally, high and indeterminate probability scores of preparation agent-induced gastropathy (p=0.001) and mean Lanza scores were significantly higher in the OST group than in the 1 L PEG/Asc group (1.3 vs. 0.4, p<0.001). Conclusions: Compared with 1 L PEG/Asc, OSTs were significantly associated with acute gastropathy during bowel preparation, thus requiring careful consideration from physicians for the simultaneous screening of EGD and colonoscopy.

A randomized prospective study comparing the effect of low-volume bowel preparations for colonoscopy preparation in China.

AIM: To evaluate the effect of sodium picosulfate/magnesium citrate (SPMC) and 3 L split-dose polyethylene glycol (PEG) with or without dimethicone on bowel preparation before colonoscopy. METHODS: In this multicenter, prospective, randomized, controlled study conducted from April 2021 to December 2021, consecutive adult patients scheduled for colonoscopy were prospectively randomized into four groups: SPMC, SPMC plus dimethicone, 3 L PEG, and 3 L PEG plus dimethicone. Primary endpoint was colon cleansing based on Boston Bowel Preparation Scale (BBPS). Secondary endpoints were bubble score, time to cecal intubation, adenoma detection rate (ADR), patient safety and compliance, and adverse events. RESULTS: We enrolled 223 and 291 patients in SPMC and 3 L PEG group, respectively. The proportion with acceptable bowel cleansing, total BBPS score and cecal intubation time were similar in all four subgroups (p > 0.05). Patient-reported acceptability and tolerability was significantly greater in SPMC than 3 L PEG group (p < 0.001); adverse events were significantly lower in SPMC than latter group (p < 0.001). ADR in both groups was greater than 30%. CONCLUSION: SPMC had significantly higher acceptability and tolerability than 3 L PEG, however, was similar in terms of bowel-cleansing effect and cecal intubation time and hence can be used before colonoscopy preparation.

Supercooled preservation of cultured primary rat hepatocyte monolayers.

Supercooled preservation (SCP) is a technology that involves cooling a substance below its freezing point without initiating ice crystal formation. It is a promising alternative to prolong the preservation time of cells, tissues, engineered tissue products, and organs compared to the current practices of hypothermic storage. Two-dimensional (2D) engineered tissues are extensively used in in vitro research for drug screening and development and investigation of disease progression. Despite their widespread application, there is a lack of research on the SCP of 2D-engineered tissues. In this study, we presented the effects of SCP at -2 and -6°C on primary rat hepatocyte (PRH) monolayers for the first time and compared cell viability and functionality with cold storage (CS, + 4°C). We preserved PRH monolayers in two different commercially available solutions: Hypothermosol-FRS (HTS-FRS) and the University of Wisconsin (UW) with and without supplements (i.e., polyethylene glycol (PEG) and 3-O-Methyl-Α-D-Glucopyranose (3-OMG)). Our findings revealed that UW with and without supplements were inadequate for the short-term preservation of PRH monolayers for both SCP and CS with high viability, functionality, and monolayer integrity. The combination of supplements (PEG and 3-OMG) in the HTS-FRS solution outperformed the other groups and yielded the highest viability and functional capacity. Notably, PRH monolayers exhibited superior viability and functionality when stored at -2°C through SCP for up to 3 days compared to CS. Overall, our results demonstrated that SCP is a feasible approach to improving the short-term preservation of PRH monolayers and enables readily available 2D-engineered tissues to advance in vitro research. Furthermore, our findings provide insights into preservation outcomes across various biological levels, from cells to tissues and organs, contributing to the advancement of bioengineering and biotechnology.

Isolation of Polyethylene Glycol with Larger Molecular Weights via Metal-Organic Frameworks.

Polymer products typically present as mixtures with a range of molecular weights, which notably influence the expression of their properties. In this study, a technique is proposed to separate polyethylene glycol (PEG) mixtures of varying molecular weights using metal-organic frameworks (MOFs), thereby narrowing down their molecular weight distribution. Due to the hydrogen bond interactions between PEG and -OH groups in the pores of NU-1000, NU-1000 can selectively adsorb PEG with larger molecular weights from PEG mixture. This separation method consistently yields with narrower molecular weight distribution across multiple cycles. This is the first application of MOFs in regulating the dispersity (Ð) of polymers in solution, providing a novel approach for separating and purifying mixed molecular weight polymers.

Hepatitis B cure: Current situation and prospects.

Achievement of a 'clinical cure' in chronic hepatitis B (CHB) implies sustained virological suppression and immunological control over the infection, which is the ideal treatment goal according to domestic and international CHB management guidelines. Clinical practice has shown encouraging results for specific patient cohorts using tailored treatment regimens. These regimens incorporate either nucleos(t)ide analogs, immunomodulatory agents such as pegylated interferon α, or a strategic combination of both, sequentially or concurrently administered. Despite these advancements in the clinical handling of hepatitis B, achieving a clinical cure remains elusive for a considerable subset of patients due to the number of challenges that preclude the realization of optimal treatment outcomes. These include, but are not limited to, the emergence of antiviral resistance, incomplete immune recovery, and the persistence of covalently closed circular DNA. Moreover, the variance in response to interferon therapy and the lack of definitive biomarkers for treatment cessation also contribute to the complexity of achieving a clinical cure. This article briefly overviews the current research progress and existing issues in pursuing a clinical cure for hepatitis B.

Recombinant Protein Production in Suspension Mammalian Cells Using the BacMam Baculovirus Expression System.

Mammalian cell lines are one of the best options when it comes to the production of complex proteins requiring specific glycosylation patterns. Plasmid DNA transfection and stable cell lines are frequently used for recombinant protein production, but they are expensive at large scale or can become time-consuming, respectively. The BacMam baculovirus (BV) is a safe and cost-effective platform to produce recombinant proteins in mammalian cells. The process of generating BacMam BVs is straightforward and similar to the generation of "insect" BVs, with different commercially available platforms. Although there are several protocols that describe recombinant protein expression with the BacMam BV in adherent cell lines, limited information is available on suspension cells. Therefore, it is of relevance to define the conditions to produce recombinant proteins in suspension cell cultures with BacMam BVs that facilitate bioprocess transfer to larger volumes. Here, we describe a method to generate a high titer BacMam BV stock and produce recombinant proteins in suspension HEK293 cells.

The effect of MgO nanoparticle on PVA/PEG-based membranes for potential application in wound healing.

The interest in wound dressings increased ten years ago. Wound care practitioners can now use interactive/bioactive dressings and tissue-engineered skin substitutes. Several bandages can heal burns, but none can treat all chronic wounds. This study formulates a composite material from 70% polyvinyl alcohol (PVA) and 30% polyethylene glycol (PEG) with 0.2, 0.4, and 0.6 wt% magnesium oxide nanoparticles. This study aims to create a biodegradable wound dressing. A Fourier Transform Infrared (FTIR) study shows that PVA, PEG, and MgO create hydrogen bonding interactions. Hydrophilic characteristics are shown by the polymeric blend's 56.289° contact angle. MgO also lowers the contact angle, making the film more hydrophilic. Hydrophilicity improves film biocompatibility, live cell adhesion, wound healing, and wound dressing degradability. Differential Scanning Calorimeter (DSC) findings suggest the PVA/PEG combination melted at 53.16 °C. However, adding different weight fractions of MgO nanoparticles increased the nanocomposite's melting temperature (Tm). These nanoparticles improve the film's thermal stability, increasing Tm. In addition, MgO nanoparticles in the polymer blend increased tensile strength and elastic modulus. This is due to the blend's strong adherence to the reinforcing phase and MgO nanoparticles' ceramic material which has a great mechanical strength. The combination of 70% PVA + 30% PEG exhibited good antibacterial spatially at 0.2% MgO, according to antibacterial test results.

Ratiometric electrochemical aptasensor with strand displacement for insulin detection in blood samples.

BACKGROUND: Diabetes patients suffer either from insulin deficiency or resistance with a high risk of severe long-term complications, thus the quantitative assessment of insulin level is highly desired for diabetes surveillance and management. Utilizing insulin-capturing aptamers may facilitate the development of affordable biosensors however, their rigid G-quadruplex structures impair conformational changes of the aptamers and diminish the sensor signals. RESULTS: Here we report on a ratiometric, electrochemical insulin aptasensor which is achieved by hybridization of an insulin-capturing aptamer and a partially complementary ssDNA to break the rigid G-quadruplex structures. To improve the durability of the aptasensor, the capturing aptamer was immobilized on gold electrodes via two dithiol-phosphoramidite functional groups while methoxy-polyethylene glycol thiol was used as a blocking molecule. The exposure of the sensor to insulin-containing solutions induced the dissociation of the hybridized DNA accompanied by a conformational rearrangement of the capturing aptamer back into a G-quadruplex structure. The reliability of sensor readout was improved by the adoption of an AND logic gate utilizing anthraquinone and methylene blue redox probes associated to the aptamer and complementary strand, respectively. Our aptasensor possessed an improved detection limit of 0.15 nM in comparison to aptasensors without strand displacement. SIGNIFICANCE: The sensor was adapted for detection in real blood and is ready for future PoC diagnostics. The capability of monitoring the insulin level in an affordably manner can improve the treatment for an increasing number of patients in developed and developing nations. The utilization of low-cost and versatile aptamer receptors together with the engineering of ratiometric electrochemical signal recording has the potential to considerably advance the current insulin detection technology toward multi-analyte diabetes sensors.

Thiol-polyethylene glycol-folic acid (HS-PEG-FA) induced aggregation of Au@Ag nanoparticles: A SERS and extinction UV-Vis spectroscopy combined study.

Plasmonic colloidal nanoparticles (NPs) functionalised with polymers are widely employed in diverse applications, offering advantages demonstrated over non-functionalised NPs such as enhanced colloidal stability or increased biocompatibility. However, functionalisation with polymers does not always increase the stability of the colloidal system. This work explores the intricate relationship between the functionalisation of plasmonic core@shell Au@Ag nanoparticles (NPs) with thiol-polyethylene glycol-folic acid (HS-PEG-FA) polymer chains and the resulting stability and spectral characteristics of Surface-Enhanced Raman Scattering (SERS) nanotags based on these NPs. We demonstrate that varying levels of HS-PEG-FA grafting influence nanotag stability, with a low level of grafting causing aggregation and subsequently affecting the spectral signature of Raman-reporter molecules attached to the surface of the NP. Electrostatic destabilisation is identified as the primary mechanism driving aggregation, impacting the SERS spectrum of Malachite Green isothiocyanate (MGITC) whose spectral shape is different between the aggregated and non-aggregated NPs. The findings provide valuable insights into NPs stability under different conditions, offering essential considerations for the design and optimisation of SERS nanotags in bio-analytical applications, particularly those involving data processing based on spectral shape, such as in multiplex approaches where experimental spectra are decomposed with several reference components.