Enhancement Of Uptake Research Articles

Metformin: Diverse molecular mechanisms, gastrointestinal effects and overcoming intolerance in type 2 Diabetes Mellitus: A review.

Metformin, the first line treatment for patients with type 2 diabetes mellitus, has alternative novel roles, including cancer and diabetes prevention. This narrative review aims to explore its diverse mechanisms, effects and intolerance, using sources obtained by searching Scopus, PubMed and Web of Science databases, and following Scale for the Assessment of Narrative Review Articles reporting guidelines. Metformin exerts it actions through duration influenced, and organ specific, diverse mechanisms. Its use is associated with inhibition of hepatic gluconeogenesis targeted by mitochondria and lysosomes, reduction of cholesterol levels involving brown adipose tissue, weight reduction influenced by growth differentiation factor 15 and novel commensal bacteria, in addition to counteraction of meta-inflammation alongside immuno-modulation. Interactions with the gastrointestinal tract include alteration of gut microbiota, enhancement of glucose uptake and glucagon like peptide 1 and reduction of bile acid absorption. Though beneficial, they may be linked to intolerance. Metformin related gastrointestinal adverse effects are associated with dose escalation, immediate release formulations, gut microbiota alteration, epigenetic predisposition, inhibition of organic cation transporters in addition to interactions with serotonin, histamine and the enterohepatic circulation. Potentially effective measures to overcome intolerance encompasses carefully objective targeted dose escalation, prescription of fixed dose combination, microbiome modulators and prebiotics, in addition to use of extended release formulations.

Differences in Grain Yield and Nitrogen Uptake between Tetraploid and Diploid Rice: The Physiological Mechanisms under Field Conditions.

Research indicates that, owing to the enhanced grain-filling rate of tetraploid rice, its yield has notably improved compared to previous levels. Studies conducted on diploid rice have revealed that optimal planting density and fertilization rates play crucial roles in regulating rice yield. In this study, we investigated the effects of different nitrogen application and planting density treatments on the growth, development, yield, and nitrogen utilization in tetraploid (represented by T7, an indica-japonica conventional allotetraploid rice) and diploid rice (Fengliangyou-4, represented by FLY4, a two-line super hybrid rice used as a reference variety for the approval of super rice with a good grain yield performance). The results indicated that the highest grain-filling rate of T7 could reach 77.8% under field experimental conditions due to advancements in tetraploid rice breeding. This is a significant improvement compared with the rate seen in previous research. Under the same conditions, T7 exhibited a significantly lower grain yield than FLY4, which could be attributed to its lower grain-filling rate, spikelets per panicle, panicle number m-2, and harvest index score. Nitrogen application and planting density displayed little effect on the grain yield of both genotypes. A higher planting density significantly enhanced the leaf area index and biomass accumulation, but decreased the harvest index score. Compared with T7, FLY4 exhibited a significantly higher nitrogen use efficiency (NUEg), which was mainly due to the higher nitrogen content in the straw. Increasing nitrogen application significantly decreased NUEg due to its minimal effect on grain yield combined with its significant enhancement of nitrogen uptake. Our results suggest that the yield and grain-filling rate of T7 have been improved compared with those of previously tested polyploid rice, but are still lower than those of FLY4, and the yield of tetraploid rice can be further improved by enhancing the grain-filling rate, panicle number m-2, and spikelets per panicle via genotype improvement.

Disulfide stoppered polyrotaxanes with enhanced cellular uptake and intracellular cyclodextrin release

Background and AimPolyrotaxanes are molecular necklaces composed of polymers, threaded macrocycles, and bulky stopper molecules to inhibit the decomposition of the first two. These supramolecular assemblies are promising active ingredients for treating lysosomal storage disorders. This study aimed to synthesize such polyrotaxanes with a novel, simple method, resulting in high threading efficacy, enhanced cellular uptake, and intracellular cyclodextrin (CD) release. MethodsIn this study, we developed two novel poly(ethylene glycol) (PEG) based polyrotaxanes, with threaded α-cyclodextrin (α-CD) or its mixture with 2-hydroxypropyl-α-CD (HP-α-CD) and glutathione sensitive disulfide connected stopper molecules. The structure and composition of these polyrotaxanes were determined by 1H NMR spectroscopy and gel permeation chromatography, while the cellular uptake was investigated by flow cytometry and confocal microscopy. ResultsHigh threading efficacy, as well as molar mass of 17.9 and 13.1 kDa, was found for the polymeric supramolecules with threaded α-CD and α-CD/HP-α-CD, respectively. Glutathion-triggered reductive removal of the stopper molecules showed potential decomposition of these polyrotaxanes in target cells. Flow cytometry revealed an up to 52-fold enhancement in cellular uptake of α- and HP-α-CD by the polyrotaxanes compared to free CD, which was also visualized by confocal microscopy. Conclusion and scope of applicationPolyrotaxanes based on α-CD and its derivative were tested in vitro for application in the treatment of lysosomal storage disease for the first time. Based on these results, polyrotaxanes with disulfide stopper molecules might be promising supramolecular excipients for cellular delivery of α-CDs.

Construction of 2D zinc(II) MOFs with tricarboxylate and N-donor mixed ligands for multiresponsive luminescence sensors and CO2 adsorption.

The solvothermal reactions of ZnCl2·6H2O, benzene-1,3,5-tribenzoic acid (H3btb), and N-heterocyclic ancillary imidazole (Im) or aminopyrimidine (a mp) ligands led to the creation of two-dimensional (2D) zinc(II) based metal-organic frameworks (MOFs), (Me2NH2)2[Zn2(btb)2(Im)2]·2DMF·3MeOH (1) and (Me2NH2)2[Zn2(btb)2(amp)]·H2O·2DMF·MeOH (2). The btb3- ligands in 1 and 2 form an anionic 2D layered structure with a (63) honeycomb (hcb) topology by linking to Zn(II) centres through their carboxylate groups. The incorporation of N-heterocyclic auxiliary ligands Im and amp into the hcb nets resulted in the formation of a 2D hydrogen-bonded and covalently pillared bilayer structure featuring two-fold interpenetrating networks. Each of these networks consists of small channels that are occupied by Me2NH2 cations and solvent molecules. Both 1 and 2 emit blue luminescence emissions in the solid state at room temperature and exhibit a great selectivity and sensitivity for the detection of acetone and multiple heavy metal ions including Hg2+, Cu2+, Fe2+, Pb2+, Cr3+, and Fe3+ ions. At 1 bar, activated 1 and 2 demonstrate moderate capacities for adsorbing CO2 at room temperature, with a preference for CO2 over N2. Notably, at higher pressures (up to 20 bar), their activated samples 1 and 2 show a temperature-dependent enhancement of CO2 uptake while retaining good stability.

The interaction of galectin-8 C-terminal domain with cell surface glycoconjugates modulates membrane elasticity to stimulate antigen uptake and presentation to CD4 T cells.

Galectins constitute a family of soluble lectins with unique capacity to induce macroscale rearrangements upon interacting with cell membrane glycoconjugates. Galectin-8 (Gal-8) is acknowledged for its role in facilitating antigen uptake and processing upon engaging with cell surface glycoconjugates on antigen-presenting cells (APCs). Gal-8 consists of two covalently fused N- and C-terminal carbohydrate recognition domains (N- and C-CRD), each exhibiting distinct glycan specificity. In this study, we utilized single N- and C-CRD recombinant proteins to dissect the nature of Gal-8-glycan interactions during antigen internalization enhancement. Single C-CRD was able to replicate the effect of full-length Gal-8 (FLGal-8) on antigen internalization in BMDCs. Antigen uptake enhancement was diminished in the presence of lactose or when N-glycosylation-deficient macrophages served as APCs, underscoring the significance of glycan recognition. Measurement of the elastic modulus using Atomic Force Microscopy unveiled that FLGal-8- and C-CRD-stimulated macrophages exhibited heightened membrane stiffness compared to untreated cells, providing a plausible mechanism for their involvement in endocytosis. C-CRD proved to be as efficient as FLGal-8 in promoting antigen degradation, suggesting its implication in antigen-processing induction. Lastly, C-CRD was able to replicate FLGal-8-induced antigen presentation in the MHC-II context both in vitro and in vivo. Our findings support the notion that Gal-8 binds through its C-CRD to cell surface N-glycans, thereby altering membrane mechanical forces conducive to soluble antigen endocytosis, processing, and presentation to cognate CD4 T-cells. These findings contribute to a deeper comprehension of Gal-8 and its mechanisms of action, paving the way for the development of more efficacious immunotherapies.

Implications of the non-neuronal cholinergic system for therapeutic interventions of inflammatory skin diseases.

The pivotal roles of acetylcholine (ACh) in physiological processes encompass both the nervous and non-neuronal cholinergic systems (NNCS). This review delineates the synthesis, release, receptor interactions, and degradation of ACh within the nervous system, and explores the NNCS in depth within skin cells including keratinocytes, endothelial cells, fibroblasts, macrophages, and other immune cells. We highlight the NNCS's essential functions in maintaining epidermal barrier integrity, promoting wound healing, regulating microcirculation, and modulating inflammatory responses. The potential of the NNCS as a therapeutic target for localized ACh regulation in the skin is discussed, though the translation of these findings into clinical practice remains uncertain due to the complexity of cholinergic signalling and the lack of comprehensive human studies. The review progresses to therapeutic modulation strategies of the NNCS, including AChE inhibitors, nicotinic and muscarinic receptor agonists and antagonists, choline uptake enhancers, and botulinum toxin, highlighting their relevance in dermatology. We highlight the impact of the NNCS on prevalent skin diseases such as psoriasis, atopic dermatitis, rosacea, acne, bullous diseases, hyperhidrosis and hypohidrosis, illustrating its significance in disease pathogenesis and therapy. This comprehensive overview aims to enhance understanding of the NNCS's role in skin health and disease, offering a foundation for future research and therapeutic innovation.

Diagnosis of Prostate Cancer with a Neurotensin-Bombesin Radioligand Combination-First Preclinical Results.

Background: The concept of radiotheranostics relies on the overexpression of a biomolecular target on malignant cells to direct diagnostic/therapeutic radionuclide-carriers specifically to cancer lesions. The concomitant expression of more than one target in pathological lesions may be elegantly exploited to improve diagnostic sensitivity and therapeutic efficacy. Toward this goal, we explored a first example of a combined application of [99mTc]Tc-DT11 (DT11, N4-Lys(MPBA-PEG4)-Arg-Arg-Pro-Tyr-Ile-Leu-OH; NTS1R-specific) and [99mTc]Tc-DB7(DB7, N4-PEG2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt; GRPR-specific) in prostate cancer models. Methods: Accordingly, the behavior of [99mTc]Tc-DT11 was compared with that of the [99mTc]Tc-DT11+[99mTc]Tc-DB7 mixture in prostate adenocarcinoma PC-3 cells and xenografts in mice. The impact of stabilizing both radiotracers by Entresto®, as a source of the potent neprilysin inhibitor sacubitrilat, was also investigated. Results: The PC-3 cell binding of the [99mTc]Tc-DT11+[99mTc]Tc-DB7 mixture surpassed that of [99mTc]Tc-DT11. Likewise, the PC-3 tumor uptake of the [99mTc]Tc-DT11+[99mTc]Tc-DB7 mixture at 4 h post-injection was superior (7.70 ± 0.89%IA/g) compared with [99mTc]Tc-DT11 (4.23 ± 0.58%IA/g; p < 0.0001). Treatment with Entresto® led to further enhancement of the tumor uptake (to 11.57 ± 1.92%IA/g; p < 0.0001). Conclusions: In conclusion, this first preclinical study on prostate cancer models revealed clear advantages of dual NTS1R/GRPR targeting, justifying further assessment of this promising concept in other cancer models.

Construction of a Methoxy-Functionalized Pillar-Layer Metal-Organic framework for low-concentration SO2 uptake and adsorption separation

We report the synthesis and structural characterization of a novel methoxy (–OCH3) −functionalized pillar-layer metal–organic framework (MOF), denoted as DZU-17 (DZU=Dezhou University), which is isoreticular to Co6-MOF-3. DZU-17 is constructed by integrating a –OCH3 modified bipyridine ligand, 1,4-dipyridine-2,5-dimethoxybenzene (BPB-OCH3), into the framework of Co6-MOF-3. Single-crystal X-ray diffraction analysis confirms that the introduction of the –OCH3 groups effectively partitions the spacious channels of Co6-MOF-3 into more confined spaces within DZU-17. This structural modification results in a significant enhancement in SO2 uptake at low −pressure (P=0.1 bar, 112.7 cm3 g−1) and improved separation capacity for SO2/CO2/N2 mixture under ambient conditions. Our findings underscore the potential of functional group engineering on MOF linkers to modulate pore dimensions and chemical environments, thereby enhancing the frameworks’ performance in gas adsorption and separation processes.

Duration of Morning Hyperinsulinemia Determines Hepatic Glucose Uptake and Glycogen Storage Later in the Day.

Morning insulin exposure primes the liver for increased hepatic glucose uptake and glycogen storage during a subsequent hyperinsulinemic-hyperglycemic clamp. This study addressed whether the pattern and/or duration of insulin delivery in the morning influences insulin's ensuing priming effect. We found that despite receiving equal total doses of insulin in the morning, a prolonged, lower rate of morning insulin delivery improved afternoon liver glucose metabolism more effectively than a shorter, higher rate of delivery.

Ligand Shell Thickness of PEGylated Gold Nanoparticles Controls Cellular Uptake and Radiation Enhancement.

The drive to improve the safety and efficacy of radiotherapies for cancers has prompted the development of nanomaterials that can locally amplify the radiation dose at a tumor without damaging the surrounding healthy tissue. Gold nanoparticles (Au NPs), in particular, exhibit promising radiosensitizing properties under kilovolt X-ray exposure, although the precise mechanism behind this enhancement is not fully understood. While most studies recognize the involvement of factors such as core composition, size, shape, and ligand chemistry in the effectiveness of Au NPs for radiation-induced cancer treatment, there is a scarcity of direct assessments that connect the photophysical properties of the nanomaterial with the observed cellular or biological outcomes. Despite previous evidence of low-energy electron (LEE) emission from Au NPs and their potential to initiate biological damage, to our knowledge, no studies directly correlate the secondary LEE emission with radiation-induced cell death. In this study we assessed Au NPs functionalized with polyethylene glycol (PEG) ligands of varying molecular weights and lengths (1, 5, and 20 kDa PEG) as potential radiosensitizers of A549 lung cancer cells using kilovolt X-ray source potentials (33-130 kVp). We assessed NP internalization using mass cytometry, radiation dose enhancement using clonogenic survival assays, and secondary LEE emission using a retarding field analyzer. Results reveal a statistically significant difference in cellular uptake and radiation dose enhancement for 5 kDa PEG-Au NPs compared to formulations using 1 and 20 kDa PEG, while analysis of secondary LEE emission spectra demonstrated that differences in the length of the PEG ligand did not cause statistically significant attenuation of secondary LEE flux. Consequently, we inferred increased cellular uptake of NPs to be the cause for the observed enhancement in radiosensitivity for 5 kDa PEGylated Au NPs. The approach used in this study establishes a more complete workflow for designing and characterizing the performance of nanomaterial radiosensitizers, allowing for quantification of secondary LEEs and cellular uptake, and ultimately correlation with localized dose enhancement that leads to cell death.

CO2 Uptake and Stability Enhancement in Vinyltrimethoxysilane-Treated SBA-15 Solid Amine-Based Sorbents.

Silica-supported amine absorbents, including materials produced by tethering aminosilanes or infusion of poly(ethyleneimine), represent a promising class of materials for CO2 capture applications, including direct air and point source capture. Various silica surface treatments and functionalization strategies are explored to enhance stability and CO2 uptake in amine-based solid sorbent systems. Here, the synthesis and characterization of novel vinyltrimethoxysilane-treated Santa Barbara Amorphous-15 (SBA-15) supports and the corresponding enhancement in CO2 uptake compared to various SBA-15-based control supports are presented. The relationship between CO2 diffusion and amine efficiency in these systems is explored using a previously reported kinetic model. The synthesized materials are characterized with CO2 and H2O isotherms, diffuse reflectance infrared Fourier transform spectroscopy, 1H T1-T2 relaxation correlation NMR, and rapid thermal cycling experiments. The novel support materials are shown to enable high amine efficiencies, approaching a fourfold improvement over standard SBA-15-supported amines, while simultaneously exhibiting excellent stability when cycled rapidly under humid conditions. As the poly(ethyleneimine) loadings are held constant across the various samples, enhancements in CO2 uptake are attributed to differences in the way the poly(ethyleneimine) interacts with the support surface.

Enhanced In Vitro Efficacy of Verbascoside in Suppressing Hepatic Stellate Cell Activation via ROS Scavenging with Reverse Microemulsion.

Numerous approaches targeting hepatic stellate cells (HSCs) have emerged as pivotal therapeutic strategies to mitigate liver fibrosis and are currently undergoing clinical trials. The investigation of herbal drugs or isolated natural active compounds is particularly valuable, due to their multifaceted functions and low risk of side effects. Recent studies have hinted at the potential efficacy of verbascoside (VB) in ameliorating renal and lung fibrosis, yet its impact on hepatic fibrosis remains to be elucidated. This study aims to evaluate the potential effects of VB on liver fibrosis by assessing its ability to inhibit HSC activation. VB demonstrated significant efficacy in suppressing the expression of fibrogenic genes in activated LX-2 cells. Additionally, VB inhibited the migration and proliferation of these activated HSCs by scavenging reactive oxygen species (ROS) and downregulating the AMPK pathway. Furthermore, a biosafe reverse microemulsion loaded with VB (VB-ME) was developed to improve VB's instability and low bioavailability. The optimal formulation of VB-ME was meticulously characterized, revealing substantial enhancements in cellular uptake, ROS-scavenging capacity, and the suppression of HSC activation.

Enhancement of cadmium uptake in Sedum alfredii through interactions between salicylic acid/jasmonic acid and rhizosphere microbial communities

The focus on phytoremediation in soil cadmium (Cd) remediation is driven by its cost-effectiveness and eco-friendliness. Selecting suitable hyperaccumulators and optimizing their growth conditions are key to enhance the efficiency of heavy metal absorption and accumulation. Our research has concentrated on the role of salicylic acid (SA) and jasmonic acid (JA) in facilitating Cd phytoextraction by “Sedum alfredii (S. alfredii)” through improved soil-microbe interactions. Results showed that SA or JA significantly boosted the growth, stress resistance, and Cd extraction efficiency in S. alfredii. Moreover, these phytohormones enhanced the chemical and biochemical attributes of the rhizosphere soil, such as pH and enzyme activity, affecting soil-root interactions. High-throughput sequencing analysis has shown that Patescibacteria and Umbelopsis enhanced S. alfredii's growth and Cd extraction by modifying the bioavailability and the chemical conditions of Cd in soil. Structural Equation Model analysis further verified that phytohormones significantly enhanced the interaction between S. alfredii, soil, and microbes, leading to a marked increase in Cd accumulation in the plant. These discoveries emphasized the pivotal role of phytohormones in modulating the hyperaccumulators' response to environmental stress and offered significant scientific support for further enhancing the potential of hyperaccumulators in ecological restoration technologies using phytohormones.

Remarkable enhancement in radio-cesium uptake from acidic feeds into an extraction chromatography resin containing a calix[4]arene-mono-crown-6 ligand

An extraction chromatography resin, prepared by the impregnation of bis-octyloxy-calix[4]arene-mono-crown-6 (BOCMC)onto an acrylic ester based polymeric support material, gave excellent uptake data for the removal of radio-cesium (Cs-137) from nitric acid feed solutions. The weight distribution coefficient (Kd) value of >300 obtained during the present study at 3 M HNO3 was the highest reported so far while using a calix-crown-6 based extraction chromatographic resin material. Analogous resin reported previously has yielded a Kd value <100 at comparable feed conditions. The sorbed metal ions could be efficiently desorbed with de-ionized water. Kinetic modeling of the uptake data indicated that both the film and the intra-particle diffusion mechanism are simultaneously operating in the sorption of Cs+ion onto the BOCMC resin. The metal ion sorption data were fitted to the sorption isotherm models and did not conform to the chemisorptions of physisorption models and indicated a pi-pi interaction between the benzene rings of the calix-crown-6 ligand and the Cs+ ion. The reusability of the resins was quite satisfactory after 5 cycles and the radiation stability of the resin material was very good upto an absorbed dose of 500 kGy. The results of column studies were quite encouraging with 15 mL (9 bed volumes) as the breakthrough volume while the elution was complete in about 12 bed volumes of de-ionized water.

Using an Uptake Enhancer to Mitigate Nitrogen Leaching While Enhancing Uptake Efficiency

Nitrogen (N) has the most crucial influence on raising agricultural productivity of all other plant nutrients given to crops. However, 50% of the N given to crops is dissipated to the environment globally, resulting in environmental concerns due to leaching. Current research shows that intensive agricultural production systems, which are still used in a large proportion around the world, are prone to N loss. This study aimed to investigate the effect of uptake enhancer applications on N movement in the soil profile based on 10 cm depth intervals, as well as its effects on N uptake and vegetative growth of oats at 4-week intervals over a 16-week period, using sandy soil as a growing medium. Oats were cultivated in a glasshouse setting in polyvinyl chloride (PVC) columns of 60 cm in height. Six treatments were employed at the 3rd leaf growth stage, and each was replicated four times. The experiment had a constructive and a destructive part, which was employed to monitor crop N uptake at four growth stages. Analyses of soil and plant samples were carried out in all the growth stages. The treatments containing the uptake enhancer prevented N from leaching, particularly at the top 20 cm soil depth, with impressive reductions of 194% at 0–10 cm depth and 186% at 10–20 cm depth, during the first 4 weeks after planting. The uptake enhancer also promoted early vegetative growth and crop performance with 15%. In conclusion, the study revealed that employing the uptake enhancer can improve the efficacy of N fertilizer, thereby reducing the application rate of the fertilizer in agroecosystems.

Pulsed high power microwave seeds priming modulates germination, growth, redox homeostasis, and hormonal shifts in barley for improved seedling growth: Unleashing the molecular dynamics

Increasing the seed germination potential and seedling growth rates play a pivotal role in increasing overall crop productivity. Seed germination and early vegetative (seedling) growth are critical developmental stages in plants. High-power microwave (HPM) technology has facilitated both the emergence of novel applications and improvements to existing in agriculture. The implications of pulsed HPM on agriculture remain unexplored. In this study, we have investigated the effects of pulsed HPM exposure on barley germination and seedling growth, elucidating the plausible underlying mechanisms. Barley seeds underwent direct HPM irradiation, with 60 pulses by 2.04 mJ/pulse, across three distinct irradiation settings: dry, submerged in deionized (DI) water, and submerged in DI water one day before exposure. Seed germination significantly increased in all HPM-treated groups, where the HPM-dry group exhibited a notable increase, with a 2.48-fold rise at day 2 and a 1.9-fold increment at day 3. Similarly, all HPM-treated groups displayed significant enhancements in water uptake, and seedling growth (weight and length), as well as elevated levels of chlorophyll, carotenoids, and total soluble protein content. The obtained results indicate that when comparing three irradiation setting, HPM-dry showed the most promising effects. Condition HPM seed treatment increases the level of reactive species within the barley seedlings, thereby modulating plant biochemistry, physiology, and different cellular signaling cascades via induced enzymatic activities. Notably, the markers associated with plant growth are upregulated and growth inhibitory markers are downregulated post-HPM exposure. Under optimal HPM-dry treatment, auxin (IAA) levels increased threefold, while ABA levels decreased by up to 65 %. These molecular findings illuminate the intricate regulatory mechanisms governing phenotypic changes in barley seedlings subjected to HPM treatment. The results of this study might play a key role to understand molecular mechanisms after pulsed-HPM irradiation of seeds, contributing significantly to address the global need of sustainable crop yield.

A chemical modification of a peroxisome proliferator-activated receptor pan agonist produced a shift to a new dual alpha/gamma partial agonist endowed with mitochondrial pyruvate carrier inhibition and antidiabetic properties

New analogs of the PPAR pan agonist AL29-26 encompassed ligand (S)-7 showing potent activation of PPARα and -γ subtypes as a partial agonist. In vitro experiments and docking studies in the presence of PPAR antagonists were performed to help interpretation of biological data and investigate the main interactions at the binding sites. Further in vitro experiments showed that (S)-7 induced anti-steatotic effects and enhancement of the glucose uptake. This latter effect could be partially ascribed to a significant inhibition of the mitochondrial pyruvate carrier demonstrating that (S)-7 also acted through insulin-independent mechanisms. In vivo experiments showed that this compound reduced blood glucose and lipid levels in a diabetic mice model displaying no toxicity on bone, kidney, and liver. To our knowledge, this is the first example of dual PPARα/γ partial agonist showing these combined effects representing, therefore, the potential lead of new drugs for treatment of dyslipidemic type 2 diabetes.

Enhancement of Solubility, Stability, Cellular Uptake, and Bioactivity of Curcumin by Polyvinyl Alcohol.

The biological activities and related mechanisms of curcumin, a major polyphenolic compound in turmeric, the rhizome of Curcuma longa, have been extensively investigated. Due to its poor solubility in water, the analysis of curcumin's biological activities is limited in most aqueous experimental systems. In the present study, the effects of polyvinyl alcohol (PVA), a dietary-compatible vehicle, on the solubility, stability, cellular uptake, and bioactivities of curcumin were investigated. Curcumin solubility was improved significantly by PVA; the color intensity of curcumin aqueous solution in the presence of PVA increased concentration-dependently with its peak shift to a shorter wavelength. Improved suspension stability and photostability of curcumin in an aqueous solution were also observed in the presence of PVA, even at 62.5 μg/mL. The scavenging activities of curcumin against DPPH, ABTS, AAPH radicals, and nitric oxide were enhanced significantly in the presence of PVA. PVA at 250 μg/mL also significantly enhanced the cytotoxic activity of curcumin against both HCT 116 colon cancer and INT 407 (HeLa-derived) embryonic intestinal cells by reducing the IC50 from 16 to 11 μM and 25 to 15 μM, respectively. PVA improved the cellular uptake of curcumin in a concentration-dependent manner in INT 407 cells; it increased the cellular levels more effectively at lower curcumin treatment concentrations. The present results indicate that PVA improves the solubility and stability of curcumin, and changes in these chemical behaviors of curcumin in aqueous systems by PVA could enhance the bioavailability and pharmacological efficacy of curcumin.

In Vitro Predictive Model for Intestinal Lymphatic Uptake: Exploration of Additional Enhancers and Inhibitors.

Drug absorption via chylomicrons holds significant implications for both pharmacokinetics and pharmacodynamics. However, a mechanistic understanding of predicting in vivo intestinal lymphatic uptake remains largely unexplored. This study aimed to delve into the intestinal lymphatic uptake of drugs, investigating both enhancement and inhibition using various excipients through our previously established in vitro model. It also examined the applicability of the model by assessing the lymphatic uptake enhancement of a lymphotropic formulation with linoleoyl polyoxyl-6 glycerides using the same model. The model successfully differentiated among olive, sesame, and peanut oils in terms of lymphatic uptake. However, it did not distinguish between oils containing long-chain fatty acids and coconut oil. Coconut oil, known for its abundance of medium-chain fatty acids, outperformed other oils. This heightened uptake was attributed to the superior emulsification of this oil in artificial chylomicron media due to its high content of medium-chain fatty acids. Additionally, the enhanced uptake of the tested formulation with linoleoyl polyoxyl-6 glycerides underscored the practical applicability of this model in formulation optimization. Moreover, data suggested that increasing the zeta potential of Intralipid® using sodium lauryl sulfate (SLS) and decreasing it using (+/-) chloroquine led to enhanced and reduced uptake in the in vitro model, respectively. These findings indicate the potential influence of the zeta potential on intestinal lymphatic uptake in this model, though further research is needed to explore the possible translation of this mechanism in vivo.

Development of PLA/HA porous scaffolds with controlled pore sizes using the combined freeze drying and sucrose leaching technique for bone tissue engineering

The combination of freeze drying and sucrose leaching technique was employed to fabricate PLA/HA scaffolds with controlled pore size. The influence of the HA content and sucrose size on the scaffold properties was investigated. The fabricated scaffolds showed porous properties with a porosity of 44% to 58% and pore size of 461 μm to 688 μm. The results indicated that the scaffolds possessed favorable porous properties, illustrated by good interconnectivity, appropriate pore size, and suitable porosity. These characteristics were crucial for facilitating bone cell growth and promoting the formation of new tissue within the scaffold structure. The compressive modulus of the scaffolds was examined and found to be in the range of 3.35 MPa to 5.75 MPa. Furthermore, the degradation behavior of the scaffolds was studied for 28 days in a Phosphate Buffered Saline solution. The results showed that the degradation rate was varied in the range of 6% to 14%. The water uptake of the scaffolds exhibited a range between 180% and 200%. Enhancement in water uptake was observed with higher HA content and increased sucrose size. Consequently, the scaffolds developed in this study hold promise as optimal candidates for bone tissue engineering applications.