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1.
J Am Chem Soc ; 146(15): 10973-10978, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38576203

RESUMO

Recent microscopy and nuclear magnetic resonance (NMR) studies have noticed substantial suppression of intracellular diffusion for positively charged proteins, suggesting an overlooked role of electrostatic attraction in nonspecific protein interactions in a predominantly negatively charged intracellular environment. Utilizing single-molecule detection and statistics, here, we quantify in aqueous solutions how protein diffusion, in the limit of low diffuser concentration to avoid aggregate/coacervate formation, is modulated by differently charged interactor proteins over wide concentration ranges. We thus report substantially suppressed diffusion when oppositely charged interactors are added at parts per million levels, yet unvaried diffusivities when same-charge interactors are added beyond 1%. The electrostatic attraction-driven suppression of diffusion is sensitive to the protein net charge states, as probed by varying the solution pH and ionic strength or chemically modifying the proteins and is robust across different diffuser-interactor pairs. By converting the measured diffusivities to diffuser diameters, we further show that in the limit of excess interactors, a positively charged diffuser molecule effectively drags along just one monolayer of negatively charged interactors, where further interactions stop. We thus unveil ubiquitous, net charge-driven protein-protein interactions and shed new light on the mechanism of charge-based diffusion suppression in living cells.


Assuntos
Proteínas , Proteínas/química , Difusão , Concentração Osmolar
2.
Environ Geochem Health ; 46(5): 153, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587707

RESUMO

The environmental fate and risks of ciprofloxacin (CIP) in the subsurface have raised intensive concerns. Herein, the transport behaviors of CIP in both saturated quartz sand and sand/multi-walled carbon nanotubes (MWCNTs) mixtures under different solution ionic strength of the solution and coexisting cation types were investigated. Batch adsorption experiments highlighted growing adsorptive capacity for CIP with the increasing content of MWCNTs in the MWCNTs-quartz sand mixtures (from 0.5% to 1.5%, w/w). Breakthrough curves (BTCs) of CIP in the MWCNTs-quartz sand mixtures were well fitted by the two-site chemical nonequilibrium model (R2 > 0.833). The estimated retardation factors for CIP increased from 9.68 to 282 with growing content of MWCNTs in the sand column, suggesting the presence of MWCNTs significantly inhibited the transport of CIP in saturated porous media. Moreover, the values of retardation factors are negatively correlated with the ionic strength and higher ionic strength could facilitate the transport of CIP in the saturated porous media. Compared with monovalent cations (Na+), the presence of divalent cations (Ca2+) significantly facilitated the transport of CIP in the columns due to the complexation between CIP and Ca2+ as well as deposition of MWCNTs aggregates on the sand surface. Results regarding CIP retention in columns indicated that MWCNTs could enhance the accumulation of CIP in the layers close to the influent of sand columns, while they could hinder upward transport of CIP to the effluent. This study improves our understanding for transport behaviors and environmental risk assessments of CIP in the saturated porous media with MWCNTs.


Assuntos
Nanotubos de Carbono , Porosidade , Quartzo , Areia , Cátions , Ciprofloxacina , Concentração Osmolar
3.
Int Ophthalmol ; 44(1): 175, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38615085

RESUMO

AIM: This study aimed to assess the efficacy of hp-guar eye drops on tear film index and ocular surface dynamics under desiccating conditions using protection and relief treatment modalities. METHODOLOGY: The 12 normal, non-dry eye participants were subjected to adverse environmental conditions using a Controlled Environment Chamber (CEC) where the relative humidity (RH) was 5% and the ambient temperature was 21 °C. The participants were screened for ocular symptoms, tear osmolarity, ocular surface temperature (OST), tear production using the Ocular Surface Disease Index questionnaire (OSDI), OcuSense TearLab Osmometer, FLIR System ThermaCAM P620, and Schirmer strips. Tear production was calculated by the Tear Function Index test (TFI). RESULTS: The mean tear film osmolarity decreased significantly from 296 mOsm/L at 40% RH to 285 mOsm/L at 5% RH (p = 0.01). Conflicting responses were seen for osmolarity in protection and relief. Mean tear osmolarity was significantly higher in the protection method in comparison to the relief method (p = 0.005). The mean TFI increased from 557 at 40% to 854 at 5% (p = 0.02). A significant increase in TFI was observed in the relief method in comparison with both 40% (p = 0.001) and 5% (p = 0.04). In the relief method, the mean TFI score went up to 1139 when hp-guar was installed. A significant improvement in ocular comfort was experienced in both the protection (p = 0.041) and relief (p = 0.010) methods at 5% RH. The instillation of hp-guar drops in the relief method resulted in a significant reduction in OST. The mean OST dropped to 33.01 ºC, significantly lower than the recorded OST for both normal (p = 0.040) and dry (p = 0.014) environmental conditions. CONCLUSION: Hp-guar drops significantly improve tear film parameters under a desiccating environment, however, tear film parameters respond differently to the management modalities. In the protection method, tear film osmolarity was protected against a dry environment, while in the relief mode, an improvement in tear production and a decrease in ocular surface temperature were seen. Hp-guar performance could be maximized for the management of exposure to adverse environments by using a treatment protocol that targets the most affected parameters in each group of patients. Using CEC has the potential to provide researchers with a readily available method to evaluate the efficiency of tear supplementation.


Assuntos
Cyamopsis , Humanos , Olho , Ambiente Controlado , Soluções Oftálmicas , Concentração Osmolar
4.
Cells ; 13(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38607028

RESUMO

Absorption spectra of red blood cell (RBC) suspensions are investigated in an osmolarity range in the medium from 200 mOsm to 900 mOsm. Three spectral parameters are used to characterize the process of swelling or shrinkage of RBC-the absorbance at 700 nm, the Soret peak height relative to the spectrum background, and the Soret peak wavelength. We show that with an increase in the osmolarity, the absorbance at 700 nm increases and the Soret peak relative height decreases. These changes are related to the changes in the RBC volume and the resulting increase in the hemoglobin intracellular concentration and index of refraction. Confocal microscopy and flow cytometry measurements supported these conclusions. The maximum wavelength of the Soret peak increases with increasing osmolarity due to changes in the oxygenation state of hemoglobin. Using these spectrum parameters, the process of osmosis in RBCs can be followed in real time, but it can also be applied to various processes, leading to changes in the volume and shape of RBCs. Therefore, we conclude that UV-Vis absorption spectrophotometry offers a convenient, easily accessible, and cost-effective method to monitor changes in RBC, which can find applications in the field of drug discovery and diagnostics of RBC and hemoglobin disorders.


Assuntos
Eritrócitos , Hemoglobinas , Pressão Osmótica , Espectrofotometria , Concentração Osmolar
5.
Nefrología (Madrid) ; 44(2): 159-164, Mar-Abr. 2024. ilus
Artigo em Espanhol | IBECS | ID: ibc-231565

RESUMO

La hiponatremia es un trastorno multifactorial definido como una disminución en la concentración plasmática de sodio. Su diagnóstico diferencial requiere una evaluación adecuada del volumen extracelular. Sin embargo, la determinación del volumen extracelular, simplemente basada en la historia clínica, las constantes vitales, el examen físico y los hallazgos de laboratorio, conducen en ocasiones a un diagnóstico erróneo por lo que el enfoque terapéutico puede ser equivocado. El empleo de ecografía a pie de cama (Point-of-Care Ultrasound [PoCUS]), mediante la combinación de ecografía pulmonar (Lung Ultrasound [LUS]), Venous Excess UltraSound (VExUS) y la ecocardioscopia (Focused Cardiac Ultrasound [FoCUS]) permiten, en combinación con el resto de los parámetros, una valoración holística mucho más precisa del estado del volumen extracelular del paciente.(AU)


Hyponatremia is a multifactorial disorder defined as a decrease in plasma sodium concentration. Its differential diagnosis requires an adequate evaluation of the extracellular volume. However, extracellular volume determination, simply based on the clinical history, vital signs, physical examination, and laboratory findings can leads to misdiagnosis and inappropriate treatment. The use of Point-of-Care Ultrasound (PoCUS), through the combination of Lung Ultrasound (LUS), Venous Excess UltraSound (VExUS) and Focused Cardiac Ultrasound (FoCUS), allows a much more accurate holistic assessment of the patient's extracellular volume status in combination with the other parameters.(AU)


Assuntos
Humanos , Feminino , Idoso , Hiponatremia/diagnóstico , Medicina de Precisão , Diagnóstico Diferencial , Ultrassonografia/métodos , Concentração Osmolar , Pacientes Internados , Exame Físico , Avaliação de Sintomas
6.
Sci Rep ; 14(1): 6677, 2024 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509217

RESUMO

The hyperarid mangrove in the Middle East is characterised by the absence of rivers or freshwater inputs and is one of the most extreme settings of this ecosystem on Earth. Endemic to Qatar's hyperarid mangroves, a Palaemon shrimp is uniquely confined to a sole mangrove site in the Arabian Gulf. Within these mangrove channels, we unveiled brine groundwater sources exceeding 70 ppt salinity, contrasting the local marine standard of 42 ppt. Concurrently, a mysid species typically linked to salt pans and groundwater coexists. Stable isotopic analysis implied the existence of a predator-prey dynamic between this mysid species and the studied shrimp. Then, investigating the endemic shrimp's adaptation to extreme salinity, we conducted osmolarity experiments and phylogenetic studies. Our findings demonstrate that this shrimp transitions from hypo- to hyper-osmoregulation, tolerating salinities from 18 to 68 ppt-an unprecedented osmoregulatory capacity among caridean shrimps. This speciation pattern likely arises from the species osmolarity adaptation, as suggested for other Palaemon congeners. Phylogenetic analysis of the studied Palaemon, along with the mangrove's geological history, suggests a profound evolutionary interplay between the ecosystem and the shrimp since the Eocene. This study proposes the hyperarid mangrove enclave as an Athalassic mangrove oasis-a distinctive, isolated ecosystem within the desert landscape.


Assuntos
Osmorregulação , Palaemonidae , Animais , Ecossistema , Filogenia , Equilíbrio Hidroeletrolítico , Concentração Osmolar , Palaemonidae/fisiologia
7.
J Colloid Interface Sci ; 664: 533-538, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38484521

RESUMO

The correct measurement of the resonance frequency and shell properties of coated microbubbles (MBs) is essential in understanding and optimizing their response to ultrasound (US) exposure parameters. In diagnostic and therapeutic ultrasound, MBs are typically surrounded by blood; however, the influence of the medium charges on the MB resonance frequency has not been systematically studied using controlled measurements. This study aims to measure the medium charge interactions on MB behavior by measuring the frequency-dependent attenuation of the same size MBs in mediums with different charge densities. In-house lipid-coated MBs with C3F8 gas core were formulated. The MBs were isolated to a mean size of 2.35 µm using differential centrifugation. MBs were diluted to ≈8×105 MBs/mL in distilled water (DW), Phosphate-Buffered Saline solution (PBS1x) and PBS10x. The frequency-dependent attenuation of the MBs solutions was measured using an aligned pair of PVDF transducers with a center frequency of 10MHz and 100% bandwidth in the linear oscillation regime (7 kPa pressure amplitude). The MB shell properties were estimated by fitting the linear equation to experiments. Using a pendant drop tension meter, the surface tension at the equilibrium of ≈6 mm diameter size drops of the same MB shell was measured inside DW, PBS1x and PBS10x. The surface tension at the C3F8/solution interface was estimated by fitting the Young-Laplace equation from the recorded images. The frequency of the peak attenuation at different salinity levels was 13, 7.5 and 6.25 MHz in DW, PBS1x and PBS-10x, respectively. The attenuation peak increased by ≈140% with increasing ion density. MBs' estimated shell elasticity decreased by 64% between DW and PBS-1x and 36% between PBS-1x and PBS-10x. The drop surface tension reduced by 10.5% between DW and PBS-1x and by 5% between PBS-1x and PBS-10x, respectively. Reduction in the shell stiffness is consistent with the drop surface tension measurements. The shell viscosity was reduced by ≈40% between DW and PBS-1x and 42% between PBS-1x and PBS-10x. The reduction in the fitted stiffness and viscosity is possibly due to the formation of a densely charged layer around the shell, further reducing the effective surface tension on the MBs. The changes in the resonance frequency and estimated shell parameters were significant and may potentially help to better understand and explain bubble behavior in applications.


Assuntos
Meios de Contraste , Microbolhas , Viscosidade , Lipídeos , Concentração Osmolar
8.
Chemosphere ; 354: 141714, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38521106

RESUMO

The widespread use of nanomaterials has raised the threat of nanoparticles (NPs) infection of soils and groundwater resources. This research aims to investigate three parameters including flow velocity, ionic strength (IS), and initial particle concentration effects on transport behavior and retention mechanism of functionalization form of graphene oxide with polyvinylpyrrolidone (GO-PVP). The transport of GO-PVP was investigated in a laboratory-scale study through saturated/unsaturated (Saturation Degree = 0.91) sand columns. Experiments were conducted on flow velocity from 1.20 to 2.04 cm min-1, initial particle concentration from 10 to 50 mg L-1, and IS of 5-20 mM. The retention of GO-PVP was best described using the one-site kinetic attachment model in HYDRUS-1D, which accounted for the time and depth-dependent retention. According to breakthrough curves (BTCs), the lower transport related to the rate of mass recovery of GO-PVP was obtained by decreasing flow velocity and initial particle concentration and increasing IS through the sand columns. Increasing IS could improve the GO-PVP retention (based on katt and Smax) in saturated/unsaturated media; katt increases from 2.81 × 10-3 to 3.54 × 10-3 s-1 and Smax increases from 0.37 to 0.42 mg g-1 in saturated/unsaturated conditions, respectively. Our findings showed that the increasing retention of GO-PVP through the sand column under unsaturated condition could be recommended for the reduction of nanoparticles danger of ecosystem exposure.


Assuntos
Grafite , Nanopartículas , Areia , Porosidade , Ecossistema , Concentração Osmolar , Dióxido de Silício
9.
BMC Ophthalmol ; 24(1): 129, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38523298

RESUMO

BACKGROUND: We aimed to check the efficacy of Emustil (oil in water emulsion) drops on tear film index and ocular surface dynamics in dry environments through protection and relief treatment modalities. METHODS: The subjects were exposed to a dry environment using a Controlled Environment Chamber (CEC) where the relative humidity (RH) was 5% and the temperature was 21 °C and screened for ocular symptoms, tear osmolarity, ocular surface temperature (OST) and tear production using ocular Surface Disease Index questionnaire (OSDI), OcuSense TearLab Osmometer, FLIR System ThermaCAM P620 and Schirmer strips/phenol red test respectively. Tear production was calculated by the Tear Function Index test (TFI). RESULTS: The mean tear film osmolarity decreased significantly from 296.8 mOsm/l at 40% RH to 291 mOsm/l at 5%. (p = 0.01). Instillation of Emustil resulted in a significant increase in tear osmolarity in the relief method compared with osmolarity seen at 5% RH when no drop was used. The mean PRT value decreased from 26 ± 9 in normal conditions (40% RH) to 22 ± 4 mm in dry conditions (5% RH). Emustil drops did not induce any significant change in tear production in the PRT test. No significant change was found in OST following exposure to 5% RH. OST did not show a statistically significant change with the emulsion when used for relief (p > 0.05). The mean score of ocular discomfort observed was 70 at 5% RH. Still, the instillation of the oil-in-water emulsion (Emustil) resulted in a noticeable decrease in visual discomfort to 37 (p = 0.00) in protection and 59 in relief (p = 0.05). Emustil drops substantially improved tear film parameters under a desiccating environment, however, tear film parameters respond differently to the management modalities. In the protection method, tear film osmolarity was protected against a dry environment, while in the relief mode, tear production was improved. CONCLUSION: CEC allows for a thorough evaluation of tear film parameters and dry eye treatment protocols in labs, providing greater confidence when applying them to patients. In addition, our study showed that Emustil not only provides protection and relief for dry eyes but also helps to maintain ocular homeostasis in desiccating environments. This indicates a promising potential for improving dry eye treatment protocols.


Assuntos
Síndromes do Olho Seco , Lacerações , Humanos , Emulsões/uso terapêutico , Lágrimas , Síndromes do Olho Seco/diagnóstico , Concentração Osmolar , Água
10.
Ultrason Sonochem ; 104: 106841, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38442572

RESUMO

In this study, the effects of high-intensity ultrasound (HIU) treatment combined with hydrogen peroxide (H2O2) addition on the thermal stability of myofibrillar protein (MP)-stabilized emulsions in low-salt conditions were investigated. Results showed that compared to using either HIU or H2O2 treatment alone, HIU treatment combined with H2O2 was most effective in enhancing the physical stability of emulsions. Moreover, the emulsion stabilized by MPs co-treated with HIU and H2O2 exhibited the most uniform distribution, highest absolute zeta potential, and optimal rheological properties upon heating. This combination effect during heating was caused by the inhibition of disulfide bond cross-linking of myosin heads by H2O2 and the dissociation of filamentous myosin structures using the HIU treatment. In addition, the results of oxidative stability analysis indicated that the addition of H2O2 increased the content of oxidation products; however, the overall influence on the oxidative stability of emulsions was not significant. In conclusion, the combination of HIU and H2O2 treatment is a promising approach to suppress heat-induced MP aggregation and improve the thermal stability of corresponding emulsions.


Assuntos
Temperatura Alta , Peróxido de Hidrogênio , Emulsões/química , Concentração Osmolar , Miosinas
11.
Optom Vis Sci ; 101(1): 71-77, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38350059

RESUMO

SIGNIFICANCE: We evaluate the relationship between tear film osmolarity measurements and quality of vision in patients presenting for routine eye clinic appointments. We found that the hyperosmolar group (>316 mOsm/L) had a worse quality-of-vision score than the normal osmolarity group, with glare being the most problematic symptom. PURPOSE: Quality of vision is a perception and measure of real-world vision, which is not measured routinely in a clinical setting. This study aimed to evaluate the relationship between tear film osmolarity measurements and quality of vision in patients presenting for routine eye clinic appointments. METHODS: This was an observational nonrandomized study. The participants were placed in groups based on tear film osmolarity (normal, ≤316 mOsm/L; hyperosmolar, >316 mOsm/L; or a difference of >8 mOsm/L between each eye). Thirty-three participants were enrolled in the study, of whom 22 were deemed to have a hyperosmolar tear film. A 30-item questionnaire including 10 symptoms rated on scales of frequency, severity, and bothersomeness was administered to participants in both groups. The quality-of-vision score ranged from 25 to 100 points, with lower scores indicating better quality of vision. RESULTS: The hyperosmolar group had a significantly worse quality-of-vision score than the normal osmolarity group across all three scales; mean differences for frequency, severity, and bothersomeness were 12.66 ± 9.75 (p=0.003), 9.44 ± 7.45 (p=0.003), and 11.90 ± 11.14 (p=0.008), respectively. Of the 10 symptoms that were included in the questionnaire, glare was the most problematic in the hyperosmolar group. CONCLUSIONS: In this study, we demonstrated a significant relationship between tear film hyperosmolarity and quality of vision, as patients with hyperosmolar tear films had worse quality of vision.


Assuntos
Síndromes do Olho Seco , Humanos , Síndromes do Olho Seco/diagnóstico , Lágrimas , Concentração Osmolar , Inquéritos e Questionários
12.
Int J Biol Macromol ; 262(Pt 1): 129992, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38331070

RESUMO

Ionic strength condition is a crucial parameter for food processing, but it remains unclear how ionic strength alters the structure and digestibility of binary complexes containing starch and protein/protein hydrolysates. Here, the binary complex with varied ionic strength (0-0.40 M) was built by native corn starch (NS) and soy protein isolate (SPI)/hydrolysates (SPIH) through NaCl. The inclusion of SPI and SPIH allowed a compact network structure, especially the SPIH with reduced molecule size, which enriched the resistant starch (RS) of NS-SPIH. Particularly, the higher ionic strength caused the larger nonperiodic structures and induced loosener network structures, largely increasing the possibility of amylase for starch digestion and resulting in a decreased RS content from 19.07 % to 15.52 %. In other words, the SPIH hindered starch digestion while increasing ionic strength had the opposite effect, which should be considered in staple food production.


Assuntos
Amido Resistente , Amido , Amido/química , Amido Resistente/farmacologia , Hidrolisados de Proteína/farmacologia , Amilases , Concentração Osmolar , Digestão
13.
J Emerg Med ; 66(3): e341-e345, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38403563

RESUMO

BACKGROUND: The estimated serum osmolality is a measurement of solutes in the blood, including sodium, glucose, and urea, but also includes ethanol and toxic alcohols (e.g., methanol, ethylene glycol, diethylene glycol, isopropyl alcohol, propylene glycol) when present. These rarely measured toxic alcohols can elevate the serum osmolality, giving the true measured osmolality. The difference between that and a calculated osmolality is the osmolal gap, which can be elevated in many clinical scenarios such as renal failure, ingestion of toxic alcohols, diabetic ketoacidosis, shock, and others. CASE REPORT: We report a patient with a history of alcohol use disorder who came to the Emergency Department with an abnormally elevated osmolal gap in the setting of altered mental status. The patient's increased osmolal gap was further investigated while he was promptly treated with fomepizole, thiamine, and urgent hemodialysis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We discuss the differential diagnosis for substances that increase the osmolal gap with respective ranges of elevation. This case demonstrates that although osmolal gap elevation is often attributed to the presence of toxic alcohols, other common etiologies may account for the gap, including acute renal failure and multiple myeloma.


Assuntos
Alcoolismo , Cetoacidose Diabética , Mieloma Múltiplo , Masculino , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Etanol , Metanol , Etilenoglicol , Concentração Osmolar
14.
Biomed Mater ; 19(3)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38364282

RESUMO

The block copolymer micelles and natural biopolymers were utilized to form layer-by-layer (LbL) films via electrostatic interaction, which were able to effectively load and controllably release favipiravir, a potential drug for the treatment of coronavirus epidemic. The LbL films demonstrated reversible swelling/shrinking behavior along with the manipulation of temperature, which could also maintain the integrity in the structure and the morphology. Due to dehydration of environmentally responsive building blocks, the drug release rate from the films was decelerated by elevating environmental temperature and ionic strength. In addition, the pulsed release of favipiravir was observed from the multilayer films under the trigger of temperature, which ensured the precise control in the content of the therapeutic reagents at a desired time point. The nanoparticle-based LbL films could be used for on-demandin vitrorelease of chemotherapeutic reagents.


Assuntos
Amidas , Micelas , Pirazinas , Liberação Controlada de Fármacos , Temperatura , Concentração Osmolar
15.
Mol Pharm ; 21(3): 1414-1423, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38386020

RESUMO

Protein self-interactions measured via second osmotic virial coefficients (B22) and dynamic light scattering interaction parameter values (kD) are often used as metrics for assessing the favorability of protein candidates and different formulations during monoclonal antibody (MAb) product development. Model predictions of B22 or kD typically do not account for glycans, though glycosylation can potentially impact experimental MAb self-interactions. To the best of our knowledge, the impact of MAb glycosylation on the experimentally measured B22 and kD values has not yet been reported. B22 and kD values of two fully deglycosylated MAbs and their native (i.e., fully glycosylated) counterparts were measured by light scattering over a range of pH and ionic strength conditions. Significant differences between B22 and kD of the native and deglycosylated forms were observed at a range of low to high ionic strengths used to modulate the effect of electrostatic contributions. Differences were most pronounced at low ionic strength, indicating that electrostatic interactions are a contributing factor. Though B22 and kD values were statistically equivalent at high ionic strengths where electrostatics were fully screened, we observed protein-dependent qualitative differences, which indicate that steric interactions may also play a role in the observed B22 and kD differences. A domain-level coarse-grained molecular model accounting for charge differences was considered to potentially provide additional insight but was not fully predictive of the behavior across all of the solution conditions investigated. This highlights that both the level of modeling and lack of inclusion of glycans may limit existing models in making quantitatively accurate predictions of self-interactions.


Assuntos
Anticorpos Monoclonais , Polissacarídeos , Anticorpos Monoclonais/química , Glicosilação , Difusão Dinâmica da Luz , Modelos Moleculares , Concentração de Íons de Hidrogênio , Concentração Osmolar
16.
Ophthalmic Surg Lasers Imaging Retina ; 55(3): 130-135, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38319057

RESUMO

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate serum osmolality and hydration status in patients with retinal vein occlusion (RVO). PATIENTS AND METHODS: This cross-sectional study consisted of 79 patients with RVO and 81 age- and sex-matched peers without ocular disease. Data were collected from patient records and included a comprehensive ophthalmological examination, laboratory data of fasting blood test results, and internal medicine outpatient examination. Complete blood count and levels of fasting glucose, sodium, blood urea nitrogen (BUN), creatinine, triglyceride, low-density lipoprotein, high-density lipoprotein, HbA1c, and serum osmolality were evaluated. BUN/creatinine ratios were calculated. RESULTS: Mean serum sodium and serum osmolality levels were 142.53 ± 2.13 and 139.74 ± 2.16 mEq/L and 286.58 ± 4.40 and 280.57 ± 4.39 mOsmol/kg H2O in the RVO and control groups, respectively. Serum osmolality and serum sodium levels, and BUN/creatinine ratio were significantly higher in the RVO group than in controls (P < 0.05 for all). CONCLUSIONS: We found that serum osmolality, sodium levels, and the BUN/creatinine ratio increased significantly in the RVO group. The results suggest dehydration status may affect the genesis of vessel occlusion in RVO. [Ophthalmic Surg Lasers Imaging Retina 2024;55:130-135.].


Assuntos
Oclusão da Veia Retiniana , Humanos , Oclusão da Veia Retiniana/diagnóstico , Estudos Transversais , Creatinina , Sódio , Concentração Osmolar , Fatores de Risco
17.
Mol Pharm ; 21(3): 1321-1333, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38334418

RESUMO

Attractive self-interactions and reversible self-association are implicated in many problematic solution behaviors for therapeutic proteins, such as irreversible aggregation, elevated viscosity, phase separation, and opalescence. Protein self-interactions and reversible oligomerization of two Fc-fusion proteins (monovalent and bivalent) and the corresponding fusion partner protein were characterized experimentally with static and dynamic light scattering as a function of pH (5 and 6.5) and ionic strength (10 mM to at least 300 mM). The fusion partner protein and monovalent Fc-fusion each displayed net attractive electrostatic self-interactions at pH 6.5 and net repulsive electrostatic self-interactions at pH 5. Solutions of the bivalent Fc-fusion contained higher molecular weight species that prevented quantification of typical interaction parameters (B22 and kD). All three of the proteins displayed reversible self-association at pH 6.5, where oligomers dissociated with increased ionic strength. Coarse-grained molecular simulations were used to model the self-interactions measured experimentally, assess net self-interactions for the bivalent Fc-fusion, and probe the specific electrostatic interactions between charged amino acids that were involved in attractive electrostatic self-interactions. Mayer-weighted pairwise electrostatic energies from the simulations suggested that attractive electrostatic self-interactions at pH 6.5 for the two Fc-fusion proteins were due to cross-domain interactions between the fusion partner domain(s) and the Fc domain.


Assuntos
Aminoácidos , Anticorpos Monoclonais , Anticorpos Monoclonais/química , Difusão Dinâmica da Luz , Concentração Osmolar , Concentração de Íons de Hidrogênio
18.
Nefrología (Madrid) ; 44(1): 10-22, ene.- feb. 2024. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-229417

RESUMO

Receptor interacting protein kinase 3 (RIPK3) is an intracellular kinase at the crossroads of cell death and inflammation. RIPK3 contains a RIP homotypic interaction motif (RHIM) domain which allows interactions with other RHIM-containing proteins and a kinase domain that allows phosphorylation of target proteins. RIPK3 may be activated through interaction with RHIM-containing proteins such as RIPK1, TRIF and DAI (ZBP1, DLM-1) or through RHIM-independent mechanisms in an alkaline intracellular pH. RIPK3 mediates necroptosis and promotes inflammation, independently of necroptosis, through either activation of NFκB or the inflammasome. There is in vivo preclinical evidence of the contribution of RIPK3 to both acute kidney injury (AKI) and chronic kidney disease (CKD) and to the AKI-to-CKD transition derived from RIPK3 deficient mice or the use of small molecule RIPK3 inhibitors. In these studies, RIPK3 targeting decreased inflammation but kidney injury improved only in some contexts. Clinical translation of these findings has been delayed by the potential of some small molecule inhibitors of RIPK3 kinase activity to trigger apoptotic cell death by inducing conformational changes of the protein. A better understanding of the conformational changes in RIPK3 that trigger apoptosis, dual RIPK3/RIPK1 inhibitors or repurposing of multiple kinase inhibitors such as dabrafenib may facilitate clinical development of the RIPK3 inhibition concept for diverse inflammatory diseases, including kidney diseases (AU)


La proteína quinasa 3 que interactúa con el receptor (RIPK3) es una quinasa intracelular que se encuentra a medio camino entre la muerte celular y la inflamación. La RIPK3 contiene un dominio motivo de interacción homotípica de RIP (RHIM), que permite las interacciones con otras proteínas que contienen RHIM, y un dominio de quinasa que permite la fosforilación de las proteínas diana. La RIPK3 puede ser activada a través de la interacción con las proteínas que contienen RHIM tales como RIPK1, TRIF y DAI (ZBP1, DLM-1), o a través de mecanismos independientes de RHIM en un pH intracelular alcalino. La RIPK3 media en la necroptosis y promueve la inflamación, independientemente de la necroptosis, bien a través de la activación de NFκB, o del inflamasoma. Existe evidencia preclínica in vivo de la contribución de RIPK3 a la insuficiencia renal aguda (IRA) y la enfermedad renal crónica (ERC), así como a la transición IRA-ERC derivada de ratones con deficiencia de RIPK3 o del uso de pequeñas moléculas inhibidoras de RIPK3. En dichos estudios, el tener a RIPK3 como objetivo redujo la inflamación, pero la nefropatía mejoró solo en algunos contextos. La traducción clínica de estos hallazgos se ha demorado debido al potencial de ciertas pequeñas moléculas inhibidoras de la actividad de la quinasa RIPK3 para activar la muerte celular induciendo cambios conformacionales de la proteína. Comprender mejor los cambios conformacionales de RIPK3 activadores de la apoptosis, los inhibidores duales RIPK3/RIPK1 o la reconversión de múltiples inhibidores de la quinasa tales como dabrafenib podría facilitar el desarrollo clínico del concepto de la inhibición de RIPK3 para diversas enfermedades inflamatorias, incluyendo las enfermedades renales (AU)


Assuntos
Humanos , Insuficiência Renal/metabolismo , Inflamação , Concentração Osmolar , Proteína Quinase 3 Ativada por Mitógeno , Doença Aguda
19.
Biol Pharm Bull ; 47(1): 72-78, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38171780

RESUMO

We recently reported that the gastrointestinal (GI) fluid volume is influenced by the solution osmolality, and proposed that this effect may play a role in beverage-drug interactions. Here, we investigated whether osmolality-dependent fluid secretion can explain the difference in the magnitudes of fruit juice-drug interactions depending on the type of fruit juice (grapefruit juice (GFJ), orange juice (OJ), and apple juice (AJ)). The osmolality of GFJ, OJ, and AJ used in this study was found to be 552, 686, and 749 mOsm/kg, respectively. Measurements of intestinal fluid movement following beverage administration by the in situ closed-loop technique revealed the following rank order for fluid volume in rat ileum: AJ > OJ > GFJ > purified water, suggesting that water movement is dependent on the osmolality of these beverages. Such changes in GI fluid volume are expected to alter the luminal drug concentration, potentially contributing to the magnitude of beverage-drug interactions. Indeed, in vivo pharmacokinetic study in rats revealed that the plasma concentration of atenolol, a low-permeability drug, was the highest after oral administration in purified water, followed by GFJ and OJ, and was the lowest after administration in AJ. In contrast, antipyrine, a high-permeability drug, showed no significant difference in plasma concentration after administration in purified water and fruit juices, suggesting that the absorption of high-permeability drugs is less affected by solution osmolality. Our findings indicate that differences in the magnitude of beverage-drug interactions can be at least partly explained by differences in the osmolality of the beverages ingested.


Assuntos
Citrus paradisi , Citrus sinensis , Malus , Ratos , Animais , Sucos de Frutas e Vegetais , Interações Alimento-Droga , Bebidas/análise , Concentração Osmolar , Água , Frutas
20.
Int J Med Sci ; 21(2): 341-356, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38169592

RESUMO

The in-situ osmolarity is an important physicochemical factor that regulates cell fate of nucleus pulposus cells (NPCs). Our previous studies demonstrated that reduced N-cadherin (NCDH) expression in nucleus pulposus cells is associated with cellular damage under hyper-osmolarity microenvironment. This study was aimed at exploring the impacts of NCDH on senescence and apoptosis of NPCs, as well as the potential molecular mechanism. By comparing NPCs from patients with lumbar fractures and lumbar disc herniation, we identified a correlation between decreased NCDH expression and increased endoplasmic reticulum stress (ERS), resulting in undesirable cell fate (senescence and apoptosis). After blocking Reactive oxygen species (ROS) or ERS, it was indicated that hyper-osmolarity microenvironment induced ERS was ROS-dependent. Further results demonstrated the correlation in rat NPCs. Upregulation of NCDH expression reduced ROS-dependent ERS, thus limiting undesirable cell fates in vitro. This was further confirmed through the rat tail acupuncture injection model. NCDH overexpression successfully mitigated ERS, preserved extracellular matrix production and alleviating intervertebral disc degeneration in vivo. Together, NCDH can alleviate senescence and apoptosis of NPCs by suppressing ROS-dependent ERS via the ATF4-CHOP signaling axis in the hyper-osmolarity microenvironment, thus highlighting the therapeutic potential of NCDH in combating degenerative disc diseases.


Assuntos
Degeneração do Disco Intervertebral , Núcleo Pulposo , Animais , Humanos , Ratos , Apoptose/genética , Caderinas/genética , Caderinas/metabolismo , Senescência Celular/genética , Estresse do Retículo Endoplasmático/genética , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/terapia , Núcleo Pulposo/metabolismo , Concentração Osmolar , Espécies Reativas de Oxigênio/metabolismo
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