Phase-Separating Peptides for Direct Cytosolic Delivery and Redox-Activated Release of Macromolecular Therapeutics.

Abstract Biomacromolecules are highly promising therapeutic modalities to treat various diseases. However, they suffer from poor cellular membrane permeability, limiting their access to intracellular targets. Strategies to overcome this challenge employ nanoscale carriers that often get trapped in endosome compartments. Here, we report on conjugated peptides forming pH- and redox-responsive coacervate microdroplets by liquid-liquid phase separation (LLPS) that readily cross the cell membrane. A wide range of macromolecules can be quickly recruited within the microdroplets, from small peptides to enzymes as large as 430 kDa to mRNAs. The therapeutic-loaded coacervates bypass endocytosis to directly enter in the cytosol, where they undergo glutathione-mediated release of payload whose bioactivity is retained in the cell, whereas mRNAs exhibit a high transfection efficiency. These peptide coacervates represent a promising platform for intracellular delivery of a large palette of macromolecular therapeutics that have potential in the treatment of various pathologies (e.g. cancers and metabolic diseases), or as carriers for mRNA-based vaccines.

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The Management of Post-Tonsillectomy Morbidity in Patients With Sleep Apnoea

Revista de Chimie ◽

10.37358/rc.19.10.3738 ◽

2019 ◽

Vol 70 (10) ◽

pp. 3738-3740

Keyword(s):

Day Surgery ◽

Sleep Apnoea ◽

Integrative Approach ◽

Multicenter Studies ◽

Therapeutic Modalities ◽

Advantages And Disadvantages ◽

Obstructive Sleep ◽

Wide Range ◽

The Impact ◽

Surgery Center

The Tonsillectomy in children or adults is an intervention commonly encountered in the ENT (Ear Nose and Throat) and Head and Neck surgeon practice. The current tendency is to perform this type of surgery in major ambulatory surgery centers. Two objectives are thus pursued: first of all, the increase of the patient quality of life through the reintegration into the family as quickly as possible and secondly, the expenses associated with continuous hospitalization are reduced. Any tertiary (multidisciplinary) sleep center must ensure the complete diagnosis and treatment (including surgery) of sleep respiratory disorders. Under these conditions the selection of patients and especially the implementation of the specific protocols in order to control the postoperative complications it becomes essential. The present paper describes our experience of tonsillectomy as treatment for selected patients with chronic rhonchopathy (snoring) and mild to moderate obstructive sleep apnoea. It was presented the impact of antibiotics protocols in reducing the main morbid outcomes following tonsillectomy, in our day surgery center. The obtained results can also be a prerequisite for the integrative approach of the patients with sleep apnoea who were recommended surgical treatment. Considering the wide range of therapeutic modalities used in sleep apnoea, each with its specific advantages and disadvantages, more extensive and multicenter studies are needed. Keywords: post-tonsillectomy morbidity, day surgery center, sleep disorders

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PHYTOCHEMICAL EVALUATION OF PUNICA GRANATUM L. LEAF EXTRACT

International Journal of Current Pharmaceutical Research ◽

10.22159/ijcpr.2017v9i4.1159 ◽

2017 ◽

Vol 9 (4) ◽

pp. 14 ◽

Cited By ~ 2

Author(s):

P. Sreedevi ◽

K. Vijayalakshmi ◽

R. Venkateswari

Keyword(s):

Metabolic Diseases ◽

Ethanolic Extract ◽

Punica Granatum ◽

Leaf Extracts ◽

Bioactive Substances ◽

Pharmaceutical Ingredients ◽

Wide Range ◽

Leaf Powder ◽

Potent Drug ◽

Punica Granatum L

Objective: This study was conducted to assess the phytochemical constituents in Punica granatum L. Leaf extracts (PGLE) using standard methods.Methods: The leaf powder was extracted using solvents namely aqueous, hydroalcohol, ethanol, ethyl acetate and n-hexane. Qualitative and Quantitative phytochemical screenings of PGLE were assessed by standard methods.Results: All the leaf extracts were positive for a wide range of bio-active compounds except n-hexane. The result has showed that the maximum amount of total phenols (394.16 mg/g DW of extract), total tannins (210.5 mg/g DW of extract), flavanoids (147.4 mg/g DW of extract) and total triterpenoids (112 mg/g DW of extract) were noted in ethanolic extract of P. granatum leaf (EPGL). The biological assay revealed that relevant amount of carbohydrate, protein, lipid and alkaloid in EPGL.Conclusion: The findings of this study concluded that the EPGL had potential bioactive substances that may be used as pharmaceutical ingredients for formulation of new or prospective potent drug to cure wide range of metabolic diseases.

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Reversible Protein Capture and Release by Redox-Responsive Hydrogel in Microfluidics

Polymers ◽

10.3390/polym14020267 ◽

2022 ◽

Vol 14 (2) ◽

pp. 267

Author(s):

Chen Jiao ◽

Franziska Obst ◽

Martin Geisler ◽

Yunjiao Che ◽

Andreas Richter ◽

...

Keyword(s):

Microfluidic Device ◽

Disulfide Bonds ◽

Stimuli Responsive ◽

Disulfide Exchange ◽

Protein Capture ◽

Wide Range ◽

Redox Responsive ◽

Potential Applications ◽

Capture And Release ◽

Cross Linker

Stimuli-responsive hydrogels have a wide range of potential applications in microfluidics, which has drawn great attention. Double cross-linked hydrogels are very well suited for this application as they offer both stability and the required responsive behavior. Here, we report the integration of poly(N-isopropylacrylamide) (PNiPAAm) hydrogel with a permanent cross-linker (N,N′-methylenebisacrylamide, BIS) and a redox responsive reversible cross-linker (N,N′-bis(acryloyl)cystamine, BAC) into a microfluidic device through photopolymerization. Cleavage and re-formation of disulfide bonds introduced by BAC changed the cross-linking densities of the hydrogel dots, making them swell or shrink. Rheological measurements allowed for selecting hydrogels that withstand long-term shear forces present in microfluidic devices under continuous flow. Once implemented, the thiol-disulfide exchange allowed the hydrogel dots to successfully capture and release the protein bovine serum albumin (BSA). BSA was labeled with rhodamine B and functionalized with 2-(2-pyridyldithio)-ethylamine (PDA) to introduce disulfide bonds. The reversible capture and release of the protein reached an efficiency of 83.6% in release rate and could be repeated over 3 cycles within the microfluidic device. These results demonstrate that our redox-responsive hydrogel dots enable the dynamic capture and release of various different functionalized (macro)molecules (e.g., proteins and drugs) and have a great potential to be integrated into a lab-on-a-chip device for detection and/or delivery.

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Neuropeptides and Behaviors: How Small Peptides Regulate Nervous System Function and Behavioral Outputs

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2021.786471 ◽

2021 ◽

Vol 14 ◽

Author(s):

Umer Saleem Bhat ◽

Navneet Shahi ◽

Siju Surendran ◽

Kavita Babu

Keyword(s):

Nervous System ◽

Behavioral Plasticity ◽

Environmental Changes ◽

Sensory Information ◽

Synaptic Activity ◽

Small Peptides ◽

C Elegans ◽

Wide Range ◽

Nervous System Function ◽

Insight Into

One of the reasons that most multicellular animals survive and thrive is because of the adaptable and plastic nature of their nervous systems. For an organism to survive, it is essential for the animal to respond and adapt to environmental changes. This is achieved by sensing external cues and translating them into behaviors through changes in synaptic activity. The nervous system plays a crucial role in constantly evaluating environmental cues and allowing for behavioral plasticity in the organism. Multiple neurotransmitters and neuropeptides have been implicated as key players for integrating sensory information to produce the desired output. Because of its simple nervous system and well-established neuronal connectome, C. elegans acts as an excellent model to understand the mechanisms underlying behavioral plasticity. Here, we critically review how neuropeptides modulate a wide range of behaviors by allowing for changes in neuronal and synaptic signaling. This review will have a specific focus on feeding, mating, sleep, addiction, learning and locomotory behaviors in C. elegans. With a view to understand evolutionary relationships, we explore the functions and associated pathophysiology of C. elegans neuropeptides that are conserved across different phyla. Further, we discuss the mechanisms of neuropeptidergic signaling and how these signals are regulated in different behaviors. Finally, we attempt to provide insight into developing potential therapeutics for neuropeptide-related disorders.

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Molecular mechanisms of endolysosomal Ca2+ signalling in health and disease

Biochemical Journal ◽

10.1042/bj20110949 ◽

2011 ◽

Vol 439 (3) ◽

pp. 349-378 ◽

Cited By ~ 212

Author(s):

Anthony J. Morgan ◽

Frances M. Platt ◽

Emyr Lloyd-Evans ◽

Antony Galione

Keyword(s):

Molecular Mechanisms ◽

Cellular Processes ◽

Late Endosomes ◽

Wide Range ◽

Health And Disease ◽

Lysosome Related Organelles ◽

Cellular Compartments ◽

Endosomal Vesicles ◽

Intracellular Targets

Endosomes, lysosomes and lysosome-related organelles are emerging as important Ca2+ storage cellular compartments with a central role in intracellular Ca2+ signalling. Endocytosis at the plasma membrane forms endosomal vesicles which mature to late endosomes and culminate in lysosomal biogenesis. During this process, acquisition of different ion channels and transporters progressively changes the endolysosomal luminal ionic environment (e.g. pH and Ca2+) to regulate enzyme activities, membrane fusion/fission and organellar ion fluxes, and defects in these can result in disease. In the present review we focus on the physiology of the inter-related transport mechanisms of Ca2+ and H+ across endolysosomal membranes. In particular, we discuss the role of the Ca2+-mobilizing messenger NAADP (nicotinic acid adenine dinucleotide phosphate) as a major regulator of Ca2+ release from endolysosomes, and the recent discovery of an endolysosomal channel family, the TPCs (two-pore channels), as its principal intracellular targets. Recent molecular studies of endolysosomal Ca2+ physiology and its regulation by NAADP-gated TPCs are providing exciting new insights into the mechanisms of Ca2+-signal initiation that control a wide range of cellular processes and play a role in disease. These developments underscore a new central role for the endolysosomal system in cellular Ca2+ regulation and signalling.

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Health benefits of physical activity with special reference to interaction with diet

Public Health Nutrition ◽

10.1079/phn2001137 ◽

2001 ◽

Vol 4 (2b) ◽

pp. 517-528 ◽

Cited By ~ 57

Author(s):

IM Vuori

Keyword(s):

Physical Activity ◽

Metabolic Diseases ◽

Biological Effects ◽

Overweight And Obesity ◽

Moderate Physical Activity ◽

Wide Range ◽

High Prevalence ◽

Inadequate Nutrition ◽

Dose Dependent ◽

Reduced Risk

AbstractRegular physical activity causes numerous and substantial performance-improving And health-enhancing effects. Most of them are highly predictable, dose-dependent and generalizable to a wide range of population groups. Many of the biological effects of regular, moderate physical activity translate into substantially reduced risk of coronary heart disease, cerebrovascular disease, hypertension, maturity onset diabetes, overweight and obesity, and osteoporosis. These effects also substantially reduce the risk of deterioration of functional capacity. In the genesis of these conditions, alack of physical activity and inadequate nutrition act synergistically and in part additively, and they operate largely through the same pathways. It is conceivable to suggest that the prevalence of, e.g, the above mentioned metabolic diseases is so high in Europe largely because of the high prevalence of sedentariness and inadequate nutrition. Thus, both physical activity and nutrition have to be given strong emphasis in policies, strategies and programmes that will be developed and implemented for improving the health of Europeans.

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An Overview of FGF19 and FGF21: The Therapeutic Role in the Treatment of the Metabolic Disorders and Obesity

Hormone and Metabolic Research ◽

10.1055/a-0623-2909 ◽

2018 ◽

Vol 50 (06) ◽

pp. 441-452 ◽

Cited By ~ 23

Author(s):

Nasim Babaknejad ◽

Hashem Nayeri ◽

Roohullah Hemmati ◽

Somaye Bahrami ◽

Ahmad Esmaillzadeh

Keyword(s):

Cellular Proliferation ◽

Metabolic Diseases ◽

Glucose And Lipid Metabolism ◽

Timely Review ◽

Wide Range ◽

Probable Role ◽

Artery Disease ◽

Treatment Of Obesity ◽

The Relationship

AbstractFibroblast growth factors (FGFs) are responsible for the regulation of a wide range of biological functions, among which cellular proliferation, survival, migration, and differentiation could be pointed out. FGF19 controls the enterohepatic bile acid/cholesterol system, and FGF21 modulates fatty acid/glucose metabolism. Obesity, type 2 diabetes, coronary artery disease, and cancer, all can alter FGF21 circulating concentrations. In contrast to FGF21, metabolic diseases exhibit reduced serum FGF19 levels. Accordingly, FGF19 and FGF21 play important roles in regulating glucose and lipid metabolism. Hence, we present here a timely review on the relationship between FGF19/21 and metabolic diseases, especially obesity, and their probable role in development and treatment of obesity seems necessary.

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Title: Human Serum/Plasma Glycoprotein Analysis by 1H-NMR, an Emerging Method of Inflammatory Assessment

Journal of Clinical Medicine ◽

10.3390/jcm9020354 ◽

2020 ◽

Vol 9 (2) ◽

pp. 354 ◽

Cited By ~ 6

Author(s):

Fuertes-Martín ◽

Correig ◽

Vallvé ◽

Amigó

Keyword(s):

1H Nmr ◽

Systemic Inflammation ◽

Metabolic Diseases ◽

Inflammatory Diseases ◽

Inflammatory Marker ◽

Point Of View ◽

Proton Nuclear Magnetic Resonance ◽

New Paradigm ◽

Reactive Protein ◽

Wide Range

Several studies suggest that variations in the concentration of plasma glycoproteins can influence cellular changes in a large number of diseases. In recent years, proton nuclear magnetic resonance (1H-NMR) has played a major role as an analytical tool for serum and plasma samples. In recent years, there is an increasing interest in the characterization of glycoproteins through 1H-NMR in order to search for reliable and robust biomarkers of disease. The objective of this review was to examine the existing studies in the literature related to the study of glycoproteins from an analytical and clinical point of view. There are currently several techniques to characterize circulating glycoproteins in serum or plasma, but in this review, we focus on 1H-NMR due to its great robustness and recent interest in its translation to the clinical setting. In fact, there is already a marker in H-NMR representing the acetyl groups of the glycoproteins, GlycA, which has been increasingly studied in clinical studies. A broad search of the literature was performed showing a general consensus that GlycA is a robust marker of systemic inflammation. The results also suggested that GlycA better captures systemic inflammation even more than C-reactive protein (CRP), a widely used classical inflammatory marker. The applications reviewed here demonstrated that GlycA was potentially a key biomarker in a wide range of diseases such as cancer, metabolic diseases, cardiovascular risk, and chronic inflammatory diseases among others. The profiling of glycoproteins through 1H-NMR launches an encouraging new paradigm for its future incorporation in clinical diagnosis.

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Liquid-liquid phase separation and viscosity within secondary organic aerosol generated from diesel fuel vapors

10.5194/acp-2019-367 ◽

2019 ◽

Author(s):

Mijung Song ◽

Adrian M. Maclean ◽

Yuanzhou Huang ◽

Natalie R. Smith ◽

Sandra L. Blair ◽

...

Keyword(s):

Phase Separation ◽

Liquid Phase ◽

Diesel Fuel ◽

Diffusion Coefficients ◽

Secondary Organic Aerosol ◽

Organic Aerosol ◽

Liquid Phase Separation ◽

Small Diffusion ◽

Wide Range ◽

Liquid Liquid Phase Separation

Abstract. Information on liquid-liquid phase separation (LLPS) and viscosity (or diffusion) within secondary organic aerosol (SOA) is needed to improve predictions of particle size, mass, reactivity, and cloud nucleating properties in the atmosphere. Here we report on LLPS and viscosities within SOA generated by the photooxidation of diesel fuel vapors. Diesel fuel contains a wide range of volatile organic compounds, and SOA generated by the photooxidation of diesel fuel vapors may be a good proxy for SOA from anthropogenic emissions. In our experiments, LLPS occurred over the relative humidity (RH) range of ~ 70 % to ~ 100 %, resulting in an organic-rich outer phase and a water-rich inner phase. These results may have implications for predicting the cloud nucleating properties of anthropogenic SOA since the organic-rich outer phase can lower the kinetic barrier for activation to a cloud droplet. At &leq; 10 % RH, the viscosity was in the range of &geq; 1 × 108 Pa s, which corresponds to roughly the viscosity of tar pitch. At 38–50 % RH the viscosity was in the range of 1 × 108–3 × 105 Pa s. These measured viscosities are consistent with predictions based on oxygen to carbon elemental ratio (O : C) and molar mass as well as predictions based on the number of carbon, hydrogen, and oxygen atoms. Based on the measured viscosities and the Stokes–Einstein relation, at &leq; 10 % RH diffusion coefficients of organics within diesel fuel SOA is &leq; 5.4 × 10−17cm2 s−1 and the mixing time of organics within 200 nm diesel fuel SOA particles (τmixing) is &gtrsim; 50 h. These small diffusion coefficients and large mixing times may be important in laboratory experiments, where SOA is often generated and studied using low RH conditions and on time scales of minutes to hours. At 38–50 % RH, the calculated organic diffusion coefficients are in the range of 5.4 × 10−17 to 1.8 × 10−13 cm2 s−1 and calculated τmixing values are in the range of ~ 0.01 h to ~ 50 h. These values provide important constraints for the physicochemical properties of anthropogenic SOA.

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Liquid–liquid phase separation and viscosity within secondary organic aerosol generated from diesel fuel vapors

Atmospheric Chemistry and Physics ◽

10.5194/acp-19-12515-2019 ◽

2019 ◽

Vol 19 (19) ◽

pp. 12515-12529 ◽

Cited By ~ 5

Author(s):

Mijung Song ◽

Adrian M. Maclean ◽

Yuanzhou Huang ◽

Natalie R. Smith ◽

Sandra L. Blair ◽

...

Keyword(s):

Phase Separation ◽

Liquid Phase ◽

Diesel Fuel ◽

Diffusion Coefficients ◽

Secondary Organic Aerosol ◽

Organic Aerosol ◽

Liquid Phase Separation ◽

Small Diffusion ◽

Wide Range ◽

Liquid Liquid Phase Separation

Abstract. Information on liquid–liquid phase separation (LLPS) and viscosity (or diffusion) within secondary organic aerosol (SOA) is needed to improve predictions of particle size, mass, reactivity, and cloud nucleating properties in the atmosphere. Here we report on LLPS and viscosities within SOA generated by the photooxidation of diesel fuel vapors. Diesel fuel contains a wide range of volatile organic compounds, and SOA generated by the photooxidation of diesel fuel vapors may be a good proxy for SOA from anthropogenic emissions. In our experiments, LLPS occurred over the relative humidity (RH) range of ∼70 % to ∼100 %, resulting in an organic-rich outer phase and a water-rich inner phase. These results may have implications for predicting the cloud nucleating properties of anthropogenic SOA since the presence of an organic-rich outer phase at high-RH values can lower the supersaturation with respect to water required for cloud droplet formation. At ≤10 % RH, the viscosity was ≥1×108 Pa s, which corresponds to roughly the viscosity of tar pitch. At 38 %–50 % RH, the viscosity was in the range of 1×108 to 3×105 Pa s. These measured viscosities are consistent with predictions based on oxygen to carbon elemental ratio (O:C) and molar mass as well as predictions based on the number of carbon, hydrogen, and oxygen atoms. Based on the measured viscosities and the Stokes–Einstein relation, at ≤10 % RH diffusion coefficients of organics within diesel fuel SOA is ≤5.4×10-17 cm2 s−1 and the mixing time of organics within 200 nm diesel fuel SOA particles (τmixing) is 50 h. These small diffusion coefficients and large mixing times may be important in laboratory experiments, where SOA is often generated and studied using low-RH conditions and on timescales of minutes to hours. At 38 %–50 % RH, the calculated organic diffusion coefficients are in the range of 5.4×10-17 to 1.8×10-13 cm2 s−1 and calculated τmixing values are in the range of ∼0.01 h to ∼50 h. These values provide important constraints for the physicochemical properties of anthropogenic SOA.

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