The Antioxidative Role of Natural Compounds from a Green Coconut Mesocarp Undeniably Contributes to Control Diabetic Complications as Evidenced by the Associated Genes and Biochemical Indexes

Background. To investigate the effects of hyperbaric oxygen (HBO) and pentoxifylline (PTX) treatment on osteotendinous junction healing of Achilles tendon in an animal model. Materials and methods. Thirty-six adult female Wistar-albino rats were randomly divided into three groups as control, PTX and HBO groups with a total of 12 rats per group. Under general anesthesia, the Achilles tendons were cut at the level of the osteotendinous junction and repaired. After the surgery, no treatment was given to the control group. Fifty mg/kg intraperitoneal PTX was administered to the PTX group daily for 1 week. The HBO group was exposed to 2,5 atmospheric pressure, 100% oxygen for 2 hours daily for 1 week. All animals were sacrificed at the end of sixth week. Biomechanical tests and histological examinations were performed. Results. Energy absorption was significantly higher in the PTX group than that in the control group after biomechanical tests (p=0.010). Histopathological evaluation results revealed no difference between the groups: however, hyalinization level was relatively better in the HBO group than that in the control group (p=0.026). Conclusions. 1. We concluded that PTX has a positive effect on the treatment of osteotendinous junction injuries based on our results. 2. Although HBO therapy did not provide statistically significant differences, it might have some positive effects on these injuries. 3. Further experimental studies and clinical trials should be conducted.

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Target-Templated de novo Design of Macrocyclic D-/L-Peptides: Inhibitors of the PD-1/PD-L1 Interaction

10.26434/chemrxiv.11663337.v3 ◽

2020 ◽

Author(s):

Salvador Guardiola ◽

Monica Varese ◽

Xavier Roig ◽

Jesús Garcia ◽

Ernest Giralt

Keyword(s):

Protein Interactions ◽

Cyclic Peptides ◽

General Framework ◽

Large Scale ◽

De Novo ◽

Inhibitory Effect ◽

Original Text ◽

Protein Protein Interactions ◽

Retraction Notice ◽

Pharmaceutical Properties

NOTE: This preprint has been retracted by consensus from all authors. See the retraction notice in place above; the original text can be found under "Version 1", accessible from the version selector above. ------------------------------------------------------------------------ Peptides, together with antibodies, are among the most potent biochemical tools to modulate challenging protein-protein interactions. However, current structure-based methods are largely limited to natural peptides and are not suitable for designing target-specific binders with improved pharmaceutical properties, such as macrocyclic peptides. Here we report a general framework that leverages the computational power of Rosetta for large-scale backbone sampling and energy scoring, followed by side-chain composition, to design heterochiral cyclic peptides that bind to a protein surface of interest. To showcase the applicability of our approach, we identified two peptides (PD-i3 and PD-i6) that target PD-1, a key immune checkpoint, and work as protein ligand decoys. A comprehensive biophysical evaluation confirmed their binding mechanism to PD-1 and their inhibitory effect on the PD-1/PD-L1 interaction. Finally, elucidation of their solution structures by NMR served as validation of our de novo design approach. We anticipate that our results will provide a general framework for designing target-specific drug-like peptides.

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A Target-Based Method for Designing Heterochiral Cyclic Peptide Binders: De Novo Inhibitors of the PD-1/PD-L1 Interaction

10.26434/chemrxiv.11663337.v2 ◽

2020 ◽

Author(s):

Salvador Guardiola ◽

Monica Varese ◽

Xavier Roig ◽

Jesús Garcia ◽

Ernest Giralt

Keyword(s):

Protein Interactions ◽

Cyclic Peptides ◽

General Framework ◽

Large Scale ◽

Cyclic Peptide ◽

De Novo ◽

Inhibitory Effect ◽

Original Text ◽

Retraction Notice ◽

Pharmaceutical Properties

NOTE: This preprint has been retracted by consensus from all authors. See the retraction notice in place above; the original text can be found under "Version 1", accessible from the version selector above. ------------------------------------------------------------------------ Peptides, together with antibodies, are among the most potent biochemical tools to modulate challenging protein-protein interactions. However, current structure-based methods are largely limited to natural peptides and are not suitable for designing target-specific binders with improved pharmaceutical properties, such as macrocyclic peptides. Here we report a general framework that leverages the computational power of Rosetta for large-scale backbone sampling and energy scoring, followed by side-chain composition, to design heterochiral cyclic peptides that bind to a protein surface of interest. To showcase the applicability of our approach, we identified two peptides (PD-i3 and PD-i6) that target PD-1, a key immune checkpoint, and work as protein ligand decoys. A comprehensive biophysical evaluation confirmed their binding mechanism to PD-1 and their inhibitory effect on the PD-1/PD-L1 interaction. Finally, elucidation of their solution structures by NMR served as validation of our de novo design approach. We anticipate that our results will provide a general framework for designing target-specific drug-like peptides.

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Target-Templated de novo Design of Macrocyclic D-/L-Peptides: Inhibitors of the PD-1/PD-L1 Interaction

10.26434/chemrxiv.11663337 ◽

2020 ◽

Author(s):

Salvador Guardiola ◽

Monica Varese ◽

Xavier Roig ◽

Jesús Garcia ◽

Ernest Giralt

Keyword(s):

Protein Interactions ◽

Cyclic Peptides ◽

General Framework ◽

Large Scale ◽

De Novo ◽

Inhibitory Effect ◽

Original Text ◽

Protein Protein Interactions ◽

Retraction Notice ◽

Pharmaceutical Properties

NOTE: This preprint has been retracted by consensus from all authors. See the retraction notice in place above; the original text can be found under "Version 1", accessible from the version selector above. ------------------------------------------------------------------------ Peptides, together with antibodies, are among the most potent biochemical tools to modulate challenging protein-protein interactions. However, current structure-based methods are largely limited to natural peptides and are not suitable for designing target-specific binders with improved pharmaceutical properties, such as macrocyclic peptides. Here we report a general framework that leverages the computational power of Rosetta for large-scale backbone sampling and energy scoring, followed by side-chain composition, to design heterochiral cyclic peptides that bind to a protein surface of interest. To showcase the applicability of our approach, we identified two peptides (PD-i3 and PD-i6) that target PD-1, a key immune checkpoint, and work as protein ligand decoys. A comprehensive biophysical evaluation confirmed their binding mechanism to PD-1 and their inhibitory effect on the PD-1/PD-L1 interaction. Finally, elucidation of their solution structures by NMR served as validation of our de novo design approach. We anticipate that our results will provide a general framework for designing target-specific drug-like peptides.

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Flavone-Rich Fractions and Extracts from Oroxylum indicum and Their Antibacterial Activities against Clinically Isolated Zoonotic Bacteria and Free Radical Scavenging Effects

Molecules ◽

10.3390/molecules26061773 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1773

Author(s):

Patchima Sithisarn ◽

Piyanuch Rojsanga ◽

Pongtip Sithisarn

Keyword(s):

Antibacterial Activities ◽

Inhibitory Effect ◽

Total Flavonoid ◽

Total Phenolic ◽

Antibacterial Effects ◽

E Coli ◽

Young Fruit ◽

Oroxylum Indicum ◽

Zoonotic Bacteria

Oroxylum indicum extracts from the seeds collected from Lampang and Pattani provinces in Thailand, and young fruits and flowers exhibited in vitro display antioxidant and antibacterial activities against clinically isolated zoonotic bacteria including Staphylococcus intermedius, Streptococcus suis, Pseudomonas aeruginosa, β-hemolytic Escherichia coli and Staphylococcus aureus. The orange crystals and yellow precipitates were obtained from the preparation processes of the seed extracts. The orange-red crystals from the seeds collected from Lampang province exhibited strong in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging effects (EC50 value = 25.99 ± 3.30 μg/mL) and antibacterial effects on S. intermedius and β-hemolytic E. coli while the yellow precipitate from the same source exhibited only antioxidant activity. Quantitative analysis of phytochemicals in O. indicum samples by spectrophotometric and HPLC techniques showed that they contained different amounts of total phenolic, total flavonoid and three major flavones; baicalin, baicalein and chrysin contents. Young fruit extract, which contained low amounts of flavone contents, still promoted antibacterial effects against the tested bacteria with IC50 values lower than 1 mg/mL and MIC values between 4 to 10 mg/mL in S. intermedius, S. aureus and S suis while higher IC50 and MIC values against P. aeruginosa and β-hemolytic E. coli were found. From scanning electron microscopy, the extract of the young fruit of O. indicum promoted morphological changes in the bacterial cells by disrupting the bacterial cell walls, inducing leakage of the cellular content, and generating the abnormal accumulation of cells. The mechanism of action of the extract for this antibacterial effect may be the disruption of the cell membrane and abnormal cell aggregations. Regression analysis of the results suggests the correlation between total phenolic and total flavonoid contents and antioxidant and antibacterial effects. Baicalin was found to have a high correlation with an inhibitory effect against β-hemolytic E. coli while three unidentified peaks, which could be flavones, showed high correlations with an inhibitory effect against S. intermedius, S. suis, P. aeruginosa and S. aureus.

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Role of Curing Temperature of Poly(Glycerol Sebacate) Substrates on Protein-Cell Interaction and Early Cell Adhesion

Polymers ◽

10.3390/polym13030382 ◽

2021 ◽

Vol 13 (3) ◽

pp. 382

Author(s):

Rubén Martín-Cabezuelo ◽

José Carlos Rodríguez-Hernández ◽

Guillermo Vilariño-Feltrer ◽

Ana Vallés-Lluch

Keyword(s):

Protein Interactions ◽

Chemical Properties ◽

Focal Adhesions ◽

Collagen Type I ◽

Inhibitory Effect ◽

Synthesis Temperature ◽

Curing Temperature ◽

Cell Protein ◽

Preliminary Treatment ◽

Type I

A novel procedure to obtain smooth, continuous polymeric surfaces from poly(glycerol sebacate) (PGS) has been developed with the spin-coating technique. This method proves useful for separating the effect of the chemistry and morphology of the networks (that can be obtained by varying the synthesis parameters) on cell-protein-substrate interactions from that of structural variables. Solutions of the PGS pre-polymer can be spin-coated, to then be cured. Curing under variable temperatures has been shown to lead to PGS networks with different chemical properties and topographies, conditioning their use as a biomaterial. Particularly, higher synthesis temperatures yield denser networks with fewer polar terminal groups available on the surface. Material-protein interactions were characterised by using extracellular matrix proteins such as fibronectin (Fn) and collagen type I (Col I), to unveil the biological interface profile of PGS substrates. To that end, atomic force microscopy (AFM) images and quantification of protein adsorbed in single, sequential and competitive protein incubations were used. Results reveal that Fn is adsorbed in the form of clusters, while Col I forms a characteristic fibrillar network. Fn has an inhibitory effect when incubated prior to Col I. Human umbilical endothelial cells (HUVECs) were also cultured on PGS surfaces to reveal the effect of synthesis temperature on cell behaviour. To this effect, early focal adhesions (FAs) were analysed using immunofluorescence techniques. In light of the results, 130 °C seems to be the optimal curing temperature since a preliminary treatment with Col I or a Fn:Col I solution facilitates the formation of early focal adhesions and growth of HUVECs.

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N-Acetylcysteine Added to Local Anesthesia Reduces Scar Area and Width in Early Wound Healing—An Animal Model Study

International Journal of Molecular Sciences ◽

10.3390/ijms22147549 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7549

Author(s):

Wiktor Paskal ◽

Adriana M. Paskal ◽

Piotr Pietruski ◽

Albert Stachura ◽

Kacper Pełka ◽

...

Keyword(s):

Wound Healing ◽

Early Stage ◽

Healing Process ◽

Wound Healing Process ◽

Sprague Dawley ◽

Time Points ◽

Model Study ◽

Sprague Dawley Rats ◽

Animal Model Study ◽

Anesthetic Solution

The aim of the study was to evaluate if a pre-incisional N-acetylcysteine (NAC) treatment altered the process of wound healing in a rat model. The dorsal skin of 24 Sprague-Dawley rats was incised in six locations. Before the incisions were made, skin was injected either with lidocaine and epinephrine (one side) or with these agents supplemented with 0.015%, 0.03%, or 0.045% NAC (contralaterally). Photographic documentation of the wound healing process was made at 11 time points. Rats were sacrificed 3, 7, 14, or 60 days after incision to excise scars for histological analysis. They included: Abramov scale scoring, histomorphometry analysis, and collagen fiber arrangement assessment. Skin pretreated with 0.03% NAC produced the shortest scars at all analyzed time points, though this result was statistically insignificant. At this NAC concentration the scars had smaller areas on the third day and were narrower on the day 4 compared with all the other groups (p < 0.05). On day 7, at the same concentration of NAC, the scars had a higher superficial concentration index (p = 0.03) and larger dermal proliferation area (p = 0.04). NAC addition to pre-incisional anesthetic solution decreased wound size and width at an early stage of scar formation at all concentrations; however, with optimal results at 0.03% concentration.

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The Phytochemical Analysis of Vinca L. Species Leaf Extracts Is Correlated with the Antioxidant, Antibacterial, and Antitumor Effects

Molecules ◽

10.3390/molecules26103040 ◽

2021 ◽

Vol 26 (10) ◽

pp. 3040

Author(s):

Alexandra Ciorîță ◽

Cezara Zăgrean-Tuza ◽

Augustin C. Moț ◽

Rahela Carpa ◽

Marcel Pârvu

Keyword(s):

Bacterial Infections ◽

Inhibitory Effect ◽

Total Phenolic ◽

Phytochemical Analysis ◽

Leaf Extracts ◽

Antitumor Effects ◽

Cytotoxic Effects ◽

E Coli ◽

Lactate Dehydrogenase Release ◽

Nitric Oxide Concentration

The phytochemical analysis of Vinca minor, V. herbacea, V. major, and V. major var. variegata leaf extracts showed species-dependent antioxidant, antibacterial, and cytotoxic effects correlated with the identified phytoconstituents. Vincamine was present in V. minor, V. major, and V. major var. variegata, while V. minor had the richest alkaloid content, followed by V. herbacea. V. major var. variegata was richest in flavonoids and the highest total phenolic content was found in V. herbacea which also had elevated levels of rutin. Consequently, V. herbacea had the highest antioxidant activity followed by V. major var. variegata. Whereas, the lowest one was of V. major. The V. minor extract showed the most efficient inhibitory effect against both Staphylococcus aureus and E. coli. On the other hand, V. herbacea had a good anti-bacterial potential only against S. aureus, which was most affected at morphological levels, as indicated by scanning electron microscopy. The Vinca extracts acted in a dose-depended manner against HaCaT keratinocytes and A375 melanoma cells and moreover, with effects on the ultrastructure, nitric oxide concentration, and lactate dehydrogenase release. Therefore, the Vinca species could be exploited further for the development of alternative treatments in bacterial infections or as anticancer adjuvants.

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Recent advances in animal model experimentation in autism research

Acta Neuropsychiatrica ◽

10.1017/neu.2013.58 ◽

2013 ◽

Vol 26 (5) ◽

pp. 264-271 ◽

Cited By ~ 6

Author(s):

Mousumi Tania ◽

Md. Asaduzzaman Khan ◽

Kun Xia

Keyword(s):

Animal Model ◽

Animal Models ◽

Human Condition ◽

Behavioral Alterations ◽

Important Place ◽

Adult Mice ◽

Recent Advances ◽

Model Study ◽

Disease Biology ◽

Animal Model Study

ObjectiveAutism, a lifelong neuro-developmental disorder is a uniquely human condition. Animal models are not the perfect tools for the full understanding of human development and behavior, but they can be an important place to start. This review focused on the recent updates of animal model research in autism.MethodsWe have reviewed the publications over the last three decades, which are related to animal model study in autism.ResultsAnimal models are important because they allow researchers to study the underlying neurobiology in a way that is not possible in humans. Improving the availability of better animal models will help the field to increase the development of medicines that can relieve disabling symptoms. Results from the therapeutic approaches are encouraging remarkably, since some behavioral alterations could be reversed even when treatment was performed on adult mice. Finding an animal model system with similar behavioral tendencies as humans is thus vital for understanding the brain mechanisms, supporting social motivation and attention, and the manner in which these mechanisms break down in autism. The ongoing studies should therefore increase the understanding of the biological alterations associated with autism as well as the development of knowledge-based treatments therapy for those struggling with autism.ConclusionIn this review, we have presented recent advances in research based on animal models of autism, raising hope for understanding the disease biology for potential therapeutic intervention to improve the quality of life of autism individuals.

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Chronic effect of exercise on liver cholesterol of normal and hypercholesteremic rats

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1963.205.3.453 ◽

1963 ◽

Vol 205 (3) ◽

pp. 453-456 ◽

Cited By ~ 12

Author(s):

Philip D. Gollnick

Keyword(s):

Exercise Program ◽

Normal Diet ◽

The Other ◽

Liver Cholesterol ◽

Albino Rats ◽

Cholesterol Diet ◽

Trained Group ◽

Sprague Dawley ◽

Cholesterol Accumulation ◽

Body Weights

Two groups of male albino rats of the Sprague-Dawley strain, with average initial body weights of about 265 g, were trained for 22 weeks on an exercise program of swimming one-half hour daily in water at 35 C. One trained group was fed a normal diet containing 18% casein. The other trained group received an isocaloric diet containing 1% cholesterol which was designed to produce hypercholesteremia. Two nonexercised groups, one fed the normal and the other the 1% cholesterol diet, served as controls. The adrenals and heart ventricles of both trained groups were larger than their respective controls. Exercise had no hypocholesteremic effect on the sera of either trained group. Fat and cholesterol accumulation in the livers of rats fed the 1% cholesterol diet were not affected by training, but training significantly lowered the fat and cholesterol of the livers of the normal rats.

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