Recently, the dramatic emergence of antimicrobial resistance has received attention from World Health Organization. Synthetic antimicrobial peptides (SAMPs) are considered new weapons to fight ...against infections caused by multi-drug resistant pathogens. Here, the authors provide an overview of the current research on SAMPs. The focus is SAMPs, how to design them, which features must be considered during design, and comparison with natural peptides. This review also includes a discussion about the natural AMPs, mechanisms of action and applications as new drugs or even as adjuvants molecules to enhance commercial drugs activity. The advances in chemical synthesis have reduced the cost to produce synthetic peptides open ways to achieve new antimicrobial agents. Therefore, synthetic peptides are new promising molecules to safeguard human and animal health.
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Senescent cells affect many physiological and pathophysiological processes. While select genetic and epigenetic elements for senescence induction have been identified, the dynamics, epigenetic ...mechanisms and regulatory networks defining senescence competence, induction and maintenance remain poorly understood, precluding the deliberate therapeutic targeting of senescence for health benefits. Here, we examined the possibility that the epigenetic state of enhancers determines senescent cell fate. We explored this by generating time-resolved transcriptomes and epigenome profiles during oncogenic RAS-induced senescence and validating central findings in different cell biology and disease models of senescence. Through integrative analysis and functional validation, we reveal links between enhancer chromatin, transcription factor recruitment and senescence competence. We demonstrate that activator protein 1 (AP-1) 'pioneers' the senescence enhancer landscape and defines the organizational principles of the transcription factor network that drives the transcriptional programme of senescent cells. Together, our findings enabled us to manipulate the senescence phenotype with potential therapeutic implications.
•Calotropis procera cysteine peptidases (CpCPs) were immobilized on glyoxyl-agarose.•Casein hydrolysis by glyoxyl-CpCPs was similar to soluble form and chymosin.•The casein micelle aggregation also ...was very similar to soluble form and chymosin.•Glyoxyl-CpCPs performed well after five reaction cycles.•Glyoxyl-CpCPs produced cheeses with characteristics similar to those using chymosin.
Calotropis procera cysteine peptidases (CpCPs) have presented several potential biotechnological applications. Here, these enzymes were immobilized on glyoxyl-agarose (glyoxyl-CpCPs) with yields of 90–95 % and the recovered activities ranged from 10 % to 15 %, according to enzyme loadings (5, 10, 20, 40, and 50 mgBSAeq/g). Spectrophotometric assays and SDS-PAGE showed that the casein hydrolysis by glyoxyl-CpCPs was similar to soluble CpCPs. In addition, glyoxyl-CpCPs exhibited similar ratio of milk-clotting activity to proteolytic activity in comparison with soluble CpCPs and chymosin. Even after being stored for six months at 8 °C, the residual proteolytic activity of glyoxyl-CpCPs remained close to 100 %. Atomic force microscopy and dynamic light scattering techniques showed that the process of casein micelle aggregation after treatment with glyoxyl-CpCPs was very similar to its soluble form and chymosin. Glyoxyl-CpCPs performed well after five reaction cycles, producing cheeses with yield, moisture, protein, and fat similar to those produced with chymosin.
•Antimicrobial peptides were generated from the hydrolysis of wheat gluten proteins.•The hydrolysates exhibited activity against the all six tested fungi.•The hydrolysates extended the shelf life of ...bread in three days.•28 peptides were sequenced and then the best four peptides were synthesized.•The peptides were able to induce damage to the fungal plasma membrane.
Antimicrobial peptides (AMPs) have been reported to be promising alternatives to chemical preservatives. Thus, this study aimed to characterise AMPs generated from the hydrolysis of wheat gluten proteins using latex peptidases of Calotropis procera, Cryptostegia grandiflora, and Carica papaya. The three hydrolysates (obtained after 16 h at 37 °C, using a 1: 25 enzyme: substrate ratio) inhibited the growth of Aspergillus niger, A. chevalieri, Trichoderma reesei, Pythium oligandrum, Penicillium sp., and Lasiodiplodia sp. by 60–90%, and delayed fungal growth on bread by 3 days when used at 0.3 g/kg. Moreover, the specific volume and expansion factor of bread were not affected by the hydrolysates. Of 28 peptides identified, four were synthesised and exhibited activity against Penicillium sp. Fluorescence and scanning electron microscopy suggested that the peptides damaged the fungal plasma membrane. Bioinformatics analysis showed that no peptide was toxic and that the antigenic ones had cleavage sites for trypsin or pepsin.
This work addresses the role of different modifiers on the overall photocurrent response, which allowed a dual material insertion, increasing the charge separation without compromise the surface ...catalysis. Sn‐addition onto nanoceramic hematite photoelectrodes clearly increased flat band potential, promoting a good charge separation, and shifting the onset to a higher potential, attributed to the surface‐trapping state created by this modification. Notoriously, Sn‐hematite photoelectrodes loaded with NiFeOx exhibited the highest photocurrent density, suggesting a partially recovered surface‐trapping states created during the electrode designing. The well‐known cocatalyst acted in the overall photoelectrocatalytic response with no significant effect on the turn‐on voltage, in other words, with minor effect related to catalytic efficiency. The dual modification contributes to understand the role of different modifiers allowing to satisfactorily improve charge separation while maintaining the conductivity attributed to IV‐group ions.
Decoupling complex parameters on hematite‐based photoanodes turned a challenge on using this material for water splitting reactions. In this recent work, it has been shown that dual elemental insertion (Sn and FeNiOx) seems promisor to maintain the electronic conductivity on bulk structure, while partially mitigate the charge transfer recombination on the solid‐liquid interface, increasing the efficiency.
Ferreira-Júnior, JB, Benine, RPC, Chaves, SFN, Borba, DA, Martins-Costa, HC, Freitas, EDS, Bemben, MG, Vieira, CA, and Bottaro, M. Effects of static and dynamic stretching performed before resistance ...training on muscle adaptations in untrained men. J Strength Cond Res 35(11): 3050-3055, 2021-This study evaluated the effects of dynamic and static stretching (SS) performed before resistance training on biceps femoris hypertrophy and knee flexor strength gains in untrained young men. Forty-five untrained young men (age, 21.2 ± 0.5 years; mass, 72.2 ± 5.6 kg; height, 178 ± 1 cm) were randomly assigned to 1 of the 3 groups: (a) 80 seconds of SS (n = 14); (b) 80 seconds of dynamic stretching (DS, n = 13); or (c) control group (CON, n = 18) in which subjects performed no stretching before exercise. Both SS and DS were performed before resistance exercise. Resistance training consisted of 4 sets of 8-12 repetition maximum of seated leg curl exercise 2 days per week for 8 weeks, with a period of at least 48 hours between sessions. Unilateral biceps femoris muscle thickness (MT) and maximal isometric strength (MIS) of the knee flexors were measured 1 week before training and 1 week after the last training session. There were significant increases in MIS (SS = 13.9 ± 10.3 kgf; DS = 10.2 ± 13.1 kgf; CON = 12.7 ± 7.6 kgf; p < 0.05) and MT (SS = 6.0 ± 3.5 mm; DS = 6.7 ± 4.1 mm; CON = 5.7 ± 3.0 mm; p < 0.05) with no significant differences across groups (p > 0.05). Additionally, all groups demonstrated moderate effect sizes for MIS (1.27-1.4), and DS was the only group that had a large effect size for MT increases (DS = 2.18; SS = 1.35; CON = 0.92). In conclusion, 80 seconds of SS and DS did not induce any additional muscular adaptations to resistance training in untrained young men.
The emergence of antibiotic-resistant microbes has stimulated research worldwide seeking new biologically active molecules. In this respect, synthetic antimicrobial peptides (SAMPs) have been ...suggested to overcome this problem. Although there are some online servers that provide putative SAMPs from protein sequences, the choice of the best peptide sequences for further analysis is still difficult. Therefore, the goal of this paper is not to launch a new tool but to provide a friendly workflow to characterize and predict potential SAMPs by employing existing tools. Using this proposed workflow, two peptides (PepGAT and PepKAA) were obtained and extensively characterized. These peptides damaged microbial membranes and cell walls, and induced overproduction of reactive oxygen species (ROS). Both peptides were found to assume random coil secondary structure in aqueous solution, organic solvent, and upon binding to negatively charged lipid systems. Peptides were also able to degrade formed biofilms but not to prevent biofilm formation. PepGAT was not resistant to proteolysis, whereas PepKAA was resistant to pepsin but not to pancreatin. Furthermore, both presented no hemolytic activity against red blood cells, even at a 10-fold higher concentration than the antimicrobial concentration. The pipeline proposed here is an easy way to design new SAMPs for application as alternatives to develop new drugs against human pathogenic microorganisms.
•Here is provided a workflow to facilitate the design of synthetic peptides.•Employing the workflow was possible to design two antimicrobial peptides.•PepGAT and PepKAA are potent antimicrobial peptides.•Both peptides have activity against human pathogenic bacteria and fungi.
The herbivores Danaus plexippus (Lepidoptera), Oncopeltus fasciatus, and Aphis nerii (Hemiptera) are special insects that feed on Calotropis procera (Apocynaceae) (Sodom Apple). At least 35 ...chemically distinct cardenolides have been reported in C. procera.
We aimed to evaluate the interaction between cardenolides and Na
/K
ATPases from herbivores.
The Na
/K
ATPases from these insects were modeled, and docking studies were performed involving cardenolides from C. procera.
The replacement of serine in sensitive Na
/K
ATPase by histidine, phenylalanine, and tyrosine in the structures examined suggested spatial impairment caused by interaction, probably making the herbivorous insects resistant against the cardenolides of C. procera. In addition, the ability of the insects to avoid cardenolide toxicity was not correlated with cardenolide polarity. Therefore, the plant fights predation through molecular diversity, and the insects, regardless of their taxonomy, face this molecular diversity through amino acid replacements at key positions of the enzyme targeted by the cardenolides.
The results show the arsenal of chemically distinct cardenolides synthesized by the C. procera.
Background
Dermatophytes belonging to the Trichophyton genus are important human pathogens, but they have developed resistance to griseofulvin, the most common antifungal drug used to treat ...dermatophytosis.
Objective
This study was aimed to evaluate the antidermatophytic activity of synthetic peptides, as well as mechanisms of action and synergistic effect with griseofulvin.
Methods
Scanning electron microscopy (SEM), atomic force microscopy (AFM) and fluorescence microscopy (FM) were employed to understand the activity and the mechanism of action of peptides.
Results
Here we report that synthetic peptides at 50 μg/mL, a concentration 20‐fold lower than griseofulvin, reduced the microconidia viability of T. mentagrophytes and T. rubrum by 100%, whereas griseofulvin decreased their viability by only 50% and 0%, respectively. The action mechanism of peptides involved cell wall damage, membrane pore formation and loss of cytoplasmic content. Peptides also induced overproduction of reactive oxygen species (ROS) and enhanced the activity of griseofulvin 10‐fold against both fungi, suggesting synergistic effects, and eliminated the toxicity of this drug to human erythrocytes. Docking analysis revealed ionic and hydrophobic interactions between peptides and griseofulvin, which may explain the decline of griseofulvin toxicity when mixed with peptides.
Conclusion
Therefore, our results strongly suggest six peptides with high potential to be employed alone as new drugs or as adjuvants to enhance the activity and decrease the toxicity of griseofulvin.
Calotropis procera cysteine peptidases (CpCPs) have been used for reducing cow’s milk allergenicity or as rennet in cheesemaking. Due to their residual presence in food products, the present study ...evaluated, for the first time, different protocols for their immobilization on different supports. Although the yield of immobilization on sulfopropyl-agarose (99%, at pH 7.0) was better than when using DEAE- and MANAE-agarose (40% and 15%, respectively), the derivatives had low recovered activity (4%). On the other hand, MANAE-agarose at pH 10.0 (200 mM buffer) exhibited the highest recovered enzymatic activity (~23%). Regarding the covalent immobilization, the peptidases immobilized on glyoxyl-agarose (glyoxyl-CpCPs) showed broader pH stability (pH 3.0–10.0), 60-fold more stable at 60 °C, and retained 70% of their initial activities after five reaction cycles, even though the immobilization has induced some structural changes analyzed by Fourier-Transform Infrared (FTIR) spectroscopy as well as altered some of enzyme kinetic parameters (Vmax, Km, Kcat, and catalytic efficiency). In addition, this biocatalyst (glyoxyl-CpCPs) hydrolyzed the major cow’s milk allergens (whey proteins) to a greater extent (65%) than the soluble enzymes (8%) and a commercial hypoallergenic formula (50%).
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•Calotropis procera cysteine peptidases (CpCPs) were immobilized on different supports.•Glyoxyl-agarose was the best among all ionic and covalent supports.•The immobilization induced structural changes and altered the enzyme kinetics.•But the biocatalyst had better pH stability and was 60-fold more stable at 60 °C.•It reduced the milk protein antigenicity to a level lower than of a commercial formula.
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