Extracellular vesicles derived from bovine adipose-derived mesenchymal stromal cells enhance in vitro embryo production from lesioned ovaries.

BACKGROUND AND AIMS: Ovum pick-up (OPU) is an intrinsic step of in vitro fertilization procedures. Nevertheless, it can cause ovarian lesions and compromise female fertility in bovines. Recently, we have shown that intraovarian injection of adipose-derived mesenchymal stromal cells (AD-MSCs) effectively preserves ovarian function in bovines. Given that MSC-derived extracellular vesicles (MSC-EVs) have been shown to recapitulate several therapeutic effects attributed to AD-MSCs and that they present logistic and regulatory advantages compared to AD-MSCs, we tested whether MSC-EVs would also be useful to treat OPU-induced lesions. METHODS: MSC-EVs were isolated from the secretome of bovine AD-MSCs, using ultrafiltration (UF) and ultracentrifugation methods. The MSC-EVs were characterized according to concentration and mean particle size, morphology, protein concentration and EV markers, miRNA, mRNA, long noncoding RNA profile, total RNA yield and potential for induction of the proliferation and migration of bovine ovarian stromal cells. We then investigated whether intraovarian injection of MSC-EVs obtained by UF would reduce the negative effects of acute OPU-induced ovarian lesions in bovines. To do so, 20 animals were divided into 4 experimental groups (n = 5), submitted to 4 OPU cycles and different experimental treatments including vehicle only (G1), MSC-EVs produced by 7.5 × 106 AD-MSCs (G2), MSC-EVs produced by 2.5 × 106 AD-MSCs (G3) or 3 doses of MSC-EVs produced by 2.5 × 106 AD-MSCs, injected after OPU sessions 1, 2 and 3 (G4). RESULTS: Characterization of the MSC-EVs revealed that the size of the particles was similar in the different isolation methods; however, the UF method generated a greater MSC-EV yield. MSC-EVs processed by both methods demonstrated a similar ability to promote cell migration and proliferation in ovarian stromal cells. Considering the higher yield and lower complexity of the UF method, UF-MSC-EVs were used in the in vivo experiment. We evaluated three therapeutic regimens for cows subjected to OPU, noting that the group treated with three MSC-EV injections (G4) maintained oocyte production and increased in vitro embryo production, compared to G1, which presented compromised embryo production following the OPU-induced lesions. CONCLUSIONS: MSC-EVs have beneficial effects both on the migration and proliferation of ovarian stromal cells and on the fertility of bovines with follicular puncture injury in vivo.

Screening of the Skin-Regenerative Potential of Antimicrobial Peptides: Clavanin A, Clavanin-MO, and Mastoparan-MO.

Skin wound healing is coordinated by a delicate balance between proinflammatory and anti-inflammatory responses, which can be affected by opportunistic pathogens and metabolic or vascular diseases. Several antimicrobial peptides (AMPs) possess immunomodulatory properties, suggesting their potential to support skin wound healing. Here, we evaluated the proregenerative activity of three recently described AMPs (Clavanin A, Clavanin-MO, and Mastoparan-MO). Human primary dermal fibroblasts (hFibs) were used to determine peptide toxicity and their capacity to induce cell proliferation and migration. Furthermore, mRNA analysis was used to investigate the modulation of genes associated with skin regeneration. Subsequently, the regenerative potential of the peptides was further confirmed using an ex vivo organotypic model of human skin (hOSEC)-based lesion. Our results indicate that the three molecules evaluated in this study have regenerative potential at nontoxic doses (i.e., 200 µM for Clavanin-A and Clavanin-MO, and 6.25 µM for Mastoparan-MO). At these concentrations, all peptides promoted the proliferation and migration of hFibs during in vitro assays. Such processes were accompanied by gene expression signatures related to skin regenerative processes, including significantly higher KI67, HAS2 and CXCR4 mRNA levels induced by Clavanin A and Mastoparan-MO. Such findings translated into significantly accelerated wound healing promoted by both Clavanin A and Mastoparan-MO in hOSEC-based lesions. Overall, the data demonstrate the proregenerative properties of these peptides using human experimental skin models, with Mastoparan-MO and Clavanin A showing much greater potential for inducing wound healing compared to Clavanin-MO.

Investigating the Promising P28 Peptide-Loaded Chitosan/Ceramic Bone Scaffolds for Bone Regeneration.

Bone has the ability to heal itself; however, bone defects fail to heal once the damage exceeds a critical size. Bone regeneration remains a significant clinical challenge, with autograft considered the ideal bone graft material due to its sufficient porosity, osteogenic cells, and biological growth factors. However, limitations to bone grafting, such as limited bone stock and high resorption rates, have led to a great deal of research into developing bone graft substitutes. The P28 peptide is a small molecule bioactive biomimetic alternative to mimic the bone morphogenetic protein 2 (BMP-2). In this study, we investigated the potential of P28-loaded hybrid scaffolds to mimic the natural bone structure for enhancing the bone regeneration process. We hypothesized that the peptide-loaded scaffolds and nude scaffolds both have the potential to promote bone healing, and the bone healing process is accelerated by the release of the peptide. To verify our hypothesis, C2C12 cells were evaluated for the presence of calcium deposits by histological stain at 7 and 14 days in cultures with hybrid scaffolds. Total RNA was isolated from C2C12 cells cultured with hybrid scaffolds for 7 and 14 days to assess osteoblast differentiation. The project findings demonstrated that the hybrid scaffold could enhance osteoblast differentiation and significantly improve the therapeutic effects of the scaffold in bone regeneration.

A systematic review on the cost-effectiveness assessment of tisagenlecleucel for refractory or relapsing B-cell acute lymphoblastic leukemia (R/R B-ALL) treatment in children and young adults.

BACKGROUND AIMS: The advanced therapy product tisagenlecleucel is a CD19-directed genetically modified autologous T-cell immunotherapy that has brought hope for children and young adults with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We sought to evaluate the cost-effectiveness of tisagenlecleucel compared with conventional salvage therapies in pediatric and young adult patients with R/R B-ALL. METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses parameters as registered in International Prospective Register of Systematic Reviews (CRD42021266998). Literature was searched using the MEDLINE databases via PubMed, EMBASE, Lilacs, the Cochrane Central Register of Controlled Trials and Web of Science in January 2022. Titles were screened independently by two reviewers. Articles deemed to meet the inclusion criteria were screened independently on abstract, and full texts were reviewed. RESULTS: In total, 5627 publications were identified, from which six eligible studies were selected. The conventional therapies identified were blinatumomab (Blina), clofarabine monotherapy (Clo-M), clofarabine combined with cyclophosphamide and etoposide (Clo-C) and the combination of fludarabine, cytarabine and idarubicin (FLA-IDA). The discounted incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained for tisagenlecleucel compared with Clo-C and Blina averages was $38 837 and $25 569, respectively. In relation to the cost of the drug, the average of tisagenlecleucel was approximately 4.3 times, 10.8 times or 4.7 times greater than the Clo-M, Clo-C and Blina, respectively. CONCLUSIONS: This systematic review highlighted that tisagenlecleucel is a much more expensive therapy than conventional alternatives. However, tisagenlecleucel performed well on the ICER, not exceeding $100 000/QALY. It was also found that the advanced therapy product was more effective than the conventional small molecule and biological drugs, in terms of life years and QALY gained.

Triangular Silver Nanoplates as a Bioanalytical Tool: Potential COVID-19 Detection.

Nanotechnology offers new possibilities in molecular diagnostics, with nanoparticles gaining attention as biosensor upgrades. This study evaluates gold-coated silver nanoplates coated with PEG for enhanced protection, aiming to detect Spike protein with higher sensitivity, and emphasizes the importance of considering complex environments and appropriate controls for specific binding and accurate analysis. The sensitivity of antibody-coated PEGAuTSNPs as tools for immunoassays is demonstrated through fibronectin (Fn)- anti-fibronectin binding within an isolated extracellular matrix as a complex and native environment of Fn. Moreover, the optimal functionalization volume of Spike protein was determined (4 µg/mL of PEGAuTSNP). Anti-Spike was added to confirm binding, while the TJP1 protein was used as a negative control. The same experiment was used in the presence of horse serum to simulate a complex environment. According to Localized Surface Plasmon Resonance analysis and Dynamic Light Scattering size measurements, anti-Spike exhibited a stronger affinity for the nanoplates, causing TJP1 to be replaced by the antibody on the nanoplates' surface. Future research will involve exploring alternative complex environments, filtering larger molecules, and the optimization of immunoassay performance.

Phenotypic and mutational spectrum of ROR2-related Robinow syndrome.

Robinow syndrome is characterized by a triad of craniofacial dysmorphisms, disproportionate-limb short stature, and genital hypoplasia. A significant degree of phenotypic variability seems to correlate with different genes/loci. Disturbances of the noncanonical WNT-pathway have been identified as the main cause of the syndrome. Biallelic variants in ROR2 cause an autosomal recessive form of the syndrome with distinctive skeletal findings. Twenty-two patients with a clinical diagnosis of autosomal recessive Robinow syndrome were screened for variants in ROR2 using multiple molecular approaches. We identified 25 putatively pathogenic ROR2 variants, 16 novel, including single nucleotide variants and exonic deletions. Detailed phenotypic analyses revealed that all subjects presented with a prominent forehead, hypertelorism, short nose, abnormality of the nasal tip, brachydactyly, mesomelic limb shortening, short stature, and genital hypoplasia in male patients. A total of 19 clinical features were present in more than 75% of the subjects, thus pointing to an overall uniformity of the phenotype. Disease-causing variants in ROR2, contribute to a clinically recognizable autosomal recessive trait phenotype with multiple skeletal defects. A comprehensive quantitative clinical evaluation of this cohort delineated the phenotypic spectrum of ROR2-related Robinow syndrome. The identification of exonic deletion variant alleles further supports the contention of a loss-of-function mechanism in the etiology of the syndrome.

Pathogenic variants in the TRIP11 gene cause a skeletal dysplasia spectrum from odontochondrodysplasia to achondrogenesis 1A.

The thyroid hormone receptor interactor 11 (TRIP11) gene encodes the Golgi microtubule-associated protein 210 (GMAP-210), a protein essential for the operation of the Golgi apparatus. It is known that null mutations in TRIP11 disrupt Golgi function and cause a lethal skeletal dysplasia known as achondrogenesis type 1A (ACG1A), however recently, hypomorphic mutations in that gene have been linked to odontochondrodysplasia (ODCD), a nonlethal skeletal dysplasia characterized by skeletal changes in the spine and in the metaphyseal regions, associated with dentinogenesis imperfecta. Here we present two patients reflecting the phenotypic spectrum related to different TRIP11 variants. The first is a female child with ODCD, for whom a homozygous in-frame splicing mutation in intron 9 of TRIP11 was identified. The mutation appears to lead to the expression of an alternative TRIP11 transcript, that may explain the less severe radiological alterations in ODCD. The second is a fetus with classical form of ACG1A, associated with typical molecular findings (frameshift) in exon 11 of TRIP11, both novel mutations. The two patients reported here represent the TRIP11 spectrum of skeletal dysplasia ranging from mild to lethal phenotypes, thereby enabling one to suggest a genotype-phenotype correlation in these diseases.

Dento-osseous anomalies in patients with familial adenomatous polyposis: A follow-up study.

OBJECTIVE: The aim of this longitudinal study was to characterize the dento-osseous phenotype of eleven familial adenomatous polyposis (FAP) patients and twenty-two family members from four Brazilian families who were followed over nine years and to investigate adenomatous polyposis coli (APC) gene variants using a targeted next-generation sequencing approach. MATERIALS AND METHODS: Medical and dental history, oral examination, and panoramic radiography were performed to diagnose and follow up the dento-osseous anomalies. The anomalies were evaluated following the validated diagnostic tool dental panoramic radiographic score (DPRS), a system developed for high-risk FAP patients. Patients diagnosed with dento-osseous anomalies underwent cone-beam computed tomography. For genetic analysis, DNA was isolated from patients' saliva. RESULTS: Dento-osseous anomalies were identified in ten of the eleven FAP patients by panoramic radiograph evaluation. DPRS ≥ 7 (significant changes) was found in 81.8% (9/11) of FAP patients. The follow-up showed an increase in osseous jaw lesions in two young patients during adolescence. Dento-osseous anomalies were not found in non-FAP patients. A novel heterozygous nonsense pathogenic variant in APC exon 5 (c.481C > T; p.Gln161*) was identified in family 2, and a heterozygous splice-site pathogenic variant was identified in family 1 (c.532-1G > A). CONCLUSION: Our study expands the mutation spectrum of the APC gene and provides evidence that dento-osseous screening by imaging is a putative tool for early diagnosis of FAP. Also, the detection of dento-osseous anomalies in young patients with increasing osseous lesions during adolescence highlights the need for dental follow-up of high-risk FAP children. CLINICAL RELEVANCE: Dental radiographs are important for the screening and the follow-up of dento-osseous anomalies associated with FAP. It can also contribute to the early diagnosis of the disease.

Correction: Altered mRNA Splicing, Chondrocyte Gene Expression and Abnormal Skeletal Development due to SF3B4 Mutations in Rodriguez Acrofacial Dysostosis.

[This corrects the article DOI: 10.1371/journal.pgen.1006307.].

Altered mRNA Splicing, Chondrocyte Gene Expression and Abnormal Skeletal Development due to SF3B4 Mutations in Rodriguez Acrofacial Dysostosis.

The acrofacial dysostoses (AFD) are a genetically heterogeneous group of inherited disorders with craniofacial and limb abnormalities. Rodriguez syndrome is a severe, usually perinatal lethal AFD, characterized by severe retrognathia, oligodactyly and lower limb abnormalities. Rodriguez syndrome has been proposed to be a severe form of Nager syndrome, a non-lethal AFD that results from mutations in SF3B4, a component of the U2 small nuclear ribonucleoprotein particle (U2 snRNP). Furthermore, a case with a phenotype intermediate between Rodriguez and Nager syndromes has been shown to have an SF3B4 mutation. We identified heterozygosity for SF3B4 mutations in Rodriguez syndrome, confirming that the phenotype is a dominant disorder that is allelic with Nager syndrome. The mutations led to reduced SF3B4 synthesis and defects in mRNA splicing, primarily exon skipping. The mutations also led to reduced expression in growth plate chondrocytes of target genes, including the DLX5, DLX6, SOX9, and SOX6 transcription factor genes, which are known to be important for skeletal development. These data provide mechanistic insight toward understanding how SF3B4 mutations lead to the skeletal abnormalities observed in the acrofacial dysostoses.

Computational Investigation of Growth Hormone Receptor Trp169Arg Heterozygous Mutation in a Child With Short Stature.

Mutations in the growth hormone receptor (GHR) gene can cause disruption of the growth hormone signaling pathway, resulting in growth deficiency due to growth hormone (GH) resistance. Both recessive and apparently dominant mutations have been described in the literature. In order to shed some light on the molecular mechanism of partial growth hormone resistance caused by heterozygous mutations, we performed an in-depth in silico analysis of a mutation found in a girl with a previous diagnosis of idiopathic short stature. An array of algorithms was used to predict pathogenicity and potential impact on the protein, and molecular modeling, docking and dynamics were used to determine structural consequences. The results suggest that both of the possible single mutation-containing heteromeric GH-GHR complexes, as well as the double GHR mutant complex result in perturbation of complex structures, with altered ability of the GHR dimers to interact with the GH peptide. J. Cell. Biochem. 118: 4762-4771, 2017. © 2017 Wiley Periodicals, Inc.

Short stature, unusual face, delta phalanx, and abnormal vertebrae and ribs in a girl born to half-siblings.

Delta phalanx is a rare abnormality typically associated with additional features. We describe a patient with a phenotype resembling Catel-Manzke syndrome, but with delta phalanx and abnormal vertebrae and ribs. The patient was the only child of half siblings born with a marked prenatal growth deficiency. At 10 years of age, she had a short stature, long face, long and tubular nose with small alae nasi, high palate, short and broad thorax, and short index fingers with radial deviation. There were hyperpigmentations following Blaschko's lines. Radiology showed a proximal delta phalanx in the index finger of hands, abnormal vertebrae, and fused and small ribs. GTG-Banding karyotype and microarray analysis yielded normal results. Exome sequencing identified 25 genes that harbored homozygous variants, but none of these is assumed to be a good candidate to explain (part of) the phenotype. The here described patient may have a new condition, possibly following an autosomal recessive pattern of inheritance, although due to the high degree of consanguinity a compound etiology of the phenotype by variants in various genes may be present as well.

Partial trisomy 17q and partial monosomy 20q in a boy with craniosynostosis.

Craniosynostosis is defined as a premature fusion of at least one cranial suture, which can be accompanied by other findings. Of syndromic cases, 14-22% have been associated with chromosomal rearrangements. This report describes a Brazilian boy with syndromic craniosynostosis who also presented with intellectual disability, microcephaly, frontal bossing, bitemporal narrowing, short neck, syndactyly, and cardiac defects. Chromosome banding showed an apparently normal male karyotype. Subsequent chromosomal microarray analysis (CMA) using the Affymetrix CytoScan 750 K Array showed a duplication of 2.1 Mb on chromosome 17q and a deletion of 1.4 Mb on chromosome 20q. The data suggested an unbalanced translocation, which was confirmed by fluorescence in-situ hybridization analysis (FISH). While there are several reports in the literature of chromosome 17q duplication syndrome accompanied by partial monosomies of other chromosomes, this is the first case featuring partial monosomy of 20q. The patient́s phenotype is generally consistent with 17q duplication syndrome, however craniosynostosis has rarely been associated with this chromosomal anomaly.

Comprehensive analysis and assessment of exposure to enteric viruses and bacteria in shellfish.

Shellfish species, including oysters, clams, and mussels, are extensively cultured in coastal waters. Its location is determined by factors such as nutrient availability, water temperature, tidal cycle, and the presence of contaminants such as Escherichia coli and enteric viruses. With the expansion and intensification of human activities at vicinities, the presence of anthropogenic contaminants has increased, threatening shellfish farms and consumer safety give the prevalent consumption of raw shellfish. This literature review aims to provide a comprehensive analysis of the dietary exposure and assess the risk associated with enteric viruses and bacteria detected in shellfish. The predominant bacteria and viruses detected in shellfish are reported, and the potential interrelation is discussed. The main characteristics of each contaminant and shellfish were reviewed for a more comprehensive understanding. To facilitate a direct estimation of exposure, the estimated daily intake (EDI) of bacteria was calculated based on the average levels of E. coli in shellfish, as reported in the literature. The mean daily ingestion of seafood in each of the five continents was considered. Asia exhibited the highest intake of contaminants, with an average of ±5.6 E. coli units/day.kg body weight in cockles. Simulations were conducted using recommended shellfish consumption levels established by state agencies, revealing significantly lower (p < 0.01) EDI for all continents compared to estimations based on recommended levels. This indicates a higher risk associated with healthy shellfish ingestion, potentially leading to increased intoxication incidents with a change in dietary habits. To promote a healthier lifestyle through increased shellfish consumptions, it is imperative to reduce the exposure of shellfish species to bacteria and enteric viruses. The conventional use of E. coli as the sole indicator for consumption safety and water quality in shellfish farms has been deemed insufficient. Instances where shellfish met E. coli limits established by state agencies were often found to be contaminated with human enteric viruses. Therefore, a holistic approach considering the entire production chain is necessary to support the shellfish industry and ensure food safety.

Senotherapeutic Peptide 14 Suppresses Th1 and M1 Human T Cell and Monocyte Subsets In Vitro.

Inflammation contributes to the onset and exacerbation of numerous age-related diseases, often manifesting as a chronic condition during aging. Given that cellular senescence fosters local and systemic inflammation, senotherapeutic interventions could potentially aid in managing or even reducing inflammation. Here, we investigated the immunomodulatory effects of the senotherapeutic Peptide 14 (Pep 14) in human peripheral blood mononuclear cells (PBMCs), monocytes, and macrophages. We found that, despite failing to significantly influence T cell activation and proliferation, the peptide promoted a Th2/Treg gene expression and cytokine signature in PBMCs, characterized by increased expression of the transcription factors GATA3 and FOXP3, as well as the cytokines IL-4 and IL-10. These observations were partially confirmed through ELISA, in which we observed increased IL-10 release by resting and PHA-stimulated PBMCs. In monocytes from the U-937 cell line, Pep 14 induced apoptosis in lipopolysaccharide (LPS)-stimulated cells and upregulated IL-10 expression. Furthermore, Pep 14 prevented LPS-induced activation and promoted an M2-like polarization in U-937-derived macrophages, evidenced by decreased expression of M1 markers and increased expression of M2 markers. We also showed that the conditioned media from Pep 14-treated macrophages enhanced fibroblast migration, indicative of a functional M2 phenotype. Taken together, our findings suggest that Pep 14 modulates immune cell function towards an anti-inflammatory and regenerative phenotype, highlighting its potential as a therapeutic intervention to alleviate immunosenescence-associated dysregulation.

Pulsed ultraviolet (PUV) disinfection of artificially contaminated seawater seeded with high levels of pathogen disease indicators as an alternative for the shellfish industry depuration systems.

The increase in pathogen levels in seawater threatens the safety of entire aquatic ecosystems. Foodborne pathogens can potentially accumulate in shellfish, especially in filter feeders such as bivalves, requiring an efficient depuration process before consumption. Alternative approaches to promote a cost-efficient purge at depuration plants are urgently needed. A small prototype pulsed ultraviolet (PUV) light recirculation system was designed, and its depuration potential was tested in a seawater matrix artificially contaminated with high levels of microbial pathogens Escherichia coli, Staphylococcus aureus, Salmonella typhimurium, Bacillus cereus and Candida albicans. The analysis of treatment parameters including voltage, number of pulses and duration of treatment was performed to ensure the highest reduction in contaminant levels. Optimal PUV disinfection was attained at 60 pulses/min at 1 kV for 10 min (a UV output of 12.9 J/cm2). All reductions were statistically significant, and the greatest was observed for S. aureus (5.63 log10), followed by C. albicans (5.15 log10), S. typhimurium (5 log10), B. cereus (4.59 log10) and E. coli (4.55 log10). PUV treatment disrupted the pathogen DNA with the result that S. aureus, C. albicans and S. typhimurium were not detectable by PCR. Regulations were reviewed to address the applicability of PUV treatment as a promising alternative to assist in the reduction of microbial pathogens at depuration plants due to its high efficiency, short treatment period, high UV dose and recirculation system as currently employed in shellfish depuration plants.

Extracellular vesicles in the context of chagas disease - A systematic review.

Extracellular vesicle (EVs) traffic is considered an important cellular communication process between cells that can be part of a single organism or belong to different living beings. The relevance of EV-mediated cellular communication is increasingly studied and appreciated, especially in relation to pathological conditions, including parasitic disorders, in which the EV release and uptake processes have been documented. In the context of Chagas Disease (CD), EVs have been explored, however, current data have not been systematically revised in order to provide an overview of the published literature and the main results obtained thus far. In this systematic review, 25 studies involving the investigation of EVs in CD were identified. The studies involved Trypanosoma cruzi -derived EVs (Tc-EVs), as well as EVs derived from T. cruzi-infected mammalian cells, mainly isolated by ultracentrifugation and poorly characterized. The objectives of the identified studies included the characterization of the protein and RNA cargo of Tc-EVs, as well as investigation of EVs in parasitic infections and immune-related processes. Overall, our systematic review reveals that EVs play critical roles in several mechanisms related to the interaction between T. cruzi and mammalian hosts, their contribution to immune system evasion by the parasite, and to chronic inflammation in the host. Future studies will benefit from the consolidation of isolation and characterization methods, as well as the elucidation of the role of EVs in CD.

Polysaccharides-Naturally Occurring Immune Modulators.

The prevention of disease and infection requires immune systems that operate effectively. This is accomplished by the elimination of infections and abnormal cells. Immune or biological therapy treats disease by either stimulating or inhibiting the immune system, dependent upon the circumstances. In plants, animals, and microbes, polysaccharides are abundant biomacromolecules. Due to the intricacy of their structure, polysaccharides may interact with and impact the immune response; hence, they play a crucial role in the treatment of several human illnesses. There is an urgent need for the identification of natural biomolecules that may prevent infection and treat chronic disease. This article addresses some of the naturally occurring polysaccharides of known therapeutic potential that have already been identified. This article also discusses extraction methods and immunological modulatory capabilities.

The Combination of Synoeca-MP Antimicrobial Peptide with IDR-1018 Stimulates Proliferation, Migration, and the Expression of Pro-Regenerative Genes in Both Human Skin Cell Cultures and 3D Skin Equivalents.

In skin lesions, the development of microbial infection affects the healing process, increasing morbidity and mortality rates in patients with severe burns, diabetic foot, and other types of skin injuries. Synoeca-MP is an antimicrobial peptide (AMP) that exhibits activity against several bacteria of clinical importance, but its cytotoxicity can represent a problem for its positioning as an effective antimicrobial compound. In contrast, the immunomodulatory peptide IDR-1018 presents low toxicity and a wide regenerative potential due to its ability to reduce apoptotic mRNA expression and promote skin cell proliferation. In the present study, we used human skin cells and a 3D skin equivalent models to analyze the potential of the IDR-1018 peptide to attenuate the cytotoxicity of synoeca-MP, as well as the influence of synoeca-MP/IDR-1018 combination on cell proliferation, regenerative processes, and wound repair. We found that the addition of IDR-1018 significantly improved the biological properties of synoeca-MP on skin cells without modifying its antibacterial activity against S. aureus. Likewise, in both melanocytes and keratinocytes, the treatment with synoeca-MP/IDR-1018 combination induces cell proliferation and migration, while in a 3D human skin equivalent model, it can accelerate wound reepithelization. Furthermore, treatment with this peptide combination generates an up-regulation in the expression of pro-regenerative genes in both monolayer cell cultures and in 3D skin equivalents. This data suggests that the synoeca-MP/IDR-1018 combination possesses a good profile of antimicrobial and pro-regenerative activity, opening the door to the development of new strategies for the treatment of skin lesions.

Plant storage proteins with antimicrobial activity: novel insights into plant defense mechanisms.

Storage proteins perform essential roles in plant survival, acting as molecular reserves important for plant growth and maintenance, as well as being involved in defense mechanisms by virtue of their properties as insecticidal and antimicrobial proteins. These proteins accumulate in storage vacuoles inside plant cells, and, in response to determined signals, they may be used by the different plant tissues in response to pathogen attack. To shed some light on these remarkable proteins with dual functions, storage proteins found in germinative tissues, such as seeds and kernels, and in vegetative tissues, such as tubercles and leaves, are extensively discussed here, along with the related mechanisms of protein expression. Among these proteins, we focus on 2S albumins, Kunitz proteinase inhibitors, plant lectins, glycine-rich proteins, vicilins, patatins, tarins, and ocatins. Finally, the potential use of these molecules in development of drugs to combat human and plant pathogens, contributing to the development of new biotechnology-based medications and products for agribusiness, is also presented.