Unwrapping the structural and functional features of antimicrobial peptides from wasp venoms.

The study of wasp venoms has captured attention due to the presence of a wide variety of active compounds, revealing a diverse array of biological effects. Among these compounds, certain antimicrobial peptides (AMPs) such as mastoparans and chemotactic peptides have emerged as significant players, characterized by their unique amphipathic short linear alpha-helical structure. These peptides exhibit not only antibiotic properties but also a range of other biological activities, which are related to their ability to interact with biological membranes to varying degrees. This review article aims to provide updated insights into the structure/function relationships of AMPs derived from wasp venoms, linking this knowledge to the potential development of innovative treatments against infections.

Excess of glucocorticoids during late gestation impairs the recovery of offspring's ß-cell function after a postnatal injury.

Since prenatal glucocorticoids (GC) excess increases the risk of metabolic dysfunctions in the offspring and its effect on ß-cell recovery capacity remains unknown we investigated these aspects in offspring from mice treated with dexamethasone (DEX) in the late pregnancy. Half of the pups were treated with streptozotocin (STZ) on the sixth postnatal day (PN). Functional and molecular analyses were performed in male offspring on PN25 and PN225. Prenatal DEX treatment resulted in low birth weight. At PN25, both the STZ-treated offspring developed hyperglycemia and had lower ß-cell mass, in parallel with higher α-cell mass and glucose intolerance, with no impact of prenatal DEX on such parameters. At PN225, the ß-cell mass was partially recovered in the STZ-treated mice, but they remained glucose-intolerant, irrespective of being insulin sensitive. Prenatal exposition to DEX predisposed adult offspring to sustained hyperglycemia and perturbed islet function (lower insulin and higher glucagon response to glucose) in parallel with exacerbated glucose intolerance. ß-cell-specific knockdown of the Hnf4α in mice from the DS group resulted in exacerbated glucose intolerance. We conclude that high GC exposure during the prenatal period exacerbates the metabolic dysfunctions in adult life of mice exposed to STZ early in life, resulting in a lesser ability to recover the islets' function over time. This study alerts to the importance of proper management of exogenous GCs during pregnancy and a healthy postnatal lifestyle since the combination of adverse factors during the prenatal and postnatal period accentuates the predisposition to metabolic disorders in adult life.

Microbial bioconversion of feathers into antioxidant peptides and pigments and their liposome encapsulation.

OBJECTIVES: The co-encapsulation of bioactive peptides obtained from degradation of chicken feathers and flexirubin-type pigment produced by Chryseobacterium sp. kr6 into phosphatidylcholine liposomes was investigated. RESULTS: Control empty liposomes showed mean diameter of 168.5 nm, varying to 185.4, 102.0 and 98.5 nm after the encapsulation of peptides, pigment and their co-encapsulation, respectively. Control liposomes presented zeta potential of - 20.9 mV, while the formulations containing the bioactive compounds showed values of - 30 mV or higher in magnitude. Infrared analysis revealed typical spectra for phosphatidylcholine, suggesting that no new chemical bonds were formed after encapsulation. ABTS radical scavenging assay showed that the antioxidant activity of the compounds was maintained after encapsulation. CONCLUSIONS: Feather waste can be a valuable substrate for simultaneous production of antioxidant peptides and pigment by Chryseobacterium sp. kr6, and their encapsulation into liposomes may be a suitable alternative for delivery of these natural antioxidants.

Glucose homeostasis in two degrees of sepsis lethality induced by caecum ligation and puncture in mice.

Sepsis is associated with high mortality. Both critically ill humans and animal models of sepsis exhibit changes in their glucose homeostasis, that is, hypoglycaemia, with the progression of infection. However, the relationship between basal glycaemia, glucose tolerance and insulin sensitivity is not well understood. Thus, we aimed to evaluate this glucose homeostasis triad at the late stage of sepsis (24 h after surgery) in male Swiss mice subjected to lethal and sublethal sepsis by the caecal ligation and puncture (CLP) model. The percentage of survival 24 h after CLP procedure in the Lethal and Sublethal groups was around 66% and 100% respectively. Both Lethal and Sublethal groups became hypoglycaemic in fasting and fed states 24 h after surgery. The pronounced fed hypoglycaemia in the Lethal group was not due to worsening anorexic behaviour or hepatic inability to deliver glucose in relation to the Sublethal group. Reduction in insulin sensitivity in CLP mice occurred in a lethality-dependent manner and was not associated with glucose intolerance. Analysis of oral and intraperitoneal glucose tolerance tests, as well as the gastrointestinal motility data, indicated that CLP mice had reduced intestinal glucose absorption. Altogether, we suggest cessation of appetite and intestinal glucose malabsorption are key contributors to the hypoglycaemic state observed during experimental severe sepsis.

Assessing Antibacterial Potential of Components of Phyllomedusa distincta Skin and its Associated Dermal Microbiota.

The granular glands of anuran skin secrete an array of bioactive molecules that protect a frog against pathogens and predators. The skin also harbors a microbial community. Although there is evidence to suggest that the microbiota complement the innate immune defense systems against pathogen infection, the effect of the frog bioactive molecules on its resident microbiota has not yet been fully investigated. In the present study, the skin microbiota of Phyllomedusa distincta obtained from two different geographical areas was evaluated with molecular and culture-based approaches. The antagonistic effects exhibited by the host's microbiota and by a novel dermaseptin peptide isolated from P. distincta skin were investigated. Four isolated bacterial colonies displayed antimicrobial activity against known frog pathogens. Our results were consistent with the hypothesis that microbiota from P. distincta may interact with pathogenic microorganisms to protect a frog's health. On the other hand, the novel dermaseptin peptide exhibited an antimicrobial effect on pathogens as well as on some of the bacteria obtained from the skin microbiota. The richness of bacteria on P. distincta skin was further investigated by 16S rRNA gene clone libraries, which revealed that the family Enterobacteriaceae was prevalent, but a high variability at the species level was observed among individual frogs. Differences observed on the microbiota of frogs from contrasting habitats indicated an influence of the environment on the structure of the skin microbiota of P. distincta.

Age- and gender-related changes in glucose homeostasis in glucocorticoid-treated rats.

The disruption to glucose homeostasis upon glucocorticoid (GC) treatment in adult male rats has not been fully characterized in older rats or in females. Thus, we evaluated the age- and gender-related changes in glucose homeostasis in GC-treated rats. We injected male and female rats at 3 months and 12 months of age with either dexamethasone (1.0 mg/kg body mass, intraperitoneally) or saline, daily for 5 days. All of the GC-treated rats had decreased body mass and food intake, and adrenal hypotrophy. Increased glycemia was observed in all of the GC-treated groups and only the 3-month-old female rats were not glucose intolerant. Dexamethasone treatment resulted in hyperinsulinemia and hypertriacylglyceridemia in all of the GC-treated rats. The glucose-stimulated insulin secretion (GSIS) was higher in all of the dexamethasone-treated animals, but it was less pronounced in the older animals. The ß-cell mass was increased in the younger male rats treated with dexamethasone. We conclude that dexamethasone treatment induces glucose intolerance in both the 3- and 12-month-old male rats as well as hyperinsulinemia and augmented GSIS. Three-month-old female rats are protected from glucose intolerance caused by GC, whereas 12-month-old female rats developed the same complications that were present in 3- and 12-month-old male rats.

Disruption of glucose tolerance caused by glucocorticoid excess in rats is partially prevented, but not attenuated, by arjunolic acid.

Arjunolic acid (AA) obtained from plants of the Combretaceae family has shown anti-diabetic effects. Here, we analyzed whether the diabetogenic effects of dexamethasone (DEX) treatment on glucose homeostasis may be prevented or attenuated by the concomitant administration of AA. Adult Wistar rats were assigned to the following groups: vehicle-treated (Ctl), DEX-treated (1 mg/kg body weight intraperitoneally for 5 days) (Dex), AA-treated (30 mg/kg body weight by oral gavage twice per day) (Aa), AA treatment previous to and concomitant to DEX treatment (AaDex), and AA treatment after initiation of DEX treatment (DexAa). AA administration significantly ameliorated (AaDex) (P > 0.05), but did not attenuate (DexAa), the glucose intolerance induced by DEX treatment. AA did not prevent or attenuate the elevation in hepatic glycogen and triacylglycerol content caused by DEX treatment. All DEX-treated rats exhibited hepatic steatosis that seemed to be more pronounced when associated with AA treatment given for a prolonged period (AaDex). Markers of liver function and oxidative stress were not significantly altered among the groups. Therefore, AA administered for a prolonged period partially prevents the glucose intolerance induced by DEX treatment, but it fails to produce this beneficial effect when given after initiation of GC treatment. Since AA may promote further hepatic steatosis when co-administered with GCs, care is required when considering this phytochemical as a hypoglycemiant and/or insulin-sensitizing agent.

Parameter evaluation for developing phosphate-solubilizing Bacillus inoculants.

Bacterial inoculants have been used in agriculture to improve plant performance. However, laboratory and field requirements must be completed before a candidate can be employed as an inoculant. Therefore, this study aimed to evaluate the parameters for inoculant formulation and the potential of Bacillus subtilis (B70) and B. pumilus (B32) to improve phosphorus availability in maize (Zea mays L.) crops. In vitro experiments assessed the bacterial ability to solubilize and mineralize phosphate, their adherence to roots, and shelf life in cassava starch (CS), carboxymethyl cellulose (CMC), peat, and activated charcoal (AC) stored at 4 °C and room temperature for 6 months. A field experiment evaluated the effectiveness of strains to increase the P availability to plants growing with rock phosphate (RP) and a mixture of RP and triple superphosphate (TS) and their contribution to improving maize yield and P accumulation in grains. The B70 was outstanding in solubilizing RP and phytate mineralization and more stable in carriers and storage conditions than B32. However, root adherence was more noticeable in B32. Among carriers, AC was the most effective for preserving viable cell counts, closely similar to those of the initial inoculum of both strains. Maize productivity using the mixture RPTS was similar for B70 and B32. The best combination was B70 with RP, which improved the maize yield (6532 kg ha-1) and P accumulation in grains (15.95 kg ha-1). Our results indicated that the inoculant formulation with AC carrier and B70 is a feasible strategy for improving phosphorus mobilization in the soil and maize productivity.

Pathogenesis-Related Proteins (PRs) with Enzyme Activity Activating Plant Defense Responses.

Throughout evolution, plants have developed a highly complex defense system against different threats, including phytopathogens. Plant defense depends on constitutive and induced factors combined as defense mechanisms. These mechanisms involve a complex signaling network linking structural and biochemical defense. Antimicrobial and pathogenesis-related (PR) proteins are examples of this mechanism, which can accumulate extra- and intracellular space after infection. However, despite their name, some PR proteins are present at low levels even in healthy plant tissues. When they face a pathogen, these PRs can increase in abundance, acting as the first line of plant defense. Thus, PRs play a key role in early defense events, which can reduce the damage and mortality caused by pathogens. In this context, the present review will discuss defense response proteins, which have been identified as PRs, with enzymatic action, including constitutive enzymes, ß-1,3 glucanase, chitinase, peroxidase and ribonucleases. From the technological perspective, we discuss the advances of the last decade applied to the study of these enzymes, which are important in the early events of higher plant defense against phytopathogens.

Obstructive sleep apnea in asthmatic children: a cross-sectional study about prevalence and risk factors.

OBJECTIVES: Primary objectives were to analyze the prevalence of obstructive sleep apnea in (1) boys and girls, and (2) severe asthma versus moderate and mild cases. The authors hypothesized that girls and severe asthma would have a higher prevalence of obstructive sleep apnea. METHODS: Cross-sectional evaluation of asthmatic children attending a tertiary Pediatric Pulmonology clinic. The authors performed a history, physical examination, pulmonary function test, and home sleep apnea test. RESULTS: The authors studied 80 consecutive patients, 7-18 years old, mean age of 11.6 years (standard deviation 2.7), 51.3% female, and 18.5% obese. Pulmonary function tests were obtained from 80 volunteers, 45% with obstruction pattern. Home sleep apnea tests were available from 76 volunteers, with a mean obstructive respiratory index of 1.8 events/h. Obstructive sleep apnea was found in 49 volunteers (61.2%). The authors did not find associations between obstructive sleep apnea and sex or asthma severity. CONCLUSIONS: Obstructive sleep apnea was frequent among these asthmatic children. Sex and asthma severity were not risk factors. Considering the interrelationship of both diseases, it is worth keeping in mind the possibility of obstructive sleep apnea among children and teenagers with asthma.

Photocatalytic degradation of Rhodamine B dye by nanostructured powder systems containing nanoencapsulated curcumin or ascorbic acid and ascorbyl palmitate liposomal.

Due to inadequate treatment and incorrect management, wastewater with dyes has a great toxic potential as an environmental liability, representing a major concern. In this context, this work aims to investigate the potential application of nanostructured powdery systems (nanocapsules and liposomes) in the photodegradation of Rhodamine B (RhB) dye, under UV and visible irradiation. Curcumin nanocapsules and liposomes containing ascorbic acid and ascorbyl palmitate were prepared, characterized, and dried using the spray drying technique. The drying processes of the nanocapsule and the liposome showed yields of 88% and 62%, respectively, and, after aqueous resuspension of the dry powders, it was possible to recover the nanocapsule size (140 nm) and liposome size (160 nm). The dry powders were characterized by Fourier transform infrared spectroscopy (FTIR), N2 physisorption at 77 K, X-ray diffraction (XRD), and diffuse reflectance spectroscopy (DRS-UV). Under UV irradiation, 64.8% and 58.48% of RhB were removed with nanocapsules and liposomes, respectively. While under visible radiation, nanocapsules and liposomes were able to degrade 59.54% and 48.79% of RhB, respectively. Under the same conditions, commercial TiO2 showed degradation of 50.02% (UV) and 42.14% (visible). After 5 cycles of reuse, there was a decrease of about 5% for dry powders under UV irradiation and 7.5% under visible irradiation. Therefore, the nanostructured systems developed have potential application in heterogeneous photocatalysis for the degradation of organic pollutants, such as RhB, as they demonstrated superior photocatalytic performance to commercial catalysts (nanoencapsulated curcumin > ascorbic acid and ascorbyl palmitate liposomal > TiO2).

Caloric restriction promotes beta cell longevity and delays aging and senescence by enhancing cell identity and homeostasis mechanisms.

Caloric restriction (CR) extends organismal lifespan and health span by improving glucose homeostasis mechanisms. How CR affects organellar structure and function of pancreatic beta cells over the lifetime of the animal remains unknown. Here, we used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis link this transcriptional phenotype to transcription factors involved in beta cell identity (Mafa) and homeostasis (Atf6). Imaging metabolomics further demonstrates that CR beta cells are more energetically competent. In fact, high-resolution light and electron microscopy indicates that CR reduces beta cell mitophagy and increases mitochondria mass, increasing mitochondrial ATP generation. Finally, we show that long-term CR delays the onset of beta cell aging and senescence to promote longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cells during aging and diabetes.

Caloric restriction promotes beta cell longevity and delays aging and senescence by enhancing cell identity and homeostasis mechanisms.

Caloric restriction (CR) extends organismal lifespan and health span by improving glucose homeostasis mechanisms. How CR affects organellar structure and function of pancreatic beta cells over the lifetime of the animal remains unknown. Here, we used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis link this transcriptional phenotype to transcription factors involved in beta cell identity (Mafa) and homeostasis (Atf6). Imaging metabolomics further demonstrates that CR beta cells are more energetically competent. In fact, high-resolution light and electron microscopy indicates that CR reduces beta cell mitophagy and increases mitochondria mass, increasing mitochondrial ATP generation. Finally, we show that long-term CR delays the onset of beta cell aging and senescence to promote longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cells during aging and diabetes.

[Nutrition and physical activity counseling practice and adherence of primary care users]. / Aconselhamento sobre alimentação e atividade física: prática e adesão de usuários da atenção primária.

The present study aimed to investigate counseling content provided by healthcare professional for primary healthcare users, as well as users' difficulties in adhering to the counseling, through a cross-sectional study design. Interviews were conducted with 499 users at a primary healthcare unit and 59.3% of them said that counseling had been provided especially by physicians (93.6%), and it was based on healthy nutrition and physical activity practice (48.9%). Counseling was more frequently to users with greater numbers of morbid conditions (p = 0.001). The main factors that made adherence difficult for users were lack of time (27.5%) and the need to change habits (23%). It was identified that counseling is still at initial stage within primary care, and there is a need for healthcare professionals, especially the nurse of the family health team to be more proactive in this process,focusing mainly on health promotion.

Structured silica materials as innovative delivery systems for the bacteriocin nisin.

Nisin was encapsulated in silica through sol-gel process by acid-catalyzed routes. The silica xerogels were characterized through nitrogen adsorption isotherms, small-angle X-ray scattering (SAXS), zeta potential, X-ray diffraction (XRD), scanning electron microscopy (SEM), diffuse reflectance spectroscopy (DRS), and Fourier transform infrared spectroscopy (FTIR). SAXS results showed that the particle diameters in a second level of aggregation varied from 4.78 to 5.86 nm. Zeta potential of silica particles were from -9.6 to -25.3 mV, while the surface area and pore diameters ranged from 216 to 598 m2 g-1 and 2.53 to 2.90 nm, respectively, indicating the formation of mesoporous nanostructures. Nisin retained the antimicrobial activity against all microorganisms tested after encapsulation in silica materials. These novel silica-based structures can be valuable carriers for nisin delivery in food systems.

Glucocorticoids and glucolipotoxicity alter the DNA methylome and function of human EndoC-ßH1 cells.

AIMS: Synthetic glucocorticoids, including dexamethasone (DEX), are clinically prescribed due to their immunoregulatory properties. In excess they can perturb glucose homeostasis, with individuals predisposed to glucose intolerance more sensitive to these negative effects. While DEX is known to negatively impact ß-cell function, it is unclear how. Hence, our aim was to investigate the effect of DEX on ß-cell function, both alone and in combination with a diabetogenic milieu in the form of elevated glucose and palmitate. MAIN METHODS: Human pancreatic EndoC-ßH1 cells were cultured in the presence of high glucose and palmitate (glucolipotoxicity) and/or a pharmacological concentration of DEX, before functional and molecular analyses. KEY FINDINGS: Either treatment alone resulted in reduced insulin content and secretion, while the combination of DEX and glucolipotoxicity promoted a strong synergistic effect. These effects were associated with reduced insulin biosynthesis, likely due to downregulation of PDX1, MAFA, and the proinsulin converting enzymes, as well as reduced ATP response upon glucose stimulation. Genome-wide DNA methylation analysis found changes on PDE4D, MBNL1 and TMEM178B, all implicated in ß-cell function, after all three treatments. DEX alone caused very strong demethylation of the glucocorticoid-regulated gene ZBTB16, also known to influence the ß-cell, while the combined treatment caused altered methylation of many known ß-cell regulators and diabetes candidate genes. SIGNIFICANCE: DEX treatment and glucolipotoxic conditions separately alter the ß-cell epigenome and function. The combination of both treatments exacerbates these changes, showing that caution is needed when prescribing potent glucocorticoids in patients with dysregulated metabolism.

Aging compromises human islet beta cell function and identity by decreasing transcription factor activity and inducing ER stress.

Pancreatic islet beta cells are essential for maintaining glucose homeostasis. To understand the impact of aging on beta cells, we performed meta-analysis of single-cell RNA sequencing datasets, transcription factor (TF) regulon analysis, high-resolution confocal microscopy, and measured insulin secretion from nondiabetic donors spanning most of the human life span. This revealed the range of molecular and functional changes that occur during beta cell aging, including the transcriptional deregulation that associates with cellular immaturity and reorganization of beta cell TF networks, increased gene transcription rates, and reduced glucose-stimulated insulin release. These alterations associate with activation of endoplasmic reticulum (ER) stress and autophagy pathways. We propose that a chronic state of ER stress undermines old beta cell structure function to increase the risk of beta cell failure and type 2 diabetes onset as humans age.

Overexpression of cotton genes GhDIR4 and GhPRXIIB in Arabidopsis thaliana improves plant resistance to root-knot nematode (Meloidogyne incognita) infection.

Gossypium hirsutum L. represents the best cotton species for fiber production, thus computing the largest cultivated area worldwide. Meloidogyne incognita is a root-knot nematode (RKN) and one of the most important species of Meloidogyne genus, which has a wide host range, including cotton plants. Phytonematode infestations can only be partially controlled by conventional agricultural methods, therefore, more effective strategies to improve cotton resistance to M. incognita disease are highly desirable. The present study employed functional genomics to validate the involvement of two previously identified candidate genes, encoding dirigent protein 4-GhDIR4 and peroxiredoxin-2-GhPRXIIB, in cotton defense against M. incognita. Transgenic A. thaliana plant lines overexpressing GhDIR4 and GhPRXIIB genes were generated and displayed significantly improved resistance against M. incognita infection in terms of female nematode abundance in the roots when compared to wild-type control plants. For our best target-gene GhDIR4, an in-silico functional analysis, including multiple sequence alignment, phylogenetic relationship, and search for specific protein motifs unveiled potential orthologs in other relevant crop plants, including monocots and dicots. Our findings provide valuable information for further understanding the roles of GhDIR and GhPRXIIB genes in cotton defense response against RKN nematode. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03282-4.

Fosfomycin and nitrofurantoin: classic antibiotics and perspectives.

Antibiotics are essential molecules for the treatment and prophylaxis of many infectious diseases. However, drugs that combat microbial infections can become a human health threat due to their high and often indiscriminate consumption, considered one of the factors of antimicrobial resistance (AMR) emergence. The AMR crisis, the decrease in new drug development by the pharmaceutical industry, and reduced economic incentives for research have all reduced the options for treating infections, and new strategies are necessary, including the return of some traditional but "forgotten" antibiotics. However, prescriptions for these older drugs including nitrofurantoin and oral fosfomycin, have been based on the results of pioneer studies, and the limited knowledge generated 50-70 years ago may not be enough. To avoid harming patients and further increasing multidrug resistance, systematic evaluation is required, mainly for the drugs prescribed for community-acquired infections, such as urinary tract infections (UTI). Therefore, this review has the objective of reporting the use of two classic drugs from the nitrofuran and phosphonic acid classes for UTI control nowadays. Furthermore, we also explore new approaches used for these antibiotics, including new combination regimes for spectral amplification, and the prospects for reducing bacterial resistance in the fight against bacteria responsible for UTI.

Reduced insulin sensitivity and increased ß/α cell mass is associated with reduced hepatic insulin-degrading enzyme activity in pregnant rats.

AIMS: Pregnancy is associated with the development of a transitory insulin resistance that parallels with the upregulation of pancreatic ß-cell function and mass. These metabolic adaptations guarantee the higher insulin demand, but there is no evidence of whether insulin clearance contributes to this process. Thus, we investigated some of the hepatic parameters related to insulin clearance during rat pregnancy. We also investigated some molecular parameters in the hypothalamus. MAIN METHODS: We evaluated the body mass and food intake, insulin sensitivity, ß- and α-cell masses, insulin clearance based on an exogenous insulin load, hepatic insulin-degrading enzyme (IDE) activity, and hepatic and hypothalamic protein content of IDE and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1) in three periods of gestation in Wistar rats. KEY FINDINGS: In the first week of pregnancy, both insulin sensitivity and clearance increased, a pattern that inverted in the third week of gestation (reduced insulin sensitivity and clearance). Diminished insulin clearance was associated with lower hepatic IDE activity and higher pancreatic ß- and α-cell masses. No alteration in the hepatic IDE and CEACAM protein content was observed throughout pregnancy, but hypothalamic IDE protein content was significantly reduced in the late gestation period. SIGNIFICANCE: In conclusion, elevated insulin demand in the late period of gestation occurs not only as a result of increased ß-cell mass and function but also by a potential reduction in hepatic insulin clearance. Knowing this physiological process may be valuable when considering gestational diabetes mellitus results from a failure in insulin supply during pregnancy.