Maternal SARS-CoV-2 infection in pregnancy disrupts gene expression in Hofbauer cells with limited impact on cytotrophoblasts.

BACKGROUND: Hofbauer cells (HBCs) and cytotrophoblasts (CTBs) are major cell populations in placenta. The indirect impact of maternal SARS-CoV-2 disease on these cells that are not directly infected has not been extensively studied. Herein, we profiled gene expression in HBCs and CTBs isolated from placentae of recovered pregnant subjects infected with SARS-CoV-2 during all trimesters of pregnancy, placentae from subjects with active infection, SARS-CoV-2 vaccinated subjects, and those who were unexposed to the virus. METHODS: Placentae were collected within 4 h post-delivery and membrane-free tissues were enzymatically digested for the isolation of HBCs and CTBs. RNA extracted from HBCs and CTBs were sequenced using 150bp paired-end reads. Differentially expressed genes (DEGs) were identified by DESeq2 package in R and enriched in GO Biological Processes, KEGG Pathway, Reactome Gene Sets, Hallmark Gene Sets, and Canonical Pathways. Protein-protein interactions among the DEGs were modelled using STRING and BioGrid. RESULTS: Pregnant subjects (n = 30) were recruited and categorized into six groups: infected with SARS-CoV-2 in i) the first (1T, n = 4), ii) second (2T, n = 5), iii) third (3T, n = 5) trimester, iv) tested positive at delivery (Delivery, n = 5), v) never infected (Control, n = 6), and vi) fully mRNA-vaccinated by delivery (Vaccinated, n = 5). Compared to the Control group, gene expression analysis showed that HBCs from infected subjects had significantly altered gene expression profiles, with the 2T group having the highest number of DEGs (1,696), followed by 3T and 1T groups (1,656 and 958 DEGs, respectively). These DEGs were enriched for pathways involved in immune regulation for host defense, including production of cytokines, chemokines, antimicrobial proteins, ribosomal assembly, neutrophil degranulation inflammation, morphogenesis, and cell migration/adhesion. Protein-protein interaction analysis mapped these DEGs with oxidative phosphorylation, translation, extracellular matrix organization, and type I interferon signaling. Only 95, 23, and 8 DEGs were identified in CTBs of 1T, 2T, and 3T groups, respectively. Similarly, 11 and 3 DEGs were identified in CTBs and HBCs of vaccinated subjects, respectively. Reassuringly, mRNA vaccination did not induce an inflammatory response in placental cells. CONCLUSIONS: Our studies demonstrate a significant impact of indirect SARS-CoV-2 infection on gene expression of inner mesenchymal HBCs, with limited effect on lining CTB cells isolated from pregnant subjects infected and recovered from SARS-CoV-2. The pathways associated with these DEGs identify potential targets for therapeutic intervention.

In-Cell Chemical Crosslinking Identifies Hotspots for SQSTM-1/p62-IκBα Interaction That Underscore a Critical Role of p62 in Limiting NF-κB Activation Through IκBα Stabilization.

We have previously documented that in liver cells, the multifunctional protein scaffold p62/SQSTM1 is closely associated with IκBα, an inhibitor of the transcriptional activator NF-κB. Such an intimate p62-IκBα association we now document leads to a marked 18-fold proteolytic IκBα-stabilization, enabling its nuclear entry and termination of the NF-κB-activation cycle. In p62-/--cells, such termination is abrogated resulting in the nuclear persistence and prolonged activation of NF-κB following inflammatory stimuli. Utilizing various approaches both classic (structural deletion, site-directed mutagenesis) as well as novel (in-cell chemical crosslinking), coupled with proteomic analyses, we have defined the precise structural hotspots of p62-IκBα association. Accordingly, we have identified such IκBα hotspots to reside around N-terminal (K38, K47, and K67) and C-terminal (K238/C239) residues in its fifth ankyrin repeat domain. These sites interact with two hotspots in p62: One in its PB-1 subdomain around K13, and the other comprised of a positively charged patch (R183/R186/K187/K189) between its ZZ- and TB-subdomains. APEX proximity analyses upon IκBα-cotransfection of cells with and without p62 have enabled the characterization of the p62 influence on IκBα-protein-protein interactions. Interestingly, consistent with p62's capacity to proteolytically stabilize IκBα, its presence greatly impaired IκBα's interactions with various 20S/26S proteasomal subunits. Furthermore, consistent with p62 interaction with IκBα on an interface opposite to that of its NF-κB-interacting interface, p62 failed to significantly affect IκBα-NF-κB interactions. These collective findings together with the known dynamic p62 nucleocytoplasmic shuttling leads us to speculate that it may be involved in "piggy-back" nuclear transport of IκBα following its NF-κB-elicited transcriptional activation and de novo synthesis, required for termination of the NF-κB-activation cycle. Consequently, mice carrying a liver-specific deletion of p62-residues 68 to 252 reveal age-dependent-enhanced liver inflammation. Our findings reveal yet another mode of p62-mediated pathophysiologically relevant regulation of NF-κB.

Nutritional management during critical illness in those with previous obesity surgery.

PURPOSE OF REVIEW: The prevalence of overweight and obesity in our society is a pressing concern that has demanded immediate attention. Traditional treatments have proven ineffective for many individuals, leading to a surge in bariatric surgery as a last resort. While the rate of early and late postoperative complications may be low, when they occur, they place these patients at higher risk of requiring intensive care treatment. Therefore, it is our aim to discuss the nutritional care of these individuals. RECENT FINDINGS: Nutritional management of critically ill postbariatric surgical patients is related to the difficulty of providing an adequate nutritional assessment, calculating the macro and micronutrient requirements, choosing the right therapy, and defining the timely moment to initiate it. The anatomic changes related to the bariatric operation pose a high risk for a nonfunctional gastrointestinal tract both in the early postoperative and late postoperative. Therefore, the route of nutrition will greatly rely on the absorptive capacity, as well as on the nutritional status, with parenteral nutrition being an early option, especially for those with high critical care severity scores. Also, these patients are known to have an altered microbiota which may influence the absorptive capacity. Immunonutrition, prebiotics, probiotics, and symbiotics may represent potential options, but there is currently little support for 'one size fits all'. SUMMARY: The nutritional care of critically ill patients postbariatric surgery is a complex and nuanced process requiring a multifaceted precision approach. The distinct nutritional challenges of early and late postoperative patients necessitate a thorough nutritional assessment and a highly individualized nutritional care plan.

Syagrus coronata fixed oil prevents rotenone-induced movement disorders and oxidative stress in Drosophila melanogaster.

One prominent aspect of Parkinson's disease (PD) is the presence of elevated levels of free radicals, including reactive oxygen species (ROS). Syagrus coronata (S. coronata), a palm tree, exhibits antioxidant activity attributed to its phytochemical composition, containing fatty acids, polyphenols, and flavonoids. The aim of this investigation was to examine the potential neuroprotective effects of S. coronata fixed oil against rotenone-induced toxicity using Drosophila melanogaster. Young Drosophila specimens (3-4 d old) were exposed to a diet supplemented with rotenone (50 µM) for 7 d with and without the inclusion of S. coronata fixed oil (0.2 mg/g diet). Data demonstrated that rotenone exposure resulted in significant locomotor impairment and increased mortality rates in flies. Further, rotenone administration reduced total thiol levels but elevated lipid peroxidation, iron (Fe) levels, and nitric oxide (NO) levels while decreasing the reduced capacity of mitochondria. Concomitant administration of S. coronata exhibited a protective effect against rotenone, as evidenced by a return to control levels of Fe, NO, and total thiols, lowered lipid peroxidation levels, reversed locomotor impairment, and enhanced % cell viability. Molecular docking of the oil lipidic components with antioxidant enzymes showed strong binding affinity to superoxide dismutase (SOD) and glutathione peroxidase (GPX1) enzymes. Overall, treatment with S. coronata fixed oil was found to prevent rotenone-induced movement disorders and oxidative stress in Drosophila melanogaster.

Phytochemical profile and determination of cytotoxicity, acute oral toxicity, genotoxicity, and mutagenicity of aqueous and ethanolic extracts of Pseudobombax marginatum (A. St.-Hil.) A. Robyns.

Pseudobombax marginatum, popularly known as "embiratanha," is widely used by traditional communities as anti-inflammatory and analgesic agent. This study aimed to determine the phytochemical profile as well as cytotoxicity, acute oral toxicity, genotoxicity, and mutagenicity attributed to exposure to aqueous (AqEx) and ethanolic (EtEx) extracts of embiratanha bark. Phytochemical screening was conducted using thin-layer chromatography (TLC). Cell viability was analyzed using MTT assay with human mammary gland adenocarcinoma (MDA-MB-231) and macrophage (J774A.1) cell lines, exposed to concentrations of 12.5, 25, 50, or 100 µg/ml of either extract. For acute oral toxicity, comet assay and micronucleus (MN) tests, a single dose of 2,000 mg/kg of either extract was administered orally to Wistar rats. TLC analysis identified classes of metabolites in the extracts, including cinnamic acid derivatives, flavonoids, hydrolyzable tannins, condensed tannins, coumarins, and terpenes/steroids. In the cytotoxicity assay, the varying concentrations of extracts derived from embiratanha induced no significant alterations in the viability of MDA-MB-231 cells. The lowest concentration of EtEx significantly increased macrophage J774A.1 viability. However, the higher concentrations of AqEx markedly lowered macrophage J774A.1 viability. Animals exhibited no toxicity in the parameters analyzed in acute oral toxicity, comet assay, and MN tests. Further, EtEx promoted a significant reduction in DNA damage index and DNA damage frequency utilizing the comet assay, while the group treated with AqEx exhibited no marked differences. Thus, data demonstrated that AqEx or EtEx of embiratanha may be considered safe at a dose of 2,000 mg/kg orgally under our experimental conditions tested.

Eugenia pohliana leaves essential oil inhibits fungal virulence and restores antibiotic efficacy in multidrug-resistant bacterial strains.

This study aims to investigate the essential oil from leaves of E. pohliana (EOEP) in regard to its chemical composition, antimicrobial and drug-enhancing activity, as well as the reduction of fungal virulence capacity. Chemical characterization using GC-MS showed as major components the sesquiterpenes δ-cadinene, Epi-α-Muurolol, and bicyclogermacrene. The results of antibacterial tests indicated that Staphylococcus aureus was more sensitive to EOEP, that also enhanced the efficacy of gentamicin, erythromycin, and norfloxacin. EOEP exhibited antifungal properties against Candida albicans, in addition to potentiating the effectiveness of fluconazole against Candida tropicalis. It showed anti-virulence effects in all fungal strains. These findings underscore Eugenia pohliana as a potential candidate for the prospection of novel therapeutic agents to treat infectious diseases caused by resistant microbes.

Development of gel containing Psidium glaziovianum essential oil has in vitro antimicrobial activity and improves healing of excisional wounds in mice.

Wounds encompass physical, chemical, biological, induced damages to the skin or mucous membranes. In wound treatment, combating infections is a critical challenge due to their potential to impede recovery and inflict systemic harm on patients. Previously, the essential oil extracted from Psidium glaziovianum (PgEO) demonstrated antinociceptive and anti-inflammatory attributes, along with negligible oral toxicity. Hence, our study aimed to assess the effects of topically applying a gel formulation containing PgEO to excisional wounds in mice. Additionally, an in vitro antimicrobial assessment was conducted. The formulated gel underwent characterization and toxicological evaluation on erythrocytes, as well as a dermal irritation test. Its antimicrobial activity was tested against both gram-positive and gram-negative bacteria, as well as fungi. Subsequently, an assessment of its efficacy in excisional wound healing was conducted in mice. The findings of this investigation highlight the gel's efficacy against both gram-positive and gram-negative bacteria, as well as fungi. Moreover, this study underscores that the PgEO-gel treatment enhances skin wound healing, potentially due to its capacity to trigger antioxidant enzymes and suppress pro-inflammatory cytokines. Furthermore, the gel exhibited minimal toxicity to erythrocytes and skin irritation. These findings hold promise for prospective preclinical and clinical trials across diverse wound types. In conclusion, this study sheds light on the potential therapeutic applications of the gel formulation containing essential oil from P. glaziovianum in the context of wound healing.

Chemical characterization of the essential oil from the leaves of Eugenia flavescens DC. (Myrtaceae) and its potential in the treatment of pain, inflammation, and ethanol- and ethanol/HCL-induced gastric ulcers in mice.

Eugenia flavescens is a species cultivated in Brazil for food purposes. Given the potential application of essential oils from plants of the genus Eugenia, this study was carried out to investigate the chemical composition, acute toxicity, antioxidant, antinociceptive, gastroprotective activities, and possible mechanisms of action of the essential oil from the leaves of E. flavescens (EOEf). The EOEf was extracted by hydrodistillation, and the chemical composition was obtained using gas chromatography-mass spectrometry. The antioxidant activity was evaluated, as well as the acute toxicity and the antinociceptive and anti-inflammatory effects in mice. In addition, the gastroprotective effect was investigated using an acute gastric lesion model, considering possible mechanisms of action. The major components found in the EOEf were guaiol (19.97%), germacrene B (12.53%), bicyclogermacrene (11.11%), and E-caryophyllene (7.53%). The EOEf did not cause signs of toxicity in the acute oral toxicity test and showed in vitro antioxidant activity with IC50 ranging from 247.29 to 472.39 µg/mL in the tests ABTS and DPPH. In the nociceptive test, EOEf showed a 72.05% reduction in nociception at a dose of 100 mg/kg. In evaluating the anti-inflammatory effect, the essential oil inhibited paw edema by 95.50% and 97.69% at doses of 50 and 100 mg/kg. The results showed that EOEf has a gastroprotective effect, acting through the sulfhydryl compounds (-SH), nitric oxide (NO), and synthesis PGE2 pathways. The results suggested that EOEf is a promising source of constituents with antioxidant, antinociceptive, anti-inflammatory, and gastroprotective properties with application in the food and pharmaceutical industries.

Fixed oil from the Caatinga palm Syagrus coronata with effect on Complete Freund's Adjuvant (CFA)-induced arthritis.

Syagrus coronata, a native palm tree in the Caatinga domain, produces fixed oil (ScFO) used therapeutically and dietary by Northeast Brazilian communities. This study evaluated its anti-inflammatory potential of CFA-induced arthritis and its effect on behavioral parameters. In the acute model, ScFO at 25, 50, and 100 mg/kg showed edematogenic effects similar to indomethacin at 4 mg/kg (p > 0.05). In the arthritis model, 100 mg/kg ScFO treatment was comparable to indomethacin (4 mg/kg) (p > 0.05). TNF-α and IL-1ß levels were significantly reduced in ScFO-treated groups at 25, 50, and 100 mg/kg, and the indomethacin group (4 mg/kg) versus the positive control (p > 0.05). Radiographs showed severe soft-tissue swelling and bone deformities in the control group, while the 100 mg/kg ScFO group had few alterations, similar to the indomethacin group. Histopathological analysis revealed intense lymphocytic infiltration in the control group, mild diffuse lymphocytic infiltration in the indomethacin group, and mild lymphoplasmacytic infiltration with focal polymorphonuclear infiltrates in the 100 mg/kg ScFO group. Behavioral analysis showed improved exploratory stimuli in ScFO and indomethacin-treated mice compared to the positive control (p > 0.05). ScFO demonstrated anti-inflammatory effects in both acute and chronic arthritis models, reducing edema and pro-inflammatory cytokines, and improved exploratory behavior due to its analgesic properties.

Unlocking the potential of probiotic administration in caries management: a systematic review.

BACKGROUND: The use of prebiotics and/or probiotic bacteria with the potential to modulate the oral ecosystem may play an important role in the prevention and management of dental caries. To assess the evidence of the potential of pre/probiotics both in the prevention and treatment of dental caries, we focused on the PICO question "In individuals with caries, after probiotic administration, is there an improvement in outcomes directly related to caries risk and development?". METHODS: An extensive systematic search was conducted in electronic databases PubMed, Web of Science, Scopus and Cochrane, to identify articles with relevant data. This systematic review included trials performed in Humans; published in English; including the observation of patients with caries, with clear indication of the probiotic used and measuring the outcomes directly involved with the cariogenic process, including the quantification of bacteria with cariogenic potential. To evaluate the methodological quality of the studies, the critical assessment tool from the Joanna Briggs Institute was used. RESULTS: Eight hundred and fifty articles, potentially relevant, were identified. Following PRISMA guidelines 14 articles were included in this systematic review. Outcomes such as reduction of cariogenic microorganism counts, salivary pH, buffer capacity, and caries activity were assessed. The probiotic most often referred with beneficial results in dental caries outcomes is Lacticaseibacillus rhamnosus. Regarding the most used administration vehicle, in studies with positive effects on the caries management, probiotic supplemented milk could be considered the best administration vehicle. CONCLUSIONS: Evidence suggests a beneficial effect of probiotic supplemented milk (Lacticaseibacillus rhamnosus) as an adjuvant for caries prevention and management. However, comparable evidence is scarce and better designed and comparable studies are needed.

White spot lesions: diagnosis and treatment - a systematic review.

BACKGROUND: White spot lesions represent the first stage of caries and their prevalence has been increasing in recent years, particularly in patients undergoing orthodontic treatment. DIferential diagnosis and lesion activity are essential to decide on the clinical approaches to treatment. The aim of this study is to understand if the new diagnostic tools such as fluorescence, microradiography and computed microtomography have the potential to change the conventional treatment of white spots". METHODS: A systematic search of available studies in the literature was carried out, using PRISMA guidelines, in Pubmed and Scopus electronic databases and manually to identify relevant articles to answer the PICO question: "Do the new diagnostic tools have the potential to change the conventional treatment of white spots?". This systematic review included randomized controlled trials (RCT), cross-sectional and longitudinal studies complying with the following inclusion criteria: (i) studies in humans, (ii) studies about white spot lesions, (iii) studies published between 2012 and 2023, (iv) studies having both diagnosis and treatment and (v) studies with full text available. In this review we excluded other systematic reviews of clinical trials and in vitro studies. The RoB tool was used to assess the risk of bias. RESULTS: The systematic literature search identified 143 potentially relevant references, which after applying the exclusion criteria, resulted in 20 articles. Regarding diagnostic methods, most articles found were based on conventional methods of visual examination (n:10) or fluorescence (n:7). The least referenced diagnostic techniques were based on the use of clinical photographs (n:2), cross-sectional microradiography (n:1) and computed microtomography (n:1). The use of DIAGNOdent was reported by 3 in vitro studies. With regard to therapies, most studies reported the use of infiltrating resin (n:7) and fluoride-based products (n:5). Other studies have reported the use of self-assembling peptide P11-4 (n:1), home care (n:1), casein phosphopeptide-amorphous calcium phosphate (n:2) and hydrochloric acid (n:1). Combination therapies were also considered. CONCLUSION: Diagnostic tool does not have the potential to change the form of treatment, whether it is a conventional method or a more differentiated one.

Findings from Positron Emission Tomography-Computed Tomography with 18F-Fluorodeoxyglucose Uncover a Potential Marker of Nutritional Status in Cancer Patients: A Cross-Sectional Pilot Study.

BACKGROUND: Cancer patients often have altered nutritional status and periodically undergo imaging tests. We hypothesized that standard uptake values (SUV) by positron emission tomography-computed tomography (PET/CT) with 18 F-fluorodeoxyglucose (18F-FDG) could be associated with the nutritional status of cancer patients. MATERIALS AND METHODS: Adult cancer patients who underwent clinical evaluation and PET/CT with 18 F-FDG on the same day were included in a cross-sectional pilot study. The focus was on evaluating 18 F-FDG findings with regard to nutritional status, with an emphasis on liver SUVmean and tumor SUVmax. RESULTS: A total of 179 patients were evaluated. One hundred and three (57.5%) were classified as well-nourished, 54 (30.1%) as suspected/moderately malnourished, and 22 (12.2%) as severely malnourished. The median hepatic SUVmean was 2.29, with 1.87 corresponding to the 10th percentile. There was a significant difference between the severely malnourished (2.02) and well-nourished or suspected/moderately malnourished (2.36) patients. Severely malnourished patients were more likely to have a SUVmean < 1.87 (p = .035). The tumor SUVmax also was significantly higher in severely malnourished patients (p = .003). CONCLUSION: Cancer patients with severe malnutrition have lower values of hepatic SUVmean and higher values of tumor SUVmax in PET/CT with 18F-FDG when compared to well-nourished patients.

Evaluation of 28-day repeated doses oral toxicity of essential oil from Psidium glaziovianum Kiaersk leaves on various biological parameters in Swiss mice.

Only a small number of the many medicinally important species in the genus Psidium L. have had their safety assessed. Psidium glaziovianum, a plant native to Brazil, is reported to exert antinociceptive and anti-inflammatory effects; however, there are no apparent reports of long-term safety following administering of repeated doses. The aim of this study was to examine the effects of 28-day oral of treatment at 250, 500 or 1,000 mg/kg Psidium glaziovianum essential oil (PgEO) on behavioral and physiological parameters in male and female Swiss mice. First, PgEO was chemically characterized by gas chromatography mass spectrometry (GC-MS). The following parameters were examined: motor activity, body temperature, blood glucose, urine, hematology, biochemistry, histology, and oxidative stress. Characterization of PgEO revealed 48 components which were dominated by sesquiterpenes 1,8-cineol (24.29%), α-pinene (19.73%) and ß-pinene (17.31%). Data showed that PgEO treatment in mice increased activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) without markedly affecting body weight, hematological or biochemical parameters, as well as water or food consumption. Administration of PgEO in repeated daily dosages over 28 days did not significantly alter exploratory or locomotor activities. Based upon our findings, PgEO administration daily for 28 days, exhibited low toxicity and absence of effects on the nervous system. Data demonstrated that PgEO produced hypoglycemic and antioxidant actions which need to be considered in safety assessment.

Toxicological safety, antioxidant activity and phytochemical characterization of leaf and bark aqueous extracts of Commiphora leptophloeos (Mart.) J.B. Gillett.

This study aimed to characterize the phytochemical profile of bark and leaves aqueous extract Commiphora leptophloeos, and conduct in vivo and in vitro assays to determine the presence of any toxicological consequences due to exposure. The phytochemical analysis was carried out using high-performance liquid chromatography (HPLC). The antioxidant activity was estimated utilizing DPPH free radical scavenging and phosphomolybdenum assays. Cell viability was measured by the MTT method on J774 and human adenocarcinoma cells, which were treated with concentrations of 12,5, 25, 50, 100 or 200 µg/ml of both extracts. Acute oral toxicity, genotoxicity, and mutagenicity assays were determined using a single oral dose of 2000 g/kg in male Swiss albino mice (Mus musculus). Biochemical analysis of the blood and histological analyses of the kidneys, liver, spleen, pylorus, duodenum and jejunum were undertaken. Genotoxicity and mutagenicity were determined utilizing blood samples. Gallic acid, catechin, and epicatechin were identified in the bark and chlorogenic acid in leaves. Data demonstrated a high content of phenolic compounds and flavonoids associated with significant antioxidant potential. No significant signs in damage or symptoms of toxicity were detected. No marked reduction in cell viability was found at lower concentrations tested. On histomorphometry, only the gastrointestinal organs exhibited significant difference. Renal hepatic and blood parameters were within the normal range. No apparent signs of toxicity, genotoxicity, mutagenicity or cytotoxicity were found in vivo and in vitro experiments.

Control of Arterial Hypertension by the AhR Blocker CH-223191: A Chronopharmacological Study in Chronic Intermittent Hypoxia Conditions.

Chronic intermittent hypoxia (CIH) is a major contributor to the development of hypertension (HTN) in obstructive sleep apnea (OSA). OSA subjects frequently display a non-dipping pattern of blood pressure (BP) and resistant HTN. After discovering that AHR-CYP1A1 axis is a druggable target in CIH-HTN, we hypothesized that CH-223191 could control BP in both active and inactive periods of the animals, recovering the BP dipping profile in CIH conditions.We evaluated the chronopharmacology of the antihypertensive efficacy of the AhR blocker CH-223191 in CIH conditions (21% to 5% of O2, 5.6 cycles/h, 10.5 h/day, in inactive period of Wistar rats). BP was measured by radiotelemetry, at 8 am (active phase) and at 6 pm (inactive phase) of the animals. The circadian variation of AhR activation in the kidney in normoxia was also assessed, measuring the CYP1A1 (hallmark of AhR activation) protein levels.Despite drug administration before starting the inactive period of the animals, CH-223191 was not able to decrease BP during the inactive phase, in CIH conditions, therefore not reverting the non-dipping profile. These results suggest that a higher dose or different time of administration of CH-223191 might be needed for an antihypertensive effect throughout the 24-h cycle.

Impairment of SK-MEL-28 Development-A Human Melanoma Cell Line-By the Crataeva tapia Bark Lectin and Its Sequence-Derived Peptides.

Melanoma is difficult to treat with chemotherapy, prompting the need for new treatments. Protease inhibitors have emerged as promising candidates as tumor cell proteases promote metastasis. Researchers have developed a chimeric form of the Bauhinia bauhinioides kallikrein inhibitor, rBbKIm, which has shown negative effects on prostate tumor cell lines DU145 and PC3. Crataeva tapia bark lectin, CrataBL, targets sulfated oligosaccharides in glycosylated proteins and has also demonstrated deleterious effects on prostate and glioblastoma tumor cells. However, neither rBbKIm nor its derived peptides affected the viability of SK-MEL-28, a melanoma cell line, while CrataBL decreased viability by over 60%. Two peptides, Pep. 26 (Ac-Q-N-S-S-L-K-V-V-P-L-NH2) and Pep. 27 (Ac-L-P-V-V-K-L-S-S-N-Q-NH2), were also tested. Pep. 27 suppressed cell migration and induced apoptosis when combined with vemurafenib, while Pep. 26 inhibited cell migration and reduced nitric oxide and the number of viable cells. Vemurafenib, a chemotherapy drug used to treat melanoma, was found to decrease the release of interleukin 8 and PDGF-AB/BB cytokines and potentiated the effects of proteins and peptides in reducing these cytokines. These findings suggest that protease inhibitors may be effective in blocking melanoma cells and highlight the potential of CrataBL and its derived peptides.

The Use of Proteins, Lipids, and Carbohydrates in the Management of Wounds.

Despite the fact that skin has a stronger potential to regenerate than other tissues, wounds have become a serious healthcare issue. Much effort has been focused on developing efficient therapeutical approaches, especially biological ones. This paper presents a comprehensive review on the wound healing process, the classification of wounds, and the particular characteristics of each phase of the repair process. We also highlight characteristics of the normal process and those involved in impaired wound healing, specifically in the case of infected wounds. The treatments discussed here include proteins, lipids, and carbohydrates. Proteins are important actors mediating interactions between cells and between them and the extracellular matrix, which are essential interactions for the healing process. Different strategies involving biopolymers, blends, nanotools, and immobilizing systems have been studied against infected wounds. Lipids of animal, mineral, and mainly vegetable origin have been used in the development of topical biocompatible formulations, since their healing, antimicrobial, and anti-inflammatory properties are interesting for wound healing. Vegetable oils, polymeric films, lipid nanoparticles, and lipid-based drug delivery systems have been reported as promising approaches in managing skin wounds. Carbohydrate-based formulations as blends, hydrogels, and nanocomposites, have also been reported as promising healing, antimicrobial, and modulatory agents for wound management.

Essential oil from leaves of Myrciaria floribunda (H. West ex Willd.) O. Berg has antinociceptive and anti-inflammatory potential.

Myrciaria floribunda is a plant that is distributed across different Brazilian biomes such as the Amazon, Caatinga, Cerrado, and Atlantic Forest, and it possesses antioxidant, antimicrobial, and anticancer properties. The antinociceptive and anti-inflammatory properties of the essential oil from M. floribunda leaves (MfEO) were examined in this study using mouse models. Gas chromatography-mass spectrometry was employed to describe the oil, and the results revealed that δ-cadinene, bicyclogermacrene, α-cadinol, and epi-α-muurolol predominated in the chemical profile. The oil stimulated a decrease in nociception in the chemical and thermal models used to evaluate acute antinociceptive activity. Findings from the use of pain pathway blockers to study the presumed underlying mechanism indicated opioid pathway activity. The anti-edematogenic effect, decreased cell migration, and generation of pro-inflammatory cytokines provided evidence of the anti-inflammatory potential of the essential oil from M. floribunda. According to this research, the essential oil from M. floribunda can effectively alleviate acute pain and inflammation.

Is oral microbiota associated with overweight and obesity in children and adolescents? A systematic review.

This article aims to verify the relationship between the composition and diversity of oral microbiota with overweight and obese children and adolescents. This systematic review was registered in PROSPERO, followed PRISMA 2020, and included an electronic search until March 2022, in PubMed/MEDLINE, Web of Science, Scopus, and The Cochrane Library databases. Studies were eligible if they compared the oral microbiota according to nutrition status among children and adolescents. Independent peers using JBI Critical Appraisal Checklists assessed the quality of studies. Eleven studies were eligible to be included in this review, with a total of 1,695 children and adolescents, 224 were obese, 190 were overweight, 1,154 were eutrophics and 127 were underweight. The most frequent phyla in overweight and obese children and adolescents, in comparison to their counterparts were Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria and Fusobacteria. It was identified that nine of the eleven articles selected showed an association between oral microbiota and overweight and obesity in children and adolescents. We observed that there is an important association between oral bacterial composition diversity and overweight and obesity. This finding indicates the relevance of the evaluation and surveillance in oral health to control cases of overweight and obesity in children and adolescents.

Obesity and critical care nutrition: current practice gaps and directions for future research.

BACKGROUND: This review has been developed following a panel discussion with an international group of experts in the care of patients with obesity in the critical care setting and focuses on current best practices in malnutrition screening and assessment, estimation of energy needs for patients with obesity, the risks and management of sarcopenic obesity, the value of tailored nutrition recommendations, and the emerging role of immunonutrition. Patients admitted to the intensive care unit (ICU) increasingly present with overweight and obesity that require individualized nutrition considerations due to underlying comorbidities, immunological factors such as inflammation, and changes in energy expenditure and other aspects of metabolism. While research continues to accumulate, important knowledge gaps persist in recognizing and managing the complex nutritional needs in ICU patients with obesity. Available malnutrition screening and assessment tools are limited in patients with obesity due to a lack of validation and heterogeneous factors impacting nutrition status in this population. Estimations of energy and protein demands are also complex in patients with obesity and may include estimations based upon ideal, actual, or adjusted body weight. Evidence is still sparse on the role of immunonutrition in patients with obesity, but the presence of inflammation that impacts immune function may suggest a role for these nutrients in hemodynamically stable ICU patients. Educational efforts are needed for all clinicians who care for complex cases of critically ill patients with obesity, with a focus on strategies for optimal nutrition and the consideration of issues such as weight stigma and bias impacting the delivery of care. CONCLUSIONS: Current nutritional strategies for these patients should be undertaken with a focus on individualized care that considers the whole person, including the possibility of preexisting comorbidities, altered metabolism, and chronic stigma, which may impact the provision of nutritional care. Additional research should focus on the applicability of current guidelines and evidence for nutrition therapy in populations with obesity, especially in the setting of critical illness.