Chemopreventive and immunomodulatory effects of phenolic-rich extract of Commiphora leptophloeos against inflammatory bowel disease: Preclinical evidence.

ETHNOPHARMACOLOGY RELEVANCE: Commiphora leptophloeos (Mart.) J.B. Gillet (Burseraceae) is a medicinal plant native to Brazil, popularly known as "imburana". Homemade leaf decoction and maceration were used to treat general inflammatory problems in the Brazilian Northeast population. Our previous research confirmed the anti-inflammatory activity of the C. leptophloeos hydroalcoholic leaf extract. AIM OF THE STUDY: Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gut with no ideal treatment to maintain the remissive status. This work aimed to characterize the phytochemical composition and physicochemical properties of the C. leptophloeos hydroalcoholic leaf extract and its efficacy in chemopreventive and immunomodulatory responses in inflammatory bowel disease in non-clinical models. MATERIALS AND METHODS: Mass spectrometry and physicochemical tests determined the phytochemical profile and physicochemical characteristics of the Commiphora leptophloeos (CL) extract. The chemopreventive and immunomodulatory effects of CL extract (50 and 125 µg/mL) were evaluated in vitro in the RAW 264.7 lipopolysaccharide (LPS) induced cell assay and in vivo in the model of intestinal inflammation induced by 2,4-Dinitrobenzenesulfonic acid (DNBS) in mice when they were treated with CL extract by intragastric gavage (i.g.) at doses of 300, 400 and 500 mg/kg. RESULTS: Phytochemical annotation of CL extract showed a complex phenolic composition, characterized as phenolic acids and flavonoids, and satisfactory physicochemical characteristics. In addition, CL extract maintained the viability of RAW macrophages, reduced ROS and NO production, and negatively regulated COX-2, iNOS, TNF-α, IL-1ß, IL-6, and IL-17 (p < 0.05). In the intestinal inflammation model, CL extract was able to downregulate NF-κB p65/COX-2, mTOR, iNOS, IL-17, decrease levels of malondialdehyde and myeloperoxidase and cytokines TNF-α, IL-1ß and IL-6 (p < 0.05). CONCLUSION: Based on these findings, CL extract reduced inflammatory responses by down-regulating pro-inflammatory markers in macrophages induced by LPS and DNBS-induced colitis in mice through NF-κB p65/COX-2 signaling. CL leaf extract requires further investigation as a candidate for treating inflammatory bowel disease.

Fast and low-cost method for direct and simultaneous determination of nitrogen and carbon in soybean leaves using benchtop and portable near-infrared devices.

BACKGROUND: The current techniques for determining carbon and nitrogen content to provide information about the nutritional status of plants are time-consuming and expensive. For this reason, the objective of this study was to develop an analytical method for the direct and simultaneous determination of nitrogen and carbon elemental content in soybean leaves using near-infrared spectroscopy and compare the performance of conventional (1100-2500 nm spectral range) and portable equipment (1100-1700 nm spectral range). Partial least-squares regression models were developed using 27 soybean leaf samples collected during the 2021 harvest and applied for the simultaneous determination of carbon and nitrogen in 13 samples collected during the 2022 harvest. RESULTS: The root-mean-square error of prediction values for nitrogen and carbon were low (2.42 g kg-1 and 4.37 g kg-1 respectively) for the benchtop method yielded low but higher for the portable method (3.82 g kg-1 and 10.7 g kg-1 respectively). The benchtop method did not show significant differences when compared with the reference method for determining nitrogen and carbon. In contrast, the portable methodology showed potential as a screening method for determining nitrogen levels, particularly in fieldwork. CONCLUSION: The methodologies evaluated in this study were implemented and evaluated under real crop monitoring conditions, using independent sets of calibration and prediction samples. Their utilization enables the acquisition of cost-effective, safe analytical data aligning with the principles of green analytical chemistry. © 2023 Society of Chemical Industry.

Cytotoxic and oxidative changes in individuals occupationally exposed to recyclable municipal solid waste.

aste collectors are exposed to a wide variety of bacteria, endotoxins, fungi, allergens, particulate matter, irritating inhalants, and vehicle exhaust, making them more prone to development of chronic diseases. Although several studies described the impact of occupational exposure on the overall health of waste collectors, few investigations were conducted regarding cellular and molecular changes that may occur due to exposure. The aim of this study was to assess biomarkers of oxidative stress such as levels of reactive oxygen species (ROS), lipoperoxidation, total antioxidant capacity (TAC), apoptosis, butyrylcholinesterase (BChE) activity and mitochondrial function (MitoTrackerTM Green FM and MitoTrackerTM Red) using the peripheral blood from individuals occupationally exposed to recyclable solid waste in Southern Brazil. The study included 30 waste collectors and 30 control individuals, who did not perform activities with recognized exposure to biological and chemical substances. Waste collectors were found to exhibit in peripheral blood leukocytes (PBL) higher rates of apoptosis, increased production of ROS, and reduced mitochondrial membrane potential (MMP), associated with decreased total antioxidant capacity (TAC) and elevated activity of BChE in plasma. Therefore, evidence indicates that cytotoxicity, oxidative stress, and inflammatory responses may be involved in the multiplicity of adverse health outcomes related to contaminant exposure in waste collectors. It is thus necessary to implement and/or improve occupational health programs aimed at workers as well as mandatory inspections for the use of personal protective equipment.

Toxicity of Heavy Metals that Affect Germination, Development and Cell Cycle of Allium cepa L.

This study aimed to investigate the impact of heavy metals copper, cadmium, lead, aluminum and nickel, on the growth, physiology, metabolism, and cell cycle of Allium cepa L. Five treatments with increasing concentrations (0, 50, 100, 250, and 500 µM) were applied to the seeds. The results showed that the highest concentrations of copper and cadmium had phytotoxic and biochemical effects on the onion. Additionally, copper concentrations caused an increase in mitodepressive effect and chromosomal abnormalities. Aluminum also induced several chromosomal abnormalities. The study found that Cd > Cu > Pb > Ni > Al and Cu > Al > Ni > Pb > Cd had the highest phytotoxic and cytotoxic potentials, respectively. Furthermore, the UPGMA method revealed three divergent groups. These results suggest that heavy metals, especially copper, have a significant pollution potential when present in high concentrations.

Erythrocyte-cancer hybrid membrane-coated reduction-sensitive nanoparticles for enhancing chemotherapy efficacy in breast cancer.

Cell-membrane-coated biomimetic nanoparticles (NPs) have attracted great attention due to their prolonged circulation time, immune escape mechanisms and homotypic targeting properties. Biomimetic nanosystems from different types of cell -membranes (CMs) can perform increasingly complex tasks in dynamic biological environments thanks to specific proteins and other properties inherited from the source cells. Herein, we coated doxorubicin (DOX)-loaded reduction-sensitive chitosan (CS) NPs with 4T1 cancer cell -membranes (CCMs), red blood cell -membranes (RBCMs) and hybrid erythrocyte-cancer membranes (RBC-4T1CMs) to enhance the delivery of DOX to breast cancer cells. The physicochemical properties (size, zeta potential and morphology) of the resulting RBC@DOX/CS-NPs, 4T1@DOX/CS-NPs and RBC-4T1@DOX/CS-NPs, as well as their cytotoxic effect and cellular NP uptake in vitro were thoroughly characterized. The anti-cancer therapeutic efficacy of the NPs was evaluated using the orthotopic 4T1 breast cancer model in vivo. The experimental results showed that DOX/CS-NPs had a DOX-loading capacity of 71.76 ± 0.87 %, and that coating of DOX/CS-NPs with 4T1CM significantly increased the NP uptake and cytotoxic effect in breast cancer cells. Interestingly, by optimizing the ratio of RBCMs:4T1CMs, it was possible to increase the homotypic targeting properties towards breast cancer cells. Moreover, in vivo tumor studies showed that compared to control DOX/CS-NPs and free DOX, both 4T1@DOX/CS-NPs and RBC@DOX/CS-NPs significantly inhibited tumor growth and metastasis. However, the effect of 4T1@DOX/CS-NPs was more prominent. Moreover, CM-coating reduced the uptake of NPs by macrophages and led to rapid clearance from the liver and lungs in vivo, compared to control NPs. Our results suggest that specific self-recognition to source cells resulting in homotypic targeting increased the uptake and the cytotoxic capacity of 4T1@DOX/CS-NPs by breast cancer cells in vitro and in vivo. In conclusion, tumor-disguised CM-coated DOX/CS-NPs exhibited tumor homotypic targeting and anti-cancer properties, and were superior over targeting with RBC-CM or RBC-4T1 hybrid membranes, suggesting that the presence of 4T1-CM is critical for treatment outcome.

Marginal Mandibulectomy and Oral Rehabilitation of Xeroderma Pigmentosum Patient.

Xeroderma pigmentosum (XP) may cause tissue deformation in patients who have undergone oral cancer surgery requiring resection of any part of the mandible. Oral rehabilitation is a pivotal factor in the restoration of function and esthetics. The aim of this study was to report a clinical case of successful prosthetic rehabilitation of a 57-year-old woman who presented with marginal mandibulectomy and a significant reduction in maximal mouth opening after treatment for XP. With her reduced opening and considerable loss of structure and tissue, she had difficulty speaking, swallowing, and altered esthetics. The oral rehabilitation was performed with complete maxilla denture and mandible overdenture retained by 2 implants. This case demonstrates that the rehabilitation with mandible overdentures and complete maxilla dentures provide function and esthetic improvement in the mutilated area for XP patients with marginal mandibulectomies.

Th17/Treg-Related Intracellular Signaling in Patients with Chronic Obstructive Pulmonary Disease: Comparison between Local and Systemic Responses.

Th17/Treg imbalance plays a pivotal role in COPD development and progression. We aimed to assess Th17/Treg-related intracellular signaling at different COPD stages in local and systemic responses. Lung tissue and/or peripheral blood samples were collected and divided into non-obstructed (NOS), COPD stages I and II, and COPD stages III and IV groups. Gene expression of STAT3 and -5, RORγt, Foxp3, interleukin (IL)-6, -17, -10, and TGF-ß was assessed by RT-qPCR. IL-6, -17, -10, and TGF-ß levels were determined by ELISA. We observed increased STAT3, RORγt, Foxp3, IL-6, and TGF-ß gene expression and IL-6 levels in the lungs of COPD I and II patients compared to those of NOS patients. Regarding the systemic response, we observed increased STAT3, RORγt, IL-6, and TGF-ß gene expression in the COPD III and IV group and increased IL-6 levels in the COPD I and II group. STAT5 was increased in COPD III and IV patients, although there was a decrease in Foxp3 expression and IL-10 levels in the COPD I and II and COPD III and IV groups, respectively. We demonstrated that an increase in Th17 intracellular signaling in the lungs precedes this increase in the systemic response, whereas Treg intracellular signaling varies between the compartments analyzed in different COPD stages.

Identification and quantification of phenolic composition from different species of Jabuticaba (Plinia spp.) by HPLC-DAD-ESI/MSn.

The aim of this study was to investigate phenolic compounds in peel, pulp and seeds of five different jabuticabas - Plinia trunciflora, "cabinho", P. cauliflora, cultivars "paulista" and "canaã-açu", P. jaboticaba, "sabará" and P. phitrantha, "branca-vinho". In addition to the commonly reported cyanidin-3-glucoside and delphinidin3-glucoside, it was also found the unreported cyanidin-3-coumaroylglucoside in the peels. Flavonols derived from quercetin and myricetin were also detected in jaboticaba peels, along with a wide variety of derivatives of ellagic acid and methyl ellagic acid. The latter derivatives occurred in acylated forms, which were not usually found in jabuticabas. The pulps and seeds of jabuticabas contained large amounts of ellagitannins vescalagin and castalagin, as well as gallic and ellagic acids. The jabuticabas showed small amounts of catechin and gallocatechin. P. jaboticaba showed the highest levels of anthocyanins and flavonols derived from myricetin, and P. phitrantha presented the highest concentration of ellagitannins and flavan-3-ols.

Smear layer removal by passive ultrasonic irrigation and 2 new mechanical methods for activation of the chelating solution.

OBJECTIVES: The aim of this study was to compare smear layer removal by conventional application (CA), passive ultrasonic irrigation (PUI), EasyClean (EC), and XP-Endo Finisher (XPF), using 17% ethylenediaminetetraacetic acid (EDTA) after chemomechanical preparation, as evaluated with scanning electron microscopy (SEM). MATERIALS AND METHODS: Forty-five single-rooted human mandibular premolars were selected for this study. After chemomechanical preparation, the teeth were randomly divided into 5 groups according to the protocol for smear layer removal, as follows: G1 (control): CA of distilled water; G2 (CA): CA of 17% EDTA; G3 (PUI): 17% EDTA activated by PUI; G4 (EC): 17% EDTA activated by EC; and G5 (XPF): 17% EDTA activated by XPF. SEM images (×1,000) were obtained from each root third and scored by 3 examiners. Data were evaluated using the Kruskal-Wallis and Dunn tests (p < 0.05). RESULTS: In the apical third, there were no statistically significant differences among the groups (p > 0.05). In the cervical and middle thirds, the experimental groups performed better than the control group (p < 0.05); however, G2 presented better results than G3, G4, and G5 (p < 0.05), which showed no differences among one another (p > 0.05). CONCLUSIONS: No irrigation method was able to completely remove the smear layer, especially in the apical third. Using CA for the chelating solution performed better than any form of activation.

Distribution of Clinical NDM-1-Producing Gram-Negative Bacteria in Brazil.

New Delhi metallo-ß-lactamase (NDM)-producing bacteria have been identified at a worrying rate in Brazil since 2013. Owing to the need to understand the extent of their spread, this study reports the dissemination of blaNDM in different species of Gram-negative bacilli in different regions and states of Brazil. A total of 81 isolates from nine states were studied, including 11 species. All isolates carried blaNDM-1 variant and were considered multidrug resistant. Colistin and amikacin were the agents with higher activity compared with the other drugs tested. The findings indicate that the NDM-1 enzyme is already widespread in the country.

Concentration and Variety of Carbapenemase Producers in Recreational Coastal Waters Showing Distinct Levels of Pollution.

Carbapenemase-producing bacteria cause difficult-to-treat infections related to increased mortality in health care settings. Their occurrence has been reported in raw sewage, sewage-impacted rivers, and polluted coastal waters, which may indicate their spread to the community. We assessed the variety and concentration of carbapenemase producers in coastal waters with distinct pollution levels for 1 year. We describe various bacterial species producing distinct carbapenemases not only in unsuitable waters but also in waters considered suitable for primary contact.

Modified Carba NP test for the detection of carbapenemase production in gram-negative rods: optimized handling of multiple samples.

The modified Carba NP test presented here may be a valuable tool for laboratories interested in investigating a large number of carbapenemase-producing bacteria in a less-costly way. The test was evaluated against 48 carbapenemase-producing and carbapenemase-non-producing gram-negative bacteria. No false-positive results were obtained, but false-negative results were observed with OXA-23- and GES-carbapenemase-producing isolates. Aeromonas sp. are not testable by Modified Carba NP.