Assessing the potential fasting and postprandial mechanisms involved in the acute hypoglycemic and anti-hyperglycemic effects of four selected plants from Iran used in traditional Persian medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Persian medicine (TPM), people often use herbal infusions as a dosage form to treat diseases related to hyperglycemia, known as 'dam-kardeh'. Traditionally, herbal preparations of Eryngium bungei Boiss. (E. b), Tragopogon buphthalmoides (DC.) Boiss. (T. b), Salvia hydrangea DC. ex Benth. (S. h), and Juniperus polycarpos K. Koch. (J. p) are used to manage diabetes in Iran. However, there is no evidence of their effectiveness in controlling glucose levels and their mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate whether traditional doses of plant infusions can have hypoglycemic and/or anti-hyperglycemic effects during fasting and/or postprandial states and establish the basis for future research on their potential mechanisms of action. MATERIALS AND METHODS: The effects of traditional doses of herbal extracts on blood glucose levels in STZ-NA-induced hyperglycemic rats were investigated in 2-h acute tests during fasting and postprandial states (with a glucose load). In addition, the potential inhibitory effect in vitro of enzymes involved in relevant pathways, such as gluconeogenesis (fructose-1,6-bisphosphatase, FBPase and glucose-6-phosphatase, G6Pase), carbohydrate breakdown (intestinal α-glucosidases), and insulin sensitivity (protein tyrosine phosphatase 1B, PTP-1B) was evaluated. Acute toxicity tests were carried out and HPLC-SQ-TOF was used to analyze the chemical profiles of the plant extracts. RESULTS: In the fasting state, T. b, S. h, and E. b were as effective as glibenclamide in lowering blood glucose levels in hyperglycemic rats. Moreover, all three suppressed G6Pase and FBPase enzymatic activity by 90-97% and 80-91%, respectively. On the other hand, significant postprandial hypoglycemic efficacy was observed for E. b, S. h, and T. b. Based on the AUC values, T. b caused a reduction comparable to the therapeutic efficacy of repaglinide. When investigating the possible mechanisms of action involved in this activity, E. b, S. h, and T. b showed significant inhibition of PTP-1B in vitro (>70%). Finally, all plant extracts showed no signs of acute toxicity. Several compounds that may contribute to biological activities were identified, including phenolic acids and flavonoid glycosides. CONCLUSIONS: The present study supports the traditional use of T. b, E. b and S. h for the control of diabetes in the fasting and postprandial state. Moreover, these plants were found to be rich in bioactive compounds with hypoglycemic and antihyperglycemic activities. On the other hand, J. p, showed a modest effect only in the fasting state and after 90 min. Further studies are needed to expand these results by analyzing the chemical composition and using complementary experimental models.

Enhancing apple postharvest protection: Efficacy of pectin coatings containing Cryptococcus laurentii against Penicillium expansum.

The aim of this work is the application of pectin coatings containing Cryptococcus laurentii as a method of biocontrol of Penicillium expansum for postharvest protection of apples. For this purpose, the yeast was incorporated into a pectin matrix, and its viability and biocontrol activity in vitro and in vivo against P. expansum was evaluated over time. In addition, the influence of the sterilization process on coating thickness was studied. Results showed that pectin coating with C. laurentii enhanced mycelial growth inhibition in vitro studies, while no significant differences were observed in disease incidence and severity reduction in vivo studies. The sterilization process reduced the viscosity of the pectin solution, resulting in coating thicknesses ranging from 0.5 to 1 µm. As a general evaluation, in vitro and in vivo, biocontrol assays were useful in demonstrating better postharvest protection of the yeast at 7 °C concerning 25 °C.

Evaluating sacha inchi (Plukenetia volubilis) oil stability and physicochemical properties: A comparison between conventional extraction and supercritical fluids.

This study aimed to compare the effects of two extraction techniques (conventional n-hexane and supercritical CO2) on the oil extraction yields, fatty acids profile, anti-hyaluronidase activity, oxidative stability, and in vitro bioactivities of oils from Sacha Inchi (Plukenetia volubilis). Higher oil extraction yield (99 %) was achieved using the SC-CO2, although similar fatty acids profiles were depicted between both treatments (p < 0.05). The SC-CO2 oil presented higher anti-hyaluronidase (31 %) activity, but lower oxidative stability (5.05 h) compared to the solvent extraction (10 %, and 5.3 h, respectively). In vitro assays further revealed that the best human normal colon cells (FHC) cell viability (100 %), anti-inflammatory (50 % lower NO production), and antioxidant (20 % ROS reduction) activities were consistently observed in both extraction treatments at concentrations of 50 µg/mL and higher. These findings highlight the potential of supercritical CO2 extraction in yielding Sacha Inchi oil with enhanced bioactive properties without the disadvantages of the use of organic solvents extraction.

Unstressing the Reticulum: Nutritional Strategies for Modulating Endoplasmic Reticulum Stress in Obesity.

The progression of obesity involves several molecular mechanisms that are closely associated with the pathophysiological response of the disease. Endoplasmic reticulum (ER) stress is one such factor. Lipotoxicity disrupts endoplasmic reticulum homeostasis in the context of obesity. Furthermore, it induces ER stress by activating several signaling pathways via inflammatory responses and oxidative stress. ER performs crucial functions in protein synthesis and lipid metabolism; thus, triggers such as lipotoxicity can promote the accumulation of misfolded proteins in the organelle. The accumulation of these proteins can lead to metabolic disorders and chronic inflammation, resulting in cell death. Thus, alternatives, such as flavonoids, amino acids, and polyphenols that are associated with antioxidant and anti-inflammatory responses have been proposed to attenuate this response by modulating ER stress via the administration of nutrients and bioactive compounds. Decreasing inflammation and oxidative stress can reduce the expression of several ER stress markers and improve clinical outcomes through the management of obesity, including the control of body weight, visceral fat, and lipid accumulation. This review explores the metabolic changes resulting from ER stress and discusses the role of nutritional interventions in modulating the ER stress pathway in obesity.

Antifungal activity of poly(lactic acid) nanofibers containing the essential oil from Corymbia citriodora Hook or the monoterpenes ß-citronellol and citronellal against mycotoxigenic fungi.

Food contamination by mycotoxigenic fungi is one of the principal factors that cause food loss and economic losses in the food industry. The objective of this work was to incorporate the essential oil from Corymbia citriodora Hook and its constituents citronellal and ß-citronellol into poly(lactic acid) nanofibers; to characterize the nanofibers by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy and differential scanning calorimetry; to evaluate the antifungal activity by the fumigation method; to evaluate the antimycotoxigenic activity against Aspergillus carbonarius, Aspergillus ochraceus, Aspergillus westerdijkiae, Aspergillus flavus, and Aspergillus parasiticus; and to evaluate the morphology of these microorganisms. All the nanofibers had a regular, smooth, and continuous morphology. FTIR analyses confirmed that the active ingredients were incorporated into the polymer matrix. All samples exhibited antifungal and ochratoxigenic inhibitory activities of up to 100% and 99%, respectively, with the best results observed for (PLA + 30 wt% ß-citronellol) nanofibers and (PLA + 30 wt% citronellal) nanofibers. However, 100% inhibition of the production of aflatoxin B1 and B2 was not observed. The images obtained by SEM indicated that the nanofibers caused damage to the hyphae, caused a decrease in the production of spores, and caused deformation, rupture, and non-formation of the conid head, might be an alternative for the control of mycotoxigenic fungi.

Invasive candidiasis in a pediatric tertiary hospital: Epidemiology, antifungal susceptibility, and mortality rates.

Invasive infections caused by non-albicans Candida are increasing worldwide. However, there is still a lack of information on invasive candidiasis (IC) in the pediatric setting, including susceptibility profiles and clonal studies. We investigated the clinical, epidemiologic, and laboratory characteristics of IC, possible changes in antifungal susceptibility profiles over time, and the occurrence of clonality in our tertiary children's hospital. We analyzed 123 non-duplicate Candida isolates from sterile sites of pediatric patients in a tertiary hospital in southern Brazil, between 2016 and 2021. Data on demographics, comorbidities, and clinical outcomes were collected. Candida species distribution, antifungal susceptibility profiles, biofilm production, and molecular epidemiology of isolates were assessed using reference methods. The range of IC incidence was 0.88-1.55 cases/1000 hospitalized patients/year, and the IC-related mortality rate was 20.3%. Of the total IC cases, 42.3% were in patients aged < 13 months. Mechanical ventilation, parenteral nutrition, and intensive care unit (ICU) admission were common in this group. In addition, ICU admission was identified as a risk factor for IC-related mortality. The main site of Candida spp. isolation was blood, and non-albicans Candida species were predominant (70.8%). No significant clonal spread was observed among isolates of the three most commonly isolated species, and 99.1% of all isolates were biofilm producers. Non-albicans Candida species were predominant in this study. Notably, clonal expansion and emergence of antifungal drug resistance were not observed in our pediatric setting.

The epidemiology of invasive candidiasis has changed over time and there is still a lack of information in the pediatric setting. Non-albicans Candida species predominated in this study, clonal expansion and emergence of antifungal drug resistance were not observed in our pediatric setting.

Essential oils from Cuminum cyminum and Laurus nobilis and their principal constituents: evaluation of antifungal and antimycotoxigenic potential in Aspergillus species.

The antifungal and antimycotoxigenic activities of the essential oils (EO) from Cuminum cyminum and Laurus nobilis, and their respective principal compounds, cuminaldehyde and 1,8-cineole, were evaluated against fungi of the genus Aspergillus: A. carbonarius, A. niger, A. ochraceus, and A. westerdijkiae. The antifungal activity was determined by the contact method and the mycelial growth of the fungi was evaluated. Scanning electron microscopic (SEM) images were obtained to suggest modes of action of the compounds analysed. The antimycotoxigenic activity was determined by high-performance liquid chromatograph. Aspergillus carbonarius was completely inhibited by cumin EO (500 µl l-1), by laurel EO and by cuminaldehyde (5000 µl l-1). The cumin EO (500 µl l-1) completely inhibited the growth of A. niger. All the samples inhibited the mycelial growth of A. ochraceus, especially cumin EO and cuminaldehyde (250 µl l-1). Aspergillus westerdijkiae was completely inhibited by cumin EO and cuminaldehyde (1000 µl l-1), by laurel EO and 1,8-cineole (10 000 µl l-1). A decrease in the production of ochratoxin A (OTA) was observed post-treatment, except in A. ochraceus, only inhibited by laurel EO. SEM images showed morphological changes in fungal structures and spore inhibition post-treatment. The results confirmed the antifungal and antimycotoxigenic effect of EO and their principal constituents on fungi evaluated.

Trade-offs between selection of crude protein and tannins in growing lambs.

Tannins are phenolic compounds that provide benefits to ruminants due to their protein-binding affinities and antioxidant properties. However, tannins may also have negative orosensorial and postingestive effects that decrease feed intake. This study explored how lambs trade off the ingestion of crude protein (CP) with the ingestion of potentially beneficial and toxic condensed and hydrolyzable tannins, and the ensuing impacts on diet digestibility, animal performance, and blood parameters. Thirty-two lambs were housed in individual pens for 8 wk and had access to 2 isoenergetic diets that varied in the concentration of CP (High-high in protein [HP] or Low-least preferred [LP]) and the presence of a mix of condensed and hydrolyzable tannins (4% DM). Animals were assigned to 4 treatment groups (N = 8 lambs/group) and received a simultaneous offer of: HP and LP (Control); HP and LP + tannins (HP - LP+); HP+ tannins and LP (HP + LP-); and both HP and LP with tannins (HP + LP+). All lambs preferred HP over LP and they avoided tannins in the diets (P < 0.001). Dry matter and CP intake were the lowest in HP + LP- (P < 0.0001), and DMD did not differ between Control and the other groups (P > 0.05), but it was greater for HP - LP + (P < 0.0001). CP digestibility was greater for groups without tannins in HP (P < 0.0001), but average daily gain (ADG) did not differ among treatments (P > 0.05). No differences between Control and HP + LP + were found in plasma antioxidant activity, total phenolic concentration, or haptoglobin concentration (P > 0.05). Intake of tannins was HP + LP+ > HP + LP- > HP - LP + (P < 0.0001), and fecal excretion of nitrogen (N) was HP + LP+ > HP - LP+ = HP + LP- > Control (P < 0.05). In addition, intake of tannins with both diets reduced blood urea nitrogen (BUN) concentration relative to Control (P < 0.05), thus suggesting a shift in the partitioning of N excretion from urine to feces. In summary, lambs prioritized the selection of HP over LP, regardless of the presence of a tannin extract in either or both diets. Nevertheless, lambs modulated their tannin consumption as a function of the specific diet where the tannin extract was added, with increasing levels of intake as tannins were present in just LP, then in just HP, and finally in both diets. Dietary tannins did not constrain ADG and resulted in a shift in the partitioning of N excretion from urine to feces. Such shifts have been found to result in reduced production of environmental pollutants such as ammonia, nitrous oxide, and nitrates.

Tannins are plant chemicals that can provide benefits to ruminants due to their antioxidant activity and positive effects on nutrient uptake. However, tannins could also promote negative (i.e., toxic) effects on herbivores. This study explored how lambs build their diets when offered between 2 diets that varied in protein concentration (low or high), both with and without tannins (4%) and the ensuing consequences on diet digestibility, animal performance, and some blood parameters indicative of antioxidant activity and inflammation. All lambs preferred the high-over the low-protein diet, regardless of the inclusion of tannins in the diets. Digestibility of dry matter did not differ between lambs that had diet choices with or without tannins, and body weight gains were not different across all treatments. No differences were found among dietary treatment groups in blood antioxidant activity or indicators of inflammation. Tannin intake promoted a shift in the fate of nitrogen excretion from urine to feces, suggesting reductions in environmental pollutants such as ammonia, nitrous oxide, and nitrates. Thus, tannins did not promote negative impacts on animal performance with potential concomitant beneficial effects on the environment.

Antimicrobial and antibiofilm effect of promethazine on bacterial isolates from canine otitis externa: an in vitro study.

Otitis externa is an inflammatory disease of the external ear canal of complex and multifactorial etiology associated with recurrent bacterial infection. This study aimed to assess the antimicrobial and antibiofilm activity of promethazine against bacterial isolates from dogs with otitis externa, as well as the effect of this compound on the dynamics of biofilm formation over 120 h. Planktonic bacterial susceptibility to promethazine was evaluated to determine the minimum inhibitory concentrations (MIC). The minimum biofilm eradication concentration (MBEC) was also determined by broth microdilution. To evaluate the effect on biofilm growth, promethazine was tested at three concentrations MIC, MIC/2 and MIC/8, with daily readings at 48, 72, 96 and 120 h. The MICs of promethazine ranged from 48.83 to 781.25 µg mL-1. Promethazine significantly (P < 0.05) reduced mature biofilm biomass, with MBECs ranging from 48.8 to 6250 µg mL-1 and reduced (P < 0.01) biofilm formation for up to the 120-h, at concentrations corresponding to the MIC obtained against each isolate. Promethazine was effective against microorganisms associated with canine otitis externa. The data suggest that promethazine presents antimicrobial and antibiofilm activity and is a potential alternative to treat and prevent recurrent bacterial otitis in dogs. These results emphasize the importance of drug repurposing in veterinary otology as an alternative to reduce antimicrobial resistance.

Epinephrine and norepinephrine regulate the expression of virulence factors in Gallibacterium anatis.

Gallibacterium anatis is a member of the Pasteurellaceae family and is an opportunistic pathogen that causes gallibacteriosis in chickens. Stress plays a relevant role in promoting the development of pathogenicity in G. anatis. Epinephrine (E) and norepinephrine (NE) are relevant to stress; however, their effects on G. anatis have not been elucidated. In this work, we evaluated the effects of E and NE on the growth, biofilm formation, expression of adhesins, and proteases of two G. anatis strains, namely, the hemolytic 12656-12 and the nonhemolytic F149T biovars. E (10 µM/mL) and NE (30 and 50 µM/mL) increased the growth of G. anatis 12656-12 by 20 % and 25 %, respectively. E did not affect the growth of F149T, whereas 40 µM/mL NE decreased bacterial growth by 25 %. E and NE at a dose of 30-50 µM/mL upregulated five fibrinogen adhesins in the 12565-12 strain, whereas no effect was observed in the F149T strain. NE increased proteolytic activity in both strains, whereas E diminished proteolytic activity in the 12656-12 strain. E and NE reduced biofilm formation (30 %) and increased Congo red binding (15 %) in both strains. QseBC is the E and NE two-component detection system most common in bacteria. The qseC gene, which is the E and NE receptor in bacteria, was identified in the genomic DNA of the 12565-12 and F149TG. anatis strains via PCR amplification. Our results suggest that QseC can detect host changes in E and NE concentrations and that catecholamines can modulate the expression of several virulence factors in G. anatis.

Marine Bacillus pumilus substances exhibit antimicrobial effect on multidrug-resistant Staphylococcus aureus.

AIMS: This study aimed to assess the antimicrobial potential of Bp1-AdE, produced by Bacillus pumilus 64-1, and to investigate its mode of action against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). METHODS AND RESULTS: Bp-1AdE, derived from sponge-associated B. pumilus, exhibited bactericidal activity at 1 550 µg ml-1 against S. aureus ATCC29213 and MRSA strains. Light and fluorescence microscopy revealed drastic cell lysis of S. aureus treated with Bp-1AdE. Scanning and transmission electron microscopy suggested that Bp-1AdE disrupts the cytoplasmic membrane. Toxicity assays showed that Bp-1AdE was non-toxic to Tenebrio molitor larvae. Liquid chromatography-mass spectrometry and Global Natural Product Social spectral libraries identified four substances within Bp-1AdE, including aliphatic alcohols [3,4-dipentylhexane-2,5-diol and 1,1'-(4,5-dibutyl-3,6-dimethylcyclohexane-1,2-diyl)bis(ethan-1-one)] and terpenoids (cholic acid and canrenone). CONCLUSIONS: Bp-1AdE demonstrated selective toxicity and bactericidal activity, highlighting its potential for controlling infections caused by multidrug-resistant S. aureus strains.

Isoflurane preconditioning protects against renal ischemia/reperfusion injury in diabetes via activation of the Brg1/Nrf2/HO-1 signaling pathway.

PURPOSE: To examine whether isoflurane preconditioning (IsoP) has a protective effect against renal ischemia/reperfusion injury (I/RI) in diabetic conditions and to further clarify the underlying mechanisms. METHODS: Control and streptozotocin-induced diabetic rats were randomly assigned to five groups, as follows: normal sham, normal I/R, diabetic sham, diabetic I/R, and diabetic I/R + isoflurane. Renal I/RI was induced by clamping renal pedicle for 45 min followed by reperfusion for 24 h. IsoP was achieved by exposing the rats to 2% isoflurane for 30 min before vascular occlusion. Kidneys and blood were collected after reperfusion for further analysis. Renal histology, blood urea nitrogen, serum creatinine, oxidative stress, inflammatory cytokines, and renal cell apoptosis were assessed. Furthermore, the expression of brahma related gene 1 (Brg1), nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and nuclear factor-κB (NF-κB) were determined. RESULTS: Compared with control, diabetic rats undergoing I/R presented more severe renal injury, oxidative stress, inflammatory reaction, and apoptosis with the impairment of Brg1/Nrf2/HO-1 signaling. All these alterations were significantly attenuated by pretreatment with isoflurane. CONCLUSIONS: These findings suggest that isoflurane could alleviate renal I/RI in diabetes, possibly through improving Brg1/Nrf2/HO-1 signaling.

The dynamin inhibitor, dynasore, prevents zoledronate-induced viability loss in human gingival fibroblasts by partially blocking zoledronate uptake and inhibiting endosomal acidification.

OBJECTIVE: For treatment of medication-related osteonecrosis of the jaw, one proposed approach is the use of a topical agent to block entry of these medications in oral soft tissues. We tested the ability of phosphonoformic acid (PFA), an inhibitor of bisphosphonate entry through certain sodium-dependent phosphate contransporters (SLC20A1, 20A2, 34A1-3) as well as Dynasore, a macropinocytosis inhibitor, for their abilities to prevent zoledronate-induced (ZOL) death in human gingival fibroblasts (HGFs). METHODOLOGY: MTT assay dose-response curves were performed to determine non-cytotoxic levels of both PFA and Dynasore. In the presence of 50 µM ZOL, optimized PFA and Dynasore doses were tested for their ability to restore HGF viability. To determine SLC expression in HGFs, total HGF RNA was subjected to quantitative real-time RT-PCR. Confocal fluorescence microscopy was employed to see if Dynasore inhibited macropinocytotic HGF entry of AF647-ZOL. Endosomal acidification in the presence of Dynasore was measured by live cell imaging utilizing LysoSensor Green DND-189. As a further test of Dynasore's ability to interfere with ZOL-containing endosomal maturation, perinuclear localization of mature endosomes containing AF647-ZOL or TRITC-dextran as a control were assessed via confocal fluorescence microscopy with CellProfiler™ software analysis of the resulting photomicrographs. RESULTS: 0.5 mM PFA did not rescue HGFs from ZOL-induced viability loss at 72 hours while 10 and 30 µM geranylgeraniol did partially rescue. HGFs did not express the SLC transporters as compared to the expression in positive control tissues. 10 µM Dynasore completely prevented ZOL-induced viability loss. In the presence of Dynasore, AF647-ZOL and FITC-dextran co-localized in endosomes. Endosomal acidification was inhibited by Dynasore and perinuclear localization of both TRITC-dextran- and AF647-ZOL-containing endosomes was inhibited by 30 µM Dynasore. CONCLUSION: Dynasore prevents ZOL-induced viability loss in HGFs by partially interfering with macropinocytosis and by inhibiting the endosomal maturation pathway thought to be needed for ZOL delivery to the cytoplasm.

Effects of Dietary Agavin on the Gut Microbiota of the Nile Tilapia (Oreochromis niloticus) Reared at High Densities.

High-density stress can lead to dysbiotic microbiota, affecting the organism's metabolic, and protective functions. Agavin is a fructan with prebiotic properties that regulate the gut microbiota by promoting the growth of beneficial bacteria. This study evaluated the effect of agavin on the gut microbiota using Next-Generation Sequencing (NGS) and its correlation with the growth parameters. Four groups of fish were fed different diets: a control diet (negative and positive control), without agavin supplementation, and two experimental diets supplemented with agavin at 20 g kg-1 and 40 g kg-1. Nile tilapias (1.04 g ± 0.01 g) were fed for 110 days. After 90 days of feeding, fish were subjected to high-density stress (63 kg m-3) for 20 days, except for the negative control. NGS detected 1579 different operational taxonomic units in the samples. In the correlation analysis of growth parameters, the families Vibrionaceae and Methyloligillaceae showed a positive correlation with fish growth parameters, these results may serve to know the relation of agavin and microbiota on the growth performance, as well as the metabolic activities of families in tilapia. Furthermore, high-density stress and agavin supplementation modify the gut microbiota in tilapia. At a low-density, supplementation with 20 g kg-1 agavin promoted the growth of the potentially beneficial families Sphingomonadaceae, Oxalobacteriaceae, and Chitinophagaceae; at high densities, reduced the abundance of pathogenic families (Vibrionaceae and Aeromonadaceae). These results suggest that, under stress conditions, agavin can stimulate the growth of potentially beneficial bacteria and reduce the growth of potentially pathogenic bacteria, suggesting its potential use as a prebiotic in aquaculture.

The therapeutic potential of reduced graphene oxide in attenuating cuprizone-induced demyelination in mice.

Reduced graphene oxide (rGO) has unique physicochemical properties that make it suitable for therapeutic applications in neurodegenerative scenarios. This study investigates the therapeutic potential of rGO in a cuprizone-induced demyelination model in mice through histomorphological techniques and analysis of biochemical parameters. We demonstrate that daily intraperitoneal administration of rGO (1 mg ml-1) for 21 days tends to reduce demyelination in theCorpus callosumby decreasing glial cell recruitment during the repair mechanism. Additionally, rGO interferes with oxidative stress markers in the brain and liver indicating potential neuroprotective effects in the central nervous system. No significant damage to vital organs was observed, suggesting that multiple doses could be used safely. However, further long-term investigations are needed to understand rGO distribution, metabolism, routes of action and associated challenges in central neurodegenerative therapies. Overall, these findings contribute to the comprehension of rGO effectsin vivo, paving the way for possible future clinical research.

Comparative transcriptional analysis between susceptible and resistant populations of Aedes (Stegomyia) aegypti (Linnaeus, 1762) after malathion exposure.

Aedes aegypti is an important vector of arboviruses, including dengue, chikungunya and Zika. The application of synthetic insecticides is a frequently used strategy to control this insect. Malathion is an organophosphate insecticide that was widely used in Brazil in the 1980s and 1990s to control the adult form of A. aegypti. In situations where resistance to currently used insecticides is detected, the use of malathion may be resumed as a control measure. Many studies have confirmed resistance to malathion, however, comparative studies of differential gene expression of the entire transcriptome of resistant and susceptible insects are scarce. Therefore, understanding the molecular basis of resistance to this insecticide in this species is extremely important. In this paper, we present the first transcriptomic description of susceptible and resistant strains of A. aegypti challenged with malathion. Guided transcriptome assembly resulted in 39,904 transcripts, where 2133 differentially expressed transcripts were detected, and three were validated by RT-qPCR. Enrichment analysis for these identified transcripts resulted in 13 significant pathways (padj < 0.05), 8 associated with down-regulated and 5 with up-regulated transcripts in treated resistant insects. It was possible to divide the transcripts according to the mechanism of action into three main groups: (i) genes involved in detoxification metabolic pathways; (ii) genes of proteins located in the membrane/extracellular region; and (iii) genes related to DNA integration/function. These results are important in advancing knowledge of genes related to resistance mechanisms in this insect, enabling the development of effective technologies and strategies for managing insecticide resistance.

Effects and mechanisms of Salvia miltiorrhiza Bunge extract on myocardial cell apoptosis in rat heart failure model.

PURPOSE: This work aimed to investigate the effects of Tanshinone IIA (Tan IIA) on myocardial cell (MC) apoptosis in a rat model of heart failure (HF). METHODS: Tan IIA was extracted from Salvia miltiorrhiza Bunge (SMB) using an ethanol reflux method. Fifty rats were randomly divided into five groups: sham (no treatment), mod (HF model establishment), low dose (LD: 0.1 mL/kg Tan IIA), medium dose (MD: 0.3 mL/kg Tan IIA), and high dose (HD: 0.5 mL/kg Tan IIA), with 10 rats in each group. The effects of different doses of Tan IIA on cardiac function, MC apoptosis, and the levels of proteins associated with the PI3K/Akt/mTOR signaling pathway were compared. RESULTS: Mod group showed a significant decrease in systolic arterial pressure, mean arterial pressure, heart rate, left ventricular systolic pressure, left ventricular ejection fraction, left ventricular fractional shortening, and the levels of p-PI3K, p-Akt, and p-mTOR proteins versus sham group (p < 0.05). Additionally, the left ventricular end-diastolic diameter (LVIDd), end-systolic diameter, diastolic pressure, and MC apoptosis were significantly increased (p < 0.05). LD, MD, and HD groups exhibited significant improvements across various indicators of cardiac function and MC apoptosis versus mod group (p < 0.05). CONCLUSIONS: Tan IIA may improve cardiac function and inhibit MC apoptosis in rats with HF by modulating the PI3K/Akt/mTOR signaling pathway.

Effect of napabucasin and doxorubicin via the Jak2/Stat3 signaling pathway in suppressing the proliferation of neuroblastoma cells.

PURPOSE: Napabucasin (NP) is a natural compound that can suppress cancer cell proliferation and cell cycle by inhibition of the signal transducer and activator of transcription 3 (STAT3) gene. We examined the effects of NP on the proliferation and invasion of neuroblastoma cells (SH-SY5Y). METHODS: Human neuroblastoma SH-SY5Y cell line was used in this study. NP was administered to groups at the doses of 0.3-1 µM. Cell viability was analyzed by MTT assay. Real-time quantitative reverse transcription polymerase chain reaction and western blot analysis assessed the expressions of interleukin (IL)-6 dependent Jak2/Stat3 signaling pathway. The MTT cell viability method was applied to determine the antagonistic-synergistic effects and inhibitory concentration (IC50) doses of doxorubicin (DX) and NP. RESULTS: It was determined that 0.3-1 µM doses of NP killed the cells almost completely after 48 hours, and also that Jak2/Stat3 expressions decreased dose-dependently via IL-6. At the protein level, NP and DX were found to reduce Jak2 and Stat3 levels. CONCLUSIONS: NP showed that it suppresses the proliferation of neuroblastoma cells. Due to its inhibitory effect on Jak2 and Stat3, it can be used to prevent invasion of SH-SY5Y cells. NP, which can inactivate Jak2/Stat3, can be used as a treatment agent by combining with DX in proliferation pathway in neuroblastoma.

Caffeine mitigates tamoxifen-induced fatty liver in Wistar rats.

PURPOSE: Tamoxifen, a widely used drug for breast cancer treatment, is associated with adverse effects on the liver, including the development of fatty liver. This study aimed to investigate the potential protective effect of caffeine against tamoxifen-induced fatty liver in Wistar rats. METHODS: Rats were divided into normal control, tamoxifen + saline, and tamoxifen + caffeine. Plasma samples were assessed for biochemical markers related to oxidative stress, inflammation, liver function, and cell damage. Additionally, liver histopathology was examined to quantify the extent of fatty infiltration. RESULTS: In the tamoxifen + saline group, elevated levels of plasma malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), alanine aminotransferase (ALT), cytokeratin 18, and soluble ST2 were observed compared to the normal control group, indicating increased oxidative stress, inflammation, and liver injury (p < 0.01). Moreover, histopathological examination revealed a significant increase in fatty infiltration (p < 0.001). However, in the tamoxifen + caffeine group, these markers were markedly reduced (p < 0.05, p < 0.01), and fatty infiltration was significantly mitigated (p < 0.001). CONCLUSIONS: The findings suggest that caffeine administration attenuates tamoxifen-induced fatty liver in rats by ameliorating oxidative stress, inflammation, liver injury, and cell damage. Histopathological evidence further supports the protective role of caffeine. This study highlights the potential of caffeine as a therapeutic intervention to counter tamoxifen-induced hepatic complications, contributing to the optimization of breast cancer treatment strategies.

Prenatal and postnatal cocaine exposure enhances the anxiety- and depressive-like behaviors in rats: An ontogenetic study.

BACKGROUND: Prenatal and postnatal exposure to drugs such as cocaine is a public health problem that causes deficits in brain development and function in humans and animals. One of the main effects of prenatal and postnatal cocaine exposure is increased vulnerability to developing the substance use disorder at an early age. Furthermore, the negative emotional states associated with cocaine withdrawal increase the fragility of patients to relapse into drug abuse. In this sense, prenatal and postnatal cocaine exposure enhanced the cocaine- and nicotine-induced locomotor activity and locomotor sensitization, and rats exposed prenatally to cocaine displayed an increase in anxiety- and depressive-like behaviors in adulthood (PND 60-70). OBJECTIVE: Therefore, the objective of this study was to determine the effect of prenatal and postnatal cocaine exposure on anxiety- and depressive-like behaviors at different ages (30, 60, 90, and 120 days of age) in rats. METHODS: The study was divided into two stages: prenatal and postnatal. In the prenatal stage, a group of pregnant female Wistar rats was administered daily from GD0 to GD21 cocaine (cocaine pre-exposure group), and another group of pregnant female rats was administered daily saline (saline pre-exposure group). In the postnatal stage, during lactation (PND0 to PND21), pregnant rats received administration of cocaine or saline, respectively. Of the litters resulting from the cocaine pre-exposed and saline pre-exposed pregnant female groups, only the male rats were used for the recording of the anxiety- and depressive-like behaviors at different postnatal ages (30, 60, 90, and 120 days), representative of adolescence, adult, adulthood, and old age. RESULTS: The study found that prenatal and postnatal cocaine exposure generated age-dependent enhancement in anxiety- and depressive-like behaviors, being greater in older adult (PND 120) rats than in adolescent (PND 30) or adults (PND 60-90) rats. CONCLUSIONS: This suggests that prenatal and postnatal cocaine exposure increases anxiety- and depressive-like behaviors, which may increase the vulnerability of subjects to different types of drugs in young and adult age.