Statins enhance the efficacy of HER2-targeting radioligand therapy in drug-resistant gastric cancers.

Human epidermal growth factor receptor 2 (HER2) is overexpressed in various cancer types. HER2-targeting trastuzumab plus chemotherapy is used as first-line therapy for HER2-positive recurrent or primary metastatic gastric cancer, but intrinsic and acquired trastuzumab resistance inevitably develop over time. To overcome gastric cancer resistance to HER2-targeted therapies, we have conjugated trastuzumab with a beta-emitting therapeutic isotope, lutetium-177, to deliver radiation locally to gastric tumors with minimal toxicity. Because trastuzumab-based targeted radioligand therapy (RLT) requires only the extramembrane domain binding of membrane-bound HER2 receptors, HER2-targeting RLT can bypass any resistance mechanisms that occur downstream of HER2 binding. Leveraging our previous discoveries that statins, a class of cholesterol-lowering drugs, can enhance the cell surface-bound HER2 to achieve effective drug delivery in tumors, we proposed that the combination of statins and [177Lu]Lu-trastuzumab-based RLT can enhance the therapeutic efficacy of HER2-targeted RLT in drug-resistant gastric cancers. We demonstrate that lovastatin elevates cell surface HER2 levels and increases the tumor-absorbed radiation dose of [177Lu]Lu-DOTA-trastuzumab. Furthermore, lovastatin-modulated [177Lu]Lu-DOTA-trastuzumab RLT durably inhibits tumor growth and prolongs overall survival in mice bearing NCI-N87 gastric tumors and HER2-positive patient-derived xenografts (PDXs) of known clinical resistance to trastuzumab therapy. Statins also exhibit a radioprotective effect, reducing radiotoxicity in a mice cohort given the combination of statins and [177Lu]Lu-DOTA-trastuzumab. Since statins are commonly prescribed to patients, our results strongly support the feasibility of clinical studies that combine lovastatin with HER2-targeted RLT in HER2-postive patients and trastuzumab-resistant HER2-positive patients.

Angiotensin-converting enzymes 1 and 2 in the feces: presence and catalytic activity in the rat 2,4,6-trinitrobenzene sulfonic acid-induced model of colitis.

BACKGROUND AND AIM: Inflammatory bowel disease is challenging to diagnose. Fecal biomarkers offer noninvasive solutions. The renin-angiotensin-aldosterone system is implicated in intestinal inflammation. Angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) regulate its activity, but conflicting findings on these enzymes in colitis require further investigation. We aimed to assess ACE and ACE2 presence and activities in the feces, serum, and colon of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced rats. METHODS: Colitis was induced in male rats by rectal instillation of a 21% ethanolic TNBS solution. After rats' sacrifice, colonic portions, serum, and feces were collected. ACE and ACE2 presence in the feces was analyzed by western Blot, and colonic and serum enzymes' concentrations were quantified using ELISA kits. ACE activity was assessed using Hippuryl-His-Leu and Z-Phe-His-Leu as substrates. ACE2 activity was assessed using Mca-APK (Dnp) as a substrate in the presence and absence of DX600 (ACE2 inhibitor). RESULTS: An ACE isoform of ~70 kDa was found only in the feces of TNBS-induced rats. ACE concentration was higher than that of ACE2 in the serum and the inflamed colon. ACE N-domain activity was higher than that of the C-domain in all matrices. ACE2 activity was higher in the feces of TNBS-induced animals compared to controls. CONCLUSION: A 70 kDa ACE isoform only detected in the feces of TNBS-induced rats may have translational relevance. ACE N-domain seems to play a significant role in regulating colonic lesions. Further research using human samples is necessary to validate these findings.

Toxicological assessment of the Achyrocline satureioides aqueous extract in the Caenorhabditis elegans alternative model.

Achyrocline satureioides, popularly called "marcela" in Brazil, is used in traditional medicine in South America. A. satureioides, inflorescences are used for many conditions, including to minimize the Sars-Cov-2 symptoms. Therefore, the aim of this study was to determine the toxicity profile of A. satureioides aqueous extract (ASAE), using the Caenorhabditis elegans (C. elegans) alternative model. Survival, reproduction, development, and transgenerational assays were performed. The effects of ASAE were investigated under conditions of thermal stress and presence of oxidant hydrogen peroxide (H2O2). In addition, C. elegans strains containing high antioxidant enzyme levels and elevated lineages of daf-16, skn-1 and daf-2 regulatory pathways were examined. The ASAE LC50 value was found to be 77.3 ± 4 mg/ml. The concentration of ASAE 10 mg/ml (frequently used in humans) did not exhibit a significant reduction in worm survival at either the L1 or L4 stage, after 24 or 72 hr treatment. ASAE did not markedly alter the body area. In N2 strain, ASAE (10 or 25 mg/ml) reversed the damage initiated by H2O2. In addition, ASAE protected the damage produced by H2O2 in strains containing significant levels of sod-3, gst-4 and ctl - 1,2,3, suggesting modulation in these antioxidant systems by this plant extract. ASAE exposure activated daf-16 and skn-1 stress response transcriptional pathways independently of daf-2, even under extreme stress. Data suggest that ASAE, at the concentrations tested in C. elegans, exhibits a reliable toxicity profile, which may contribute to consideration for safe use in humans.

Biodistribution and intestinal inflammatory response following voluntary oral intake of silver nanoparticles by C57BL/6J mice.

Silver nanoparticles (AgNP) are among the most widely commercialized nanomaterials globally, with applications in medicine and the food industry. Consequently, the increased use of AgNP in the food industry has led to an unavoidable rise  in human exposure to these nanoparticles. Their widespread use raises concerns about potential hazards to human health, specifically their intestinal pro-inflammatory effects. Thus, the main objective of this study was to evaluate the biological effects of two subacute doses of 5 nm polyvinylpyrrolidone (PVP)-AgNP in C57BL/6J mice. One mg/kg body weight or 10 mg/kg bw was provided once a day for 14 days, using a new technology (HaPILLness) that allows voluntary, stress-free, and accurate oral dosing. It was observed that after oral ingestion, while AgNP is biodistributed throughout the entire organism, most of the ingested dose is excreted in the feces. The passage and accumulation of AgNP throughout the intestine instigated a prominent inflammatory response, marked by significant histological, vascular, and cellular transformations. This response was driven by the activation of the nuclear factor-кB (NF-кB) inflammatory pathway, ultimately leading to the generation of multiple cytokines and chemokines.

Toxicological profile of the Hymenaea courbaril stem bark hydroalcoholic extract using in vitro bioassays and an alternative in vivo Caenorhabditis elegans model.

Hymenaea genus has been used in folk medicine in Brazil, but few studies investigated its toxicity profile. Thus, the aim of this study was to determine toxicological parameters of Hymenaea courbaril stem bark hydroalcoholic extract by utilizing three cell lines including murine macrophages (RAW 264.7), mouse fibroblast cells (L929) and human lung fibroblast (MRC-5), as well as Salmonella/microsome assay, and in vivo Caenorhabditis elegans model. The predominant detected phytoconstituents in the extract were coumarins, flavonoids, phenolics, tannins and saponins and by HPLC analysis, astilbin (AST) was found to be the main component. The DPPH assay demonstrated that H. courbaril hydroalcoholic extract exhibited potent antioxidant activity, with an IC50 of 3.12 µg/ml. The extract at concentrations of 400 and 800 µg/ml decreased cell viability 48 hr after treatment in L929 and MRC-5 cell lines. In the Raw 264.7 strain, just the highest concentration (800 µg/ml) lowered cell viability within 48 hr following exposure. The concentration of 100 µg/ml did not markedly affect cell viability in the trypan blue assay. In the alkaline comet assay the extract was found to be non-genotoxic. In the Ames test, the extract exhibited low mutagenic potential without metabolic activation, since only the highest concentrations produced an effect. H. courbaril extract only affected the survival of C. elegans at concentrations of 800 and 1600 µl/ml. These findings demonstrate that H. courbaril extract appears to exert low toxicity as evidenced in vitro and mutagenicity assays; however, the biological relevance of the response of C. elegans survival to safety assessments needs further studies.

Recommended rates of azoxystrobin and tebuconazole seem to be environmentally safe but ineffective against target fungi.

The use of fungicides in agriculture has been playing a role in the enhancement of agricultural yields through the control of pathogens causing serious diseases in crops. Still, adverse environmental and human health effects resulting from its application have been reported. In this study, the possibility of readjusting the formulation of a commercial product combining azoxystrobin and tebuconazole (active ingredients - AIs; Custodia®) towards environmentally safer alternative(s) was investigated. Specifically, the sensitivity of non-target aquatic communities to each AI was first evaluated by applying the Species Sensitivity Distributions (SSDs) approach. Then, mixtures of these AIs were tested in a non-target organism (Raphidocelis subcapitata) denoting sensitivity to both AIs as assessed from SSDs. The resulting data supported the design of the last stage of this study, where mixtures of those AIs at equivalent vs. alternative ratios and rates as in the commercial formulation were tested against two target fungal species: Pyrenophora teres CBS 123929 and Rhynchosporium secalis CBS 110524. The comparison between the sensitivity of non-target aquatic species and the corresponding efficacy towards target fungi revealed that currently applied mixture and rates of these AIs are generally environmentally safe (antagonistic interaction; concentrations below the EC1 for R. subcapitata and generally below the HC5 for aquatic non-target communities), but ineffective against target organisms (maximum levels of inhibition of 70 and 50% in P. teres CBS 123929 and R. secalis CBS 110524, respectively). Results additionally suggest a potentiation of the effects of the AIs by the other formulants added to the commercial product at tested rates. Overall, this study corroborates that commercial products can be optimized during design stages based on a systematic ecotoxicological testing for ingredient interactions and actual efficacy against targets. This could be a valuable pathway to reduce environmental contamination during transition to a more sustainable agricultural production.

Effect of hydrocolloid concentration in low-calorie orange jellies on preservation of bioactive compounds and antioxidant capacity.

The purpose of this paper was to avaliate of the concentration of hydrocolloids (low methoxyl pectin [LMP], guar gum [GG], and carrageenan gum [CG]) in low-calorie orange jellies in order to maximize the amount of bioactive compounds and antioxidant capacity, and to study the influence on degradation these compounds. A mixture design with seven tests was used to analyze the total phenolic compounds, ascorbic acid (vitamin C) and antioxidant capacity (ABTS, DPPH and ß-carotene/linoleic acid methods). The results were analyzed by response surface methodology and the Scott-Knott mean test at a significance level of 5% (p ≤ 0.05). In general, the regions containing 0.5% GG and 0.5% GC had higher levels of the variables under study, and this combination preserved the bioactive compounds and antioxidant activity of jellies in relation to that of orange juice.

Effect of calcium chloride and gelling agents on the physicochemical and sensory characteristics of sugar-free banana preserves.

Banana preserve is produced by mixing the puree of the fruit with sucrose and organic acids. However, concerns about body esthetics or health reasons have encouraged the search for low-calorie products. Therefore, the objective of this study was to evaluate the effect of calcium chloride (CaCl2), carrageenan gum, and low methoxyl pectin (LM-pectin) on the physicochemical and sensory characteristics of sugar-free banana preserves. By using a central composite rotational design (CCRD) of 2³ + 6 axial points + 4 central points, we obtained 18 formulations that were further tested. Lower CaCl2 concentrations (0.54% to 0.61%) resulted in preserves with lower pH and more vivid color. The increased concentration of LM-pectin (1.40% to 1.64%) resulted in formulations with a yellowish-red hue and with lower moisture, thus, reducing the flavor and purchase intention of the product. Higher concentrations of carrageenan gum (1.04% to 1.15%) decreased the perception of banana preserve aroma. Therefore, concentrations of CaCl2 ranging from 0.54% to 0.61%, carrageenan gum ranging from 0.74% to 0.89% and LM-pectin ranging from 1.40% to 1.64% resulted in sugar-free banana preserves with ideal sweetness and consistency and were, therefore, more acceptable.

Rheological parameters of mixed Brazilian Cerrado fruits sugar-free preserves: the effect of body agents.

The aim of this study was to evaluate the effect of the bodying agents (erythritol, sorbitol, xylitol, and polydextrose) and their mixtures on the preparation of mixed Brazilian Cerrado fruit preserves (marolo, soursop, and sweet passion fruit). Mixture design was used for product optimization and the preserves were evaluated by texture profile, stress relaxation test, and uniaxial compression test. The research data were analyzed using regression equations on SAS software. The results indicated that the rheological parameters were affected by the body agents. Erythritol should not be used as an isolated component because it provoked changes in the properties of the final product (harder and brittle preserves); xylitol and sorbitol made preserves more elastic, cohesive, and more fragile; and polydextrose showed a synergistic effect with erythritol for rupture deformation and lesser effects for hardness, adhesiveness, and gumminess.

Preputial lymphangioma in a stallion: First report.

This short communication describes a case of a 30-year-old stallion with a mass on the base of the penis causing paraphimosis. The patient was submitted to anti-inflammatory and diuretic therapy with no signs of improvement, so 16 days after the lesion was detected, the animal was euthanized. Necropsy was performed, and histopathological assessment of the lesion was conducted. The mass was composed primarily of channels and cavernous structures, lined by elongated cells of vascular origin, located in the preputium. The lesion was diagnosed as a preputial lymphangioma. To the authors' best knowledge, the anatomical location of this neoplasm (which is rare in veterinary medicine) has not been previously reported.

Using artificial intelligence to predict the final color of leucite-reinforced ceramic restorations.

OBJECTIVES: The aim of this study was to evaluate the accuracy of machine learning regression models in predicting the final color of leucite-reinforced glass CAD/CAM ceramic veneer restorations based on substrate shade, ceramic shade, thickness and translucency. METHODS: Leucite-reinforced glass ceramics in four different shades were sectioned in thicknesses of 0.3, 0.5, 0.7, and 1.2 mm. The CIELab coordinates of each specimen were obtained over four different backgrounds (black, white, A1, and A3) interposed with an experimental translucent resin cement using a calibrated spectrophotometer. The color change (CIEDE2000) values, as well as all the CIELab values for each one of the experimental groups, were submitted to 28 different regression models. Each regression model was adjusted according to the weights of each dependent variable to achieve the best-fitting model. RESULTS: Different substrates, ceramic shades, and thicknesses influenced the L, a, and b of the final restoration. Of all variables, the substrate influenced the final ceramic shade most, followed by the ceramic thickness and the L, a, and b of the ceramic. The decision tree regression model had the lowest mean absolute error and highest accuracy to predict the shade of the ceramic restoration according to the substrate shade, ceramic shade and thickness. CLINICAL SIGNIFICANCE: The machine learning regression model developed in the study can help clinicians predict the final color of the ceramic veneers made with leucite-reinforced glass CAD/CAM ceramic HT and LT when cemented with translucent cements, based on the color of the substrate and ceramic thicknesses.

A review on aquatic toxins - Do we really know it all regarding the environmental risk posed by phytoplankton neurotoxins?

Aquatic toxins are potent natural toxins produced by certain cyanobacteria and marine algae species during harmful cyanobacterial and algal blooms (CyanoHABs and HABs, respectively). These harmful bloom events and the toxins produced during these events are a human and environmental health concern worldwide, with occurrence, frequency and severity of CyanoHABs and HABs being predicted to keep increasing due to ongoing climate change scenarios. These contexts, as well as human health consequences of some toxins produced during bloom events have been thoroughly reviewed before. Conversely, the wider picture that includes the non-human biota in the assessment of noxious effects of toxins is much less covered in the literature and barely covered by review works. Despite direct human exposure to aquatic toxins and related deleterious effects being responsible for the majority of the public attention to the blooms' problematic, it constitutes a very limited fraction of the real environmental risk posed by these toxins. The disruption of ecological and trophic interactions caused by these toxins in the aquatic biota building on deleterious effects they may induce in different species is paramount as a modulator of the overall magnitude of the environmental risk potentially involved, thus necessarily constraining the quality and efficiency of the management strategies that should be placed. In this way, this review aims at updating and consolidating current knowledge regarding the adverse effects of aquatic toxins, attempting to going beyond their main toxicity pathways in human and related models' health, i.e., also focusing on ecologically relevant model organisms. For conciseness and considering the severity in terms of documented human health risks as a reference, we restricted the detailed revision work to neurotoxic cyanotoxins and marine toxins. This comprehensive revision of the systemic effects of aquatic neurotoxins provides a broad overview of the exposure and the hazard that these compounds pose to human and environmental health. Regulatory approaches they are given worldwide, as well as (eco)toxicity data available were hence thoroughly reviewed. Critical research gaps were identified particularly regarding (i) the toxic effects other than those typical of the recognized disease/disorder each toxin causes following acute exposure in humans and also in other biota; and (ii) alternative detection tools capable of being early-warning signals for aquatic toxins occurrence and therefore provide better human and environmental safety insurance. Future directions on aquatic toxins research are discussed in face of the existent knowledge, with particular emphasis on the much-needed development and implementation of effective alternative (eco)toxicological biomarkers for these toxins. The wide-spanning approach followed herein will hopefully stimulate future research more broadly addressing the environmental hazardous potential of aquatic toxins.

Influence of genetics on the occurrence of enamel hypomineralization affecting permanent and primary teeth: A scoping review.

BACKGROUND: Molar incisor hypomineralization (MIH) is prevalent worldwide and is a challenge for clinicians who provide oral care to children. Molar incisor hypomineralization has been considered a multifactorial disturbance that results from a combination of environmental and genetic factors. AIM: This scoping review followed the Joanna Briggs Institute protocol and aimed to identify the available evidence of the genetic influence on the etiology of MIH. DESIGN: The search strategy was conducted in multiple databases, including PubMed, BVS, Embase, Web of Science, and Scopus. Two trained reviewers, requiring a third reviewer in case of disagreements, collected evidence. RESULTS: Of 563 retrieved studies, 17 were included in the review. From 14 studies performed in humans, 10 investigated DNA polymorphisms, one analyzed DNA methylation, one aimed model of inheritance, and two focused on the phenotype in twins or in the family. Three animal studies were based on the null expression of genes. CONCLUSION: This scoping review, based on the studies that used different methodologies, reinforces the hypothesis of a genetic contribution to the multifactorial etiology of MIH. The available data are limited in terms of size and origin of the samples. Hence, further genetic studies are still required.

Protective Effects of a synthetic glycosaminoglycan mimetic (OTR4132) in a rat immunotoxic lesion model of septohippocampal cholinergic degeneration.

Using a partial hippocampal cholinergic denervation model, we assessed the effects of the RGTA® named OTR4132, a synthetic heparan-mimetic biopolymer with neuroprotective/neurotrophic properties. Long-Evans male rats were injected with the cholinergic immunotoxin 192 IgG-saporin into the medial septum/diagonal band of Broca (0.37 µg); vehicle injections served as controls. Immediately after surgery, OTR4132 was injected into the lateral ventricles (0.25 µg/5 µl/rat) or intramuscularly (1.5 mg/kg). To determine whether OTR4132 reached the lesion site, some rats received intracerebroventricular (ICV) or intramuscular (I.M.) injections of fluorescent OTR4132. Rats were sacrificed at 4, 10, 20, or 60 days post-lesion (DPL). Fluorescein-labeled OTR4132 injected ICV or I.M. was found in the lesion from 4 to 20 DPL. Rats with partial hippocampal cholinergic denervation showed decreases in hippocampal acetylcholinesterase reaction products and in choline acetyltransferase-positive neurons in the medial septum. These lesions were the largest at 10 DPL and then remained stable until 60 DPL. Both hippocampal acetylcholinesterase reaction products and choline acetyltransferase-positive neurons in the medial septum effects were significantly attenuated in OTR4132-treated rats. These effects were not related to competition between OTR4132 and 192 IgG-saporin for the neurotrophin receptor P75 (p75NTR), as OTR4132 treatment did not alter the internalization of Cy3-labelled 192 IgG. OTR4132 was more efficient at reducing the acetylcholinesterase reaction products and choline acetyltransferase-positive neurons than a comparable heparin dose used as a comparator. Using the slice superfusion technique, we found that the lesion-induced decrease in muscarinic autoreceptor sensitivity was abolished by intramuscular OTR4132. After partial cholinergic damage, OTR4132 was able to concentrate at the brain lesion site possibly due to the disruption of the blood-brain barrier and to exert structural and functional effects that hold promises for neuroprotection/neurotrophism.

Anthropometric and body composition parameters in adolescents with the metabolically obese normal-weight phenotype.

We aimed to investigate the anthropometric and body composition parameters associated with the metabolically obese normal-weight (MONW) phenotype. This cross-sectional study was conducted with 506 adolescents in Brazil (aged 10-19 y). The MONW phenotype was defined as normal-weight, according to BMI/age, and at least one metabolic alteration. Anthropometric measurements were obtained and the DEXA was used for body composition analysis. Crude and adjusted Poisson regression models with robust variance were used to estimate the associations. The phenotype was positively associated with waist circumference (male: prevalence ratio (PR) = 1·05; 95% CI 1·01, 1·09; female: PR = 1·06; 95% CI 1·02, 1·09), waist:height ratio (male: PR = 1·26; 95% CI 1·07, 1·49; female: PR = 1·29; 95% CI 1·07, 1·56) and android:gynoid fat ratio (male: PR = 1·25; 95% CI 1·03, 1·51; female: PR = 1·39; 95% CI 1·20, 1·62), in both sexes. Furthermore, there was a positive association of phenotype with waist:hip ratio (PR = 1·32; 95% CI 1·06, 1·65) and trunk:arm fat ratio (PR = 1·13; 95% CI 1·02, 1·24) only in males and with trunk:leg fat ratio (PR = 2·84; 95% CI 1·46, 5·53), BAIp (PR = 1·06; 95% CI 1·01, 1·12), fat mass index (PR = 1·24; 95% CI 1·10, 1·41) and regional indices of metabolic load and capacity (PR = 1·29; 95% CI 1·09, 1·53), in females. Anthropometric and body composition parameters indicative of central and total fat are associated with the MONW phenotype.

Factors associated with normal-weight obesity in adolescents.

A new phenotype of obesity has been studied: normal-weight obesity (NWO), which describes individuals with normal-weight by BMI and excess body fat. Despite normal-weight, individuals with NWO have a higher cardiometabolic risk. There is still a gap in the literature on the subject, especially in adolescents, as studies with this population are scarce. This study aims to investigate the sociodemographic factors, family history of chronic non-communicable diseases, body perception, lifestyle and food consumption associated with NWO in adolescents. This is a cross-sectional study, with 506 normal-weight adolescents aged 10­19 years, of both sexes. Weight and height were obtained, and BMI/age was calculated. Body fat analysis was performed using dual-energy X-ray absorptiometry. Sociodemographic data, level of physical activity, food consumption, body self-perception and lifestyle habits were also obtained. Logistic regression with hierarchical approach was used to analyse the associations. The odds of NWO are greater with age (OR = 1·14; 95 % CI = 1·04, 1·26), lower in male adolescents (OR = 0·21; 95 % CI = 0·11, 0·41) and higher in those with a history of familial dyslipidemia (OR = 1·81; 95 % CI = 1·01, 3·28). Adolescents satisfied with their body (OR = 0·30; 95 % CI 0·16, 0·56) and physically active (OR = 0·44; 95 % CI = 0·24, 0·81) have a lower odds of NWO, compared with the others. In addition, it was observed that the odds of NWO is greater among adolescents who use sweeteners (sugar substitutes) (OR = 3·84; 95 % CI = 1·70, 8·65). The factors associated with NWO were female sex, older age, positive family history of dyslipidemia, lower body satisfaction, lower level of physical activity and greater use of sweeteners.

Morbidity and mortality in elderly dogs - a model for human aging.

Over the last decades, canines have experienced a marked increase in their lifespan, mirroring human populations. Several authors have pointed out the domestic dog as a suitable animal model for geropathology translational research. The aim of this study is to assess age-related morbidities and mortality in a population of 269 elderly canines (130 males and 139 females) submitted to necropsy. The organic systems exhibiting the higher number of age-related morbidities were the reproductive, cardiovascular and urinary systems and, in females, also the mammary gland. The prevalence of cardiovascular and urinary disease was significantly higher in males and mammary lesions were exclusively found in females. Urinary disease was more frequent in small breeds dogs, while peritoneum and male genital morbidities were significantly higher in larger breeds. Hyperplastic and degenerative lesions were common morbidities found in this elderly dog population. The main cause of death was neoplasia, which accounted for almost half of the deaths. Cardiovascular and urinary pathology also emerged as a frequent cause of mortality. These findings partially parallel data obtained for human species, displaying cancer and cardiovascular pathology as major causes of disease and death in elderlies. Our data reinforce the potential of the domestic dog for further translational investigations on gerontology, meeting the concept of One Health.

Progression of non-carious cervical lesions: 3D morphological analysis.

OBJECTIVES: This longitudinal study aimed to investigate morphologically and quantitatively the progression of non-carious cervical lesions (NCCLs) using a confocal laser scanning microscope (CLSM) and replica models. MATERIALS AND METHODS: The samples examined comprised sets of replicas annually obtained from 83 lesions in 16 participants over 3 to 5 years. All lesions were visually categorized as wedge-shaped, saucer-shaped, or mixed-shaped lesions. CLSM images of the replicas were analyzed in terms of axial depth, occlusogingival width (height) in the buccolingual cross-section, and estimated volume using a custom code of the image analysis software to estimate the progression of the NCCLs over time. The morphological characteristics of the NCCLs were also objectively divided into three groups according to the depth to height ratio (D/H ratio). Fisher's exact test and the Cochran-Armitage trend test were used for statistical analysis. RESULTS: Saucer-shaped lesions progressed mainly in height, whereas wedge-shaped lesions increased both in height and depth. Annual progression in depth and volume significantly increased as the D/H ratio increased. More than half of the NCCLs with a small D/H ratio progressed 50 µm or more in height, whereas none of them progressed more than 50 µm in depth. Annual progression in depth significantly increased as the lesion depth at baseline increased. CONCLUSIONS: Progression patterns significantly differed between NCCLs of different shapes. Most NCCLs progressed slowly in depth regardless of their shape. Moreover, NCCLs may progress through active and inactive stages.

Aldehyde Accumulation in Aged Alcoholic Beer: Addressing Acetaldehyde Impacts on Upper Aerodigestive Tract Cancer Risks.

Aldehydes, particularly acetaldehyde, are carcinogenic molecules and their concentrations in foodstuffs should be controlled to avoid upper aerodigestive tract (UADT) and liver cancers. Highly reactive, acetaldehyde forms DNA and protein adducts, impairing physiological functions and leading to the development of pathological conditions. The consumption of aged beer, outside of the ethanol metabolism, exposes habitual drinkers to this carcinogen, whose concentrations can be over-increased due to post-brewing chemical and biochemical reactions. Storage-related changes are a challenge faced by the brewing industry, impacting volatile compound formation and triggering flavor instability. Aldehydes are among the volatile compounds formed during beer aging, recognized as off-flavor compounds. To track and understand aldehyde formation through multiple pathways during beer storage, consequent changes in flavor but particularly quality losses and harmful compound formation, this systematic review reunited data on volatile compound profiles through gas chromatography analyses from 2011 to 2021. Conditions to avoid flavor instability and successful methods for reducing beer staling, and consequent acetaldehyde accumulation, were raised by exploring the dynamic conversion between free and bound-state aldehydes. Future research should focus on implementing sensory analyses to investigate whether adding aldehyde-binding agents, e.g., cysteine and bisulfite, would contribute to consumer acceptance, restore beer flavor, and minimize acetaldehyde-related health damage.

Histomorphometry Changes and Decreased Reactivity to Angiotensin II in the Ileum and Colon of Streptozotocin-Induced Diabetic Rats.

Diabetes mellitus (DM) is a chronic progressive metabolic disorder associated with several gastrointestinal complications, affecting up to 75% of patients. Knowing that Angiotensin II (AngII) also regulates intestinal contraction, we decided to evaluate changes in ileum and colon histomorphometry and AngII reactivity in a rat model of DM. Streptozotocin (STZ, 55 mg/kg) was administered to induce DM to 24 adult male Wistar rats. Diabetic rats displayed all the characteristic signs of type 1 DM (T1DM) and fecal excretion increased about 4-fold over 14 days, while the excretion of controls remained unaltered. Compared to controls, diabetic ileum and colon presented an increase in both macroscopic (length, perimeter and weight) and microscopic (muscular wall thickness) parameters. Functionally, AngII-induced smooth muscle contraction was lower in diabetic rats, except in the distal colon. These differences in the contractile response to AngII may result from an imbalance between AngII type 1 (antagonized by candesartan, 10 nM) and type 2 receptors activation (antagonized by PD123319, 100 nM). Taken together, these results indicate that an early and refined STZ-induced T1DM rat model already shows structural remodelling of the gut wall and decreased contractile response to AngII, findings that may help to explain diabetic dysmotility.