Susceptibility artifact morphology is more conspicuous on susceptibility-weighted imaging compared to T2* gradient echo sequences in the brains of dogs and cats with suspected intracranial disease.

Susceptibility-weighted imaging (SWI) has been found to be more reliable in the detection of vessels and blood products than T2*-weighted gradient echo (GE) in several human brain diseases. In veterinary medicine, published information on the diagnostic usefulness of SWI is lacking. The aim of this retrospective observational study was to investigate the value of SWI compared to T2*-weighted GE images in a population of dogs and cats with presumed, MRI-based diagnoses grouped as neoplastic (27), cerebrovascular (14), inflammatory (14), head trauma (5), other pathologies (4), or that were normal (36). Areas of signal void (ASV) were assessed based on shape, distribution, number, and conspicuity. Presence of ASV was found in 31 T2*-weighted GE and 40 SWI sequences; the conspicuity of lesions increased in 92.5% of cases with SWI. A 44.7% increase in the number of cerebral microbleeds (CMBs) was identified within the population using SWI (110) compared to T2*-weighted GE (76). Linear ASV presumed to be abnormal vascular structures, as are reported in humans, were identified in 12 T2*-weighted GE and 19 SWI sequences. In presumed brain tumors, abnormal vascular structures were detected in 11 of 27 (40.7%) cases on T2*-weighted GE and in 16 of 27 (59.3%) cases on SWI, likely representing tumor neovascularization; amorphous ASV interpreted as presumed hemorrhages on T2*-weighted GE were diagnosed as vessels on SWI in five of 27 (18.5%) cases. Since SWI shows ASV more conspicuously than T2*-weighted GE, the authors advocate the use of SWI in veterinary patients.

Evaluation of the Effect of the Fibroblast Growth Factor Type 2 (FGF-2) Administration on Placental Gene Expression in a Murine Model of Preeclampsia Induced by L-NAME.

The abnormal implantation of the trophoblast during the first trimester of pregnancy precedes the appearance of the clinical manifestations of preeclampsia (PE), which is a hypertensive disorder of pregnancy. In a previous study, which was carried out in a murine model of PE that was induced by NG-nitro-L-arginine methyl ester (L-NAME), we observed that the intravenous administration of fibroblast growth factor 2 (FGF2) had a hypotensive effect, improved the placental weight gain and attenuated the fetal growth restriction, and the morphological findings that were induced by L-NAME in the evaluated tissues were less severe. In this study, we aimed to determine the effect of FGF2 administration on the placental gene expression of the vascular endothelial growth factor (VEGFA), VEGF receptor 2 (VEGFR2), placental growth factor, endoglin (ENG), superoxide dismutase 1 (SOD1), catalase (CAT), thioredoxin (TXN), tumor protein P53 (P53), BCL2 apoptosis regulator, Fas cell surface death receptor (FAS), and caspase 3, in a Sprague Dawley rat PE model, which was induced by L-NAME. The gene expression was determined by a real-time polymerase chain reaction using SYBR green. Taking the vehicle or the L-NAME group as a reference, there was an under expression of placental VEGFA, VEGFR2, ENG, P53, FAS, SOD1, CAT, and TXN genes in the group of L-NAME + FGF2 (p < 0.05). The administration of FGF2 in the murine PE-like model that was induced by L-NAME reduced the effects that were generated by proteinuria and the increased BP, as well as the response of the expression of genes that participate in angiogenesis, apoptosis, and OS. These results have generated valuable information regarding the identification of molecular targets for PE and provide new insights for understanding PE pathogenesis.

The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases.

Matrix metalloproteinases (MMPs) are a family of zinc-dependent extracellular matrix (ECM) remodeling endopeptidases that have the capacity to degrade almost every component of the ECM. The degradation of the ECM is of great importance, since it is related to embryonic development and angiogenesis. It is also involved in cell repair and the remodeling of tissues. When the expression of MMPs is altered, it can generate the abnormal degradation of the ECM. This is the initial cause of the development of chronic degenerative diseases and vascular complications generated by diabetes. In addition, this process has an association with neurodegeneration and cancer progression. Within the ECM, the tissue inhibitors of MMPs (TIMPs) inhibit the proteolytic activity of MMPs. TIMPs are important regulators of ECM turnover, tissue remodeling, and cellular behavior. Therefore, TIMPs (similar to MMPs) modulate angiogenesis, cell proliferation, and apoptosis. An interruption in the balance between MMPs and TIMPs has been implicated in the pathophysiology and progression of several diseases. This review focuses on the participation of both MMPs (e.g., MMP-2 and MMP-9) and TIMPs (e.g., TIMP-1 and TIMP-3) in physiological processes and on how their abnormal regulation is associated with human diseases. The inclusion of current strategies and mechanisms of MMP inhibition in the development of new therapies targeting MMPs was also considered.

Design of a synthetic miniR1 plasmid and its production by engineered Escherichia coli.

A synthetic plasmid consisting of the minimal elements for replication control of the R1 replicon and kanamycin resistance marker, which was named pminiR1, was developed. pminiR1 production was tested at 30 °C under aerobic and microaerobic conditions in Escherichia coli W3110 recA- (W1). The plasmid DNA yields from biomass (YpDNA/X) were only 0.06 ± 0.02 and 0.22 ± 0.11 mg/g under aerobic and microaerobic conditions, respectively. As an option to increase YpDNA/X values, pminiR1 was introduced in an engineered E. coli strain expressing the Vitreoscilla hemoglobin inserted in chromosome (W12). The YpDNA/X values using strain W12 increased to 0.85 ± 0.05 and 1.53 ± 0.14 mg/g under aerobic and microaerobic conditions, respectively. pminiR1 production in both strains was compared with that of pUC57Kan at 37 °C under aerobic and microaerobic conditions. The YpDNA/X values for pminiR1 using strain W12 were 6.25 ± 0.16 and 9.27 ± 0.95 mg/g under aerobic and microaerobic conditions, respectively. Such yields were similar to those obtained for plasmid pUC57Kan using strain W12 (6.9 ± 0.64 and 10.85 ± 1.06 mg/g for aerobic and microaerobic cultures, respectively). Therefore, the synthetic minimal plasmid based on the R1 replicon is a valuable alternative to pUC plasmids for biotechnological applications.

KRas4B-PDE6δ complex stabilization by small molecules obtained by virtual screening affects Ras signaling in pancreatic cancer.

BACKGROUND: The GTPase KRas4B has been utilized as a principal target in the development of anticancer drugs. PDE6δ transports KRas4B to the plasma membrane, where it is released to activate various signaling pathways required for the initiation and maintenance of cancer. Therefore, identifying new small molecules that prevent activation of this GTPase by stabilizing the KRas4B-PDE6δ molecular complex is a practical strategy to fight against cancer. METHODS: The crystal structure of the KRas4B-PDE6δ heterodimer was employed to locate possible specific binding sites at the protein-protein interface region. Virtual screening of Enamine-database compounds was performed on the located potential binding sites to identify ligands able to simultaneously bind to the KRas4B-PDE6δ heterodimer. A molecular dynamics approach was used to estimate the binding free-energy of the complex. Cell viability and apoptosis were measured by flow cytometry. G-LISA was used to measure Ras inactivation. Western blot was used to measure AKT and ERK activation. MIA PaCa-2 cells implanted subcutaneously into nude mice were treated with D14 or C22 and tumor volumes were recorded. RESULTS: According to the binding affinity estimation, D14 and C22 stabilized the protein-protein interaction in the KRas4B-PDE6δ complex based on in vitro evaluation of the 38 compounds showing antineoplastic activity against pancreatic MIA PaCa-2 cancer cells. In this work, we further investigated the antineoplastic cellular properties of two of them, termed D14 and C22, which reduced the viability in the human pancreatic cancer cells lines MIA PaCa-2, PanC-1 and BxPC-3, but not in the normal pancreatic cell line hTERT-HPNE. Compounds D14 and C22 induced cellular death via apoptosis. D14 and C22 significantly decreased Ras-GTP activity by 33% in MIA PaCa-2 cells. Moreover, D14 decreased AKT phosphorylation by 70% and ERK phosphorylation by 51%, while compound C22 reduced AKT phosphorylation by 60% and ERK phosphorylation by 36%. In addition, compounds C22 and D14 significantly reduced tumor growth by 88.6 and 65.9%, respectively, in a mouse xenograft model. CONCLUSIONS: We identified two promising compounds, D14 and C22, that might be useful as therapeutic drugs for pancreatic ductal adenocarcinoma treatment.

Tumor suppressor miR-29c regulates radioresistance in lung cancer cells.

Radiotherapy is an important treatment option for non-small cell lung carcinoma patients. Despite the appropriate use of radiotherapy, radioresistance is a biological behavior of cancer cells that limits the efficacy of this treatment. Deregulation of microRNAs contributes to the molecular mechanism underlying resistance to radiotherapy in cancer cells. Although the functional roles of microRNAs have been well described in lung cancer, their functional roles in radioresistance are largely unclear. In this study, we established a non-small cell lung carcinoma Calu-1 radioresistant cell line by continuous exposure to therapeutic doses of ionizing radiation as a model to investigate radioresistance-associated microRNAs. Our data show that 50 microRNAs were differentially expressed in Calu-1 radioresistant cells (16 upregulated and 34 downregulated); furthermore, well-known and novel microRNAs associated with resistance to radiotherapy were identified. Gene ontology and enrichment analysis indicated that modulated microRNAs might regulate signal transduction, cell survival, and apoptosis. Accordingly, Calu-1 radioresistant cells were refractory to radiation by increasing cell survival and reducing the apoptotic response. Among deregulated microRNAs, miR-29c was significantly suppressed. Reestablishment of miR-29c expression in Calu-1 radioresistant cells overcomes the radioresistance through the activation of apoptosis and downregulation of Bcl-2 and Mcl-1 target genes. Analysis of The Cancer Genome Atlas revealed that miR-29c is also suppressed in tumor samples of non-small cell lung carcinoma patients. Notably, we found that low miR-29c levels correlated with shorter relapse-free survival of non-small cell lung carcinoma patients treated with radiotherapy. Together, these results indicate a new role of miR-29c in radioresistance, highlighting their potential as a novel biomarker for outcomes of radiotherapy in lung cancer.

Maternal distress and the development of hypertensive disorders of pregnancy.

Despite the implementation of programmes to improve maternal health, maternal and foetal mortality rates still remain high. The presence of maternal distress and its association with the development of pregnancy hypertensive disorders is not well established. The aim of this study was to evaluate the association between maternal distress and the development of hypertensive disorders in pregnancy in a prospective cohort of 321 Mexican women. Symptoms of maternal distressing were evaluated at week 20th of gestation using the General Health Questionnaire. The presence of acute somatic symptoms, social dysfunction, anxiety and insomnia increased the odds of developing a pregnancy hypertensive disorder by 5.1-26.4 times in study population (p values < .05). Our results support the participation of maternal distress in the development of hypertensive disorders of pregnancy. The implementation of effective programmes prioritising risk factors during pregnancy including the presence of maternal distressing factors is recommended. Impact statement What is already known on this subject: Changes in the nervous, endocrine, and immune systems have been observed in pregnant women with distress conditions leading to gestational disorders. What do the results of this study add: The presence of acute somatic symptoms, social dysfunction, anxiety and insomnia increased the developing of hypertensive disorders in Mexican population. What are the implications of these findings for clinical practice and/or further research: These findings may contribute to a better understanding of the role of the maternal stress in the development of hypertensive disorders of pregnancy, and in the implementation of effective programmes for clinical practice prioritising risk factors during pregnancy, including the presence of maternal distressing factors.

Gene Variants of the OAS/RNase L Pathway and Their Association with Severity of Symptoms and Outcome of SARS-CoV-2 Infection.

INTRODUCTION: The interferon pathway plays a critical role in triggering the immune response to SARS-CoV-2, and these gene variants may be involved in the severity of COVID-19. This study aimed to analyze the frequency of three gene variants of OAS and RNASEL with the occurrence of COVID-19 symptoms and disease outcome. METHODS: This cross-sectional study included 104 patients with SARS-CoV-2 infection, of which 34 were asymptomatic COVID-19, and 70 were symptomatic cases. The variants rs486907 (RNASEL), rs10774671 (OAS1), rs1293767 (OAS2), and rs2285932 (OAS3) were screened and discriminated using a predesigned 5'-nuclease assay with TaqMan probes. RESULTS: Patients with the allele C of the OAS2 gene rs1293767 (OR = 0.36, 95% CI: 0.15-0.83, p = 0.014) and allele T of the OAS3 gene rs2285932 (OR = 0.39, 95% CI: 0.2-0.023, p = 0.023) have lower susceptibility to developing symptomatic COVID-19. The genotype frequencies (G/G, G/C, and C/C) of rs1293767 for that comparison were 64.7%, 29.4%, and 5.9% in the asymptomatic group and 95.2%, 4.8%, and 0% in severe disease (p < 0.05). CONCLUSIONS: Our data indicate that individuals carrying the C allele of the OAS2 gene rs1293767 and the T allele of the OAS3 gene rs2285932 are less likely to develop symptomatic COVID-19, suggesting these genetic variations may confer a protective effect among the Mexican study population. Furthermore, the observed differences in genotype frequencies between asymptomatic individuals and those with severe disease emphasize the potential of these variants as markers for disease severity. These insights enhance our understanding of the genetic factors that may influence the course of COVID-19 and underscore the potential for genetic screening in identifying individuals at increased risk for severe disease outcomes.

DOMINO trial post hoc analysis: evaluation of the diet effects on symptoms in IBS subtypes.

Background: Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction characterized by recurrent abdominal pain related to defecation and/or associated to a change in bowel habits. According to the stool type, four different IBS subtypes can be recognized, constipation predominant (IBS-C), diarrhea predominant (IBS-D), mixed (IBS-M), and undefined (IBS-U). Patients report that their IBS symptoms are exacerbated by food. Thus, it is important to find a nutritional approach that could be effective in reducing IBS symptoms. Objective: The present work is a post hoc analysis of the previously published DOMINO trial. It aimed to evaluate the effects of a self-instructed FODMAP-lowering diet smartphone application on symptoms and psychosocial aspects in primary care IBS stratifying the results for each IBS subtypes. Design: Post hoc analysis. Methods: Two hundred twenty-two primary care IBS patients followed a FODMAP-lowering diet for 8 weeks with the support of a smartphone application. Two follow-up visits were scheduled after 16 and 24 weeks. IBS-Symptoms Severity Score (IBS-SSS), quality of life (QoL), and adherence and dietary satisfaction were evaluated. Results: After 8 weeks, IBS-SSS improved in all IBS subtypes (p < 0.0001). Physician Health Questiionnaire (PHQ-15) improved only in IBS-D (p = 0.0006), whereas QoL improved both in IBS-D (p = 0.01) and IBS-M (p = 0.005). Conclusion: This post hoc analysis showed that the app is useful in all IBS subtypes; thus, it could be used as an effective tool by both general practitioners and patients to manage symptoms in primary care. Trial registration: Ethical Commission University Hospital of Leuven reference number: S59482. Clinicaltrial.gov reference number: NCT04270487.

What is already known about this subject? The low FODMAP (fermentable oligo-, di-, and monosaccharides and polyols) diet has shown efficacy for controlling IBS (irritable bowel syndrome) symptoms in small controlled trials in tertiary care patients. As this approach requires several visits with an experienced dietitian, it seems less suitable for primary care. What are the new findings? The benefit of the FODMAP lowering app was already present at 4 weeks and persisted during follow-up until 24 weeks. How might it impact on clinical practice in the foreseeable future? Given its superiority to standard first-line pharmacotherapy, and its ease of use, a FODMAP lowering app has the potential to become the preferred first-line treatment for primary care IBS.

Direct Single-Operator Cholangioscopy and Intraductal Ultrasonography in Patients with Indeterminate Biliary Strictures: A Single Center Experience.

The evaluation of biliary strictures poses a challenge due to the low sensitivity of standard diagnostic approaches, but the advent of direct single-operator cholangioscopy (DSOC) has revolutionized this paradigm. Our study aimed to assess the diagnostic performance of DSOC and DSOC-targeted biopsies, intraductal ultrasound (IDUS), and standard brush cytology in patients with indeterminate biliary strictures (IBS). We reviewed patients who underwent advanced diagnostic evaluation for IBS at our endoscopy unit from January 2018 to December 2022, all of whom had previously undergone at least one endoscopic attempt to characterize the biliary stricture. Final diagnoses were established based on surgical pathology and/or clinical and radiological follow-up spanning at least 12 months. A total of 57 patients, with a mean age of 67.2 ± 10.0 years, were included, with a mean follow-up of 18.2 ± 18.1 months. The majority of IBS were located in the distal common bile duct (45.6%), with malignancy confirmed in 35 patients (61.4%). DSOC and IDUS demonstrated significantly higher accuracies (89.5% and 82.7%, respectively) compared to standard cytology (61.5%, p < 0.05). Both DSOC visualization and IDUS exhibited optimal diagnostic yields in differentiating IBS with an acceptable safety profile.

Activation of Akt pathway by transcription-independent mechanisms of retinoic acid promotes survival and invasion in lung cancer cells.

BACKGROUND: All-trans retinoic acid (ATRA) is currently being used in clinical trials for cancer treatment. The use of ATRA is limited because some cancers, such as lung cancer, show resistance to treatment. However, little is known about the molecular mechanisms that regulate resistance to ATRA treatment. Akt is a kinase that plays a key role in cell survival and cell invasion. Akt is often activated in lung cancer, suggesting its participation in resistance to chemotherapy. In this study, we explored the hypothesis that activation of the Akt pathway promotes resistance to ATRA treatment at the inhibition of cell survival and invasion in lung cancer. We aimed to provide guidelines for the proper use of ATRA in clinical trials and to elucidate basic biological mechanisms of resistance. RESULTS: We performed experiments using the A549 human lung adenocarcinoma cell line. We found that ATRA treatment promotes PI3k-Akt pathway activation through transcription-independent mechanisms. Interestingly, ATRA treatment induces the translocation of RARα to the plasma membrane, where it colocalizes with Akt. Immunoprecipitation assays showed that ATRA promotes Akt activation mediated by RARα-Akt interaction. Activation of the PI3k-Akt pathway by ATRA promotes invasion through Rac-GTPase, whereas pretreatment with 15e (PI3k inhibitor) or over-expression of the inactive form of Akt blocks ATRA-induced invasion. We also found that treatment with ATRA induces cell survival, which is inhibited by 15e or over-expression of an inactive form of Akt, through a subsequent increase in the levels of the active form of caspase-3. Finally, we showed that over-expression of the active form of Akt significantly decreases expression levels of the tumor suppressors RARß2 and p53. In contrast, over-expression of the inactive form of Akt restores RARß2 expression in cells treated with ATRA, indicating that activation of the PI3k-Akt pathway inhibits the expression of ATRA target genes. CONCLUSION: Our results demonstrate that rapid activation of Akt blocks transcription-dependent mechanism of ATRA, promotes invasion and cell survival and confers resistance to retinoic acid treatment in lung cancer cells. These findings provide an incentive for the design and clinical testing of treatment regimens that combine ATRA and PI3k inhibitors for lung cancer treatment.

Methods to extract and study the biological effects of murine gut microbiota using Caenorhabditis elegans as a screening host.

Gut microbiota has been established as a main regulator of health. However, how changes in gut microbiota are directly associated with physiological and cellular alterations has been difficult to tackle on a large-scale basis, notably because of the cost and labor-extensive resources required for rigorous experiments in mammals. In the present study, we used the nematode Caenorhabditis elegans as a model organism to elucidate microbiota-host interactions. We developed a method to extract gut microbiota (MCB) from murine feces, and tested its potential as food source for and its impact on C. elegans biology compared to the standard bacterial diet Escherichia coli OP50. Although less preferred than OP50, MCB was not avoided but had a lower energy density (triglycerides and glucose). Consistently, MCB-fed worms exhibited smaller body length and size, lower fertility, and lower fat content than OP50-fed worms, but had a longer mean lifespan, which resembles the effects of calorie restriction in mammals. However, these outcomes were altered when bacteria were inactivated, suggesting an important role of symbiosis of MCB beyond nutrient source. Taken together, our findings support the effectiveness of gut MCB processing to test its effects in C. elegans. More work comparing MCB of differently treated mice or humans is required to further validate relevance to mammals before large-scale screening assays.

Effects of Animal and Vegetable Proteins on Gut Microbiota in Subjects with Overweight or Obesity.

The gut microbiota plays a pivotal role in the balance between host health and obesity. The composition of the gut microbiota can be influenced by external factors, among which diet plays a key role. As the source of dietary protein is important to achieve weight loss and gut microbiota modulation, in the literature there is increasing evidence to suggest consuming more plant proteins than animal proteins. In this review, a literature search of clinical trials published until February 2023 was conducted to examine the effect of different macronutrients and dietary patterns on the gut microbiota in subjects with overweight and obesity. Several studies have shown that a higher intake of animal protein, as well as the Western diet, can lead to a decrease in beneficial gut bacteria and an increase in harmful ones typical of obesity. On the other hand, diets rich in plant proteins, such as the Mediterranean diet, lead to a significant increase in anti-inflammatory butyrate-producing bacteria, bacterial diversity and a reduction in pro-inflammatory bacteria. Therefore, since diets rich in fiber, plant protein, and an adequate amount of unsaturated fat may help to beneficially modulate the gut microbiota involved in weight loss, further studies are needed.

Prevalence, MRI findings, and clinical features of lumbosacral intervertebral disc protrusion in French Bulldogs diagnosed with acute thoracic or lumbar intervertebral disc extrusion.

Introduction: Intervertebral disc protrusion (IVDP) is a neurological disorder commonly observed at the lumbosacral junction of old, medium-to-large breeds, non-chondrodystrophic dogs. Although uncommon, lumbosacral IVDP can also be seen in chondrodystrophic dogs, among them French Bulldogs (FBs) and could be associated with congenital vertebral malformations in this breed. This study aims to evaluate the prevalence, clinical features, and MRI characteristics of lumbosacral IVDP and congenital vertebral malformations in FBs diagnosed with thoracic or lumbar intervertebral disc extrusion (IVDE) and to evaluate the possible interference of the neurologic deficits related to chronic IVDP on neurological examination. Materials and methods: This is a single-center, retrospective case series. A search for FBs diagnosed with IVDE affecting the thoracic or lumbar regions is done on the database of the AniCura I Portoni Rossi Veterinary Hospital (Zola Predosa, Bologna, Italy). Eligible dogs have a complete medical report and a high-field MRI of the lumbosacral junction. MRIs of the lumbosacral junction are evaluated to determine the position of IVDP, cranial intervertebral foraminal stenosis, and signs of nerve root involvement. Radiographs, when available, are reviewed to identify the presence of lumbosacral congenital vertebral malformations. Results: Eighty FBs are included in the study. The prevalence of lumbosacral IVDP among FBs is 91.3%. Among FBs with lumbosacral IVDP, 45.0% show concurrent cranial intervertebral foraminal stenosis, 28.8% exhibit concurrent nerve root involvement, 56.2% appear to be asymptomatic for lumbosacral changes, while 15.1% manifest a decreased or absent withdrawal reflex as a supposed consequence of chronic lumbosacral IVDP. Congenital vertebral malformations are detected in 10 dogs. Conclusion: The results of this study support the hypothesis that lumbosacral IVDP is frequent in FBs presenting with thoracic or lumbar IVDE. In over half the dogs lumbosacral IVDP appears to be asymptomatic; however, in other cases, chronic lumbosacral IVDP seems to cause neurological deficits that may lead to erroneous localization of acute IVDE, representing a confounding factor for clinicians.

Nutritional Approaches in Children with Overweight or Obesity and Hepatic Steatosis.

Childhood obesity is a global public health problem. Worldwide, 41 million children under 5 years and 340 million children and adolescents between 5 and 19 years are overweight. In addition, the recent COVID-19 epidemic has further amplified this social phenomenon. Obesity is a condition associated with various comorbidities, such as nonalcoholic fatty liver disease (NAFLD). The pathophysiology of NAFLD in obesity is intricate and involves the interaction and dysregulation of several mechanisms, such as insulin resistance, cytokine signaling, and alteration of the gut microbiota. NAFLD is defined as the presence of hepatic steatosis in more than 5% of hepatocytes, evaluated by histological analysis. It can evolve from hepatic steatosis to steatohepatitis, fibrosis, cirrhosis, hepatocellular carcinoma, and end-stage liver failure. Body weight reduction through lifestyle modification remains the first-line intervention for the management of pediatric NAFLD. Indeed, studies suggest that diets low in fat and sugar and conversely rich in dietary fibers promote the improvement of metabolic parameters. This review aims to evaluate the existing relationship between obesity and NAFLD in the pediatric population and to assess the dietary patterns and nutritional supplementations that can be recommended to prevent and manage obesity and its comorbidities.

Short- and long-term effects of very low- and low-calorie ketogenic diets on metabolism and cardiometabolic risk factors: a narrative review.

Worldwide obesity and cardiovascular diseases have encouraged the adoption of new and efficient dietary strategies. Among various proposed diets, ketogenic diets, both the very-low-calorie ketogenic diet (VLCKD) and the low-calorie ketogenic diet (LCKD), have been suggested in recent years as an effective nutritional approach for obesity management. The VLCKD and the LCKD are characterized by a low carbohydrate content (<50 g/day), 1-1.5 g of protein/kg of ideal body weight, less than 20-30 g of lipids, and a daily intake of about 800 calories for VLCKD and about 1200-1400 calories for LCKD. The purpose of our narrative review is to offer an overview of the most impactful studies in the scientific literature regarding VLCKD and LCKD to discuss their short- and long-term effects (less than 12 months and more than 12 months respectively) on weight loss, metabolic and cardiovascular aspects. Articles we focused on were cohort studies, case-control studies, cross-sectional studies, randomized controlled trials, and meta-analyses. Results indicate that VLCKD and LCKD could be helpful to ameliorate metabolic and cardiovascular risk factors such as weight loss, glucose, and cholesterol levels, both in the short and long term. Further research in this area may include more randomized controlled trials to gather more data.

Design of Biodegradable Films Using Pecan Nut Cake Extracts for Food Packing.

The excessive consumption of plastic packaging and its consequent disposal and accumulation in the environment have aroused the interest of researchers in developing packaging that can cause less harm to nature. In this sense, this article presents research on the addition of antioxidant extracts from pecan nut cake in biodegradable packaging made with a polymeric mixture of gelatin and corn starch. The films produced were characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, thickness, mechanical properties, water vapor permeability (WVP), solubility, water contact angle, optical properties, in vitro bioactive activity, and biodegradability. A higher concentration of total phenolic compounds (101.61 mg GAE/g) was found for the condition where alcohol content and extraction time were 65% and 20 min, respectively. Pecan nut cake (PNC( extracts did not influence the film's tensile strength, and elongation at break was tightly increased by adding 10-20% extracts. The film's characterization pointed to more than 67% solubility, and adding PNC extract implied more hydrophilic surfaces (contact angles lower than 65°). Furthermore, the film opacity showed a linear relation with PNC extract concentration, and a higher luminosity (L*) was observed for the film without extract. Furthermore, the antioxidant activity of the films was enhanced with the addition of PNC extracts, and complete biodegradation was observed until the ninth day. Therefore, biodegradable films prepared from a mixture of gelatin starch and enriched with PNC extracts showed excellent mechanical properties and potential as carriers of antioxidant compounds, allowing us to propose their use as active packing.

"Nutripiatto": A tool for nutritional education. A survey to assess dietary habits in preschool children.

Childhood obesity is a global public health concern linked to metabolic and psychological comorbidities. There is growing evidence that children's lifestyle habits are shifting towards obesity, with dire consequences for their future well-being and healthcare costs. In this interventional study, we enrolled 115 children aged between 4-5 years (53% females and 47% males) and carried out nutrition education interventions to improve their dietary habits. We introduced "Nutripiatto", a visual plate icon and easy guide, which was used by the children during the study. We investigated the children's dietary habits using a Food Frequency Questionnaire at the beginning and end of the study, after one month of using "Nutripiatto". The results showed that the children significantly increased the portion sizes and frequency of vegetable consumption (P<0.001) and reduced the consumption of several junk foods such as French fries and crisps (P<0.001), reaching the recommended dietary allowances and frequency of consumption. Daily consumption of water also significantly increased, reaching the suggested amount of six glasses per day. Based on these results, "Nutripiatto" can be considered an effective visual guide and helpful tool to achieve small changes and empower families to make healthier food choices. It can also be considered an effective educational tool for nutritionists and healthcare professionals to improve children's dietary behavior.

Mutant p53 Gain-of-Function Induces Migration and Invasion through Overexpression of miR-182-5p in Cancer Cells.

The master-key TP53 gene is a tumor suppressor that is mutated in more than 50% of human cancers. Some p53 mutants lose their tumor suppressor activity and acquire new oncogenic functions, known as a gain of function (GOF). Recent studies have shown that p53 mutants can exert oncogenic effects through specific miRNAs. We identified the differentially expressed miRNA profiles of the three most frequent p53 mutants (p53R273C, p53R248Q, and p53R175H) after their transfection into the Saos-2 cell line (null p53) as compared with p53WT transfected cells. The associations between these miRNAs and the signaling pathways in which they might participate were identified with miRPath Software V3.0. QRT-PCR was employed to validate the miRNA profiles. We observed that p53 mutants have an overall negative effect on miRNA expression. In the global expression profile of the human miRNome regulated by the p53R273C mutant, 72 miRNAs were underexpressed and 35 overexpressed; in the p53R175H miRNAs profile, our results showed the downregulation of 93 and upregulation of 10 miRNAs; and in the miRNAs expression profile regulated by the p53R248Q mutant, we found 167 decreased and 6 increased miRNAs compared with p53WT. However, we found overexpression of some miRNAs, like miR-182-5p, in association with processes such as cell migration and invasion. In addition, we explored whether the induction of cell migration and invasion by the p53R48Q mutant was dependent on miR-182-5p because we found overexpression of miR-182-5p, which is associated with processes such as cell migration and invasion. Inhibition of mutant p53R248Q and miR-182-5p increased FOXF2-MTSS1 levels and decreased cell migration and invasion. In summary, our results suggest that p53 mutants increase the expression of miR-182-5p, and this miRNA is necessary for the p53R248Q mutant to induce cell migration and invasion in a cancer cell model.