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1.
Animals (Basel) ; 14(16)2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39199874

ABSTRACT

Brazil is the second largest beef producer and a leading exporter, contributing to some 3000 t CWE in global markets (27.7% of market share). The sector has experienced substantial development, but yields remain far below potential, and there are growing concerns regarding land use change and greenhouse gas emissions. The need for sustainable technologies, such as sound pasture management and integrated farming systems, is evident, but adoption may be low amongst farmers unable to keep up with technological advances. This article describes the historical developments of Brazilian beef farming towards sustainability and discusses possible socioenvironmental outcomes. We combined an extensive literature review, public data, and our own insights as senior researchers to achieve that. The trajectory shown here evidenced the technological intensification of Brazilian beef farming, with strong support of public policies for decarbonizing agriculture. Nonetheless, the pace of this transition may affect small to medium farmers with limited access to information, technologies, and credit. Our recommendations involve a broad program of technical assistance and training on sustainable technologies, including financial and digital literacy. A novel approach to financing farmers is suggested to support a sustainable and inclusive transition in beef farming in Brazil.

2.
Microorganisms ; 12(7)2024 Jul 09.
Article in English | MEDLINE | ID: mdl-39065160

ABSTRACT

Leishmaniasis is a group of infectious diseases transmitted to humans during vector bites and caused by protozoans of the genus Leishmania. Conventional therapies face challenges due to their serious side effects, prompting research into new anti-leishmania agents. In this context, we investigated the effectiveness of morolic acid, a pentacyclic triterpene, on L. amazonensis promastigotes and amastigotes. The present study employed the MTT assay, cytokine analysis using optEIATM kits, an H2DCFDA test, and nitric oxide dosage involving nitrite production and Griess reagent. Morolic acid inhibited promastigote and axenic amastigote growth forms at IC50 values of 1.13 µM and 2.74 µM, respectively. For cytotoxicity to macrophages and VERO cells, morolic acid obtained respective CC50 values of 68.61 µM and 82.94 µM. The compound causes damage to the parasite membrane, leading to cellular leakage. In the infection assay, there was a decrease in parasite load, resulting in a CI50 of 2.56 µM. This effect was associated with immunomodulatory activity, altering macrophage structural and cellular parasite elimination mechanisms. Morolic acid proved to be an effective and selective natural compound, making it a strong candidate for future in vivo studies in cutaneous leishmaniasis.

3.
Nutr Neurosci ; : 1-23, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38963807

ABSTRACT

OBJECTIVES: The present study aims to evaluate the impact of early exposure to brain injury and malnutrition on episodic memory and behavior. METHODS: For this, a systematic review was carried out in the Medline/Pubmed, Web of Science, Scopus, and LILACS databases with no year or language restrictions. RESULTS: Initially, 1759 studies were detected. After screening, 53 studies remained to be read in full. The meta-analysis demonstrated that exposure to double insults worsens episodic recognition memory but does not affect spatial memory. Early exposure to low-protein diets has been demonstrated to aggravate locomotor and masticatory sequelae. Furthermore, it reduces the weight of the soleus muscle and the muscle fibers of the masseter and digastric muscles. Early exposure to high-fat diets promotes an increase in oxidative stress and inflammation in the brain, increasing anxiety- and depression-like behavior and reducing locomotion. DISCUSSION: Epigenetic modifications were noted in the hippocampus, hypothalamus, and prefrontal cortex depending on the type of dietetic exposure in early life. These findings demonstrate the impact of the double insult on regions involved in cognitive and behavioral processes. Additional studies are essential to understand the real impact of the double insults in the critical period.

4.
J Trace Elem Med Biol ; 85: 127498, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39024850

ABSTRACT

AIM: to estimate the level of metallic chemical elements in the population living in the Steel company vicinity in Santa Cruz, Rio de Janeiro, Brazil; and estimate the association between exposure to the Steel company and the blood metals concentrations patterns. METHOD: A cross-sectional study was carried out on 463 individuals aged 18+ years old residing 1+ years in the Steel company vicinity. Mg, Be, Co, Ba, Ni, Cd, Al, and Pb were assessed in blood by DRC-ICP-MS. Metallic chemical element concentration patterns were obtained by exploratory factor analysis in the studied population. Exposure was set as the distance (Km) from each participant's residence to the Steel company in Santa Cruz, georeferenced by GPS. The outcome was set as the positive factor loadings in the factor analysis, including Mg and Be (Factor-1), Co, Ba, and Ni (Factor-2), Cd, Al, and Pb (Factor-4). Crude and adjusted OR, and their respective 95 %CI, were estimated to explore associations between independent variables and the exposures to metallic elements positively associated with the factors using polychotomous logistic regression. RESULTS: A reduction of 19 % was found between each km distance from the residence and the Steel company and P50 concentration of Cd, Al, and Pb (ORP50=0.81; 95 %CI:0.67-0.97), after adjusting by age, sex, and smoking. No statistically significant associations were observed for the distance from residences and the Steel company, after adjusting for age, gender, having a domestic vegetable garden and chewing gum for Mg and Be concentrations (Factor-1) (ORP50=0.84; 95 %CI:0.70-1.01; ORP75=1.10; 95 %CI:0.91-1.34); nor for Co, Ba and Ni (Factor-2) blood concentrations(ORP50=1.10; 95 %CI:0.91-1.33; ORP75=1.03; 95 %CI:0.84-1.26), in the adjusted analysis. CONCLUSIONS: For each Km distance from residences to the Steel company, a 19 % reduction in the risk of Cd, Al, and Pb blood concentration was observed in the population living in Santa Cruz, Rio de Janeiro, Brazil.


Subject(s)
Metals , Humans , Brazil , Male , Female , Adult , Middle Aged , Cross-Sectional Studies , Young Adult , Metals/blood , Adolescent , Environmental Exposure/analysis , Aged , Industry
5.
Int J Biol Macromol ; 274(Pt 2): 133048, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38857734

ABSTRACT

Epiisopiloturine (EPI) is a compound found in jaborandi leaves with antiparasitic activity, which can be enhanced when incorporated into nanoparticles (NP). Cashew Gum (CG), modified by carboxymethylation, is used to produce polymeric nanomaterials with biological activity. In this study, we investigated the antimicrobial potential of carboxymethylated CG (CCG) NP containing EPI (NPCCGE) and without the alkaloid (NPCCG) against bacteria and parasites of the genus Leishmania. We conducted theoretical studies, carboxymethylated CG, synthesized NP by nanoprecipitation, characterized them, and tested them in vitro. Theoretical studies confirmed the stability of modified carbohydrates and showed that the EPI-4A30 complex had the best interaction energy (-8.47 kcal/mol). CCG was confirmed by FT-IR and presented DSabs of 0.23. NPCCG and NPCCGE had average sizes of 221.94 ± 144.086 nm and 247.36 ± 3.827 nm, respectively, with homogeneous distribution and uniform surfaces. No NP showed antibacterial activity or cytotoxicity to macrophages. NPCCGE demonstrated antileishmanial activity against L. amazonensis, both in promastigote forms (IC50 = 9.52 µg/mL, SI = 42.01) and axenic amastigote forms (EC50 = 6.6 µg/mL, SI = 60.60). The results suggest that nanostructuring EPI in CCG enhances its antileishmanial activity.


Subject(s)
Anacardium , Anti-Infective Agents , Nanoparticles , Plant Gums , Anacardium/chemistry , Nanoparticles/chemistry , Plant Gums/chemistry , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Animals , Mice , Leishmania/drug effects , Computer Simulation , Imidazoles , 4-Butyrolactone/analogs & derivatives
6.
Nutr Rev ; 2024 May 08.
Article in English | MEDLINE | ID: mdl-38719205

ABSTRACT

CONTEXT: Riboflavin (vitamin B2) is a water-soluble micronutrient considered to be a precursor of the nucleotides flavin adenine dinucleotide and flavin mononucleotide. This vitamin makes up mitochondrial complexes and participates as an enzymatic cofactor in several mechanisms associated with energy metabolism. OBJECTIVE: This systematic review collected and discussed the most relevant results on the role of riboflavin in the energy metabolism of lipids, proteins, and carbohydrates. DATA SOURCES: A systematic search was carried out in the PubMed-Medline, Scopus, Embase, and Web of Science databases using the PICOS (Population, Intervention, Comparison, Outcome, Study design) strategy. DATA EXTRACTION: The screening of studies went through 2 stages following predefined eligibility criteria. The information extracted covered reference details, study design, population characteristics, experimental model, treatment parameters and dosage, route of administration, duration of treatment, and results found. DATA ANALYSIS: The risk of bias was assessed using the SYRCLE Risk of Bias (RoB) tool for in vivo studies and the QUIN tool adapted for in vitro studies, utilizing 10 domains, including selection bias, performance bias, detection bias, attrition bias, reporting bias, and other biases, to evaluate the methodological quality of the included studies. CONCLUSION: This review concludes that riboflavin regulates energy metabolism by activating primary metabolic pathways and is involved in energy balance homeostasis.

7.
Exp Neurol ; 378: 114835, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38789024

ABSTRACT

Cerebral Palsy (CP) is the main motor disorder in childhood resulting from damage to the developing brain. Treatment perspectives are required to reverse the primary damage caused by the early insult and consequently to recover motor skills. Resveratrol has been shown to act as neuroprotection with benefits to skeletal muscle. This study aimed to investigate the effects of neonatal resveratrol treatment on neurodevelopment, skeletal muscle morphology, and cerebellar damage in CP model. Wistar rat pups were allocated to four experimental groups (n = 15/group) according CP model and treatment: Control+Saline (CS), Control+Resveratrol (CR), CP + Saline (CPS), and CP + Resveratrol (CPR). CP model associated anoxia and sensorimotor restriction. CP group showed delay in the disappearance of the palmar grasp reflex (p < 0.0001) and delay in the appearance of reflexes of negative geotaxis (p = 0.01), and free-fall righting (p < 0.0001), reduced locomotor activity and motor coordination (p < 0.05) than CS group. These motor skills impairments were associated with a reduction in muscle weight (p < 0.001) and area and perimeter of soleus end extensor digitorum longus muscle fibers (p < 0.0001), changes in muscle fibers typing pattern (p < 0.05), and the cerebellum showed signs of neuroinflammation due to elevated density and percentage of activated microglia in the CPS group compared to CS group (p < 0.05). CP animals treated with resveratrol showed anticipation of the appearance of negative geotaxis and free-fall righting reflexes (p < 0.01), increased locomotor activity (p < 0.05), recovery muscle fiber types pattern (p < 0.05), and reversal of the increase in density and the percentage of activated microglia in the cerebellum (p < 0.01). Thus, we conclude that neonatal treatment with resveratrol can contribute to the recovery of the delay neurodevelopment resulting from experimental CP due to its action in restoring the skeletal muscle morphology and reducing neuroinflammation from cerebellum.


Subject(s)
Animals, Newborn , Cerebellum , Cerebral Palsy , Microglia , Muscle, Skeletal , Rats, Wistar , Resveratrol , Resveratrol/pharmacology , Animals , Cerebellum/drug effects , Cerebellum/pathology , Rats , Microglia/drug effects , Microglia/pathology , Cerebral Palsy/drug therapy , Cerebral Palsy/pathology , Muscle, Skeletal/drug effects , Muscle, Skeletal/pathology , Disease Models, Animal , Stilbenes/pharmacology , Stilbenes/therapeutic use , Male , Recovery of Function/drug effects , Female
8.
Future Microbiol ; 19(8): 647-654, 2024.
Article in English | MEDLINE | ID: mdl-38661711

ABSTRACT

Aim: We evaluated Diacetylcurcumin (DAC), a derivative of curcumin, for its antibacterial and antibiofilm properties against Enterococcus faecalis. Methods: Minimum inhibitory concentration (MIC) and minimum bactericidal concentration were determined, along with antibiofilm potential and toxicity in Galleria mellonella. Additionally, in silico computational analysis was performed to understand its mechanisms of action. Results & conclusion: DAC demonstrated significant antibacterial effects, with MIC and MBC values of 15.6 and 31.25 µg/ml, respectively, and reduced biofilm formation. A synergistic effect, reducing biofilm by 77%, was observed when combined with calcium hydroxide. G. mellonella toxicity tests confirmed DAC's safety at tested concentrations, suggesting its potential for use in root canal disinfection products.


Diacetylcurcumin (DAC) comes from turmeric, a natural spice often used in food. DAC may have the ability to fight germs, including the bacteria Enterococcus faecalis. We tested DAC's ability to kill E. faecalis and stopping the formation of films of the bacteria. We found that a small amount of DAC did kill E. faecalis. When used with calcium hydroxide, DAC works even better to reduce the formation of bacterial films by 77%. DAC is safe to be used on teeth, so may be a useful ingredient for preserving mouth health.


Subject(s)
Anti-Bacterial Agents , Biofilms , Curcumin , Enterococcus faecalis , Microbial Sensitivity Tests , Moths , Biofilms/drug effects , Enterococcus faecalis/drug effects , Enterococcus faecalis/physiology , Curcumin/pharmacology , Curcumin/analogs & derivatives , Curcumin/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Animals , Moths/drug effects , Moths/microbiology , Disinfection/methods , Drug Synergism , Calcium Hydroxide/pharmacology , Dental Pulp Cavity/microbiology
9.
Scand J Pain ; 24(1)2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38557595

ABSTRACT

OBJECTIVES: Despite the fact that fibromyalgia, a widespread disease of the musculoskeletal system, has no specific treatment, patients have shown improvement after pharmacological intervention. Pregabalin has demonstrated efficacy; however, its adverse effects may reduce treatment adherence. In this context, neuromodulatory techniques such as transcranial direct current stimulation (tDCS) may be employed as a complementary pain-relieving method. Consequently, the purpose of this study was to evaluate the effect of pregabalin and tDCS treatments on the behavioral and biomarker parameters of rats submitted to a fibromyalgia-like model. METHODS: Forty adult male Wistar rats were divided into two groups: control and reserpine. Five days after the end of the administration of reserpine (1 mg/kg/3 days) to induce a fibromyalgia-like model, rats were randomly assigned to receive either vehicle or pregabalin (30 mg/kg) along with sham or active- tDCS treatments. The evaluated behavioral parameters included mechanical allodynia by von Frey test and anxiety-like behaviors by elevated plus-maze test (time spent in opened and closed arms, number of entries in opened and closed arms, protected head-dipping, unprotected head-dipping [NPHD], grooming, rearing, fecal boluses). The biomarker analysis (brain-derived neurotrophic factor [BDNF] and tumor necrosis factor-α [TNF-α]) was performed in brainstem and cerebral cortex and in serum. RESULTS: tDCS reversed the reduction in the mechanical nociceptive threshold and the decrease in the serum BDNF levels induced by the model of fibromyalgia; however, there was no effect of pregabalin in the mechanical threshold. There were no effects of pregabalin or tDCS found in TNF-α levels. The pain model induced an increase in grooming time and a decrease in NPHD and rearing; while tDCS reversed the increase in grooming, pregabalin reversed the decrease in NPHD. CONCLUSIONS: tDCS was more effective than pregabalin in controlling nociception and anxiety-like behavior in a rat model-like fibromyalgia. Considering the translational aspect, our findings suggest that tDCS could be a potential non-pharmacological treatment for fibromyalgia.


Subject(s)
Fibromyalgia , Transcranial Direct Current Stimulation , Humans , Adult , Rats , Male , Animals , Transcranial Direct Current Stimulation/methods , Fibromyalgia/drug therapy , Pregabalin/pharmacology , Brain-Derived Neurotrophic Factor , Rats, Wistar , Tumor Necrosis Factor-alpha , Nociception/physiology , Reserpine , Pain , Anxiety/drug therapy , Biomarkers
10.
Int J Mol Sci ; 25(7)2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38612588

ABSTRACT

Lung adenocarcinoma (LUAD) is a highly prevalent and lethal form of lung cancer, comprising approximately half of all cases. It is often diagnosed at advanced stages with brain metastasis (BM), resulting in high mortality rates. Current BM management involves complex interventions and conventional therapies that offer limited survival benefits with neurotoxic side effects. The tumor microenvironment (TME) is a complex system where cancer cells interact with various elements, significantly influencing tumor behavior. Immunotherapies, particularly immune checkpoint inhibitors, target the TME for cancer treatment. Despite their effectiveness, it is crucial to understand metastatic lung cancer and the specific characteristics of the TME, including cell-cell communication mechanisms, to refine treatments. Herein, we investigated the tumor microenvironment of brain metastasis from lung adenocarcinoma (LUAD-BM) and primary tumors across various stages (I, II, III, and IV) using single-cell RNA sequencing (scRNA-seq) from publicly available datasets. Our analysis included exploring the immune and non-immune cell composition and the expression profiles and functions of cell type-specific genes, and investigating the interactions between different cells within the TME. Our results showed that T cells constitute the majority of immune cells present in primary tumors, whereas microglia represent the most dominant immune cell type in BM. Interestingly, microglia exhibit a significant increase in the COX pathway. Moreover, we have shown that microglia primarily interact with oligodendrocytes and endothelial cells. One significant interaction was identified between DLL4 and NOTCH4, which demonstrated a relevant association between endothelial cells and microglia and between microglia and oligodendrocytes. Finally, we observed that several genes within the HLA complex are suppressed in BM tissue. Our study reveals the complex molecular and cellular dynamics of BM-LUAD, providing a path for improved patient outcomes with personalized treatments and immunotherapies.


Subject(s)
Adenocarcinoma of Lung , Brain Neoplasms , Lung Neoplasms , Neurotoxicity Syndromes , Humans , Endothelial Cells , Adenocarcinoma of Lung/genetics , Brain Neoplasms/genetics , Lung Neoplasms/genetics , Gene Expression Profiling , Tumor Microenvironment/genetics
11.
Lasers Med Sci ; 39(1): 70, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38378954

ABSTRACT

Inflammatory bowel diseases (IBD) are chronic and multifactorial diseases characterized by dysfunction of the intestinal mucosa and impaired immune response. Data show an important relationship between intestine and respiratory tract. The treatments of IBD are limited. Photobiomodulation (PBM) is an effective anti-inflammatory therapy. Our objective was to evaluate the repercussion of IBD as well as its treatment with PBM on pulmonary homeostasis. Male Wistar rats were submitted to IBD induction by acetic acid and treated or not with PBM. Rats were irradiated with red LED on both right and left sides of the ventral surface and beside the external anal region during 3 consecutive days (wavelenght 660 nm, power 100 mw, total energy 15 J and time of irradiation 150 s per point). Our results showed that IBD altered pulmonary homeostasis, since we observed an increase in the histopathological score, in myeloperoxidase activity (MPO), in mast cell degranulation, and in the release and gene expression of cytokines. We also showed that PBM treatment reduced biomarkers of IBD and reverted all augmented parameters in the lung, restoring its homeostasis. Thus, we confirm experimentally the important gut-lung axis and the role of PBM as a promising therapy.


Subject(s)
Inflammatory Bowel Diseases , Low-Level Light Therapy , Rats , Male , Animals , Rats, Wistar , Low-Level Light Therapy/methods , Inflammatory Bowel Diseases/radiotherapy , Antioxidants , Lung
12.
Child Adolesc Psychiatr Clin N Am ; 33(2): 207-218, 2024 04.
Article in English | MEDLINE | ID: mdl-38395506

ABSTRACT

There is an ongoing diagnostic and treatment challenge for migrant youth with posttraumatic stress disorder (PTSD) that many clinicians face. Current studies have helped clinicians to develop a better understanding of the migrant youth's journey including potentially traumatic and adverse events they encounter. This includes determining if premigration, migration, and postmigration stressors have had an impact on the individual. This has also helped clinicians, educators, and legal advocates to use a collaborative approach to address the migrant youth's needs for managing the severity of PTSD symptoms.


Subject(s)
Stress Disorders, Post-Traumatic , Transients and Migrants , Humans , Adolescent , Stress Disorders, Post-Traumatic/diagnosis , Stress Disorders, Post-Traumatic/therapy , Longitudinal Studies
13.
Vet Immunol Immunopathol ; 269: 110729, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38377627

ABSTRACT

Bovine tuberculosis (bTB), which is caused by Mycobacterium bovis, is a single health concern, which causes economic losses, is a sanitary barrier and is a zoonotic concern. The golden-pattern intradermic tests have low sensitivity of about 50%. To fix this sensitivity problem, immunoassays could be a powerful tool. However, few studies produced antigens for bTB immunoassays, which needs improvements. Aim of this study was to produce multiepitope chimeric antigens (MCA) to use for bTB diagnosis. To achieve MCA design and development, extensive bibliographic search, antigenic epitope prediction, specificity, hydrophobicity, and 3D structure modeling analyses were performed, as well as cloning, expression and purification. Seven epitopes from four different target proteins (MPB-70, MPB-83, ESAT-6 and GroEL) were combined in five chimeras containing five repetitions of each epitope to enhance antibodies affinity. 3D predicted models revealed that all chimeras have a high percentage of disorder, which could enhance antibody recognition, although taking to protein instability. Each chimera was cloned into pET28a (+) expression plasmids and expressed in six Escherichia coli expression strains. Chimeras 3, 4 and 5 could be solubilized in 8 M urea and purified by ion exchange affinity chromatography. Against bTB positive and negative sera, purified chimera 5 had the best results in indirect dot blot and ELISA, as well as in lateral flow dot blot immunoassay. In conclusion, chimera 5, an MPB-83 containing MCA, could be used for further studies, aimed to develop a serologic or rapid test for bTB diagnosis.


Subject(s)
Cattle Diseases , Tuberculosis, Bovine , Animals , Cattle , Tuberculosis, Bovine/diagnosis , Antigens, Bacterial/genetics , Bacterial Proteins/genetics , Serologic Tests/veterinary , Enzyme-Linked Immunosorbent Assay/veterinary , Enzyme-Linked Immunosorbent Assay/methods , Epitopes/genetics , Computational Biology , Sensitivity and Specificity , Recombinant Proteins
14.
J Trace Elem Med Biol ; 83: 127376, 2024 May.
Article in English | MEDLINE | ID: mdl-38183920

ABSTRACT

INTRODUCTION: The increasing prevalence of obesity has become a major health problem worldwide. The causes of obesity are multifactorial and could be influenced by dietary patterns and genetic factors. Obesity has been associated with a decrease in micronutrient intake and consequently decreased blood concentrations. Selenium is an essential micronutrient for human health, and its metabolism could be affected by obesity, especially severe obesity. This study aimed to identify differential methylation genes associated with serum selenium concentration in women with and without obesity. METHODOLOGY: Thirty-four patients were enrolled in the study and divided into two groups: Obese (Ob) n = 20 and Non-Obese (NOb) n = 14, according to the Body Mass Index (BMI). Anthropometry, body composition, serum selenium, selenium intake, and biochemical parameters were evaluated. DNA extraction and bisulfite conversion were performed to hybridize the samples on the 450k Methylation Chip Infinium Beadchip (Illumina). Bioinformatics analysis was performed using the R program and the Champ package. The differentially methylated regions (DMRs) were identified using the Bumphunter method. In addition, logarithmic conversion was performed for the analysis of serum selenium and methylation. RESULTS: In the Ob group, the body weight, BMI, fat mass, and free fat mass were higher than in the NOb group, as expected. Interestingly, the serum selenium was lower in the Ob than in the NOb group without differences in selenium intake. One DMR corresponding to the CPT1B gene, involved in lipid oxidation, was related to selenium levels. This region was hypermethylated in the Ob group, indicating that the intersection between selenium deficiency and hypermethylation could influence the expression of the CPT1B gene. The transcriptional analysis confirmed the lower expression of the CPT1B gene in the Ob group. CONCLUSION: Studies connecting epigenetics to environmental factors could offer insights into the mechanisms involving the expression of genes related to obesity and its comorbidities. Here we demonstrated that the mineral selenium might play an essential role in lipid oxidation via epigenetic and transcriptional regulation of the CPT1B gene in obesity.


Subject(s)
Carnitine O-Palmitoyltransferase , Epigenesis, Genetic , Obesity , Selenium , Female , Humans , Carnitine O-Palmitoyltransferase/metabolism , DNA Methylation/genetics , Epigenesis, Genetic/genetics , Gene Expression Regulation , Lipids , Obesity/genetics , Obesity/metabolism , Selenium/metabolism
16.
Clin Pharmacol Ther ; 115(1): 139-146, 2024 01.
Article in English | MEDLINE | ID: mdl-37897056

ABSTRACT

Study sponsors and market authorization holders are required by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) to enroll patients administered a gene therapy product, whether in a trial setting or post-licensure, in a long term follow-up safety study to continue the safety assessments of their product. These follow-up studies range between 5 and 15 years after dosing. This unprecedented duration of engagement with patients and caregivers raises logistical challenges that will require innovation and collaboration across sponsors and regulators. In this paper we delineate some of the key considerations for designing long term follow-up protocols in the gene therapy setting, with an eye toward platform and master protocol approaches, and offer guidance for innovative operational and statistical methods that can help assess the safety profile and durability of response for these novel therapeutics.


Subject(s)
Genetic Therapy , United States , Humans , Follow-Up Studies , Genetic Therapy/adverse effects , United States Food and Drug Administration
17.
Reprod Domest Anim ; 59(1): e14496, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37888854

ABSTRACT

This study aimed to compare the postpartum uterine dynamics of primiparous precocious (PP), primiparous conventional (PC) and multiparous conventional (MC) Bos indicus beef cows. For this purpose, PP (n = 8), PC (n = 18) and MC (n = 12) cows were enrolled in this study. These cows were evaluated at 20 and 10 days prepartum and weekly from parturition to 42 days postpartum (DPP). During this period, body weight (BW), subcutaneous fat thickness (SFT) and serum concentrations of glucose, ß-hydroxybutyrate, albumin and haptoglobin were measured. Proportion of polymorphonuclear (PMN) cells, and abundance of mRNA transcripts of genes involved in uterine inflammation and uterine health were evaluated. The PP cows had lower (p < .05) BW and SFT than that for PC and MC cows during the study period. The serum concentration of albumin after 35 DPP was lower (p < .05) in PP cows. The PP cows had the highest proportion of PMN on 28 and 35 DPP compared to PC and MC cows. The relative mRNA abundance of IL-1ß and IL-8 increased after 21 DPP in PP cows compared to the other groups. The PC had the highest, MC had an intermediate, and PP cows had the lowest relative abundance of IL10 mRNA. Overall, these findings indicated that uterine inflammation was more pronounced in PP cows. Moreover, based on the proportion of PMN and abundance of transcripts associated with inflammation in the uterus, PP cows may require a longer period to recover their uterine health after calving.


Subject(s)
Cattle Diseases , Uterine Diseases , Pregnancy , Female , Cattle , Animals , Lactation , Postpartum Period , Uterine Diseases/veterinary , Inflammation/veterinary , Body Weight , RNA, Messenger , Albumins , Milk
18.
Fisioter. Mov. (Online) ; 37: e37117, 2024. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1557766

ABSTRACT

Abstract Introduction Ultrasound used in diathermic therapies aims to achieve temperatures between 40 and 45 °C, since temperatures above 45 °C are known to cause tissue necrosis and burns. Many studies have been conducted to investigate the effect of therapeutic ultrasound in the presence of metallic implants, using phantoms (test samples) and in vivo and ex vivo animal models. In most of these studies, the ultrasound probe is fixed in one area, while in clinical practice, it is recommended that it be moved to avoid possible local overheating. Objective To analyze the thermal field at the muscle-bone interface in phantoms in the presence or absence of metallic implants after the application of therapeutic ultrasound. Methods Phantoms composed of layers simulating fat and muscle, and a layer of beef rib bone, with and without a titanium metallic implant, were prepared. The experiment involved different intensities (1.0, 1.5, and 2.0 W/cm2) and exposure times (5 and 10 minutes), common in clinics, with linear scanning of the probe. Results The experiments indicated that the muscle/implant interface heated less than the muscle/bone interface, especially at intensities of 1.5 and 2.0 W/cm2, after 5 and 10 minutes of treatment. Conclusion The results suggest the possibility of using therapeutic ultrasound in patients with metallic implants, encouraging future research to develop evidence-based protocols and safe recommendations in physiotherapy.


Resumo Introdução O ultrassom utilizado em terapias diatérmicas visa atingir temperaturas entre 40 e 45 °C, sabendo-se que temperaturas acima de 45 °C podem causar necrose tecidual e queimaduras. Muitas pesquisas têm sido realizadas para estudar o efeito do ultrassom terapêutico na presença de implantes metálicos, utilizando phantoms (corpos de prova) e animais in vivo e ex vivo. Na maioria dessas pesquisas, o cabeçote ultrassônico está fixo em uma área, enquanto que na prática clínica recomenda-se que ele seja movimentado para evitar eventuais sobreaquecimentos locais. Objetivo Analisar o campo térmico na interface músculo-osso em phantoms na presença ou ausência de implantes metálicos após a aplicação do ultrassom terapêutico. Métodos Foram elaborados phantoms compostos de camadas simuladoras de gordura e músculo e de uma camada de osso de costela bovina, sendo esta com e sem implante metálico de titânio. O experimento envolveu diferentes intensidades (1.0, 1.5 e 2.0 W/cm2) e tempos de exposição (5 e 10 minutos) comuns em clínica, com varredura linear do cabeçote. Resultados Os experimentos indicaram que a interface músculo/implante aqueceu menos do que a interface músculo/osso, especialmente nas intensidades de 1.5 e 2.0 W/cm2, após 5 e 10 minutos de tratamento. Conclusão Os resultados obtidos apontam para a possibilidade de utilização do ultrassom terapêutico em pacientes com implantes metálicos, incentivando pesquisas futuras para desenvolver protocolos baseados em evidências e recomendações seguras na fisioterapia.

19.
J Med Food ; 27(1): 47-59, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38156814

ABSTRACT

This study evaluates the effects of supplementation of murici (Byrsonima crassifolia) and taperebá (Spondias mombin) pulp extracts on dietary intake, body composition, biochemical parameters, and markers of oxidative stress. Two experiments were conducted with a total of 80 healthy male Wistar rats and a 30-day supplementation. In the first experiment, animals were divided into control (C) group, murici group 50 mg/(kg⸱day) (50Mu), murici group 100 mg/(kg⸱day) (100Mu), and murici group 200 mg/(kg⸱day) (200Mu). In the second experiment, animals were divided into C group, taperebá group 50 mg/(kg⸱day) (50Tap), taperebá group 100 mg/(kg⸱day) (100Tap), and taperebá group 200 mg/(kg⸱day) (200Tap). Results showed lower feed intake in 50Mu, 100Mu, and 100Tap groups (13%, 12%, and 10%, respectively, P < .05) and lower body fat in 200Mu, 100Tap, and 200Tap groups (16.0%, 29.1%, and 27.1%, respectively, P < .05). Only the 100Tap group showed reduced adipose tissue content (30.4%; P < .05). Increased plasma antioxidant capacity was observed at all doses for both fruits. Taperebá supplementation reduced ferrous oxidation-xylenol orange levels (50Tap: 8.4%, 100Tap: 16.1%, 200Tap: 24.3%; P < .05) and increased thiol levels (50Tap: 39%, 100Tap: 31%; P < .05). Serum thiobarbituric acid reactive substances levels were reduced in all groups receiving taperebá (50Tap: 77.7%, 100Tap: 73.1%, 200Tap: 73.8%; P < .05) and murici (50Mu: 44.5%, 100Mu: 34%, 200Mu: 43%; P < .05). Therefore, it is suggested that the inclusion of these fruits in the diet can contribute to health maintenance and disease prevention, through their effects on controlling food intake, improving body composition, and in combating oxidative stress.


Subject(s)
Anacardiaceae , Oxidative Stress , Rats , Male , Animals , Rats, Wistar , Antioxidants/pharmacology , Eating , Dietary Supplements
20.
Cells ; 12(24)2023 12 08.
Article in English | MEDLINE | ID: mdl-38132121

ABSTRACT

In recent years, there has been a growing interest in the relationship between microorganisms in the surrounding environment and cancer cells. While the tumor microenvironment predominantly comprises cancer cells, stromal cells, and immune cells, emerging research highlights the significant contributions of microbial cells to tumor development and progression. Although the impact of the gut microbiome on treatment response in lung cancer is well established, recent investigations indicate complex roles of lung microbiota in lung cancer. This article focuses on recent findings on the human lung microbiome and its impacts in cancer development and progression. We delve into the characteristics of the lung microbiome and its influence on lung cancer development. Additionally, we explore the characteristics of the intratumoral microbiome, the metabolic interactions between lung tumor cells, and how microorganism-produced metabolites can contribute to cancer progression. Furthermore, we provide a comprehensive review of the current literature on the lung microbiome and its implications for the metastatic potential of tumor cells. Additionally, this review discusses the potential for therapeutic modulation of the microbiome to establish lung cancer prevention strategies and optimize lung cancer treatment.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Gastrointestinal Microbiome , Lung Neoplasms , Microbiota , Humans , Stromal Cells , Tumor Microenvironment
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