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2.
Arch Public Health ; 82(1): 172, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39354567

RESUMEN

AIM: This study examined the association of low handgrip strength (HGS) for falls in middle-aged adults and older adults every half-decade of life. METHODS: This cross-sectional study was conducted using the public data from the first wave of the Brazilian Longitudinal Study of Aging (ELSI-Brazil). The participants were allocated into seven age groups 50-54, 55-59, 60-64, 65-69, 70-74, 75-79, and ≥ 80 years. Binary logistic regression analysis was performed to identify the odds ratio (OR) of low HGS to the falls regardless of confounding variables such as sex, balance, gait speed, and total number of health conditions. RESULTS: A total of 8,112 participants aged 50-105 years (median = 62.0 years): 3,490 males (median = 60.0 years) and 4,622 females (median = 63.0 years) attended the study. Altogether, 21.5% of participants experienced at least one fall. HGS gradually decreases over each half-decade of life. In addition, low HGS presented a significative OR (p < 0.05) for falls for age groups, until 80 s, even when considering confounding variables. CONCLUSIONS: Low HGS is associated with falls in middle-aged adults over their 50 s and remained a strong measure of falls across each subsequent half-decade of life, until 80 s.

3.
Planta Med ; 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39227040

RESUMEN

Monoterpenes and sesquiterpenes are classes of organic compounds found in various natural products, such as the essential oil of Hyptis crenata (EOHc). The therapeutic potential of these terpenes present in EOHc is evidenced by their effect on smooth muscle and potential clinical applications. Among the highlighted monoterpenes, such as sabinene, α-pinene, and ß-pinene, a relaxing effect on rat intestinal smooth muscles is observed, attributed to interaction with calcium channels. Furthermore, monoterpenoids like borneol, cineole, and linalool also demonstrate vasorelaxant properties, suggesting potential in the treatment of cardiovascular conditions. Sesquiterpenes, such as caryophyllene and aromadendrenes, exhibit relaxing effects in various smooth muscle tissues, such as rat uterus and guinea pig ileum, indicating pharmacological potential in these areas. The translational exploration of targets, such as calcium channels and G protein-coupled receptors, highlights the importance of these compounds in discovering new therapies based on natural products for treating various medical conditions.

4.
J Peripher Nerv Syst ; 29(3): 356-362, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39165030

RESUMEN

BACKGROUND AND AIMS: Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae), an intracellular bacillus that systematically invades the peripheral nerves. Diagnosing leprosy neuropathy is still a defying skill, and late diagnosis and treatment are still a reality. Based on the biological characteristics of M. leprae, particularly its preference for invading the Schwann cells localized at the coldest areas of human body, we hypothesized that these areas have focal demyelination that may escape detection through standard nerve conduction studies (NCSs) protocols. METHODS: Twenty-five patients with confirmed multibacillary leprosy and 14 controls were accessed. A multisegmented NCS protocol (MP) was performed, targeting short segments through the coldest areas, to identify focal areas of slowed conduction velocity. The effectiveness of this multisegmented protocol was compared to the standard protocol (SP) to detect abnormalities. RESULTS: All leprosy patients presented an abnormal study with the MP, contrasting to 19 with the SP. The most frequent NCS pattern was an asymmetric neuropathy with focal slowing of conduction velocity, found in 23 out of 25 leprosy patients. Significant differences favoring the proposed method were observed when comparing the MP with the SP. Notably, the MP increased the sensitivity to detect abnormalities by 122%, 133%, and 257% for the median, peroneal, and tibial nerves, respectively. MP also increases sensitivity to detect focal abnormalities in the ulnar nerve. INTERPRETATION: The MP protocol significantly increases the sensitivity of NCSs to detect neurophysiological abnormalities in leprosy neuropathy.


Asunto(s)
Conducción Nerviosa , Humanos , Conducción Nerviosa/fisiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Lepra/fisiopatología , Lepra/complicaciones , Adulto Joven , Nervios Periféricos/fisiopatología , Lepra Multibacilar/fisiopatología , Lepra Multibacilar/diagnóstico
5.
Pathogens ; 13(8)2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39204310

RESUMEN

One Health (OH) is an integrative approach to human, animal, and environmental health and can be used as a comprehensive indicator for comparative purposes. Although an OH index has been proposed for comparing cities, states, and countries, to date, no practical study has compared countries using this approach. Accordingly, this study aimed to assess OH initiatives using a survey with a veterinary public health focus. The questionnaire contained 104 quantitative questions and was sent to representatives of governmental institutions of 32 countries in the Americas. After exclusion criteria were considered, a total of 35 questionnaires from 17 countries were analyzed, with country names remaining undisclosed during the statistical analyses to protect potentially sensitive information. Principal component analysis (PCA) of health parameters in Latin America and the Caribbean (LAC) as a function of country perception (self-vector) showed that food safety was ranked higher than public policies (p = 0.009), and that both (p = 0.003) were ranked higher than institutional routines related to zoonosis programs. National policies in accordance with international standards, regulations, recommendations, and guidelines was considered the standout topic for public policy, with higher-ranking topics including standard. Meanwhile, challenging topics included tools, preparedness, governance, and research. Food safety showed both strengths and challenges in the coordination of its activities with other sectors. Food safety communication was scored as a strength, while foodborne diseases prevention was ranked as a challenge. Institutional routines for zoonosis maintained both strong and challenging topics in the execution and implementation of attributions and daily routine. Thus, the survey showed that topics such as access to and compliance with international guidelines and intercountry integration were ranked higher than in-country articulation, particularly among food safety, zoonoses, and environmental institutions.

6.
World J Clin Oncol ; 15(8): 992-1001, 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39193152

RESUMEN

Cancer, the second leading global cause of death, impacts both physically and emotionally. Conventional treatments such as surgeries, chemotherapy, and radiotherapy have adverse effects, driving the need for more precise approaches. Precision medicine enables more targeted treatments. Genetic mapping, alongside other molecular biology approaches, identifies specific genes, contributing to accurate prognoses. The review addresses, in clinical use, a molecular perspective on treatment. Biomarkers like alpha-fetoprotein, beta-human chorionic gonadotropin, 5-hydroxyindoleacetic acid, programmed death-1, and cytotoxic T lymphocyte-associated protein 4 are explored, providing valuable information. Bioinformatics, with an emphasis on artificial intelligence, revolutionizes the analysis of biological data, offering more accurate diagnoses. Techniques like liquid biopsy are emphasized for early detection. Precision medicine guides therapeutic strategies based on the molecular characteristics of the tumor, as evidenced in the molecular subtypes of breast cancer. Classifications allow personalized treatments, highlighting the role of trastuzumab and endocrine therapies. Despite the benefits, challenges persist, including high costs, tumor heterogeneity, and ethical issues. Overcoming obstacles requires collaboration, ensuring that advances in molecular biology translate into accessible benefits for all.

7.
Infect Dis Health ; 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39107205

RESUMEN

BACKGROUND: Peripheral venous catheters (PVCs) remain the primary mode of short-term venous access for managing intravenous fluid, obtaining blood samples, and peripheral parenteral nutrition. They may get contaminated and require regular monitoring to prevent complications. This study evaluated the occurrence of phlebitis and its associated-clinical and microbiological indicators. METHODS: The frequency of phlebitis was evaluated in hospitalized patients of both medical and surgical fields. Subsequently, the dichotomous association between the presence of phlebitis and the clinical aspects was investigated. In parallel, the bacterial contamination of PVCs was assessed through culture-based methods, microscopy observation, and 16S rRNA gene sequencing. RESULTS: Approximately one in four patients presented phlebitis (28.4%). The most frequent symptom was erythema at access site, with or without pain, corresponding to Score 1 on the phlebitis scale (17.9%). Colonization of both lumen and external surface of PVC was observed in 31.3% of the samples. Staphylococcus and Pseudomonas were the most isolated bacterial genera on the PVC surface. No significant association was observed between the presence of phlebitis and the clinical aspects, as well as the presence of microorganisms. CONCLUSION: Microorganism were present on both internal and external PVC surface, without being associated to phlebitis.

8.
Mitochondrial DNA B Resour ; 9(7): 892-896, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39027116

RESUMEN

Freshwater mussels perform important ecological functions in ecosystems, such as water filtration and energy cycling. Unlike marine bivalves, freshwater mussels have unique characteristics including internal fertilization and parental care. Some freshwater mussels are facing a high risk of extinction due to several factors such as climate change and habitat loss. Potomida semirugata (Lamarck, 1819) is one of the freshwater mussel species with a high risk of extinction and listed as Endangered in the Red List of the International Union for Conservation of Nature. Here, we present the first F-type mitogenome sequence of P. semirugata. The genome was sequenced on an Illumina high-throughput platform from a P. semirugata specimen collected from the Tersakan River (Turkey). The 16,093 bp mitochondrial genome sequence contains 13 protein-coding genes, 22 transfer RNAs, and two ribosomal RNAs. Phylogenetic analysis placed P. semirugata in the Lamprotulini clade with Potomida littoralis, as expected. Potomida semirugata is a poorly studied species and the genomic resource provided here will contribute to a better understanding of its biological characterization.

9.
Mitochondrial DNA B Resour ; 9(7): 886-891, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39027115

RESUMEN

Holocephali is a subclass of chondrichthyans with ample geographic distribution in marine ecosystems. Holocephalan species are organized into three families: Callorhinchidae, Chimaeridae, and Rhinochimaeridae. Despite the critical ecological and evolutionary importance, genomic information from holocephalans is still scarce, particularly from rhinochimaerids. The present study provides the first complete mitogenome of the Atlantic longnose chimaera Rhinochimaera atlantica (Holt & Byrne, 1909). The whole mitogenome was sequenced from an R. atlantica specimen, collected on the Porcupine Bank (NE Atlantic), by Illumina high-throughput sequencing. The R. atlantica mitogenome has 17,852 nucleotides with 13 protein-coding genes, 22 transfer RNA, and two ribosomal RNA genes. Nine of these genes are in the complementary strand. This mitogenome has a GC content of 41.5% and an AT content of 58.5%. The phylogenetic reconstruction provided here, using all the available complete and partial Holocephali mitogenomes, places R. atlantica in the Rhinochimaeridae family, as expected. This genomic resource will be useful in the genomic characterization of this species.

10.
Front Chem ; 12: 1412288, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39050373

RESUMEN

Candida auris and Candida haemulonii are two emerging opportunistic pathogens that have caused an increase in clinical cases in the recent years worldwide. The differentiation of some Candida species is highly laborious, difficult, costly, and time-consuming depending on the similarity between the species. Thus, this study aimed to develop a new, faster, and less expensive methodology for differentiating between C. auris and C. haemulonii based on near-infrared (NIR) spectroscopy and multivariate analysis. C. auris CBS10913 and C. haemulonii CH02 were separated in 15 plates per species, and three isolated colonies of each plate were selected for Fourier transform near-infrared (FT-NIR) analysis, totaling 90 spectra. Subsequently, principal component analysis (PCA) and variable selection algorithms, including the successive projections algorithm (SPA) and genetic algorithm (GA) coupled with linear discriminant analysis (LDA), were employed to discern distinctive patterns among the samples. The use of PCA, SPA, and GA algorithms associated with LDA achieved 100% sensitivity and specificity for the discriminations. The SPA-LDA and GA-LDA algorithms were essential in selecting the variables (infrared wavelengths) of most importance for the models, which could be attributed to binding of cell wall structures such as polysaccharides, peptides, proteins, or molecules resulting from yeasts' metabolism. These results show the high potential of combined FT-NIR and multivariate analysis techniques for the classification of Candida-like fungi, which can contribute to faster and more effective diagnosis and treatment of patients affected by these microorganisms.

11.
Otolaryngol Head Neck Surg ; 171(4): 1042-1051, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38895862

RESUMEN

OBJECTIVE: The recent surge in popularity of large language models (LLMs), such as ChatGPT, has showcased their proficiency in medical examinations and potential applications in health care. However, LLMs possess inherent limitations, including inconsistent accuracy, specific prompting requirements, and the risk of generating harmful hallucinations. A domain-specific model might address these limitations effectively. STUDY DESIGN: Developmental design. SETTING: Virtual. METHODS: Otolaryngology-head and neck surgery (OHNS) relevant data were systematically gathered from open-access Internet sources and indexed into a knowledge database. We leveraged Retrieval-Augmented Language Modeling to recall this information and utilized it for pretraining, which was then integrated into ChatGPT4.0, creating an OHNS-specific knowledge question & answer platform known as ChatENT. The model is further tested on different types of questions. RESULTS: ChatENT showed enhanced performance in the analysis and interpretation of OHNS information, outperforming ChatGPT4.0 in both the Canadian Royal College OHNS sample examination questions challenge and the US board practice questions challenge, with a 58.4% and 26.0% error reduction, respectively. ChatENT generated fewer hallucinations and demonstrated greater consistency. CONCLUSION: To the best of our knowledge, ChatENT is the first specialty-specific knowledge retrieval artificial intelligence in the medical field that utilizes the latest LLM. It appears to have considerable promise in areas such as medical education, patient education, and clinical decision support. The model has demonstrated the capacity to overcome the limitations of existing LLMs, thereby signaling a future of more precise, safe, and user-friendly applications in the realm of OHNS and other medical fields.


Asunto(s)
Otolaringología , Humanos , Otolaringología/educación , Almacenamiento y Recuperación de la Información/métodos , Procedimientos Quirúrgicos Otorrinolaringológicos/educación , Lenguaje
12.
Ann Transl Med ; 12(3): 44, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38911564

RESUMEN

Background: There is a limited research on predictive models of fat mass ratio (FMR) in people living with human immunodeficiency virus (HIV) (PWH). This study aimed to develop models considering anthropometric and health-related factors to predict and validate FMR in PWH regardless of sex. Methods: One hundred and six Brazilian PWH (46.4±9.8 years) were evaluated for body composition using dual-energy X-ray absorptiometry (DXA), body circumference (BC), and skinfold thicknesses (SKs). FMR predictive models were developed using stepwise linear regression, and their agreement with DXA was assessed using Bland-Altman plots. Cross-validation was performed using the predicted residual error sum of squares (PRESS) method. Results: Six FMR estimation models were developed for PWH, with adjusted R2 ranging from 0.43 to 0.72, standard error of the estimate (SEE) from 0.16% to 0.22%, and 95% confidence interval (CI) from 1.03 to 1.15. Model 6, including thigh SK, waist BC, therapy duration, subscapular SK, education years, and abdominal SK, exhibited the highest determination power (R2 adjusted 0.72, SEE 0.16%, and 95% CI: 1.06-1.15). The agreement between DXA-based FMR and predictive models showed minimal bias (-0.03 to +0.04) and narrower limits of agreement, particularly for the top-performing model (-0.33 to +0.30). Model 6 exhibited a high adjusted Q2PRESS (0.70) and low SPRESS (0.17). Conclusions: Our predictive models advance the study of body composition in PWH by consolidating the use of anthropometry for diagnosing and monitoring lipodystrophy regardless of sex.

13.
Chemosphere ; 362: 142504, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38825243

RESUMEN

The aerobic granular sludge (AGS) biotechnology has been explored for wastewater treatment for over two decades. AGS is gaining increased interest due to its enhanced treatment performance ability and the potential for resource recovery from AGS-based wastewater treatment systems. Resource recovery from AGS is a promising approach to sustainable wastewater treatment and attaining a circular economy in the wastewater management industry. Currently, research is at an advanced stage on recovering value-added resources such as phosphorus, polyhydroxyalkanoates, alginate-like exopolysaccharides, and tryptophan from waste aerobic granules. Recently, other value-added resources, including curdlan, have been identified in the aerobic granule matrix, and this may increase the sustainability of biotechnology in the wastewater industry. This paper provides an overview of AGS resource recovery potential. In particular, the potential for enhanced curdlan biosynthesis in the granule matrix and its recovery from AGS wastewater treatment systems is outlined.


Asunto(s)
Aguas del Alcantarillado , Eliminación de Residuos Líquidos , Aguas Residuales , beta-Glucanos , beta-Glucanos/metabolismo , Aguas del Alcantarillado/microbiología , Aguas del Alcantarillado/química , Aguas Residuales/química , Eliminación de Residuos Líquidos/métodos , Aerobiosis
14.
Environ Res ; 258: 119412, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38876418

RESUMEN

Human activities have changed the natural rates at which metals are moved and accumulated in both land and water environments, resulting in negative impacts on local wildlife. In this study, concentrations of Cr, Ni, Cd, Pb, Cu, Mn, Co, and Zn were evaluated in water and riverbed sediment samples collected from the Verde River basin (VR), as well as in tissue samples from five native Loricariidae species. Sediment samples collected from the central section of the VR riverbed indicated the presence of metal concentrations, which were primarily attributed to scattered pollution sources linked to rural activities in the surrounding areas. The bioconcentration factor in the Loricariids liver presented the highest average values for Zn (1.27-58.21), Co (0.48-14.91) and Cu (1.15-11.14). The same pattern was observed in the muscle, but in a lower proportion. Regarding the bioaccumulation factor, Co (1.54-34.84), Cu (5.85-25.22) and Zn (0.64-18.08) attained the highest average values in the liver. The co-inertia analysis examined the spatial distribution of metal concentrations in riverbed sediments and in tissues of Loricariids from the upper, middle, and lower stretches of the river, including the river mouth. The analysis revealed varying patterns, with samples from some regions showing higher bioaccumulation levels. This suggests that riverbed sediments are a primary source of metal contamination in Loricariids from these areas. The pollution has had a significant impact on the bioaccumulation of metals in the VR' Loricariids, which are good indicators of sediment-associated metal bioaccumulation. The metal concentrations recorded in both the riverbed sediments and Loricariids surpassed international and Brazilian limits set for aquatic health and safe human consumption. Given the importance of the Verde River in terms of its ecological, social, cultural, and economic roles, it is essential to implement biomonitoring and control measures to safeguard both terrestrial and aquatic resources.


Asunto(s)
Bagres , Monitoreo del Ambiente , Sedimentos Geológicos , Ríos , Contaminantes Químicos del Agua , Sedimentos Geológicos/química , Sedimentos Geológicos/análisis , Animales , Contaminantes Químicos del Agua/análisis , Ríos/química , Bagres/metabolismo , Brasil , Hígado/química , Hígado/metabolismo , Metales Pesados/análisis , Metales/análisis , Bioacumulación
15.
Genetica ; 152(2-3): 71-81, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38888686

RESUMEN

Freshwater ecosystems are among the most endangered ecosystems worldwide. While numerous taxa are on the verge of extinction as a result of global changes and direct or indirect anthropogenic activity, genomic and transcriptomic resources represent a key tool for comprehending species' adaptability and serve as the foundation for conservation initiatives. The Loire grayling, Thymallus ligericus, is a freshwater European salmonid endemic to the upper Loire River basin. The species is comprised of fragmented populations that are dispersed over a small area and it has been identified as a vulnerable species. Here, we provide a multi-tissue de novo transcriptome assembly of T. ligericus. The completeness and integrity of the transcriptome were assessed before and after redundancy removal with lineage-specific libraries from Eukaryota, Metazoa, Vertebrata, and Actinopterygii. Relative gene expression was assessed for each of the analyzed tissues, using the de novo assembled transcriptome and a genome-based analysis using the available T. thymallus genome as a reference. The final assembly, with a contig N50 of 1221 and Benchmarking Universal Single-Copy Orthologs (BUSCO) scores above 94%, is made accessible along with structural and functional annotations and relative gene expression of the five tissues (NCBI SRA and FigShare databases). This is the first transcriptomic resource for this species, which provides a foundation for future research on this and other salmonid species that are increasingly exposed to environmental stressors.


Asunto(s)
Salmonidae , Transcriptoma , Animales , Salmonidae/genética , Agua Dulce , Anotación de Secuencia Molecular , Perfilación de la Expresión Génica , Especies en Peligro de Extinción , Genoma
16.
Mitochondrial DNA B Resour ; 9(6): 696-700, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38835640

RESUMEN

Freshwater mussels (Bivalvia, Unionida) play essential roles in the well-functioning of ecosystems, even providing essential services to humans. However, these bivalves face numerous threats (e.g. habitat loss and fragmentation, pollution, introduction of invasive species, and climate change) which have already led to the extinction of many populations. This underscores the need to fully characterize the biology of these species, particularly those, such as Potomida acarnanica, that are still poorly studied. This study presents the first mitogenome of P. acarnanica (Kobelt, 1879), an endemic species of Greece with a distribution limited to only two river basins. The mitochondrial genome of a P. acarnanica specimen, collected at Pamisos River (Peloponnese, Greece), was sequenced by Illumina high-throughput sequencing. This mitogenome (16,101 bp) is characterized by 13 protein-coding genes, 22 transfer RNA and 2 ribosomal RNA genes. The size of this mitogenome is within the range of another Potomida mitogenome already published for the species Potomida littoralis. In the phylogenetic inference, P. acarnanica was recovered as monophyletic with P. littoralis mitogenome in the Lamprotulini tribe, as expected. This genomic resource will assist in genetically characterizing the species, potentially benefiting future evolutionary studies and conservation efforts.

17.
BMC Biotechnol ; 24(1): 43, 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38909197

RESUMEN

Fungal diseases are often linked to poverty, which is associated with poor hygiene and sanitation conditions that have been severely worsened by the COVID-19 pandemic. Moreover, COVID-19 patients are treated with Dexamethasone, a corticosteroid that promotes an immunosuppressive profile, making patients more susceptible to opportunistic fungal infections, such as those caused by Candida species. In this study, we analyzed the prevalence of Candida yeasts in wastewater samples collected to track viral genetic material during the COVID-19 pandemic and identified the yeasts using polyphasic taxonomy. Furthermore, we investigated the production of biofilm and hydrolytic enzymes, which are known virulence factors. Our findings revealed that all Candida species could form biofilms and exhibited moderate hydrolytic enzyme activity. We also proposed a workflow for monitoring wastewater using Colony PCR instead of conventional PCR, as this technique is fast, cost-effective, and reliable. This approach enhances the accurate taxonomic identification of yeasts in environmental samples, contributing to environmental monitoring as part of the One Health approach, which preconizes the monitoring of possible emergent pathogenic microorganisms, including fungi.


Asunto(s)
COVID-19 , Candida , Aguas Residuales , Flujo de Trabajo , Aguas Residuales/microbiología , Aguas Residuales/virología , Brasil/epidemiología , Candida/aislamiento & purificación , Candida/genética , Candida/clasificación , COVID-19/epidemiología , COVID-19/virología , Humanos , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Biopelículas , Monitoreo del Ambiente/métodos , Pandemias
18.
Mol Cell ; 84(10): 1842-1854.e7, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38759624

RESUMEN

Genomic context critically modulates regulatory function but is difficult to manipulate systematically. The murine insulin-like growth factor 2 (Igf2)/H19 locus is a paradigmatic model of enhancer selectivity, whereby CTCF occupancy at an imprinting control region directs downstream enhancers to activate either H19 or Igf2. We used synthetic regulatory genomics to repeatedly replace the native locus with 157-kb payloads, and we systematically dissected its architecture. Enhancer deletion and ectopic delivery revealed previously uncharacterized long-range regulatory dependencies at the native locus. Exchanging the H19 enhancer cluster with the Sox2 locus control region (LCR) showed that the H19 enhancers relied on their native surroundings while the Sox2 LCR functioned autonomously. Analysis of regulatory DNA actuation across cell types revealed that these enhancer clusters typify broader classes of context sensitivity genome wide. These results show that unexpected dependencies influence even well-studied loci, and our approach permits large-scale manipulation of complete loci to investigate the relationship between regulatory architecture and function.


Asunto(s)
Factor de Unión a CCCTC , Elementos de Facilitación Genéticos , Factor II del Crecimiento Similar a la Insulina , ARN Largo no Codificante , Factores de Transcripción SOXB1 , Animales , Ratones , Factor de Unión a CCCTC/metabolismo , Factor de Unión a CCCTC/genética , Factor II del Crecimiento Similar a la Insulina/genética , Factor II del Crecimiento Similar a la Insulina/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismo , Región de Control de Posición/genética , Impresión Genómica , Genómica/métodos
19.
Pharmaceuticals (Basel) ; 17(5)2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38794204

RESUMEN

Safer analgesic drugs remain a hard challenge because of cardiovascular and/or gastrointestinal toxicity, mainly. So, this study evaluated in vivo the antiproliferative actions of a fraction with casearins (FC) from Casearia sylvestris leaves against human colorectal carcinomas and antihyperalgesic effects on inflammatory- or opiate-based pain relief and oncologic pain in Sarcoma 180 (S180)-bearing mice. Moreover, docking investigations evaluated the binding among Casearin X and NMDA(N-methyl-D-aspartate)-type glutamate receptors. HCT-116 colorectal carcinoma-xenografted mice were treated with FC for 15 days. Antinociceptive assays included chemically induced algesia and investigated mechanisms by pharmacological blockade. Intraplantar region S180-bearing animals received a single dose of FC and were examined for mechanical allodynia and behavior alterations. AutoDock Vina determined molecular interactions among Cas X and NMDA receptor subunits. FC reduced tumor growth at i.p. (5 and 10 mg/kg) and oral (25 mg/kg/day) doses (31.12-39.27%). FC reduced abdominal pain, as confirmed by formalin and glutamate protocols, whose antinociception activity was blocked by naloxone and L-NAME (neurogenic phase) and naloxone, atropine, and flumazenil (inflammatory phase). Meanwhile, glibenclamide potentiated the FC analgesic effects. FC increased the paw withdrawal threshold without producing changes in exploratory parameters or motor coordination. Cas X generated a more stable complex with active sites of the NMDA receptor GluN2B subunits. FC is a promising antitumor agent against colorectal carcinomas, has peripheral analgesic effects by desensitizing secondary afferent neurons, and inhibits glutamate release from presynaptic neurons and/or their action on cognate receptors. These findings emphasize the use of clerodane diterpenes against cancer-related pain conditions.

20.
Curr Med Chem ; 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38808714

RESUMEN

Leishmaniasis is a neglected tropical disease caused by protozoa parasites from the Leishmania genus. Vertebrate hosts acquire the infection through the bite of a female sandfly, initiating a complex parasite development cycle. Contrary to previous beliefs regarding cats' resistance, these animals have recently been identified as potential reservoirs for leishmaniasis. Clinical symptoms in cats can manifest in diverse forms, including cutaneous, mucocutaneous, and visceral manifestations. The diagnosis of feline leishmaniasis is complicated by nonspecific symptoms and the relatively lower specificity of serological tests. The recommended treatment for feline leishmaniasis involves the administration of medications; however, success varies in each cat. This review aims to present cases of feline leishmaniasis, highlighting clinical symptoms, diagnostic methods, therapy schedules, and outcomes. Among the 24 cases documented in the available literature, 12 achieved successful treatment without relapses, resulting in a reduced parasite load and improved symptoms. Three cases responded well but presented persistent sequelae. Two feline leishmaniasis cases initially had treatment success but later experienced recurrences. Finally, no response was observed in seven cases, leading to the euthanasia of cats due to ineffectiveness or irregularities along the therapy. Conventional treatments, despite potential hepatotoxicity and nephrotoxicity, exhibit a high efficacy in reducing parasitic load, thereby improving clinical symptoms and increasing the life expectancy of affected cats. Nevertheless, consistent adherence is crucial, as interruptions may render the therapy ineffective and contribute to parasite resistance. Therefore, addressing the challenges associated with feline leishmaniasis treatment necessitates the development of new strategies to ensure a more effective and sustained approach.

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