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1.
Vet Sci ; 11(8)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39195801

RESUMEN

Assisted reproduction technologies (ARTs) are generally considered safe; however, emerging evidence highlights the need to evaluate potential risks in adulthood to improve safety further. ART procedures like rederivation of embryos by vitrification differ from natural conditions, causing significant disparities between in vitro and in vivo embryos, affecting foetal physiology and postnatal life. This study aims to investigate whether hepatic transcriptome and metabolome changes observed postnatally are already present in foetal livers at the end of gestation. This study compared fresh and vitrified rabbit embryos, finding differences between foetuses obtained by the transfer of fresh and vitrified embryos at 24 days of gestation. Rederived embryos had reduced foetal and liver weights and crown-rump length. However, the offspring of vitrified embryos tended to be born with higher weight, showing compensatory growth in the final week of gestation (59.2 vs. 49.8 g). RNA-Seq analysis revealed 43 differentially expressed genes (DEGs) in the foetal liver of vitrified embryos compared to the fresh group. Notably, downregulated genes included BRAT1, CYP4A7, CYP2B4, RPL23, RPL22L1, PPILAL1, A1BG, IFGGC1, LRRC57, DIPP2, UGT2B14, IRGM1, NUTF2, MPST, and PPP1R1B, while upregulated genes included ACOT8, ERICH3, UBXN2A, METTL9, ALDH3A2, DERPC-like, NR5A2-like, AP-1, COG8, INHBE, and PLA2G4C. Overall, a functional annotation of these DEGs indicated an involvement in lipid metabolism and the stress and inflammatory process or immune response. Thus, our results suggest that vitrification and embryo transfer manipulation induce an adaptive response that can be observed in the liver during the last week of gestation.

2.
J Med Virol ; 96(8): e29851, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39132689

RESUMEN

Here, we performed single-cell RNA sequencing of S1 and receptor binding domain protein-specific B cells from convalescent COVID-19 patients with different clinical manifestations. This study aimed to evaluate the role and developmental pathway of atypical memory B cells (MBCs) in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The results revealed a proinflammatory signature across B cell subsets associated with disease severity, as evidenced by the upregulation of genes such as GADD45B, MAP3K8, and NFKBIA in critical and severe individuals. Furthermore, the analysis of atypical MBCs suggested a developmental pathway similar to that of conventional MBCs through germinal centers, as indicated by the expression of several genes involved in germinal center processes, including CXCR4, CXCR5, BCL2, and MYC. Additionally, the upregulation of genes characteristic of the immune response in COVID-19, such as ZFP36 and DUSP1, suggested that the differentiation and activation of atypical MBCs may be influenced by exposure to SARS-CoV-2 and that these genes may contribute to the immune response for COVID-19 recovery. Our study contributes to a better understanding of atypical MBCs in COVID-19 and the role of other B cell subsets across different clinical manifestations.


Asunto(s)
COVID-19 , Células B de Memoria , SARS-CoV-2 , Análisis de la Célula Individual , Humanos , COVID-19/inmunología , COVID-19/virología , COVID-19/genética , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Células B de Memoria/inmunología , Masculino , Adulto , Femenino , Persona de Mediana Edad , Perfilación de la Expresión Génica , Transcriptoma , Centro Germinal/inmunología , Linfocitos B/inmunología , Anciano
3.
EMBO Rep ; 25(9): 3990-4012, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39075237

RESUMEN

Metabolic dysregulation is one of the most common causes of pediatric neurodegenerative disorders. However, how the disruption of ubiquitous and essential metabolic pathways predominantly affect neural tissue remains unclear. Here we use mouse models of a childhood neurodegenerative disorder caused by AMPD2 deficiency to study cellular and molecular mechanisms that lead to selective neuronal vulnerability to purine metabolism imbalance. We show that mouse models of AMPD2 deficiency exhibit predominant degeneration of the hippocampal dentate gyrus, despite a general reduction of brain GTP levels. Neurodegeneration-resistant regions accumulate micron-sized filaments of IMPDH2, the rate limiting enzyme in GTP synthesis, while these filaments are barely detectable in the hippocampal dentate gyrus. Furthermore, we show that IMPDH2 filament disassembly reduces GTP levels and impairs growth of neural progenitor cells derived from individuals with human AMPD2 deficiency. Together, our findings suggest that IMPDH2 polymerization prevents detrimental GTP deprivation, opening the possibility of exploring the induction of IMPDH2 assembly as a therapy for neurodegeneration.


Asunto(s)
AMP Desaminasa , IMP Deshidrogenasa , Enfermedades Neurodegenerativas , Animales , Humanos , Ratones , Modelos Animales de Enfermedad , Guanosina Trifosfato/metabolismo , IMP Deshidrogenasa/metabolismo , IMP Deshidrogenasa/genética , Ratones Noqueados , Células-Madre Neurales/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/etiología , Esfingomielina Fosfodiesterasa , AMP Desaminasa/deficiencia , AMP Desaminasa/metabolismo
4.
Rev. Fac. Med. UNAM ; 67(3): 32-36, may.-jun. 2024. graf
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1569544

RESUMEN

Resumen El pseudomixoma peritoneal (PMP) es una afección poco común, inicialmente descrita en 1884 por Werth en relación con la ascitis y tumores mucinosos de ovario, y posteriormente en 1901 por Frankel, asociado a tumores mucinosos apendiculares. Se ha observado una alta prevalencia de mutaciones en el gen K-RAS y TP53 en pacientes con PMP de bajo grado, lo que desencadena la proliferación y producción excesiva de moco. Los estudios han demostrado que la cavidad peritoneal, especialmente la superficie hepática, es el sitio principal de depósito de estos tumores. La tomografía computada se considera el estándar de oro para el diagnóstico, mientras que la resonancia magnética es más sensible para detectar el origen tumoral y evaluar la extensión de la enfermedad. Aunque la laparotomía exploratoria es el método tradicional para la toma de biopsias, se están explorando alternativas menos invasivas como la biopsia guiada por ultrasonido y tomografía computarizada, que han demostrado ser eficaces. El diagnóstico diferencial incluye la endometriosis y tumores mixoides, con énfasis en la invasión al mesenterio y las características quísticas. Es crucial reconocer las diferencias en etapas avanzadas, ya que el PMP tiende a invadir los órganos desde afuera, mientras que los tumores mixoides presentan metástasis sólidas a distancia.


Abstract Pseudomyxoma peritonei (PMP) is a rare condition, first described by Werth in 1884 in association with ascites and ovarian mucinous tumors, and later in 1901 by Frankel, associated with appendicular mucinous tumors. High prevalence of mutations in the K-RAS and TP53 genes has been observed in patients with low-grade PMP, triggering proliferation and excessive mucus production. Studies have shown that the peritoneal cavity, especially the hepatic surface, is the main site for deposition of these tumors. Computed tomography is considered the gold standard for diagnosis, while magnetic resonance imaging is more sensitive for detecting the tumor origin and assessing disease extent. Although exploratory laparotomy is the traditional method for biopsy, less invasive alternatives such as ultrasound-guided and computed tomography-guided biopsy are being explored, which have proven to be effective. The differential diagnosis includes endometriosis and mixoid tumors, with emphasis on mesentery invasion and cystic characteristics. Recognizing differences in advanced stages is crucial, as PMP tends to invade organs from the outside, while mixoid tumors present distant solid metastases.

5.
Urol Case Rep ; 55: 102759, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38846926

RESUMEN

A 31-year-old male came to emergency department with acute abdominal pain from the right flank, diaphoresis and, palpitations. Contrasted abdominal CT revealed a tumor dependent from right adrenal gland and kidney. A laparoscopic radical nephrectomy was made to resect the tumor and pain relief. Pathological analysis reported poorly differentiated neuroblastoma from the right adrenal gland without involvement to kidney and ureter. The patient was sent to oncology clinic to continue with chemotherapy treatment. This is the third case of adult neuroblastoma reported in South America. Adult neuroblastoma is an uncommon cause of malignant neoplasm with an exceptional incidence reported.

6.
Theriogenology ; 224: 26-33, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38723471

RESUMEN

Pigs are usually bred through artificial insemination with liquid semen preserved at 15-20 °C. While this method of preservation brings many benefits, including a greater reproductive performance compared to frozen-thawed sperm, the period of storage is a limiting factor. As the mitochondrion regulates many facets of sperm physiology, modulating its activity could have an impact on their lifespan. Aligned with this hypothesis, the present study sought to investigate whether inhibition of voltage-dependent anion channels (VDACs), which reside in the outer mitochondrial membrane and regulate the flux of ions between mitochondria and the cytosol in somatic cells, influences the resilience of pig sperm to liquid preservation at 17 °C. For this purpose, semen samples (N = 7) were treated with two different concentrations of TRO19622 (5 µM and 50 µM), an inhibitor of VDACs, and stored at 17 °C for 10 days. At days 0, 4 and 10, sperm quality and functionality parameters were evaluated by flow cytometry and computer-assisted sperm analysis (CASA). The effects of inhibiting VDACs depended on the concentration of the inhibitor. On the one hand, the greatest concentration of TRO19622 (50 µM) led to a decrease in sperm motility, viability and mitochondrial membrane potential, which could be related to the observed intracellular Ca2+ increase. In contrast, total sperm motility was higher in samples treated with 5 µM TRO19622 than in the control, suggesting that when VDACs channels are inhibited by the lowest concentration of the blocking agent the resilience of pig sperm to liquid storage increases. In conclusion, the current research indicates that mitochondrial function, as regulated by ion channels in the outer mitochondrial membrane like VDACs, is related to the sperm resilience to liquid preservation and may influence cell lifespan.


Asunto(s)
Colestenonas , Preservación de Semen , Semen , Porcinos , Canales Aniónicos Dependientes del Voltaje , Aniones , Animales , Preservación de Semen/métodos , Inseminación Artificial , Temperatura , Motilidad Espermática , Calcio/análisis
7.
Animals (Basel) ; 14(9)2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38731285

RESUMEN

In the ex situ conservation of chondrichthyan species, successful reproduction in aquaria is essential. However, these species often exhibit reduced reproductive success under human care. A key aspect is that conventional sperm analyses do not provide insights into the functional competence of sperm. However, proteomics analysis enables a better understanding of male physiology, gaining relevance as a powerful tool for discovering protein biomarkers related to fertility. The present work aims to build the first proteome database for shark semen and to investigate the proteomic profiles of seminal plasma and spermatozoa from small-spotted catsharks (Scyliorhinus canicula) related to the underlying adaptations to both natural and aquarium environments, thereby identifying the reproductive impact in aquarium specimens. A total of 305 seminal plasma and 535 spermatozoa proteins were identified. Among these, 89 proteins (29.2% of the seminal plasma set) were common to both spermatozoa and seminal plasma. In the seminal plasma, only adenosylhomocysteinase protein showed differential abundance (DAP) between wild and aquarium animals. With respect to the spermatozoa proteins, a total of 107 DAPs were found between groups. Gene Ontology enrichment analysis highlighted the primary functional roles of these DAPs involved in oxidoreductase activity. Additionally, KEGG analysis indicated that these DAPs were primarily associated with metabolic pathways and carbon metabolism. In conclusion, we have successfully generated an initial proteome database for S. canicula seminal plasma and spermatozoa. Furthermore, we have identified protein variations, predominantly within spermatozoa, between aquarium and wild populations of S. canicula. These findings provide a foundation for future biomarker discovery in shark reproduction studies. However, additional research is required to determine whether these protein variations correlate with reproductive declines in captive sharks.

8.
PLoS One ; 19(5): e0302854, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38722950

RESUMEN

For management efforts to succeed in Caribbean fisheries, local fishers must support and be willing to comply with fishing regulations. This is more likely when fishers are included in a stock assessment process that utilizes robust scientific evidence, collected in collaboration with fishers, to evaluate the health of fish stocks. Caribbean parrotfishes are important contributors to coral reef ecosystem health while also contributing to local fisheries. Scientifically robust stock assessments require regional species-specific information on age-based key life history parameters, derived from fish age estimates. Evaluation of the accuracy of age estimation methods for fish species is a critical initial step in managing species for long-term sustainable harvest. The current study resulted from a collaborative research program between fish biologists and local fishers investigating age, growth, and reproductive biology of the seven parrotfish species landed in U.S. Caribbean fisheries; specifically, we validated age estimation for stoplight parrotfish Sparisoma viride and queen parrotfish Scarus vetula. This is the first study to directly validate age estimation for any parrotfish species through analysis of Δ14C from eye lens cores. Our age estimation validation results show that enumeration of opaque zones from thin sections of sagittal otoliths for a Sparisoma and a Scarus species provides accurate age estimates. The oldest stoplight parrotfish and queen parrotfish in the Δ14C age estimation validation series were 14 y and 16 y; while the oldest stoplight parrotfish and queen parrotfish we aged to-date using the Δ14C validated age estimation method were 20 y and 21 y, respectively. Fish longevity (maximum age attained/life span) is a key life history parameter used for estimation of natural mortality, survivorship, and lifetime reproductive output. Past reviews on parrotfishes from the Pacific and Atlantic concluded that most Caribbean/western Atlantic parrotfish species are relatively short-lived with estimated maximum ages ranging from 3-9 y. However, information from our collaborative research in the U.S. Caribbean combined with recently published age estimates for Brazilian parrotfish species indicate that many western Atlantic parrotfishes are relatively long-lived with several species attaining maximum ages in excess of 20 y.


Asunto(s)
Explotaciones Pesqueras , Longevidad , Animales , Perciformes/crecimiento & desarrollo , Perciformes/fisiología , Conservación de los Recursos Naturales/métodos , Región del Caribe , Datación Radiométrica/métodos , Océano Atlántico
9.
Histol Histopathol ; 39(10): 1295-1302, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38567534

RESUMEN

HSP47, a chaperone whose main function is the maturation of collagen molecules, is considered a marker of fibrotic diseases. Increased collagen synthesis in the testis has been associated with various pathologies leading to seminiferous tubule regression. Our aim was to study whether HSP47 is expressed in hamster Sertoli cells both in the adult and in two physiological situations of seminiferous tubule atrophy: irreversible testicular ageing and testicular regression due to short photoperiod (reversible). Eighteen animals were divided as follows: a group of 6 young animals aged 6 months, a group of 6 animals aged 24 months, which were exposed to a long photoperiod, and a final group of 6 young animals subjected to a short photoperiod. Testicular samples were fixed in methacarn and an immunohistochemical technique was used to detect HSP47. A semiquantitative study of of this protein expresion was performed between tubular sections of aged animals with complete spermatogenesis and arrested spermatogenesis and tubular sections with arrest spermatogenesis of photoinhibited testes. Sertoli cells were positive for HSP47, the intensity being greater in tubular sections with arrested spermatogenesis in both aged and photoinhibited animals. Semiquantitative analysis corroborated this observation in the sense that the expression of this protein differed according to the functional state of the seminiferous tubules. Thus, the radio of immunoreactivity was significantly higher in tubular sections with arrested spermatogenesis in aged animals compared with regressed animals, and in the latter compared with those whose tubular sections showed complete spermatogenesis. In conclusion, HSP47 expression in Sertoli cells was found for the first time in mammals. Moreover, increased expression seemed to be related to the degree of atrophy of the seminiferous epithelium and to the reversible or non-reversible physiological state of the seminiferous epithelium.


Asunto(s)
Proteínas del Choque Térmico HSP47 , Inmunohistoquímica , Células de Sertoli , Espermatogénesis , Masculino , Animales , Células de Sertoli/metabolismo , Células de Sertoli/patología , Cricetinae , Proteínas del Choque Térmico HSP47/metabolismo , Espermatogénesis/fisiología , Mesocricetus , Túbulos Seminíferos/metabolismo , Túbulos Seminíferos/patología , Testículo/metabolismo , Testículo/patología , Envejecimiento/metabolismo , Envejecimiento/patología , Fotoperiodo
10.
Genes Immun ; 25(2): 158-167, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38570727

RESUMEN

In this study, antibody response and a single-cell RNA-seq analysis were conducted on peripheral blood mononuclear cells from five different groups: naïve subjects vaccinated with AZD1222 (AZ) or Ad5-nCoV (Cso), individuals previously infected and later vaccinated (hybrid) with AZD1222 (AZ-hb) or Ad5-nCoV (Cso-hb), and those who were infected and had recovered from COVID-19 (Inf). The results showed that AZ induced more robust neutralizing antibody responses than Cso. The single-cell RNA data revealed a high frequency of memory B cells in the Cso and Cso-hb. In contrast, AZ and AZ-hb groups exhibited the highest proportion of activated naïve B cells expressing CXCR4. Transcriptomic analysis of CD4+ and CD8+ T cells demonstrated a heterogeneous response following vaccination, hybrid immunity, or natural infection. However, a single dose of Ad5-nCoV was sufficient to strongly activate CD4+ T cells (naïve and memory) expressing ANX1 and FOS, similar to the hybrid response observed with AZ. An interesting finding was the robust activation of a subset of CD8+ T cells expressing GZMB, GZMH, and IFNG genes in the Cso-hb group. Our findings suggest that both vaccines effectively stimulated the cellular immune response; however, the Ad5-nCoV induced a more robust CD8+ T-cell response in previously infected individuals.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Humanos , Linfocitos T CD8-positivos , Adenoviridae/genética , ChAdOx1 nCoV-19 , Leucocitos Mononucleares , Perfilación de la Expresión Génica , Inmunidad Adaptativa , Anticuerpos Neutralizantes/genética , Anticuerpos Antivirales/genética
11.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38521441

RESUMEN

INTRODUCTION AND OBJECTIVES: Most of the complications associated with acute and symptomatic bradyarrhythmia (ASB) occur in the time from diagnosis to permanent pacemaker implantation (PPI). We aimed to evaluate the outcomes of an urgent 24/7 PPI service (PPI-24/7) for patients with ASB. METHODS: A total of 664 patients undergoing first-time PPI for ASB were prospectively assessed during 2 periods of identical length (18 months): 341 patients who underwent the procedure during working hours only (PPI-WH), and 323 patients who underwent the procedure after the implementation of the PPI-24/7 service. The primary safety endpoint was established as the cumulative 180-day incidence of complications related to the index arrhythmia and device implant. The primary efficacy endpoint was determined as the average number of hospital stays per patient. RESULTS: The PPI-24/7 period was associated with a significant shortening of the time from diagnosis to implantation (median [interquartile range]): 3hours [2-6] vs 16 [5-21]). The cumulative incidence of patients with complications at 180 days was lower in the PPI-24/7 period: 9% vs 17% (adjusted odds ratio, 0.5; P=.002), due to a significant reduction in preimplant complications: 2.5% vs 12% (P <.001). The average number of hospital stays was reduced by 2 per patient in the PPI-24/7 period (nonparametric P <.001). PPI-24/7 implants performed outside working hours (n=178) were safe, with a 180-day cumulative incidence in procedure-related complications of 3.9%. CONCLUSIONS: Among patients with ASB, PPI-24/7 was associated with a significant reduction in patient morbidity and efficient hospital resource use.

12.
Cancer Rep (Hoboken) ; 7(2): e2002, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38389406

RESUMEN

BACKGROUND: Several studies describe an inverse statistical relationship between the presence of an allergy and development of cancer. However, the immunological mechanism involved in the relationship between these two degenerative diseases has not been explored. AIMS: The main objective of this study was to explore the possibility that the lymphocyte T helper (Th) 2 response, a characteristic of allergy, induces recognition of tumor antigens. METHODS AND RESULTS: Patients with a clinical diagnosis of breast ductal carcinoma were included. Histopathological markers related to proliferation of tumor cells were determined (Her-2-neu, Ki-67, estrogen receptor, and progesterone receptor). IHC was performed using IgE antibodies purified from an allergy patient and from each biopsy donor patient. Serum concentrations of cytokines representative of Th1 and Th2 inflammatory responses were determined. A total of 14 patients with a confirmed diagnosis of breast ductal carcinoma were included. IHC performed on biopsies showed a weak response when using purified IgE antibodies from an allergy patient; however, IHC using the IgE of each patient as the primary antibody showed an intense and highly specific signal. Serum concentrations of cytokines of the Th2 response, that is, IL-4 (130.5 pg/mL (116-135 pg/mL)), IL-5 (202 pg/mL (191-213 pg/mL)), and IL-13 (105.5 pg/mL (98-117 pg/mL)), were significantly higher than those of the Th1 response, that is, IL-6 (86 pg/mL (79-90 pg/mL)) and INF-γ (93 pg/mL (79-99 pg/mL)). CONCLUSION: Purified IgE antibodies specifically recognize tumor cells in breast ductal carcinoma.


Asunto(s)
Neoplasias de la Mama , Carcinoma Ductal de Mama , Hipersensibilidad , Humanos , Femenino , Células Th2 , Neoplasias de la Mama/diagnóstico , Antígenos de Neoplasias , Citocinas , Carcinoma Ductal de Mama/diagnóstico , Inmunoglobulina E
13.
Injury ; 55(4): 111424, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38402710

RESUMEN

INTRODUCTION: Patients with above-knee amputations (AKA) are normally treated with the traditional socket-mounted prosthesis (SMP), which is associated with a high incidence of problems. Osseointegration has been proposed as a promising option for avoiding many common SMP drawbacks. Several concerns have arisen regarding amputee osseointegration, however, mainly with respect to infection. We report on the safety of a single-stage osseointegration protocol using an antibiotic-loaded hydrogel to coat the intramedullary implant. MATERIALS AND METHODS: We retrospectively reviewed all AKA cases treated at our center between January 2019 and April 2022, in which a transcutaneous osseointegrated implant was used in a single-stage strategy, together with a rapid-resorbable hydrogel loaded with vancomycin and gentamicin. The specific protocol used, infection rate, implant osseointegration rate and implant survivorship were determined after a minimum follow-up of 12 months. RESULTS: Eleven osseointegration cases were included in the study, with an average of 16 years post-amputation (range: 3-35 years). After a median follow-up of 24 months (range 12-49 months) no patient had suffered any implant-related infection. Osseointegration of the implant had been achieved in all cases. The mid-term survivorship of the implant in our series was 100 % at the end of follow-up. Radiographs of all cases showed no loosening of the implant. Further, 91 % of the series patients were able to walk without restrictions after the rehabilitation process. CONCLUSIONS: The single-stage osseointegration protocol for AKA, using a rapid-resorbable hydrogel loaded with vancomycin and gentamicin, yields low rates of implant-related deep infection. This protocol consistently delivers high rates of radiological osseointegration, with no hydrogel-associated complications.


Asunto(s)
Miembros Artificiales , Oseointegración , Humanos , Estudios Retrospectivos , Antibacterianos , Vancomicina , Hidrogeles , Resultado del Tratamiento , Amputación Quirúrgica , Complicaciones Posoperatorias , Gentamicinas
14.
bioRxiv ; 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38328116

RESUMEN

Metabolic dysregulation is one of the most common causes of pediatric neurodegenerative disorders. However, how the disruption of ubiquitous and essential metabolic pathways predominantly affect neural tissue remains unclear. Here we use mouse models of AMPD2 deficiency to study cellular and molecular mechanisms that lead to selective neuronal vulnerability to purine metabolism imbalance. We show that AMPD deficiency in mice primarily leads to hippocampal dentate gyrus degeneration despite causing a generalized reduction of brain GTP levels. Remarkably, we found that neurodegeneration resistant regions accumulate micron sized filaments of IMPDH2, the rate limiting enzyme in GTP synthesis. In contrast, IMPDH2 filaments are barely detectable in the hippocampal dentate gyrus, which shows a progressive neuroinflammation and neurodegeneration. Furthermore, using a human AMPD2 deficient neural cell culture model, we show that blocking IMPDH2 polymerization with a dominant negative IMPDH2 variant, impairs AMPD2 deficient neural progenitor growth. Together, our findings suggest that IMPDH2 polymerization prevents detrimental GTP deprivation in neurons with available GTP precursor molecules, providing resistance to neurodegeneration. Our findings open the possibility of exploring the involvement of IMPDH2 assembly as a therapeutic intervention for neurodegeneration.

16.
Genet Sel Evol ; 56(1): 12, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38347496

RESUMEN

BACKGROUND: Intramuscular fat (IMF) content and its fatty acid (FA) composition are typically controlled by several genes, each with a small effect. In the current study, to pinpoint candidate genes and putative regulators involved in FA composition, we performed a multivariate integrative analysis between intramuscular FA and transcriptome profiles of porcine longissimus dorsi (LD) muscle. We also carried out a combination of network, regulatory impact factor (RIF), in silico prediction of putative target genes, and functional analyses to better support the biological relevance of our findings. RESULTS: For this purpose, we used LD RNA-Seq and intramuscular FA composition profiles of 129 Iberian × Duroc backcrossed pigs. We identified 378 correlated variables (13 FA and 365 genes), including six FA (C20:4n-6, C18:2n-6, C20:3n-6, C18:1n-9, C18:0, and C16:1n-7) that were among the most interconnected variables in the predicted network. The detected FA-correlated genes include genes involved in lipid and/or carbohydrate metabolism or in regulation of IMF deposition (e.g., ADIPOQ, CHUK, CYCS, CYP4B1, DLD, ELOVL6, FBP1, G0S2, GCLC, HMGCR, IDH3A, LEP, LGALS12, LPIN1, PLIN1, PNPLA8, PPP1R1B, SDR16C5, SFRP5, SOD3, SNW1, and TFRC), meat quality (GALNT15, GOT1, MDH1, NEU3, PDHA1, SDHD, and UNC93A), and transport (e.g., EXOC7 and SLC44A2). Functional analysis highlighted 54 over-represented gene ontology terms, including well-known biological processes and pathways that regulate lipid and carbohydrate metabolism. RIF analysis suggested a pivotal role for six transcription factors (CARHSP1, LBX1, MAFA, PAX7, SIX5, and TADA2A) as putative regulators of gene expression and intramuscular FA composition. Based on in silico prediction, we identified putative target genes for these six regulators. Among these, TADA2A and CARHSP1 had extreme RIF scores and present novel regulators in pigs. In addition, the expression of TADA2A correlated (either positively or negatively) with C20:4n-6, C18:2n-6, C20:3n-6, C18:1n-9, and that of CARHSP1 correlated (positively) with the C16:1n-7 lipokine. We also found that these two transcription factors share target genes that are involved in lipid metabolism (e.g., GOT1, PLIN1, and TFRC). CONCLUSIONS: This integrative analysis of muscle transcriptome and intramuscular FA profile revealed valuable information about key candidate genes and potential regulators for FA and lipid metabolism in pigs, among which some transcription factors are proposed to control gene expression and modulate FA composition differences.


Asunto(s)
Ácidos Grasos , Músculo Esquelético , Porcinos/genética , Animales , Ácidos Grasos/metabolismo , Músculo Esquelético/metabolismo , Perfilación de la Expresión Génica , Factores de Transcripción/metabolismo , Genes Reguladores , Transcriptoma
17.
Cancers (Basel) ; 16(2)2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38254804

RESUMEN

Traditional microbiological methodology is valuable and essential for microbiota composition description and microbe role assignations at different anatomical sites, including cervical and vaginal tissues; that, combined with molecular biology strategies and modern identification approaches, could give a better perspective of the microbiome under different circumstances. This pilot work aimed to describe the differences in microbiota composition in non-cancer women and women with cervical cancer through a culturomics approach combining culture techniques with Vitek mass spectrometry and 16S rDNA sequencing. To determine the possible differences, diverse statistical, diversity, and multivariate analyses were applied; the results indicated a different microbiota composition between non-cancer women and cervical cancer patients. The Firmicutes phylum dominated the non-cancer (NC) group, whereas the cervical cancer (CC) group was characterized by the predominance of Firmicutes and Proteobacteria phyla; there was a depletion of lactic acid bacteria, an increase in the diversity of anaerobes, and opportunistic and non-typical human microbiota isolates were present. In this context, we hypothesize and propose a model in which microbial composition and dynamics may be essential for maintaining the balance in the cervical microenvironment or can be pro-oncogenesis microenvironmental mediators in a process called Ying-Yang or have a protagonist/antagonist microbiota role.

18.
Biol Res Nurs ; 26(2): 231-239, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37844913

RESUMEN

Obesity is highly prevalent in breast cancer (BC) survivors. Adipose tissue promotes inflammation, affecting recurrence, morbidity, and quality of life. This study aimed to determine the relationship of body composition parameters with the levels of C-reactive protein (CRP) and interleukin 6 (IL-6) in female BC survivors. Additionally, we evaluated the association of log-transformed serum concentrations of CRP and IL-6 with the appendicular skeletal lean mass index (ASMI). The results showed that CRP was positively associated with body fat percentage (BFP; ß adjusted = .08, 95% CI: .02-.14) in all participants, and with fat mass index (FMI; ß = .24, 95% CI: .08-.40) only in premenopausal women. IL-6 was positively associated with FMI (ß adjusted = .16, 95% CI: .03-.29), while ASMI decreased as CRP levels increased (ß adjusted = -.30, 95% CI: -.53 to -.06). Interventions to improve body composition in BC survivors should also consider the role of inflammatory markers in changes in body composition to avoid sarcopenic obesity (SO) and the risk of BC recurrence.


Asunto(s)
Neoplasias de la Mama , Supervivientes de Cáncer , Humanos , Femenino , Interleucina-6 , Proteína C-Reactiva , Neoplasias de la Mama/complicaciones , Calidad de Vida , Recurrencia Local de Neoplasia/complicaciones , Composición Corporal , Obesidad/complicaciones , Sobrevivientes , Índice de Masa Corporal
20.
Ginecol. obstet. Méx ; 92(4): 137-144, ene. 2024. tab, graf
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1557867

RESUMEN

Resumen OBJETIVO: Determinar la incidencia del espectro del acretismo placentario en pacientes ingresadas a la unidad de cuidados intensivos obstétricos del Hospital de la Mujer, Culiacán, Sinaloa. MATERIALES Y MÉTODOS: Estudio retrospectivo, transversal y descriptivo fundamentado en el análisis de la base de datos del Hospital de la Mujer de pacientes internadas entre los años 2017 a 2020 con diagnóstico de espectro de placenta acreta, referidas o diagnosticadas en la institución e intervenidas para histerectomía por la complicación estudiada. RESULTADOS: Se analizaron 22 pacientes con diagnóstico de acretismo placentario que dieron una incidencia de 0.09%; de éstas, a 1 se le indicó cesárea; 19 de las 22 pacientes tenían antecedente de cicatriz uterina previa, todas con placenta previa. El promedio de edad fue de 30.86 ± 4 años. La cesárea se practicó, en promedio, a las 34 semanas de embarazo con dos técnicas quirúrgicas. El sangrado promedio estimado fue de 1.947 mL. Las complicaciones transoperatorias fueron las lesiones: ureteral (n = 2) y vesical (n = 1). La principal complicación posoperatoria fue la fístula vesicouterina (n = 1). El promedio de estancia fue de 2 días en 16 de las 22 pacientes y de 7 días en las 6 restantes. CONCLUSIONES: Lo importante del acretismo placentario es el diagnóstico oportuno que permita derivar a las pacientes a centros hospitalarios que cuenten con especialistas experimentados en la atención de estos casos.


Abstract OBJECTIVE: To determine the incidence of placental accretism spectrum in pregnant women admitted to the obstetric intensive care unit of the Hospital de la Mujer, Culiacán, Sinaloa. MATERIALS AND METHODS: Retrospective, cross-sectional, descriptive study based on the analysis of the database of the Hospital de la Mujer of patients admitted between 2017 and 2020 with a diagnosis of placenta accreta spectrum, referred or diagnosed at the institution and underwent hysterectomy for the complication studied. RESULTS: Twenty-two patients with a diagnosis of placenta accreta were analysed, giving a prevalence of 0.09%; of these, caesarean section was indicated in 0.2%. 19 of the 22 patients had a history of previous uterine scarring, all with placenta praevia. Mean age was 30.86 ± 4 years. Caesarean section was performed at a mean gestational age of 34 weeks using two surgical techniques. The mean estimated blood loss was 1,947 mL. The most common operative complications were ureteral (n = 2) and bladder (n = 1) injuries. The most common postoperative complication was vesico-uterine fistula (n = 1). The mean length of stay was 2 days in 16 of the 22 patients and 7 days in the remaining 6 patients. CONCLUSIONS: The most important aspect of placenta accreta is early diagnosis, which allows referral to hospital centres with specialists experienced in the management of these cases.

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