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1.
AMIA Jt Summits Transl Sci Proc ; 2024: 295-304, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38827082

RESUMEN

Text and audio simplification to increase information comprehension are important in healthcare. With the introduction of ChatGPT, evaluation of its simplification performance is needed. We provide a systematic comparison of human and ChatGPT simplified texts using fourteen metrics indicative of text difficulty. We briefly introduce our online editor where these simplification tools, including ChatGPT, are available. We scored twelve corpora using our metrics: six text, one audio, and five ChatGPT simplified corpora (using five different prompts). We then compare these corpora with texts simplified and verified in a prior user study. Finally, a medical domain expert evaluated the user study texts and five, new ChatGPT simplified versions. We found that simple corpora show higher similarity with the human simplified texts. ChatGPT simplification moves metrics in the right direction. The medical domain expert's evaluation showed a preference for the ChatGPT style, but the text itself was rated lower for content retention.

2.
Sci Rep ; 13(1): 16703, 2023 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-37794118

RESUMEN

In pregnant animals, communication between the mother and conceptus occurs via extracellular vesicles (EVs) that carry several biomolecules such as nucleic acids (miRNAs, mRNAs), proteins, and lipids. At the time of implantation, the endometrium undergoes several morphological and physiological changes, such as angiogenesis, apoptosis, and cell proliferation regulation at the implantation site, to attain a receptive state. This study was conducted to detect pregnancy-specific miRNAs derived from extracellular vesicles in the systemic circulation of Bubalus bubalis (water buffalo) and to assess their functional significance in the modulation of endometrial primary cells. The extracellular vesicles were isolated from the blood plasma using a precipitation-based method and further characterized by various methods such as Differential light scattering, Nanoparticle tracking assay, Western blot, and transmission electron microscopy. The relative expression of the selected extracellular vesicles associated miRNAs (EV-miRNA) at different intervals (days 15, 19, 25, and 30) post artificial insemination (AI) was analyzed using RT-qPCR, and expression of miR-195-5p was found to be significantly higher (P < 0.01) in pregnant animals on day 19 post AI (implantation window) as compared to day 15 post AI. The elevated expression might indicate the involvement of this miRNA in the maternal-conceptus cross-talk occurring during the implantation period. The KEGG pathway enrichment and Gene Ontology analyses of the miR-195-5p target genes revealed that these were mostly involved in the PI3-Akt, MAPK, cell cycle, ubiquitin-mediated proteolysis, and mTOR signaling pathways, which are related to the regulation of cell proliferation. Transfecting the in vitro cultured cells with miR-195-5p mimic significantly suppressed (P < 0.05) the expression of its target genes such as YWHAQ, CDC27, AKT-3, FGF-7, MAPK8, SGK1, VEGFA, CACAND1, CUL2, MKNK1, and CACAN2D1. Furthermore, the downregulation of the miR-195-5p target genes was positively correlated with a significant increase in the apoptotic rate and a decrease in the proliferation. In conclusion, the current findings provide vital information on the presence of EV miR-195-5p in maternal circulation during the implantation window indicating its important role in the modulation of buffalo endometrium epithelial cells via promoting cell death. Altogether, the milieu of miR-195-5p may serve as a novel and potential molecular factor facilitating the implantation of the early embryo during the establishment of pregnancy in buffaloes. Thus, miR-195-5p may be identified as a unique circulatory EV biomarker related to establishing pregnancy in buffaloes as early as day 19 post-AI.


Asunto(s)
Vesículas Extracelulares , MicroARNs , Embarazo , Femenino , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Búfalos/genética , Búfalos/metabolismo , Cultivo Primario de Células , MicroARNs/genética , MicroARNs/metabolismo , Endometrio/metabolismo , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Proliferación Celular/genética , Apoptosis/genética
3.
Sci Rep ; 13(1): 9102, 2023 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-37277402

RESUMEN

Agrichemicals such as organophosphorus pesticides' metabolites (OPPMs) are more hazardous and pervasive than their parent pesticides. Parental germline exposure to such xenobiotics leads to an elevated susceptibility towards reproductive failures e.g. sub- or in-fertility. This study sought to examine the effects of low-dose, acute OPPM exposure on mammalian sperm function using buffalo as the model organism. The buffalo spermatozoa were briefly (2 h) exposed to metabolites of the three most prevalent organophosphorus pesticides (OPPs) viz. Omethoate (from Dimethoate), paraoxon-methyl (from methyl/ethyl parathion) and 3, 5, 6-trichloro-2-pyridinol (from chlorpyrifos). Exposure to OPPMs resulted in compromised structural and functional integrity (dose-dependent) of the buffalo spermatozoa typified by elevated membrane damage, increased lipid peroxidation, precocious capacitation and tyrosine phosphorylation, perturbed mitochondrial activity and function and (P < 0.05). This led to a decline in the in vitro fertilizing ability (P < 0.01) of the exposed spermatozoa, as indicated by reduced cleavage and blastocyst formation rates. Preliminary data indicate that acute exposure to OPPMs, akin to their parent pesticides, induces biomolecular and physiological changes in spermatozoa that compromise their health and function ultimately affecting their fertility. This is the first study demonstrating the in vitro spermatotoxic effects of multiple OPPMs on male gamete functional integrity.


Asunto(s)
Metil Paratión , Plaguicidas , Animales , Masculino , Búfalos , Fertilidad , Compuestos Organofosforados/toxicidad , Plaguicidas/toxicidad , Semen , Motilidad Espermática , Espermatozoides/metabolismo
4.
Front Cell Dev Biol ; 11: 1119220, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36891514

RESUMEN

The water buffalo (Bubalus bubalis) is an indispensable part of the Indian dairy sector and in several instances, the farmers incur economic losses due to failed pregnancy after artificial insemination (AI). One of the key factors for the failure of conception is the use of semen from the bulls of low fertilizing potential and hence, it becomes important to predict the fertility status before performing AI. In this study, the global proteomic profile of high fertile (HF) and low fertile (LF) buffalo bull spermatozoa was established using a high-throughput LC-MS/MS technique. A total of 1,385 proteins (≥1 high-quality PSM/s, ≥1 unique peptides, p < 0.05, FDR < 0.01) were identified out of which, 1,002 were common between both the HF and LF groups while 288 and 95 proteins were unique to HF and LF groups respectively. We observed 211 and 342 proteins were significantly high (log Fc ≥ 2) and low abundant (log Fc ≤ 0.5) in HF spermatozoa (p < 0.05). Gene ontology analysis revealed that the fertility associated high abundant proteins in HF were involved in spermatogenesis, sperm motility, acrosome integrity, zona pellucida binding and other associated sperm functions. Besides this, the low abundant proteins in HF were involved in glycolysis, fatty acid degradation and inflammation. Furthermore, fertility related differentially abundant proteins (DAPs) on sperm viz., AKAP3, Sp17, and DLD were validated through Western blotting and immunocytochemistry which was in coherence with the LC-MS/MS data. The DAPs identified in this study may be used as potential protein candidates for predicting fertility in buffaloes. Our findings provide an opportunity in mitigating the economic losses that farmers incur due to male infertility.

5.
Int J Biol Macromol ; 221: 1504-1511, 2022 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-36122776

RESUMEN

Human paraoxonase 1(hPON1) belongs to the paraoxonase (PON) family. It is a calcium-dependent enzyme with a size of ∼43 kDa and is composed of 6 bladed beta-barrel structures with two calcium ions in its active site. In humans, it is synthesized in the liver and remains bound with the high-density lipoproteins (HDL) within the blood. It has immense potential to tackle the poisoning associated with the use of organophosphates (OPs) and their derivatives, such as nerve agents, due to role in their degradation. Therefore, hPON1 serves as a potential bio-scavenger that can be used as an antidote or as a surface decontaminating agent in OPs poisoning. However, present systems prove insufficient to produce it in sufficient quantity to make it industrially relevant. Here, our efforts involve producing it recombinantly in an E. coli system with enhanced expression levels by altering cellular and environmental conditions. This has been further improved by the development of in-vitro refolding process for the denatured recombinant hPON1 (rhPON1) protein. This methodology resulted in approximately 200 mg of the enzymatically functional protein from 1 l of E. coli culture. Proper refolding of rhPON1 was confirmed by comparing its enzymatic activity and conformation with serum purified hPON1.


Asunto(s)
Arildialquilfosfatasa , Escherichia coli , Humanos , Arildialquilfosfatasa/genética , Arildialquilfosfatasa/química , Escherichia coli/genética , Escherichia coli/metabolismo , Calcio , Organofosfatos , Ingeniería Celular , Pliegue de Proteína , Proteínas Recombinantes/química
6.
Polymers (Basel) ; 14(14)2022 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-35890569

RESUMEN

The current study aims to evaluate the effect of tamarind gum (TG) on the optical, mechanical, and drug release potential of poly(vinyl alcohol) (PVA)-based films. This involves preparing PVA-TG composite films with different concentrations of TG through a simple solvent casting method. The addition of TG has enhanced the phase separation and aggregation of PVA within the films, and it becomes greater with the increase in TG concentration. Brightfield and polarized light micrographs have revealed that aggregation is favored by forming crystalline domains at the PVA-TG interface. The interconnected network of PVA-TG aggregates influenced the swelling and drying properties of the films. Using Peleg's analysis, the mechanical behavior of films was determined by their stress relaxation profiles. The addition of TG has made no significant changes to the firmness and viscoelastic properties of films. However, long-durational relaxation times indicated that the interconnected network might break down in films with higher TG concentration, suggesting their brittleness. The controlled release of ciprofloxacin in HCl solution (0.5% (w/v)) appears to decrease with the increase in TG concentration. In fact, TG has inversely affected the impedance and altered the ionic conductivity within the films. This seems to have directly influenced the drug release from the films as the mechanism was found to be non-Fickian diffusion (based on Korsmeyer-Peepas and Peppas-Sahlin kinetic models). The antimicrobial study using Escherichia coli was carried out to evaluate the activity of the drug-loaded films. The study proves that TG can modulate the properties of PVA films and has the potential to fine-tune the controlled release of drugs from composite films.

7.
Front Cell Dev Biol ; 9: 673765, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34513824

RESUMEN

Precise early pregnancy diagnosis in dairy animals is of utmost importance for an efficient dairy production system. Not detecting a dairy animal pregnant sufficiently early after the breeding results to extending the unproductive time of their milk production cycle and causes substantial economic loss for a dairy producer. At present, the most conventional and authentic pregnancy confirmation practice in cows and buffaloes is rectal palpation of the reproductive organs at Days 35-40 after insemination, which sometime leads to considering an animal as false pregnant. Other alternative methods available for early pregnancy diagnosis lack either accuracy or reproducibility or require elaborate instrumentation and laboratory setup not feasible to practice at farmers' doorstep. The present study was aimed at establishment of the microRNA (miRNA) repertoire of the placentome in buffaloes, which could capture the event of the cross talk between a growing embryo and a dam, through fetal cotyledons and maternal caruncles, and thus could hint at the early pregnancy establishment event in ruminants. Total RNA was isolated from buffalo placentome tissues during early stages of pregnancy (at Day < 25 and Days 30-35), and global small RNA analysis was performed by using Illumina single-end read chemistry and Bubalus bubalis genome. A total of 2,199 miRNAs comprising 1,620 conserved and 579 non-conserved miRNAs were identified. Stringent functional miRNA selection criteria could predict 20 miRNAs worth evaluating for their abundance in the plasma of pregnant, non-pregnant, cyclic non-bred, and non-cyclic prepubertal animals. Eight of them (viz., miR-195-5p, miR-708-3p, miR-379-5p, miR-XX1, miR-XX2, miR-130a-3p, miR-200a-3p, and miR-27) displayed typical abundance patterns in the plasma samples of the animals on Day 19 as well as Day 25 post-insemination, thus making them ambiguous candidates for early pregnancy detection. Similarly, higher abundance of miR-200a-3p and miR130a-3p in non-pregnant animals was indicative of their utility for detecting the animals as not pregnant. Most interestingly, miR-XX1 and miR-XX2 were very characteristically abundant only in pregnant animals. In silico target prediction analysis confirmed that these two miRNAs are important regulators of cyclooxygenase-2 (COX-2) and cell adhesion molecule-2 (CADM-2), both of which play a significant role in the implantation process during feto-maternal cross talk. We interpret that circulatory miR-XX1 and miR-XX2 in blood plasma could be the potential biomarkers for early pregnancy detection in buffaloes.

8.
BMC Genomics ; 22(1): 480, 2021 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-34174811

RESUMEN

BACKGROUND: Low conception rate (CR) despite insemination with morphologically normal spermatozoa is a common reproductive restraint that limits buffalo productivity. This accounts for a significant loss to the farmers and the dairy industry, especially in agriculture-based economies. The immune-related proteins on the sperm surface are known to regulate fertility by assisting the spermatozoa in their survival and performance in the female reproductive tract (FRT). Regardless of their importance, very few studies have specifically catalogued the buffalo sperm surface proteome. The study was designed to determine the identity of sperm surface proteins and to ascertain if the epididymal expressed beta-defensins (BDs), implicated in male fertility, are translated and applied onto buffalo sperm surface along with other immune-related proteins. RESULTS: The raw mass spectra data searched against an in-house generated proteome database from UniProt using Comet search engine identified more than 300 proteins on the ejaculated buffalo sperm surface which were bound either by non-covalent (ionic) interactions or by a glycosylphosphatidylinositol (GPI) anchor. The singular enrichment analysis (SEA) revealed that most of these proteins were extracellular with varied binding activities and were involved in either immune or reproductive processes. Flow cytometry using six FITC-labelled lectins confirmed the prediction of glycosylation of these proteins. Several beta-defensins (BDs), the anti-microbial peptides including the BuBD-129 and 126 were also identified amongst other buffalo sperm surface proteins. The presence of these proteins was subsequently confirmed by RT-qPCR, immunofluorescence and in vitro fertilization (IVF) experiments. CONCLUSIONS: The surface of the buffalo spermatozoa is heavily glycosylated because of the epididymal secreted (glyco) proteins like BDs and the GPI-anchored proteins (GPI-APs). The glycosylation pattern of buffalo sperm-surface, however, could be perturbed in the presence of elevated salt concentration or incubation with PI-PLC. The identification of numerous BDs on the sperm surface strengthens our hypothesis that the buffalo BDs (BuBDs) assist the spermatozoa either in their survival or in performance in the FRT. Our results suggest that BuBD-129 is a sperm-surface BD that could have a role in buffalo sperm function. Further studies elucidating its exact physiological function are required to better understand its role in the regulation of male fertility.


Asunto(s)
Búfalos , Proteoma , Animales , Epidídimo , Femenino , Inmunidad Innata , Masculino , Reproducción , Espermatozoides
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