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1.
iScience ; 27(8): 109700, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39220407

RESUMEN

This paper presents the design of an ultra-wide-angle multispectral narrow-band absorber for reconstructing infrared spectra. The absorber offers several advantages, including polarization sensitivity, robustness against structural wear, wide azimuthal angle coverage, high narrow-band absorption, and adjustable working wavelength. To accomplish infrared spectrum reconstruction, an absorber is employed as a spectral sampling channel, eliminating the influence of slits or complex optical splitting elements in spectral imaging technology. Additionally, we propose using a truncation regularization algorithm based on the design matrix singular value ratio, namely IReg, which can enable high-precision spectral reconstruction under largely disturbed environments. The results demonstrate that, even when the number of absorption spectrum curve is reduced to a range of 1/2 to 1/3, high-precision spectral reconstruction is achievable for both flat and high-energy steep mid- and long-infrared spectral targets, while effectively accomplishing data dimension reduction.

2.
Reprod Domest Anim ; 59(6): e14631, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38828566

RESUMEN

This study examines the impact of Notoginsenoside R1 (NGR1), a compound from Panax notoginseng, on the maturation of porcine oocytes and their embryonic development, focusing on its effects on antioxidant levels and mitochondrial function. This study demonstrates that supplementing in vitro maturation (IVM) medium with NGR1 significantly enhances several biochemical parameters. These include elevated levels of glutathione (GSH), nuclear factor erythrocyte 2-related factor 2 (NRF2) and mRNA expression of catalase (CAT) and GPX. Concurrently, we observed a decrease in reactive oxygen species (ROS) levels and an increase in JC-1 immunofluorescence, mitochondrial distribution, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and nuclear NRF2 mRNA levels. Additionally, there was an increase in ATP production and lipid droplets (LDs) immunofluorescence. These biochemical improvements correlate with enhanced embryonic outcomes, including a higher blastocyst rate, increased total cell count, enhanced proliferative capacity and elevated octamer-binding transcription factor 4 (Oct4) and superoxide dismutase 2 (Sod2) gene expression. Furthermore, NGR1 supplementation resulted in decreased apoptosis, reduced caspase 3 (Cas3) and BCL2-Associated X (Bax) mRNA levels and decreased glucose-regulated protein 78 kD (GRP78) immunofluorescence in porcine oocytes undergoing in vitro maturation. These findings suggest that NGR1 plays a crucial role in promoting porcine oocyte maturation and subsequent embryonic development by providing antioxidant levels and mitochondrial protection.


Asunto(s)
Antioxidantes , Desarrollo Embrionario , Ginsenósidos , Técnicas de Maduración In Vitro de los Oocitos , Mitocondrias , Oocitos , Animales , Antioxidantes/farmacología , Ginsenósidos/farmacología , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Mitocondrias/efectos de los fármacos , Desarrollo Embrionario/efectos de los fármacos , Oocitos/efectos de los fármacos , Femenino , Porcinos , Especies Reactivas de Oxígeno/metabolismo , Técnicas de Cultivo de Embriones/veterinaria
3.
Domest Anim Endocrinol ; 88: 106848, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38574690

RESUMEN

Insulin is a potent adipogenic hormone that triggers a series of transcription factors that regulate the differentiation of preadipocytes into mature adipocytes. Ciglitazone specifically binds to peroxisome proliferator-activated receptor-γ (PPARγ), thereby promoting adipocyte differentiation. As a natural ligand of PPARγ, oleic acid (OA) can promote the translocation of PPARγ into the nucleus, regulate the expression of downstream genes, and promote adipocyte differentiation. We hypothesized that ciglitazone and oleic acid interact with insulin to enhance bovine preadipocyte differentiation. Preadipocytes were cultured 96 h in differentiation medium containing 10 mg/L insulin (I), 10 mg/L insulin + 10 µM cycloglitazone (IC), 10 mg/L insulin + 100 µM oleic acid (IO), or 10 mg/L insulin + 10 µM cycloglitazone+100 µM oleic acid (ICO). Control preadipocytes (CON) were cultured in differentiation medium (containing 5% fetal calf serum). The effects on the differentiation of Yanbian cattle preadipocytes were examined using molecular and transcriptomic techniques, including differentially expressed genes (DEGs) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis. I, IC, IO, and ICO treatments produced higher concentrations of triglycerides (TAG) and lipid droplet accumulation in preadipocytes compared with CON treatment (P < 0.05). Co-treatment of insulin and PPARγ agonists significantly increased the expression of genes involved in regulating adipogenesis and fatty acid synthesis. (P < 0.05). Differential expression analysis identified 1488, 1764, 1974 and 1368 DEGs in the I, IC, IO and ICO groups, respectively. KEGG pathway analysis revealed DEGs mainly enriched in PPAR signalling, FOXO signaling pathway and fatty acid metabolism. These results indicate that OA, as PPARγ agonist, can more effectively promote the expression of bovine lipogenesis genes and the content of TAG and adiponectin when working together with insulin, and stimulate the differentiation of bovine preadipocytes. These findings provide a basis for further screening of relevant genes and transcription factors in intramuscular fat deposition and meat quality to enhance breeding programs.


Asunto(s)
Adipocitos , Diferenciación Celular , Insulina , Ácido Oléico , PPAR gamma , Tiazolidinedionas , Animales , Bovinos , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , PPAR gamma/genética , PPAR gamma/metabolismo , Insulina/metabolismo , Diferenciación Celular/efectos de los fármacos , Tiazolidinedionas/farmacología , Ácido Oléico/farmacología , Adipogénesis/efectos de los fármacos , Células Cultivadas , Regulación de la Expresión Génica/efectos de los fármacos
4.
Reprod Domest Anim ; 59(4): e14565, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38646981

RESUMEN

Mangiferin (MGN) is primarily found in the fruits, leaves, and bark of plants of the Anacardiaceae family, including mangoes. MGN exhibits various pharmacological effects, such as protection of the liver and gallbladder, anti-lipid peroxidation, and cancer prevention. This study aimed to investigate the effects of MGN supplementation during in vitro culture (IVC) on the antioxidant capacity of early porcine embryos and the underlying mechanisms involved. Porcine parthenotes in the IVC medium were exposed to different concentrations of MGN (0, 0.01, 0.1, and 1 µM). The addition of 0.1 µM MGN significantly increased the blastocyst formation rate of porcine embryos while reducing the apoptotic index and autophagy. Furthermore, the expression of antioxidation-related (SOD2, GPX1, NRF2, UCHL1), cell pluripotency (SOX2, NANOG), and mitochondria-related (TFAM, PGC1α) genes was upregulated. In contrast, the expression of apoptosis-related (CAS3, BAX) and autophagy-related (LC3B, ATG5) genes decreased after MGN supplementation. These findings suggest that MGN improves early porcine embryonic development by reducing oxidative stress-related genes.


Asunto(s)
Técnicas de Cultivo de Embriones , Desarrollo Embrionario , Estrés Oxidativo , Xantonas , Animales , Estrés Oxidativo/efectos de los fármacos , Desarrollo Embrionario/efectos de los fármacos , Xantonas/farmacología , Técnicas de Cultivo de Embriones/veterinaria , Apoptosis/efectos de los fármacos , Antioxidantes/farmacología , Autofagia/efectos de los fármacos , Porcinos , Blastocisto/efectos de los fármacos , Femenino , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Partenogénesis
5.
Huan Jing Ke Xue ; 45(3): 1428-1438, 2024 Mar 08.
Artículo en Chino | MEDLINE | ID: mdl-38471858

RESUMEN

To understand the water pollution status and environmental risks of Changshou Lake, the concentrations of heavy metals (Cr, Cu, Zn, As, Cd, and Pb) in the water were collected and analyzed during different seasons. The study investigated temporal and spatial variations, distribution characteristics, pollution levels, and health risks associated with heavy metals in Changshou Lake. The results showed that all six heavy metals were below than the Class Ⅰ standard of the Surface Water Environmental Quality Standard (GB 3838-2002), but recent years have witnessed an increasing trend, with Cu, As, and Pb showing a significant increase (P<0.05). The temporal and spatial distributions of these heavy metals were different. Temporally, Cr and Cd concentrations in surface water were higher in summer, As and Zn were higher in spring, and Pb and Cu were higher in autumn and winter. Spatially, the concentrations of Cr, As, Cu, Zn, and Pb showed higher concentrations in the southern outlet of the reservoir, the northwestern Longxi River inlet, and the central part of the reservoir, whereas Cd was higher in the northern stagnant area. The overall levels of heavy metals in the water body of Changshou Lake were low, with Cr and Cu slightly polluted, while other heavy metals were identified as having an insignificant pollution level. Drinking water was the primary exposure pathway to carcinogenic and non-carcinogenic heavy metals in surface water bodies. The health risk values of Cr and As in water bodies were high, ranging from 6.2×10-10 to 3.0×10-4 and 5.1×10-8 to 3.9×10-5, respectively. The corresponding contribution rates for children and adults to the total health risk were high, with Cr accounting for 87.18% and 87.20%, respectively, while As accounted for 12.73% and 12.71%, respectively. Therefore, it is crucial to prioritize environmental risks associated with Cr and Cu, as well as the health risks associated with Cr and As in Changshou Lake These findings provide a scientific foundation for water pollution control and environmental quality improvement in Changshou Lake, and rational development and utilization of water resources.


Asunto(s)
Agua Potable , Metales Pesados , Contaminantes Químicos del Agua , Cadmio , China , Monitoreo del Ambiente , Sedimentos Geológicos , Lagos/análisis , Plomo , Metales Pesados/análisis , Medición de Riesgo , Contaminantes Químicos del Agua/análisis , Humanos , Niño , Adulto
6.
Opt Lett ; 49(3): 746-749, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38300105

RESUMEN

As is well known, a light beam with a helical phase carries an optical orbital angular momentum (OAM), which can cause the orbital motion of trapped microparticles around the beam axis. Usually, the speed of the orbital motion is uniform along the azimuthal direction and depends on the amount of OAM and the light intensity. Here, we present the reverse customized method to tailor the nonuniform local OAM density along the azimuthal direction of the focal field, which has a hybrid polarization distribution and maintains a doughnut-shaped intensity profile. Theoretical analysis and experimental results about the orbital motion of the trapped polystyrene sphere show that the nonuniform local OAM density can be tailored by manipulating the polarization states of the focal field. Our results provide an ingenious way to control the local tangential optical force and the speed of the orbital motion of particles driven by the local OAM density and will promote exciting possibilities for exploring ways to control the mechanical dynamics of microparticles in optical trapping and microfluidics.

7.
Theriogenology ; 218: 89-98, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38308957

RESUMEN

After ovulation, senescent oocytes inevitably experience reduced quality and defects in embryonic development. Apigenin (API) is a flavonoid with a wide range of pharmacological effects. Therefore, this study examined the protective effects of API on the quality of porcine oocytes during in-vitro ageing and the underlying mechanisms. The results showed that API treatment could reduce the activation rate after aging for 48 h. In addition, API significantly reduced reactive oxygen species, abnormal distribution of mitochondria, early apoptosis in ageing oocytes, increased glutathione, and mitochondrial adenosine triphosphate levels in ageing oocytes. Importantly, API increased the embryonic development rate in aged oocytes. We also examined molecular changes, finding decreased sirtuin 1 expression in in-vitro postovulatory oocytes, but API reversed this effect. Our results suggest that API attenuates the deterioration of oocyte quality during in-vitro ageing, possibly by reducing oxidative stress through the upregulation of sirtuin 1.


Asunto(s)
Apigenina , Sirtuina 1 , Femenino , Animales , Porcinos , Sirtuina 1/genética , Sirtuina 1/metabolismo , Apigenina/farmacología , Apigenina/metabolismo , Regulación hacia Arriba , Senescencia Celular/fisiología , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Oocitos/fisiología
8.
Animals (Basel) ; 14(3)2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38338092

RESUMEN

Eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone) is a flavonoid derived from Artemisia plants that has beneficial biological activities, such as anti-apoptotic, anti-oxidant, and anti-inflammatory activities. However, the protective effects of eupatilin against oxidative stress and endoplasmic reticulum stress in porcine oocyte maturation are still unclear. To investigate the effect of eupatilin on the development of porcine oocytes after in vitro maturation and parthenogenetic activation, we added different concentrations of eupatilin in the process of porcine oocyte maturation in vitro, and finally selected the optimal concentration following multiple comparisons and analysis of test results using SPSS (version 17.0; IBM, Chicago, IL, USA) software. The results showed that 0.1 µM eupatilin supplementation did not affect the expansion of porcine cumulus cells, but significantly increased the extrusion rate of porcine oocyte polar bodies, the subsequent blastocyst formation rate, and the quality of parthenogenetically activated porcine embryos. Additionally, it reduced the level of reactive oxygen species in cells and increased glutathione production. Further analysis revealed that eupatilin supplementation could reduce apoptosis, DNA double-strand breaks, and endoplasmic reticulum stress. In conclusion, supplementation with 0.1 µM eupatilin during in vitro maturation improved oocyte maturation and subsequent embryo development by reducing oxidative stress and endoplasmic reticulum stress.

9.
Antioxidants (Basel) ; 13(1)2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38275647

RESUMEN

Our previous study established that chrysoeriol (CHE) can reduce reactive oxygen species (ROS) accumulation, apoptosis, and autophagy in vitro culture (IVC) of porcine embryos. However, the role of CHE in oocyte maturation and lipid homeostasis is unclear. Herein, we aimed to elucidate the effect of CHE on porcine oocyte competence in vitro maturation (IVM) and subsequent embryo development. The study chooses parthenogenetic activated porcine oocytes as the research model. The study revealed that the cumulus expansion index and related gene expressions are significantly elevated after supplementing 1 µM CHE. Although there were no significant differences in nuclear maturation and cleavage rates, the blastocyst formation rate and total cell numbers were significantly increased in the 1 µM CHE group. In addition, CHE improved the expression of genes related to oocyte and embryo development. ROS was significantly downregulated in all CHE treatment groups, and intracellular GSH (glutathione) was significantly upregulated in 0.01, 0.1, and 1 µM CHE groups. The immunofluorescence results indicated that mitochondrial membrane potential (MMP) and lipid droplet (LD), fatty acid (FA), ATP, and functional mitochondria contents significantly increased with 1 µM CHE compared to the control. Furthermore, CHE increased the expression of genes related to lipid metabolism, mitochondrial biogenesis, and ß-oxidation.

10.
Int J Artif Organs ; 47(2): 96-106, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38186004

RESUMEN

OBJECTIVE: To systematically evaluate the clinical efficacy of pulmonary rehabilitation in patients with mechanical ventilation in an intensive care unit (ICU). METHODS: Relevant studies were identified in the PubMed, Web of Science, National Library of Medicine, China National Knowledge Infrastructure and Wanfang databases. A meta-analysis was performed after screening based on the inclusion and exclusion criteria, data extraction and literature quality evaluation. RESULTS: In total, 19 studies involving 2181 participants were included. The results of the meta-analysis revealed that compared with patients with conventional rehabilitation measures, patients with pulmonary rehabilitation measures had a higher offline success rate (relative risk (RR) = 1.16; 95% confidence interval (CI): 1.09, 1.24; p < 0.00001) and higher arterial oxygen partial pressure levels (mean difference (MD) = 8.96; 95%CI: 5.98, 11.94; p < 0.0001) and these measures significantly shortened the duration of mechanical ventilation (standardised MD (SMD) = -1.08; 95%CI: -1.58, -0.59; p < 0.0001) and ICU stay (SMD = -1.41; 95%CI: -1.94, -0.88; p < 0.0001). Aspiration significantly reduced the incidence of ventilator-associated pneumonia (RR = 0.35; 95%CI: 0.24, 0.51; p < 0.00001) and deep vein thrombosis (RR = 0.32; 95%CI: 0.13, 0.76; p = 0.01) in ICU patients with mechanical ventilation. CONCLUSION: Pulmonary rehabilitation measures can improve the success rate of weaning from mechanical ventilation in ICU patients, shorten the time of mechanical ventilation and ICU hospitalisation and reduce the incidence of related adverse reactions, but the impact on mortality requires further study.


Asunto(s)
Neumonía Asociada al Ventilador , Respiración Artificial , Humanos , Respiración Artificial/efectos adversos , Neumonía Asociada al Ventilador/prevención & control , Unidades de Cuidados Intensivos , Cuidados Críticos , Resultado del Tratamiento
11.
Chinese Pharmacological Bulletin ; (12): 224-228, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1013629

RESUMEN

In addition to providing energy for cells, mitochondria also participate in calcium homeostasis, cell information transfer, cell apoptosis, cell growth and differentiation. Therefore, maintaining mitochondrial homeostasis is very crucial for the body to carry out normal life activities. Ubiquitination, a post-translational modification of proteins, is involved in various physiological and pathological processes of cells by regulating mitochondrial homeostasis. However, the mechanism by which ubiquitination regulates mitochondrial homeostasis has not been summarized, especially the effect of Parkin protein on cardiovascular diseases. In this paper, the specific mechanism of mitochondrial homeostasis regulated by ubiquitination of Parkin protein is discussed, and the influence of mitochondrial homeostasis imbalance on cardiovascular diseases is reviewed, with a view to providing potential therapeutic strategies for the clinical treatment of cardiovascular diseases.

12.
Differentiation ; 135: 100742, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38104501

RESUMEN

Hepatic organoids might provide a golden opportunity for realizing precision medicine in various hepatic diseases. Previously described hepatic organoid protocols from pluripotent stem cells rely on complicated multiple differentiation steps consisting of both 2D and 3D differentiation procedures. Therefore, the spontaneous formation of hepatic organoids from 2D monolayer culture is associated with a low-throughput production, which might hinder the standardization of hepatic organoid production and hamper the translation of this technology to the clinical or industrial setting. Here we describe the stepwise and fully 3D production of hepatic organoids from human pluripotent stem cells. We optimized every differentiation step by screening for optimal concentrations and timing of differentiation signals in each differentiation step. Hepatic organoids are stably expandable without losing their hepatic functionality. Moreover, upon treatment of drugs with known hepatotoxicity, we found hepatic organoids are more sensitive to drug-induced hepatotoxicity compared with 2D hepatocytes differentiated from PSCs, making them highly suitable for in vitro toxicity screening of drug candidates. The standardized fully 3D protocol described in the current study for producing functional hepatic organoids might serve as a novel platform for the industrial and clinical translation of hepatic organoid technology.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Células Madre Pluripotentes Inducidas , Células Madre Pluripotentes , Humanos , Diferenciación Celular/genética , Organoides
13.
Stem Cells Int ; 2023: 3320211, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37810631

RESUMEN

Brain organoids have been considered as an advanced platform for in vitro disease modeling and drug screening, but numerous roadblocks exist, such as lack of large-scale production technology and lengthy protocols with multiple manipulation steps, impeding the industrial translation of brain organoid technology. Here, we describe the high-speed and large-scale production of midbrain organoids using a high-throughput screening-compatible platform within 30 days. Micro midbrain organoids (µMOs) exhibit a highly uniform morphology and gene expression pattern with minimal variability. Notably, µMOs show dramatically accelerated maturation, resulting in the generation of functional µMOs within only 30 days of differentiation. Furthermore, individual µMOs display highly consistent responsiveness to neurotoxin, suggesting their usefulness as an in vitro high-throughput drug toxicity screening platform. Collectively, our data indicate that µMO technology could represent an advanced and robust platform for in vitro disease modeling and drug screening for human neuronal diseases.

14.
Opt Lett ; 48(17): 4428-4431, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37656520

RESUMEN

Grover's search algorithm is a well-known quantum algorithm that has been extensively studied and improved to increase its success rate and enhance its flexibility. However, most improved search algorithms require an adjustment of the oracle, which may not be feasible in practical problem-solving scenarios. In this work, we report an experimental demonstration of a deterministic quantum search for multiple marked states without adjusting the oracle. A linear optical setup is designed to search for two marked states, one in a 16-state database with an initial equal-superposition state and the other in an 8-state database with different initial nonequal-superposition states. The evolution of the probability of finding each state in the database is also measured and displayed. Our experimental results agree well with the theoretical predictions, thereby proving the feasibility of the search protocol and the implementation scheme. This work is a pioneering experimental demonstration of deterministic quantum search for multiple marked states without adjusting the oracle.

15.
Reprod Domest Anim ; 58(11): 1583-1594, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37696770

RESUMEN

Notoginsenoside R1 (NGR1), derived from the Panax notoginseng root and rhizome, exhibits diverse pharmacological influences on the brain, neurons, and osteoblasts, such as antioxidant effects, mitochondrial function protection, energy metabolism regulation, and inhibition of oxygen radicals, apoptosis, and cellular autophagy. However, its effect on early porcine embryonic development remains unclear. Therefore, we investigated NGR1's effects on blastocyst quality, reactive oxygen species (ROS) levels, glutathione (GSH) levels, mitochondrial function, and embryonic development-related gene expression in porcine embryos by introducing NGR1 during the in vitro culture (IVC) of early porcine embryos. Our results indicate that an addition of 1 µM NGR1 significantly increased glutathione (GSH) levels, blastocyst formation rate, and total cell number and proliferation capacity; decreased ROS levels and apoptosis rates in orphan-activated porcine embryos; and improved intracellular mitochondrial distribution, enhanced membrane potential, and reduced autophagy. In addition, pluripotency-related factor levels were elevated (NANOG and octamer-binding transcription factor 4 [OCT4]), antioxidant-related genes were upregulated (nuclear factor-erythroid 2-related factor 2 [NRF2]), and apoptosis- (caspase 3 [CAS3]) and autophagy-related genes (light chain 3 [LC3B]) were downregulated. These results indicate that NGR1 can enhance early porcine embryonic development by protecting mitochondrial function.


Asunto(s)
Desarrollo Embrionario , Partenogénesis , Porcinos , Animales , Especies Reactivas de Oxígeno/metabolismo , Antioxidantes/farmacología , Mitocondrias/metabolismo , Blastocisto , Glutatión/metabolismo , Apoptosis
16.
Animals (Basel) ; 13(16)2023 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-37627386

RESUMEN

Imidacloprid (IMI) is an endogenous neonicotinoid insecticide widely used in agriculture and has attracted researchers' attention because of its risks to the environment and human health. Melatonin (MT) is an antioxidant hormone produced by the pineal gland of the brain. Studies have shown that it has a variety of physiological functions and plays a crucial role in the development of animal germ cells and embryos. The potential protective effects of MT against oocyte damage caused by neonicotinoid pesticide toxicity remain unclear. In this study, we report the toxicity of IMI against, and its effects on the quality of, porcine oocytes and the protective effect of MT on IMI-exposed oocytes. The results show that IMI exposure adversely affected oocyte maturation, while MT supplementation ameliorated its toxic effects. Specifically, IMI exposure increased oxidative stress (OS), endoplasmic reticulum stress (ERS), and apoptosis, which may affect polar body expulsion rates and blastocyst formation. Also, IMI exposure reduced oocyte cleavage rates and the number of cells in blastocysts. However, all of these toxic effects can be restored after a melatonin supplementation treatment. In conclusion, these results suggest that melatonin has a protective effect on IMI-induced defects during porcine oocyte maturation.

17.
Int J Biol Sci ; 19(11): 3595-3613, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37497008

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) and its progressive form non-alcoholic steatohepatitis (NASH) have presented a major and common health concern worldwide due to their increasing prevalence and progressive development of severe pathological conditions such as cirrhosis and liver cancer. Although a large number of drug candidates for the treatment of NASH have entered clinical trial testing, all have not been released to market due to their limited efficacy, and there remains no approved treatment for NASH available to this day. Recently, organoid technology that produces 3D multicellular aggregates with a liver tissue-like cytoarchitecture and improved functionality has been suggested as a novel platform for modeling the human-specific complex pathophysiology of NAFLD and NASH. In this review, we describe the cellular crosstalk between each cellular compartment in the liver during the pathogenesis of NAFLD and NASH. We also summarize the current state of liver organoid technology, describing the cellular diversity that could be recapitulated in liver organoids and proposing a future direction for liver organoid technology as an in vitro platform for disease modeling and drug discovery for NAFLD and NASH.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/patología , Hígado/patología , Cirrosis Hepática/etiología , Descubrimiento de Drogas , Organoides/patología
18.
Animals (Basel) ; 13(14)2023 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-37508068

RESUMEN

Widely used as a flame retardant, 2,2'4,4'-tetrabromodiphenyl ether (BDE-47) is a persistent environmental pollutant with toxicological effects, including hepatotoxicity, neurotoxicity, reproductive toxicity, and endocrine disruption. To investigate the toxicological effects of BDE-47 on early porcine embryogenesis in vitro, cultured porcine embryos were exposed to BDE-47 during early development. Exposure to 100 µM BDE-47 decreased the blastocyst rate and mRNA level of pluripotency genes but increased the level of LC3 and the expression of autophagy-related genes. After BDE-47 exposure, porcine embryos' antioxidant capability decreased; ROS levels increased, while glutathione (GSH) levels and the expression of antioxidant-related genes decreased. In addition, BDE-47 exposure reduced mitochondrial abundance and mitochondrial membrane potential levels, downregulated mitochondrial biogenesis-associated genes, decreased endoplasmic reticulum (ER) abundance, increased the levels of GRP78, a marker of ER stress (ERS), and upregulated the expression of ERS-related genes. However, ER damage and low embryo quality induced by BDE-47 exposure were reversed with the ERS inhibitor, the 4-phenylbutyric acid. In conclusion, BDE-47 inhibits the development of early porcine embryos in vitro by inducing mitochondrial dysfunction and ERS. This study sheds light on the mechanisms of BDE-47-induced embryonic toxicity.

19.
J Enzyme Inhib Med Chem ; 38(1): 2230388, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37439326

RESUMEN

Recent studies on biphenyl-containing compounds, a type of PD-1/PD-L1 blocker which binds to PD-L1 and induces dimerisation, have focussed on its immune function. Herein, 10 novel biphenyl derivatives were designed and synthesised. The results of the CCK-8 showed that compounds have different anti-tumour activities for tumour cells in the absence of T cells. Particularly, 12j-4 can significantly induce the apoptosis of MDA-MB-231 cells (IC50 = 2.68 ± 0.27 µM). In further studies, 12j-4 has been shown to prevent the phosphorylation of AKT by binding to cytoplasmic PD-L1, which induces apoptosis in MDA-MB-231 cells through non-immune pathways. The inhibition of AKT phosphorylation restores the activity of GSK-3ß, ultimately resulting in the degradation of PD-L1. Besides, in vivo study indicated that 12j-4 repressed tumour growth in nude mice. As these biphenyls exert their anti-tumour effects mainly through non-immune pathways, they are worthy of further study as PD-L1 inhibitors.


Asunto(s)
Compuestos de Bifenilo , Neoplasias de la Mama , Proteínas Proto-Oncogénicas c-akt , Animales , Ratones , Antígeno B7-H1 , Glucógeno Sintasa Quinasa 3 beta , Ratones Desnudos , Neoplasias de la Mama/tratamiento farmacológico , Compuestos de Bifenilo/farmacología
20.
Zygote ; 31(5): 451-456, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37337719

RESUMEN

Mammalian oocytes not fertilized immediately after ovulation can undergo ageing and a rapid decline in quality. The addition of antioxidants can be an efficient approach to delaying the oocyte ageing process. Onion peel extract (OPE) contains quercetin and other flavonoids with natural antioxidant activities. In this study, we investigated the effect of OPE on mouse oocyte ageing and its mechanism of action. The oocytes were aged in vitro in M16 medium for 16 h after adding OPE at different concentrations (0, 50, 100, 200, and 500 µg/ml). The addition of 100 µg/ml OPE reduced the oocyte fragmentation rate, decreased the reactive oxygen species (ROS) level, increased the glutathione (GSH) level, and improved the mitochondrial membrane potential compared with the control group. The addition of OPE also increased the expression of SOD1, CAT, and GPX3 genes, and the caspase-3 activity in OPE-treated aged oocytes was significantly lower than that in untreated aged oocytes and similar to that in fresh oocytes. These results indicated that OPE delayed mouse oocyte ageing by reducing oxidative stress and apoptosis and enhancing mitochondrial function.


Asunto(s)
Antioxidantes , Cebollas , Femenino , Ratones , Animales , Cebollas/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Oocitos , Quercetina/farmacología , Estrés Oxidativo , Glutatión/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Mamíferos
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