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1.
Chemistry ; : e202402231, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39008402

RESUMEN

Supramolecular polymers (SPs) are constructed through non-covalent interactions. The dynamic or reversible nature of SPs endows them unique physical and chemical properties, such as self-adaptive and stimuli-response abilities. The topological structures of SPs play an important role in determining the physicochemical properties and functionality. Hyperbranched polymers (HBPs) are highly branched 3D macromolecules with linear, dendritic, and terminal units, which makes them versatile candidates for the construction of SPs with fascinating architectures. The resultant HBP-based SPs perfectly integrated the dynamic/reversible nature of SPs and the 3D topological features and multifunctionality of HBP polymers. To date, various types of HBP-based SPs and their assemblies have been constructed, and their potential applications have been explored as well. This article overviews the current progress on self-assembly of HBP-based SPs. The strategies for construction of HBP-based SPs and their assemblies are discussed. Typical potential applications of the assemblies of HBP-based SPs are also introduced.

2.
Foods ; 13(13)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38998550

RESUMEN

Rosa roxburghii Tratt pomace (RRTP), an underutilized byproduct, is rich in polyphenol compounds. This study aimed to further explore the purification, characterization, anti-inflammatory activities, and underlying molecular mechanisms of free polyphenols (RRTP-FP) and bound polyphenols (RRTP-BP) from RRTP. The results indicated that AB-8 macroporous resin emerged as the preferred choice for subsequent separation and purification. The purities of purified RRTP-FP (P-RRTP-FP) and purified RRTP-BP (P-RRTP-BP) increased by 103.34% and 66.01%, respectively. Quantitative analysis identified epigallocatechin, epicatechin, and ellagic acid as the main phenolic compounds in P-RRTP-FP. In P-RRTP-BP, the primary phenolic compounds were ellagic acid, epicatechin, and gallic acid. In vitro antioxidant assays demonstrated the superior DPPH and ABTS radical scavenging activities of P-RRTP-FP and P-RRTP-BP compared to vitamin C. Treatment with P-RRTP-FP and P-RRTP-BP reduced nitric oxide (NO) and reactive oxygen species (ROS) production, mitigated the decline in cellular membrane potential, and significantly downregulated the mRNA expression of pro-inflammatory cytokines and inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Additionally, P-RRTP-FP and P-RRTP-BP inhibited the phosphorylation of pertinent proteins in the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. This finding suggests potential utility of RRTP-derived polyphenols as anti-inflammatory agents for managing severe inflammatory conditions.

3.
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
4.
J Mater Chem B ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38919138

RESUMEN

The clinical application of photodynamic therapy (PDT) has some limitations including poor tumor targeting properties, a high reductive tumor microenvironment, and inefficient activation of single cell death machinery. We herein report pH-sensitive polymeric nanomodulators (NBS-PDMC NPs) for ferroptosis-enhanced photodynamic therapy. NBS-PDMC NPs were constructed using a positively charged type-I photosensitizer (NBS) coordinated with a demethylcantharidin (DMC)-decorated block copolymer via electrostatic interactions. NBS-PDMC NPs had a negative surface charge, which ensures their high stability in bloodstream circulation, while exposure to lysosomal acidic environments reverses their surface charge to positive for tumor penetration and the release of DMC and NBS. Under NIR light irradiation, NBS generated ROS to induce cell damage; in the meantime, DMC inhibited the expression of the GPX4 protein in tumor cells and promoted ferroptosis of tumor cells. This polymer design concept provides some novel insights into smart drug delivery and combinational action to amplify the antitumor effect.

5.
Nutrients ; 16(12)2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38931321

RESUMEN

Adenovirus (HAdV) can cause severe respiratory infections in children and immunocompromised patients. There is a lack of specific therapeutic drugs for HAdV infection, and the study of anti-adenoviral drugs has far-reaching clinical implications. Elemental selenium can play a specific role as an antioxidant in the human immune cycle by non-specifically binding to the amino acid methionine in body proteins. Methods: The antiviral mechanism of selenomethionine was explored by measuring cell membrane status, intracellular DNA status, cytokine secretion, mitochondrial membrane potential, and ROS production. Conclusions: Selenomethionine improved the regulation of ROS-mediated apoptosis by modulating the expression of Jak1/2, STAT3, and BCL-XL, which led to the inhibition of apoptosis. It is anticipated that selenomethionine will offer a new anti-adenoviral therapeutic alternative.


Asunto(s)
Apoptosis , Especies Reactivas de Oxígeno , Factor de Transcripción STAT3 , Selenometionina , Transducción de Señal , Humanos , Selenometionina/farmacología , Apoptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Factor de Transcripción STAT3/metabolismo , Quinasas Janus/metabolismo , Antivirales/farmacología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Células A549
6.
J Neuroeng Rehabil ; 21(1): 77, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38745227

RESUMEN

BACKGROUND: Over 80% of patients with stroke experience finger grasping dysfunction, affecting independence in activities of daily living and quality of life. In routine training, task-oriented training is usually used for functional hand training, which may improve finger grasping performance after stroke, while augmented therapy may lead to a better treatment outcome. As a new technology-supported training, the hand rehabilitation robot provides opportunities to improve the therapeutic effect by increasing the training intensity. However, most hand rehabilitation robots commonly applied in clinics are based on a passive training mode and lack the sensory feedback function of fingers, which is not conducive to patients completing more accurate grasping movements. A force feedback hand rehabilitation robot can compensate for these defects. However, its clinical efficacy in patients with stroke remains unknown. This study aimed to investigate the effectiveness and added value of a force feedback hand rehabilitation robot combined with task-oriented training in stroke patients with hemiplegia. METHODS: In this single-blinded randomised controlled trial, 44 stroke patients with hemiplegia were randomly divided into experimental (n = 22) and control (n = 22) groups. Both groups received 40 min/day of conventional upper limb rehabilitation training. The experimental group received 20 min/day of task-oriented training assisted by a force feedback rehabilitation robot, and the control group received 20 min/day of task-oriented training assisted by therapists. Training was provided for 4 weeks, 5 times/week. The Fugl-Meyer motor function assessment of the hand part (FMA-Hand), Action Research Arm Test (ARAT), grip strength, Modified Ashworth scale (MAS), range of motion (ROM), Brunnstrom recovery stages of the hand (BRS-H), and Barthel index (BI) were used to evaluate the effect of two groups before and after treatment. RESULTS: Intra-group comparison: In both groups, the FMA-Hand, ARAT, grip strength, AROM, BRS-H, and BI scores after 4 weeks of treatment were significantly higher than those before treatment (p < 0.05), whereas there was no significant difference in finger flexor MAS scores before and after treatment (p > 0.05). Inter-group comparison: After 4 weeks of treatment, the experimental group's FMA-Hand total score, ARAT, grip strength, and AROM were significantly better than those of the control group (p < 0.05). However, there were no statistically significant differences in the scores of each sub-item of the FMA-Hand after Bonferroni correction (p > 0.007). In addition, there were no statistically significant differences in MAS, BRS-H, and BI scores (p > 0.05). CONCLUSION: Hand performance improved in patients with stroke after 4 weeks of task-oriented training. The use of a force feedback hand rehabilitation robot to support task-oriented training showed additional value over conventional task-oriented training in stroke patients with hand dysfunction. CLINICAL TRIAL REGISTRATION INFORMATION: NCT05841108.


Asunto(s)
Fuerza de la Mano , Hemiplejía , Robótica , Rehabilitación de Accidente Cerebrovascular , Humanos , Rehabilitación de Accidente Cerebrovascular/métodos , Rehabilitación de Accidente Cerebrovascular/instrumentación , Masculino , Femenino , Persona de Mediana Edad , Robótica/instrumentación , Fuerza de la Mano/fisiología , Hemiplejía/rehabilitación , Hemiplejía/fisiopatología , Hemiplejía/etiología , Anciano , Método Simple Ciego , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/fisiopatología , Dedos/fisiología , Dedos/fisiopatología , Mano/fisiopatología , Adulto , Retroalimentación Sensorial/fisiología , Resultado del Tratamiento , Recuperación de la Función
7.
ACS Omega ; 9(19): 20919-20926, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38764630

RESUMEN

Cervical cancer is a significant global health concern, and novel therapeutic strategies are continually being sought to combat this disease. In recent years, selenadiazole found latent therapeutic effects on tumors. Herein, investigating the mechanism of selenadiazole in Hela cells holds promise for advancing cervical cancer treatment. Hela cells, a widely utilized model for studying cervical cancer, were treated with selenadiazole, and cell viability was assessed by using the cell counting kit-8 (CCK-8) assay. Changes in mitochondrial membrane potential were evaluated using JC-1 staining, while apoptosis induction was examined using AnnexinV-PI double staining. Intracellular ROS levels were measured by using specific fluorescent probes and the ELIASA system. Additionally, Western blotting was performed to assess the activation of related proteins in response to selenadiazole. Data analysis was performed using GraphPad. Exposure to selenadiazole led to a substantial increase in intracellular redox oxygen species (ROS) levels in Hela cells. Importantly, the induction of ROS by selenadiazole was associated with a marked increase in mitochondrial apoptosis, as evidenced by elevated levels of AnnexinV-positive cells, the JC-1 monomer, caspase-9, and Bcl-2. Furthermore, activation of the JAK2/STAT3 pathway was observed following the selenadiazole treatment. Selenadiazole holds the potential to suppress tumor growth in cervical cancer cells by increasing reactive oxygen species (ROS) levels and inducing mitochondrial apoptosis via the JAK2/STAT3 pathway. This study offers valuable insights into potential cervical cancer therapies and underscores the need for further research into the specific mechanisms of selenadiazole.

8.
Polymers (Basel) ; 16(10)2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38794576

RESUMEN

Acute pneumonia (AP), triggered primarily by pathogens like bacteria and viruses, is a leading cause of human mortality. Ribavirin, a broad-spectrum antiviral agent, plays a pivotal role in the treatment of AP. However, its therapeutic use is hindered by the need for high dosages and the associated cardiac and hepatic toxicities. In this study, we synthesized polyethylene glycol-modified cationic liposomes to encapsulate ribavirin (RBV-PCL) and formulated it into a spray, aiming to enhance the effectiveness of RBV through respiratory administration. Lipopolysaccharide (LPS), a compound known to induce AP models in animals, was utilized in our research. Successfully, we established an acute pneumonia model in mice using aerosol inhalation. Through animal experiments, we investigated the therapeutic effects of RBV-PCL on mice with AP. In vivo studies revealed promising results. RBV-PCL effectively prolonged the survival of mice with AP, significantly reduced the levels of inflammatory markers such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and inhibited the infiltration of neutrophils in the lungs and spleens of mice. These findings suggest that RBV-PCL can effectively suppress the inflammatory response in mice with AP, thus holding significant potential as a novel therapeutic approach for the treatment of acute pneumonia.

9.
Bioact Mater ; 38: 276-291, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38745588

RESUMEN

Human adenovirus (HAdV) can cause severe respiratory infections in immunocompromised patients, but its clinical treatment is seriously limited by side effects of drugs such as poor efficacy, low bioavailability and severe nephrotoxicity. Trace element selenium (Se) has been found will affect the disease progression of pneumonia, but its antivirus efficacy could be improved by speciation optimization. Therefore, herein we performed anti-HAdV effects of different Se speciation and found that lentinan (LNT)-decorated selenium nanoparticles (SeNPs) exhibited low cytotoxicity and excellent anti-HAdV antiviral activity. Furthermore, SeNPs@LNT reduced the HAdV infection-induced mitochondrial damage and excessive production of reactive oxygen species (ROS). It was also involved in the repair of host cell DNA damage and inhibition of viral DNA replication. SeNPs@LNT inhibited HAdV-induced apoptosis mainly by modulating the p53/Bcl-2 apoptosis signaling pathway. In vivo, SeNPs@LNT replenished Se by targeting the infected site through the circulatory system and was involved in the synthesis of Glutathione peroxidase 1 (GPx1). More importantly, GPx1 played an antioxidant and immunomodulatory role in alleviating HAdV-induced inflammatory cytokine storm and alleviating adenovirus pneumonia in Se-deficient mice. Collectively, this study provides a Se speciation of SeNPs@LNT with anti-HAdV activity, and demonstrate that SeNPs@LNT is a promising pharmaceutical candidate for the treatment of HAdV.

10.
J Biomater Appl ; : 8853282241258311, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38820587

RESUMEN

BACKGROUND: Diclofenac sodium (DS) and celecoxib (CEL) are primary anti-inflammatory agents used in the treatment of osteoarthritis (OA). Formulating these drugs into extended-release versions can effectively address the issue of multiple daily doses. In this study, we designed and synthesized a novel poly(lactic-co-glycolic acid) (PLGA) nanoliposome as a dual-drug delivery sustained-release formulation (PPLs-DS-CEL) to achieve long-lasting synergistic treatment of OA with both DS and CEL. METHODS: PPLs-DS-CEL was synthesized by the reverse evaporation method and evaluated for its physicochemical properties, encapsulation efficiency, drug release kinetics and biological properties. A rat OA model was established to assess the therapeutic efficacy and biosafety of PPLs-DS-CEL. RESULTS: The particle size of PPLs-DS-CEL was 218.36 ± 6.27 nm, with a potential of 32.56 ± 3.28 mv, indicating a homogeneous vesicle size. The encapsulation of DS and CEL by PPLs-DS-CEL was 95.18 ± 4.43% and 93.63 ± 5.11%, with drug loading of 9.56 ± 0.32% and 9.68 ± 0.34%, respectively. PPLs-DS-CEL exhibited low cytotoxicity and hemolysis, and was able to achieve long-lasting synergistic analgesic and anti-inflammatory therapeutic effects in OA through slow release of DS and CEL, demonstrating good biosafety properties. CONCLUSION: This study developed a novel sustained-release nanoliposomes formulation capable of co-loading two drugs for the long-acting synergistic treatment of OA. It offers a new and effective therapeutic strategy for OA treatment in the clinic settings and presents a promising approach for drug delivery systems.

12.
Sci Total Environ ; 927: 172243, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38582118

RESUMEN

Globally, over 287 million tons of plastic are disposed in landfills, rivers, and oceans or are burned every year. The results are devastating to our ecosystems, wildlife and human health. One promising remedy is the yellow mealworm (Tenebrio molitor larvae), which has proved capable of degrading microplastics (MPs). This paper presents a new investigation into the biodegradation of aged polyethylene (PE) film and polystyrene (PS) foam by the Tenebrio molitor larvae. After a 35 - day feeding period, both pristine and aged MPs can be consumed by larvae. Even with some inhibitions in larvae growth due to the limited nutrient supply of aged MPs, when compared with pristine MPs, the aged MPs were depolymerized more efficiently in gut microbiota based on gel permeation chromatography (GPC) and Fourier transform infrared spectroscopy (FTIR) analysis. With the change in surface chemical properties, the metabolic intermediates of aged MPs contained more oxygen-containing functional groups and shortened long-chain alkane, which was confirmed by gas chromatography and mass spectrometry (GC-MS). High-throughput sequencing revealed that the richness and diversity of gut microbes were restricted in the MPs-fed group. Although MPs had a negative effect on the relative abundance of the two dominant bacteria Enterococcaceae and Lactobacillaceae, the aged MPs may promote the relative abundance of Enterobacteriaceae and Streptococcaceae. Redundancy analysis (RDA) further verified that the aged MPs are effectively biodegraded by yellow mealworm. This work provides new insights into insect-mediated mechanisms of aged MP degradation and promising strategies for MP sustainable and efficient solutions.


Asunto(s)
Biodegradación Ambiental , Larva , Microplásticos , Polietileno , Poliestirenos , Tenebrio , Animales , Microplásticos/metabolismo , Tenebrio/metabolismo , Polietileno/metabolismo , Microbioma Gastrointestinal , Contaminantes Químicos del Agua/metabolismo
13.
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
14.
Drug Alcohol Depend ; 258: 111258, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38503243

RESUMEN

BACKGROUND: The prevalence of cigarette smoking among women is significantly different from that of men, however, cigarette use by women is little known. The study aims to describe cigarette use prevalence and patterns among Chinese females by age and province. METHODS: This study was based on the 2018 China Health Literacy Survey (2018 CHLS), a nationally representative cross-sectional study, and our analysis included 43,319 female participants aged 20-69 with valid data. The prevalence of cigarette use was estimated overall by sociodemographic factors and weighted based on the census population data. The logistic regression model was conducted to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the risk factors associated with cigarette use and dependency. RESULTS: In China, the estimated female current cigarette use prevalence was 1.85%, with over half of the population suffering from tobacco dependence (7.34 million). Jilin Province has the highest cigarette prevalence among women (10.59%), while Fujian Province has the lowest (0.27%). Participants over 60 years old (aOR=1.61, 95%CI=1.20-2.14), single (aOR=1.54, 95%CI=1.07-2.21), with primary education (aOR=1.93, 95%CI=1.47-2.52) were more likely to smoke. The age of smoking initiation among women intergenerational advanced, and compared to the cigarette users without tobacco dependence, those who have tobacco dependence start smoking earlier in all age groups (25.69 years vs. 19.36 years, p<0.001). CONCLUSIONS: The cigarette use prevalence among Chinese women was 1.85%, and there are significant differences among provinces. We noted a trend of women initiating smoking at increasingly younger ages, particularly among those with tobacco dependence.


Asunto(s)
Fumar Cigarrillos , Humanos , Femenino , Persona de Mediana Edad , Adulto , China/epidemiología , Prevalencia , Fumar Cigarrillos/epidemiología , Fumar Cigarrillos/tendencias , Anciano , Estudios Transversales , Adulto Joven , Alfabetización en Salud , Tabaquismo/epidemiología , Factores de Edad , Encuestas Epidemiológicas , Pueblos del Este de Asia
15.
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
16.
Sci Rep ; 14(1): 2845, 2024 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-38310124

RESUMEN

Phenotype-guided gene prioritizers have proved a highly efficient approach to identifying causal genes for Mendelian diseases. In our previous study, we preliminarily evaluated the performance of ten prioritizers. However, all the selected software was run based on default settings and singleton mode. With a large-scale family dataset from Deciphering Developmental Disorders (DDD) project (N = 305) and an in-house trio cohort (N = 152), the four optimal performers in our prior study including Exomiser, PhenIX, AMELIE, and LIRCIAL were further assessed through parameter optimization and/or the utilization of trio mode. The in-depth assessment revealed high diagnostic yields of the four prioritizers with refined preferences, each alone or together: (1) 83.3-91.8% of the causal genes were presented among the first ten candidates in the final ranking lists of the four tools; (2) Over 97.7% of the causal genes were successfully captured within the top 50 by either of the four software. Exomiser did best in directly hitting the target (ranking the causal gene at the very top) while LIRICAL displayed a predominant overall detection capability. Besides, cases affected by low-penetrance and high-frequency pathogenic variants were found misjudged during the automated prioritization process. The discovery of the limitations shed light on the specific directions of future enhancement for causal-gene ranking tools.


Asunto(s)
Programas Informáticos , Humanos , Fenotipo
17.
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.

18.
Curr Cancer Drug Targets ; 24(6): 668-679, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38178673

RESUMEN

BACKGROUND: Oral cancer is a malignant tumor with a high impact and poor prognosis. Naringenin, a flavonoid found in citrus fruits and its anti-inflammatory and antioxidant properties offer potential therapeutic benefits. However, limited studies have been conducted on the impact of naringenin on human tongue carcinoma CAL-27 cells. This study aims to elucidate the correlation between naringenin and tongue cancer, thereby identifying a potential therapeutic candidate for drug intervention against tongue cancer. METHODS: The effect of naringenin on the apoptosis of CAL-27 cells and its mechanism were studied by cell counting kit-8, mitochondrial membrane potential assay with JC-1, Annexin V-- FITC apoptosis detection, cell cycle, and apoptosis analysis, Reactive Oxygen Species assay and Western blot. RESULTS: The results showed that naringenin significantly induced apoptosis in CAL-27 cells in a dose-dependent manner. Mechanistically, naringenin-induced apoptosis was mediated through the upregulation of Bid and downregulation of Bcl-xl, which led to increased generation of ROS. CONCLUSION: The findings suggested that naringenin may represent a promising candidate for the treatment of oral cancer by inducing apoptotic cell death via modulation of the Bid and Bcl-xl signaling pathways.


Asunto(s)
Apoptosis , Proteína Proapoptótica que Interacciona Mediante Dominios BH3 , Flavanonas , Especies Reactivas de Oxígeno , Transducción de Señal , Proteína bcl-X , Flavanonas/farmacología , Humanos , Especies Reactivas de Oxígeno/metabolismo , Proteína bcl-X/metabolismo , Apoptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Proteína Proapoptótica que Interacciona Mediante Dominios BH3/metabolismo , Línea Celular Tumoral , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/patología , Neoplasias de la Boca/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neoplasias de la Lengua/tratamiento farmacológico , Neoplasias de la Lengua/patología , Neoplasias de la Lengua/metabolismo
19.
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.

20.
Chem Commun (Camb) ; 60(15): 2058-2061, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38288669

RESUMEN

A simple method is explored for the scission of C-CN bonds into aldehyde and CN- in air. The transformation was mediated by chloride anions. The cyanide anions were extracted from the reaction solution to form (Et4N)2[Zn(CN)4] and (Et4N)2[Ni(CN)4]. A chloride-induced reaction mechanism is proposed based on experimental studies and DFT calculations. This work might guide the study of halogen catalysts for C-C bond cleavage.

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