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1.
Sheng Wu Gong Cheng Xue Bao ; 40(4): 1040-1049, 2024 Apr 25.
Artículo en Chino | MEDLINE | ID: mdl-38658147

RESUMEN

Bacterial blight, a major disease in rice, poses a serious impact on rice production. In this study, a doubled haploid (DH) population derived from a cross between the introduced japonica cultivar 'Maybelle' and the indica landrace 'Baiyeqiu' was used to investigate the pathogenicity of four pathogen races causing bacterial blight. The results showed that the pathogenicity of all the pathogen races exhibited continuous, transgressive distribution in the DH population. Moreover, strong correlations existed between every two pathogen races, with the correlation coefficients ranging from 0.3 to 0.6. A total of 12 quantitative trait loci (QTLs) distributed on chromosomes 1, 2, 3, 5, 6, 7, 9, and 12 were detected for rice bacterial blight, explaining 4.95% to 16.05% of the phenotype. Among these QTLs, a major QTL located in the interval RM6024-RM163 on chromosome 5 was detected in three pathogen races. In addition, the pyramiding of the positive alleles can apparently improve the rice resistance to bacterial blight. This study is of great significance for broadening the genetic resources with resistance to bacterial blight in China.


Asunto(s)
Resistencia a la Enfermedad , Oryza , Enfermedades de las Plantas , Sitios de Carácter Cuantitativo , Oryza/genética , Oryza/microbiología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética , Resistencia a la Enfermedad/genética , Xanthomonas/genética , Xanthomonas/patogenicidad , Haploidia , Cromosomas de las Plantas/genética
2.
Contraception ; 135: 110439, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38552820

RESUMEN

OBJECTIVE: The majority of intrauterine devices (IUDs) inserted in China are tailless, requiring intrauterine manipulations for removal and causing pain. This study aimed to investigate the analgesic efficacy of lidocaine injection into a novel disposable injectable cervical dilator for IUD removal procedures. STUDY DESIGN: A double-blinded, placebo-controlled, randomized clinical trial was conducted with women aged 18-65 years old requesting outpatient IUD removal. The study randomly assigned participants to either lidocaine (injecting 5 ml of 2% lidocaine into the injectable cervical dilator) or placebo (injecting 5 ml of normal saline into the device) group. All participants received a standardized paracervical block. The primary outcome was pain reported during IUD removal on a 100 mm Visual Analog Scale (VAS). Intention-to-treat were conducted to evaluate the analgesic effectiveness of injecting lidocaine into the injectable cervical dilators. RESULTS: We enrolled seventy-four eligible participants (37 in lidocaine group and 37 in placebo group). The results showed that the median intraoperative VAS score in the lidocaine group was lower than the placebo group (30.0 mm [IQR 20.0-46.0, n = 37] vs 46.0 mm [IQR 30.0-55.0, n = 37], p = 0.01. In subgroup analyses, among participants with IUD removal and without uterine manipulation and additional procedures, there was no statistically significant disparity observed in intraoperative VAS scores between the lidocaine and placebo group (15.0 mm [IQR 10.0-27.5, n = 8] vs 20.0 mm [IQR 20.0-40.0, n = 6]), p = 0.28). Among participants with an IUD removal necessitating intrauterine manipulations and without additional procedures, showing lower intraoperative VAS scores in lidocaine group (25.0 mm [IQR 15.0-40.5, n = 17]) compared to placebo group (46.0 mm [IQR 38.5-50.0, n = 23]), p < 0.01. Among participants with additional procedures in addition to IUD removal, there was no statistically significant disparity observed in intraoperative VAS scores between the lidocaine and placebo group (41.0 mm [IQR 32.5-57.5, n = 12] vs 45.0 mm [IQR 22.5-69.0, n = 8]), p = 0.97). CONCLUSIONS: Injecting lidocaine into the novel disposable injectable cervical dilator for cervix dilation can significantly reduce pain during an IUD removal, particularly in patients necessitating intrauterine manipulations during IUD removal. IMPLICATIONS: When we have to perform intrauterine manipulations to remove an IUD, surgical pain and narrow cervical canal undoubtedly affect the implementation of the procedure. Injecting lidocaine into the injectable cervical dilator can achieve local anesthesia while dilating the cervix, and might reduce the choice of general anesthesia for IUD removal.


Asunto(s)
Anestésicos Locales , Remoción de Dispositivos , Dispositivos Intrauterinos , Lidocaína , Humanos , Lidocaína/administración & dosificación , Femenino , Adulto , Anestésicos Locales/administración & dosificación , Método Doble Ciego , Adulto Joven , Persona de Mediana Edad , Dimensión del Dolor , Dolor Asociado a Procedimientos Médicos/prevención & control , Dolor Asociado a Procedimientos Médicos/etiología , Adolescente , Equipos Desechables , China , Inyecciones
3.
Behav Res Ther ; 175: 104502, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38402674

RESUMEN

Disgust imagery represents a potential pathological mechanism for disgust-related disorders. However, it remains controversial as to whether disgust can be conditioned with disgust-evoking mental imagery serving as the unconditioned stimulus (US). Therefore, we examined this using a conditioned learning paradigm in combination with event-related potential (ERP) analysis in 35 healthy college students. The results indicated that the initial neutral face (conditioned stimulus, CS+) became more disgust-evoking, unpleasant, and arousing after pairing with disgust-evoking imagery (disgust CS+), compared to pairing with neutral (neutral CS+) and no (CS-) imagery. Moreover, we observed that mental imagery-based disgust conditioning was resistant to extinction. While the disgust CS + evoked larger P3 and late positive potential amplitudes than CS- during acquisition, no significant differences were found between disgust CS+ and neutral CS+, indicating a dissociation between self-reported and neurophysiological responses. Future studies may additionally acquire facial EMG as an implicit index of conditioned disgust. This study provides the first neurobiological evidence that associative disgust learning can occur without aversive physical stimuli, with implications for understanding how disgust-related disorders may manifest or deteriorate without external perceptual aversive experiences, such as in obsessive-compulsive disorder (OCD).


Asunto(s)
Asco , Trastorno Obsesivo Compulsivo , Humanos , Emociones/fisiología , Miedo/psicología , Aprendizaje , Trastorno Obsesivo Compulsivo/psicología , Extinción Psicológica/fisiología
4.
Sheng Wu Gong Cheng Xue Bao ; 40(1): 292-303, 2024 Jan 25.
Artículo en Chino | MEDLINE | ID: mdl-38258648

RESUMEN

Innovation is an important way to promote economic development and social progress. Recent years have seen rapid development of biological sciences. In response to social demands and the needs for developing an innovative country, fostering innovative talents in the field of biosciences has become a significant initiative supported by national policies and the needs from talent market. Taking the innovative talent training mode implemented by Zhejiang Normal University in the field of biological sciences as an example, this paper comprehensively introduces several key aspects of the mode. This includes establishing a mentorship system as the foundation, carrying out curriculum reform through project competitions and practical platforms, and promoting synergy among industry, academia, and research in talent training. This training mode has achieved positive results in practice, promoting the training of outstanding innovative talents in biological science majors, and may facilitate the reform of talent training in similar majors.


Asunto(s)
Disciplinas de las Ciencias Biológicas , Humanos , Industrias , Políticas , Universidades
5.
J Minim Invasive Gynecol ; 31(1): 57-63, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37838016

RESUMEN

STUDY OBJECTIVE: To evaluate the feasibility and effectiveness of hysteroscopic suture fixation of the levonorgestrel-releasing intrauterine system (LNG-IUS) for the treatment of adenomyosis. DESIGN: A retrospective case series. SETTING: Two teaching hospitals with the technology of hysteroscopic suture fixation of the LNG-IUS. PATIENTS: The study reviewed 79 adenomyosis patients who received the hysteroscopic suture fixation of the LNG-IUS from January 2021 to May 2022. INTERVENTION: Hysteroscopic suture fixation of the LNG-IUS to the posterior uterine wall with nondissolvable suture. MEASUREMENTS AND MAIN RESULTS: All patients underwent one-year postoperative follow-up to evaluate the LNG-IUS expulsion rate, postoperative efficacy, and side effects. Two patients (2.6%) experienced expulsion of the LNG-IUS at 8 months and 12 months postoperatively, respectively. The visual analog pain scale, pictorial blood loss assessment chart score and carbohydrate antigen 125 markedly decreased after the suture fixation of the LNG-IUS compared with baseline in all patients (p <.001). Hemoglobin increased significantly (p <.001). The most common side effect was irregular bleeding, which accounted for 44.3%. The second common side effect was weight gain, which accounted for 29.2%. The composite effectiveness based on pain and bleeding showed that the effective treatment rates at 1, 3, 6, and 12 months after surgery were 92.4%, 97.4%, 96.2%, and 97.4% respectively. CONCLUSIONS: Hysteroscopic suture fixation of the LNG-IUS to the uterine fundus was associated with low expulsion rates and significantly improved dysmenorrhea and bleeding.


Asunto(s)
Adenomiosis , Dispositivos Intrauterinos Medicados , Femenino , Humanos , Adenomiosis/tratamiento farmacológico , Adenomiosis/cirugía , Adenomiosis/complicaciones , Levonorgestrel/uso terapéutico , Estudios Retrospectivos , Estudios de Factibilidad , Dispositivos Intrauterinos Medicados/efectos adversos , Suturas
6.
Integr Zool ; 2023 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-37427560

RESUMEN

Honeybees are the most critical pollinators providing key ecosystem services that underpin crop production and sustainable agriculture. Amidst a backdrop of rapid global change, this eusocial insect encounters a succession of stressors during nesting, foraging, and pollination. Ectoparasitic mites, together with vectored viruses, have been recognized as central biotic threats to honeybee health, while the spread of invasive giant hornets and small hive beetles also increasingly threatens colonies worldwide. Cocktails of agrochemicals, including acaricides used for mite treatment, and other pollutants of the environment have been widely documented to affect bee health in various ways. Additionally, expanding urbanization, climate change, and agricultural intensification often result in the destruction or fragmentation of flower-rich bee habitats. The anthropogenic pressures exerted by beekeeping management practices affect the natural selection and evolution of honeybees, and colony translocations facilitate alien species invasion and disease transmission. In this review, the multiple biotic and abiotic threats and their interactions that potentially undermine bee colony health are discussed, while taking into consideration the sensitivity, large foraging area, dense network among related nestmates, and social behaviors of honeybees.

7.
Int J Oncol ; 62(5)2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37052244

RESUMEN

Gynecological malignancies are a leading cause of mortality among females worldwide, and difficulties in early diagnosis and acquired drug resistance constitute obstacles to effective therapies. Ovarian cancer causes more deaths than any other cancer of the female reproductive system. Specifically, in females aged 20 to 39 years, cervical cancer is the third leading cause of cancer­related mortality, and the incidence rates of cervical adenocarcinoma are increasing. Endometrial carcinoma is the most common gynecological cancer in developed countries, such as the United States. Vulvar cancer and uterine sarcomas are considered rare, and therefore require further investigation. Notably, the development of novel treatment options is critical. Previous research has revealed metabolic reprogramming as a distinct feature of tumor cells, which includes aerobic glycolysis. In this instance, cells produce adenosine triphosphate and various precursor molecules through glycolysis, despite oxygen levels being sufficient. This is to meet the energy required for rapid DNA replication. This phenomenon is also known as the Warburg effect. The Warburg effect results in an increased glucose uptake, lactate production and reduced pH values in tumor cells. The results of previous studies have demonstrated that microRNAs (miRNAs/miRs) regulate glycolysis, and participate in tumorigenesis and tumor progression via interactions with glucose transporters, essential enzymes, tumor suppressor genes, transcription factors and multiple cellular signaling pathways that play critical roles in glycolysis. Notably, miRNAs affect the levels of glycolysis in ovarian, cervical and endometrial cancers. The present review article provides a comprehensive overview of the literature surrounding miRNAs in the glycolysis of gynecological malignant cells. The present review also aimed to determine the role of miRNAs as potential therapeutic options rather than diagnostic markers.


Asunto(s)
Neoplasias de los Genitales Femeninos , MicroARNs , Neoplasias Ováricas , Neoplasias del Cuello Uterino , Humanos , Femenino , MicroARNs/metabolismo , Neoplasias de los Genitales Femeninos/genética , Neoplasias de los Genitales Femeninos/metabolismo , Neoplasias de los Genitales Femeninos/patología , Glucólisis/genética
8.
Diabetes ; 72(5): 562-574, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36724137

RESUMEN

Thyroid hormone (TH) has a profound effect on energy metabolism and systemic homeostasis. Adipose tissues are crucial for maintaining whole-body homeostasis; however, whether TH regulates systemic metabolic homeostasis through its action on adipose tissues is unclear. Here, we demonstrate that systemic administration of triiodothyronine (T3), the active form of TH, affects both inguinal white adipose tissue (iWAT) and whole-body metabolism. Taking advantage of the mouse model lacking adipocyte TH receptor (TR) α or TRß, we show that TRß is the major TR isoform that mediates T3 action on the expression of genes involved in multiple metabolic pathways in iWAT, including glucose uptake and use, de novo fatty acid synthesis, and both UCP1-dependent and -independent thermogenesis. Moreover, our results indicate that glucose-responsive lipogenic transcription factor in iWAT is regulated by T3, thereby being critically involved in T3-regulated glucose and lipid metabolism and energy dissipation. Mice with adipocyte TRß deficiency are susceptible to diet-induced obesity and metabolic dysregulation, suggesting that TRß in adipocytes may be a potential target for metabolic diseases. ARTICLE HIGHLIGHTS: How thyroid hormone (TH) achieves its diverse biological activities in the regulation of metabolism is not fully understood. Whether TH regulates systemic metabolic homeostasis via its action on white adipose tissue is unclear. Adipocyte TH receptor (TR) ß mediates the triiodothyronine effect on multiple metabolic pathways by targeting glucose-responsive lipogenic transcription factor in white adipose tissue; mice lacking adipocyte TRß are susceptible to high-fat diet-induced metabolic abnormalities. TRß in white adipocytes controls intracellular and systemic metabolism and may be a potential target for metabolic diseases.


Asunto(s)
Metabolismo de los Lípidos , Triyodotironina , Ratones , Animales , Triyodotironina/farmacología , Metabolismo de los Lípidos/genética , Glucosa , Hormonas Tiroideas/metabolismo , Receptores de Hormona Tiroidea/metabolismo , Factores de Transcripción/metabolismo , Homeostasis , Receptores beta de Hormona Tiroidea/genética , Receptores beta de Hormona Tiroidea/metabolismo , Adipocitos Blancos/metabolismo
9.
Nutrients ; 15(4)2023 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-36839245

RESUMEN

Iodine is an essential micronutrient for producing thyroid hormone (TH); however, iodide excess can lead to adverse thyroidal effects. Unfortunately, the lack of a proper in vitro model system hampered the studies of the effect of iodide excess on thyroid physiology and pathology. Here, we demonstrated that excessive iodide intake downregulated the genes related to TH synthesis in the thyroids of mice. Since sodium iodide has no effect on these genes in cultured cell lines, we developed a three-dimensional (3D) culture system to enable the murine thyrocytes to form organoids in vitro with thyroid follicle-like structures and function and found that the in vivo effect of iodide excess could be mimicked in these thyroid organoids. Our data indicate that iodide excess mainly activated the XBP1-mediated unfolded protein response in both murine thyroid and thyroid organoids, while activation of XBP1 was able to mimic the sodium iodide effect on genes for the synthesis of TH in murine thyroid organoids. Lastly, our results suggest that XBP1 might transcriptionally repress the genes involved in the synthesis of TH. Based on these findings, we propose that iodide excess inhibits the transcription of genes related to TH synthesis through a mechanism involving XBP1-mediated action.


Asunto(s)
Yoduros , Yoduro de Sodio , Ratones , Animales , Yoduro de Sodio/metabolismo , Yoduro de Sodio/farmacología , Hormonas Tiroideas/metabolismo , Glándula Tiroides/metabolismo , Línea Celular , Proteína 1 de Unión a la X-Box/metabolismo
10.
Cancer Cell Int ; 23(1): 4, 2023 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-36639695

RESUMEN

The three most common gynaecologic cancers that seriously threaten female lives and health are ovarian cancer, cervical cancer, and endometrial cancer. Glycolysis plays a vital role in gynaecologic cancers. Several long noncoding RNAs (lncRNAs) are known to function as oncogenic molecules. LncRNAs impact downstream target genes by acting as ceRNAs, guides, scaffolds, decoys, or signalling molecules. However, the role of glycolysis-related lncRNAs in regulating gynaecologic cancers remains poorly understood. In this review, we emphasize the functional roles of many lncRNAs that have been found to promote glycolysis in gynaecologic cancers and discuss reasonable strategies for future research.

11.
Int J Oncol ; 61(6)2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36321774

RESUMEN

As one of the three major malignant tumor types of the female reproductive system, endometrial cancer (EC) is the most prevalent gynecologic cancer in developed countries. In recent years, the incidence of EC has increased worldwide, threatening the health and well­being of women. Recent research has indicated that the expression of multiple N6­methyladenosine (m6A) regulators is up­ or downregulated in EC and that abnormalities in m6A methylation and the expression of associated regulators are critical to the pathogenesis and progression of EC. m6A is the most abundant internal modification of mRNA. Several studies have demonstrated a close association between the development and progression of malignant tumors and the epigenetic phenomenon of m6A methylation. In the present study, the current status of research on m6A methylation in EC was reviewed. The mechanisms of methyltransferase, demethylase and m6A binding protein in regulating the development and progression of EC by modifying mRNA were introduced. The related research results will provide novel methods and approaches for the prevention and treatment of EC.


Asunto(s)
Adenosina , Neoplasias Endometriales , Femenino , Humanos , Metilación , Metiltransferasas/metabolismo , ARN Mensajero/metabolismo , ARN/genética
12.
Nat Commun ; 13(1): 6408, 2022 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-36302774

RESUMEN

Thyroid hormones (TH) regulate systemic glucose metabolism through incompletely understood mechanisms. Here, we show that improved glucose metabolism in hypothyroid mice after T3 treatment is accompanied with increased glucagon-like peptide-1 (GLP-1) production and insulin secretion, while co-treatment with a GLP-1 receptor antagonist attenuates the effects of T3 on insulin and glucose levels. By using mice lacking hepatic TH receptor ß (TRß) and a liver-specific TRß-selective agonist, we demonstrate that TRß-mediated hepatic TH signalling is required for both the regulation of GLP-1 production and the insulinotropic and glucose-lowering effects of T3. Moreover, administration of a liver-targeted TRß-selective agonist increases GLP-1 and insulin levels and alleviates hyperglycemia in diet-induced obesity. Mechanistically, T3 suppresses Cyp8b1 expression, resulting in increased the levels of Farnesoid X receptor (FXR)-antagonistic bile acids, thereby potentiating GLP-1 production and insulin secretion by repressing intestinal FXR signalling. T3 correlates with both plasma GLP-1 and fecal FXR-antagonistic bile acid levels in people with normal thyroid function. Thus, our study reveals a role for hepatic TH signalling in glucose homeostasis through the regulation of GLP-1 production via bile acid-mediated FXR antagonism.


Asunto(s)
Ácidos y Sales Biliares , Péptido 1 Similar al Glucagón , Animales , Ratones , Péptido 1 Similar al Glucagón/metabolismo , Glucosa , Homeostasis , Insulina , Hígado/metabolismo , Ratones Endogámicos C57BL , Receptores Citoplasmáticos y Nucleares , Receptores Acoplados a Proteínas G/metabolismo , Hormonas Tiroideas , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/antagonistas & inhibidores
13.
Environ Pollut ; 310: 119900, 2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-35940484

RESUMEN

Under intensive human activity, sewage discharge causes eutrophication-driven cyanobacteria blooms as well as nanomaterial pollution. In biological control of harmful cyanobacteria, top-down effect of protozoan has great potentials for removing cyanobacterial populations, degrading cyanotoxins, and improving phytoplankton community. ZnO nanoparticles as a kind of emerging contaminants have attracted increasing attention because of wide application and their high bio-toxicity effects on reducing the ingestion of aquatic animals including Paramecium, thereby possibly disturbing top-down control of cyanobacteria. Therefore, this study investigated the effects of ZnO nanoparticles at environmental-relevant concentrations on the protozoan Paramecium removing toxic Microcystis. Results showed Paramecium effectively eliminated all the Microcystis, despite exposure to ZnO nanoparticles. However, their ingestion rate was significantly reduced at more than 0.1 mg L-1 ZnO nanoparticles, thereby delaying Microcystis removal. Nevertheless, at 0.1 mg L-1 ZnO nanoparticles, the time to Microcystis extinction decreased compared to the group without ZnO nanoparticles, because Microcystis populations were reduced under this circumstance, while ingestion rate of Paramecium was unaffected. Furthermore, ZnO nanoparticles obviously accumulated in food vacuoles of Paramecium, and the size of nanoparticles aggregates and zinc concentrations in Paramecium were increased with ZnO nanoparticles concentrations. At the end of experiment, these food vacuoles were not dissipated. Overall, these findings suggest that ZnO nanoparticles impair protozoan top-down effects through reducing Microcystis and ingestion rate as well as disturbing functions of their digestive organelles, and highlight the need to consider the interfering effects of environmental pollutants on cyanobacterial removal efficiency by protozoans in natural waters.


Asunto(s)
Cianobacterias , Microcystis , Paramecium , Óxido de Zinc , Animales , Eutrofización , Humanos , Microcistinas
14.
Nat Commun ; 13(1): 3394, 2022 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-35697700

RESUMEN

The thyroid hormone (TH)-controlled recruitment process of brown adipose tissue (BAT) is not fully understood. Here, we show that long-term treatment of T3, the active form of TH, increases the recruitment of thermogenic capacity in interscapular BAT of male mice through hyperplasia by promoting the TH receptor α-mediated adipocyte progenitor cell proliferation. Our single-cell analysis reveals the heterogeneous nature and hierarchical trajectory within adipocyte progenitor cells of interscapular BAT. Further analyses suggest that T3 facilitates cell state transition from a more stem-like state towards a more committed adipogenic state and promotes cell cycle progression towards a mitotic state in adipocyte progenitor cells, through mechanisms involving the action of Myc on glycolysis. Our findings elucidate the mechanisms underlying the TH action in adipocyte progenitors residing in BAT and provide a framework for better understanding of the TH effects on hyperplastic growth and adaptive thermogenesis in BAT depot at a single-cell level.


Asunto(s)
Tejido Adiposo Pardo , Triyodotironina , Adipocitos/metabolismo , Adipocitos Marrones/metabolismo , Tejido Adiposo Pardo/metabolismo , Animales , Proliferación Celular , Hiperplasia/metabolismo , Masculino , Ratones , Receptores de Hormona Tiroidea/metabolismo , Termogénesis , Hormonas Tiroideas/metabolismo , Triyodotironina/metabolismo , Triyodotironina/farmacología
15.
Diabetes ; 2021 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-34957482

RESUMEN

The mechanisms underlying the pathogenesis of steatosis and insulin resistance in nonalcoholic fatty liver disease remain elusive. Increased phosphorylation of hepatic p38 has long been noticed in fatty liver; however, whether the activation of hepatic p38 is a cause or consequence of liver steatosis is unclear. Here, we demonstrate that hepatic p38 activation by MKK6 overexpression in the liver of mice induces severe liver steatosis, reduces fat mass, and elevates circulating fatty acid levels in a hepatic p38α- and FGF21-dependent manner. Mechanistically, through increasing the FGF21 production from liver, hepatic p38 activation increases the influx of fatty acids from adipose tissue to liver, leading to hepatic ectopic lipid accumulation and insulin resistance. Although hepatic p38 activation exhibits favorable effects in peripheral tissues, it impairs the hepatic FGF21 action by facilitating the ubiquitination and degradation of FGF21 receptor cofactor ß-Klotho. Consistently, we show that p38 phosphorylation and FGF21 expffression are increased, ß-Klotho protein levels are decreased in the fatty liver of either mice or patients. In conclusion, our study reveals previously undescribed effects of hepatic p38 activation on systemic metabolism and provides new insights into the roles of hepatic p38α, FGF21, and ß-Klotho in the pathogenesis of nonalcoholic fatty liver disease.

16.
Diabetes ; 2021 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-34675006

RESUMEN

The mechanisms underlying the pathogenesis of steatosis and insulin resistance in nonalcoholic fatty liver disease remain elusive. Increased phosphorylation of hepatic p38 has long been noticed in fatty liver; however, whether the activation of hepatic p38 is a cause or consequence of liver steatosis is unclear. Here, we demonstrate that hepatic p38 activation by MKK6 overexpression in the liver of mice induces severe liver steatosis, reduces fat mass, and elevates circulating fatty acid levels in a hepatic p38α- and FGF21-dependent manner. Mechanistically, through increasing the FGF21 production from liver, hepatic p38 activation increases the influx of fatty acids from adipose tissue to liver, leading to hepatic ectopic lipid accumulation and insulin resistance. Although hepatic p38 activation exhibits favorable effects in peripheral tissues, it impairs the hepatic FGF21 action by facilitating the ubiquitination and degradation of FGF21 receptor cofactor ß-Klotho. Consistently, we show that p38 phosphorylation and FGF21 expffression are increased, ß-Klotho protein levels are decreased in the fatty liver of either mice or patients. In conclusion, our study reveals previously undescribed effects of hepatic p38 activation on systemic metabolism and provides new insights into the roles of hepatic p38α, FGF21, and ß-Klotho in the pathogenesis of nonalcoholic fatty liver disease.

17.
EMBO Rep ; 22(9): e52247, 2021 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-34358402

RESUMEN

Our knowledge of the coordination of fuel usage in skeletal muscle is incomplete. Whether and how microRNAs are involved in the substrate selection for oxidation is largely unknown. Here we show that mice lacking miR-183 and miR-96 have enhanced muscle oxidative phenotype and altered glucose/lipid homeostasis. Moreover, loss of miR-183 and miR-96 results in a shift in substrate utilization toward fat relative to carbohydrates in mice. Mechanistically, loss of miR-183 and miR-96 suppresses glucose utilization in skeletal muscle by increasing PDHA1 phosphorylation via targeting FoxO1 and PDK4. On the other hand, loss of miR-183 and miR-96 promotes fat usage in skeletal muscle by enhancing intramuscular lipolysis via targeting FoxO1 and ATGL. Thus, our study establishes miR-183 and miR-96 as master coordinators of fuel selection and metabolic homeostasis owing to their capability of modulating both glucose utilization and fat catabolism. Lastly, we show that loss of miR-183 and miR-96 can alleviate obesity and improve glucose metabolism in high-fat diet-induced mice, suggesting that miR-183 and miR-96 may serve as therapeutic targets for metabolic diseases.


Asunto(s)
Glucosa , MicroARNs , Animales , Dieta Alta en Grasa/efectos adversos , Ratones , MicroARNs/genética , Músculo Esquelético , Obesidad/genética
18.
Opt Express ; 22(26): 32071-81, 2014 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-25607173

RESUMEN

An tapered hyperbolic metal waveguide is suggested for the nanofocusing of terahertz waves. We numerically show that, at the frequency of 1 THz, the focal spot can be as small as only 5 nm, which is smaller than that of a plate waveguide by 2 orders of magnitude. Correspondingly, the longitudinal component of the energy flow density is stronger than that of a plate waveguide by 3 orders of magnitude for the same input. It is shown that these significant improvements come from the small imaginary part of the effective index of the hyperbolic metal waveguide.


Asunto(s)
Nanopartículas del Metal/química , Modelos Teóricos , Nanotecnología/instrumentación , Dispersión de Radiación , Resonancia por Plasmón de Superficie/instrumentación , Radiación Terahertz , Simulación por Computador , Diseño Asistido por Computadora , Diseño de Equipo , Análisis de Falla de Equipo , Nanopartículas del Metal/ultraestructura
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