RESUMEN
Uncontrolled diabetes causes a catabolic state with multi-organic complications, of which impairment on skeletal muscle contributes to the damaged mobility. Kcnma1 gene encodes the pore-forming α-subunit of Ca2+ - and voltage-gated K+ channels of large conductance (BK channels), and loss-of-function mutations in Kcnma1 are in regards to impaired myogenesis. Herein, we observed a time-course reduction of Kcnma1 expression in the tibialis anterior muscles of leptin receptor-deficient (db/db) diabetic mice. To investigate the role of Kcnma1 in diabetic muscle atrophy, muscle-specific knockdown of Kcnma1 was achieved by mice receiving intravenous injection of adeno-associated virus-9 (AAV9)-encoding shRNA against Kcnma1 under the muscle creatine kinase (MCK) promoter. Impairment on muscle mass and myogenesis were observed in m/m mice with AAV9-shKcnma1 intervention, while this impairment was more obvious in diabetic db/db mice. Simultaneously, damaged mitochondrial dynamics and biogenesis showed much severer in db/db mice with AAV9-shKcnma1 intervention. RNA sequencing revealed the large transcriptomic changes resulted by Kcnma1 knockdown, and changes in mitochondrial homeostasis-related genes were validated. Besides, the artificial alteration of Kcnma1 in mouse C2C12 myoblasts was achieved with an adenovirus vector. Consistent results were demonstrated by Kcnma1 knockdown in palmitate-treated cells, whereas opposite results were exhibited by Kcnma1 overexpression. Collectively, we document Kcnma1 as a potential keeper of mitochondrial homeostasis, and the loss of Kcnma1 is a critical event in priming skeletal muscle loss in diabetes.
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Diabetes Mellitus Experimental , Canales de Potasio de Gran Conductancia Activados por el Calcio , Ratones , Animales , Canales de Potasio de Gran Conductancia Activados por el Calcio/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Subunidades alfa de los Canales de Potasio de Gran Conductancia Activados por Calcio/genética , Atrofia Muscular/genética , Atrofia Muscular/metabolismo , Músculo Esquelético/metabolismo , HomeostasisRESUMEN
BACKGROUND: Pre-gestational diabetes mellitus (PGDM) has been known to be a risk factor for congenital heart defects (CHDs) for decades. However, the associations between maternal PGDM and gestational diabetes mellitus (GDM) and the risk of specific types of CHDs and congenital anomalies (CAs) in other systems remain under debate. We aimed to investigate type-specific CAs in offspring of women with diabetes and to examine the extent to which types of maternal diabetes are associated with increased risk of CAs in offspring. METHODS AND FINDINGS: We searched PubMed and Embase from database inception to 15 October 2021 for population-based studies reporting on type-specific CAs in offspring born to women with PGDM (combined type 1 and 2) or GDM, with no limitation on language. Reviewers extracted data for relevant outcomes and performed random effects meta-analyses, subgroup analyses, and multivariable meta-regression. Risk of bias appraisal was performed using the Cochrane Risk of Bias Tool. This study was registered in PROSPERO (CRD42021229217). Primary outcomes were overall CAs and CHDs. Secondary outcomes were type-specific CAs. Overall, 59 population-based studies published from 1990 to 2021 with 80,437,056 participants met the inclusion criteria. Of the participants, 2,407,862 (3.0%) women had PGDM and 2,353,205 (2.9%) women had GDM. The meta-analyses showed increased risks of overall CAs/CHDs in offspring born to women with PGDM (for overall CAs, relative risk [RR] = 1.99, 95% CI 1.82 to 2.17, P < 0.001; for CHDs, RR = 3.46, 95% CI 2.77 to 4.32, P < 0.001) or GDM (for overall CAs, RR = 1.18, 95% CI 1.13 to 1.23, P < 0.001; for CHDs, RR = 1.50, 95% CI 1.38 to 1.64, P < 0.001). The results of the meta-regression analyses showed significant differences in RRs of CAs/CHDs in PGDM versus GDM (all P < 0.001). Of the 23 CA categories, excluding CHD-related categories, in offspring, maternal PGDM was associated with a significantly increased risk of CAs in 21 categories; the corresponding RRs ranged from 1.57 (for hypospadias, 95% CI 1.22 to 2.02) to 18.18 (for holoprosencephaly, 95% CI 4.03 to 82.06). Maternal GDM was associated with a small but significant increase in the risk of CAs in 9 categories; the corresponding RRs ranged from 1.14 (for limb reduction, 95% CI 1.06 to 1.23) to 5.70 (for heterotaxia, 95% CI 1.09 to 29.92). The main limitation of our analysis is that some high significant heterogeneity still persisted in both subgroup and sensitivity analyses. CONCLUSIONS: In this study, we observed an increased rate of CAs in offspring of women with diabetes and noted the differences for PGDM versus GDM. The RRs of overall CAs and CHDs in offspring of women with PGDM were higher than those in offspring of women with GDM. Screening for diabetes in pregnant women may enable better glycemic control, and may enable identification of offspring at risk for CAs.
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Diabetes Gestacional/epidemiología , Cardiopatías Congénitas/epidemiología , Vigilancia de la Población , Efectos Tardíos de la Exposición Prenatal/epidemiología , Estudios de Casos y Controles , Estudios de Cohortes , Estudios Transversales , Diabetes Gestacional/diagnóstico , Femenino , Cardiopatías Congénitas/diagnóstico , Humanos , Embarazo , Efectos Tardíos de la Exposición Prenatal/diagnóstico , Factores de RiesgoRESUMEN
Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset or first recognition in the second or third trimester of pregnancy. GDM has a considerable impact on health outcomes of the mother and offspring during pregnancy, delivery, and beyond. Although the exact mechanism regarding GDM remains unclear, numerous studies have suggested that non-coding RNAs, including long non-coding (lnc)RNAs, microRNAs, and circular RNAs, were involved in the pathogenesis of GDM in which they played vital regulatory roles. Additionally, several studies have revealed that extracellular vehicles also participated in the pathogenesis of GDM, highlighting their important role in this disease. Considering the lack of effective biomarkers for the early identification of and specific treatment for GDM, non-coding RNAs and extracellular vehicles may be promising biomarkers and even targets for GDM therapies. This review provides an update on our understanding of the role of non-coding RNAs and extracellular vehicles in GDM. As our understanding of the function of lncRNAs and extracellular vehicles improves, the future appears promising for their use as potential biomarkers and treatment targets for GDM in clinical practice.
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Diabetes Gestacional/patología , Vesículas Extracelulares/patología , ARN Largo no Codificante/genética , Diabetes Gestacional/genética , Femenino , Humanos , EmbarazoRESUMEN
Globally, lung cancer is the most commonly diagnosed cancer and carries with it the greatest mortality rate, with 5-year survival rates varying from 4-17% depending on stage and geographical differences. For decades, researchers have studied disease mechanisms, occurrence rates and disease development, however, the mechanisms underlying disease progression are not yet fully elucidated, thus an increased understanding of disease pathogenesis is key to developing new strategies towards specific disease diagnoses and targeted treatments. Circular RNAs (circRNAs) are a class of non-coding RNA widely expressed in eukaryotic cells, and participate in various biological processes implicated in human disease. Recent studies have indicated that circRNAs both positively and negatively regulate lung cancer cell proliferation, migration, invasion and apoptosis. Additionally, circRNAs could be promising biomarkers and targets for lung cancer therapies. This review systematically highlights recent advances in circRNA regulatory roles in lung cancer, and sheds light on their use as potential biomarkers and treatment targets for this disease.
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Long non-coding RNAs (lncRNAs) are a type of non-coding RNA with a length that exceeds 200 nucleotides. Previous studies have shown that lncRNAs play an important role in the pathogenesis of various diseases. Research in both animal models and humans has begun to unravel the profound complexity of lncRNAs and demonstrated that lncRNAs exert direct effects on glucose and lipid metabolism both in vivo and in vitro. Such research has elucidated the regulatory role of lncRNAs in glucose and lipid metabolism in human disease. lncRNAs mediate glucose and lipid metabolism under physiological and pathological conditions and contribute to various metabolism disorders. This review provides an update on our understanding of the regulatory role of lncRNAs in glucose and lipid metabolism in various diseases. As our understanding of the function of lncRNAs improves, the future is promising for the development of new diagnostic biomarkers that utilize lncRNAs and treatments that target lncRNAs to improve clinical outcomes.
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Glucosa/metabolismo , Metabolismo de los Lípidos , Enfermedades Metabólicas/epidemiología , ARN Largo no Codificante/genética , Animales , Humanos , Enfermedades Metabólicas/genética , Enfermedades Metabólicas/metabolismoRESUMEN
2'-5'-Oligoadenylate synthetase-like protein (OASL) is an interferon-inducible antiviral protein that exerts antiviral effects through the RNase L- or retinoic acid-inducible gene I (RIG-I)-dependent signalling pathway. In this study, we identified and cloned the OASL gene (named duOASL) from healthy adult Cherry Valley ducks. Full-length duOASL cDNA (1630bp) encoded a 504-amino acid polypeptide containing three conserved domains, namely, nucleotidyltransferase domain, 2'-5'-oligoadenylate synthetase domain, and two ubiquitin-like repeats. DuOASL mRNA expression was quantified by performing quantitative reverse transcription-PCR (qRT-PCR). Results of qRT-PCR showed that duOASL was broadly expressed in all examined tissues, with the highest mRNA expression in the large intestine. Antiviral activity of duOASL was measured by determining its effect on Duck Tembusu virus (DTMUV) replication in vitro. We found that duOASL overexpression slightly inhibited DTMUV replication, whereas duOASL knockdown by using a specific small interfering RNA increased DTMUV replication in DF-1 cells. Thus, we successfully cloned and characterized the antiviral protein duOASL from Cherry Valley ducks and found that it exerted antiviral effects against DTMUV. These results provide a solid foundation for performing further studies to determine the mechanism underlying the antiviral effect of duOASL at the cellular level.
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2',5'-Oligoadenilato Sintetasa/genética , Proteínas Aviares/genética , Clonación Molecular , Patos/genética , Flavivirus/inmunología , 2',5'-Oligoadenilato Sintetasa/análisis , 2',5'-Oligoadenilato Sintetasa/química , 2',5'-Oligoadenilato Sintetasa/inmunología , Secuencia de Aminoácidos , Animales , Proteínas Aviares/análisis , Proteínas Aviares/química , Proteínas Aviares/inmunología , Flavivirus/clasificación , Especificidad de Órganos , Filogenia , Alineación de SecuenciaRESUMEN
OBJECTIVE: To investigate the protective effects and mechanisms of Radix Astragali Injection on multiple organs of rats with obstructive jaundice (OJ). METHODS: A total of 180 rats were randomly divided into the sham-operated, model control and treated groups (60 in each group). On 7, 14, 21 and 28 days after operation, the serum contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), r-glutamyl transpeptidase (r-GT), total bilirubin (TBil), direct bilirubin (DBil), blood urine nitrogen (BUN), and creatinine (CREA) were determined. And the pathological changes of livers, kidneys and lungs, and protein expressions of toll-like receptor-4 (TLR-4) of livers, intercellular adhesion molecule-1 (ICAM-1) of lungs, Bax and nuclear factor-kappa B (NF-κB), as well as apoptotic indexes of multiple organs were observed, respectively. RESULTS: The pathological severity scores of multiple organs (including livers on 7, 14, 21 and 28 days, kidneys on 14 and 28 days, and lungs on 14 days), serum contents of ALT (14 and 21 days), AST (14 days), TBil (7, 14, 21 and 28 days), DBil (14 and 21 days), BUN (28 days), protein expressions of TLR-4 (in livers, 28 days), Bax (in livers and kidneys, 21 days), and apoptotic indexes in livers (7 and 21 days) in the treated group were significantly lower than those in the model control group (P<0.05 or P<0.01). CONCLUSION: Radix Astragali Injection exerts protective effects on multiple organs of OJ rats by improving the pathological changes of lung, liver and kidney, decreasing the serum index of hepatic and renal function as well as inhibiting the protein expression of TLR-4 and Bax in the livers and Bax in the kidneys.
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Medicamentos Herbarios Chinos/uso terapéutico , Ictericia Obstructiva/tratamiento farmacológico , Especificidad de Órganos , Sustancias Protectoras/uso terapéutico , Alanina Transaminasa/sangre , Animales , Apoptosis/efectos de los fármacos , Aspartato Aminotransferasas/sangre , Astragalus propinquus , Bilirrubina/sangre , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Medicamentos Herbarios Chinos/farmacología , Inmunohistoquímica , Inyecciones , Molécula 1 de Adhesión Intercelular/metabolismo , Ictericia Obstructiva/sangre , Riñón/efectos de los fármacos , Riñón/patología , Hígado/efectos de los fármacos , Hígado/patología , Pulmón/efectos de los fármacos , Pulmón/patología , Masculino , FN-kappa B/metabolismo , Especificidad de Órganos/efectos de los fármacos , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Ratas Sprague-Dawley , Receptor Toll-Like 4/metabolismo , Proteína X Asociada a bcl-2/metabolismo , gamma-Glutamiltransferasa/metabolismoRESUMEN
Berberine is the major active component of Rhizoma Coptidis derived from a traditional Chinese herbal medicine and is known to regulate micro (mi)RNA levels, although the mechanism for this action remains unknown. The present study confirmed that treatment of 3T3L1 cells with berberine inhibited cell viability and differentiation in a dose and timedependent manner, and significantly increased the mRNA expression levels of miRNA27a and miRNA27b. In addition, in 3T3L1 cells treated with berberine, overexpression of miRNA27a and miRNA27b improved the berberine-mediated inhibition of cell differentiation and reduction of triglyceride contents. By contrast, miRNA27a and miRNA27b inhibitors attenuated the berberinemediated inhibition of cell differentiation and reduction of triglyceride contents. Additionally, peroxisome proliferatoractivated receptors (PPAR)γ was confirmed to be a target of miRNA27a in the 3T3L1 cells. A dualluciferase reporter assay indicated that the expression of PPARγ was negatively regulated by miRNA-27a. These findings may provide novel mechanistic insight into the antiobesity effects of certain compounds in traditional Chinese herbal medicine.
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Berberina/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , MicroARNs/genética , Regiones no Traducidas 3' , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Animales , Sitios de Unión , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Ratones , PPAR gamma/genética , Interferencia de ARN , Triglicéridos/metabolismoRESUMEN
Since the first H7N9 human case in Shanghai, February 19, 2013, the emerging avian-origin H7N9 influenza A virus has become an epizootic virus in China, posing a potential pandemic threat to public health. From April 2 to April 28, 2013, some 422 oral-pharyngeal and cloacal swabs were collected from birds and environmental surfaces at five live poultry markets (LPMs) and 13 backyard poultry farms (BPFs) across three cities, Wuxi, Suzhou, and Nanjing, in the Yangtze Delta region. In total 22 isolates were recovered, and six were subtyped as H7N9, nine as H9N2, four as H7N9/H9N2, and three unsubtyped influenza A viruses. Genomic sequences showed that the HA and NA genes of the H7N9 viruses were similar to those of the H7N9 human isolates, as well as other avian-origin H7N9 isolates in the region, but the PB1, PA, NP, and MP genes of the sequenced viruses were more diverse. Among the four H7N9/H9N2 mixed infections, three were from LPM, whereas the other one was from the ducks at one BPF, which were H7N9 negative in serologic analyses. A survey of the bird trading records of the LPMs and BPFs indicates that trading was a likely route for virus transmission across these regions. Our results suggested that better biosecurity and more effective vaccination should be implemented in backyard farms, in addition to biosecurity management in LPMs.
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Subtipo H7N9 del Virus de la Influenza A/aislamiento & purificación , Gripe Aviar/virología , Enfermedades de las Aves de Corral/virología , Animales , Pollos , China/epidemiología , Brotes de Enfermedades , Patos , Subtipo H7N9 del Virus de la Influenza A/clasificación , Subtipo H7N9 del Virus de la Influenza A/genética , Subtipo H7N9 del Virus de la Influenza A/fisiología , Subtipo H9N2 del Virus de la Influenza A/clasificación , Subtipo H9N2 del Virus de la Influenza A/genética , Subtipo H9N2 del Virus de la Influenza A/aislamiento & purificación , Subtipo H9N2 del Virus de la Influenza A/fisiología , Gripe Aviar/epidemiología , Filogenia , Enfermedades de las Aves de Corral/epidemiologíaRESUMEN
All couples attending the premarital examination at four selected sites in Zhejiang and Yunnan provinces in China were included in this study. Blood from 9952 individuals was tested for HIV-1 using a gelatin particle agglutination technique. There were no HIV-positive individuals in Zhejiang. In Yunnan, 28 of 3742 individuals were positive, a prevalence of 0.75%. The premarital examination should be used for voluntary counselling and testing and anonymous surveillance for HIV in high prevalence areas.