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1.
Mol Microbiol ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38629786

RESUMO

Minute virus of canines (MVC) belongs to the genus Bocaparvovirus (formerly Bocavirus) within the Parvoviridae family and causes serious respiratory and gastrointestinal symptoms in neonatal canines worldwide. A productive viral infection relies on the successful recruitment of host factors for various stages of the viral life cycle. However, little is known about the MVC-host cell interactions. In this study, we identified that two cellular proteins (Hsc70 and Hsp70) interacted with NS1 and VP2 proteins of MVC, and both two domains of Hsc70/Hsp70 were mediated for their interactions. Functional studies revealed that Hsp70 was induced by MVC infection, knockdown of Hsc70 considerably suppressed MVC replication, whereas the replication was dramatically promoted by Hsp70 knockdown. It is interesting that low amounts of overexpressed Hsp70 enhanced viral protein expression and virus production, but high amounts of Hsp70 overexpression weakened them. Upon Hsp70 overexpressing, we observed that the ubiquitination of viral proteins changed with Hsp70 overexpression, and proteasome inhibitor (MG132) restored an accumulation of viral proteins. In addition, we verified that Hsp70 family inhibitors remarkably decreased MVC replication. Overall, we identified Hsc70 and Hsp70 as interactors of MVC NS1 and VP2 proteins and were involved in MVC replication, which may provide novel targets for anti-MVC approach.

2.
iScience ; 27(4): 109615, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38632997

RESUMO

In the smart era, big data analysis based on sensor units is important in intelligent motion. In this study, a dance sports and injury monitoring system (DIMS) based on a recyclable flexible triboelectric nanogenerator (RF-TENG) sensor module, a data processing hardware module, and an upper computer intelligent analysis module are developed to promote intelligent motion. The resultant RF-TENG exhibits an ultra-fast response time of 17 ms, coupled with robust stability demonstrated over 4200 operational cycles, with 6% variation in output voltage. The DIMS enables immersive training by providing visual feedback on sports status and interacting with virtual games. Combined with machine learning (K-nearest neighbor), good classification results are achieved for ground-jumping techniques. In addition, it shows some potential in sports injury prediction (i.e., ankle sprains, knee hyperextension). Overall, the sensing system designed in this study has broad prospects for future applications in intelligent motion and healthcare.

3.
J Virol ; 98(3): e0169523, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38349085

RESUMO

Histone modifications function in both cellular and viral gene expression. However, the roles of acetyltransferases and histone acetylation in parvoviral infection remain poorly understood. In the current study, we found the histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), promoted the replication and transcription of parvovirus minute virus of canines (MVC). Notably, the expression of host acetyltransferases KAT5, GTF3C4, and KAT2A was increased in MVC infection, as well as H4 acetylation (H4K12ac). KAT5 is not only responsible for H4K12ac but also crucial for viral replication and transcription. The viral nonstructural protein NS1 interacted with KAT5 and enhanced its expression. Further study showed that Y44 in KAT5, which may be tyrosine-phosphorylated, is indispensable for NS1-mediated enhancement of KAT5 and efficient MVC replication. The data demonstrated that NS1 interacted with KAT5, which resulted in an enhanced H4K12ac level to promote viral replication and transcription, implying the epigenetic addition of H4K12ac in viral chromatin-like structure by KAT5 is vital for MVC replication.IMPORTANCEParvoviral genomes are chromatinized with host histones. Therefore, histone acetylation and related acetyltransferases are required for the virus to modify histones and open densely packed chromatin structures. This study illustrated that histone acetylation status is important for MVC replication and transcription and revealed a novel mechanism that the viral nonstructural protein NS1 hijacks the host acetyltransferase KAT5 to enhance histone acetylation of H4K12ac, which relies on a potential tyrosine phosphorylation site, Y44 in KAT5. Other parvoviruses share a similar genome organization and coding potential and may adapt a similar strategy for efficient viral replication and transcription.


Assuntos
Lisina Acetiltransferase 5 , Infecções por Parvoviridae , Animais , Cães , Acetilação , Acetiltransferases/metabolismo , Cromatina , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Histonas/genética , Histonas/metabolismo , Infecções por Parvoviridae/metabolismo , Infecções por Parvoviridae/veterinária , Infecções por Parvoviridae/virologia , Tirosina/metabolismo , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Linhagem Celular , Doenças do Cão/metabolismo , Doenças do Cão/virologia , Lisina Acetiltransferase 5/metabolismo
4.
Orphanet J Rare Dis ; 19(1): 75, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365697

RESUMO

BACKGROUND: Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder characterized by impaired glucose and galactose utilization as well as proximal renal tubular dysfunction. METHODS: Clinical, biochemical, genetic, treatment, and follow-up data for 11 pediatric patients with FBS were retrospectively analysed. RESULTS: Hepatomegaly (10/11), short stature (10/11) and hypophosphataemic rickets (7/11) were the most common initial symptoms. At diagnosis, all patients had decreased fasting blood glucose (FBG), plasma bicarbonate (HCO3-) and serum phosphorus, as well as elevated liver transaminases, alkaline phosphatase (AKP) and proximal renal tubular dysfunction. Two infant patients were misdiagnosed with transient neonatal diabetes mellitus. After therapy with uncooked cornstarch and conventional rickets treatment, remission of hepatomegaly was observed in all patients, with significant improvements in pre-prandial blood glucose, liver transaminases, triglyceride, plasma HCO3- and AKP (p < 0.05). At the last follow-up, 5/7 patients with elevated AKP had nephrocalcinosis. The mean height standard deviation score (Ht SDS) of eight patients with regular treatment increased from - 4.1 to -3.5 (p = 0.02). Recombinant human growth hormone (rhGH) was administered to 4/9 patients, but their Ht SDS did not improve significantly (p = 0.13). Fourteen variants of the SLC2A2 gene were identified, with six being novel, among which one was recurrent: c.1217T > G (p.L406R) (allele frequency: 4/22, 18%). Patients with biallelic missense variants showed milder metabolic acidosis than those with null variants. Two of five patients from nonconsanguineous families with rare homozygous variations showed 5.3 Mb and 36.6 Mb of homozygosity surrounding the variants, respectively; a region of homozygosity (ROH) involving the entire chromosome 3 covering the SLC2A2 gene, suggesting uniparental disomy 3, was detected in one patient. CONCLUSIONS: Early diagnosis of FBS is difficult due to the heterogeneity of initial symptoms. Although short stature is a major issue of treatment for FBS, rhGH is not recommended in FBS patients who have normal GH stimulation tests. Patients with biallelic null variants may require alkali supplementation since urine bicarbonate loss is genetically related. ROH is a mechanism for rare homozygous variants of FBS in nonconsanguineous families.


Assuntos
Síndrome de Fanconi , Lactente , Recém-Nascido , Humanos , Criança , Síndrome de Fanconi/tratamento farmacológico , Síndrome de Fanconi/genética , Hepatomegalia , Glicemia , Bicarbonatos , Perfil Genético , Estudos Retrospectivos , China , Transaminases/genética
5.
J Orthop Surg Res ; 18(1): 967, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38098039

RESUMO

BACKGROUND: Eccentric muscle contraction can cause muscle damage, which reduces the efficiency of exercise. Previous evidence suggested that Sodium salicylate (SS) could improve the repair of aged muscle. This study intends to investigate whether SS can impact skeletal muscle damage caused by eccentric exercise. METHODS: Eccentric treadmill exercise was performed to induce muscle damage in mice. Plasma levels of muscle damage markers were estimated. RT-qPCR was employed for detecting mRNA levels of proinflammatory mediators in murine gastrocnemius muscle. Immunofluorescence staining of laminin/DAPI was utilized for quantifying centrally nucleated myofibers in the gastrocnemius muscle. Western blotting was implemented to examine protein levels of mitsugumin 53 (MG53), matrix metalloproteinase (MMP)-2/9, and NF-κB signaling-related markers. RESULTS: SS administration reduced muscle damage marker production in the plasma and decreased the levels of proinflammatory mediators, MG53 and MMP-2/9 in mice after exercise. SS alleviated the severity of muscle damage in the gastrocnemius of mice after eccentric exercise. SS blocked NF-κB signaling pathway in the gastrocnemius muscle. CONCLUSION: SS administration ameliorates skeletal muscle damage caused by eccentric exercise in the mouse model.


Assuntos
NF-kappa B , Salicilato de Sódio , Camundongos , Animais , NF-kappa B/metabolismo , Salicilato de Sódio/farmacologia , Salicilato de Sódio/metabolismo , Transdução de Sinais , Músculo Esquelético/metabolismo , Contração Muscular/fisiologia , Proteínas de Membrana/metabolismo
6.
ACS Omega ; 8(46): 43883-43894, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38027363

RESUMO

Understanding of continuous damage and cracking process of compressed jointed coal is critical to predict its stability. Herein, for jointed coal under uniaxial compression with bedding planes perpendicular (sample A) and parallel (sample B) to the loading direction, an acoustic emission (AE) monitoring device and a computed tomography (CT) scanner were employed to study the damage and cracking process. Furthermore, the correlations between the AE signals and internal fracture parameters were analyzed. Results show that (1) shear and tension cracks are respectively main damage forms in samples A and B; (2) there is a drop valley of variations of AE count fractal dimension (D1) over time before the stress peak, and compared with sample B, the drop valley for sample A are much wider; (3) many fractures between joint planes formed at yielding and postpeak stages, fracture fractal dimensions (D2) first increase slightly with loading and then increase significantly at yielding and postpeak stages; especially D2 of sample A is larger than that of sample B; (4) the accumulative value of D1 (AD1) increases with D2 monotonously, and an expression of porosity or connectivity of the compressed jointed coal was developed, by which the porosity and connectivity of jointed coal could be calculated. The study outcomes could contribute to predict coal stability and the variations of water and gas flowing channels in seam in underground coal mines.

7.
J Clin Lipidol ; 17(6): 808-817, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37858495

RESUMO

BACKGROUND: Lipoprotein lipase (LPL) deficiency, the most common familial chylomicronemia syndrome (FCS), is a rare autosomal recessive disease characterized by chylomicronemia and severe hypertriglyceridemia (HTG), with limited clinical and genetic characterization. OBJECTIVE: To describe the manifestations and management of 19 pediatric patients with LPL-FCS. METHODS: LPL-FCS patients from 2014 to 2022 were divided into low-fat (LF), very-low-fat (VLF) and medium-chain-triglyceride (MCT) groups. Their clinical data were evaluated to investigate the effect of different diets. The genotype-phenotype relationship was assessed. Linear regression comparing long-chain triglyceride (LCT) intake and TG levels was analyzed. RESULTS: Nine novel LPL variants were identified in 19 LPL-FCS pediatric patients. At baseline, eruptive xanthomas occurred in 3/19 patients, acute pancreatitis in 2/19, splenomegaly in 6/19 and hepatomegaly in 3/19. The median triglyceride (TG) level (30.3 mmol/L) was markedly increased. The MCT group and VLF group with LCT intakes <20 en% (energy percentage) had considerably lower TG levels than the LF group (both p<0.05). The LF group presented with severe HTG and significantly decreased TG levels after restricting LCT intakes to <20 en% (p<0.05). Six infants decreased TG levels to <10 mmol/L by keeping LCT intake <10 en%. TG levels and LCT intake were positively correlated in both patients under 2 years (r=0.84) and those aged 2-9 years (r=0.89). No genotype-phenotype relationship was observed. CONCLUSIONS: This study broadens the clinical and genetic spectra of LPL-FCS. The primary therapy for LPL-FCS pediatric patients is restricting dietary LCTs to <10 en% or <20 en% depending on different ages. MCTs potentially provide extra energy.


Assuntos
Hiperlipoproteinemia Tipo I , Hipertrigliceridemia , Pancreatite , Lactente , Humanos , Criança , Hiperlipoproteinemia Tipo I/terapia , Hiperlipoproteinemia Tipo I/tratamento farmacológico , Doença Aguda , Perfil Genético , Pancreatite/genética , Hipertrigliceridemia/genética , Triglicerídeos , China , Lipase Lipoproteica/genética
8.
J Med Genet ; 61(1): 27-35, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-37586839

RESUMO

BACKGROUND: Primary adrenal insufficiency (PAI) is a rare but life-threatening condition. Differential diagnosis of numerous causes of PAI requires a thorough understanding of the condition. METHODS: To describe the genetic composition and presentations of PAI. The following data were collected retrospectively from 111 patients with non-21OHD with defined genetic diagnoses: demographic information, onset age, clinical manifestations, laboratory findings and genetic results. Patients were divided into four groups based on the underlying pathogenesis: (1) impaired steroidogenesis, (2) adrenal hypoplasia, (3) resistance to adrenocorticotropic hormone (ACTH) and (4) adrenal destruction. The age of onset was compared within the groups. RESULTS: Mutations in the following genes were identified: NR0B1 (n=39), STAR (n=33), CYP11B1 (n=12), ABCD1 (n=8), CYP17A1 (n=5), HSD3B2 (n=4), POR (n=4), MRAP (n=2), MC2R (n=1), CYP11A1 (n=1), LIPA (n=1) and SAMD9 (n=1). Frequent clinical manifestations included hyperpigmentation (73.0%), dehydration (49.5%), vomiting (37.8%) and abnormal external genitalia (23.4%). Patients with adrenal hypoplasia typically presented manifestations earlier than those with adrenal destruction but later than those with impaired steroidogenesis (both p<0.01). The elevated ACTH (92.6%) and decreased cortisol (73.5%) were the most common laboratory findings. We generated a differential diagnosis flowchart for PAI using the following clinical features: 17-hydroxyprogesterone, very-long-chain fatty acid, external genitalia, hypertension and skeletal malformation. This flowchart identified 84.8% of patients with PAI before next-generation DNA sequencing. CONCLUSIONS: STAR and NR0B1 were the most frequently mutated genes in patients with non-21OHD PAI. Age of onset and clinical characteristics were dependent on aetiology. Combining clinical features and molecular tests facilitates accurate diagnosis.


Assuntos
Doença de Addison , Insuficiência Adrenal , Humanos , Doença de Addison/genética , Estudos Retrospectivos , Hormônio Adrenocorticotrópico , China , Insuficiência Adrenal/diagnóstico , Insuficiência Adrenal/genética , Peptídeos e Proteínas de Sinalização Intracelular
10.
Orphanet J Rare Dis ; 18(1): 126, 2023 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-37237297

RESUMO

BACKGROUND: X-linked adrenal hypoplasia congenita (AHC) is a rare disorder characterized by primary adrenal insufficiency (PAI) and hypogonadotropic hypogonadism (HH), with limited clinical and genetic characterization. METHODS: The clinical, biochemical, genetic, therapeutic, and follow-up data of 42 patients diagnosed with X-linked AHC were retrospectively analysed. RESULTS: Hyperpigmentation (38/42, 90%), vomiting/diarrhoea (20/42, 48%), failure to thrive (13/42, 31%), and convulsions (7/42, 17%) were the most common symptoms of X-linked AHC at onset. Increased adrenocorticotropic hormone (ACTH) (42/42, 100%) and decreased cortisol (37/42, 88%) were the most common laboratory findings, followed by hyponatremia (32/42, 76%) and hyperkalaemia (29/42, 69%). Thirty-one patients presented with PAI within the first year of life, and 11 presented after three years of age. Three of the thirteen patients over the age of 14 exhibited spontaneous pubertal development, and ten of them experienced delayed puberty due to HH. Six patients receiving human chorionic gonadotropin (hCG) therapy exhibited a slight increase in testicular size and had rising testosterone levels (both P < 0.05). The testicular volumes of the three patients with pulsatile gonadotropin-releasing hormone (GnRH) therapy were larger than those of the six patients undergoing hCG therapy (P < 0.05), and they also exhibited some growth in terms of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. Of the 42 patients, three had an Xp21 deletion, and 39 had an isolated DAX1 defect. Most patients (9/10) with entire DAX1 deletion accounting for 23.8% (10/42) of the total variants had early onset age of less than one year. CONCLUSIONS: This study details the clinical features and genetic spectra of X-linked AHC. Patients with X-linked AHC show a bimodal distribution of the age of onset, with approximately 70% presenting within the first year of life. Pulsatile GnRH may be recommended for HH when hCG therapy is not satisfactory, although it is difficult to achieve normal testicular volume. The combination of clinical features and molecular tests provides information for an accurate diagnosis.


Assuntos
População do Leste Asiático , Hipogonadismo , Criança , Humanos , Masculino , Hormônio Liberador de Gonadotropina/uso terapêutico , Hipoadrenocorticismo Familiar/genética , Hipoadrenocorticismo Familiar/tratamento farmacológico , Hipogonadismo/tratamento farmacológico , Hipogonadismo/genética , Mutação , Estudos Retrospectivos , Testosterona
11.
Pers Soc Psychol Bull ; : 1461672221150238, 2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36727610

RESUMO

Building on earlier research that examined the characteristics people associate with heroes, our research examined similarities and differences of the hero stereotype across cultures. Specifically, in Study 1 (N = 209) and Study 2 (N = 298), we investigated lay perceptions of heroes among participants from a collectivistic culture. In Study 3 (N = 586), we examined whether group membership could be determined by participants' centrality ratings of the combined set of hero features. In Study 4 (N = 197), we tested whether the hero features that distinguish American and Chinese participants, when used to describe a target person, influence the impression that the target person is a hero. In Study 5 (N = 158) and Study 6 (N = 591), we investigated cultural differences in perceptions of different types of heroes (e.g., social, martial, civil) and the influence of individualism and collectivism on the perception of those heroes.

12.
J Med Virol ; 95(1): e28367, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36458544

RESUMO

Lower respiratory tract infection (LRTI) is one of the major reasons for childhood mortality that threaten the health of the public. We aimed to investigate the epidemiological pathogens and their infection analysis among children with LRTI. Sputum specimens were collected for polymerase chain reaction detection and microbiological tests to identify the viral infection and bacterial infection. The serological specimens were separated from venous blood using for Mycoplasma pneumoniae and Chlamydia pneumoniae detection. The virus was confirmed in 86.2% of the children. Human rhinovirus (38.3%), respiratory syncytial virus (32.1%), and parainfluenza virus type 3 (27.2%) were the most frequently identified pathogens. Patients with viral and bacterial coinfection showed younger age (p = 0.032), a higher proportion of wheezing rales (p = 0.032), three depressions sign (p = 0.028), and tachypnea (p = 0.038), and more likely associated with severe pneumonia (p = 0.035). Additionally, older children were more susceptible to viral-atypical bacterial coinfection (p = 0.032). Vomiting (p = 0.011) and fever (p = 0.003) were more likely to occur in children with viral-atypical bacterial coinfection. Attention should be paid to the virus infection of LRTI, as viral-bacterial coinfection and viral-atypical bacterial co-infection may have a detrimental impact on the gravity of LTRI.


Assuntos
Infecções Bacterianas , Coinfecção , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Viroses , Vírus , Humanos , Criança , Lactente , Adolescente , Incidência , Vírus/genética , Viroses/epidemiologia , Bactérias , Infecções Bacterianas/epidemiologia
13.
Foods ; 12(23)2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38231785

RESUMO

American ginseng (Panax quinquefolius L.) is known for its health benefits, which are attributed to various terpenoids. However, the specific composition and activities of these terpenoids in forest-grown wild American ginseng remain understudied. This study aimed to characterize the terpenoid composition, particularly triterpene saponins, in forest-grown wild American ginseng. The analysis revealed that triterpene saponins, notably American ginseng ginsenosides (AGGs), are the predominant active components, as identified through LC-MS/MS and HPLC. A subsequent in vitro evaluation of AGGs showcased their potent antioxidant capabilities, displaying the dose-dependent scavenging of free radicals and reducing agents. Moreover, AGGs demonstrated efficacy in reducing oxidative injury and intracellular ROS levels in RAW 264.7 macrophages treated with H2O2. In addition to their antioxidant properties, AGGs exhibited anti-inflammatory effects, significantly inhibiting NO and inflammatory substance production in lipopolysaccharide-treated RAW 264.7 macrophages. These findings highlight the potential of AGG-rich forest-grown wild American ginseng as a functional food with promising implications for improving human health.

14.
15.
Res Vet Sci ; 151: 149-155, 2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36027684

RESUMO

OBJECTIVE: Mastitis is the most prevalent disease in dairy cows worldwide. Evidence has emerged that oxidative stress plays a crucial role in the development of mastitis. This study aimed to investigate the antioxidative effects of tanshinone IIa (Tan IIa) on LPS-induced oxidative stress in dairy cow mammary epithelial cells (CMECs). METHODS AND RESULTS: We examined the levels of ROS and MDA in LPS-treated CMECs after supplementation with Tan IIa using detection kits and found that Tan IIa significantly inhibited the upregulation of these factors. In addition, we also found that Tan IIa significantly reversed the decrease in mitochondrial membrane potential induced by LPS. Moreover, Tan IIa improved the activities of antioxidant enzymes, which were decreased by LPS. Finally, we examined the probable pathway in which Tan IIa exerted its antioxidant effects using qPCR and western blotting and found that Tan IIa significantly activated the Keap1/Nrf2 signalling pathway. CONCLUSION: These results suggest that Tan IIa might become a possible therapeutic agent for the treatment of dairy cow mastitis by weakening oxidative stress induced by LPS in CMECs.


Assuntos
Abietanos , Doenças dos Bovinos , Mastite Bovina , Animais , Bovinos , Feminino , Abietanos/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Doenças dos Bovinos/tratamento farmacológico , Células Epiteliais/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Mastite Bovina/tratamento farmacológico
16.
Nat Commun ; 13(1): 1003, 2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35194047

RESUMO

Time-restricted feeding (TRF) improves metabolic health. Both early TRF (eTRF, food intake restricted to the early part of the day) and mid-day TRF (mTRF, food intake restricted to the middle of the day) have been shown to have metabolic benefits. However, the two regimens have yet to be thoroughly compared. We conducted a five-week randomized trial to compare the effects of the two TRF regimens in healthy individuals without obesity (ChiCTR2000029797). The trial has completed. Ninety participants were randomized to eTRF (n=30), mTRF (n=30), or control groups (n=30) using a computer-based random-number generator. Eighty-two participants completed the entire five-week trial and were analyzed (28 in eTRF, 26 in mTRF, 28 in control groups). The primary outcome was the change in insulin resistance. Researchers who assessed the outcomes were blinded to group assignment, but participants and care givers were not. Here we show that eTRF was more effective than mTRF at improving insulin sensitivity. Furthermore, eTRF, but not mTRF, improved fasting glucose, reduced total body mass and adiposity, ameliorated inflammation, and increased gut microbial diversity. No serious adverse events were reported during the trial. In conclusion, eTRF showed greater benefits for insulin resistance and related metabolic parameters compared with mTRF. Clinical Trial Registration URL: http://www.chictr.org.cn/showproj.aspx?proj=49406 .


Assuntos
Resistência à Insulina , Jejum/metabolismo , Glucose , Voluntários Saudáveis , Humanos , Obesidade
17.
ACS Nano ; 16(3): 3808-3820, 2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35199998

RESUMO

Inducing autophagy of macrophages to improve abnormal lipid metabolism is an important way to treat atherosclerosis (AS). Yet, the current application of the mammalian target of rapamycin (mTOR)-dependent autophagy inducers is limited by the side effects and lack of targeting and low biological availability. Herein, a kind of nitric oxide (NO)-driven carrier-free nanomotor based on the reaction between trehalose (Tr, one of the mTOR-independent autophagy inducers), L-arginine (Arg), and phosphatidylserine (PS) is reported. The developed nanomotors use NO as the driving force, which is generated from the reaction between Arg and excessive reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS) specifically presenting in the AS microenvironment. The high expression of ROS and iNOS in the AS site can be used as chemoattractants to induce chemotaxis behavior of the nanomotors to achieve the first-step targeting an AS plaque. Subsequently, the "eat me" signal sent by PS is exploited to precisely target to the macrophages in the AS plaque, realizing the plaque-macrophage-targeted effect by this step-by-step strategy. In vitro and in vivo results confirm that the introduction of the concept of carrier-free nanomotors has greatly improved the biological availability of trehalose (the dose can be reduced from 2.5 g kg-1 in previous reports to 0.01 g kg-1 in this work). Particularly, consumed ROS and the production of NO during the targeting process also play positive roles, in which the former regulates the M2 polarization of macrophages and the latter promotes the reconstruction of an endothelial barrier, which contributes to the multilink treatment of AS.


Assuntos
Aterosclerose , Placa Aterosclerótica , Arginina/farmacologia , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Autofagia , Humanos , Macrófagos/metabolismo , Óxido Nítrico/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/farmacologia , Trealose/farmacologia
18.
Virol J ; 18(1): 212, 2021 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-34715898

RESUMO

BACKGROUND: Pneumonia has a high incidence rate and is a major cause of mortality in children, mostly community-acquired pneumonia (CAP). Human bocavirus (HBoV), since it first identified in 2005, has been repeatedly associated with respiratory tract infections. Nevertheless, the role and related information of HBoV as a pathogen of CAP has not been fulfilled. Here our study is to assess the epidemiological and clinical features in HBoV-positive children with CAP. METHODS: A total of 878 secretions of lower respiratory samples were obtained, multiplex PCR was used to detect HBoV and other respiratory viruses. RESULTS: Of all cases, HBoV was detected in 10.0%, with a peak incidence of infection among children < 2 year old, and predominantly noted in autumn and winter. Only 8 patients were HBoV single infection. Co-infection with other respiratory viruses was observed in 86.4%. Moreover, co-infection with bacteria occurred in 27.3% and with Mycoplasma pneumoniae (MP) in 33.0% of HBoV-positive patients. Among all HBoV-positive samples co-infected with bacteria, 87.5% are gram negative bacteria. Compared with HBoV-negative group, age (P = 0.048), wheezing (P = 0.015), tachypnea (P = 0.016), lactate dehydrogenase (P = 0.026) and severe pneumonia (P = 0.023) were statistically significant in HBoV-positive patients. Furthermore, HBoV-positive patients less than 1 year old were more likely to have co-infection with bacteria (P = 0.007). CONCLUSIONS: HBoV can be detected alone in respiratory samples of children with CAP, maybe it is one of the causes of CAP in infants. The high incidence of severe pneumonia was found in HBoV-positive patients compared with HBoV-negative cases may indicate a relationship between severe pneumonia and HBoV.


Assuntos
Bocavirus , Bocavirus Humano , Infecções por Parvoviridae , Pneumonia , Infecções Respiratórias , Bocavirus/genética , Criança , Pré-Escolar , China/epidemiologia , Humanos , Lactente , Infecções por Parvoviridae/diagnóstico , Infecções por Parvoviridae/epidemiologia , Pneumonia/epidemiologia
19.
Rev. psicol. deport ; 30(2): 132-144, Ago 9, 2021. tab, graf, ilus
Artigo em Inglês | IBECS | ID: ibc-213814

RESUMO

There is substantial evidence linked with the positive outcomes of sports-based activities on the health and well-being of individual which natural tends to deteriorate once they reach a certain age. From a positive aging view, the promotion of sports participation for improving the health, physical and mental, and wellbeing outcomes have been used as a key strategy. The present study considers this strategy and formulates a framework to evaluate the impacts imposed by sports participation on the general happiness and wellbeing of the older population. To better understand the role of sports participation among older adults, the role of social capital on the relationship between sport participation and happiness among the older population and the relationship between sport participation and well-being has also been considered. For this purpose, a convenience-based sample of 310 sports-participating older population is studied in China. The results show that sports participation predicts both well-being and general happiness in older individuals. Moreover, two of the sub-dimensions of the social capital, neighborhood connections, and feelings of trust and safety, are found to significantly mediate the associations. The study is novel from the standpoint that the context of the study is set in China and it produces new empirical findings as well. The main limitation of the study is that a convenience sample has been used and the scope is restricted to China. The study lends a number of important contributions to sports psychology and epidemiological perspectives.(AU)


Assuntos
Humanos , Masculino , Feminino , Esportes , Planejamento em Saúde , Felicidade , Idoso , Confiança , Psicologia do Esporte , Medicina Esportiva , China
20.
Front Nutr ; 7: 596285, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33425971

RESUMO

Background: Time-restricted feeding, also known as intermittent fasting, can confer various beneficial effects, especially protecting against obesity, and related metabolic disorders, but little is known about the underlying mechanisms. Therefore, the present study aims to investigate the effects of time-restricted feeding on the circadian rhythm of gut microbiota and hepatic metabolism. Methods: Eight-week-old male Kunming mice received either a normal diet ad libitum, a high-fat diet ad libitum, or a high-fat diet restricted to an 8-h temporal window per day for an experimental period of 8 weeks. Weight gain and calorie intake were measured weekly. Serum metabolites, hepatic sections and lipid metabolites, gut microbiota, and the hepatic expression of Per1, Cry1, Bmal1, SIRT1, SREBP, and PPARα were measured at the end of the experimental period. The composition of gut microbiota and the expression of hepatic genes were compared between four timepoints. Results: Mice that received a time-restricted high-fat diet had less weight gain, milder liver steatosis, and lower hepatic levels of triglycerides than mice that received a high-fat diet ad libitum (p < 0.05). The numbers of Bacteroidetes and Firmicutes differed between mice that received a time-restricted high-fat diet and mice that received a high-fat diet ad libitum (p < 0.05). Mice fed a time-restricted high-fat diet showed distinct circadian rhythms of hepatic expression of SIRT1, SREBP, and PPARα compared with mice fed a normal diet ad libitum, as well as the circadian rhythm of the abundance of Bacteroidetes and Firmicutes. Conclusions: Time-restricted feeding is associated with better metabolic conditions, perhaps owing to alterations in gut microbiota and the circadian pattern of molecules related to hepatic lipid metabolism, which were first to report.

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