Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.777
Filtrar
1.
Medicine (Baltimore) ; 101(2): e28491, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35029199

RESUMO

ABSTRACT: There is a scarcity of research into the impact of medication beliefs on adherence in patients with non-dialysis chronic kidney disease (CKD). This study is to determine the psychometric properties of the Chinese version of the Beliefs about Medicines Questionnaire (BMQ)-Specific among patients with non-dialysis CKD stages 3-5, and to assess the beliefs of CKD patients and their association with medication adherence.A cross-sectional study was conducted in CKD patients who recruited at the nephrology clinics of Xi'an Central Hospital, Xi'an, Shaanxi, China. The original BMQ-Specific was translated into Chinese. The internal consistency and test-retest reliability of the Chinese version of the BMQ-Specific scale were assessed, while exploratory and confirmatory factor analyses were also applied to determine its reliability and validity. The Kruskal-Wallis test and multiple ordered logistic regression were performed to identify the relationship between beliefs about and adherence to medication among CKD patients.This study recruited 248 patients. Cronbach's α values of the BMQ-Specific necessity and concern subscales were 0.826 and 0.820, respectively, with intraclass correlation coefficients of 0.784 and 0.732. Factor analysis showed that BMQ-Specific provided a good fit to the two-factor model. The adherence of patients was positively correlated with perceived necessity (r = 0.264, P < .001) and negatively correlated with concern (r = -0.294, P < .001). Medication adherence was significantly higher for the accepting group (high necessity and low concern scores) than for the ambivalent group (high necessity and concern scores; ß = -0.880, 95% confidence interval [CI] = -1.475 to -0.285), skeptical group (low necessity and high concern scores; ß = -2.620, 95% CI = -4.209 to -1.031) and indifferent group (low necessity and concern scores; ß = -0.918, 95% CI = -1.724 to -0.112).The Chinese version of BMQ-Specific exhibited satisfactory reliability and validity for use in patients with non-dialysis CKD stages 3-5 and has been demonstrated to be a reliable screening tool for clinicians to use to predict and identify the non-adherence behaviors of patients.

2.
Sensors (Basel) ; 22(1)2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-35009939

RESUMO

Circularly polarized photocurrent, observed in p-doped bulk GaAs, varies nonlinearly with the applied bias voltage at room temperature. It has been explored that this phenomenon arises from the current-induced spin polarization in GaAs. In addition, we found that the current-induced spin polarization direction of p-doped bulk GaAs grown in the (001) direction lies in the sample plane and is perpendicular to the applied electric field, which is the same as that in GaAs quantum well. This research indicates that circularly polarized photocurrent is a new optical approach to investigate the current-induced spin polarization at room temperature.

3.
Mol Biomed ; 3(1): 1, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34984525

RESUMO

MicroRNA-22 (miR-22) was suggested to be important for type 2 diabetes but its functions for this disease remained unclear. Recombinant adeno-associated virus (rAAV)-mediated miR delivery is a powerful approach to study miR functions in vivo, however, the overexpression of miR-22 by rAAV remains challenging because it is one of the most abundant miRs in the liver. In this study, a series of expression cassettes were designed and compared. It was shown that different lengths of primary miR-22 were overexpressed in HEK293 and HeLa cells but the longer ones were more efficiently expressed. miR-22 may be placed in either introns or the 3' UTR of a transgene for efficient overexpression. RNA polymerase III or II promoters were successfully utilized for miR expression but the latter showed higher expression levels in cell lines. Specifically, miR-22 was expressed efficiently together with an EGFP gene. After screening, a liver-specific TTR promoter was chosen to overexpress miR-22 in diabetic mice fed a high-fat diet. It was shown that miR-22 was overexpressed 2-3 folds which improved the insulin sensitivity significantly. The approach utilized in this study to optimize miR overexpression is a powerful tool for the creation of efficient rAAV vectors for the other miRs.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34976307

RESUMO

Most marine mollusks have a pelagic larval phase, and they need to undergo metamorphosis to develop into adults. Metamorphosis is affected by many factors, including abiotic factors such as temperature, salinity and illumination as well as biological factors such as food and microorganisms. In our previous study, we found that the metamorphosis of Rapana venosa requires induction by juvenile oysters, which are the food source of R. venosa. However, the regulatory mechanism of this induction is largely unknown. In the present study, we evaluated the impacts of induction by juvenile oysters on competent larvae of R. venosa. Competent larvae were experimentally divided into two pools, and scallop shells without juvenile oysters and scallop shells with juvenile oysters were added for 2 h and 12 h to monitor alterations in critical gene expression, symbiotic microbiota and metabolomic responses. The carboxypeptidase gene was increased while the cellulase gene was decreased, which may mean that the food habit transition was induced by juvenile oysters. Meanwhile, critical genes in the neuroendocrine system were also significantly altered in juvenile oysters. Furthermore, dramatic changes in the symbiotic microbiota and metabolism profiles were observed, with many of them associated with the digestive system and neuroendocrine system. In conclusion, juveniles as food resources may induce metamorphosis in R. venosa by regulating the neuroendocrine system and promoting the development of the digestive system and changes in digestive enzymes. This study may provide evidence that induction by juvenile oysters can promote food habit transition and metamorphosis in R. venosa by regulating the metabolome and microbiome and further altering the digestive and neuroendocrine systems of R. venosa, which expands our understanding of the regulatory mechanism of metamorphosis in R. venosa. However, further studies are needed to explore the specific substance inducing metamorphosis released by juvenile oysters.

5.
Anal Bioanal Chem ; 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34982177

RESUMO

A simple and rapid method for screening of tyrosinase (TYR) inhibitors present in traditional Chinese medicines (TCMs) was developed by combining ligand fishing and the fluorescent enzymatic assay based on dopamine-functionalized carbon quantum dots (CQDs-Dopa). Ligands of the enzyme present in the TCM extractions were firstly adsorbed on the enzyme-modified magnetic beads, and then the beads were magnetically separated and subjected directly to the CQDs-Dopa-based fluorescent assay. Finally, compounds were desorbed from the "active" beads and identified with ultra-performance liquid chromatography-triple quadrupole mass spectrometry. A known natural TYR inhibitor quercetin was selected to assess the feasibility and quantification performance of this method, and good linearity in the range of 0.01-0.16 mM (R2 = 0.992) with a low detection limit of 0.004 mM was obtained. This method was then applied to screen TYR inhibitors present in Scutellaria baicalensis and Sophora flavescens. Six TYR inhibitors including baicalin (1), baicalein (2), wogonin (3), oroxylin A (4), kurarinone (5), and sophoraflavanone G (6) were found, among which 1-4 were firstly discovered in this work. This is the first report on the in situ assessment of the target compounds obtained by ligand fishing in the form of a mixture, which exhibited the combined advantages of specific extraction ability of ligand fishing and the high sensitivity of CQDs-based fluorescent assay, showing great potential for fast screening of enzyme inhibitors from TCMs.

6.
Carbohydr Polym ; 281: 119034, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35074114

RESUMO

To achieve long-term patent small-diameter (<6 mm) vascular implants, biomimetic vascular grafts have gained much attention in promoting in situ blood vessel regeneration. In this study, hierarchical-structured bacterial cellulose/potato starch (BC/PS) composites were biosynthesized by the addition of swollen PS. Investigations on the physicochemical properties of BC/PS composites showed that the properties could be improved and tailored by the addition of swollen PS. The composites displayed a morphology, water content, thermal properties, mechanical properties, and biocompatibility appropriate for vascular tissue engineering. Most importantly, the BC/PS grafts, with a dense inner surface and a circumferential macroporous outer layer, possessed 75% patency and promoted rapid blood vessel regeneration in in vivo assessment on rabbits, with complete endothelium monolayer, organized smooth muscle cells, rich new capillaries, and deposited extracellular matrix. Collectively, these findings demonstrate that hierarchical-structured BC/PS tubes hold great promise as artificial small-diameter vascular grafts.

7.
Dev Comp Immunol ; 129: 104348, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35026231

RESUMO

Matrix metalloproteinases (MMPs) are highly expressed in leukocytes and macrophages, which play a role in the innate immune response. Here, the cDNA sequence of MMP25 from Japanese sea bass (Lateolabrax japonicus) (LjMMP25) was identified. Phylogenetic analysis revealed that LjMMP25 was most closely related to large yellow croaker MMP25. Multiple sequence alignment of LjMMP25 with MMP25 sequences from other teleosts revealed that regions of known functional importance were highly conserved. Expression analysis revealed that LjMMP25 was highly expressed in the head kidney and widely expressed in other tissues including gill, spleen, and liver. LjMMP25 was found to regulate inflammatory cytokine production and promote phagocytosis and bacterial killing in monocytes/macrophages (MO/MФ). Furthermore, LjMMP25 regulated the inflammatory response by modulating NF-κB signaling. These findings reveal new information about the role of LjMMP25 in regulating pro-inflammatory responses in this species.

8.
Artigo em Inglês | MEDLINE | ID: mdl-35015652

RESUMO

In order to solve the time-varying quadratic programming (TVQP) problem more effectively, a new self-adaptive zeroing neural network (ZNN) is designed and analyzed in this article by using the Takagi-Sugeno fuzzy logic system (TSFLS) and thus called the Takagi-Sugeno (T-S) fuzzy ZNN (TSFZNN). Specifically, a multiple-input-single-output TSFLS is designed to generate a self-adaptive convergence factor to construct the TSFZNN model. In order to obtain finite- or predefined-time convergence, four novel activation functions (AFs) [namely, power-bi-sign AF (PBSAF), tanh-bi-sign AF (TBSAF), exp-bi-sign AF (EBSAF), and sinh-bi-sign AF (SBSAF)] are developed and applied in the TSFZNN model for solving the TVQP problem. Both theoretical proofs and experimental simulations show that the TSFZNN model using PBSAF or TBSAF has the property of converging in a finite time, and the TSFZNN model using EBSAF or SBSAF has the property of converging in a predefined time, which have superior convergence performance compared to the traditional ZNN model.

9.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(1): 43-48, 2022 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-35048598

RESUMO

The study is aimed to help promote the development of the oral healthcare system and dental public health system in China and to help achieve the goal of improving the nation's oral health. We herein provided an overview and critical evaluation of recent developments in oral healthcare systems and dental public health systems in China and other countries, and discussed a number of potential directions for the future development of dental public health. The current global public health emergency of the coronavirus disease 2019 (COVID-19) pandemic was also taken into account in our discussions. Thus, to facilitate the accomplishment of the goals of the Healthy China 2030 Program, we suggested the establishment of a community-based, prevention-oriented model for the oral healthcare system and dental public health system. The model we proposed features the integration of oral and general health services, the utilization of technological innovations and big data concerning health, and a forceful promotion of remote dental services focused on prevention and early diagnosis and treatment. Furthermore, under the background of COVID-19 becoming a normal part of people's lives, we should adopt differentiated prevention and protection measures and emergency response preplans appropriate for the actual epidemic situation of a particular region so that clinical services are strengthened while unnecessary wastes of resources are avoided. We should actively explore for alternative approaches to care in the face of special circumstances.


Assuntos
COVID-19 , Saúde Pública , China/epidemiologia , Atenção à Saúde , Humanos , SARS-CoV-2
10.
Mol Immunol ; 143: 27-40, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35016116

RESUMO

CXC chemokine receptor 4 (CXCR4), a member of the G-protein-coupled receptor family, plays an important role in host immune responses. Within the teleost lineage, there are two paralogs of CXCR4; however, the role of CXCR4 in teleost B cells is poorly understood. In this study, we determined the cDNA sequences of the two CXCR4 paralogs from the Japanese sea bass (Lateolabrax japonica; LjCXCR4a and LjCXCR4b). Sequence and phylogenetic tree analyses revealed that LjCXCR4a and LjCXCR4b are most closely related to CXCR4a and CXCR4b, respectively, in the large yellow croaker (Larimichthys crocea). CXCR4 transcripts were mainly expressed in the gills, and their expression in different tissues was altered upon infection with Vibrio harveyi. LjCXCR4a and LjCXCR4b protein levels were upregulated in infected B cells. Knockdown of LjCXCR4a and LjCXCR4b in B cells by RNA interference, the phagocytic activity of B cells was not affected. Furthermore, knockdown of LjCXCR4a, not of LjCXCR4b, was observed to inhibit LjIgM expression in lipopolysaccharide-stimulated B cells. In addition, knockdown of LjCXCR4a, not of LjCXCR4b, was found to reduce reactive oxygen species levels in B cells. Our results indicate that LjCXCR4a and LjCXCR4b modulate the immune response of Japanese sea bass B cells against bacterial infection, albeit via different pathways.

11.
Exp Neurol ; 347: 113918, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34748756

RESUMO

In temporal lobe epilepsy (TLE), abnormal axon guidance and synapse formation lead to sprouting of mossy fibers in the hippocampus, which is one of the most consistent pathological findings in patients and animal models with TLE. Glypican 4 (Gpc4) belongs to the heparan sulfate proteoglycan family, which play an important role in axon guidance and excitatory synapse formation. However, the role of Gpc4 in the development of mossy fibers sprouting (MFS) and its underlying mechanism remain unknown. Using a pilocarpine-induced mice model of epilepsy, we showed that Gpc4 expression was significantly increased in the stratum granulosum of the dentate gyrus at 1 week after status epilepticus (SE). Using Gpc4 overexpression or Gpc4 shRNA lentivirus to regulate the Gpc4 level in the dentate gyrus, increased or decreased levels of netrin-1, SynI, PSD-95, and Timm score were observed in the dentate gyrus, indicating a crucial role of Gpc4 in modulating the development of functional MFS. The observed effects of Gpc4 on MFS were significantly antagonized when mice were treated with L-leucine or rapamycin, an agonist or antagonist of the mammalian target of rapamycin (mTOR) signal, respectively, demonstrating that mTOR pathway is an essential requirement for Gpc4-regulated MFS. Additionally, the attenuated spontaneous recurrent seizures (SRSs) were observed during chronic stage of the disease by suppressing the Gpc4 expression after SE. Altogether, our findings demonstrate a novel control of neuronal Gpc4 on the development of MFS through the mTOR pathway after pilocarpine-induced SE. Our results also strongly suggest that Gpc4 may serve as a promising target for antiepileptic studies.


Assuntos
Glipicanas/biossíntese , Fibras Musgosas Hipocampais/metabolismo , Pilocarpina/toxicidade , Transdução de Sinais/fisiologia , Estado Epiléptico/metabolismo , Serina-Treonina Quinases TOR/biossíntese , Animais , Células Cultivadas , Glipicanas/antagonistas & inibidores , Masculino , Camundongos , Fibras Musgosas Hipocampais/efeitos dos fármacos , Agonistas Muscarínicos/toxicidade , Transdução de Sinais/efeitos dos fármacos , Estado Epiléptico/induzido quimicamente , Serina-Treonina Quinases TOR/antagonistas & inibidores
12.
J Cell Biol ; 221(1)2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34813648

RESUMO

Primary cilia transduce diverse signals in embryonic development and adult tissues. Defective ciliogenesis results in a series of human disorders collectively known as ciliopathies. The CP110-CEP97 complex removal from the mother centriole is an early critical step for ciliogenesis, but the underlying mechanism for this step remains largely obscure. Here, we reveal that the linear ubiquitin chain assembly complex (LUBAC) plays an essential role in ciliogenesis by targeting the CP110-CEP97 complex. LUBAC specifically generates linear ubiquitin chains on CP110, which is required for CP110 removal from the mother centriole in ciliogenesis. We further identify that a pre-mRNA splicing factor, PRPF8, at the distal end of the mother centriole acts as the receptor of the linear ubiquitin chains to facilitate CP110 removal at the initial stage of ciliogenesis. Thus, our study reveals a direct mechanism of regulating CP110 removal in ciliogenesis and implicates the E3 ligase LUBAC as a potential therapy target of cilia-associated diseases, including ciliopathies and cancers.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Centríolos/metabolismo , Cílios/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Organogênese , Fosfoproteínas/metabolismo , Ubiquitina/metabolismo , Animais , Linhagem Celular , Humanos , Camundongos , Complexos Multiproteicos , Proteínas de Ligação a RNA/metabolismo , Especificidade por Substrato , Ubiquitinação , Peixe-Zebra
13.
J Pharmacol Sci ; 148(1): 56-64, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34924130

RESUMO

Acute kidney injury (AKI) is a serious complication in critically ill patients. Accumulating evidences indicated that macrophages play an important pro-inflammatory role in AKI and isoliquiritigenin (ISL) can inhibit macrophagic inflammation, but its role in AKI and the underlying mechanism are unknown. The present study aims to investigate the renoprotective effect of ISL on AKI and the role of Formyl peptide receptors 2 (FPR2) in this process. In this study, cisplatin-induced AKI model and lipopolysaccharide-induced macrophage inflammatory model were employed to perform the in vivo and in vitro experiments. The results showed that ISL strongly relieved kidney injury and inhibited renal inflammation in vivo and suppress macrophagic inflammatory response in vitro. Importantly, it was found that FPR2 was significantly upregulated compared to the control group in AKI and LPS-induced macrophage, whereas it was strongly suppressed by ISL. Interestingly, overexpression of FPR2 with transfection of pcDNA3.1-FPR2 effectively reversed the anti-inflammatory effect of ISL in macrophage, suggesting that FPR2 may be the potential target for ISL to prevent inflammation and improve kidney injury of AKI. Take together, these findings indicated that ISL improved cisplantin-induced kidney injury by inhibiting FPR2 involved macrophagic inflammation, which may provide a potential therapeutic option for AKI.

14.
Mol Plant Pathol ; 23(1): 133-147, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34636149

RESUMO

Endocytosis plays key roles during infection of plant-pathogenic fungi, but its regulatory mechanisms are still largely unknown. Here, we identified a putative endocytosis-related gene, PAL1, which was highly expressed in appressorium of Magnaporthe oryzae, and was found to be important for appressorium formation and maturation. Deletion of PAL1 significantly reduced the virulence of M. oryzae due to defects in appressorial penetration and invasive growth in host cells. The Pal1 protein interacted and colocalized with the endocytosis protein Sla1, suggesting it is involved in endocytosis. The Δpal1 mutant was significantly reduced in appressorium formation, which was recovered by adding exogenous cAMP and 3-isobutyl-1-methylxanthine (IBMX). Moreover, the phosphorylation level of Pmk1 in Δpal1 was also reduced, suggesting Pal1 functions upstream of both the cAMP and Pmk1 signalling pathways. As a consequence, the utilization of glycogen and lipid, appressorial autophagy, actin ring formation, localization of septin proteins, as well as turgor accumulation were all affected in the Δpal1 mutant. Taken together, Pal1 regulates cAMP and the Pmk1 signalling pathway for appressorium formation and maturation to facilitate infection of M. oryzae.

15.
Mol Med Rep ; 25(2)2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34935053

RESUMO

Targeting excessive osteoclast differentiation and activity is considered a valid therapeutic approach for osteoporosis. Zoledronic acid (ZOL) plays a pivotal role in regulating bone mineral density. However, the exact molecular mechanisms responsible for the inhibitory effects of ZOL on receptor activator of nuclear factor (NF)­κB ligand (RANKL)­induced osteoclast formation are not entirely clear. The present study aimed to investigate the role of ZOL in osteoclast differentiation and function, and to determine whether NF­κB and mitogen­activated protein kinase, and their downstream signalling pathways, are involved in this process. RAW264.7 cells were cultured with RANKL for differentiation into osteoclasts, in either the presence or absence of ZOL. Osteoclast formation was observed by tartrate­resistant acid phosphatase staining and bone resorption pit assays using dentine slices. The expression of osteoclast­specific molecules was analysed using reverse transcription­quantitative polymerase chain reaction and western blotting assays to deduce the molecular mechanisms underlying the role of ZOL in osteoclastogenesis. The results showed that ZOL significantly attenuated osteoclastogenesis and bone resorptive capacity in vitro. ZOL also suppressed the activation of NF­κB and the phosphorylation of c­Jun N­terminal kinase. Furthermore, it inhibited the expression of the downstream factors c­Jun, c­Fos and nuclear factor of activated T cells c1, thereby decreasing the expression of dendritic cell­specific transmembrane protein and other osteoclast­specific markers. In conclusion, ZOL may have therapeutic potential for osteoporosis.

16.
Spectrochim Acta A Mol Biomol Spectrosc ; 264: 120230, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34358784

RESUMO

Luminescent metal-organic frameworks (LMOFs) and their functional materials with unique characteristics can provide the basis for the construction of new analytical techniques, which can meet the continuous demand for various fields. In this work, guanosine monophosphate (GMP), terbium ion (Tb3+) and zeolitic imidazolate framework-8 (ZIF-8) are self-assembled to form a ZIF-8@GMP-Tb nanocomplex, which can be utilized as a ratiometric fluorescent probe to monitor alkaline phosphatase (ALP) activity. Specifically, with adding ALP, the fluorescence intensity at 547 nm (one of the characteristic emission peaks of Tb3+) obviously decreased. Meanwhile, the conjugated structure of GMP increased the fluorescence of ZIF-8 (located at 330 nm). The possible mechanism was proposed through the characterization of the materials. Based on the variation of the emission peaks at 330 and 547 nm, the ratiometric fluorescent sensor of ALP has a linear range of 0.25-20 U/L. Moreover, applying this sensing system to the detection of ALP in the human serum sample and ALP inhibitor investigation possesses satisfactory results. This work provides a new perspective for the utilization of ZIF-8 and lanthanide ions in manufacturing simple and sensitive sensors.


Assuntos
Guanosina Monofosfato , Zeolitas , Fosfatase Alcalina , Corantes Fluorescentes , Humanos , Térbio
17.
Neural Regen Res ; 17(6): 1318-1323, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34782577

RESUMO

Oscillating field stimulation (OFS) is a potential method for treating spinal cord injury. Although it has been used in spinal cord injury (SCI) therapy in basic and clinical studies, its underlying mechanism and the correlation between its duration and nerve injury repair remain poorly understood. In this study, we established rat models of spinal cord contusion at T10 and then administered 12 weeks of OFS. The results revealed that effectively promotes the recovery of motor function required continuous OFS for more than 6 weeks. The underlying mechanism may be related to the effects of OFS on promoting axon regeneration, inhibiting astrocyte proliferation, and improving the linear arrangement of astrocytes. This study was approved by the Animal Experiments and Experimental Animal Welfare Committee of Capital Medical University (supplemental approval No. AEEI-2021-204) on July 26, 2021.

18.
Glia ; 70(1): 106-122, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34498776

RESUMO

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized primarily by impaired social communication and rigid, repetitive, and stereotyped behaviors. Many studies implicate abnormal synapse development and the resultant abnormalities in synaptic excitatory-inhibitory (E/I) balance may underlie many features of the disease, suggesting aberrant neuronal connections and networks are prone to occur in the developing autistic brain. Astrocytes are crucial for synaptic formation and function, and defects in astrocytic activation and function during a critical developmental period may also contribute to the pathogenesis of ASD. Here, we report that increasing hippocampal astrogenesis during development induces autistic-like behavior in mice and a concurrent decreased E/I ratio in the hippocampus that results from enhanced GABAergic transmission in CA1 pyramidal neurons. Suppressing the aberrantly elevated GABAergic synaptic transmission in hippocampal CA1 area rescues autistic-like behavior and restores the E/I balance. Thus, we provide direct evidence for a developmental role of astrocytes in driving the behavioral phenotypes of ASD, and our results support that targeting the altered GABAergic neurotransmission may represent a promising therapeutic strategy for ASD.

19.
Chemosphere ; 288(Pt 1): 132437, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34627817

RESUMO

Cadmium (Cd), a widespread, severely toxic heavy metal, can cause serious reproductive toxicity in animals. However, the molecular pathways associated with Cd-induced effects remain unknown. In this study, we first cloned the vasa gene (Shvasa) and characterized the VASA protein (ShVASA) in Sinopotamon henanense. We then investigated the molecular mechanisms of Cd-induced reproductive toxicity. Shvasa was specifically expressed in the ovary and testis. ShVASA was abundant in early ovarian development and significantly less abundant in mature ovaries. During oogenesis, ShVASA was abundant and evenly distributed in the cytoplasm of the oogonium and previtellogenic oocytes, but gradually accumulated in the nuclear periphery of vitellogenic and mature oocytes. As Cd concentration increased, ShVASA abundance decreased gradually in proliferation-stage ovaries, and increased gradually in mature ovaries. Notably, at the small and large growth stages, ShVASA was upregulated following exposure to 14.5 mg/L Cd and downregulated following exposure to 29 mg/L Cd. In contrast to the unexposed control, ShVASA accumulated around the nuclear periphery in Cd-exposed previtellogenic oocytes and scattered gradually into the cytoplasm in Cd-exposed vitellogenic and mature oocytes. Shvasa RNA interference (RNAi) downregulated Shnanos and Shpiwi, but simultaneous Cd exposure and Shvasa RNAi significantly upregulated Shnanos and downregulated Shpiwi. These data suggested that Cd disrupted Shvasa expression and function, as well as the functions of Shnanos and Shpiwi, leading to severe reproductive toxicity in S. henanense.


Assuntos
Braquiúros , Animais , Cádmio/toxicidade , Clonagem Molecular , Feminino , Água Doce , Masculino , Reprodução
20.
Front Pharmacol ; 12: 793374, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34880768

RESUMO

The cholinergic anti-inflammatory pathway (CAIP) has been proposed to regulate gastrointestinal inflammation via acetylcholine released from the vagus nerve activating α7 nicotinic receptor (α7nAChR) on macrophages. Parkinson's disease (PD) patients and PD rats with substantia nigra (SN) lesions exhibit gastroparesis and a decayed vagal pathway. To investigate whether activating α7nAChR could ameliorate inflammation and gastric dysmotility in PD rats, ELISA, western blot analysis, and real-time PCR were used to detect gastric inflammation. In vitro and in vivo gastric motility was investigated. Proinflammatory mediator levels and macrophage numbers were increased in the gastric muscularis of PD rats. α7nAChR was located on the gastric muscular macrophages of PD rats. The α7nAChR agonists PNU-282987 and GTS-21 decreased nuclear factor κB (NF-κB) activation and monocyte chemotactic protein-1 mRNA expression in the ex vivo gastric muscularis of PD rats, and these effects were abolished by an α7nAChR antagonist. After treatment with PNU-282987 in vivo, the PD rats showed decreased NF-κB activation, inflammatory mediator production, and contractile protein expression and improved gastric motility. The present study reveals that α7nAChR is involved in the development of gastroparesis in PD rats and provides novel insight for the treatment of gastric dysmotility in PD patients.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...