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1.
Chemosphere ; 287(Pt 1): 132044, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34474391

RESUMO

Bisphenol A (BPA) is a known endocrine disruptor and has been gradually replaced in industrial applications by other bisphenols, such as bisphenol S (BPS). However, whether these analogues are any safer for the central nervous system remains elusive. Here, we investigated behavioral impairments in mice after BPA and BPS exposure from postnatal days 21-49 (P21~P49). Results showed that BPA (0.1 and 1 mg/kg/d) and BPS (1 mg/kg/d) impaired emotion and social interaction of mice, while low dose exposure (0.1 mg/kg/d) induced no observable changes on emotion in mice. The behavioral deficits were accompanied by hyperactivation of the basolateral amygdala (BLA), i.e., dose-dependent increase in neuronal firing rates and local field potential power. In addition, glutamate receptors were up-regulated in the BLA, showing the same activation trend after exposure to different doses of BPA and BPS. Taken together, these findings imply that BPA and BPS cause behavioral impairments in juvenile mice by disrupting local neuronal activation in the BLA. Although BPS exerted less adverse effects on mice than BPA at the low dose, it does not appear to be a safe alternative to BPA in regard to brain function after prolonged high-volume exposure.


Assuntos
Complexo Nuclear Basolateral da Amígdala , Disruptores Endócrinos , Animais , Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Camundongos , Neurônios , Fenóis
2.
Inquiry ; 58: 469580211055630, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34818922

RESUMO

The current situation of Coronavirus Disease 2019 (COVID-19) worldwide is still very severe. Presently, many breakthroughs have been accomplished in the research and development of drugs for the treatment of COVID-19, especially vaccines; however, some of the so-called COVID-19-specific drugs highlighted in the early stage failed to achieve the expected curative effect. There is no antiviral therapy available, by stimulating protective immunity vaccine is the best choice for the future management of infection. Therefore, we aimed to identify the latest developments in the research and development of these drugs and vaccines and provide a reference for the prevention and treatment of COVID-19.

3.
Arch Toxicol ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34783864

RESUMO

Contrast perception is a fundamental visual ability that allows us to distinguish objects from the background. However, whether it is perturbed by chronic exposure to environmental xenoestrogen, bisphenol A (BPA), is still elusive. Here, we used adult cats to explore BPA-induced changes in contrast sensitivity (CS) and its underlying neuronal coding mechanism. Behavioral results showed that 14 days of BPA exposure (0.4 mg/kg/day) was sufficient to induce CS declines at the tested spatial frequencies (0.05-2 cycles/deg) in all four cats. Furthermore, based on multi-channel electrophysiological recording and interneuronal correlation analysis, we found that the BPA-exposed cats exhibited an obvious up-regulation in noise correlation in the primary visual cortex (area 17, A17), thus providing a population neuronal coding basis for their perceptual dysfunction. Moreover, single neuron responses in A17 of BPA-exposed cats revealed a slight but marked decrease in CS compared to that of control cats. Additionally, these neuronal responses presented an overt decrease in signal-to-noise ratio, accompanied by increased trial-to-trial response variability (i.e., noise). To some extent, these neuron population and unit dysfunctions in A17 of BPA-exposed cats were attributable to decreased response activity of fast-spiking neurons. Together, our findings demonstrate that chronic BPA exposure restricts contrast perception, in response to impoverished neuronal coding ability in A17.

4.
Nat Commun ; 12(1): 6403, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34737329

RESUMO

The reticulotegmental nucleus (RtTg) has long been recognized as a crucial component of brainstem reticular formation (RF). However, the function of RtTg and its related circuits remain elusive. Here, we report a role of the RtTg in startle reflex, a highly conserved innate defensive behaviour. Optogenetic activation of RtTg neurons evokes robust startle responses in mice. The glutamatergic neurons in the RtTg are significantly activated during acoustic startle reflexes (ASR). Chemogenetic inhibition of the RtTg glutamatergic neurons decreases the ASR amplitudes. Viral tracing reveals an ASR neural circuit that the cochlear nucleus carrying auditory information sends direct excitatory innervations to the RtTg glutamatergic neurons, which in turn project to spinal motor neurons. Together, our findings describe a functional role of RtTg and its related neural circuit in startle reflexes, and demonstrate how the RF connects auditory system with motor functions.

5.
J Inflamm Res ; 14: 5051-5058, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34629885

RESUMO

Purpose: We explored the expression levels of IgG4 and interleukin (IL)-21 in the serum and ankle joints of collagen-induced arthritis (CIA) rats at different disease stages. Materials and Methods: Wistar rats were randomly divided into normal and model groups, and the latter group was administered bovine type II collagen to induce arthritis. Enzyme-linked immunosorbent assay was performed at 21, 28, 35, and 42 days to detect IgG4 and IL-21 in the serum, followed by histological and immunohistochemical analyses of IgG4 and IL-21r in the ankle joint of rats. Results: The contents of IgG4 and IL-21 in the serum of the CIA model group were positively correlated and increased with disease progression. The expression of IgG4 and IL-21 receptors in the ankle joint of the CIA model group was significantly higher than that in the control group. These proteins were closely related to the pathological score. The serum IL-21 level in the model group was closely related to the level of IL-21 receptor in the ankle joint. Conclusion: IL-21 may promote the occurrence and development of rheumatoid arthritis by combining with IL-21r to regulate the content of IgG4.

6.
IEEE Trans Med Imaging ; PP2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34710042

RESUMO

Uniquely capable of simultaneous imaging of the hemoglobin concentration, blood oxygenation, and flow speed at the microvascular level in vivo, multi-parametric photoacoustic microscopy (PAM) has shown considerable impact in biomedicine. However, the multi-parametric PAM acquisition requires dense sampling and thus a high laser pulse repetition rate (up to MHz), which sets a strict limit on the applicable pulse energy due to safety considerations. A similar limitation is shared by high-speed PAM, which also uses lasers with high pulse repetition rates. To achieve high quantitative accuracy besides good structural visualization at low levels of laser fluence in PAM, we have developed a new, sparse coding-based two-step denoising technique. In the setting of intravital brain imaging, we demonstrated that this unsupervised learning approach enabled the reduction of the laser fluence in PAM by 5 times without compromise of the image quality (structural similarity index measure or SSIM: >0.92) and the quantitative accuracy (errors: <4.9%). Offering a significant relaxation in the requirement of PAM on laser fluence while maintaining the quality of structural imaging and accuracy of quantitative measurements, this sparse coding-based approach is expected to facilitate the application and clinical translation of multi-parametric PAM and high-speed PAM, which have a tight photon budget due to either safety considerations or laser source limitations.

7.
BMC Cancer ; 21(1): 1069, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34592939

RESUMO

BACKGROUND: Colorectal cancer (CRC) represents one of the major malignant cancers in the world. It has been demonstrated that long non-coding RNAs (lncRNAs) can cause great influences on various human cancers. Though MCF.2 cell line derived transforming sequence like antisense RNA 1 (MCF2L-AS1) and its carcinogenic effect in CRC has been elucidated by several previous researches, the underlying mechanism remains unknown. AIM: We aimed at exploring the function and regulatory mechanism of MCF2L-AS1 in CRC. METHODS: MCF2L-AS1 expression in CRC cells was tested via RT-qPCR assay. The effects of MCF2L-AS1 on the biological properties of CRC cells were testified through functional experiments. The molecular mechanism of MCF2L-AS1 was verified through mechanism experiments. RESULTS: MCF2L-AS1 was highly expressed in CRC cells, and it could enhance the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process of CRC cells. MiR-105-5p was sponged by MCF2L-AS1 in CRC cells and Ras-related protein Rab-22A (RAB22A) was verified to be the downstream target of miR-105-5p. It was verified through rescue assays that RAB22A overexpression or miR-105-5p silencing could reverse the repressive impact of MCF2L-AS1 silencing on CRC progression. CONCLUSION: MCF2L-AS1 accelerated the malignant development of CRC cells by targeting the miR-105-5p/RAB22A axis.


Assuntos
Neoplasias Colorretais/metabolismo , MicroRNAs/metabolismo , Proteínas de Neoplasias/metabolismo , Fatores de Troca de Nucleotídeo Guanina Rho/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/patologia , Progressão da Doença , Transição Epitelial-Mesenquimal , Inativação Gênica , Humanos , MicroRNAs/genética , Invasividade Neoplásica
8.
J Mater Chem B ; 9(41): 8686-8693, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34617098

RESUMO

Short peptides with self-assembled nanostructures are widely applied in the areas of drug delivery systems and biomaterials. In this article, we create a new peptide-based hydrogelator (Fmoc-FFRRVR) based on N-fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF) through an approach to improve its hydrophilicity. Compared to Fmoc-FF, Fmoc-FFRRVR prefers to form a hydrogel under mild conditions, and the gelation time is only 2 s. Fmoc-FFRRVR self-assembles into organized arrays of ß-sheets in nanofibers via π-stacking of Fmoc-FF, which are supported by circular dichroism and fluorescence emission spectroscopy. Rheology results confirm that the hydrogel of Fmoc-FFRRVR is elastic, reversible and injectable. The newly discovered hydrogel not only retains some excellent performances of Fmoc-FF, but also can be used as a drug carrier for biomedical applications.

9.
J Biol Chem ; 297(5): 101182, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34534547

RESUMO

Circular RNAs (circRNAs) are a novel class of widespread noncoding RNAs that regulate gene expression in mammals. Recent studies demonstrate that functional peptides can be encoded by short open reading frames in noncoding RNAs, including circRNAs. However, the role of circRNAs in various physiological and pathological states, such as cancer, is not well understood. In this study, through deep RNA sequencing on human endometrial cancer (EC) samples and their paired adjacent normal tissues, we uncovered that the circRNA hsa-circ-0000437 is significantly reduced in EC compared with matched paracancerous tissue. The hsa-circ-0000437 contains a short open reading frame encoding a functional peptide termed CORO1C-47aa. Overexpression of CORO1C-47aa is capable of inhibiting angiogenesis at the initiation stage by suppressing endothelial cell proliferation, migration, and differentiation through competition with transcription factor TACC3 to bind to ARNT and suppress VEGF. CORO1C-47aa directly bound to ARNT through the PAS-B domain, and blocking the association between ARNT and TACC3, which led to reduced expression of VEGF, ultimately lead to reduced angiogenesis. The antitumor effects of CORO1C-47aa on EC progression suggest that CORO1C-47aa has potential value in anticarcinoma therapies and warrants further investigation.

10.
Atten Percept Psychophys ; 83(8): 3294-3310, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34240340

RESUMO

We investigated the eight decision rules for a same-different task, as summarized in Petrov (Psychonomic Bulletin & Review, 16(6), 1011-1025, 2009). These rules, including the differencing (DF) rule and the optimal independence rule, are all based on the standard model in signal detection theory. Each rule receives two stimulus values as inputs and uses one or two decision criteria. We proved that the false alarm rate p(F) ≤ 1/2 for four of the rules. We also conducted a same-different rating experiment on motion discrimination (n = 54), with 4∘ or 8∘ directional difference. We found that the human receiver operating characteristic (ROC) spanned its full range [0,1] in p(F), thus rejecting these four rules. The slope of the human Z-ROC was also < 1, further confirming that the independence rule was not used. We subsequently fitted in the four-dimensional (pAA, pAB, pBA, pBB) space the human data to the remaining four rules-DF and likelihood ratio rules, each with one or two criteria, where pXY = p(responding "different" given stimulus sequence XY). We found that, using residual distribution analysis, only the two criteria DF rule (DF2) could account for the human data.


Assuntos
Curva ROC , Humanos
12.
J Cereb Blood Flow Metab ; : 271678X211034096, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34304622

RESUMO

Multi-parametric photoacoustic microscopy (PAM) has emerged as a promising new technique for high-resolution quantification of hemodynamics and oxygen metabolism in the mouse brain. In this work, we have extended the scope of multi-parametric PAM to longitudinal, cortex-wide, awake-brain imaging with the use of a long-lifetime (24 weeks), wide-field (5 × 7 mm2), light-weight (2 g), dual-transparency (i.e., light and ultrasound) cranial window. Cerebrovascular responses to the window installation were examined in vivo, showing a complete recovery in 18 days. In the 22-week monitoring after the recovery, no dura thickening, skull regrowth, or changes in cerebrovascular structure and function were observed. The promise of this technique was demonstrated by monitoring vascular and metabolic responses of the awake mouse brain to ischemic stroke throughout the acute, subacute, and chronic stages. Side-by-side comparison of the responses in the ipsilateral (injury) and contralateral (control) cortices shows that despite an early recovery of cerebral blood flow and an increase in microvessel density, a long-lasting deficit in cerebral oxygen metabolism was observed throughout the chronic stage in the injured cortex, part of which proceeded to infarction. This longitudinal, functional-metabolic imaging technique opens new opportunities to study the chronic progression and therapeutic responses of neurovascular diseases.

13.
J Inflamm Res ; 14: 2713-2721, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34194234

RESUMO

Purpose: Spermidine (SPD) is a naturally occurring polyamine. In this study, we examined the role and possible mechanism of SPD in collagen-induced arthritis (CIA) mice. Materials and Methods: CIA mice were intraperitoneally injected with SPD (2 and 50 mg/kg), dexamethasone (0.5 mg/kg), or saline daily for 21 days. The severity of the disease and inflammatory responses in the serum and joint tissue were assessed through macroscopic, immunohistochemical, and histological analyses. Results: Macroscopic and histological results indicated that SPD protected against the development of CIA. SPD suppressed the levels of the pro-inflammatory cytokines IL-6 and IL-1ß and increased the levels of the anti-inflammatory factor IL-10 in the serum. Immunohistochemical staining showed that 50 mg/kg SPD inhibited iNOS expression in synovial macrophages in the ankle joints of CIA mice. Conclusion: These results suggest that SPD may protect CIA mice by inhibiting the polarization of M1 macrophages in the synovial tissue, reducing pro-inflammatory cytokines, and promoting anti-inflammatory factor release.

14.
Front Neurosci ; 15: 682229, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34290580

RESUMO

Moderate alcohol consumption is considered to enhance the cortical GABA-ergic inhibitory system and it also variously affects visual perception. However, little behavioral evidence indicates changes of visual perception due to V1 modulated by alcohol intoxication. In this study, we investigated this issue by using center-surround tilt illusion (TI) as a probe of V1 inhibitory interactions, by taking into account possible higher-order effects. Participants conducted TI measures under sober, moderate alcohol intoxication, and placebo states. We found alcohol significantly increased repulsive TI effect and weakened orientation discrimination performance, which is consistent with the increase of lateral inhibition between orientation sensitive V1 neurons caused by alcohol intoxication. We also observed no visible changes in the data for global orientation processing but a presence of global attentional modulation. Thus, our results provide psychophysics evidence that alcohol changed V1 processing, which affects visual perception of contextual stimuli.

15.
Opt Lett ; 46(11): 2561-2564, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34061056

RESUMO

Pathological aggregation of Aß peptides results in the deposition of amyloid in the brain parenchyma (senile plaques in Alzheimer's disease [AD]) and around cerebral microvessels (cerebral amyloid angiopathy [CAA]). Our current understanding of the amyloid-induced microvascular changes has been limited to the structure and hemodynamics-leaving the oxygen-metabolic aspect unattended. In this Letter, we report a dual-contrast photoacoustic microscopy (PAM) technique, which integrates the molecular contrast of dichroism PAM and the physiological contrast of multi-parametric PAM for simultaneous, intravital imaging of amyloid deposition and cerebrovascular function in a mouse model that develops AD and CAA. This technique opens up new opportunities to study the spatiotemporal interplay between amyloid deposition and vascular-metabolic dysfunction in AD and CAA.


Assuntos
Angiopatia Amiloide Cerebral , Placa Amiloide , Animais , Camundongos , Microscopia
16.
Opt Lett ; 46(11): 2690-2693, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34061089

RESUMO

Improving the imaging speed of multi-parametric photoacoustic microscopy (PAM) is essential to leveraging its impact in biomedicine. However, to avoid temporal overlap, the A-line rate is limited by the acoustic speed in biological tissues to a few megahertz. Moreover, to achieve high-speed PAM of the oxygen saturation of hemoglobin, the stimulated Raman scattering effect in optical fibers has been widely used to generate 558 nm from a commercial 532 nm laser for dual-wavelength excitation. However, the fiber length for effective wavelength conversion is typically short, corresponding to a small time delay that leads to a significant overlap of the A-lines acquired at the two wavelengths. Increasing the fiber length extends the time interval but limits the pulse energy at 558 nm. In this Letter, we report a conditional generative adversarial network-based approach that enables temporal unmixing of photoacoustic A-line signals with an interval as short as ${\sim}{38}\;{\rm ns}$, breaking the physical limit on the A-line rate. Moreover, this deep learning approach allows the use of multi-spectral laser pulses for PAM excitation, addressing the insufficient energy of monochromatic laser pulses. This technique lays the foundation for ultrahigh-speed multi-parametric PAM.


Assuntos
Aprendizado Profundo , Técnicas Fotoacústicas
17.
J Cancer ; 12(15): 4542-4551, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149918

RESUMO

Tumor distant metastasis is the primary cause of death in colorectal cancer (CRC) patients. GL-V9 is a newly synthesized flavonoid derivative with several beneficial biological functions including anti-tumor and anti-inflammation. However, the anti-metastatic effect of GL-V9 and related mechanisms in CRC remains unknown. In this study, the anti-invasive and anti-migratory activities of GL-V9 were investigated in CRC cells. Using MTT assay, cell wound healing assay, and transwell migration assay, we showed that GL-V9 suppressed CRC cell viability, migration, and invasion in a concentration-dependent manner. In addition, the protein expression levels as well as activities of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) were significantly reduced after GL-V9 treatment. Further analysis of the underlying mechanism revealed that GL-V9 inhibited PI3K/Akt signaling pathway upstream of MMP-2 and MMP-9. In conclusion, our study demonstrated that GL-V9 could suppress CRC cell invasion and migration through PI3K/Ak and MMP-2/9 axis. Therefore, GL-V9 might be a potential novel therapeutic agent against CRC metastasis.

18.
Adv Clin Exp Med ; 30(4): 361-367, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33928768

RESUMO

BACKGROUND: Hepatitis B virus (HBV) remains one of the most serious and prevalent health problems in the world. OBJECTIVES: To determine the serum hepatitis B virus (HBV) RNA levels in patients with chronic hepatitis B (CHB) with low HBV DNA levels and analyze the influencing factors. MATERIAL AND METHODS: Seventy-two CHB patients with low HBV DNA levels were enrolled and divided into 2 groups according to hepatitis B e antigen (HBeAg) status; their age, sex, the incidence of HBV RNA level < lower limit of detection (LLD), and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), quantitative determination of HBsAg (qHBsAg), HBV DNA, and HBV RNA levels were compared. The factors influencing serum HBV RNA levels < LLD and the correlation between serum HBV RNA levels, and serum ALT, AST, qHBsAg and HBV DNA levels were analyzed. RESULTS: In HBeAg-positive patients, serum AST, qHBsAg and HBV RNA levels were higher, and serum HBV DNA levels and incidence of HBV RNA < LLD were lower than those in HBeAg-negative patients (p < 0.05). Multivariate linear regression analysis revealed that HBeAg is a factor that significantly influences serum HBV RNA levels in patients with CHB (p < 0.05). Multivariate logistic regression analysis indicated that HBeAg and qHBsAg are factors that influence serum HBV RNA levels < LLD in patients with CHB. In HBeAg-positive patients, serum HBV RNA levels were positively correlated with qHBsAg and HBeAg. CONCLUSIONS: The serum HBV RNA levels in CHB patients with low HBV DNA levels varied according to HBeAg status. The HBeAg is a factor that significantly influences serum HBV RNA levels in patients with CHB, while HBeAg and qHBsAg are factors that significantly influence serum HBV RNA levels < LLD in patients with CHB.


Assuntos
Vírus da Hepatite B , Hepatite B Crônica , DNA Viral/genética , Antígenos E da Hepatite B , Vírus da Hepatite B/genética , Hepatite B Crônica/diagnóstico , Humanos , RNA
19.
J Org Chem ; 86(7): 4986-4993, 2021 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-33726491

RESUMO

Reported herein is a synthetic method of polysubstituted pyrroles from easily available materials, 1,3-dicarbonyl compounds and primary amines, via electro-oxidative intermolecular annulation. Under similar conditions, enamines are also converted smoothly into desired products, indicating that in situ formed enamines are crucial intermediates for the first transformation. Neither transition-metal salts nor harsh conditions are required to facilitate the dehydrocyclization process.


Assuntos
Aminas , Pirróis , Estresse Oxidativo
20.
Org Lett ; 22(24): 9568-9573, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33284633

RESUMO

A copper/palladium-catalyzed annulation from benzoic acids and propiophenones for the synthesis of isobenzofuranones was reported. The Cu-(2,2,6,6-tetramethylpiperidin-1-yl)oxyl system showed a great ability to activate the C-H bond on the α- and ß-carbons of a carbonyl group, and the in situ-generated enone intermediate in this reaction could be further transformed to construct isobenzofuranones with the catalysis of Pd(dba)2 (dba = dibenzylideneacetone). Various isobenzofuranones could be obtained in moderate to good yields, and a great atom economy was highlighted by utilizing this method.

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