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1.
J Clin Med ; 13(7)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38610608

RESUMO

Background: Percutaneous nephrolithotomy (PNL) poses a risk of hypothermia. Additionally, general anesthesia lowers the thresholds for shivering and vasoconstriction, which leads to dysfunction of central thermoregulation. Perioperative hypothermia is associated with adverse outcomes after surgery. In this study, we aimed to demonstrate that prewarming for 10 min can effectively prevent early hypothermia during PNL. Methods: A total of 68 patients scheduled for elective PNL were recruited to this study from January to June 2022, but two patients were excluded because of a change in the surgical plan. After randomization, patients in the prewarming group (n = 32) received warming using a forced-air warming device for 10 min in the preoperative area before being transferred to the operating room, while the controls (n = 34) did not. The incidence of hypothermia within the first hour after inducing general anesthesia was the primary outcome. Perioperative body temperatures and postoperative recovery findings were also evaluated. Results: Early intraoperative hypothermia decreased significantly more in the prewarming group than in the control group (9.4% vs. 41.2%, p = 0.003). Moreover, the net decrease in core body temperature during surgery was smaller in the prewarming group than in the control group (0.2 °C, vs. 0.5 °C, p = 0.003). In addition, the prewarmed patients had a lower incidence of postoperative shivering and a shorter post-anesthesia-care unit (PACU) stay (12.5% vs. 35.3%, p = 0.031; and 46 vs. 50 min, p = 0.038, respectively). Conclusions: Prewarming for 10 min decreased early hypothermia, preserved intraoperative body temperature, and improved postoperative recovery in the PACU.

2.
Exp Neurobiol ; 32(5): 328-342, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37927131

RESUMO

Various probiotic strains have been reported to affect emotional behavior. However, the underlying mechanisms by which specific probiotic strains change brain function are not clearly understood. Here, we report that extracellular vesicles derived from Lactobacillus paracasei (Lpc-EV) have an ability to produce genome-wide changes against glucocorticoid (GC)-induced transcriptional responses in HT22 hippocampal neuronal cells. Genome-wide analysis using microarray assay followed by Rank-Rank Hypergeometric Overlap (RRHO) method leads to identify the top 20%-ranked 1,754 genes up- or down-regulated following GC treatment and their altered expressions are reversed by Lpc-EV in HT22 cells. Serial k-means clustering combined with Gene Ontology enrichment analyses indicate that the identified genes can be grouped into multiple functional clusters that contain functional modules of "responses to stress or steroid hormones", "histone modification", and "regulating MAPK signaling pathways". While all the selected genes respond to GC and Lpc-EV at certain levels, the present study focuses on the clusters that contain Mkp-1, Fkbp5, and Mecp2, the genes characterized to respond to GC and Lpc-EV in opposite directions in HT22 cells. A translational study indicates that the expression levels of Mkp-1, Fkbp5, and Mecp2 are changed in the hippocampus of mice exposed to chronic stress in the same directions as those following GC treatment in HT22 cells, whereas Lpc-EV treatment restored stress-induced changes of those factors, and alleviated stress-induced depressive-like behavior. These results suggest that Lpc-EV cargo contains bioactive components that directly induce genome-wide transcriptional responses against GC-induced transcriptional and behavioral changes.

3.
Exp Mol Med ; 55(9): 2067-2082, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37704750

RESUMO

Mounting evidence suggests that probiotics are beneficial for treating Alzheimer's disease (AD). However, the mechanisms by which specific probiotics modify AD pathophysiology are not clearly understood. In this study, we investigated whether Lactobacillus paracasei-derived extracellular vesicles (Lpc-EV) can directly act on neuronal cells to modify amyloid-beta (Aß)-induced transcriptional changes and Aß pathology in the brains of Tg-APP/PS1 mice. Lpc-EV treatment in HT22 neuronal cells counteracts Aß-induced downregulation of Brain-derived neurotrophic factor (Bdnf), Neurotrophin 3 (Nt3), Nt4/5, and TrkB receptor, and reverses Aß-induced altered expression of diverse nuclear factors, including the downregulation of Methyl-CpG binding protein 2 (Mecp2) and Sirtuin 1 (Sirt1). Systematic siRNA-mediated knockdown experiments indicate that the upregulation of Bdnf, Nt3, Nt4/5, and TrkB by Lpc-EV is mediated via multiple epigenetic factors whose activation converges on Mecp2 and Sirt1. In addition, Lpc-EV reverses Aß-induced downregulation of the Aß-degrading proteases Matrix metalloproteinase 2 (Mmp-2), Mmp-9, and Neprilysin (Nep), whose upregulation is also controlled by MeCP2 and Sirt1. Lpc-EV treatment restores the downregulated expression of Bdnf, Nt4/5, TrkB, Mmp-2, Mmp-9, and Nep; induces the upregulation of MeCP2 and Sirt1 in the hippocampus; alleviates Aß accumulation and neuroinflammatory responses in the brain; and mitigates cognitive decline in Tg-APP/PS1 mice. These results suggest that Lpc-EV cargo contains a neuroactive component that upregulates the expression of neurotrophic factors and Aß-degrading proteases (Mmp-2, Mmp-9, and Nep) through the upregulation of MeCP2 and Sirt1, and ameliorates Aß pathology and cognitive deficits in Tg-APP/PS1 mice.


Assuntos
Doença de Alzheimer , Vesículas Extracelulares , Camundongos , Animais , Metaloproteinase 2 da Matriz/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Regulação para Cima , Lactobacillus/metabolismo , Camundongos Transgênicos , Peptídeos beta-Amiloides/metabolismo , Doença de Alzheimer/metabolismo , Endopeptidases/metabolismo , Vesículas Extracelulares/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Modelos Animais de Doenças , Presenilina-1/genética
4.
J Chem Phys ; 158(21)2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37260005

RESUMO

The coupling between the symmetric (νs) and antisymmetric (νa) OD stretch modes of monomeric D2O in CHCl3 is investigated using polarization-dependent two-dimensional infrared (2D IR) spectroscopy supported by numerical 2D IR simulations based on the exciton-band theory. The relationship between the local modes' and the exciton states' parameters is systematically studied, including center frequencies, diagonal anharmonicities, coupling, and off-diagonal anharmonicity. The mean coupling between νs and νa is accurately evaluated to be -49.96 ± 0.14 cm-1. The degree of relaxation in the harmonic approximation is quantified, and the angle between the exciton-state dipoles is accurately evaluated to be 101.4° ± 3.6°. In addition, the effect of the local-mode frequency correlation on the resulting exciton-state frequency correlation and the spectral shape of the linear and 2D IR spectra are also investigated.

5.
Korean J Anesthesiol ; 76(4): 336-347, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36577507

RESUMO

BACKGROUND: Propofol-based total intravenous anesthesia (TIVA) improves long-term outcomes after cancer surgery compared with inhalation anesthesia. However, its effect on patients undergoing non-small cell lung cancer (NSCLC) surgery remains unclear. We aimed to compare the oncological outcomes of TIVA and inhalation anesthesia after curative resection of early-stage NSCLC. METHODS: We analyzed the medical records of patients diagnosed with stage I or II NSCLC who underwent curative resection at a tertiary university hospital between January 2010 and December 2017. The primary outcomes were recurrence-free survival (RFS) and overall survival (OS) according to anesthesia type. RESULTS: We included 1,508 patients with stage I/II NSCLC. The patients were divided into the TIVA (n = 980) and Inhalation (n = 528) groups. The two groups were well-balanced in terms of baseline clinical characteristics. The TIVA group demonstrated significantly improved RFS (7.7 years, 95% CI [7.37, 8.02]) compared with the Inhalation group (6.8 years, 95% CI [6.30, 7.22], P = 0.003). Similarly, TIVA was superior to inhalation agents with respect to OS (median OS; 8.4 years, 95% CI [8.08, 8.69] vs. 7.3 years, 95% CI [6.81, 7.71]; P < 0.001). Multivariable Cox regression analysis revealed that TIVA was an independent prognostic factor related to recurrence (hazard ratio [HR]: 1.24, 95% CI [1.04, 1.47], P = 0.014) and OS (HR: 1.39, 95% CI [1.12, 1.72], P = 0.002). CONCLUSIONS: Propofol-based TIVA was associated with better RFS and OS than inhalation anesthesia in patients with stage I/II NSCLC who underwent curative resection.


Assuntos
Anestésicos Inalatórios , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Propofol , Humanos , Propofol/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/etiologia , Anestésicos Intravenosos/efeitos adversos , Estudos Retrospectivos , Anestésicos Inalatórios/efeitos adversos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/etiologia , Anestesia por Inalação/efeitos adversos
6.
World J Clin Cases ; 10(35): 12990-12995, 2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36569009

RESUMO

BACKGROUND: Nearly-complete labial adhesions diagnosed with repetitive cystitis in postmenopausal women: A case report. CASE SUMMARY: The case of an 83-year-old woman who presented with dysuria, urination disorders, recurrent cystitis, and bacteriuria and was admitted to a private hospital after 1 mo of antibiotic treatment without improvement of her symptoms. Upon examination, labial adhesions were observed with nearly-complete labial fusion with a pinpoint opening. Bacteriuria was detected in urine analysis, and the urine culture test was positive for Escherichia coli. Therefore, a parenteral antibiotic (Fosfomycin) and topical estrogen cream were administered. However, since the adhesion did not separate after 2 wk of treatment, surgical correction was performed. First, adhesiolysis was conducted with a blunt instrument. Then, hysteroscopy and cystoscopy were performed. Hysteroscopic findings showed no abnormalities of the endometrium and endocervix, and the cystoscopic results were also normal. Finally, labiaplasty was completed to prevent adhesion recurrence. One month after the surgery, the discomfort while urinating was eliminated and the adhesion did not recur. CONCLUSION: Labial adhesions in postmenopausal women cannot be successfully treated with estrogen creams, and surgical treatment should be considered.

7.
Clin Psychopharmacol Neurosci ; 20(4): 694-700, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36263644

RESUMO

Objective: The ratio of 2nd and 4th digit length (2D:4D) is considered to be a sexually dimorphic trait. Low 2D:4D is implicated in alcohol dependence and heroin dependence and correlated with psychological traits such as aggression, physical aggression, and sensation. The purpose of this study is to compare the 2D:4D between methamphetamine (METH) dependence and controls and the 2D:4D ratio that is a potential biomarker for METH dependence. Methods: In this study, 40 patients diagnosed with METH dependence in Eulji University Gangnam Eulji Hospital and 50 healthy volunteers were all employees in the same hospital. Images of participants' hands were created using a scanning device. The images contained both the right and left hands; computer software was used to measure the 2D:4D ratio for both hands. We compared the ratios, analyzed by t test, between the METH dependence group and the control group. Results: The mean 2D:4D values were 0.941 (right hand) and 0.943 (left hand) for the patients with METH dependence; in contrast, they were 0.961 (right hand) and 0.961 (left hand) for the control group. These values were significantly smaller than the control in patients' right hands (p = 0.003) and left hands (p = 0.012). Conclusion: Patients with METH dependence had smaller 2D:4D ratios than those in the control group, which is similar to the results from the previous substance use disorder studies. Thus, elevated prenatal testosterone levels during the gonadal period could be related to future METH problems. Furthermore, the 2D:4D ratio is a potential marker for the prediction of METH dependence.

8.
Nanoscale ; 14(38): 14276-14285, 2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36134555

RESUMO

The cycloparaphenylene (CPP) nanocarbons are an appealing family of macrocyclic organic semiconductors with size-tunable structures and unique optoelectronic properties, which can be further modulated by complexation with guest molecules. While many π-π-stabilized CPP-fullerene host-guest complexes are known, CPPs can also host polycyclic guests stabilized by aromatic CH-π interactions. Here we combine experimental and computational results to report that CH-π interactions can also be tapped to include redox-active metallocene guests in [8]cycloparaphenylene ([8]CPP). Oxidation of a metallocene guest is accompanied by an increase in binding affinity and tilt angle. Crystallographically determined solid-state structures reveal CH-π interactions in the ferrocene complex (Fc⊂[8]CPP) and additional π-π interactions in the cobaltocenium complex (CoCp2+⊂[8]CPP). Functionalizing Fc with oxygen-bearing side chains also improves complex stability to a similar extent as oxidation, due to the formation of CH-O hydrogen bonds with the host's p-phenylene units. This work shows that CH-π bonding can be generalized as a driving force for CPP host-guest complexes and combined with other supramolecular forces to enhance stability. Owing to their semiconducting nature, amenability to functionalization, and reversible redox-dependent behavior, the [8]CPP-metallocene host-guest complexes may expand the library of synthons available for designing bespoke nanoelectronics and artificial molecular machines.

9.
Korean J Orthod ; 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35504730

RESUMO

Objective: The objectives of this study were to compare the time-dependent changes in occlusal contact area (OCA) and bite force (BF) of the deviated and non-deviated sides in mandibular prognathic patients with mandibular asymmetry before and after orthognathic surgery and investigate the factors associated with the changes in OCA and BF on each side. Methods: The sample consisted of 67 patients (33 men and 34 women; age range 15-36 years) with facial asymmetry who underwent 2-jaw orthognathic surgery. OCA and BF were taken before presurgical orthodontic treatment, within 1 month before surgery, and 1 month, 3 months, 6 months, 1 year, and 2 years after surgery. OCA and BF were measured using the Dental Prescale System. Results: The OCA and BF decreased gradually before surgery and increased after surgery on both sides. The OCA and BF were significantly greater on the deviated side than on the non-deviated side before surgery, and there was no difference after surgery. According to the linear mixed-effect model, only the changes in the mandibular plane angle had a significant effect on BF (p < 0.05). Conclusions: There was a difference in the amount of the OCA and BF between the deviated and non-deviated sides before surgery. The change in mandibular plane angle affects the change, especially on the non-deviated side, during the observation period.

10.
Sci Rep ; 12(1): 8997, 2022 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-35637212

RESUMO

Numerous organisms use the Earth's magnetic field as a sensory cue for migration, body alignment, or food search. Despite some contradictory reports, yet it is generally accepted that humans do not sense the geomagnetic field. Here, we demonstrate that a magnetic field resonance mechanism mediates light-dependent magnetic orientation in men, using a rotary chair experiment combined with a two-alternative forced choice paradigm. Two groups of subjects were classified with different magnetic orientation tendencies depending on the food context. Magnetic orientation of the subjects was sensitive to the wavelength of incident light and was critically dependent on blue light reaching the eyes. Importantly, it appears that a magnetic field resonance-dependent mechanism mediates these responses, as evidenced by disruption or augmentation of the ability to orient by radiofrequency magnetic fields at the Larmor frequency and the dependence of these effects on the angle between the radiofrequency and geomagnetic fields. Furthermore, inversion of the vertical component of the geomagnetic field revealed a non-canonical inclination compass effect on the magnetic orientation. These results establish the existence of a human magnetic sense and suggest an underlying quantum mechanical magnetoreception mechanism.


Assuntos
Campos Magnéticos , Orientação , Humanos , Magnetismo , Masculino , Orientação/fisiologia , Ondas de Rádio , Vibração
11.
Mol Neurobiol ; 59(5): 2715-2728, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35171438

RESUMO

Chronic stress causes maladaptive changes in the brain that lead to depressive behavior. In the present study, we investigate whether chronic stress alters gut microbiota compositions that are related to stress-induced maladaptive changes in the brain. Mice treated with daily 2-h restraint for 14 days (CRST) exhibit depressive-like behavior. Sequence readings of 16S rRNA genes prepared from fecal samples taken from CRST-treated mice suggest that chronic stress induces gut microbiota changes that are pronounced in the post-stress period, relative to those that occur in the 14-day stress phase. The genus Lactobacillus is one such microbiota substantially changed following chronic stress. In contrast, intraperitoneal injection of extracellular vesicles (EVs) isolated from culture media of the Gram-positive probiotic Lactobacillus plantarum is sufficient to ameliorate stress-induced depressive-like behavior. Interestingly, EVs from the Gram-positive probiotic Bacillus subtilis and EVs from the Gram-negative probiotic Akkermansia muciniphila also produce anti-depressive-like effects. While chronic stress decreases the expression of MeCP2, Sirt1, and/or neurotrophic factors in the hippocampus, EVs from the three selected probiotics differentially restore stress-induced changes of these factors. These results suggest that chronic stress produces persistent changes in gut microbiota composition, whereas purified EVs of certain probiotics can be used for treatment of stress-induced depressive-like behavior.


Assuntos
Vesículas Extracelulares , Microbioma Gastrointestinal , Probióticos , Animais , Fezes , Camundongos , Probióticos/farmacologia , Probióticos/uso terapêutico , RNA Ribossômico 16S/genética
12.
J Phys Chem B ; 126(1): 239-248, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-34961310

RESUMO

Ionic electrolytes are known to form various complexes which exist in dynamic equilibrium in a low dielectric medium. However, structural characterization of these complexes has always posed a great challenge to the scientific community. An additional challenge is the estimation of the dynamic association-dissociation time scales (lifetime of the complexes), which are key to the fundamental understanding of ion transport. In this work, we have used a combination of infrared absorption spectroscopy, two-dimensional infrared spectroscopy, molecular dynamics simulations, and density functional theory calculations to characterize the various ion complexes formed by the thiocyanate-based ionic electrolytes as a function of different cations in a low dielectric medium. Our results demonstrate that thiocyanate is an excellent vibrational reporter of the heterogeneous ion complexes undergoing association-dissociation dynamics. We find that the ionic electrolytes exist as contact ion pairs, dimers, and clusters in a low dielectric medium. The relative ratios of the various ion complexes are sensitive to the cations. In addition to the interactions between the thiocyanate anion and the countercation, the solute-solvent interactions drive the dynamic equilibrium. We have estimated the association-dissociation dynamics time scales from two-dimensional infrared spectroscopy. The exchange time scale involving the cluster is faster than that between a dimer and an ion pair. Moreover, we find that the dynamic equilibrium between the cluster and another ion complex is correlated to the solvent fluctuations.

13.
Biol Psychiatry ; 91(7): 676-689, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34961622

RESUMO

BACKGROUND: The reward system regulates motivated behavior, and repeated practice of specific motivated behavior might conversely modify the reward system. However, the detailed mechanisms by which they reciprocally regulate each other are not clearly understood. METHODS: Mice subjected to chronic restraint stress show long-lasting depressive-like behavior, which is rescued by continual engagement with playable objects. A series of molecular, pharmacological, genetic, and behavioral analyses, combined with microarray, liquid chromatography, and chemogenetic tools, are used to investigate the neural mechanisms of antidepressive effects of playable objects. RESULTS: Here, we show that repeated restraint induces dopamine surges into the nucleus accumbens-lateral shell (NAc-lSh), which cause upregulation of the neuropeptide PACAP in the NAc-lSh. As repeated stress is continued, the dopamine surge by stressors is adaptively suppressed without restoring PACAP upregulation, and the resulting enhanced PACAP inputs from NAc-lSh neurons to the ventral pallidum facilitate depressive-like behaviors. Continual engagement with playable objects in mice subjected to chronic stress remediates reduced dopamine response to new stressors, enhanced PACAP upregulation, and depressive-like behaviors. Overactivation of dopamine D1 receptors over the action of D2 receptors in the NAc-lSh promotes depressive-like behaviors. Conversely, inhibition of D1 receptors or PACAP upregulation in the NAc-lSh confers resilience to chronic stress-induced depressive-like behaviors. Histochemical and chemogenetic analyses reveal that engagement with playable objects produces antidepressive effects by reshaping the ventral tegmental area-to-NAc-lSh and NAc-lSh-to-ventral pallidum circuits. CONCLUSIONS: These results suggest that behavioral engagement with playable objects remediates depressive-like behaviors by resolving stress-induced maladaptive changes in the reward system.


Assuntos
Dopamina , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Animais , Antidepressivos/farmacologia , Camundongos , Núcleo Accumbens , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Recompensa , Área Tegmentar Ventral
14.
Medicina (Kaunas) ; 59(1)2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36676688

RESUMO

Relapsing polychondritis (RP) is a rare autoimmune disorder that causes inflammation and deterioration of cartilaginous structures such as the ears, nose, joints and laryngotracheobronchial tree. A 42-year-old man receiving treatment for RP underwent open reduction and internal fixation of a femur fracture under spinal anesthesia and with sedation by propofol and remifentanil. The level of sedation was monitored via a bispectral index (BIS), and maintained at between 60 and 80. At the end of the operation, he lost consciousness and displayed weak respiratory effort. During mask ventilation, the patient was judged to have respiratory failure due to high end-tidal CO2 (EtCO2) concentration and respiratory acidosis in an arterial-blood-gas analysis (ABGA). Ventilation through a properly inserted laryngeal-mask-airway or endotracheal intubation were impossible; instead, a surgical tracheotomy was performed. After recovering from respiratory failure with ventilatory support in the intensive care unit (ICU), he experienced the same symptoms three more times, requiring ventilatory support. He was discharged with bilevel positive-airway-pressure (BiPAP), after successful adaptation.


Assuntos
Anestesia , Policondrite Recidivante , Propofol , Insuficiência Respiratória , Masculino , Humanos , Adulto , Policondrite Recidivante/complicações , Policondrite Recidivante/diagnóstico , Policondrite Recidivante/cirurgia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Respiração , Anestesia/efeitos adversos
15.
Nat Commun ; 12(1): 6682, 2021 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795225

RESUMO

Chronic stress induces adaptive changes in the brain via the cumulative action of glucocorticoids, which is associated with mood disorders. Here we show that repeated daily five-minute restraint resolves pre-existing stress-induced depressive-like behavior in mice. Repeated injection of glucocorticoids in low doses mimics the anti-depressive effects of short-term stress. Repeated exposure to short-term stress and injection of glucocorticoids activate neurons in largely overlapping regions of the brain, as shown by c-Fos staining, and reverse distinct stress-induced gene expression profiles. Chemogenetic inhibition of neurons in the prelimbic cortex projecting to the nucleus accumbens, basolateral amygdala, or bed nucleus of the stria terminalis results in anti-depressive effects similarly to short-term stress exposure, while only inhibition of neurons in the prelimbic cortex projecting to the bed nucleus of the stria terminalis rescues defective glucocorticoid release. In summary, we show that short-term stress can reverse adaptively altered stress gains and resolve stress-induced depressive-like behavior.


Assuntos
Agressão/fisiologia , Transtorno Depressivo/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Estresse Psicológico/fisiopatologia , Agressão/psicologia , Animais , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Corticosterona/sangue , Corticosterona/metabolismo , Corticosterona/farmacologia , Transtorno Depressivo/psicologia , Feminino , Perfilação da Expressão Gênica/métodos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Gravidez , Efeitos Tardios da Exposição Pré-Natal/psicologia , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Receptores de Mineralocorticoides/genética , Receptores de Mineralocorticoides/metabolismo , Restrição Física , Fatores de Tempo
16.
Chem Commun (Camb) ; 57(83): 10887-10890, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34604870

RESUMO

Large scale synthesis of cycloparaphenyleneacetylenes has been challenging due to low macrocyclization yields and harsh aromatization methods that often decompose strained alkynes. Herein, a cis-stilbene-based building block is subjected to alkyne metathesis macrocylization. The following sequence of alkene-selective bromination and dehydrobromination afforded a [8]cycloparaphenyleneacetylene derivative in high yield with good scalability. X-Ray crystal structure and computational analysis revealed a unique same-rim conformation for the eight methyl groups on the nanohoop.

17.
Exp Neurobiol ; 30(4): 294-307, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34483143

RESUMO

Recently we reported that hyperoxygenation treatment reduces amyloid-beta accumulation and rescues cognitive impairment in the Tg-APP/PS1 mouse model of Alzheimer's disease. In the present study, we continue to investigate the mechanism by which hyperoxygenation reduces amyloid-beta deposition in the brain. Hyperoxygenation treatment induces upregulation of matrix metalloproteinase-2 (MMP-2), MMP-9, and tissue plasminogen activator (tPA), the endopeptidases that can degrade amyloid-beta, in the hippocampus of Tg-APP/PS1 mice. The promoter regions of the three proteinase genes all contain potential binding sites for MeCP2 and Pea3, which are upregulated in the hippocampus after hyperoxygenation. Hyperoxygenation treatment in HT22 neuronal cells increases MeCP2 but not Pea3 expression. In HT22 cells, siRNA-mediated knockdown of Mecp2 decreases Mmp-9 expression and to a lesser extent, Mmp-2 and tPA expression. In mice, siRNA-mediated Mecp2 knockdown in the hippocampus reduces Mmp-9 expression, but not significantly Mmp-2 and tPA expression. The ChIP assay indicates that hyperoxygenation treatment in Tg-APP/PS1 mice increases MeCP2 binding to the promoter regions of Mmp-2 , Mmp-9 and tPA genes in the hippocampus. Together, these results suggest that hyperoxygenation increases the expression of MMP-2, MMP-9, and tPA, of which MMP-9 is upregulated via MeCP2 in neuronal cells, and MMP-2 and tPA are upregulated through MeCP2 and other nuclear factors.

18.
Exp Neurobiol ; 30(6): 415-429, 2021 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-34983882

RESUMO

Hyperoxygenation therapy remediates neuronal injury and improves cognitive function in various animal models. In the present study, the optimal conditions for hyperoxygenation treatment of stress-induced maladaptive changes were investigated. Mice exposed to chronic restraint stress (CRST) produce persistent adaptive changes in genomic responses and exhibit depressive-like behaviors. Hyperoxygenation treatment with 100% O2 (HO2) at 2.0 atmospheres absolute (ATA) for 1 h daily for 14 days in CRST mice produces an antidepressive effect similar to that of the antidepressant imipramine. In contrast, HO2 treatment at 2.0 ATA for 1 h daily for shorter duration (3, 5, or 7 days), HO2 treatment at 1.5 ATA for 1 h daily for 14 days, or hyperbaric air treatment at 2.0 ATA (42% O2) for 1 h daily for 14 days is ineffective or less effective, indicating that repeated sufficient hyperoxygenation conditions are required to reverse stress-induced maladaptive changes. HO2 treatment at 2.0 ATA for 14 days restores stress-induced reductions in levels of mitochondrial copy number, stress-induced attenuation of synaptophysin-stained density of axon terminals and MAP-2-staining dendritic processes of pyramidal neurons in the hippocampus, and stress-induced reduced hippocampal neurogenesis. These results suggest that HO2 treatment at 2.0 ATA for 14 days is effective to ameliorate stress-induced neuronal and behavioral deficits.

20.
ACS Nano ; 14(10): 13619-13628, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-32961057

RESUMO

While tattooable nanotechnology for in-skin sensing and communication has been a popular concept in science fiction since the 1990s, the first tattooable intradermal nanosensors have only emerged in the past few years, and none have been demonstrated in human skin. We developed a photochromic tattoo that serves as an intradermal ultraviolet (UV) radiometer that provides naked-eye feedback about UV exposure in real time. These small tattoos, or "solar freckles", comprise dermally implanted colorimetric UV sensors in the form of nanoencapsulated leuco dyes that become more blue in color with increasing UV irradiance. We demonstrate the tattoos' functionality for both quantitative and naked-eye UV sensing in porcine skin ex vivo, as well as in human skin in vivo. Solar freckles offer an alternative and complementary approach to self-monitoring UV exposure for the sake of skin cancer prevention. Activated solar freckles provide a visual reminder to protect the skin, and their color disappears rapidly upon removal of UV exposure or application of topical sunscreen. The sensors are implanted in a minimally invasive procedure that lasts only a few seconds, yet remain functional for months to years. These semipermanent tattoos provide an early proof-of-concept for long-term intradermal sensing nanomaterials that provide users with biomedically relevant information in the form of an observable color change.


Assuntos
Melanose , Tatuagem , Humanos , Radiometria , Pele , Luz Solar , Raios Ultravioleta
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