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1.
Neural Regen Res ; 17(4): 819-823, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34472481

RESUMO

Leukoaraiosis (LA) results from ischemic injury in small cerebral vessels, which may be attributable to decreased vascular density, reduced cerebrovascular angiogenesis, decreased cerebral blood flow, or microcirculatory dysfunction in the brain. In this study, we enrolled 357 patients with mild intracerebral hemorrhage (ICH) from five hospitals in China and analyzed the relationships between LA and clinical symptom severity at admission, neurological function prognosis at 3 months, and 1-year stroke recurrence. Patients were divided into groups based on Fazekas scale scores: no LA (n = 83), mild LA (n = 64), moderate LA (n = 98) and severe LA (n = 112). More severe LA, larger hematoma volume, and higher blood glucose level at admission were associated with more severe neurological deficit. More severe LA, older age and larger hematoma volume were associated with worse neurological function prognosis at 3 months. In addition, moderate-to-severe LA, admission glucose and symptom-free cerebral infarction were associated with 1-year stroke recurrence. These findings suggest that LA severity may be a potential marker of individual ICH vulnerability, which can be characterized by poor tolerance to intracerebral attack or poor recovery ability after ICH. Evaluating LA severity in patients with mild ICH may help neurologists to optimize treatment protocols. This study was approved by the Ethics Committee of Ruijin Hospital Affiliated to Shanghai Jiao Tong University (approval No. 12) on March 10, 2011.

2.
J Cancer ; 12(23): 7003-7009, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34729102

RESUMO

In addition to cancer-related death, malignant progression also leads to a series of symptoms and side-effects, which would detrimentally affect cancer patients' the quality of life, adversely influence their adherence to treatments, and, therefore, negatively affect their long-term survival. Acupuncture and electroacupuncture (EA), as two classic treatment methods in traditional Chinese medicine, have been widely employed to cure various diseases. Recently, the clinical application of acupuncture and EA in cancer patients has received great attention. In this review, we summarized the clinical application of acupuncture and EA in alleviating the cancer symptoms, reducing the cancer treatment-related side-effects, and relieving the cancer pain. The symptoms and side-effects discussed in this review include fatigue, insomnia, chemotherapy-associated dyspepsia syndrome (CADS), pain, xerostomia, and anxiety and depression. The underlying mechanisms of the therapeutic effects of acupuncture and EA might be related to the regulation of the mitochondrial function, coordination of the activity of the nervous system, adjustment of the production of neurotransmitters, and alleviation of the immune responses. In conclusion, acupuncture and EA have been proved to be beneficial for cancer patients. More research, however, is required to clarify the potential mechanisms behind acupuncture and EA for widespread adoption in clinical application.

3.
J Hazard Mater ; : 127774, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34801300

RESUMO

The demand for facial masks remains high. However, little is known about discarded masks as a potential refuge for contaminants and to facilitate enrichment and spread of antibiotic resistance genes (ARG) in the environment. We address this issue by conducting an in-situ time-series experiment to investigate the dynamic changes of ARGs, bacteria and protozoa associated with discarded masks. Masks were incubated in an estuary for 30 days. The relative abundance of ARGs in masks increased after day 7 but levelled off after 14 days. The absolute abundance of ARGs at 30 days was 1.29 × 1012 and 1.07 × 1012 copies for carbon and surgical masks, respectively. According to normalized stochasticity ratio analysis, the assembly of bacterial and protistan communities was determined by stochastic (NST = 62%) and deterministic (NST = 40%) processes respectively. A network analysis highlighted potential interactions between bacteria and protozoa, which was further confirmed by culture-dependent assays, that showed masks shelter and enrich microbial communities. An antibiotic susceptibility test suggested that antibiotic resistant pathogens co-exist within protozoa. This study provides an insight into the spread of ARGs through discarded masks and highlights the importance of managing discarded masks with the potential ecological risk of mask contamination.

4.
Front Pharmacol ; 12: 714586, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34764866

RESUMO

Sennoside A (SA) is a natural dianthrone glycoside mainly from medicinal plants of Senna and Rhubarb, and used as a folk traditional irritant laxative and slimming health food. Accumulating evidences suggest that SA possesses numerous pharmacological properties, such as laxative, anti-obesity, hypoglycemic, hepatoprotective, anti-fibrotic, anti-inflammatory, anti-tumor, anti-bacterial, anti-fungal, anti-viral, and anti-neurodegenerative activities. These pharmacological effects lay the foundation for its potential application in treating a variety of diseases. However, numerous published studies suggest that a long-term use of SA in large doses may have some adverse effects, including the occurrence of melanosis coli and carcinogenesis of colon cancer, thereby limiting its clinical use. It remains to be established whether SA or its metabolites are responsible for the pharmacological and toxicity effects. In this review, the latest advances in the pharmacology, toxicology, and metabolism of SA were summarizedbased on its biological characteristics and mechanism.

5.
Plant Physiol ; 186(4): 2064-2077, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34618109

RESUMO

Sugar is considered as the primary regulator of plant apical dominance, whereby the outgrowth of axillary buds is inhibited by the shoot tip. However, there are some deficiencies in this theory. Here, we reveal that Fatty Acid Export 6 (BnFAX6) functions in FA transport, and linoleic acid or its derivatives acts as a signaling molecule in regulating apical dominance of Brassica napus. BnFAX6 is responsible for mediating FA export from plastids. Overexpression of BnFAX6 in B. napus heightened the expression of genes involved in glycolysis and lipid biosynthesis, promoting the flow of photosynthetic products to the biosynthesis of FAs (including linoleic acid and its derivatives). Enhancing expression of BnFAX6 increased oil content in seeds and leaves and resulted in semi-dwarf and increased branching phenotypes with more siliques, contributing to increased yield per plant relative to wild-type. Furthermore, decapitation led to the rapid flow of the carbon from photosynthetic products to FA biosynthesis in axillary buds, consistent with the overexpression of BnFAX6 in B. napus. In addition, free FAs, especially linoleic acid, were rapidly transported from leaves to axillary buds. Increasing linoleic acid in axillary buds repressed expression of a key transcriptional regulator responsible for maintaining bud dormancy, resulting in bud outgrowth. Taken together, we uncovered that BnFAX6 mediating FA export from plastids functions in lipid biosynthesis and in axillary bud dormancy release, possibly through enhancing linoleic acid level in axillary buds of B. napus.

6.
EMBO Rep ; : e52254, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34633746

RESUMO

Promyelocytic leukemia protein (PML) is a tumor suppressor possessing multiple modes of action, including induction of apoptosis. We unexpectedly find that PML promotes necroptosis in addition to apoptosis, with Pml-/- macrophages being more resistant to TNF-mediated necroptosis than wild-type counterparts and PML-deficient mice displaying resistance to TNF-induced systemic inflammatory response syndrome. Reduced necroptosis in PML-deficient cells is associated with attenuated receptor-interacting protein kinase 1 (RIPK1) activation, as revealed by reduced RIPK1[S166] phosphorylation, and attenuated RIPK1-RIPK3-MLKL necrosome complex formation. We show that PML deficiency leads to enhanced TNF-induced MAPK-activated kinase 2 (MK2) activation and elevated RIPK1[S321] phosphorylation, which suppresses necrosome formation. MK2 inhibitor treatment or MK2 knockout abrogates resistance to cell death induction in PML-null cells and mice. PML binds MK2 and p38 MAPK, thereby inhibiting p38-MK2 interaction and MK2 activation. Moreover, PML participates in autocrine production of TNF induced by cellular inhibitors of apoptosis 1 (cIAP1)/cIAP2 degradation, since PML-knockout attenuates autocrine TNF. Thus, by targeting MK2 activation and autocrine TNF, PML promotes necroptosis and apoptosis, representing a novel tumor-suppressive activity for PML.

7.
Front Pharmacol ; 12: 738630, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630113

RESUMO

Photothermal therapy (PTT) has become effective method for the treatment of malignant cancer. The development of PTT system with high anti-tumour effect is still the feasible research direction. Here, a new type of gold nanorods (AuNRs)-doxorubicin (DOX)/mPEG10K-peptide/P(AAm-co-AN) (APP-DOX) nano drug delivery system was proposed. Among them, AuNRs was used as high-efficiency photothermal agent. APP-DOX had a suitable size and can be targeted to accumulate in tumour tissues through circulation in the body. The abundant matrix metalloproteinase 2 (MMP-2) in the tumour environment intercepted and cut off the short peptide chain structure grafted on APP-DOX. At the same time, the removal of the PEG segment leaded to an increase in the hydrophobic properties of the system. Nanoparticles aggregated into large particles, causing them to stay and aggregate further at the tumour site. When irradiated by 808 nm near-infrared laser, APP-DOX achieved a gradual heating process. High temperature can effectively ablate tumours and enable UCST polymer to achieve phase transition, resulting in more anti-cancer drugs loaded in the polymer layer DOX was released, effectively killing cancer cells. Animal experiments had verified the possibility of the nano drug-carrying system and good tumour treatment effect. What's more worth mentioning is that compared with free DOX, the nano drug delivery system had lower biological toxicity and not cause obvious harmful effects on normal organs and tissues.

8.
Front Endocrinol (Lausanne) ; 12: 720784, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659115

RESUMO

Metformin (MET), the most common medicine for type 2 diabetes (T2DM), improves insulin sensitivity by targeting the liver, intestine and other organs. Its impact on expression of the solute carrier (Slc) transporter genes have not been reported in the mechanism of insulin sensitization. In this study, we examined Slc gene expression in the liver and colon of diet-induced obese (DIO) mice treated with MET by transcriptomic analysis. There were 939 differentially expressed genes (DEGs) in the liver of DIO mice vs lean mice, which included 34 Slc genes. MET altered 489 DEGs in the liver of DIO mice, in which 23 were Slc genes. Expression of 20 MET-responsive Slc DEGs was confirmed by qRT-PCR, in which 15 Slc genes were altered in DIO mice and their expressions were restored by MET, including Slc2a10, Slc2a13, Slc5a9, Slc6a14, Slc7a9, Slc9a2, Slc9a3, Slc13a2, Slc15a2, Slc26a3, Slc34a2, Slc37a1, Slc44a4, Slc51b and Slc52a3. While, there were only 97 DEGs in the colon of DIO mice with 5 Slc genes, whose expression was not restored by MET. The data suggest that more genes were altered in the liver over the colon by the high fat diet (HFD). There were 20 Slc genes with alteration confirmed in the liver of DIO mice and 15 of them were restored by MET, which was associated with improvement of insulin sensitivity and obesity. The restoration may improve the uptake of glucose, amino acids, mannose, fructose, 1,5-anhydro-D-glucitol and bumetanide in hepatocytes of the liver of DIO mice. The study provides new insight into the mechanism of metformin action in insulin sensitization and obesity.

9.
Jpn J Radiol ; 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34655044

RESUMO

AIM: Noninvasive evaluation of hypoxia in rabbit VX2 lung transplant tumors using spectral CT parameters and texture analysis. MATERIALS AND METHODS: Twenty-five VX2 lung transplant tumors of twenty-two rabbits were included in the study. Contrast-enhanced spectral CT scanning in the arterial phase (AP) and venous phase (VP) was performed. Tumors were divided into strong and weak hypoxic groups by hypoxic probe staining results. Spectral CT image-related parameters [70 keV CT value, normalized iodine concentration (NIC), slope of spectral HU curve (λHU)] were measured and the texture analysis on the monochromatic images was performed. Imaging parameters and texture features between tumors with different hypoxic degrees were compared and their diagnostic efficacies for predicting hypoxia in lung cancers were analyzed using receiver operating characteristic (ROC) curve. RESULTS: NIC in VP and λHU in VP of the strong hypoxic group were significantly higher than those in the weak hypoxic group (p < 0.05). For the texture features, entropy in VP and kurtosis in AP were significantly different between the two hypoxic groups. According to ROC analysis, λHU in VP had a better diagnostic ability for predicting hypoxia in tumors [Area Under Curve (AUC): 0.883, sensitivity: 85.7%, specificity: 100%]. The combination of four features improved AUC to 0.955. CONCLUSION: NIC in VP, λHU in VP, entropy in VP and kurtosis in AP have certain values in predicting tumor hypoxia and a combination of image parameters and texture features improves diagnostic efficiency.

10.
Bull Math Biol ; 83(11): 116, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34643801

RESUMO

In this paper, a two-strain model with coinfection that links immunological and epidemiological dynamics across scales is formulated. On the with-in host scale, the two strains eliminate each other with the strain having the larger immunological reproduction number persisting. However, on the population scale coinfection is a common occurrence. Individuals infected with strain one can become coinfected with strain two and similarly for individuals originally infected with strain two. The immunological reproduction numbers [Formula: see text], the epidemiological reproduction numbers [Formula: see text] and invasion reproduction numbers [Formula: see text] are computed. Besides the disease-free equilibrium, there are strain one and strain two dominance equilibria. The disease-free equilibrium is locally asymptotically stable when the epidemiological reproduction numbers [Formula: see text] are smaller than one. In addition, each strain dominance equilibrium is locally asymptotically stable if the corresponding epidemiological reproduction number is larger than one and the invasion reproduction number of the other strain is smaller than one. The coexistence equilibrium exists when all the reproduction numbers are greater than one. Simulations suggest that when both invasion reproduction numbers are smaller than one, bistability occurs with one of the strains persisting or the other, depending on initial conditions.

11.
J Matern Fetal Neonatal Med ; : 1-7, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34670464

RESUMO

PURPOSE: The association between maternal vitamin D concentrations and birth weight is controversial. We conducted a large-scale retrospective cohort study in southern China to explore this relationship. METHODS: From July 2017 to April 2019, we enrolled 10,586 pregnant women and measured serum vitamin D [via 25-hydroxyvitamin D, 25(OH)D] in the second trimester using electrochemiluminescence immunoassays. The association between macrosomia and 25(OH)D was analyzed using logistic regression and ROC curve. RESULTS: Average vitamin D concentration was 61.1 ± 20.2 nmol/L. Additionally, 31.1% participants had 25(OH)D concentrations <50.0 nmol/L, while 68.9% exhibited concentrations ≥50.0 nmol/L. Of the subjects, 3.2% of women delivered macrosomic infants (neonatal birth weight ≥4000 g) and 96.8% did not. The macrosomia group had lower vitamin D concentrations than the non-macrosomia group (59.5 ± 22.3 vs. 61.2 ± 20.1, p < .05). Approximately a third of each group had vitamin D < 50.0 nmol/L (non-macrosomia, 31.3%; macrosomia, 35.9%; p = .055). After adjusting for confounding variables, women with 25(OH)D ≥ 50.0 nmol/L had 24.3% lower macrosomia risk than women with 25(OH)D < 50.0 nmol/L (adjusted OR = 0.757, 95% CI = 0.599-0.956, p = .0193). The predictive accuracy of vitamin D concentrations for evaluating macrosomia risk was 0.667 area under the ROC curve. CONCLUSION: Maternal vitamin D levels are negatively correlated with macrosomia. Elevating vitamin D above 50.0 nmol/L may reduce macrosomia incidence.

12.
BMC Cancer ; 21(1): 1165, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34717566

RESUMO

BACKGROUND: Early recurrence is the major cause of poor prognosis in hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) are deeply involved in HCC prognosis. In this study, we aimed to establish a prognostic lncRNA signature for HCC early recurrence. METHODS: The lncRNA expression profile and corresponding clinical data were retrieved from total 299 HCC patients in TCGA database. LncRNA candidates correlated to early recurrence were selected by differentially expressed gene (DEG), univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. A 25-lncRNA prognostic signature was constructed according to receiver operating characteristic curve (ROC). Kaplan-Meier and multivariate Cox regression analyses were used to evaluate the performance of this signature. ROC and nomogram were used to evaluate the integrated models based on this signature with other independent clinical risk factors. Gene set enrichment analysis (GSEA) was used to reveal enriched gene sets in the high-risk group. Tumor infiltrating lymphocytes (TILs) levels were analyzed with single sample Gene Set Enrichment Analysis (ssGSEA). Immune therapy response prediction was performed with TIDE and SubMap. Chemotherapeutic response prediction was conducted by using Genomics of Drug Sensitivity in Cancer (GDSC) pharmacogenomics database. RESULTS: Compared to low-risk group, patients in high-risk group showed reduced disease-free survival (DFS) in the training (p < 0.0001) and validation cohort (p = 0.0132). The 25-lncRNA signature, AFP, TNM and vascular invasion could serve as independent risk factors for HCC early recurrence. Among them, the 25-lncRNA signature had the best predictive performance, and combination of those four risk factors further improves the prognostic potential. Moreover, GSEA showed significant enrichment of "E2F TARGETS", "G2M CHECKPOINT", "MYC TARGETS V1" and "DNA REPAIR" pathways in the high-risk group. In addition, increased TILs were observed in the low-risk group compared to the high-risk group. The 25-lncRNA signature negatively associates with the levels of some types of antitumor immune cells. Immunotherapies and chemotherapies prediction revealed differential responses to PD-1 inhibitor and several chemotherapeutic drugs in the low- and high-risk group. CONCLUSIONS: Our study proposed a 25-lncRNA prognostic signature for predicting HCC early recurrence, which may guide postoperative treatment and recurrence surveillance in HCC patients.

13.
Diagnostics (Basel) ; 11(9)2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34574066

RESUMO

Thalassemia and iron deficiency are the most common etiologies for microcytic anemia and there are indices discriminating both from common laboratory simple automatic counters. In this study a new classifier for discriminating thalassemia and non-thalassemia microcytic anemia was generated via combination of exciting indices with machine-learning techniques. A total of 350 Taiwanese adult patients whose anemia diagnosis, complete blood cell counts, and hemoglobin gene profiles were retrospectively reviewed. Thirteen prior established indices were applied to current cohort and the sensitivity, specificity, positive and negative predictive values were calculated. A support vector machine (SVM) with Monte-Carlo cross-validation procedure was adopted to generate the classifier. The performance of our classifier was compared with original indices by calculating the average classification error rate and area under the curve (AUC) for the sampled datasets. The performance of this SVM model showed average AUC of 0.76 and average error rate of 0.26, which surpassed all other indices. In conclusion, we developed a convenient tool for primary-care physicians when deferential diagnosis contains thalassemia for the Taiwanese adult population. This approach needs to be validated in other studies or bigger database.

14.
J Hazard Mater ; 424(Pt A): 127268, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34583167

RESUMO

Heavy metal cadmium (Cd), a classical environmental pollutant, causes placental apoptosis and fetal growth restriction (FGR), whereby the mechanism remains unclear. Here, our human case-control study firstly showed that there was a positive association of Parkin mitochondrial translocation, MCL-1 reduction, placental apoptosis, and all-cause FGR. Subsequently, Cd was administered to establish in vitro and in vivo models of placental apoptosis or FGR. Our models demonstrated that Parkin mitochondrial translocation was observed in Cd-administrated placental trophoblasts. Meaningfully, Parkin siRNA (siR) dramatically mitigated Cd-triggered apoptosis in placental trophoblasts. Mdivi-1 (M-1), an inhibitor for Parkin mitochondrial translocation, mitigated Cd-induced apoptosis in placental trophoblasts, which further ameliorated the effect of attenuated placental sizes in Cd-exposed mice. Furthermore, the interaction of MCL-1 with Parkin or Ub in Cd-stimulated cells was stronger than that in controls. MG132, an inhibitor for proteasome, abolished MCL-1 degradation in Cd-stimulated cells. Importantly, Parkin siR and M-1 memorably abolished the ubiquitin-dependent degradation of MCL-1 in placental trophoblasts. Interestingly, mito-TEMPO and melatonin, two mitochondria-targeted antioxidants, obviously rescued Cd-caused mitochondrial membrane potential (MMP) decrease, Parkin mitochondrial translocation, MCL-1 degradation, and apoptosis in placental trophoblasts. In conclusion, cadmium induces placental apoptosis and FGR via mtROS-mediated Parkin-modulated degradation of MCL-1.

15.
Anal Chem ; 93(39): 13311-13318, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34569224

RESUMO

As a global health challenge, hepatocellular carcinoma (HCC) is strongly associated with chronic inflammation. Targeting inflammation, particularly inflammatory factors, is regarded as an important strategy for HCC diagnosis and treatment. Pyroglutamic aminopeptidase I (PGP-I), a common exopeptidase, was recently identified as a novel inflammatory cytokine in cells. However, whether PGP-I is involved in HCC development and can be regarded as a biomarker remains unclear. To address this issue, endogenous PGP-I was imaged in live cells and in vivo, and the related biochemical and pathological processes were analyzed accordingly with a newly developed fluorogenic PGP-I biosensor. Bioimaging with the specific biosensor demonstrated the aberrant expression of PGP-I in HCC cell lines and tumor-bearing nude mice. Moreover, overexpression of PGP-I in HCC cells promoted tumor progression, whereas knockdown of PGP-I significantly suppressed tumor cell growth and migration. The activity of PGP-I was further identified to be highly related to the phosphorylation of STAT3, which could be impeded by the natural product parthenolide. Collectively, these findings suggest that PGP-I, which can promote hepatocellular tumor progression through the classical inflammation-/tumor-related IL-6/STAT3 pathway, may serve as a potential HCC biomarker and therapeutic target.


Assuntos
Técnicas Biossensoriais , Carcinoma Hepatocelular , Interleucina-6/metabolismo , Neoplasias Hepáticas , Piroglutamil-Peptidase I , Fator de Transcrição STAT3/metabolismo , Animais , Camundongos , Camundongos Nus , Ácido Pirrolidonocarboxílico
16.
Front Pharmacol ; 12: 734090, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34483945

RESUMO

Currently, there are no satisfactory noninvasive methods for the diagnosis of fibrosis in patients with chronic drug-induced liver injury (DILI). Our goal was to develop an algorithm to improve the diagnostic accuracy of significant fibrosis in this population. In the present study, we retrospectively investigated the biochemical and pathological characteristics of consecutive patients with biopsy-proven chronic DILI, who presented at our hospital from January 2013 to December 2017. A noninvasive algorithm was developed by using multivariate logistic regression, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA) to diagnose significant fibrosis in the training cohort, and the algorithm was subsequently validated in the validation cohort. Totally, 1,130 patients were enrolled and randomly assigned into a training cohort (n = 848) and a validation cohort (n = 282). Based on the multivariate analysis, LSM, CHE, and APRI were independently associated with significant fibrosis. A novel algorithm, LAC, was identified with the AUROC of 0.81, which was significantly higher than LSM (AUROC 0.78), CHE (AUROC 0.73), and APRI (AUROC 0.68), alone. The best cutoff value of LAC in the training cohort was 5.4. When the LAC score was used to diagnose advanced fibrosis and cirrhosis stages, the optimal cutoff values were 6.2 and 6.7, respectively, and the AUROC values were 0.84 and 0.90 in the training cohort and 0.81 and 0.83 in the validation cohort. This study proved that the LAC score can contribute to the accurate assessment of high-risk disease progression and the establishment of optimal treatment strategies for patients with chronic DILI.

17.
Ann Palliat Med ; 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34498472

RESUMO

Doubling of the optic disc is rare in clinic, which appears as true doubling or pseudo-doubling. Bilateral doubling of the optic discs is even more less seen in clinic. Here, we report the case of a 35-year-old woman who presented to the clinic for a physical examination. The patient's best-corrected visual acuity was 0.6 OD with +2.25 DS/3.50 DC×175°, and 0.9 OS with -3.00 DS/0.50 DC×145°. The intraocular pressure of each eye was normal. Fundoscopy examination revealed an enlarged suspected optic disc in both eyes. Visual field examination revealed an additional blind spot in each eye. Optical coherence tomography (OCT) analysis showed a normal macular thickness and profile. B-scan ultrasound revealed a single optic nerve shadow in each eye. Cranial computed tomography (CT) showed only 1 optic foramen and 1 optic nerve in each eye. Although double-blind spots were demonstrated by visual field examination, and pits in both optic disc regions for both eyes were shown by OCT, it was not enough to support the diagnosis of true doubling of the optic disc. Consequently, the diagnosis of bilateral pseudo-doubling of optic discs was made based on the clinical evidence, leading to the consideration of possible causality of other ophthalmic diseases.

18.
J Nippon Med Sch ; 88(4): 375-379, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34471065

RESUMO

The artery of Percheron (AOP) is an anatomical variant of the thalamoperforating arteries. AOP occlusion can cause bilateral paramedian thalamic infarctions and is referred to as a "stroke chameleon" because it lacks the classic signs of stroke. Coexistence of AOP occlusion and other neurologic disease is rare and can cause disturbance of consciousness. A 78-year-old woman had acute onset of left limb weakness and drowsy consciousness. Brain magnetic resonance angiography (MRA) revealed acute bilateral paramedian thalamic infarctions. However, serum and cerebrospinal fluid (CSF) cryptococcal antigen titers were 1:16 and 1:128, respectively. The CSF culture grew Cryptococcus neoformans. Although consciousness and muscle power improved after treatment, the patient later died of pneumonia. A 68-year-old woman developed acute disturbance of consciousness followed by delirium. Brain MRA revealed acute bilateral paramedian thalamic infarctions. Elevated free thyroxine, anti-thyroperoxidase, and anti-thyroglobulin antibodies were detected. She received 3 days of steroid pulse therapy followed by oral prednisolone. Her consciousness gradually improved after Hashimoto encephalopathy and stroke were controlled. AOP occlusion was diagnosed early in these two patients. However, other concomitant life-threatening diseases could have been overlooked because of the complicated diagnostic determination. Further serum cryptococcal antigen, anti-TPO Ab, and anti-TG Ab surveys might help to exclude cryptococcal meningitis and Hashimoto encephalopathy. CSF study is warranted when central nervous system infection is strongly suspected. This "Percheron artery-plus syndrome" comprises multifaceted disorders beyond the stroke chameleon and requires attention.

19.
Transl Neurodegener ; 10(1): 34, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496956

RESUMO

BACKGROUND: ß Amyloid (Aß)-mediated neuronal hyperactivity, a key feature of the early stage of Alzheimer's disease (AD), is recently proposed to be initiated by the suppression of glutamate reuptake. Nevertheless, the underlying mechanism by which the impaired glutamate reuptake causes neuronal hyperactivity remains unclear. Chronic suppression of the glutamate reuptake causes accumulation of ambient glutamate that could diffuse from synaptic sites at the dendrites to the soma to elevate the tonic activation of somatic N-methyl-D-aspartate receptors (NMDARs). However, less attention has been paid to the potential role of tonic activity change in extrasynaptic glutamate receptors (GluRs) located at the neuronal soma on generation of neuronal hyperactivity. METHODS: Whole-cell patch-clamp recordings were performed on CA1 pyramidal neurons in acute hippocampal slices exposed to TFB-threo-ß-benzyloxyaspartic acid (TBOA) or human Aß1-42 peptide oligomer. A series of dendritic patch-clamp recordings were made at different distances from the soma to identify the location of the changes in synaptic inputs. Moreover, single-channel recording in the cell-attached mode was performed to investigate the activity changes of single NMDARs at the soma. RESULTS: Blocking glutamate uptake with either TBOA or the human Aß1-42 peptide oligomer elicited potentiation of synaptic inputs in CA1 hippocampal neurons. Strikingly, this potentiation  specifically occurred at the soma, depending on the activation of somatic GluN2B-containing NMDARs (GluN2B-NMDARs) and accompanied by a substantial and persistent increment in the open probability of somatic NMDARs. Blocking the activity of GluN2B-NMDARs at the soma completely reversed both the TBOA-induced or the Aß1-42-induced somatic potentiation and neuronal hyperactivity. CONCLUSIONS: The somatic potentiation of synaptic inputs may represent a novel amplification mechanism that elevates cell excitability and thus contributes to neuronal hyperactivity initiated by impaired glutamate reuptake in AD.

20.
Eur Heart J ; 42(42): 4373-4385, 2021 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-34534287

RESUMO

AIMS: Aortic aneurysm and dissection (AAD) are high-risk cardiovascular diseases with no effective cure. Macrophages play an important role in the development of AAD. As succinate triggers inflammatory changes in macrophages, we investigated the significance of succinate in the pathogenesis of AAD and its clinical relevance. METHODS AND RESULTS: We used untargeted metabolomics and mass spectrometry to determine plasma succinate concentrations in 40 and 1665 individuals of the discovery and validation cohorts, respectively. Three different murine AAD models were used to determine the role of succinate in AAD development. We further examined the role of oxoglutarate dehydrogenase (OGDH) and its transcription factor cyclic adenosine monophosphate-responsive element-binding protein 1 (CREB) in the context of macrophage-mediated inflammation and established p38αMKOApoe-/- mice. Succinate was the most upregulated metabolite in the discovery cohort; this was confirmed in the validation cohort. Plasma succinate concentrations were higher in patients with AAD compared with those in healthy controls, patients with acute myocardial infarction (AMI), and patients with pulmonary embolism (PE). Moreover, succinate administration aggravated angiotensin II-induced AAD and vascular inflammation in mice. In contrast, knockdown of OGDH reduced the expression of inflammatory factors in macrophages. The conditional deletion of p38α decreased CREB phosphorylation, OGDH expression, and succinate concentrations. Conditional deletion of p38α in macrophages reduced angiotensin II-induced AAD. CONCLUSION: Plasma succinate concentrations allow to distinguish patients with AAD from both healthy controls and patients with AMI or PE. Succinate concentrations are regulated by the p38α-CREB-OGDH axis in macrophages.


Assuntos
Aneurisma Aórtico , Animais , Biomarcadores , Dissecação , Humanos , Metabolômica , Camundongos , Ácido Succínico
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