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1.
Acta Histochem ; 122(7): 151601, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33066846

RESUMO

BACKGROUND: Osteoporosis is characterised by impairment of microarchitecture and bone mass. Therapeutic strategy promoting osteoblast differentiation is considered as a promising direction for the treatment of osteoporosis. Artesunate (ART) is related to osteoporosis, but the relationship between ART and osteogenic differentiation is still unknown. METHODS: Cells proliferation were measured by MTT, ALP activity assay and Alizarin Red S staining were used to assess osteogenic differentiation of hBMSCs. Western blotting and qRT-PCR were applied for measuring expression of protein and mRNA, respectively. The relationship between miR-34a and Dickkopf-1 (DKK1) was detected by dual luciferase reporter assay. RESULTS: The expression of osteoblasts differentiation related proteins (Runx2, OCN, and OPN) were significantly increased by ART. And ART accelerates the osteoblasts differentiation of hBMSCs through promoting Wnt signaling pathway by DKK1 inhibition. Significant higher expression of miR-34a and lower expression of DKK1 could be induced by ART. We firstly proved that miR-34a could bind DKK1 specifically. CONCLUSION: ART could promote osteoblast differentiation through miR-34a/DKK1/Wnt pathway. Therefore, our findings may provide a new thought for the treatment of osteoporosis by ART through osteoblast differentiation promotion.

2.
J Ethnopharmacol ; 266: 113421, 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33022337

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Irinotecan (CPT-11) is a valuable chemotherapeutic compound, but its use is associated with severe diarrhea in some patients. The CPT-11 prodrug is converted into the active 7-ethyl-10-hydroxycamptothecin (SN-38) metabolite, which can then be retained for extended periods in the intestine, leading to the onset of diarrhea and related symptoms. Banxia Xiexin Decoction (BXD) is commonly employed for the treatment of gastroenteritis in traditional Chinese medicine (TCM), and in clinical settings, it is used to prevent diarrhea in patients undergoing CPT-11 treatment. To date, however, there have been no studies specifically examining which components of BXD can alleviate the gastrointestinal symptoms associated with CPT-11 administration. AIM: This study aimed to identify the main herbal components of BXD associated with protection against CPT-11-induced intestinal toxicity in a murine model system. MATERIALS AND METHODS: SN-38 levels were measured by UPLC-ESI-MS/MS in samples collected from mice subjected to CPT-11-induced diarrhea that had been administered BXD or different components thereof. Pearson correlation and Grey relational analyses were then used to explore spectrum-effect relationships between reductions in intestinal SN-38 levels and specific chemical fingerprints in samples from mice administered particular combinations of BXD component herbs. RESULTS: We found that different herbal combinations were associated with significant differences in intestinal SN-38 reductions in treated mice. Our spectrum-effect analysis revealed that BXD components including chrysin 6-C-arabinoside-8-C-glucoside, coptisine, hydroxyl oroxylin A 7-O-glucuronide (hydroxyl wogonoside), baicalin, an isomer of 5,6,7-trihydroxyl-flavanone-7-O-glucuronide, berberine, palmatine, and chrysin-7-O-glucuronide were all directly linked with reductions in intestinal SN-38 levels. We therefore speculate that these compounds are the primary bioactive components of BXD, suggesting that they offer protection against CPT-11-induced diarrhea. CONCLUSION: By utilizing UPLC to analyze SN-38 levels in mice treated with a variety of herbal combinations, we were able to effectively explore BXD spectrum-effect relationships and to thereby establish the components of this medicinal preparation that were bioactive and capable of preventing CPT-11-induced diarrhea in mice. This and similar spectrum-effect studies represent a robust means of exploring the mechanistic basis for the pharmacological activity of TCM preparations.

3.
Crit Rev Oncol Hematol ; 156: 103114, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33045493

RESUMO

BACKGROUND: Extended endocrine therapy (EET) with aromatase inhibitors (AIs) therapy can further reduce the risk of recurrence in breast cancer patients. But the conclusion that whether EET with AIs increases the risk of some side effects compared with nonextended endocrine therapy (NEET) is still controversial and not exhaustive. METHODS: We searched for Randomized controlled trials (RCT) trials published in EMBASE and PubMed between March 2008 and December 2019. Studies comparing the side effects of adjuvant EET with those of NEET were included. The objective was to determine whether EET with AIs increases the risk of side effects compared with NEET. RESULTS: Overall, 11 trials comprising 24,187 participants were identified. EET with AIs increased the risk of cardiotoxicity [odds ratio (OR) 1.19, 95 % confidence interval (CI) 1.04-1.36; P < 0.05; 438 vs 423], bone pain (OR 1.18, 95 % CI 1.02-1.36; P < 0.05; 446 vs 404), osteoporosis (OR 1.53, 95 % CI 1.35-1.72; P < 0.05; 866 vs 641), fractures (OR 1.33, 95 % CI 1.18-1.50; P < 0.05; 596 vs 438), arthralgia (OR 1.27, 95 % CI 1.19-1.36; P < 0.05; 2404 vs 2060), myalgia (OR 1.29, 95 % CI 1.16-1.43; P < 0.05; 960 vs 776), and hot flashes (OR 1.40, 95 % CI 1.15-1.69; P < 0.05; 2418 vs 2174) and was associated with opposite risk of vaginal bleeding (OR 0.74, 95 % CI 0.59-0.92; P < 0.05; 148 vs 197). However, the extended therapy did not increase the risk of hypertension (OR 1.03, 95 % CI 0.80-1.33; P = 0.80; 364 vs 353), hypercholesterolemia (OR 1.03, 95 % CI 0.91-1.16; P = 0.62; 643 vs 627), vaginal dryness (OR 1.19, 95 % CI 1.00-1.42; P = 0.05; 294 vs 257), fatigue (OR 1.20, 95 % CI 0.96-1.50; P = 0.12; 1501 vs 1462), dizziness (OR 1.04, 95 % CI 0.92-1.17; P = 0.55; 614 vs 595), headaches (OR 1.06, 95 % CI 0.95-1.18; P = 0.30; 885 vs 848), constipation (OR 0.91, 95 % CI 0.79-1.04; P = 0.15; 480 vs 522), nausea (OR 1.83, 95 % CI 0.49-6.83; P =0.37; 340 vs 325), and dyspnea (OR 0.96, 95 % CI 0.82-1.13; P = 0.64; 340 vs 351). The risk of grade ≥ 3 hot flashes increased following extended endocrine therapy (OR 2.01, 95 % CI 1.23-3.29; P < 0.05; 47 vs 23). We observed no evidence for a difference in the risk of grade ≥3 fatigue, arthralgia, myalgia, bone pain, osteoporosis, fractures, hypertension, and headache between both endocrine therapies. Secondary outcomes shows that after receive EET with AIs, patients can benefit from the control of the local recurrence, distant recurrence, contralateral breast cancer, and second cancers. CONCLUSIONS: Compared with NEET, EET with AIs significantly increased the risk of cardiotoxicity, bone pain, osteoporosis, fractures, hot flashes, arthralgia, myalgia, and grade ≥3 hot flashes, and EET with AIs can reduced the risks of local recurrence, distant recurrence, contralateral breast cancer, and second cancers. These findings offer an important guide for clinicians and patients.

4.
Ital J Pediatr ; 46(1): 153, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054802

RESUMO

BACKGROUND: Pediatric COVID-19 is relatively mild and may vary from that in adults. This study was to investigate the epidemic, clinical, and imaging features of pediatric COVID-19 pneumonia for early diagnosis and treatment. METHODS: Forty-one children infected with COVID-19 were analyzed in the epidemic, clinical and imaging data. RESULTS: Among 30 children with mild COVID-19, seven had no symptoms, fifteen had low or mediate fever, and eight presented with cough, nasal congestion, diarrhea, headache, or fatigue. Among eleven children with moderate COVID-19, nine presented with low or mediate fever, accompanied with cough and runny nose, and two had no symptoms. Significantly (P < 0.05) more children had a greater rate of cough in moderate than in mild COVID-19. Thirty children with mild COVID-19 were negative in pulmonary CT imaging, whereas eleven children with moderate COVID-19 had pulmonary lesions, including ground glass opacity in ten (90.9%), patches of high density in six (54.5%), consolidation in three (27.3%), and enlarged bronchovascular bundles in seven (63.6%). The lesions were distributed along the bronchus in five patients (45.5%). The lymph nodes were enlarged in the pulmonary hilum in two patients (18.2%). The lesions were presented in the right upper lobe in two patients (18.1%), right middle lobe in one (9.1%), right lower lobe in six (54.5%), left upper lobe in five (45.5%), and left lower lobe in eight (72.7%). CONCLUSIONS: Children with COVID-19 have mild or moderate clinical and imaging presentations. A better understanding of the clinical and CT imaging helps ascertaining those with negative nucleic acid and reducing misdiagnosis rate for those with atypical and concealed symptoms.

5.
BMC Microbiol ; 20(1): 274, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32878596

RESUMO

BACKGROUND: Clostridioides (formerly Clostridium) difficile infection is the leading cause of antibiotic-associated colitis. Studies have demonstrated that C. difficile toxin A (TcdA) can cause apoptosis of many human cell types. The purpose of this study was to investigate the relationships among exposure to TcdA, the role of the receptor for the globular heads of C1q (gC1qR) gene and the underlying intracellular apoptotic mechanism in human colonic epithelial cells (NCM 460). In this study, gC1qR expression was examined using real-time polymerase chain reaction (PCR), western blotting and immunohistochemical staining. Cell viability was assessed by the water-soluble tetrazolium salt (WST-1) assay, and cell apoptosis was assessed by flow cytometry and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Mitochondrial function was assessed based on reactive oxygen species (ROS) generation, changes in the mitochondrial membrane potential (ΔΨm) and the content of ATP. RESULTS: Our study demonstrated that increasing the concentration of TcdA from 10 ng/ml to 20 ng/ml inhibited cell viability and induced cell apoptosis (p < 0.01). Moreover, the TcdA-induced gC1qR expression and enhanced expression of gC1qR caused mitochondrial dysfunction (including production of ROS and decreases in the ΔΨm and the content of ATP) and cell apoptosis. However, silencing of the gC1qR gene reversed TcdA-induced cell apoptosis and mitochondrial dysfunction. CONCLUSION: These data support a mechanism by which gC1qR plays a crucial role in TcdA-induced apoptosis of human colonic epithelial cells in a mitochondria-dependent manner.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32940891

RESUMO

OBJECTIVES: To compare antithrombotic strategies in Chinese patients undergoing bioprosthetic mitral valve implantation discharged in normal sinus rhythm. METHODS: At 28 hospitals in China, 1603 patients were followed for 2991.5 person-years. Adverse event and death rates during five postoperative time intervals (≤ 30, 31-90, 91-180, 181-365, and 366-730 days) were calculated in patients administered warfarin, aspirin, warfarin + aspirin, or neither treatment. RESULTS: Thromboembolic and hemorrhagic events occurred in 22 (0.74/100 patient-years, 95%CI 0.43-1.05) and 28 (0.94/100 patient-years, 95%CI 0.59-1.29) patients, respectively. In the first 3 months post-surgery, warfarin-treated patients had significantly lower rates of thromboembolic events than the aspirin or untreated groups (P = 0.01, P<0.01), and a significantly lower risk of bleeding than the aspirin + warfarin group (P = 0.02). From 91 to 180 days post-surgery, thromboembolism risk was significantly lower in warfarin-treated patients relative to the aspirin-treated and untreated patients (P = 0.04, P = 0.04), but bleeding and overall adverse event rates were similar (P = 1.00). From 181 to 365 days, thromboembolic event rates did not differ significantly between the untreated and anticoagulant-treated groups (P = 1.00). CONCLUSION: Warfarin is the most effective intervention for preventing thromboembolism within 6 months post-bioprosthetic MVR surgery in Chinese patients in sinus rhythm. After 6 months, further warfarin therapy was unnecessary, and aspirin should not be routinely administered.

7.
Yi Chuan ; 42(9): 889-897, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32952123

RESUMO

Osteoporosis is a typical polygenic disease, and its heritability is as high as 85%. The incidence of osteoporosis has jumped to the fifth among the common diseases. Although a large number of osteoporosis-susceptible SNPs have been identified, most of them are in the non-coding regions of the genome and the functional mechanisms are unknown. The purpose of this study was to explore the function of non-coding osteoporosis-susceptible SNP rs4325274 and dissect the molecular regulatory mechanisms through integrating bioinformatics analysis and functional experiments. Firstly, we found the SNP rs4325274 resided in a putative enhancer element through functional annotation. eQTL and Hi-C analysis found that the SOX6 gene might be a potential distal target of rs4325274. We conducted the motif prediction using multiple databases and verified the result using ChIP-seq data from GEO database. The result showed that the transcription factor HNF1A could preferentially bind to SNP rs4325274-G allele. We further demonstrated that SNP rs4325274 acted as an enhancer regulating SOX6 gene expression by using dual-luciferase reporter assays. Knockdown of HNF1A decreased the SOX6 gene expression. Taken together, our results uncovered a new mechanism of a non-coding functional SNP rs4325274 as a distal enhancer to modulate SOX6 expression, which provides new insights into deciphering molecular regulatory mechanisms underlying non-coding susceptibility SNPs on complex diseases.


Assuntos
Osteoporose , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição SOXD/genética , Alelos , Predisposição Genética para Doença , Humanos , Osteoporose/genética , Locos de Características Quantitativas
8.
Chin Med Sci J ; 35(3): 207-214, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32972498

RESUMO

Objective Linguistic problem is common in Huntington's disease (HD) patients. It has been studied before in native speakers of alphabetic languages, such as English. As a hieroglyphic language, Chinese differs from alphabetic languages in terms of phonology, morphology, semantics and syntax. We aimed to investigate the linguistic characteristics of manifest HD in native speakers of Mandarin. Meanwhile, we expected to explore the linguistic differences associated with cortical or subcortical pathology.Methods Five HD patients and five Alzheimer's disease (AD) patients matched in age, gender, disease course and educational level were enrolled. All the participants were Mandarin native speakers. All finished history inquiry, physical examination, basic test, genetic test and neuropsychological assessment. Language evaluation was performed by Aphasia Battery of Chinese.Results HD patients had a mean disease course of 5.4±2.97 (range, 2-10) years. They showed a linguistic disorder close to transcortical motor aphasia. They exhibited prominent phonological impairment, as well as slight semantic and syntactic abnormality. Tonic errors were found in speech. Character structural errors and substitutions were detected in writing. In comparison, AD patients showed a more severe linguistic impairment, characterized by global aphasia with more semantic errors. Conclusion Mandarin-speaking HD patients have a transcortical motor aphasia-like disturbance with prominent phonological impairment, whereas AD patients have a more severe global aphasia with salient semantic impairment.

9.
Phytomedicine ; 78: 153309, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32890914

RESUMO

BACKGROUND: Combination drug therapy has become an effective strategy for inflammation control. The anti­inflammatory capacities of silibinin and thymol have each been investigated on its own, but little is known about the synergistic anti-inflammatory effects of these two compounds. PURPOSE: This study aims to investigate the synergistic anti-inflammatory effects of silibinin and thymol when administered in combination to lipopolysaccharide (LPS)-induced RAW264.7 cells. METHODS: RAW264.7 cells were pre-treated with silibinin and thymol individually or in combination for 2 h before LPS stimulation. Cell viability was detected by the MTT assay. Nitric oxide (NO) production was measured by Griess reagent. Reactive oxygen species (ROS) was evaluated by 2',7'-dichlorofluorescein-diacetate. ELISA was used to detect tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Western blot was performed to analyse the protein expression of LPS-induced RAW264.7 cells. RESULTS: We observed a synergistic anti-inflammatory effect of silibinin and thymol when administered in combination to LPS-induced RAW264.7 cells. Silibinin combined with thymol (40 µM and 120 µM respectively, with the molar ratio 1:3) had more potent effects on the inhibition of NO, TNF-α, and IL-6 than those exerted by individual administration of these compounds in LPS-induced RAW264.7 cells. The combination of silibinin and thymol (40 µM and 120 µM respectively, with the molar ratio 1:3) strongly inhibited ROS and cyclooxygenase-2 (COX-2). More importantly, the combination of silibinin and thymol (40 µM and 120 µM respectively, with the molar ratio 1:3) was also successful in inhibiting nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) activities. Our results suggest that the synergistic anti-inflammatory effects of silibinin with thymol were associated with the inhibition of NF-κB and MAPK signalling pathways. CONCLUSION: The combination of silibinin and thymol (40 µM and 120 µM, respectively, with the molar ratio 1:3) could inhibit inflammation by suppressing NF-κB and MAPK signalling pathways in LPS-induced RAW264.7 cells.

10.
J Med Virol ; 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32926424

RESUMO

BACKGROUND: This study aimed to evaluate the clinical performance of low serum calcium and phosphorus in discriminative diagnosis of the severity of patients with coronavirus disease 2019 (COVID-19). We conducted a single-center hospital-based study and consecutively recruited 122 suspected and 104 confirmed patients with COVID-19 during January 24 to April 25, 2020. Clinical risk factors of COVID-19 were identified. The discriminative power of low calcium and phosphorus regarding the disease severity was evaluated. Low calcium and low phosphorus are more prevalent in severe or critical COVID-19 patients than moderate COVID-19 patients (odds ratio [OR], 15.07; 95% confidence interval [CI], 1.59-143.18 for calcium; OR, 6.90; 95% CI, 2.43-19.64 for phosphorus). The specificity in detecting the severe or critical patients among COVID-19 patients reached 98.5% (95% CI, 92.0%-99.7%) and 84.8% (95% CI, 74.3%-91.6%) by low calcium and low phosphorus, respectively, albeit with suboptimal sensitivity. Calcium and phosphorus combined with lymphocyte count could obtain the best discriminative performance for the severe COVID-19 patients (area under the curve [AUC] = 0.80), and combined with oxygenation index was promising (AUC = 0.71). Similar discriminative performances of low calcium and low phosphorus were found between suspected and confirmed COVID-19 patient. Low calcium and low phosphorus could indicate the severity of COVID-19 patients, and may be utilized as promising clinical biomarkers for discriminative diagnosis.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32912487

RESUMO

The sulfite reductase gene in Medicago sativa L. (MsSiR) encodes sulfite reductase (SiR) and catalyses the conversion of sulfite to sulfate in the sulfite assimilation pathway. In this study, we investigated the role of MsSiR in alfalfa by generating transgenic alfalfa that ectopically expressed MsSiR under the control of the CaMV35S promoter. The differences in alkali tolerance between the MsSiR-overexpressing and wild-type (WT) plants were analyzed, and the MsSiR-overexpressing plants exhibited an improved phenotype under alkali stress. Compared to WT plants, these plants demonstrated improved antioxidant activity as well as decreased H2O2 and O2- contents and increased glutathione reduced (GSH), Cysteine (Cys) and glutathione oxidized (GSSG) contents. MsSiR-overexpressing plants also exhibited high levels of adenosyl phosphosulfate reductases (APR), sulfite oxidase (SO) and MsSiR expression under alkali stress. It was speculated that MsSiR is involved in sulfur metabolism pathways, including the stabilization of sulfate and sulfite levels and the synthesis of GSH. These two processes achieve alkali tolerance by positively regulating the detoxification and antioxidant activities of alfalfa.

12.
Environ Sci Technol ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32929958

RESUMO

Long-term exposure to fine particulate matter (PM2.5) is associated with kidney dysfunction. However, few studies have investigated acute effects of PM2.5 elemental constituents on renal function. We evaluated associations between personal PM2.5 and its elemental constituents and kidney function, assessed by an estimated glomerular filtration rate (eGFR) in Biomarkers of Air Pollutants Exposure in the Chinese aged 60-69 study. Seventy one older individuals were visited monthly between September 2018 and January 2019. Each participant wore a PM2.5 monitor for 72 h, responded to a questionnaire, and underwent a physical examination with blood sampling. Linear mixed-effect models were used to estimate associations between personal PM2.5 elemental constituents and eGFR. We found that significant changes in eGFR from -1.69% [95% confidence interval (CI): -3.34%, -0.01%] to -3.27% (95% CI: -5.04%, -1.47%) were associated with interquartile range (IQR) increases in individual PM2.5 exposures at various lag periods (7-12, 13-24, 0-24, 25-48, and 49-72 h). An IQR increase in 72 h moving averages of copper, manganese, and titanium in personal PM2.5 corresponded to -2.34% (95% CI: -3.67%, -0.99%) to -4.56% (95% CI: -7.04%, -2.00%) changes in eGFR. Personal PM2.5 and some of its elemental constituents are inversely associated with eGFR in older individuals.

13.
Invest Ophthalmol Vis Sci ; 61(11): 37, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32955561

RESUMO

Purpose: To investigate the prevalence of epiretinal membranes (ERMs) and their risk factors in a Chinese population. Methods: The community-based Kailuan Eye Study included 14,440 participants (9835 male, 4605 female) with a mean age of 54.0 ± 13.3 years (range, 20-110 years). They underwent a systemic and ophthalmologic examination. ERMs were diagnosed on fundus photographs. Results: Retinal photographs assessable for the presence of ERMs were available for 13,295 (92.0%) individuals (9094 male) with a mean age of 53.6 ± 13.3 years (range, 20-110 years). ERMs were found in 1013 participants (1489 eyes) with a prevalence of 7.6% (95% confidence interval [CI], 7.1%-8.1%). Secondary ERMs caused by intraocular reasons were found 46 (4.5%) individuals (69 [4.6%] eyes). A higher prevalence of any ERMs (and of primary ERMs) was associated with older age (odds ratio [OR]: 1.08; 95% CI:1.07-1.10), higher body mass index (OR: 1.05; 95% CI: 1.00-1.11), higher prevalence of smoking (OR:1.43; 95% CI: 1.01-2.03), higher serum concentration of glucose (OR: 1.08; 95% CI: 1.04-1.13), and lower serum concentration of uric acid (OR: 0.99; 95% CI: 0.99-1.00). Visual acuity was significantly (P = 0.002) lower in eyes with premacular fibroses than in eyes with cellophane macular reflexes. Conclusions: In our cross-sectional community-based study, the prevalence of all ERMs was 7.6%. Among the group of participants with ERMs, secondary ERMs caused by intraocular reasons were detected in 46 (4.5%) individuals (69 [4.6%] eyes). A higher prevalence of any ERM and of primary ERMs was associated with older age, higher body mass index, higher prevalence of smoking, a higher serum concentration of glucose, and a lower serum concentration of uric acid.

14.
IEEE Trans Biomed Eng ; PP2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32976091

RESUMO

GOAL: Idiopathic generalized epilepsy (IGE) represents generalized spike-wave discharges (GSWD) and distributed changes in thalamocortical circuit. The purpose of this paper is to investigate how the ongoing alpha oscillation acts upon the local temporal dynamics and spatial hyperconnectivity during epileptic state. METHODS: We evaluated the spatiotemporal regulation of alpha oscillations in epileptic state based on simultaneous EEG-fMRI recordings in 45 IGE patients. The alpha-BOLD temporal consistency, as well as the effect of alpha power windows on dynamic functional connectivity strength (dFCS) was analyzed. Then, stable synchronization networks during GSWD were constructed, and the spatial covariation with alpha-based network integration was investigated. RESULTS: Increased temporal covariation was demonstrated between alpha power and BOLD fluctuations in thalamus and distributed cortical regions in IGE. High alpha power had inhibition effect on dFCS in healthy controls, while in epilepsy, high alpha windows arose along with the enhancement of dFCS in thalamus, caudate and some default mode network (DMN) regions. Moreover, synchronization networks in GSWD-before, GSWD-onset and GSWD-after stages were demonstrated, and the connectivity strength in prominent hub nodes (precuneus, thalamus) was associated with the spatially disturbed alpha-based network integration. CONCLUSION: The results indicated the spatiotemporal regulation of alpha in epilepsy by means of increased power and decreased coherence communication. It provided links between alpha rhythm and the altered temporal dynamics, as well as the hyperconnectivity in thalamus-DMN circuit. SIGNIFICANCE: The combination between neural oscillations and epileptic representations may be of clinical importance in terms of seizure prediction and non-invasive interventions.

15.
J Virol ; 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32967962

RESUMO

As the most severely lethal viral pathogen for crustaceans both in brackish water and freshwater, the white spot syndrome virus (WSSV) has a mechanism of infection that remains largely unknown, which profoundly limits the control of WSSV disease. By using a hematopoietic tissue (Hpt) stem cell culture from red claw crayfish Cherax quadricarinatus suitable for WSSV propagation in vitro, the intracellular trafficking of live WSSV was determined for the first time via live-cell imaging, in which the acidic pH-dependent endosomal environment was a prerequisite for WSSV fusion. When the acidic pH within the endosome was alkalized by chemicals, the intracellular WSSV virions were detained in dysfunctional endosomes, resulting in appreciable blocking of the viral infection. Furthermore, disrupted valosin-containing protein (CqVCP) activity resulted in considerable aggregation of endocytic WSSV virions in the disordered endosomes, which subsequently recruited autophagosomes, likely by binding to CqGABARAP via CqVCP, to eliminate the aggregated virions within the dysfunctional endosomes. Importantly, both autophagic sorting and the degradation of intracellular WSSV virions were clearly enhanced in the Hpt cells with increased autophagic activity, demonstrating that autophagy played a defensive role against the WSSV infection. Intriguingly, most of the endocytic WSSV virions were directed to the endosomal delivery system facilitated by CqVCP activity such that they avoided autophagy degradation and successfully delivered the viral genome into Hpt cell nucleus, which was followed by the propagation of progeny virions. These findings will benefit anti-WSSV target design against the most severe viral disease currently affecting farmed crustaceans.IMPORTANCEWhite spot disease is currently the most devastating viral disease in farmed crustaceans, such as shrimp and crayfish, which has resulted in a severe ecological problem for both brackish water and fresh water aquaculture areas worldwide. The efficient antiviral control against WSSV disease is still lacking due to our limited knowledge of its pathogenesis. Importantly, research on the WSSV infection mechanism is also quite meaningful for the elucidation of viral pathogenesis and virus-host coevolution, as WSSV is one of the largest animal viruses in terms of genome size which infects only crustaceans. Here, we found that most of the endocytic WSSV virions were directed to the endosomal delivery system strongly facilitated by CqVCP, such that they avoided autophagic degradation and successfully delivered the viral genome into the Hpt cell nucleus for propagation. Our data point to a virus-sorting model that might also explain the escape of other enveloped DNA viruses.

16.
Sci Transl Med ; 12(562)2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32967970

RESUMO

Patient-derived xenografts (PDXs) and PDX-derived cells (PDCs) are useful in preclinical research. We performed a drug screening assay using PDCs and identified proteasome inhibitors as promising drugs for cholangiocarcinoma (CCA) treatment. Furthermore, we determined that phosphate and tensin homology deleted on chromosome ten (PTEN) deficiency promotes protein synthesis and proteasome subunit expression and proteolytic activity, creating a dependency on the proteasome for cancer cell growth and survival. Thus, targeting the proteasome machinery with the inhibitor bortezomib inhibited the proliferation and survival of CCA cells lacking functional PTEN. Therapeutic evaluation of PDXs, autochthonous mouse models, and patients confirmed this dependency on the proteasome. Mechanistically, we found that PTEN promoted the nuclear translocation of FOXO1, resulting in the increased expression of BACH1 and MAFF BACH1 and MAFF are transcriptional regulators that recognize the antioxidant response element, which is present in genes encoding proteasome subunits. PTEN induced the accumulation and nuclear translocation of these proteins, which directly repressed the transcription of genes encoding proteasome subunits. We revealed that the PTEN-proteasome axis is a potential target for therapy in PTEN-deficient CCA and other PTEN-deficient cancers.

17.
Neurosci Lett ; 738: 135401, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32976920

RESUMO

Accumulating evidence suggests that abnormal fatty acid composition is related to the development of Alzheimer's disease (AD). However, there is no consistency in the fatty acid profile and metabolism associated with AD pathogenesis. This study aims to define the characteristics of fatty acid composition and metabolism in AD. Using 6-month-old APP/PS1 transgenic mice with wild-type mice as a control, we examined the serum lipids, brain fatty acid composition, and the expression levels of various genes involved in liver fatty acid ß-oxidation. The results of our study demonstrate that APP/PS1 mice present decreased serum free fatty acids, altered brain fatty acid profiles, and minimal change in liver fatty acid ß-oxidation. Our results suggest that abnormal fatty acid compositions and contents may play potential roles in AD progression. This study provides further evidence for the metabolic basis of AD pathogenesis.

18.
Microb Pathog ; 149: 104490, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32956791

RESUMO

Porcine circovirus type 2 (PCV2) causes infectious diseases in pigs leading to considerable economic losses in the pig industry. To prevent and control PCV2 infections, is important to understand the prevalence and geographical distribution of the virus. We performed the first systematic review and meta-analysis to estimate the prevalence of PCV2 in China. From PubMed, ScienceDirect, Chinese Web of Knowledge, Wanfang, and VIP Chinese Journal, we extracted 53 studies published in China between 2015 and 2019. There were 29,051 samples, 14,230 of which were positive for PCV2. The pooled prevalence of PCV2 was 46.0%, with the highest in Northeastern China (58.1%). The highest prevalence was 86.3% in Xinjiang province. Nursery pigs had the highest prevalence of PCV2 (50.9%), and the serological test detected the highest number of cases (58.5%). PCV2 prevalence was 50.1% in intensive farms and 37.5% in extensive farms. Our findings showed that PCV2 is common throughout China. Effective control measures are necessary to reduce PCV2 infections.

19.
FASEB J ; 2020 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-32799354

RESUMO

To examine the influence of epidermal growth factor (EGF) and its receptor (EGFR) on axial ocular elongation, we intraocularly injected an EGF antibody and an EGFR antibody into young guinea pigs with lens-induced axial elongation (myopization). Mean axial elongation was reduced in the eyes injected with the EGF/EGFR-antibody compared with the contralateral control eyes injected with PBS (phosphate-buffered solution) (0.43 ± 0.13 mm vs 0.53 ± 0.13 mm; P < .001). The intereye difference in axial length increased (P = .005) as the doses of the EGF antibody and EGFR antibody increased. As a corollary, the thickness of the retina at the posterior pole was dose-dependently increased in the injected eyes compared to the contralateral control eyes. Immunohistochemical staining for EGF and the relative mRNA expression of EGF and EGFR were the highest in eyes not injected with the EGF antibody or EGFR antibody and decreased (P < .05) as the dose of EGF antibody or EGFR antibody increased. In an in vitro study, EGF had a stimulating effect and the EGF antibody had an inhibitory effect on the proliferation and migration of RPE cells. The findings showed that the intravitreal application of an EGF antibody and EGFR antibody is associated with a dose-dependent reduction in lens-induced axial elongation in young guinea pigs. The EGFR family may play a role in axial elongation of the eye and in the development of myopia.

20.
Sci Rep ; 10(1): 13202, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32764599

RESUMO

RNA silencing is a conserved mechanism in eukaryotic organisms to regulate gene expression. Argonaute (AGO), Dicer-like (DCL) and RNA-dependent RNA polymerase (RDR) proteins are critical components of RNA silencing, but how these gene families' functions in sugarcane were largely unknown. Most stress-resistance genes in modern sugarcane cultivars (Saccharum spp.) were originated from wild species of Saccharum, for example S. spontaneum. Here, we used genome-wide analysis and a phylogenetic approach to identify four DCL, 21 AGO and 11 RDR genes in the S. spontaneum genome (termed SsDCL, SsAGO and SsRDR, respectively). Several genes, particularly some of the SsAGOs, appeared to have undergone tandem or segmental duplications events. RNA-sequencing data revealed that four SsAGO genes (SsAGO18c, SsAGO18b, SsAGO10e and SsAGO6b) and three SsRDR genes (SsRDR2b, SsRDR2d and SsRDR3) tended to have preferential expression in stem tissue, while SsRDR5 was preferentially expressed in leaves. qRT-PCR analysis showed that SsAGO10c, SsDCL2 and SsRDR6b expressions were strongly upregulated, whereas that of SsAGO18b, SsRDR1a, SsRDR2b/2d and SsRDR5 was significantly depressed in S. spontaneum plants exposed to PEG-induced dehydration stress or infected with Xanthomonas albilineans, causal agent of leaf scald disease of sugarcane, suggesting that these genes play important roles in responses of S. spontaneum to biotic and abiotic stresses.

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