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1.
J Ethnopharmacol ; 264: 113021, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32479885

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Liver fibrosis is an outcome of many chronic liver diseases and often results in cirrhosis, liver failure, and even hepatocarcinoma. Xiaoyaosan decoction (XYS) as a classical Traditional Chinese Medicine (TCM) formula is used to liver fibrosis in clinical practice while its mechanism is unclear. AIM OF THE STUDY: The aim of this study was to investigate the anti-fibrosis effect of XYS and to explore the molecular mechanisms by combining network pharmacology and transcriptomic technologies. MATERIALS AND METHODS: The carbon tetrachloride (CCl4)-induced liver fibrosis rat were treated with three doses of XYS. The liver fibrosis and function were evaluated by histopathological examination and serum biochemical detection. The fibrosis related protein a-SMA and collagen I were assessed by Western blot. Different expressed genes (DEGs) between XYS-treated group and model group were analyzed. The herb-component-target network was constructed combined the network pharmacology. The predict targets and pathways were validated by in vitro and in vivo experiments. RESULTS: With XYS treatment, the liver function was significantly improved, and fibrotic changes were alleviated. The a-SMA and collagen I expression levels in the liver were also decreased in XYS-treated rats compared with CCl4 model rats. 108 active components and 42 targets from 8 herbs constituted herb-compound-target network by transcriptomics and network pharmacology analysis. The KEGG pathway and GO enrichment analyses showed that the FoxO, TGFß, AMPK, MAPK, PPAR, and hepatitis B and C pathways were involved in the anti-fibrosis effects of XYS. In the liver tissues, p-FoxO3a and p-Akt expression levels were significantly increased in the CCl4 model group but decreased in the XYS-treated group. The TGFß1/Smad pathway and Akt/FoxO3 pathway were verified in LX2 cells by inhibiting phosphorylation of Smad3 and Akt activity, respectively. CONCLUSIONS: Our findings suggested that XYS markedly alleviated CCl4-induced liver fibrosis in histopathological and serum liver function analyses, and this effect may occur via the TGFß1/Smad and Akt/FoxO signaling pathways.

2.
J Colloid Interface Sci ; 581(Pt B): 627-634, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32810728

RESUMO

HYPOTHESIS: Previous use of linear elastic fracture mechanics to estimate toughness of wet particulate materials underestimates the toughness because it does not account for plastic deformation as a dissipation mechanism. Plastic deformation is responsible for the majority of energy dissipated during the fracture of wet colloidal particulate materials. Plastic deformation around the crack tip increases with saturation of the particulate body. The toughness of the body increases with increasing saturation. EXPERIMENTS: Elastic plastic fracture mechanics using the J-integral approach was used for the first time to measure the fracture toughness (JIC) of wet micron sized alumina powder bodies as a function of saturation. The samples were prepared by slip casting. The saturation was controlled by treatment in a humidity chamber. The elastic modulus (E) and the energy dissipated by plastic flow (Apl) were measured in uniaxial compression. The critical stress intensity factor (KIC) was measured using a diametral compression sample with a flaw of known size. The fracture toughness (JIC) was calculated from these measured quantities and the geometry of the specimen. FINDINGS: Elastic plastic fracture mechanics was used for the first time to quantitively account for plastic deformation of wet particulate materials. The linear elastic fracture mechanics approach previously used accounted for less than 1% of the total energy dissipated in fracture. Toughness (JIC) was found to increase with increasing saturation due to plastic deformation that increased with saturation level. The improved understanding of toughness as a function of saturation will aid in providing quantitative analysis of cracking in drying colloidal films and bodies.

3.
World J Gastroenterol ; 26(39): 5997-6014, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33132650

RESUMO

BACKGROUND: Autophagy is an evolutionarily conserved biological process in eukaryotic cells that involves lysosomal-mediated degradation and recycling of related cellular components. Recent studies have shown that autophagy plays an important role in the pathogenesis of Crohn's disease (CD). Herbal cake-partitioned moxibustion (HM) has been historically practiced to treat CD. However, the mechanism by which HM regulates colonic autophagy in CD remains unclear. AIM: To observe whether HM can alleviate CD by regulating colonic autophagy and to elucidate the underlying mechanism. METHODS: Rats were randomly divided into a normal control (NC) group, a CD group, an HM group, an insulin + CD (I + CD) group, an insulin + HM (I + HM) group, a rapamycin + CD (RA + CD) group, and a rapamycin + HM (RA + HM) group. 2,4,6-trinitrobenzenesulfonic acid was administered to establish a CD model. The morphology of the colonic mucosa was observed by hematoxylin-eosin staining, and the formation of autophagosomes was observed by electron microscopy. The expression of autophagy marker microtubule-associated protein 1 light chain 3 beta (LC3B) was observed by immunofluorescence staining. Insulin and rapamycin were used to inhibit and activate colonic autophagy, respectively. The mRNA expression levels of phosphatidylinositol 3-kinase class I (PI3KC1), Akt1, LC3B, sequestosome 1 (p62), and mammalian target of rapamycin (mTOR) were evaluated by RT-qPCR. The protein expression levels of interleukin 18 (IL-18), tumor necrosis factor-α (TNF-α), nuclear factor κB/p65 (NF-κB p65), LC3B, p62, coiled-coil myosin-like BCL2-interacting protein (Beclin-1), p-mTOR, PI3KC1, class III phosphatidylinositol 3-kinase (PI3KC3/Vps34), and p-Akt were evaluated by Western blot analysis. RESULTS: Compared with the NC group, the CD group showed severe damage to colon tissues and higher expression levels of IL-18 and NF-κB p65 in colon tissues (P < 0.01 for both). Compared with the CD group, the HM group showed significantly lower levels of these proteins (P IL-18 < 0.01 and P p65 < 0.05). There were no significant differences in the expression of TNF-α protein in colon tissue among the rat groups. Typical autophagic vesicles were found in both the CD and HM groups. The expression of the autophagy proteins LC3B and Beclin-1 was upregulated (P < 0.01 for both) in the colon tissues of rats in the CD group compared with the NC group, while the protein expression of p62 and p-mTOR was downregulated (P < 0.01 for both). However, these expression trends were significantly reversed in the HM group compared with the CD group (P LC3B < 0.01, P Beclin-1 < 0.05, P p62 < 0.05, and P m-TOR < 0.05). Compared with those in the RA + CD group, the mRNA expression levels of PI3KC1, Akt1, mTOR, and p62 in the RA + HM group were significantly higher (P PI3KC1 < 0.01 and P Akt1, mTOR, and p62 < 0.05), while those of LC3B were significantly lower (P < 0.05). Compared with the RA + CD group, the RA + HM group exhibited significantly higher PI3KC1, p-Akt1, and p-mTOR protein levels (P PI3KC1 < 0.01, P p-Akt1 < 0.05, and P p-mTOR < 0.01), a higher p62 protein level (P = 0.057), and significantly lower LC3B and Vps34 protein levels (P < 0.01 for both) in colon tissue. CONCLUSION: HM can activate PI3KC1/Akt1/mTOR signaling while inhibiting the PI3KC3 (Vps34)-Beclin-1 protein complex in the colon tissues of CD rats, thereby inhibiting overactivated autophagy and thus exerting a therapeutic effect.

4.
J Craniofac Surg ; 31(8): e802-e805, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33136917

RESUMO

OBJECTIVE: The surgical treatment of myogenic ptosis accompanying extraocular muscle paralysis is an intractable problem in the field of oculoplastic surgery due to the severe complications such as exposure keratopathy. It is promising to find an appropriate procedure to treat this kind of patients, which is able to ensure the safety and efficacy. METHODS: The authors retrospectively reviewed 12 eyes of 6 patients who underwent the under-corrected "double V-Loop" frontalis suspension sling procedure for myogenic ptosis accompanying extraocular muscle paralysis and access the safety and efficacy of this kind of surgery. All the patients underwent corneal fluorescein staining and confocal microscopy before and after the surgery to inspect the corneal condition. The density of central corneal epithelial cells and endothelial cells were observed. RESULTS: After the surgery, the eyelids contour was natural, and the symmetry was achieved in these cases. The average palpebral fissures height changed from 2.75 ±â€Š1.41 mm to 4.50 ±â€Š0.35 mm (P = 0.0007) and margin reflex distance 1 changed from -1.25 ±â€Š1.22 mm to +0.50 ±â€Š0.35 mm (P = 0.0002). Out of 12 operated eyes, mild postoperative lagophthalmos was present in 4 cases but without exposure keratopathy during the follow-up, the confocal microscopy showed that there were no significant differences in central corneal superficial epithelial cells (P = 0.93) and endothelial cells (P = 0.90) before and after the surgery. CONCLUSION: The under-corrected "double V-Loop" frontalis suspension sling is a proper surgery in myogenic ptosis accompanying extraocular muscle paralysis, which leads to a low occurrence of exposure keratopathy, maintains the integrity of the cornea, and remains the patients' vision function.

5.
World J Urol ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33141318

RESUMO

PURPOSE: We conducted the study to investigate the relationship between anogenital distance (AGD) and benign prostatic hyperplasia (BPH) related lower urinary tract symptoms (LUTS). METHODS: From May 2018 to January 2020, 220 subjects: 110 men with BPH-related LUTS (BPH-LUTS group) and 110 men without any urination complaints (control group) were selected. Clinical questionnaires, detailed physical examinations, including AGDas (distance between the anus and posterior base of the scrotum) and AGDap (distance between the anus and upper penis) measurements, and blood tests were all assessed. RESULTS: The two groups were similar in terms of basic features (P > 0.05). The AGDap and AGDas in the control group were significantly shorter than the BPH-LUTS group (P < 0.001). Adjusted multivariate analyses showed that AGDas was significantly related to International Prostate Symptom Score (IPSS), post-voiding residual volume (PVR), total prostate volume (TPV) and maximum urine flow rate (Qmax) (P = 0.002, P = 0.009, P = 0.001, P = 0.028, respectively). However, the associations between AGDap and IPSS score, PVR, TPV, Qmax and total testosterone (TT) were all negligible (P > 0.05 for all). The associations between TT and BPH-LUTS related evaluations were also negligible (P > 0.05 for all). Furthermore, the study revealed that the AGDas cut-off values for mild, moderate, and severe symptom (based on IPSS score) in BPH-LUTS cases were 27.4 mm and 46.8 mm [area under curve (AUC): 0.802 and AUC: 0.779, respectively], respectively. CONCLUSION: Longer AGDas was related to more severe BPH related symptoms. It may be useful to consider AGD as a marker for BPH-LUTS. Further well-designed studies are remained to be done to explore the intriguing problem.

6.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33162187

RESUMO

BACKGROUND: Swallowed topical steroids are a mainstay drug therapy for eosinophilic esophagitis (EoE), studies have demonstrated good histologic response, but with enormous discrepancy in clinical and endoscopic improvement. We conducted this meta-analysis to investigate the efficacy of topical steroids in EoE in histological, clinical and endoscopic improvement. METHODS: Several databases were searched from inception to August 1, 2019 for randomized controlled trials (RCTs) comparing topical steroids with placebo for EoE in the short-term. The outcomes of interest mainly included basic characteristics of the studies, histologic, clinical, endoscopic response rate and adverse events. The results were pooled together using Reviewer Manager 5.3.5 software, and inconsistency was quantified using I2 statistics. RESULTS: Nine studies were eventually selected. The results showed that topical steroids were effective in inducing histologic response compared with placebo for both complete (OR 35.82, 95% CI 14.98-85.64, P<0.0001; I2=0, P=0.72) and partial response (OR 28.44, 95% CI 8.56-94.47, P<0.0001; I2=70%, P=0.0009). Moreover, topical steroids were useful in gaining clinical response (OR 2.53, 95% CI 1.14-5.60, P=0.02; I2=60%, P=0.02) and endoscopic response (OR 3.51, 95% CI 1.47-8.36, P=0.005; I2=0, P=0.57). Generally, topical steroids are well tolerated. The most common adverse events are infections and infestations (59 cases). CONCLUSION: Topical steroids were effective in inducing histological, clinical and endoscopic response in the short-term, and the adverse events were almost tolerable; however, we should interpret the result of clinical and endoscopic response with caution.

7.
J Cell Mol Med ; 2020 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-33164320

RESUMO

To evaluate the clinical utility of neutrophil (n)CD64 index to diagnose pulmonary tuberculosis (PTB) and extrapulmonary TB (ePTB) and to predict the outcome of Mycobacterium tuberculosis infection. We recruited 189 patients with active TB and 140 controls and measured the differential expression of nCD64 index using flow cytometry. The receiver operating characteristics (ROC) curve analysis was performed to estimate the diagnostic performance of the nCD64 index and T-SPOT.TB assay for the diagnosis of TB. Furthermore, we analysed whether the nCD64 index in patients with TB was correlated with inflammatory indicators. Finally, we assessed the prognosis of patients by following the dynamic changes of the nCD64 index once a week. The nCD64 index was significantly higher in active TB group (PTB and ePTB), than in the anti-TB and healthy controls (HC) groups. The sensitivity and specificity of nCD64 index for the differential diagnosis of PTB and pneumonia (PN) patients were 68.33% and 77.55%, respectively. The sensitivity and specificity of nCD64 index for the diagnosis of tuberculous meningitis (TBM) were 53.85% and 100%, respectively. Furthermore, there was a weak correlation between the nCD64 index and inflammatory indicators. More importantly, with the improvement in patient condition, the nCD64 index started to decline in the first week of anti-TB therapy and significantly decreased at 4 weeks after treatment. Our study demonstrated that the CD64 assay is a rapid, non-invasive and stable method for clinical application, and the nCD64 index can serve as a potential biomarker for the diagnosis and prognosis of TB.

8.
Clin Breast Cancer ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33148479

RESUMO

BACKGROUND: Abemaciclib is a selective cyclin-dependent kinase 4 and 6 inhibitor administered continuously for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Abemaciclib is associated with dose-dependent early-onset diarrhea. nextMONARCH evaluated abemaciclib monotherapy (with or without prophylactic loperamide) and combined with tamoxifen for endocrine refractory metastatic breast cancer (MBC) after chemotherapy. PATIENTS AND METHODS: nextMONARCH is an open-label, controlled, randomized, phase II study of women with endocrine-refractory HR+, HER2- MBC previously treated with chemotherapy. Patients received abemaciclib 150 mg plus tamoxifen 20 mg (A+T), abemaciclib 150 mg every 12 hours (A-150), or abemaciclib 200 mg plus prophylactic loperamide (A-200). The primary objective was progression-free survival (PFS). PFS analyses tested superiority of A+T to A-200 and informal noninferiority of A-150 to A-200. The secondary objectives included the objective response rate (ORR), safety, and pharmacokinetics. RESULTS: The median PFS was 9.1 months for A+T versus 7.4 months for A-200 (hazard ratio, 0.815; 95% confidence interval, 0.556-1.193; P = .293). The A-200 PFS was comparable to that with A-150 at 6.5 months (hazard ratio, 1.045; 95% confidence interval, 0.711-1.535; P = .811). The ORR was 34.6%, 24.1%, and 32.5% for A+T, A-150, and A-200, respectively. No new safety signals were identified. The incidence and severity of diarrhea (62.3%; grade 3, 7.8%) with A-200 was similar to that with A-150 (67.1%; grade 3, 3.8%). The pharmacokinetics were comparable to previous observations. CONCLUSIONS: The addition of tamoxifen to abemaciclib did not significantly improve PFS or ORR compared with abemaciclib monotherapy but confirmed the single-agent activity of abemaciclib in heavily pretreated HR+, HER2- MBC. Dose reductions and antidiarrheal medication generally managed diarrhea while maintaining efficacy.

9.
World J Mens Health ; 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-33151043

RESUMO

PURPOSE: We conducted a systematic review and meta-analysis to quantify the association between phosphodiesterase type 5 inhibitors (PDE5Is) use and skin cancers and we also examined whether down-expression of the PDE5A gene was related to worse prognosis for malignant melanoma (MM) patients. MATERIALS AND METHODS: The PubMed, Cochrane Library, Web of Science, EMBASE, and ClinicalTrails.gov databases were searched. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the association between PDE5Is use and risk of skin cancers. Cumulative meta-analysis and trial sequential analysis (TSA) were also conducted. Survival outcomes were analyzed online. RESULTS: After pooling all 8 eligible studies comprising 7,479,852 subjects, we found that PDE5Is use was significantly associated with slightly increased risk of developing MM (OR: 1.13, 95% CI: 1.05 to 1.21, I²=67.1%), basal cell carcinoma (OR: 1.16, 95% CI: 1.13 to 1.19, I²=49.6%), and squamous cell carcinoma (OR: 1.07, 95% CI: 1.01 to 1.13, I²=0.0%). Totally, PDE5Is increased the risk of developing skin cancers (OR: 1.13, 95% CI: 1.09 to 1.17, I²=70.8%). TSA results showed that the sample size was enough to reach a positive conclusion. CONCLUSIONS: The use of PDE5Is may be slightly associated with increased risk of developing skin cancers. There should be a balance between drug benefits and potential safety issues. However, the pooled results should be considered tentative until confounding factors such as sun exposure and lifestyle are well-controlled in further studies.

10.
Anal Bioanal Chem ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33145646

RESUMO

Because of its widespread distribution in the environment, bisphenol A (BPA) has become a global concern as an endocrine disruptor and a threat to human health through the food chain. Thus an efficient determination method is urgently needed for monitoring the levels of BPA. Herein, a novel electrochemical technique for the detection of BPA was performed by synchronous extraction and pre-concentration of BPA onto magnetic molecularly imprinted polymer (BMMIP), with subsequent readout on a magneto-actuated glassy carbon electrode (MGCE) by differential pulse voltammetry. Compared to the current methods of BPA determination, this BMMIP-based electrochemical sensor (BMMIPs@MGCE) not only simplifies the sample handling procedures substantially, without filtration, centrifugation, or other complex operations, but also can be easily renewed by a controllable magnetic field. As a sensor component, the core-shell BMMIPs exhibited excellent binding capacity (Qe = 82.5 mg g-1), short adsorption equilibrium time (30 s), and outstanding selectivity (k' = 7.239) towards BPA, as well as stability and recyclability. Importantly, the BMMIPs@MGCE sensor was successfully applied for the on-site monitoring and rapid detection of BPA in complicated real-world specimens, with good recoveries (81.31-119.77%) and a low limit of detection (0.133 µmol L-1). Therefore, the stable and low-cost BMMIPs@MGCE sensor provides a new approach for the rapid determination of BPA in the field of environmental control and food safety. Graphical abstract.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33219607

RESUMO

Enantioenriched unnatural α-amino acids are significant building blocks for organic synthesis and play an essential role in pharmaceuticals and biological materials by augmenting the functions of peptides. An unprecedented radical cross-coupling reaction was achieved between glycine esters and racemic α-bromoketones catalyzed by synergistic Brønsted acid/photoredox catalysis , thus serving as an efficient platform for the synthesis of highly valuable enantioenriched unnatural α-amino acid derivatives. This dual catalysis provides a powerful capability to control the reactive radical intermediate and iminium ion, thereby enabling enantioconvergent bond-formation in a highly stereochemical manner. An array of valuable enantioenriched unnatural α-amino acid derivatives bearing two contiguous stereogenic centers are readily accessible with high diastereoselectivity and excellent enantioselectivity, which include α-amino acids with a unique ß-fluorinated quaternary stereocenter or its ß-all-carbon counterpart. Notably, a strong chiral amplification effect was observed in this dual catalytic system..

12.
Sci Total Environ ; : 143473, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33203566

RESUMO

Animal manures are commonly applied to soil which possibly promote the spread of antibiotic resistance from soil to human beings via food chains. Biogas slurry is an end product of anaerobic digestion of animal manures, which has been widely applied as fertilizers in the agricultural soil. However, effect of long-term biogas slurry application on the soil antibiotic resistance and the associated mechanism still remains unclear. The present study characterized antibiotics, antibiotic resistance genes (ARGs), mobile genetic elements (MGEs) and bacterial community, in different agricultural soils unamended (BS-) and amended (BS+) with biogas slurry (8-18 years) in five field experiments. Our results indicated that long-term application of biogas slurry largely increased the concentrations of tetracyclines in soils, and greatly increased the abundances of ARGs, transposase gene (Tn916/1545) and ARGs-associated bacteria. Long-term application of biogas slurry led to tetracyclines accumulation and ARGs enrichment in agricultural soil, and the selection pressure from tetracyclines and the increase of Tn916/1545 abundace become potential contributors for the increase of soil antibiotic resistance via promoting the enrichment of ARG-associated bacteria. The results of the present study should be taken into consideration to develop policy and practice for mitigating the enrichment and spread of antibiotic resistance during the recycling of biogas slurry into agricultural soil.

13.
Org Lett ; 22(22): 8786-8790, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33147030

RESUMO

An oxyacetamide-directed Rh(III)-catalyzed Z-type alkenyl C-H functionalization through a rare exo-rhodacyle intermediate is described, forming multisubstituted dienes and allenes. A variety of alkenes and propargylic carbonate coupling partners are suitable for this transformation with high regio- and stereoselectivity. The synthetic utility is demonstrated by the selective late-stage modification of the Z-type natural products as well as the synthesis of the unnatural ß-amino acid.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33181624

RESUMO

PURPOSE: To describe the distribution of angle alpha and angle kappa in a population with cataract in Shanghai. SETTING: Eye and Ear, Nose, Throat Hospital, Fudan University, Shanghai, China. DESIGN: Hospital-based, cross-sectional study. METHODS: We included 15,127 eyes of 15,127 cataract patients in this study. Angle alpha, angle kappa, and other ocular biometric parameters were determined by IOLMaster 700 (Carl Zeiss Meditec AG, Germany). The distributions of angle alpha and angle kappa and their associations with systemic and ocular parameters were assessed. RESULTS: The mean angle alpha and angle kappa values were 0.45 ± 0.21 mm and 0.30 ± 0.18 mm, respectively. Angle alpha and angle kappa were both predominantly located temporal to the visual axis. A greater angle alpha or angle kappa was associated with older age, lower corneal power, shorter white-to-white distance, and shallower anterior chamber depth (all P < 0.05). Angle alpha correlated positively with angle kappa. With increasing axial length (AXL), angle alpha gradually decreased in a nonlinear way and shifted to the nasal side of the visual axis, whereas angle kappa decreased in eyes with AXL < 27.5 mm but increased again in eyes with longer AXL. CONCLUSIONS: Angle alpha and angle kappa, both predominantly located temporal to the visual axis, are influenced by multiple anterior segment parameters. As AXL increases, the changes in angle alpha and angle kappa are nonlinear, and their locations gradually shift from the temporal to the nasal side of the visual axis.

15.
J Recept Signal Transduct Res ; : 1-4, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172325

RESUMO

Parkinson's disease is a brain disorder that is featured by shaking palsy, which affect the motor system. The pathogenesis of Parkinson's disease has been ascribed to neurodegenerative disorder, neural oxidative stress, neuroinflammation, and neurotransmitter disorder. In the present study, we explored the influence of Sirt1/PGC1α pathway in regulating BV-2 cells viability under TNFα treatment. Our results demonstrated that the activity of Sirt1/PGC1α pathway was significantly downregulated in response to TNFα treatment. Reactivation of Sirt1/PGC1α pathway through supplementation of SRT1720 significantly elevated the viability of BV-2 cells under an in vitro neuroinflammation model. Therefore, our results report a novel signaling pathway responsible for the survival of neuron under neuroinflammation. Re-activation of Sirt1/PGC1α pathway may be a potential therapeutic approach for the treatment of Parkinson's disease through enhancing neuronal viability.

16.
Curr Opin Hematol ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33186151

RESUMO

PURPOSE OF REVIEW: This review focuses on our current understanding of fate decisions in bipotent megakaryocyte-erythroid progenitors (MEPs). Although extensive research has been carried out over decades, our understanding of how MEP commit to the erythroid versus megakaryocyte fate remains unclear. RECENT FINDINGS: We discuss the isolation of primary human MEP, and focus on gene expression patterns, epigenetics, transcription factors and extrinsic factors that have been implicated in MEP fate determination. We conclude with an overview of the open debates in the field of MEP biology. SUMMARY: Understanding MEP fate is important because defects in megakaryocyte and erythrocyte development lead to disease states such as anaemia, thrombocytopenia and leukaemia. MEP also represent a model system for studying fundamental principles underlying cell fate decisions of bipotent and pluripotent progenitors, such that discoveries in MEP are broadly applicable to stem/progenitor cell biology.

17.
J Am Chem Soc ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33207870

RESUMO

The predictive synthesis of metal nanocrystals with desired structures relies on the precise control of the crystal formation process. Using a capping ligand is an effective method to affect the reduction of metal ions and the formation of nanocrystals. However, predictively synthesizing nanostructures has been difficult to achieve using conventional capping ligands. DNA, as a class of the promising biomolecular capping ligands, has been used to generate sequence-specific morphologies in various metal nanocrystals. However, mechanistic insight into the DNA-mediated nanocrystal formation remains elusive due to the lack of quantitative experimental evidence. Herein, we quantitatively analyzed the precise control of DNA over Ag+ reduction and the structures of resulting Au-Ag core-shell nanocrystals. We derived the equilibrium binding constants between DNA and Ag+, the kinetic rate constants of sequence-specific Ag+ reduction pathways, and the percentage of active surface sites remaining on the nanocrystals after DNA passivation. These three synergistic factors influence the nucleation and growth process both thermodynamically and kinetically, which contributed to the morphological evolution of Au-Ag nanocrystals synthesized with different DNA sequences. This study demonstrates the potential of using functional DNA sequences as a versatile and tunable capping ligand system for the predictable synthesis of metal nanostructures.

18.
Biomed Pharmacother ; 132: 110778, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33068927

RESUMO

AIMS: Long non-coding RNAs (lncRNAs) FOXD3-AS1 was reported to be increased in cardiomyocyte ischemic injury. However, its role and underlying molecular mechanism in ischemic stroke remain unknown. This study was to investigate the role of FOXD3-AS1 in cerebral ischemia/reperfusion injury. METHODS: The expression of FOXD3-AS1 and miR-765 were measured with qRT-PCR. The shared putative miR-765 binding sites both in BCL2L13 and FOXD3-AS1 were identified with bioinformatics, luciferase reporter assay and RNA immunoprecipitation. Apoptosis and its related proteins were detected by TUNEL assay, Hoechst 33,258 staining, flow cytometry and western blot. Infarct volume and the neurological status were evaluated with TTC staining and neurologic deficit score, respectively. RESULTS: The up-regulation of FOXD3-AS1 and down-regulation of miR-765 were found in both mouse brains after cerebral ischemia/reperfusion (I/R) and neuroblastoma cells of neuro-2A (N2a) after oxygen-glucose deprivation/reoxygenation (OGD/R). Moreover, the overexpression of miR-765 reduced N2a cell apoptosis caused by OGD/R. MiR-765 could target BCL2L13 directly. In addition, we found that FOXD3-AS1 bound to miR-765 directly, acting as a ceRNA to modulate the expression of BCL2L13. Overexpression of FOXD3-AS1 antagonized the inhibitory impact of miR-765 on the expression of BCL2L13 and the apoptosis of N2a cells treated with OGD/R, while FOXD3-AS1 knockdown promoted the inhibitory impact of miR-765 on the expression of BCL2L13 and the apoptosis of N2a cells treated with OGD/R. Furthermore, we found that neurological deficits and brain injury induced by I/R in vivo were attenuated by FOXD3-AS1 knockdown. CONCLUSIONS: We verified a critical signaling pathway of FOXD3-AS1/miR-765/BCL2L13 in regulating cerebral ischemia/reperfusion injury.

19.
J Cataract Refract Surg ; 46(10): 1353-1359, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33060472

RESUMO

PURPOSE: To compare the rotational stability of a plate-haptic toric intraocular lens (IOL) vs a C-loop haptic toric IOL in myopic cataract eyes. SETTING: Eye and Ear, Nose, and Throat Hospital of Fudan University, China. DESIGN: Prospective, randomized, controlled study. METHODS: Cataract eyes with axial length (AL) more than 24.5 mm were randomly assigned to receive implantation of a C-loop haptic toric IOL (AcrySof Toric IOL) (Group A) or a plate-haptic toric IOL (AT TORBI 709M IOL) (Group B). IOL rotation, residual astigmatism, visual acuity, and higher-order aberrations (HOAs) evaluated with OPD-Scan III aberrometer were compared at 3 months postoperatively. RESULTS: In total, 62 eyes of 62 patients were eligible for analysis: 31 in Group A and 31 in Group B. The mean rotation of toric IOLs was greater in Group A than that in Group B (8.00 ± 3.60 degrees vs 4.42 ± 3.24 degrees, respectively, P < .001), especially when IOLs were vertically placed. IOL rotation was positively correlated with AL in Group A, whereas no such correlations were found in Group B. Residual astigmatism in Group A was greater than that in Group B (-0.76 ± 0.30 diopter [D] vs -0.51 ± 0.29 D, respectively, P = .001). Fewer eyes achieved residual astigmatism of 0.50 D or less in Group A than in Group B (38.71% vs 64.52%). Group A had worse postoperative uncorrected visual acuity and higher total HOAs and coma for a 6.0 mm pupil than Group B, whereas postoperative corrected visual acuity was not different between the 2 groups. CONCLUSIONS: The plate-haptic toric IOL might be a better choice for myopic cataract eyes with corneal astigmatism because of reduced postoperative rotation.

20.
Sci Rep ; 10(1): 17851, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33082530

RESUMO

To demonstrate the identification of corneal diseases using a novel deep learning algorithm. A novel hierarchical deep learning network, which is composed of a family of multi-task multi-label learning classifiers representing different levels of eye diseases derived from a predefined hierarchical eye disease taxonomy was designed. Next, we proposed a multi-level eye disease-guided loss function to learn the fine-grained variability of eye diseases features. The proposed algorithm was trained end-to-end directly using 5,325 ocular surface images from a retrospective dataset. Finally, the algorithm's performance was tested against 10 ophthalmologists in a prospective clinic-based dataset with 510 outpatients newly enrolled with diseases of infectious keratitis, non-infectious keratitis, corneal dystrophy or degeneration, and corneal neoplasm. The area under the ROC curve of the algorithm for each corneal disease type was over 0.910 and in general it had sensitivity and specificity similar to or better than the average values of all ophthalmologists. Confusion matrices revealed similarities in misclassification between human experts and the algorithm. In addition, our algorithm outperformed over all four previous reported methods in identified corneal diseases. The proposed algorithm may be useful for computer-assisted corneal disease diagnosis.

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