ccordmg to Reese-Ellsworth Classification tot .retmoblastoma, retinoblastoma with vitreousseeding initially is grade 5B with poor prognosis and was proposed tbr enucleation. Chemotherapy combined ...with local treatment for retinoblasloma has been proposed as conservative treatment.1 Because of the lack of blood supply to vitreous seeding, the chemotherapy drugs could not reach the vitreous body through blood-retinal barrier. This has been one of the important limiting factors in the treatment of children with retmoblastoma with vitreous seeding.
Proteomics was used to identify a protein encoded by ORF 3a in a SARS-associated coronavirus (SARS-CoV). Immuno-blotting revealed that interchain disulfide bonds might be formed between this protein ...and the spike protein. ELISA indicated that sera from SARS patients have significant positive reactions with synthesized peptides derived from the 3a protein. These results are concordant with that of a spike protein-derived peptide. A tendency exists for co-mutation between the 3a protein and the spike protein of SARS-CoV isolates, suggesting that the function of the 3a protein correlates with the spike protein. Taken together, the 3a protein might be tightly correlated to the spike protein in the SARS-CoV functions. The 3a protein may serve as a new clinical marker or drug target for SARS treatment.
Herein, a hetero(S,N)‐quintuple 9helicene (SNQ9H) molecule with an azacorannulene core was synthesized, currently representing the highest hetero‐helicene reported in the field of multiple ...nhelicenes. X‐ray crystallography indicated that SNQ9H includes not only a propeller‐shaped conformer SNQ9H‐1, but also an unforeseen quasi‐propeller‐shaped conformer SNQ9H‐2. Different conformers were observed for the first time in multiple n≥9helicenes, likely owing to the doping of heteroatomic sulfurs in the helical skeletons. Remarkably, the ratio of SNQ9H‐1 to SNQ9H‐2 can be regulated in situ by the reaction temperature. Experimental studies on the photophysical and redox properties of SNQ9H and theoretical calculations clearly demonstrated that the electronic structures of SNQ9H depend on their molecular conformations. The strategy of introducing heteroatomic sulfurs into the helical skeleton may be useful in constructing various conformers of higher multiple nhelicenes in the future.
Two conformers of a novel quintuple 9helicene with an azabuckybowl as the core were obtained by the deliberate introduction of sulfur heteroatoms into the helical skeleton. The structure–property relationship of different conformers was investigated through detailed experiment and theoretical calculations. The success of the sulfur‐doped strategy implies the potential of realizing higher multiple nhelicenes with various conformers.
With a worldwide distribution, Eimeria spp. could result in serious economic losses to the poultry industry. Due to drug resistance and residues, there are no ideal drugs and vaccines against Eimeria ...spp. in food animals. In the current study, a bioinformatics approach was employed to design a multiepitope antigen, named NSLC protein, encoding antigenic epitopes of E. necatrix NA4, E. tenella SAG1, E. acervulina LDH, and E. maxima CDPK. Thereafter, the protective immunity of NSLC protein along with five adjuvants and two nanospheres in laying chickens was evaluated. Based on the humoral immunity, cellular immunity, oocyst burden, and the coefficient of growth, the optimum adjuvant was evaluated. Furthermore, the optimum immune route and dosage were also investigated according to the oocyst burden and coefficient of growth. Accompanied by promoted secretion of antibodies and enhanced CD4
and CD8
T lymphocyte proportions, NSLC proteins entrapped in PLGA nanospheres were more effective in stimulating protective immunity than other adjuvants or nanospheres, indicating that PLGA nanospheres were the optimum adjuvant for NSLC protein. In addition, a significantly inhibited oocyst burden and growth coefficient promotion were also observed in animals vaccinated with NSLC proteins entrapped in PLGA nanospheres, indicating that the optimum adjuvant for NSLC proteins was PLGA nanospheres. The results also suggested that the intramucosal route with PLGA nanospheres containing 300 μg of NSLC protein was the most efficient approach to induce protective immunity against the four Eimeria species. Collectively, PLGA nanospheres loaded with NSLC antigens are potential vaccine candidates against avian coccidiosis.
Acute myocardial infarction (AMI) is a leading cause of mortality and morbidity worldwide. Using a validated and efficient ICP-MS/MS-based workflow, a total of 30 metallomic features were profiled in ...a study comprising 101 AMI patients and 66 age-matched healthy controls. The metallomic features include 12 essential elements (Ca, Co, Cu, Fe, K, Mg, Mn, Na, P, S, Se, Zn), 8 non-essential/toxic elements (Al, As, Ba, Cd, Cr, Ni, Rb, Sr, U, V), and 10 clinically relevant element-pair product/ratios (Ca/Mg, Ca×P, Cu/Se, Cu/Zn, Fe/Cu, P/Mg, Na/K, Zn/Se). Preliminary linear regression with feature selection confirmed smoking status as a predominant determinant for the non-essential/toxic elements, and revealed potential routes of action. Univariate assessments with adjustments for covariates revealed insights into the ambivalent relationships of Cu, Fe, and P with AMI, while also confirming cardioprotective associations of Se. Also, beyond their roles as risk factors, Cu and Se may be involved in the response mechanism in AMI onset/intervention, as demonstrated via longitudinal data analysis with 2 additional time-points (1-/6-month follow-up). Finally, based on both univariate tests and multivariate classification modelling, potentially more sensitive markers measured as element-pair ratios were identified (e.g., Cu/Se, Fe/Cu). Overall, metallomics-based biomarkers may have utility for AMI prediction.
Display omitted
•Comprehensive metallomics of 30 elements and product/ratios was conducted.•Ambivalent relationships of elements with acute myocardial infarction were revealed.•Cardioprotective role of Se in acute myocardial infarction was confirmed.•Divergent roles of elements as risk factors or specific markers were investigated.•Element-pair product/ratios may be more sensitive biomarkers than single elements.
Background: Despite its established significance in fibrotic cardiac remodeling, clinical benefits of global inhibition of TGF (transforming growth factor)-β1 signaling remain controversial. LRG1 ...(leucine-rich-α2 glycoprotein 1) is known to regulate endothelial TGFβ signaling. This study evaluated the role of LRG1 in cardiac fibrosis and its transcriptional regulatory network in cardiac fibroblasts. Methods: Pressure overload–induced heart failure was established by transverse aortic constriction. Western blot, quantitative reverse transcription polymerase chain reaction, immunofluorescence, and immunohistochemistry were used to evaluate the expression level and pattern of interested targets or pathology during fibrotic cardiac remodeling. Cardiac function was assessed by pressure-volume loop analysis. Results: LRG1 expression was significantly suppressed in left ventricle of mice with transverse aortic constriction–induced fibrotic cardiac remodeling (mean difference, −0.00085 95% CI, −0.0013 to −0.00043; P =0.005) and of patients with end-stage ischemic-dilated cardiomyopathy (mean difference, 0.13 95% CI, 0.012–0.25; P =0.032). More profound cardiac fibrosis (mean difference, −0.014% 95% CI, −0.029% to −0.00012%; P =0.048 for interstitial fibrosis; mean difference, −1.3 95% CI, −2.5 to −0.2; P =0.016 for perivascular fibrosis), worse cardiac dysfunction (mean difference, −2.5 ms 95% CI, −4.5 to −0.4 ms; P =0.016 for Tau-g; mean difference, 13% 95% CI, 2%–24%; P =0.016 for ejection fraction), and hyperactive TGFβ signaling in transverse aortic constriction–operated Lrg1 -deficient mice (mean difference, −0.27 95% CI, −0.47 to −0.07; P <0.001), which could be reversed by cardiac-specific Lrg1 delivery mediated by adeno-associated virus 9. Mechanistically, LRG1 inhibits cardiac fibroblast activation by competing with TGFβ1 for receptor binding, while PPAR (peroxisome proliferator-activated receptor)-β/δ and TGFβ1 collaboratively regulate LRG1 expression via SMRT (silencing mediator for retinoid and thyroid hormone receptor). We further demonstrated functional interactions between LRG1 and PPARβ/δ in cardiac fibroblast activation. Conclusions: Our results established a highly complex molecular network involving LRG1, TGFβ1, PPARβ/δ, and SMRT in regulating cardiac fibroblast activation and cardiac fibrosis. Targeting LRG1 or PPARβ/δ represents a promising strategy to control pathological cardiac remodeling in response to chronic pressure overload.
Immunological disease-related chronic cerebrospinal venous insufficiency (CCSVI) is rarely reported. This study aimed to analyze clinical characteristics, inflammation, and coagulation status in ...patients with immunological disease-related CCSVI.
Patients with CCSVI were enrolled from 2017 to 2019 and divided into three cohorts based on their immunological disease backgrounds, including groups with confirmed autoimmune disease, with suspected/subclinical autoimmune disease, and with non-immunological etiology. Immunological, inflammatory, and thrombophilia biomarker assay in blood samples were obtained. Mann-Whitney U test or Fisher's exact test was used to compare continuous variables or categorical variables between the CCSVI patients with or without the immunological etiology. Spearman's correlation analysis was conducted among age, baseline neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), interleukin-6 (IL-6), C-reactive protein (CRP), and neuron-specific enolase (NSE) in the three groups.
A total of 255 consecutive patients with CCSVI were enrolled, including three subgroups: CCSVI with confirmed autoimmune disease (n=41), CCSVI with suspected/subclinical autoimmune disease (n=116) and CCSVI with non-immunological etiology (n=98). In the first subgroup, a series of 41 cases was confirmed with eight different autoimmune diseases including antiphospholipid syndrome (n=18), Sjögren's syndrome (n=8), immunoglobulin G4-related disease (n=7), Behçet's disease (n=2), autoimmune hepatitis (n=2), Wegener's granulomatosis (n=2), systemic sclerosis (n=1) and AQP4 antibody-positive neuromyelitis optica spectrum disorder (n=1). Groups with immunological etiology did not show a higher incidence of thrombophilia or increased pro-inflammatory biomarkers (e.g., neutrophil, IL-6). However, patients with non-immunological etiology had a higher baseline level of CRP. Additionally, baseline PLR was moderately correlated to NLR and CRP in CCSVI patients with non-immunological etiology and suspected/subclinical autoimmune disease.
The formation of CCSVI may be based on the inflammatory process, facilitated by multiple risk factors, among which medical history of immunological diseases may play a significant role due to the intricate relationship between inflammation and coagulation. Moreover, CCSVI may also cause an independent inflammatory injury in venous walls, leading to focal stenosis or thrombus, without attacks from autoimmune antibodies.
Silent information regulator 2 (SIR2) in histone deacetylase (HDAC) is particularly conserved and widely expressed in all eukaryotic cells. HDAC is a crucial post-translational modification protein ...regulating gene expression. In the present study, a Toxoplasma gondii (T. gondii) silent information regulator 2 (TgSIR2) gene in HDAC was cloned and the modulation effects of recombinant TgSIR2 (rTgSIR2) on murine Ana-1 macrophages were characterized in vitro. The results indicated that rTgSIR2 had a good capacity to eliminate T. gondii by promoting proliferation, apoptosis, and phagocytosis, and modulating the secretion of nitric oxide (NO), pro-inflammatory cytokines, and anti-inflammatory cytokines. In in vivo experiments, animals were immunized with recombinant TgSIR2, followed by a lethal dose of T. gondii RH strain challenge 14 days after the second immunization. As compared to the blank and control group, the animals immunized with rTgSIR2 could generate specific humoral responses, as demonstrated by the significantly high titers of total IgG and subclasses IgG1 and IgG2a. Significant increases of IFN-γ, IL-4, and IL-10 were seen, while no significant changes were detected in IL-17. The percentage of CD4+ and CD8+ T lymphocytes in animals immunized with rTgSIR2 significantly increased. A significantly long survival time was also observed in animals vaccinated with rTgSIR2 14 days after the last immunization. All these results clearly indicate that rTgSIR2 played an essential role in modulating host macrophages and offered the potential to develop a therapeutic strategy against T. gondii.
Display omitted
•Recombinant TgSIR2 can modulate the functions of murine macrophages in vitro.•Recombinant TgSIR2 can induce the release of pro-inflammatory and anti-inflammatory cytokines from macrophages in vitro.•Recombinant TgSIR2 can upregulate CD4+ and CD8+ T lymphocytes in vivo.•Recombinant TgSIR2 can provide immune protection against acute T. gondii infection in vivo.
The regulatory effect of luteolin on the progression of Alzheimer's disease (AD) remains unclear from the perspective of apoptosis. The present study aimed to investigate the protective effects of ...luteolin against A
-induced cell apoptosis in pheochromocytoma (PC-12) cells. A
was used to induce an in vitro model of AD. Estradiol was used as a positive control. The PC-12 cells were incubated with luteolin alone or in combination with fulvestrant or U0126. The results showed that luteolin treatment significantly prevents A
-induced decrease in cell viability and inhibits A
-induced cell apoptosis. After the addition of fulvestrant and U0126, the apoptosis rate of PC-12 cells increased significantly. In addition, luteolin treatment significantly upregulated the expression of Bcl-2 and downregulated the expression of Bax and caspase-3, whereas fulvestrant and U0126 partially reversed the effects of luteolin. Moreover, luteolin treatment upregulated the expression of ER
and p-ERK1/2, whereas fulvestrant blocked the expression of p-ERK1/2. The study showed that luteolin could activate the ER/ERK/MAPK signalling pathway to protect PC-12 cells against A
-induced cell apoptosis via selectively acting on ER
. Thus, luteolin may be considered as a potential novel therapeutic strategy for AD.
PDF
![Sulfur‐Doped Quintuple [9]H...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0044-8249/small "Sulfur‐Doped Quintuple [9]Helicene with Azacorannulene as Core")
