A biomimetic nanogel with tumor microenvironment responsive property is developed for the combinatorial antitumor effects of chemotherapy and immunotherapy. Nanogels are formulated with hydroxypropyl-β-cyclodextrin acrylate and two opposite charged chitosan derivatives for entrapping anticancer drug paclitaxel and precisely controlling the pH responsive capability, respectively. The nanogel supported erythrocyte membrane can achieve "nanosponge" property for delivering immunotherapeutic agent interleukin-2 without reducing the bioactivity. By responsively releasing drugs in tumor microenvironment, the nanogels significantly enhanced antitumor activity with improved drug penetration, induction of calreticulin exposure, and increased antitumor immunity. The tumor microenvironment is remodeled by the combination of these drugs in low dosage, as evidenced by the promoted infiltration of immune effector cells and reduction of immunosuppressive factors.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Introduction: In ischemia-reperfusion acute kidney injury (AKI) interleukin-8 (IL8) attracts neutrophils to the site of injury. Neutrophils interact with the damaged endothelium triggering the pro-inflammatory response that prolongs the underperfused state of the kidney and exacerbates injury. Hypothesis: We tested the hypothesis that intravenous transfusion of rat aortic endothelial cells (ECs) transduced with IL8 receptors (IL8RA/RB-ECs) ameliorates renal dysfunction and promotes structural recovery of the kidney post AKI. Methods and Results: Male Sprague-Dawley rats were subjected to sham surgery or AKI by clamping the left renal artery for 45 min and removing the right kidney. At time of reperfusion, 1.5x10 6 IL8RA/RB-ECs, ECs with empty adenoviral vector (AdNull-ECs), or vehicle were infused in the femoral vein. At 24 hrs after AKI, serum creatinine increased ~ 10 fold in the vehicle-treated group and then decreased towards baseline. IL8RA/RB-ECs but not AdNull-ECs significantly blunted the rise in serum creatinine (Fig) and decreased the local expression in the kidney and the circulating levels of inflammatory mediators at 24 hrs after AKI. At 6 wks after AKI, vehicle-treated rats had significant albuminuria compared to sham controls and EC treatment decreased albuminuria by ~65% (Fig). Stained kidney sections at 6 wks after AKI showed that vehicle-treated rats had increased interstitial collagen and decreased capillary density compared to sham controls. IL-8RA/RB-ECs were more effective at reducing interstitial collagen staining than AdNull-ECs. IL8RA/RB-ECs but not AdNull-ECs increased capillary density compared to vehicle (Fig). Conclusions: Following ischemia-reperfusion AKI, ECs equipped with IL8 receptors are attracted to the site of injury in order to inhibit inflammation, accelerate tissue repair, and preserve renal function. Our innovative cell-based strategy holds promise for improving outcomes after AKI.
Background: The changes before and after fluid resuscitation in patients with septic shock and their relationship with prognosis have rarely been reported. Objectives: We aimed to observe the correlation between pulmonary vascular permeability index (PVPI), shock index (SI), and severity of septic shock. Methods: This case-control study retrospectively analyzed the clinical data of 154 patients with septic shock treated at our hospital (Weifang, China) from October 2016 to October 2018. They were divided into a survival group or a death group according to the 28-day prognosis. Univariate analysis was performed for vital signs, the acute physiology and chronic health evaluation II (APACHE-II) score, the sequential organ failure assessment (SOFA) score at admission, SI at admission (SI1), SI at 3 h after fluid resuscitation (SI2), PVPI at admission (PVPI1), PVPI at 3 h after fluid resuscitation (PVPI2), and lactate clearance rate (LCR). The correlations of PVPI and SI with the APACHE-II score, SOFA score, and LCR were analyzed by plotting the receiver operating characteristic curves. Results: Among the 154 cases, 70 survived after 28 days and 84 died. We observed that SI1, SI2, PVPI1, PVPI2, APACHE-II score, and SOFA score were significantly lower in the survival group than in the death group, while LCR was significantly higher (P < 0.05). Also, SI1, SI2, PVPI1, and PVPI2 were positively correlated with APSCHE-II and SOFA scores of patients with septic shock, but negatively correlated with LCR (P < 0.05). Moreover, SI2 predicted the prognosis of patients with septic shock significantly better than SI1, PVPI1, and PVPI2 did. When SI2 was 1.22, the Youden index was 0.822, the sensitivity was 91.23%, the specificity was 89.47%, the positive predictive value was 0.912, and the negative predictive value was 0.924. The positive and negative likelihood ratios were 0.897 and 0.375, respectively. Conclusions: Based on the study, SI after fluid resuscitation was more valuable for evaluating the prognosis of patients with septic shock than SI at admission, as well as PVPI values at admission and after fluid resuscitation.
Objective
To evaluate the applicability of several estimated glomerular filtration rate (eGFR) prediction equations in patients with renal cell carcinoma, and analyze the related factors.
Methods
A total of 132 patients with renal cell carcinoma were collected in the Department of Urology of the First Affiliated Hospital of Bengbu Medical College from January 2017 to December 2018. Serum creatinine, age, sex, body mass index(BMI), complications and T stage were recorded before operation. Base on the standard result by dectecting exogenous radioactive marker technetium-99m diethylenetriamine penta-acetic acid (99mTc-DTPA), the following eight equations were evaluated with Bland-Altman analysis: modified MDRD-1, modified MDRD-2, CKD-EPI equation, combined SCr and cystatin C equation, Cockcroft-Gault (CG) equation, cystatin C-based equation 1, cystatin C-based equation 2 and simplified MDRD equation. And the influencing factors on these eight equations were analyzed by univariate analysis.
Results
Compared with the 95% consistency analysis of the eight formulas based on rGFR, the two formulas related to cystatin C underestimated the actual level of GFR, and the other six formulas overestimated the actual level of GFR in different ranges. The three formulas with smaller deviation were CKD-EPI(7.74), combined creatinine cystatin(7.87) and modified MDRD-1(7.98). The three formulas with the lowest percentage out of boundaries were improved MDRD-2(1.98%), improved MDRD-1(2.48%) and C-G formulas(2.97%). The formula with the greatest deviation was improved MDRD-2(22.22). The effects of sex, age, BMI, T stage and complications on the predictive formula were analyzed by univariate analysis. The results showed that there was no significant difference in the results of the eight methods in different sex, BMI and T stages of renal cancer patients(all P values>0.05). Except for cystatin C-1 and cystatin C-2, the results of the other six methods were different in different age groups. The eGFR value decreased with the increase of age, and the difference was statistically significant (all P values<0.05). Similar to the results, except for cystatin C-1 and cystatin C-2, the results of the other six calculation methods in the patients with complications were significantly lower than those in the patients without complications, and the difference was statistically significant (all P values<0.05).
Conclusions
CKD-EPI, creatinine cystatin and modified MDRD-1 are better for evaluating the applicability of renal cancer patients. The factors affecting the accuracy of eGFR are various. The age of patients and the presence of complications have a greater impact on the consistency of the prediction formula.
Key words:
Kidney function tests; Glomerular filtration rate; Prediction equation; Renal cell carcinoma; Applicability
The reductase domains of neuronal NOS, endothelial NOS and two constitutive nitric oxide synthase (cNOS) share higher sequence similarity (>60%). In order to evaluate the role of ferredoxin‑NADP+ reductase (FNR) module in adjusting NOS catalytic activities, chimeras were by interchanging the FNR‑like module between endothelial NOS and neuronal NOS in the present study. The assays of steady‑state enzymatic activities for cytochrome c and ferricyanide reduction, NO synthesis and NADPH oxidation were performed spectrophotometrically. The two NOS FNR modules transferred their ferricyanide reductase character to the chimera enzymes. Results showed that the FNR module was important in adjusting electrons flow through the reductase domain and out of the FMN module. Results indicated that the FNR module was critical in controlling the electron transfer capacities of the FMN module.
Probiotics can colonize both the human and animal bodies and consist of active microorganisms that are beneficial to health. The use of probiotics has been shown to alleviate certain neurological diseases and disturbances in gut microbiota resulting from chronic ethanol exposure. Research indicates that probiotics can influence the nervous system via the microbial-gut-brain axis, wherein extracellular vesicles secreted by the gut microbiota play a significant role in this process. In this study, we first established a 30-day ethanol exposure and probiotic gavage mouse model, both of which influenced behavior and the composition of gut microbiota. We then extracted gut microbiota-derived extracellular vesicles from the feces of these model mice and injected them into new mice via the tail vein to assess the role of each set of extracellular vesicles. The results indicated that the extracellular vesicles derived from the intestinal microbiota in the ethanol group induced anxiety-like behavior and hippocampal neuroinflammation in the recipient mice. In contrast, the extracellular vesicles secreted by the gut microbiota from the probiotic group mitigated the anxiety-like behavior and neuroinflammation induced by ethanol-influenced extracellular vesicles. Our study demonstrates that extracellular vesicles secreted by the gut microbiota can influence the nervous system via the microbial-gut-brain axis. Furthermore, we found that the extracellular vesicles secreted by the gut microbiota from the probiotic group exert a beneficial therapeutic effect on anxiety and hippocampal neuroinflammation.
The purpose of this study was to evaluate the clinicopathological features of different degrees of extraglomerular renal vascular lesions (RVLs) in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis and explore their clinical determinants. This is a retrospective study of 186 patients with ANCA-associated renal vasculitis diagnosed at the First Affiliated Hospital of Zhengzhou University from January 2014 to April 2019. The patients who met the inclusion criteria were divided into non-renal RVLs, mild RVLs, moderate RVLs, and severe RVLs. It was found that there were significant differences in serum creatinine (SCR), estimated glomerular filtration rate (eGFR), erythrocyte sedimentation rate (ESR), high-density lipoprotein (HDL), systolic blood pressure (SBP), the prevalence rate of hypertension, the proportion of normal glomeruli, and the proportion of sclerotic glomeruli and interstitial fibrosis integral. SCR and ESR are independent risk factors for RVLs. The participants were followed up for 1 year, and the progression to end-stage renal disease (ESRD) and death was defined as endpoint events. We found that the survival rate of patients without RVLs was significantly higher than that of patients with RVLs and that the RVLs were an independent risk factor for ESRD or death. Early intervention in the progression of RVLs can improve the prognosis.
The microbiota-gut-brain axis, especially the microbial tryptophan (Trp) biosynthesis and metabolism pathway (MiTBamp), may play a critical role in the pathogenesis of major depressive disorder (MDD). However, studies on the MiTBamp in MDD are lacking. The aim of the present study was to analyze the gut microbiota composition and the MiTBamp in MDD patients.We performed shotgun metagenomic sequencing of stool samples from 26 MDD patients and 29 healthy controls (HCs). In addition to the microbiota community and the MiTBamp analyses, we also built a classification based on the Random Forests (RF) and Boruta algorithm to identify the gut microbiota as biomarkers for MDD.The Bacteroidetes abundance was strongly reduced whereas that of Actinobacteria was significantly increased in the MDD patients compared with the abundance in the HCs. Most noteworthy, the MDD patients had increased levels of Bifidobacterium, which is commonly used as a probiotic. Four Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K01817, K11358, K01626, K01667) abundances in the MiTBamp were significantly lower in the MDD group. Furthermore, we found a negative correlation between the K01626 abundance and the HAMD scores in the MDD group. Finally, RF classification at the genus level can achieve an area under the receiver operating characteristic curve of 0.890.The present findings enabled a better understanding of the changes in gut microbiota and the related Trp pathway in MDD. Alterations of the gut microbiota may have the potential as biomarkers for distinguishing MDD patients form HCs.
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