Antiurolithiatic effect of triptonide in ethylene glycol-induced urolithiasis in rats.

Urolithiasis is one of the most prevalent benign urological disorders globally with a high incidence rate. Male Sprague-Dawley rats were chemically induced to have urolithiasis and treated with triptonide and the standard antiurolithic drug cystone. Kidney weight was measured to detect calculi formation, and urinary parameters such as pH, 24-h urine volume, and protein content were measured to analyze the urolithiasis induction in rats. The inorganic ions, organic solutes, antioxidant levels, and inflammatory cytokines were measured in the experimental rats. Triptonide treatment significantly modulated the urinary pH, decreased the protein concentration, and increased the urinary outflow in urolithiasis induced rats. It also significantly decreased the urinary excretion of calcium and phosphorous and increased the excretion of magnesium, potassium, sodium, creatinine, and uric acid. SOD, CAT, and GPx levels were increased in triptonide-treated rats, and it significantly reduced the MDA levels. Triptonide treatment also decreased the levels of inflammatory cytokines and prevented the renal tissue from inflammation. To conclude, our results prove that triptonide significantly prevents calculi formation and protects renal tissue from urolithiasis-induced damage in rats. Further studies may prove triptonide a potent alternative to currently available antiurolithic drugs.

Diagnosis of SPECT/CT bone imaging combined with two serum examinations in patients with bone metastases from pulmonary cancer.

PURPOSE: To study the clinical diagnostic value of SPECT/CT bone imaging combined with two serum examinations in patients with bone metastases from pulmonary cancer. METHODS: The clinical data of 120 patients consistent with pulmonary cancer admitted to the First Affiliated Hospital of Hebei North University from March 2019 to December 2019 were selected for retrospective analysis, and they were divided into the bone metastasis group (n = 58) and non-bone metastasis group (n = 62) according to comprehensive evaluation result of X-ray, CT, MRI and clinical follow-up. The CT values of patients were obtained by SPECT/CT bone imaging to compare serum levels of ALP (alkaline phosphatase belongs to phosphoric monoester hydrolases, as a specific phosphatase, mainly in body tissues and body fluid) and BAP (bone alkaline phosphatase is formed by different modification and processing of alkaline phosphatase, and is mainly released by osteoblasts) and CT values of patients in both groups, using receiver operating characteristic (ROC) curve to evaluate the diagnostic efficacy of single detection and combined detection. RESULTS: SPECT/CT bone imaging in patients with bone metastasis from pulmonary cancer showed abnormal radioactive accumulation in spine, pelvis and bilateral ribs. Serum ALP, BAP and CT values in bone metastasis group were overtly higher than the non-bone metastasis group (P < 0.001). Logistic regression analysis showed that serum ALP, BAP and CT value were independent risk factors for bone metastasis from pulmonary cancer. The AUC value and Youden index of combined diagnosis were higher than those of single diagnosis. CONCLUSION: SPECT/CT bone imaging combined with serum detection of ALP and BAP in patients with pulmonary cancer is helpful for early diagnosis of bone metastasis, which provides more basis for the formulation and selection of clinical treatment options.

Molecular PET/CT mapping of rhACE2 distribution and quantification in organs to aid in SARS-CoV-2 targeted therapy.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, poses a significant threat to public health. Angiotensin-converting enzyme 2 (ACE2) is a key receptor for SARS-CoV-2 infection. Recombinant human ACE2 (RhACE2), as a soluble supplement for human ACE2, can competitively block SARS-CoV-2 infection. In this study, a mouse organ in situ rhACE2 high aggregation model was constructed for the first time, and in vivo real-time positron emission tomography (PET) imaging of rhACE2 in the mouse model was performed using an ACE2-specific agent 68 Ga-HZ20. This radiotracer exhibits reliable radiochemical properties in vitro and maintains a high affinity for rhACE2 in vivo. In terms of probe uptake, 68 Ga-HZ20 showed a good target-to-nontarget ratio and was rapidly cleared from the circulatory system and excreted by the kidneys and urinary system. PET imaging with this radiotracer can noninvasively and accurately monitor the content and distribution of rhACE2 in the body, which clarifies that rhACE2 can aggregate in multiple organs, suggesting the preventive and therapeutic potential of rhACE2 for SARS-CoV-2 and COVID-19.

A model for predicting overall survival in bladder cancer patients with signet ring cell carcinoma: a population-based study.

INTRODUCTION: This study is to examine the predictors of survival and to construct a nomogram for predicting the overall survival (OS) of primary bladder signet ring cell carcinoma (SRCC) patients based on the analysis of the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: A total of 219 eligible patients diagnosed with SRCC were analyzed using the 2004-2015 data from SEER database. Univariate and multivariate Cox regression were used to determine independent prognostic factors, followed by development of a nomogram based on the multivariate Cox regression models. The consistency index (C-index), receiver operating characteristic (ROC) curve, and calibration curve were used to validate the prognostic nomogram. RESULTS: The nomograms indicated appreciable accuracy in predicting the OS, with C-index of 0.771 and 0.715, respectively. The area under the curve (AUC) of the nomogram was 0.713 for 1 year, 0.742 for 3 years, and 0.776 for 5 years in the training set, while was 0.730 for 1 year, 0.727 for 3 years, and 0.697 for 5 years in the validation set. The calibration curves revealed satisfactory consistency between the prediction of deviation correction and ideal reference line. CONCLUSIONS: The prognostic nomogram developed in the analytical data of SEER it provided high accuracy and reliability in predicting the survival outcomes of primary bladder SRCC patients and could be used to comprehensively assess the risk of SRCC. Moreover, they could enable clinicians to make more precise treatment decisions for primary bladder SRCC patients.

Urine PD-L1 is a tumor tissue candidate substitute and is associated with poor survival in muscle-invasive bladder cancer patients.

Programmed death molecule ligand 1 (PD-L1) expression in urothelial carcinoma is a predictive marker used to guide immunotherapy. As expression of PD-L1 may be heterogeneous in the tumor tissue space, it cannot be accurately determined by immunohistochemical analysis. In this study, we examined PD-L1 protein levels in preoperative urine samples from bladder cancer patients, evaluated the prevalence of PD-L1 in urine, examined the usefulness of urine as a surrogate for PD-L1 expression in tumors, and compared PD-L1 expression in postoperative pathological sections. We found that PD-L1 in urine and tumor tissue correlated well and that it may be able to some extent serve as a surrogate for tissues in bladder cancer and thus predict risk of recurrence in muscle-invasive bladder cancer (MIBC) patients. Our findings reveal the clinical relevance of urine PD-L1 as a noninvasive prognostic indicator for immunotherapy and offer clinical translational suggestions for eventual development of a prognostic model for immunotherapy for bladder cancer.

Effects of Different Organ Metastases on the Prognosis of Stage IV Urothelial Carcinoma of the Bladder.

Objective: To assess the prognosis of stage IV metastatic urinary bladder urothelial carcinoma (UBUC) at initial diagnosis and determine prognostic factors based on distant organ metastasis. Methods: A retrospective cohort analysis of UBUC was conducted based on the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression analyses were used to determine the variables associated with overall survival (OS). Kaplan-Meier curves were used to compare survival curves among different groups. Results: A total of 3103 patients with stage IV UBUC were selected for analysis. The number of distant organ metastatic sites independently predicted the OS. The OS was not different in other metastatic sites when bone metastasis was used as a reference (P > 0.05). However, the OS was shorter for a single metastatic site (P < 0.001) and multiple metastatic sites when metastasis was not used as a reference (P < 0.001). Multivariable Cox regression analysis indicated that low survivorship was independently associated with no surgery for the entire cohort and patients with only one metastatic organ. Sex (P = 0.019) and grade (P = 0.046) were the independent risk factors for patients with only one metastatic organ. Conclusions: These results show that the prognosis of stage IV metastatic UBUC is not different between any single metastatic organ. The prognosis of stage IV metastatic UBUC depends on the number of distant organ metastasis. This study determined some predictors of survival and thus may help therapists to choose appropriate treatment strategies for metastatic UBUC.

Suppressive function of bone marrow-derived mesenchymal stem cell-derived exosomal microRNA-187 in prostate cancer.

Application of bone marrow-derived mesenchymal stem cell-derived exosomes (BMSC-exos) in cancer treatment has been widely studied. Here, we elaborated the function of BMSC-exos containing microRNA-187 (miR-187) in prostate cancer. Differentially expressed miRs and genes were screened with microarray analysis. The relationship between CD276 and miR-187 in prostate cancer was evaluated. Following miR-187 mimic/inhibitor or CD276 overexpression transfection, their actions in prostate cancer cell biological processes were analyzed. Prostate cancer cells were then exposed to BMSC-exos that were treated with either miR-187 mimic/inhibitor or CD276 overexpression for pinpointing the in vitro and in vivo effects of exosomal miR-187. miR-187 was poorly expressed while CD276 was significantly upregulated in prostate cancer. Additionally, restoring miR-187 inhibited the prostate cancer cell malignant properties by targeting CD276. Upregulation of miR-187 led to declines in CD276 expression and the JAK3-STAT3-Slug signaling pathway. Next, BMSC-exos carrying miR-187 contributed to repressed cell malignant features as well as limited tumorigenicity and tumor metastasis. Collectively, this study demonstrated that BMSC-derived exosomal miR-187 restrained prostate cancer by reducing CD276/JAK3-STAT3-Slug axis.

The protective role of corilagin on renal calcium oxalate crystal-induced oxidative stress, inflammatory response, and apoptosis via PPAR-γ and PI3K/Akt pathway in rats.

Kidney stones, also known as calcium oxalate (CaOx) nephrolithiasis, are often asymptomatic, leading to kidney injury and renal failure complications. Corilagin is a gallotannin found in various plants and is known to elicit various biological activities. The present study aimed to elucidate the renoprotective effect of corilagin against the rats' renal stones deposition. The rats were induced for nephrolithiasis (CaOx deposition) using 0.75% ethylene glycol in their drinking water. Then, they were treated with corilagin at 50 and 100 mg/kg/day for 4 weeks. At the end of the experimental period, the rats were killed; blood and renal tissues were collected for various histological, biochemical, and gene expression analyses. The results demonstrated that the rats had renal calculi displaying a significant increase in serum creatinine (59.39 µmol/L) and blood urea nitrogen (19.03 mmol/L) levels compared with controls. Moreover, the malondialdehyde (13.29 nmol/mg) level was found to increase with a profound reduction in antioxidants' activities with upregulated inflammatory cytokines. In contrast, the RT-PCR and immunohistochemistry analysis demonstrated a substantial reduction in cell survival markers PPAR-γ and PI3K/Akt with an apparent increase in apoptosis markers genes expressions in rats suffering from renal stones. Thus, the present study results suggest that corilagin could suppress renal CaOx crystal-induced oxidative stress, inflammatory response, and apoptosis via PPAR-γ and PI3K/Akt-mediated pathway.

Thoracic manifestation of Wegener's granulomatosis: Computed tomography findings and analysis of misdiagnosis.

The aim of the present study was to investigate the computed tomography (CT) manifestations of Wegener granulomatosis (WG) in the chest and potential reasons for misdiagnosis. Conventional CT scans and clinical data of 45 patients with WG were retrospectively analyzed. Patients typically presented with multiple system involvement, primarily in the upper and lower respiratory tract. The incidence of thoracic involvement was 75.56% (34/45). Radiographic features were varied between cases in the present study, with the most common features being numerous cavitary nodules and masses in the lungs. Cavitations were usually irregular, with uneven wall thickness, partial centrality, fuzzy inner edges and piecemeal necrosis. These results indicate that WG typically has multiple system involvement, with the chest being most prominent. Multiple variable-sized cavitary nodules with irregular edges and piecemeal necrosis were the most notable features revealed using CT scanning; however, in order to give a definitive diagnosis, biopsies should be performed.

Design and discovery of 4-anilinoquinazoline-urea derivatives as dual TK inhibitors of EGFR and VEGFR-2.

EGFR and VEGFR-2 are involved in pathological disorders and the progression of different kinds of tumors, the combined blockade of EGFR and VEGFR signaling pathways appears to be an attractive approach to cancer therapy. In this work, a series of 4-anilinoquinazoline derivatives containing substituted diaryl urea or glycine methyl ester moiety were designed and identified as EGFR and VEGFR-2 dual inhibitors. Compounds 19i, 19j and 19l exhibited the most potent inhibitory activities against EGFR (IC50 = 1 nM, 78 nM and 51 nM, respectively) and VEGFR-2 (IC50 = 79 nM, 14 nM and 14 nM, respectively), they showed good antiproliferative activities as well. Molecular docking established the interaction of 19i with the DFG-out conformation of VEGFR-2, suggesting that they might be type II kinase inhibitors.

Design and discovery of 4-anilinoquinazoline-acylamino derivatives as EGFR and VEGFR-2 dual TK inhibitors.

Both EGFR and VEGFR-2 are important targets for cancer therapy, the combined inhibition of both EGFR and VEGFR-2 signaling pathway represents a promising approach to the treatment of cancers with a synergistic effect. In this study, a series of novel 4-anilinoquinazoline-acylamino derivatives designed as EGFR and VEGFR-2 dual inhibitors were synthesized and evaluated for biological activities. Most of them exhibited interesting inhibitory potencies against EGFR and VEGFR-2 as well as good antiproliferative activities. Compounds 15a, 15b and 15e exhibited the most potent inhibitory activity against EGFR (IC50 = 0.13 µM, 0.15 µM and 0.69 µM, respectively) and VEGFR-2 (IC50 = 0.56 µM, 1.81 µM and 0.87 µM, respectively), among them, compound 15b showed the highest antiproliferative activities against three cancer cell lines (HT-29, MCF-7 and H460) with IC50 of 5.27 µM, 4.41 µM and 11.95 µM, respectively. Molecular docking established the interaction of 15a with the DFG-out conformation of VEGFR-2, suggesting that they might be type II kinase inhibitors.