Ischemia-reperfusion- (IR-) induced kidney injury is difficult to avoid during renal transplantation and robot-assisted partial nephrectomy. Renal IR injury is characterized by tubular damage, microcirculation failure, and inflammation, which coordinately augment renal injury; however, no specific treatment is available for these conditions. Protease-activated receptor-1 (PAR-1) and its ligand, thrombin, are involved in coagulation and were shown to be associated with epithelial cell injury. Here, we hypothesized that PAR-1 exaggerated renal IR-induced tubular cell damage and microcirculation failure and that pharmacological inhibition of PAR-1 by Q94 could prevent these injuries. Renal warm IR increased the expression of PAR-1 in the renal tubules. Q94 attenuated renal IR-induced changes and histopathological damage. Microcirculation failure analyzed by congestion in the histopathology and blood cell flow examined by intravital multiphoton microscopy were suppressed by Q94 treatment. Q94 also dramatically increased tubular cell proliferation despite the lower renal damage. Thrombin suppressed cell proliferation and induced apoptosis in the tubules; these effects were prevented by Q94 treatment. Taken together, PAR-1 was associated with renal IR injury. Inhibition of PAR-1 ameliorated injury possibly by improving renal microcirculation and tubular cell survival/proliferation.
Assessing knee joint orientation changes after SMO may help clinical advancement in managing patients with ipsilateral ankle and knee joint arthritis. However, knee joint changes after supramalleolar osteotomy (SMO) have not been reported. We investigated changes in coronal alignment of the knee joint after SMO.
In this multicentre study, from January 2014 to December 2018, 47 ankles with varus osteoarthritis treated with SMO were retrospectively identified. Ankle joint changes were assessed using the tibiotalar angle, talar tilt angle, and lateral distal tibial angle (LDTA); knee joint changes using the medial proximal tibial angle (MPTA), medial and lateral joint space widths (mJSW and lJSW, respectively), and medial and lateral joint line convergence angles (JLCA); and lower limb alignment changes using mechanical axis deviation angle (MADA) and the hip-knee-ankle (HKA) angle measured on full-length anteroposterior radiographs of the lower extremity. Correlation analysis and binary logistic regression s ankle joint varus deformity, followed by significant lower limb alignment changes. Despite meaningful changes in JLCA, the relationship between the amount of osteotomy near the ankle joint and improvement in knee joint radiographic parameters was not significant. Radiographic parameters of the knee joint would less likely be changed following SMO.Psoriasis is an inflammatory skin disease with substantial morbidity. Numerous patients with psoriasis experience recurrence after therapy. The underlying mechanism about psoriasis is still not fully understood. Some evidences suggest that innate immunity may play an unexpected and important role in active severe psoriasis. In this work, the deconvolution algorithm CIBERSORT was conducted to identify the infiltration of innate immune cells and related core genes in psoriatic plaque. Datasets from the Gene Expression Omnibus, including skin samples from 405 psoriasis patients and 91 healthy donors, were downloaded for analysis. Considerable differences of the innate immune cell composition were uncovered between psoriatic plaque and control skin. Results revealed that Ξ³Ξ΄ T cells, resting NK cells, M0 macrophages, M1 macrophages, activated dendritic cells, and neutrophils were significantly increased in psoriatic skin, while resting mast cells and active NK cells were significantly decreased. Vitamin A aldehyde Moreover, the proportion of M0 macrophages or resting mast cells was found to be associated with disease severity. Spearman correlation analysis suggests that RORC and S100A12 genes were related to disease severity, while genes including S100A12, CLEC4C, IL-19, AIM2, IL-17F, and PPARGC1A were correlated with biologic treatment response. In conclusion, this work displays innate immune status in psoriatic skin and provides novel clues for clinical decisions and mechanism study.
Cancer of unknown primary (CUP) is a type of malignant tumor, which is histologically diagnosed as a metastatic carcinoma while the tissue-of-origin cannot be identified. CUP accounts for roughly 5% of all cancers. Traditional treatment for CUP is primarily broad-spectrum chemotherapy; however, the prognosis is relatively poor. Thus, it is of clinical importance to accurately infer the tissue-of-origin of CUP.
We developed a gradient boosting framework to trace tissue-of-origin of 20 types of solid tumors. Specifically, we downloaded the expression profiles of 20,501 genes for 7713 samples from The Cancer Genome Atlas (TCGA), which were used as the training data set. The RNA-seq data of 79 tumor samples from 6 cancer types with known origins were also downloaded from the Gene Expression Omnibus (GEO) for an independent data set.
400 genes were selected to train a gradient boosting model for identification of the primary site of the tumor. The overall 10-fold cross-validation accuracy of our method was 96.1% across 20 types of cancer, while the accuracy for the independent data set reached 83.5%.
Our gradient boosting framework was proven to be accurate in identifying tumor tissue-of-origin on both training data and independent testing data, which might be of practical usage.
Our gradient boosting framework was proven to be accurate in identifying tumor tissue-of-origin on both training data and independent testing data, which might be of practical usage.
This study is set out to determine the relationship between IL-32 and radiosensitivity of esophageal squamous cell carcinoma (ESCC).
Western blot was adopted for measuring IL-32 expression in Eca-109 and TE-10 cells. Eca-109 and TE-10 cells with interference or overexpression of IL-32 were treated with the presence or absence of X-ray irradiation. Then, the use of CCK8 assay was to detect proliferation ability, and effects of IL-32 expression on radiosensitivity of ESCC were tested by colony formation assay. The cell apoptosis was detected using flow cytometry. STAT3 and p-STAT expression, and apoptotic protein Bax were detected by western blot.
Colony formation assay and CCK8 assay showed that compared with the NC group without treatment, the growth of the ESCC cells, that is Eca-109 and TE-10, was significantly inhibited in the OE+IR group with highly expressed IL-32 and irradiation. In flow cytometry analysis, in Eca-109 and TE-10 cells, highly expressed IL-32 combined with irradiation significantly increased apoptosis compared with the control group.Vitamin A aldehyde
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