Patient-derived xenograft (PDX) models provide a promising preclinical platform for hepatocellular carcinoma (HCC). However, the molecular features associated with successful engraftment of PDX models have not been revealed.HCC tumor samples from 76 patients were implanted in immunodeficient mice. The molecular expression was evaluated by immunohistochemistry. Patient and tumor characteristics as well as tumor molecular expressions were compared for PDX engraftment using the Chi-square test. The independent prediction parameters were identified by logistic regression analyses.The engraftment rate for PDX models from patients with HCC was 39.47% (30/76). Tumors from younger patients and patients with elevated preoperative alpha-fetoprotein level had higher engraftment rates. Tumors with poor differentiation and vascular invasion were related to engraftment success. The positive expression of CK19, CD133, glypican-3 (GPC3), and Ki67 in tumor samples was associated with engraftment success. Logistic regression analyses indicated that GPC3 and Ki67 were two of the strongest predictors of PDX engraftment. Tumors with GPC3/Ki67 phenotypes showed heterogeneous engraftment rates, with 71.9% in GPC3+/Ki67+ tumors, 30.8% in GPC3-/Ki67+ tumors, 15.0% in GPC3+/Ki67- tumors, and 0 in GPC3-/Ki67- tumors.Successful engraftment of HCC PDXs was significantly related to molecular features. Tumors with the GPC3+/Ki67+ phenotype were the most likely to successfully establish HCC PDXs.
The present study was to investigate antitumor effects of Extract from Cruciferous Vegetables 6320 (isothiocyanate, basically). In vitro, MTT assay, cell morphological changes, cell growth curve were used to observe the inhibitory effects of Extract 6320 on tumor cells. Cell cycle and apoptosis were analyzed by flow cytometry. In vivo, the antitumor effect of Extract 6320 was evaluated by observation of growth inhibition of B16 melanoma inoculated into mice. The results suggest that Extract 6320 can obviously inhibit the growth and proliferation of tumor cells in vitro and in vivo, induce apoptosis of B16 cells, but Extract 6320 have side effects on immunologic system possibly.
Abstract Primary systemic amyloidosis (PSA) is a systemic disease caused by amyloid deposition in various tissues and organs. In the early stages of the disease, approximately 40% of patients have skin damage, which may be the only clinical manifestation. This report described the case of a 67-year-old male with PSA who presented with characteristic cutaneous manifestations. Physical examination showed seborrheic keratotic-like plaques around the orbit, purpura and ecchymosis on the neck and dorsum manus, as well as nail dystrophy. An auxiliary examination indicated a 24-h urine protein content of 2.89 g, and serum immunoelectrophoresis showed a monoclonal λ light chain. Echocardiography showed decreased left ventricular diastolic function and mild pulmonary hypertension. The dermoscopic features were multiple comedo-like openings and milia-like cysts. Histopathology showed multiple keratinous cysts in the dermis and eosinophilic, acellular, homogenous material in the dermis that was Congo red-positive. The diagnosis was confirmed through biopsy of skin lesions and kidney.Skin lesions of this case are rare.Skin lesions around the orbit need to arouse the vigilance of dermatologists. PSA should be considered if the patient with multisystemic symptoms.Skin biopsy and Congo red staining were very important for early diagnosis of PSA.
Under stress conditions, Hog1 is required for cell survival through transiently phosphorylating downstream targets and reprogramming gene expression. Here, we report that Candida glabrata Hog1 (CgHog1) interacts with and phosphorylates CgRds2, a zinc cluster transcription factor, in response to osmotic stress. Additionally, we found that deletion of CgRDS2 led to decreases in cell growth and cell survival by 23.4% and 39.6%, respectively, at 1.5 M NaCl, compared with levels of the wild-type strain. This is attributed to significant downregulation of the expression levels of glycerophospholipid metabolism genes. As a result, the content of total glycerophospholipid decreased by 30.3%. Membrane integrity also decreased 47.6% in the Cgrds2Δ strain at 1.5 M NaCl. In contrast, overexpression of CgRDS2 increased the cell growth and cell survival by 10.2% and 6.3%, respectively, owing to a significant increase in the total glycerophospholipid content and increased membrane integrity by 27.2% and 12.1%, respectively, at 1.5 M NaCl, compared with levels for the wild-type strain. However, a strain in which the CgRDS2 gene encodes the replacement of Ser64 and Thr97 residues with alanines (Cgrds22A ), harboring a CgRds2 protein that was not phosphorylated by CgHog1, failed to promote glycerophospholipid metabolism and membrane integrity at 1.5 M NaCl. Thus, the above results demonstrate that CgHog1-mediated CgRds2 phosphorylation enhanced glycerophospholipid composition and membrane integrity to resist osmotic stress in C. glabrataIMPORTANCE This study explored the role of CgHog1-mediated CgRds2 phosphorylation in response to osmotic stress in Candida glabrataCgHog1 interacts with and phosphorylates CgRds2, a zinc cluster transcription factor, under osmotic stress. Phosphorylated CgRds2 plays an important role in increasing glycerophospholipid composition and membrane integrity, thereby enhancing cell growth and survival.
Abstract Background BRAF V600E mutation has high specificity in diagnosing papillary thyroid cancer (PTC) in benign cytological thyroid nodules. However, to avoid overdiagnosis and overtreatment, the BRAF V600E mutation detection was un-practical and not required immediately in benign cytology. A definitive diagnosis to distinguish positive BRAF V600E mutation in benign cytological results is desperately needed. Our objective was to identify the clinical characteristics associated with positive BRAF V600E mutation in cytologically benign thyroid nodules, which would allow to screen patients who may benefit from BRAF V600E mutation testing and further surgical intervention. Methods We analysis the clinical characteristics correlated with BRAF V600E mutation in our detection cohort, including 204 patients with 217 thyroid nodules, and separate analyses were performed in benign cytology and in patients with thyroid imaging reporting and data system (TI-RADS) classification 4a. Differential expression genes between positive and negative BRAF V600E mutation groups and older and younger age groups were assessed in Asian patients with thyroid cancer from the Cancer Genome Atlas (TCGA) dataset, and the association of age and BRAF V600E mutation with immune response were also evaluated. Results BRAF V600E mutations is a risk factor in screening malignancy in benign cytological classification, furthermore, the positive BRAF V600E mutation frequency was higher in patients older than 50 years (p = 0.0012) of cytologically benign thyroid nodules. Similarly, the positive BRAF V600E mutation was associated with patients age in TI-RADS classification 4a (p < 0.001), which ultrasound features could not provided predictive information for BRAF V600E mutation detection. BRAF V600E mutations as a risk factor for malignancy, had upregulated in advanced pathological T stage (p < 0.001) and N stage (p < 0.001) in TCGA-THCA cohort. And in thyroid nodules, BRAF V600E mutation was significantly associated with Ultrasound classification (p < 0.001) and fine needle aspiration (FNA) category (p < 0.001). Conclusions BRAF V600E mutation is an accurate adjunctive diagnostic marker on FNA to screen malignancy. In benign cytology, patients older than 50 years are more likely to have positive BRAF V600E mutation, which may associate with immune response and have higher risk of malignancy. Thus, the BRAF V600E mutation detection and further surgery should be strengthened in older patients with benign cytologically thyroid nodules.
AbstractBackground: This study aimed to investigate the association between multimorbidity and frailty, and the potential mediating role of depressive symptoms in Chinese middle-aged and older community-dwelling adults. Methods: We selected a total of 5232 adults with two or more chronic diseases from the China Health and Retirement Longitudinal Study (CHARLS) database. Clusters of participants with similar multimorbidity patterns were identified through fuzzy c-means cluster analyses. The cross-sectional association between multimorbidity and frailty was measured through logistic regression analyses. Mediation analysis was applied to examine direct and indirect associations within the counterfactual framework. Results: At baseline, we identified five multimorbidity patterns. Two of these patterns significantly increased the risk of frailty compared to a non-specific pattern. Depression mediated 35.20% of the effect of multimorbidity on frailty (p = 0.042). Notably, in adults aged 60 years and older, this mediation accounted for 69.84% of the total effect, surpassing the direct impact of multimorbidity on frailty. Among individuals with economic support (0.020, 95% CI: 0.002-0.040), high school education (0.062, 95% CI: 0.007-0.120), and no alcohol consumption (0.024, 95% CI: 0.003-0.050), depression entirely mediated the impact of comorbidities. Conclusions: This study reveals strong links between specific multimorbidity patterns and physical frailty, with depression significantly mediating these effects, particularly in certain populations. Findings emphasize tailored mental health interventions' necessity in specific groups. Trial registration：The data was extracted from China Health and Retirement Longitudinal Study (CHARLS). The ethical approval number of CHARLS is IRB00001052-11015.
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