Combination of mathematics and label-free proteomics for discovering keratin-derived specific peptide biomarkers to distinguish animal horn-derived traditional Chinese medicines.

Saiga antelope horn and Rhinoceros horn have been used in traditional Chinese medicine for thousands of years. However, due to the protection of wildlife, the application of these rare animal horns has been restricted or prohibited. Therefore, water buffalo horn, goat horn, and yak horn have been applied as alternatives to Rhinoceros horn or Saiga antelope horn in a clinic. It is extremely difficult to distinguish normal animal horns in powdered or decocted form, especially identifying related species such as water buffalo horn, yak horn, and cattle horn. In this work, mathematics set and label-free proteomics analysis were combined for discovering keratin-derived specific peptide biomarkers. By using mathematics set analysis after nano liquid chromatography-tandem mass spectrometry-based proteomics, the selected species-specific peptides could be used to identify the authenticity of the Saiga antelope horn and goat horn. Furthermore, peptide biomarkers were selected to distinguish related species-derived horns, water buffalo horn, yak horn, and cattle horn. In total, eight peptide biomarkers were selected and applied for simultaneously distinguishing different horn samples. The present strategy provides a method for peptide biomarkers discovery and also has positive significance for ensuring the quality and efficacy of animal horn-derived traditional Chinese medicines and their products.

LACTB suppresses migration and invasion of glioblastoma via downregulating RHOC/Cofilin signaling pathway.

Glioblastoma (GBM) is the most malignant tumor in human brain. High invasiveness of this tumor is the main reason causing treatment failure and recurrence. Previous study has found that LACTB is a novel tumor suppressor in breast cancer. Moreover, the function of LACTB in other tumors and mechanisms involving LACTB were also reported. However, the role and relevant mechanisms of LACTB in GBM invasion remains to be revealed. Our aim is to investigate the role LACTB in GBM migration and invasion. We found that LACTB was downregulated in gliomas compared to normal brain tissues. Overexpression of LACTB suppressed migration and invasion of LN229 and U87 cell lines. Mechanistically, LACTB overexpression downregulated the mesenchymal markers. Moreover, LACTB overexpression downregulated the expression of RHOC and inhibited RHOC/Cofilin signaling pathway. The study suggests that LACTB suppresses migration and invasion of GBM cell lines via downregulating RHOC/Cofilin signaling pathway. These findings suggest that LACTB may be a potential treatment target of GBM.

IKIP downregulates THBS1/FAK signaling to suppress migration and invasion by glioblastoma cells.

Background: Inhibitor of NF-κB kinase-interacting protein (IKIP) is known to promote proliferation of glioblastoma (GBM) cells, but how it affects migration and invasion by those cells is unclear. Methods: We compared levels of IKIP between glioma tissues and normal brain tissue in clinical samples and public databases. We examined the effects of IKIP overexpression and knockdown on the migration and invasion of GBM using transwell and wound healing assays, and we compared the transcriptomes under these different conditions to identify the molecular mechanisms involved. Results: Based on data from our clinical samples and from public databases, IKIP was overexpressed in GBM tumors, and its expression level correlated inversely with survival. IKIP overexpression in GBM cells inhibited migration and invasion in transwell and wound healing assays, whereas IKIP knockdown exerted the opposite effects. IKIP overexpression in GBM cells that were injected into mouse brain promoted tumor growth but inhibited tumor invasion of surrounding tissue. The effects of IKIP were associated with downregulation of THBS1 mRNA and concomitant inhibition of THBS1/FAK signaling. Conclusions: IKIP inhibits THBS1/FAK signaling to suppress migration and invasion of GBM cells.

Determinants of acute and subacute case-fatality in elderly patients with hypertensive intracerebral hemorrhage.

Background: Given that limited reports have described the survival and risk factors for elderly patients with hypertensive intracerebral hemorrhage (HICH), we aimed to develop a valid but simple prediction nomogram for the survival of HICH patients. Methods: All elderly patients ≥65 years old who were diagnosed with HICH between January 2011 and December 2019 were identified. We performed the least absolute shrinkage and selection operator (Lasso) on the Cox regression model with the R package glmnet. A concordance index was performed to calculate the nomogram discrimination; and calibration curves and decision curves were graphically evaluated by depicting the observed rates against the probabilities predicted by the nomogram. Results: A total of 204 eligible patients were analyzed, and over 20 % of the population was above the age of 80 (65-79 years old, n = 161; 80+ years old, n = 43). A hematoma volume ≥13.64 cm3 was associated with higher 7-day mortality (OR = 6.773, 95 % CI = 2.622-19.481; p < 0.001) and higher 90-day mortality (OR = 3.955, 95 % CI = 1.611-10.090, p = 0.003). A GCS score between 13 and 15 at admission was associated with a 7-day favorable outcome (OR = 0.025, 95 % CI = 0.005-0.086; p < 0.001) and a 90-day favorable outcome (OR = 0.033, 95 % CI = 0.010-0.099; p < 0.001). Conclusions: Our nomogram models were visualized and accurate. Neurosurgeons could use them to assess the prognostic factors and provide advice to patients and their relatives.