<i>Spilanthes filicaulis</i> (Schumach. & Thonn.) C.D. Adams leaves protects against streptozotocin-induced diabetic nephropathy

by Oluwafemi Adeleke Ojo, Akingbolabo Daniel Ogunlakin, Christopher Oloruntoba Akintayo, Olaoluwa Sesan Olukiran, Juliana Bunmi Adetunji, Omolola Adenike Ajayi-Odoko, Theophilus Oghenenyoreme Ogwa, Olorunfemi Raphael Molehin, Omolara Olajumoke Ojo, Ramzi A. Mothana, Abdullah R. Alanzi

Background and objective

Diabetic neuropathy (DN) is a complex type of diabetes. The underlying cause of diabetic nephropathy remains unclear and may be due to a variety of pathological conditions resulting in kidney failure. This study examines the protective effect of the methanolic extract of Spilanthes filicaulis leaves (MESFL) in fructose-fed streptozotocin (STZ)-induced diabetic nephropathy and the associated pathway.

Methods

Twenty-five rats were equally divided randomly into five categories: Control (C), diabetic control, diabetic + metformin (100 mg/kg), diabetic + MESFL 150 mg/kg bw, and diabetic + MESFL 300 mg/kg bw. After 15 days, the rats were evaluated for fasting blood glucose (FBG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea, uric acid, serum creatinine, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (MDA). Gene expression levels of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response element-binding (CREB), cFOS and the antiapoptotic protein Bcl-2 were examined.

Results

We observed that MESFL at 150 and 300 mg/kg bw significantly downregulated the protein expression of cAMP, PKA, CREB, and cFOS and upregulated the Bcl-2 gene, suggesting that the nephroprotective action of MESFL is due to the suppression of the cAMP/PKA/CREB/cFOS signaling pathway. In addition, MESFL increases SOD and CAT activities and GSH levels, reduces MDA levels, and reduces renal functional indices (ALP, urea, uric acid, and creatinine).

Conclusion

Therefore, our results indicate that MESFL alleviates the development of diabetic nephropathy via suppression of the cAMP/PKA/CREB/cFOS pathways.

CTIVA: Censored time interval variable analysis

by Insoo Kim, Junhee Seok, Yoojoong Kim

Traditionally, datasets with multiple censored time-to-events have not been utilized in multivariate analysis because of their high level of complexity. In this paper, we propose the Censored Time Interval Analysis (CTIVA) method to address this issue. It estimates the joint probability distribution of actual event times in the censored dataset by implementing a statistical probability density estimation technique on the dataset. Based on the acquired event time, CTIVA investigates variables correlated with the interval time of events via statistical tests. The proposed method handles both categorical and continuous variables simultaneously—thus, it is suitable for application on real-world censored time-to-event datasets, which include both categorical and continuous variables. CTIVA outperforms traditional censored time-to-event data handling methods by 5% on simulation data. The average area under the curve (AUC) of the proposed method on the simulation dataset exceeds 0.9 under various conditions. Further, CTIVA yields novel results on National Sample Cohort Demo (NSCD) and proteasome inhibitor bortezomib dataset, a real-world censored time-to-event dataset of medical history of beneficiaries provided by the National Health Insurance Sharing Service (NHISS) and National Center for Biotechnology Information (NCBI). We believe that the development of CTIVA is a milestone in the investigation of variables correlated with interval time of events in presence of censoring.