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Pharmacokinetics, pharmacology, and toxicology are the major determinants of the success or failure of candidates during drug development. Because inappropriate pharmacokinetics often leads to inefficacy, even toxicity, pharmacokinetics studies have been regarded as crucial components in drug preclinical and clinical research. However, new data increasingly reveal that drug concentrations in plasma or tissues cannot totally explain the efficacy of drug on the target organ. For most drugs that interact with targets localized in cells, intracellular penetration, accumulation, distribution, and elimination are important parameters governing the efficacy in the target cells. So, there is a pressing need to clarify the cellular pharmacokinetics and thus evaluate the efficacy of drugs in the target cells. This review provides a general overview regarding current knowledge about cellular pharmacokinetics in some specific cells and also summarizes the factors that can influence cellular pharmacokinetics. It concludes by discussing potential strategies for optimizing cellular pharmacokinetics and advocating that global cellular pharmacokinetics studies be conducted in future research toward improving drug efficacy.

KNN-based crystals with ultrahigh piezoelectric coefficients (d33 = 1050 pC N−1, and d33* = 2290 pm V−1) were fabricated.

The long noncoding RNA HOTAIR promotes the development and progression of several tumors. Here, the clinical significance and role of HOTAIR in renal cell carcinoma (RCC) tumorigenesis were explored. The results showed that increased expression of HOTAIR predicted a poor prognosis of RCC after surgery. HOTAIR promoted RCC cell proliferation and growth in vitro and in vivo. The expressions of HOTAIR and Salvador homolog 1 (SAV1) were inversely correlated in clinical RCC samples. HOTAIR downregulated SAV1 by directly binding to the SAV1 protein and enhanced histone H3K27 methylation. Loss of function of SAV1 activated the Hippo pathway. HOTAIR could be a potential therapeutic target in RCC.

Berberine is a plant-derived compound used in traditional Chinese medicine, which has been shown to inhibit cell proliferation and migration in breast cancer. On the other hand, vasodilator-stimulated phosphoprotein (VASP) promotes actin filament elongation and cell migration. We previously showed that VASP is overexpressed in high-motility breast cancer cells. Here we investigated whether the anti-tumorigenic effects of berberine are mediated by binding VASP in basal-like breast cancer. Our results show that berberine suppresses proliferation and migration of MDA-MB-231 cells as well as tumor growth in MDA-MB-231 nude mouse xenografts. We also show that berberine binds to VASP, inducing changes in its secondary structure and inhibits actin polymerization. Our study reveals the mechanism underlying berberine's inhibition of cell proliferation and migration in basal-like breast cancer, highlighting the use of berberine as a potential adjuvant therapeutic agent.

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