An Improved PDE6D Inhibitor Combines with Sildenafil To Inhibit Mutant Cancer Cell Growth.

The trafficking chaperone PDE6D (or PDEδ) was proposed as a surrogate target for K-Ras, leading to the development of a series of inhibitors that block its prenyl binding pocket. These inhibitors suffered from low solubility and suspected off-target effects, preventing their clinical development. Here, we developed a highly soluble, low nanomolar PDE6D inhibitor (PDE6Di), Deltaflexin3, which has the lowest off-target activity as compared to three prominent reference compounds.

Bacterial contamination of multi-use tear drops, gels, and ointments.

Purpose: This study aimed to investigate the bacterial contamination of multi-use tear drops, gels, and ointments that patients use at home.

Method: A total of 271 multi-use containers used by 168 patients were examined. Conjunctival culture samples were obtained from patients who used tear drops, gels, and ointments that were found to be contaminated.

Percutaneous revision of dysfunctional shunts in patients who underwent intrahepatic portosystemic shunt procedure via percutaneous or conventional method: 11-years single center experience.

Background And Aim: Our primary objective is to report the results of the ultrasound (US)-guided revision technique of transhepatic shunt in patients in whom intrahepatic portosystemic shunt was created by the percutaneous or conventional route. Our secondary objective is to investigate whether there is an association between the indication for a portosystemic shunt and the need for post-shunt revision.

Methods: Data from 117 consecutive patients who had a transjugular intrahepatic portosystemic shunt placed percutaneously or conventionally were extracted from hospital electronic medical records and examined those who underwent revision within 11 years and those who did not.

Eliminating oncogenic RAS: back to the future at the drawing board.

RAS drug development has made enormous strides in the past ten years, with the first direct KRAS inhibitor being approved in 2021. However, despite the clinical success of covalent KRAS-G12C inhibitors, we are immediately confronted with resistances as commonly found with targeted drugs. Previously believed to be undruggable due to its lack of obvious druggable pockets, a couple of new approaches to hit this much feared oncogene have now been carved out.

Traditional Medicine (Mahuang-Tang) Improves Ovarian Dysfunction and the Regulation of Steroidogenic Genes in Letrozole-Induced PCOS Rats.

Ethnopharmacological Relevance: Mahuang-Tang (MHT) has traditionally been used in Asia to treat a variety of diseases, such as fever without sweating, joint pain, lower back pain, asthma, and gynecological conditions. Polycystic ovary syndrome (PCOS) is a kind of gynecological disease that causes amenorrhea, infertility, and menopausal and urogenital disorders that could benefit from MHT treatment.

Aim Of The Study: In this study, we examined the effects of MHT on ovarian hormones and steroidogenic enzymes in female PCOS rats.

Curcumae Radix Extract Decreases Mammary Tumor-Derived Lung Metastasis via Suppression of C-C Chemokine Receptor Type 7 Expression.

Curcumae radix is the dry root of (turmeric) that can be used either as a spice or traditional medicine. The aim of this study was to investigate the survival benefits and the anti-metastatic activity of curcumae radix extract (CRE) in MCF7 cells and in MMTV-PyMT transgenic mice-a mouse model of breast cancer metastasis. In vitro wound scratch assay revealed that CRE treatment inhibited cell motility and cell migration in a dose-dependent manner.

Dietary intake of genistein suppresses hepatocellular carcinoma through AMPK-mediated apoptosis and anti-inflammation.

Background: Women have a lower risk of hepatocellular carcinoma (HCC) than men, and the decreased possibility of HCC in women is thought to depend on estrogen levels. As a soybean-isoflavone product, genistein has estrogenic activity in various reproductive tissues, because it mimics 17β-estradiol and binds the estrogen receptor. Though genistein is a known liver cancer suppressor, its effects have not been studies in long-term experiment, where genistein is fed to a female animal model of HCC.

Loss of progesterone receptor membrane component 1 promotes hepatic steatosis via the induced de novo lipogenesis.

Non-alcoholic fatty liver disease (NAFLD) results from triglyceride accumulation within the liver and some of them advances to non-alcoholic steatohepatitis (NASH). It is important to note that in NAFLD development, hepatic de novo lipogenesis (DNL) derives from excess carbohydrates and fats under a condition of excess energy through β-oxidation. As a main regulator for DNL, sterol regulatory element-binding protein 1 (Srebp-1) forms complex with progesterone receptor membrane component 1 (Pgrmc1).

Upregulation of multi drug resistance genes in doxorubicin resistant human acute myelogeneous leukemia cells and reversal of the resistance.

The major problem in the treatment of acute myeloid leukemia (AML) patients results from multidrug resistance to administered anticancer agents. Drug resistance proteins, MDR1 and MRP1, which work as drug efflux pumps, can mediate the multidrug resistance of human leukemia cells. In this study, the mechanisms of resistance to doxorubicin-induced cell death in human HL60 AML cells were examined.

Identification of polymorphisms on the MDR1 gene among Turkish population and their effects on multidrug resistance in acute leukemia patients.

Multidrug-resistance (MDR) phenotype is a serious limitation to the effective chemotherapeutic treatment of many cancer types, including leukemia. One of the most important proteins, the over-expression of which is responsible for the multidrug-resistance phenotype in many cancer types, is P-glycoprotein. This protein is the product of the MDR1 gene.