Mongolian Medicine RuXian-I Treatment of Estrogen-Induced Mammary Gland Hyperplasia in Rats Related to TCTP Regulating Apoptosis.

Mongolian medicine RuXian-I is composed of 30 Mongolian herbs, which is a traditional Mongolian recipe for clinical treatment of breast "Qi Su Bu Ri Le Du Sen" disease (hyperplasia of mammary glands, HMG). Based on the previous study, this dissertation further explores the therapeutic mechanism of RuXian-I on estrogen-induced HMG in rats. RuXian-I had no effect on the body weight and food intake of HMG rats and had no toxic effects on the five organs (heart, lung, spleen, and kidney).

CKLF1 Aggravates Focal Cerebral Ischemia Injury at Early Stage Partly by Modulating Microglia/Macrophage Toward M1 Polarization Through CCR4.

CKLF1 is a chemokine with increased expression in ischemic brain, and targeting CKLF1 has shown therapeutic effects in cerebral ischemia model. Microglia/macrophage polarization is a mechanism involved in poststroke injury expansion. Considering the quick and obvious response of CKLF1 and expeditious evolution of stroke lesions, we focused on the effects of CKLF1 on microglial/macrophage polarization at early stage of ischemic stroke (IS).

The major effective components in Shengmai Formula interact with sodium taurocholate co-transporting polypeptide.

Background: Shengmai Formula (SMF) is widely used to treat cardiovascular disease such as chronic heart disease, coronary atherosclerotic heart disease, viral myocarditis, and others. Our previous studies have shown that OATP1B1/1B3 mediates the interactions between ophiopogon D and ginsenoside Rb1/Rd, which are the major active components in SMF. The herb-drug interactions that involve sodium taurocholate co-transporting polypeptide (NTCP) have been drawing increasing amounts of attention.

Pros and Cons of Clinically Relevant Methods to Assess Pain in Rodents.

The primary objective of preclinical pain research is to improve the treatment of pain. Decades of research using pain-evoked tests has revealed much about mechanisms but failed to deliver new treatments. Evoked pain-tests are often limited because they ignore spontaneous pain and motor or disruptive side effects confound interpretation of results.

A genome-wide association study of sodium levels and drug metabolism in an epilepsy cohort treated with carbamazepine and oxcarbazepine.

Objective: To ascertain the clinical and genetic factors contributing to carbamazepine- and oxcarbazepine-induced hyponatremia (COIH), and to carbamazepine (CBZ) metabolism, in a retrospectively collected, cross-sectional cohort of people with epilepsy.

Methods: We collected data on serum sodium levels and antiepileptic drug levels in people with epilepsy attending a tertiary epilepsy center while on treatment with CBZ or OXC. We defined hyponatremia as Na+ ≤134 mEq/L.

A Systems Pharmacology Approach for Identifying the Multiple Mechanisms of Action of the Wei Pi Xiao Decoction for the Treatment of Gastric Precancerous Lesions.

The Wei Pi Xiao (WPX) decoction, based on the theory of traditional Chinese medicine, has been widely used for the treatment of gastric precancerous lesions (GPL). Although WPX is known to be effective for the treatment of GPL, its active ingredients, cellular targets, and the precise molecular mechanism of action are not known. This study aimed to identify the multiple mechanisms of action of the WPX decoction in the treatment of GPL.

Procollagen C-Proteinase Enhancer 1 (PCPE-1) in Liver Fibrosis.

Fibrosis is characterized by excessive deposition of collagen and additional extracellular matrix (ECM) components in response to chronic injuries. Liver fibrosis often results from chronic hepatitis C virus infection and alcohol abuse that can deteriorate to cirrhosis and liver failure. Current noninvasive diagnostic methods of liver fibrosis are limited in their ability to detect and differentiate between early and intermediate stages of fibrosis.

Comparative Effectiveness of Two Tiotropium Formulations: A Retrospective Cohort Study.

The effectiveness of the tiotropium Respimat formulation in routine clinical practice is still an open issue due to concern about the generalizability of the Tiotropium Safety and Performance in Respimat (TIOSPIR) trial findings. Our aim was to compare the incidence of acute respiratory events between new users of tiotropium Respimat and HandiHaler. The study population comprised patients aged ≥45 years resident in two Italian regions who received a first tiotropium prescription (HandiHaler or Respimat) between 1 July 2011 and 30 November 2013.

Gamma oscillations in somatosensory cortex recruit prefrontal and descending serotonergic pathways in aversion and nociception.

In humans, gamma-band oscillations in the primary somatosensory cortex (S1) correlate with subjective pain perception. However, functional contributions to pain and the nature of underlying circuits are unclear. Here we report that gamma oscillations, but not other rhythms, are specifically strengthened independently of any motor component in the S1 cortex of mice during nociception.

MiR-378 modulates energy imbalance and apoptosis of mitochondria induced by doxorubicin.

Doxorubicin (DOX) is an effective anticancer drug, however its clinical application is limited due to its cardiotoxicity. Therefore, understanding the mechanisms of cardiotoxicity induced by DOX is essential. We found that the level of miR-378 was decreased in the hearts of DOX-treated rats.

Effect of panaxytriol on cytochrome P450 3A4 via the pregnane X receptor regulatory pathway.

Panaxytriol (PXT) is one of the major effective components of red ginseng and Shenmai injection. The present study aimed to explore the effect of PXT on cytochrome P450 3A4 (CYP3A4) based on the pregnane X receptor (PXR)-CYP3A4 regulatory pathway in HepG2 cells and hPXR-overexpressing HepG2 cells treated with PXT for different time periods using quantitative polymerase chain reaction, Western blot, and dual-luciferase reporter gene assays. PXT could upregulate the levels of PXR and CYP3A4 mRNA in HepG2 cells treated with PXT for 1 hr, with no impact on the expression of their protein levels.

OATP1B3 (699G>A) and CYP2C9*2, *3 significantly influenced the transport and metabolism of glibenclamide and glipizide.

Glibenclamide and glipizide show large substantial inter-individual variation in clinical efficacy, which may be resulted from the genetic differences of metabolic enzymes and transporters in individuals. This study purposed to investigate the effect of OATP1B3 and CYP2C9 genetic polymorphisms on the transport and metabolism of glibenclamide and glipizide in human. An LC-MS method was used to determine the uptake of glibenclamide and glipizide in OATP1B3, OATP1B3 (344T > G) and OATP1B3 (699G > A)-HEK293T cells and their metabolism in CYP2C9*1, *2 and *3 recombinase system.

Evaluation of antioxidant and antimicrobial potential of a novel Himalayan plant Reinwardtia indica dumort: Scientifically unexplored.

Reinwardtia indica (Lineceae) is a medicinal plant cultivated in the Himalayan region. It is effectively used in folk medicines for the treatment of various health complications. In the present study, the shade dried leaves and stem were extracted in three different solvents such as ethyl acetate, ethanol, and hydro-alcoholic.

Comprehensive Circular RNA Profiling Reveals the Regulatory Role of the CircRNA-0067835/miR-155 Pathway in Temporal Lobe Epilepsy.

Background/aims: Temporal lobe epilepsy (TLE) is the most common form of adult localization-related epilepsy that is accompanied by progressive etiopathology and high incidences of drug resistance. Circular RNAs (circRNAs) play important roles in fine-tuning gene expression, however, the expression profile and clinical significance of circRNAs in TLE remains unknown.

Methods: Circular RNA microarray was conducted to identify TLE-related circRNAs.

The Epidemiological Characteristics of Epilepsy in the Province of Khyber Pakhtunkhwa, Pakistan.

Previous studies have shown that Khyber Pakhtunkhwa, Pakistan has a high incidence of epilepsy and a high proportion of low socioeconomic background and high treatment gap. Considering the changes over the past 20 years little is known about the current epidemiological characteristics of epilepsy in Khyber Pakhtunkhwa, Pakistan. The current study was focused to find the impact of various contributing factors on the clinical response to anti-epileptic drugs in the KP population, Pakistan.

Epilepsy control with carbamazepine monotherapy from a genetic perspective.

Background: Ethnicity variation is one of the main factors that may affect drug response in clinical practice. As MTHFR gene affects different transcriptome and proteome which affect the clinical response of drugs. Purpose of the current study was to observe possible variations in plasma levels of carbamazepine monotherapy and seizures' control in Pakhtun population of Khyber Pakhtunkhwa (KP) in the context of MTHFR (C677T and A1298C) gene polymorphisms.

Constitutive androstane receptor weakens the induction of panaxytriol on CYP3A4 by repressing the activation of pregnane X receptor.

Nuclear receptors pregnane X receptor (PXR; NR1I2) and constitutive androstane receptor (CAR; NR1I3) play a vital role in regulating CYP3A4. Our previous studies have demonstrated that panaxytriol (PXT) upregulates the expression of CYP3A4 via the PXR regulatory pathway. This study aimed to explore how CAR mediates the regulation of CYP3A4 in the presence of PXT using HepG2 cell, hCAR-overexpressing HepG2 cell and hCAR-silenced HepG2 cell models.

Evaluation of a Potential Clinical Significant Drug-Drug Interaction between Digoxin and Bupropion in Cynomolgus Monkeys.

Purpose: A three-period digoxin-bupropion drug-drug interaction study was performed in cynomolgus monkeys to assess the effect of bupropion and its metabolites on digoxin disposition.

Methods: Monkeys were administered either an i.v.

Tissue and organ decellularization in regenerative medicine.

The advancement and improvement in decellularization methods can be attributed to the increasing demand for tissues and organs for transplantation. Decellularized tissues and organs, which are free of cells and genetic materials while retaining the complex ultrastructure of the extracellular matrix (ECM), can serve as scaffolds to subsequently embed cells for transplantation. They have the potential to mimic the native physiology of the targeted anatomic site.

Peripheral Kappa Opioid Receptor Signaling Takes on a Central Role.

With the current unmet demand for effective analgesics and the opioid crisis, pain relief without major central adverse effects is highly appealing. In this issue of Neuron, Snyder et al. (2018) report on the localization, functions, and therapeutic potential of kappa opioid receptors in peripheral sensory neurons.

Ginsenoside Rb1 and Rd Remarkably Inhibited the Hepatic Uptake of Ophiopogonin D in Shenmai Injection Mediated by OATPs/oatps.

Shenmai injection (SMI) is derived from traditional Chinese herbal prescription Shendong yin and widely used for treating cardiovascular diseases. Ophiopogonin D (OPD) is one of the main active components of SMI. The hepatic uptake of OPD is mediated by organic anion-transporting polypeptides (OATPs/oatps) and inhibited by some other components in SMI.

Potential roles of brain barrier dysfunctions in the early stage of Alzheimer's disease.

Though Alzheimer's disease (AD) has been studied for more than a century, to date, no drug has provided a definitive cure. The slow development of the disease and the time lag between pathological changes and the appearance of symptoms make AD difficult to diagnose and result in a missed window of opportunity for effective treatment. Currently, there is still no effective treatment for the late stage of AD, though delayed onset or attenuation of symptoms is possible in the early stages of the disease.

Multiple-Condition Analysis in a Retrievable Subcutaneous Animal Model for Drug Screening on Full Pancreatic Tissue Digest.

In vitro in vivo