Slo1 deficiency impaired skeletal muscle regeneration and slow-twitch fibre formation.

Background: It has been observed that Slo1 knockout mice have reduced motor function, and people with certain Slo1 mutations have movement problems, but there is no answer whether the movement disorder is caused by the loss of Slo1 in the nervous system, or skeletal muscle, or both. Here, to ascertain in which tissues Slo1 functions to regulate motor function and offer deeper insight in treating related movement disorder, we generated skeletal muscle-specific Slo1 knockout mice, studied the functional changes in Slo1-deficient skeletal muscle and explored the underlying mechanism.

Methods: We used skeletal muscle-specific Slo1 knockout mice (Myf5-Cre; Slo1 mice, called CKO) as in vivo models to examine the role of Slo1 in muscle growth and muscle regeneration.

Paraquat is an agonist of STIM1 and increases intracellular calcium levels.

Paraquat (PQ) is an efficient herbicide but leads to high mortality with no antidote in mammals. PQ produces reactive oxygen species (ROS), leading to epithelial-mesenchymal transition (EMT) for pulmonary fibrosis in type II alveolar (AT II) cells. Intriguingly, strategies reducing ROS exhibit limited therapeutic effects, indicating other targets existing for PQ toxicity.

Paraquat but not diquat induces TGF-β expression and thus activates calcium-NFAT axis for epithelial-mesenchymal transition.

Paraquat (PQ) and diquat (DQ), two highly efficient herbicides sharing similar chemical backbone, both induce reactive oxygen species and are highly toxic to humans and livestock, however, PQ but not DQ poisoning result in pulmonary fibrosis, the leading cause of high mortality rate in patients suffering PQ toxicity. Understanding the unique mechanism of PQ different from DQ therefore would provide potential strategies to reduce PQ-induced pulmonary fibrosis. Here, we identified that PQ but not DQ continuously upregulates TGF-β expression in alveolar type II (AT II) cells.

Generation and Characterization of Cytochrome P450 2J3/10 CRISPR/Cas9 Knockout Rat Model.

Cytochrome P450 2J2 (CYP2J2) enzyme attracts more attention because it not only metabolizes clinical drugs but also mediates the biotransformation of important endogenous substances and the regulation of physiologic function. Although CYP2J2 is very important, few animal models are available to study its function In particular, a gene knockout (KO) rat model for drug metabolism and pharmacokinetics is not available. In this report, the CRISPR/Cas9 technology was used to delete rat , the orthologous genes of in humans.

Characterization of organic anion transporting polypeptide 1b2 knockout rats generated by CRISPR/Cas9: a novel model for drug transport and hyperbilirubinemia disease.

Organic anion transporting polypeptide 1B1 and 1B3 (OATP1B1/3) as important uptake transporters play a fundamental role in the transportation of exogenous drugs and endogenous substances into cells. Rat OATP1B2, encoded by the gene, is homologous to human OATP1B1/3. Although OATP1B1/3 is very important, few animal models can be used to study its properties.

Calcium Homeostasis: A Potential Vicious Cycle of Bone Metastasis in Breast Cancers.

Cancers have been considered as one of the most severe health problems in the world. Efforts to elucidate the cancer progression reveal the importance of bone metastasis for tumor malignancy, one of the leading causes for high mortality rate. Multiple cancers develop bone metastasis, from which breast cancers exhibit the highest rate and have been well-recognized.

Organic anion transport polypeptide 1b2 selectively affects the pharmacokinetic interaction between paclitaxel and sorafenib in rats.

Paclitaxel, a broad-spectrum antitumor drug, is widely used as a cytotoxic drug, while sorafenib as a multi-kinase inhibitor is a classic targeted drug. A number of clinical trials have combined paclitaxel and sorafenib for cancer treatment, with the expectation of better therapeutic effects. However, the toxicity and side effects in the treatment are significantly increased.

Diet-induced obese alters the expression and function of hepatic drug-metabolizing enzymes and transporters in rats.

Obesity increases the incidences of metabolic syndrome, including type 2 diabete, fatty liver, dyslipidemia, hyperglycemia, heart disease, hypertension and cancer. In particular, pharmacokinetics and pharmacodynamics of many drugs have changed in obese patients. However, little is known about the hepatic drug-metabolizing enzymes and transporters that are influenced by diet-induced obese.

Preclinical toxicology and toxicokinetic evaluation of ailanthone, a natural product against castration-resistant prostate cancer, in mice.

Ailanthone (AIL) has many biological activities including antimalarial, antiviral and anticancer. Our previous study also found that AIL targets p23 against castration-resistant prostate cancer. In this report, the preclinical safety of AIL was evaluated by acute toxicity, subacute toxicity and toxicokinetics in mice.

Development and Characterization of MDR1 () CRISPR/Cas9 Knockout Rat Model.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease (Cas9) technology is widely used as a tool for gene editing in rat genome site-specific engineering. Multidrug resistance 1 [MDR1 (also known as P-glycoprotein)] is a key efflux transporter that plays an important role not only in the transport of endogenous and exogenous substances, but also in tumor MDR. In this report, a novel MDR1 () double-knockout (KO) rat model was generated by the CRISPR/Cas9 system without any off-target effect detected.