s.Drug resistance is a major challenge in breast cancer (BC) treatment at present. Accumulating studies indicate that breast cancer stem cells (BCSCs) are responsible for the BC drugs resistance, causing relapse and metastasis in BC patients. Thus, BCSCs elimination could reverse drug resistance and improve drug efficacy to benefit BC patients. Consequently, mastering the knowledge on the proliferation, resistance mechanisms, and separation of BCSCs in BC therapy is extremely helpful for BCSCs-targeted therapeutic strategies. Herein, we summarize the principal BCSCs surface markers and signaling pathways, and list the BCSCs-related drug resistance mechanisms in chemotherapy (CT), endocrine therapy (ET), and targeted therapy (TT), and display therapeutic strategies for targeting BCSCs to reverse drug resistance in BC. Even more importantly, more attention should be paid to studies on BCSC-targeted strategies to overcome the drug resistant dilemma of clinical therapies in the future.Background Phenylephrine and atropine can cause serious adverse effects when applied in combination. We investigated the effect of phenylephrine eye drops combined with intravenous atropine on the cardiovascular system in patients under general anesthesia undergoing intraocular surgery. Methods The effects of the drugs were observed through clinical study. Thirteen patients undergoing intraocular surgery under general anesthesia were observed in this study; all were injected intravenously with atropine due to the oculocardiac reflex during surgery. To study the combination of drugs, an in vivo study was performed on rats. Seventy-two standard deviation rats that received phenylephrine eye drops and intravenous atropine treatment under general anesthesia were assessed, of which 18 treated with these drugs simultaneously were administered normal saline, neostigmine or esmolol. Blood pressure and heart rate were recorded and analyzed. Findings The age of the patients ranged from seven to 14 years old with an avelmic surgery, especially in patients with cardio-cerebrovascular diseases.Temporomandibular joint disorders (TMD) are a common health condition caused by the structural or functional disorders of masticatory muscles and the temporomandibular joint (TMJ). Abnormal mandibular movement in TMD patients may cause pain, chronic inflammation, and other discomfort, which could be relieved by a variety of drugs through various delivery systems. In this study, we summarized commonly used therapeutic agents in the management of TMD as well as novel bioactive molecules in preclinical stage and clinical trials. The emerging therapy strategies such as novel intra-TMJ delivery systems and implants based on tissue engineering are also discussed. This comprehensive review will strengthen our understanding of pharmacological approaches for TMD therapy.Berberine, a well-known alkaloid, has been proved to possess various pharmacological activities. Previous studies demonstrated that berberine could be extensively metabolized and the metabolites also contributed to its therapeutic effects. However, as for berberine's metabolites, especially phase II metabolites, pharmacokinetics and excretion studies were rarely reported. https://www.selleckchem.com/products/rmc-6236.html The objective of this study was to thoroughly investigate the pharmacokinetic and excretion profiles of berberine and its nine metabolites, namely, berberrubine (M1), demethyleneberberine (M2), jatrorrhizine (M3), jatrorrhizine-3-O-β-D-glucuronide (M4), jatrorrhizine-3-O-sulfate (M5), thalfendine-10-O-β-D-glucuronide (M6), berberrubine-9-O-β-D-glucuronide (M7), demethyleneberberine-2-O-sulfate (M8) and demethyleneberberine-2-O-β-D-glucuronide (M9) in rats. An accurate and reliable LC-MS/MS method was developed and validated for the determination of berberine and its nine metabolites in rat biosamples. Pharmacokinetic profiles of berberine an.Xianglian pill (XLP) is a typical traditional Chinese herbal medicine prescription composed of Coptidis Rhizoma and Aucklandiae Radix. It has been used to treat gastrointestinal disease for centuries. In the present study, the potential mechanisms of XLP in the treatment of ulcerative colitis (UC) were predicted by integrative pharmacology-based approach. Then, the main compounds of XLP were detected by liquid chromatography-mass spectrometry (LC-MS/MS). Finally, we verified the mechanism of XLP in the treatment of UC in a dextran sulfate sodium (DSS) model. C57BL/6 mice were randomly divided into the control group, DSS group, 5-aminosalicylic acid (5-ASA) group which was used as the positive drug control, XLP low, medium, and high dose group, with 10 mice per group. Except for the control group, acute colitis model was induced in the other mice by administering 3% DSS for consecutive 7 days. Mice in 5-ASA and XLP groups were administered with 5-ASA (50 mg/kg) or XLP (0.8, 1.6, 3.2 g/kg) via oral gavage once per day respectively. Body wight and disease activity index were assay during drug intervention. On day 8, all animals in this experiment were sacrificed and colon tissues were collected for analysis after measurement of the length. The results showed that XLP alleviate DSS -induced acute colitis in mice, including inhibition the secretion of pro-inflammatory cytokines, repairing the dysfunction of intestinal epithelial barrier, enhanced autophagy, and blocked the activation of PI3K/Akt/mTOR pathway. Furthermore, inhibiting autophagy by 3-methyladenine attenuated the protective effects of XLP on colitis. The underlying mechanism may be that Xianglian pill promote autophagy by blocking the activation of PI3K/Akt/mTOR signaling pathway.Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by fibroblast proliferation and extracellular matrix remodeling; however, the molecular mechanisms underlying its occurrence and development are not yet fully understood. Despite it having a variety of beneficial pharmacological activities, the effects of catalpol (CAT), which is extracted from Rehmannia glutinosa, in IPF are not known. In this study, the differentially expressed genes, proteins, and pathways of IPF in the Gene Expression Omnibus database were analyzed, and CAT was molecularly docked with the corresponding key proteins to screen its pharmacological targets, which were then verified using an animal model. The results show that collagen metabolism imbalance, inflammatory response, and epithelial-mesenchymal transition (EMT) are the core processes in IPF, and the TGF-β1/Smad3 and Wnt/β-catenin pathways are the key signaling pathways for the development of pulmonary fibrosis. Our results also suggest that CAT binds to TGF-βR1, Smad3, Wnt3a, and GSK-3β through hydrogen bonds, van der Waals bonds, and other interactions to downregulate the expression and phosphorylation of Smad3, Wnt3a, GSK-3β, and β-catenin, inhibit the expression of cytokines, and reduce the degree of oxidative stress in lung tissue.