Effects of home medication review on drug-related problems and health-related quality of life among community-dwelling older adults in China.

BACKGROUND: There is a lack of research on the nature of drug-related problems (DRPs) in older adult communities in China and the impact of home medication review on DRP reduction and health-related quality-of-life (HRQoL) improvement. OBJECTIVES: To identify and categorize DRPs in older adults in China and to assess the impact of home medication review. METHODS: The prospective study was conducted in 2 community health service centers in Shanghai, China from December 2018 to December 2019. Eligible patients received a home medication review by a clinical pharmacist to assess for DRPs and adherence, propose pharmaceutical interventions, and measure outcomes of HRQoL. All enrolled patients were followed up for 3 months. RESULTS: Medication use in 412 patients was analyzed. A total of 362 DRPs were identified, an average of 0.88 per patient. Treatment effectiveness was the primary DRP type (249; 68.8%). The most common causes of DRPs were patient-related (35.1%) and drug selection (31.0%). Pharmacists made 733 interventions, an average of 2 per DRP. A total of 82.1% of these interventions were accepted. At a 3-month follow-up, home medication review led to a statistically significant reduction in the mean number of DRPs (0.4 vs. 0.88, P < 0.001) and an increase in medication adherence (1.42 vs. 0.85, P < 0.001). Both HRQoL indicators also improved, EuroQol 5 Dimension scale (0.75 vs. 0.78, P < 0.001) and EuroQol-visual analog scale (70 vs. 77.65, P < 0.001). CONCLUSION: Home medication review is a practical means to optimize drug therapy and improve patients' HRQoL in community settings.

Drug-related problems among community-dwelling elderly with ischemic stroke in China.

BACKGROUND: Ischemic stroke incidence is increasing amongst elderly patients in China; this is closely associated with drug-related problems (DRPs). OBJECTIVES: To evaluate the influencing factors of DRPs among elderly patients with a history of ischemic stroke in the Chinese community and the role clinical pharmacists play in providing solutions. MATERIAL AND METHODS: This study was conducted in 2 community health service centers in Putuo District, Shanghai, China, between December 2018 and June 2019. Demographics and clinical characteristics of the 130 selected patients were collected. Drug-related problems were classified using the Pharmaceutical Care Network Europe (PCNE)-DRP V8.03 classification system. The number, types, causes, interventions, and status of DRPs were then analyzed. RESULTS: The average number of DRPs per patient was 1.3, corresponding to 256 causes. "Treatment effectiveness P1" was identified as the most common problem (75.0%). The main causes were "drug selection C1" (33.2%) and "patient-related C7" (30.9%). Antihypertensive drugs, statins, aspirin, and Chinese patent medicines were the top 4 drugs for DRPs. Age, unintentional medication discrepancy and medication compliance were independent predictors of DRPs. Pharmacists provided 339 interventions, mainly "at drug level I3" (38.9%) and "at patient level I2" (30.7%). Most of the interventions (85.5%) were accepted by the patients and 65.9% of the problems were solved. CONCLUSIONS: The number, types and etiology of DRPs in elderly patients with ischemic stroke in our community are diverse and treatment effectiveness is the main cause of their occurrence. Clinical pharmacists play an important role in providing interventions for major causes of DRPs.

A mechanism-based fluorescent probe for labeling O6-methylguanine-DNA methyltransferase in live cells.

A mechanism-based small molecular fluorescent probe has been developed to label active O(6)-methylguanine-DNA methyltransferase in live cells.

5k, a novel ß-O-demethyl-epipodophyllotoxin analogue, inhibits the proliferation of cancer cells in vitro and in vivo via the induction of G2 arrest and apoptosis.

Etoposide (VP-16), a topoisomerase II (Topo II) inhibitor, has been widely used to treat malignancies. Its clinical application, however, has been hindered by the rise of acquired multidrug resistance (MDR). Here, we report that 4ß-{[4-(pyrrolidin-1-ylmethyl)phenyl]amino}-4'-O-Demethyl-4-Epipodophyllotoxin (5k), a novel ß-O-demethyl-epipodophyllotoxin analogue, possesses higher antitumor activity than its parent compound (VP-16) in a panel of various human tumor cell lines. More importantly, it was also effective against MDR cells both in vitro and in vivo. Using a KB/VCR MDR tumor xenograft model that overexpresses P-gp, 5k (2.5 mg/kg) exhibited a 2.4-fold higher growth inhibition rate versus VP-16 (5 mg/kg). In contrast, 5k and VP-16 displayed similar antitumor activities in a KB tumor xenograft model. Molecular and cellular mechanism studies revealed that 5k targeted Topo II by trapping DNA-Topo II cleavage complexes that could directly cause DNA damage. There were two distinct cellular responses to DNA damage elicited by the treatment with 5k: at low concentrations (20-80 nM), mitotic entry was arrested through the suppression of the activity of Cyclin B1/Cdc 2 complexes via the ATM/ATR signaling pathway; at high concentrations (1.25-5.00 µM), 5k-induced apoptotic signaling was mediated by the mitochondrial death pathways. Collectively, these data demonstrate the potential value of 5k as an antitumor drug candidate that should be further developed.

SMT-A07, a 3-(Indol-2-yl) indazole derivative, induces apoptosis of leukemia cells in vitro.

N-(2-(1H-indazol-3-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-4-chloro-N-methylbenzamide (SMT-A07) is a novel 3-(Indol-2-yl) indazole derivative. The anticancer activities in vitro and the cell apoptosis-induction abilities of SMT-A07 on human leukemia HL60 and NB4 cell lines were investigated in this study. The results of MTT assay showed SMT-A07 was a potential and highly efficient antitumor compound with IC(50) values ranging from 0.09 to 1.19 µM in five leukemia cell lines. SMT-A07 treatment for 24 h caused the increment of apoptosis rate from 6.88 to 49.72% in HL60 cells and from 8.72 to 56.28% in NB4 cells by flow cytometry analysis. Agarose gel electrophoresis showed DNA fragmentation that appeared after cells were exposed to SMT-A07. After SMT-A07 incubation, DAPI staining revealed the presence of DNA fragmentation, and perinuclear apoptotic body. SMT-A07 also resulted in a loss of ΔΨm in both HL60 and NB4 cells by JC-1 staining. Moreover, apoptosis-related proteins were examined by western blotting to explore the mechanism of its cytotoxicity. SMT-A07 exposure caused down-regulation and cleavage of procaspase-8, procaspase-3, Bid, PARP and up-regulation of cleaved caspase-8, cleaved caspase-3, PARP (Cleaved Fragment). In addition, the presence of pan-caspase inhibitor BOC-D-FMK prevented cells from caspase-3 activation, PARP cleavage, and subsequent apoptosis. Our study demonstrates that SMT-A07 displays an apparent antitumor activity with extensive anti-leukemia spectrum, and SMT-A07 can induce the apoptosis of HL60 and NB4 cells activation of the caspase cascade, which deserves further development.

Design and synthesis of a highly selective fluorescent turn-on probe for thiol bioimaging in living cells.

A new fluorescent turn-on probe for the rapid optical sensing of thiols has been designed and synthesized. The probe displays high on/off signal ratios and high selectivity towards thiols. The potential of the probe as a biosensor for thiols was demonstrated by imaging of thiols in living cells.

Paris saponin VII extracted from Trillium tschonoskii induces autophagy and apoptosis in NSCLC cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Trillium tschonoskii Maxim, a perennial herb of the Trilliaceae, has been widely used to treat inflammation, hypertension and cancer. We investigated Paris saponin VII's (PS VII), isolated from Trillium tschonoskii Maxim, function in mediating autophagy and apoptosis in NSCLC cells. MATERIALS AND METHODS: We treated various NSCLC cells with different concentrations of PS Ⅶ and then measure the cell apoptosis by using flow cytometry assays and western blot. Autophagy were investigated by using western blot, transmission electron microscopy and immunofluorescence analysis. We also use a xenograft model of nude mice to measure the effect of PS Ⅶ in vivo. RESULTS: Treatment with PS Ⅶ significantly inhibit NSCLC cell growth, especially for A549 (IC50 = 1.53 µM). Moreover, PS VII induces caspase-dependent apoptosis and autophagy through AMPK-ULK1 pathway. After blocking autophagy by 3-methyladenine (3-MA), PS VII induced cell death was significantly increased. In vivo, the co-treatment with PS VII and 3-MA dramatically inhibited A549 tumor growth in immune deficient mice and has similar inhibition rates as cisplatin group. CONCLUSION: Our results suggest that a combination of PS VII and autophagy inhibitor may be a potential anticancer strategy in the NSCLC therapy.

GL3, a Novel 4ß-Anilino-4'-O-Demethyl-4-Desoxypodophyllotoxin Analog, Traps Topoisomerase II Cleavage Complexes and Exerts Anticancer Activities.

A novel VP-16 derivative, 4ß-[N -(4‴-acetyloxyl-phenyl-1‴-carbonyl)-4″-aminoanilino]-4'-O-demethyl-4-desoxypodophyllotoxin (GL3), displayed a wide range of cytotoxicity in a panel of human tumor cell lines, with half-maximal inhibitory concentration (IC(50)) values ranging from 0.82 to 4.88 µM, much less than that of VP-16 (4.18-39.43 µM). Importantly, GL3 induces more significant apoptosis and cell cycle arrest than VP-16. The molecular and cellular machinery studies showed that GL3 functions as a topoisomerase II (Top 2) poison through direct binding to the enzyme, and the advanced cell-killing activities of GL3 were ascribed to its potent effects on trapping Top 2-DNA cleavage complex, Moreover, GL3-triggered DNA double-strand breaks and apoptotic cell death were in a Top 2-dependent manner, because the catalytic inhibitor aclarubicin attenuated these biologic consequences caused by Top 2 poisoning in GL3-treated cells. Taken together, among a series of 4ß-anilino-4'-O-demethyl-4-desoxypodophyllotoxin analog, GL3 stood out by its improved anticancer activity and well-defined Top 2 poisoning mechanisms, which merited the potential value of GL3 as an anticancer lead compound/drug candidate deserving further development.

Synthesis and in vitro cytotoxic evaluation of some thiazolylbenzimidazole derivatives.

A novel kind of thiazolylbenzimidazole derivatives were designed and synthesized and evaluated for their antitumor activity against SMMC-7721 and A549 cell lines. Most compounds showed good antitumor activities, and compound 11b displayed remarkable in vitro anticancer activity comparable to taxol. The preliminary structure-activity relationship of these benzimidazole derivatives was discussed based on the experimental data obtained.

Novel 4 beta-anilino-podophyllotoxin derivatives: design synthesis and biological evaluation as potent DNA-topoisomerase II poisons and anti-MDR agents.

A new series of 4 beta-anilino-podophyllotoxin analogs have been designed, synthesized and evaluated their bioactivities as novel DNA-topoisomerase II poisons as well as P-glycoprotein (P-gp)-dependent multidrug resistance (MDR) inhibitors. The new compounds show improved potency and efficacy with respect to the parent molecule etoposide (VP-16), one of the semisynthetic derivatives of podophyllotoxin. The treatment of 5k-n in KB/VCR cells caused G(2)/M phase arrest and finally induced apoptosis. Furthermore, molecular docking is applied to testify that 5k-n could not be the substrates of P-gp, which is consistent with the result of MDR1 and P-glycoprotein express tests. The most potent compound 5n is chosen for in vivo studies, the administration of 5n was effective in treatment of cancer with a lower dose than VP-16 in drug-sensitive xenograft model and drug-resistant xenograft model. Compound 5n is a potential drug candidate for anticancer chemotherapy.