Knockdown of FOXD3-AS1 attenuated reduction of cell survival and increase of LDH release, apoptosis, caspase-3/7 activity, and Bcl-2 associated X (Bax) expression induced by hypoxia in AC16 cells. Notably, we demonstrated that FOXD3-AS1 directly interacted with miR-150-5p to inhibit its expression. miR-150-5p knockdown reinforced the reduction of survival and induction of apoptosis by hypoxia and attenuated the effects of FOXD3-AS1 silencing on the same parameters in AC16 cells. In conclusion, FOXD3-AS1 knockdown protected AC16 cardiomyocytes from hypoxia-induced injury by increasing cell survival and inhibiting apoptosis through upregulating miR-150-5p.The key hormone of the renin-angiotensin system (RAS), angiotensin II (AngII), and thrombin are known to play major roles in the vascular system and its related disorders. Previous studies reported connections between AngII and thrombin in both physiological and pathophysiological models. However, the molecular mechanisms controlling such interplay at the level of their receptors belonging to the family of G protein-coupled receptors (GPCRs) are not fully understood. In this study, we investigated the functional interaction between the AngII type 1 receptor (AT1R) and the thrombin receptor [or protease-activated receptor 1 (PAR1)] in human embryonic kidney 293 (HEK293) cells. For this, we used various bioluminescence resonance energy transfer (BRET) proximity-based assays to profile the coupling to the heterotrimeric Gαq protein, β-arrestin recruitment, and receptor internalization and trafficking in intact cells. https://www.selleckchem.com/products/blu9931.html The overall dose-response and real-time kinetic BRET data demonstrated the specific molecular prallosteric modulation of AT1R and inhibition of its desensitization and internalization. This finding may constitute the molecular basis of the well-known interplay between RAS and thrombin. Thus, our data should lead to revising some findings on the implication of RAS and thrombin in vascular physiology and pathophysiology revealing the importance to consider the functional and pharmacological interaction between AT1R and thrombin receptors.Ectonucleoside triphosphate diphosphohydrolases (NTPDases) catalyze the hydrolysis of nucleoside tri- and di-phosphates to mono-phosphates. The products are subsequently hydrolyzed by ecto-5'-nucleotidase (ecto-5'-NT) to nucleosides. NTPDase inhibitors have potential as novel drugs, e.g., for the treatment of inflammation, neurodegenerative diseases, and cancer. In this context, a series of anthraquinone derivatives structurally related to the anthraquinone dye reactive blue-2 (RB-2) was synthesized and evaluated as inhibitors of human NTPDases utilizing a malachite green assay. We identified several potent and selective inhibitors of human NTPDase2 and -3. Among the most potent NTPDase2 inhibitors were 1-amino-4-(9-phenanthrylamino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (20, PSB-16131, IC50 of 539 nM) and 1-amino-4-(3-chloro-4-phenylsulfanyl)phenylamino-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (48, PSB-2020, IC50 of 551 nM). The most potent NTPDase3 inhibitors were 1-amino-4-[3-(4,6-dichlorotriazin-2-ylamino)-4-sulfophenylamino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (42, PSB-1011, IC50 of 390 nM) and 1-amino-4-(3-carboxy-4-hydroxyphenylamino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (33, PSB-2046, IC50 of 723 nM). The best NTPDase2 inhibitor 20 showed a non-competitive inhibition type, while the NTPDase3 inhibitor 42 behaved as a mixed-type inhibitor. These potent compounds were found to be selective vs. other NTPDases. They will be useful tools for studying the roles of NTPDase2 and -3 in physiology and under pathological conditions.
This study aimed to investigate the household medication-taking behavior and affordability of patients with chronic diseases in Gansu Province. As well as to propose suggestions to assist improvement of related policies.
A multistage stratified cluster sampling technique was used to select the research sites and households according to the WHO manual for the "Household Survey to Measure Access and Use of Medicines". The impact factors of medication-taking behavior were estimated using binary logistic regression models. Medication treatment affordability of hypertension patients was evaluated.
A total of 1,080 completed questionnaires were collected, in which 690 families reported to have chronic patients in their home. The total number of chronic disease patients were 915. About 93% of the patient reported scheduled medicine intake. Approximately 86.60% of patients with chronic medical conditions were able to adhere to the physicians' prescriptions. Age, gender, and the number of household chronic disease patients were the main factors influencing whether the patients take medication. Respondents' self-reported monthly expenditure on household medicine accounted for 16.95% of their total monthly expenditure. The total cost of irbesartan and valsartan for hypertension treatment was two-fold higher than the minimum daily wage of the families.
This study found that patients with chronic diseases have a high proportion of medication and medication compliance. However, family drug burden, especially for those living with hypertension are among the key challenges. Related policy needs to be revised to promote the affordability of medication under chronic conditions.
This study found that patients with chronic diseases have a high proportion of medication and medication compliance. However, family drug burden, especially for those living with hypertension are among the key challenges. Related policy needs to be revised to promote the affordability of medication under chronic conditions.
This study was designed to evaluate the efficacy of remote medication management of rivaroxaban by pharmacists for geriatric patients with nonvalvular atrial fibrillation during the COVID-19 pandemic.
A single-site, prospective cohort study was conducted among patients with non-valvular atrial fibrillation who received rivaroxaban therapy from July 2019 to December 2019. Patients in the pharmacist-led education and follow-up service (PEFS) group were managed remotely by a pharmacist. In contrast, those in the usual care (UC) group were managed by other providers. Data of routine blood tests, coagulation function tests, which also included cardiac function parameters were collected. The number and type of provider encounters, interventions related to rivaroxaban therapy, the occurrence of thromboembolism or bleeding, and the time of the first outpatient visit after discharge were recorded.
A total of 600 patients were recruited, and results of 381 patients were analyzed in the end, of which 179 patients roxaban could reduce bleeding complications of the gastrointestinal tract and skin ecchymosis and postpone the first outpatient revisit after discharge.
Remote pharmacist-led medication instruction of rivaroxaban could reduce bleeding complications of the gastrointestinal tract and skin ecchymosis and postpone the first outpatient revisit after discharge.Cellular senescence is an irreversible cell growth arrest and is associated with aging and age-related diseases. High plasma phosphate (Pi) and deficiency of Klotho contribute to aging and kidney fibrosis, a pathological feature in the aging kidney and chronic kidney disease. This study examined the interactive role of Pi and Klotho in kidney senescence and fibrosis. Homozygous Klotho hypomorphic mice had high plasma Pi, undetectable Klotho in plasma and kidney, high senescence with massive collagen accumulation in kidney tubules, and fibrin deposits in peritubular capillaries. To examine the Pi effect on kidney senescence, a high (2%) Pi diet was given to wild-type mice. One week of high dietary Pi mildly increased plasma Pi, and upregulated kidney p16/p21 expression, but did not significantly decrease Klotho. Two weeks of high Pi intake led to increase in plasminogen activator inhibitor (PAI)-1, and decrease in kidney Klotho, but still without detectable increase in kidney fibrosis. More prolonged dietary Pas kidney fibrosis.
Deprescribing has been recommended for managing polypharmacy but deprescribing preventive medication in older patients is still uncommon. We aimed to investigate older patients' barriers to and enablers of deprescribing cardiometabolicmedication.
Two focus groups were conducted among patients ≥70 years with polypharmacy, including cardiometabolic medication. Purposive sampling through four community pharmacies was used in two regions in the Netherlands. A topic list was developed using literature and the theoretical domains framework (TDF). The meetings were audio recorded, transcribed verbatim and coded using thematic coding, attribute coding and the TDF. In addition, patients were categorized on attitudes towards medication and willingness to stop.
The meetings were attended by 17 patients and 1 caregiver (71 to 84 years). In total 15 barriers and 13 enablers were identified within four themes, partly related to beliefs, fears and experiences regarding using or stopping medication, and partly related rily translate into willingness or unwillingness to stop specific medication. For deprescribing cardiometabolic medication, patient involvement when setting new treatment targets and monitoring the effects on short-term outcomes are important.
Fears, beliefs, and experiences regarding using and stopping medication as well as trust in the HCP influence willingness to have medication deprescribed. Attitudes towards medication in general do not necessarily translate into willingness or unwillingness to stop specific medication. For deprescribing cardiometabolic medication, patient involvement when setting new treatment targets and monitoring the effects on short-term outcomes are important.
The World Health Organization identified Pharmaceutical and Therapeutics Committees (PTCs) at district and hospital levels as one of the pivotal models to promote rational use of medicines (RUM). This is endorsed by the Government in South Africa. Formulary development and management is one of the main functions of PTCs. This study aimed to describe the formulary management activities among PTCs in public hospitals in Gauteng Province, South Africa, following initiatives to promote RUM in South Africa.
Qualitative, nonparticipatory, observational study, observing 26 PTC meetings. Data were coded and categorized using NVivo9
qualitative data analysis software. Themes and sub-themes were developed. The themes and sub-themes on formulary management are the principal focus of this paper.
More than half of the observed PTCs reviewed their formulary lists. There was variation in the review process among institutions providing different levels of care. Various aspects were considered for formulary managementble additions to the NEML.
This is the first study from Gauteng Province, South Africa, reporting on how decisions are actually taken to include or exclude medicines onto formularies within public sector hospitals providing different levels of care. Various approaches are adopted at different levels of care when adding to- or removing medicines from the formulary lists. Future programs should strengthen PTCs in specialized aspects of formulary management. A more structured approach to formulary review at the local PTC level should be encouraged in line with the national approach when reviewing possible additions to the NEML.