Skovsgaardlohmann7385

A series of novel artemisinin ester derivatives were designed and synthesized for targeting mitochondria. Cytotoxicity against SMMC-7721, HepG2, OVCAR3, A549 and J82 cancer cell lines was evaluated. Compound 2c (IC50 = 3.0 μM) was the most potent anti-proliferative molecule against the OVCAR3 cells with low cytotoxicity in normal HUVEC cells. The mechanism of action of compound 2c was further investigated by analyzing cell apoptosis, mitochondrial membrane potential (Δψm) and intracellular ROS generation. The results indicated that compound 2c targeted mitochondria and induced cell apoptosis. ROS and heme attributed to the cytotoxicity and cell apoptosis of compound 2c. These promising findings indicated the compound 2c could serve as a great candidate against ovarian cancer for further investigation.A total of 106 marine microbial metabolites were evaluated for their antiproliferative activity against human lung cancer cells. Results showed that 23 compounds exhibited activity in inhibiting the proliferation of A549 and H157 cells with IC50 values ranging from 1.5 to 48.2 μM. Pyrrospirone F, chrysophanol, physcion, and purpuride G are the four most active compounds with IC50 values of 1.5-7.3 μM. Further investigation of purpuride G (a newly discovered sesquiterpene lactone) demonstrated its potent antiproliferative activity against six different lung cancer cells of A549, H157, H460, H1299, H1703, and PC9 with IC50 values of 2.1-3.3 μM. The antiproliferative activity of purpuride G against cancer cells is related to block cell cycle, induce apoptosis through regulating the apoptotic proteins Bcl-2 and Bax, and inhibit glycolysis by downregulating two key glycolytic enzymes of hexokinase 2 and pyruvate kinase M2.Amyloids have long been associated with a variety of human degenerative diseases. Discoveries indicate, however, that there are several amyloids that serve functional roles in the human body. These amyloids are involved in a variety of biological processes ranging from storage of peptide hormones to necroptosis of cells. Additionally, there are distinct differences between toxic amyloids and their functional counterparts including kinetics of assembly/disassembly and structural features. Selleckchem Etoposide This digest article surveys the biological roles of functional amyloids found in the human body, key differences between functional and toxic amyloids, and potential therapeutic applications.Metabolic syndrome is linked to an increased risk of cardiovascular complications by a mechanism involving mainly decreased nitric oxide (NO) bioavailability and impaired NO-soluble guanylate cyclase (sGC)- cyclic guanosine monophosphate (cGMP) signalling (NO-sGC-cGMP). To further develop this scientific point, this study aimed to investigate the effects of long-term treatment with BAY 41-2272 (a sGC stimulator) on cardiovascular reactivity of spontaneously hypertensive rats (SHR) as a model of metabolic syndrome. SHR were randomly divided into 3 groups control group, cafeteria diet (CD)-fed group and CD-fed group treated daily with BAY 41-2272 (5 mg/kg) by gastric gavage for 12 weeks. In vivo measurements of body weight, abdominal circumference, blood pressure and glucose tolerance test were performed. At the end of the feeding period, ex vivo cumulative concentration-response curves were performed on isolated perfused heart (isoproterenol (0.1 nM - 1 μM)) and thoracic aorta (phenylephrine (1 nM-10 μM), acetylcholine (1 nM-10 μM), and sodium nitroprusside (SNP) (0.1 nM-0.1 μM)). We showed that chronic CD feeding induced abdominal obesity, hypertriglyceridemia, glucose intolerance and exacerbated arterial hypertension in SHR. Compared to control group, CD-fed group showed a decrease in β-adrenoceptor-induced cardiac inotropy, in coronary perfusion pressure and in aortic contraction to phenylephrine. While relaxing effects of acetylcholine and SNP were unchanged. BAY 41-2272 long-term treatment markedly prevented arterial hypertension development and glucose intolerance, enhanced the α1-adrenoceptor-induced vasoconstriction, and restored cardiac inotropy and coronary vasodilation. These findings suggest that BAY 41-2272 may be a potential novel drug for preventing metabolic and cardiovascular complications of metabolic syndrome.To highlight the urgent need to save lives by implementing best practices in health care delivery, the slogan for 5 May 2021, world hand hygiene day, is "Seconds save lives - clean your hands". The WHO campaign calls to action key stakeholders health care workers, IPC practitioners, patients and families, facility managers, policy-makers, vaccinators, and the general public who can play critical roles in achieving optimal hand hygiene at the point of care, helping to strengthen society involvement.

Exposure to environmental toxicants may play a role in the pathogenesis of Non Alcoholic Fatty Liver Disease (NAFLD). Cumulative exposure to lead (Pb) has chronic and permanent effects on liver function. Pediatric populations are vulnerable to the toxic effects of Pb, even at low exposure levels. The purpose of the study was to estimate the association between cumulative Pb exposure during childhood and hepatic steatosis biomarkers in young Mexican adults.

A subsample of 93 participants from the ELEMENT cohort were included in this study. Childhood blood samples were collected annually from ages 1-4 years and were used to calculate the Cumulative Childhood Blood Lead Levels (CCBLL). Hepatic steatosis during adulthood was defined as an excessive accumulation of hepatic triglycerides (>5%) determined using Magnetic Resonance Imaging (MRI). Liver enzymes were also measured at this time, and elevated liver enzyme levels were defined as ALT (≥30 IU/L), AST (≥30 IU/L), and GGT (≥40 IU/L). Adjusted linear regrkers and hepatocellular injury in young adulthood. More actions should be taken to eliminate sources of Pb during the first years of life.

Studies have demonstrated an association between phthalate exposure and childhood asthma, although results have been inconsistent. No epidemiological studies have examined exposure during the first year of life.

To investigate the association between phthalate exposures in the home environment during the first year of life, and subsequent development of childhood asthma and related symptoms.

This study used a case-cohort design including 436 randomly selected children and all additional cases of asthma at 5 years (n

=129) and recurrent wheeze between 2 and 5 years (n

=332) within the CHILD Cohort Study, a general population Canadian birth cohort of 3455 children. Phthalate exposure was assessed using house dust samples collected during a standardized home visit when children were 3-4 months of age. All children were assessed by specialist clinicians for asthma and allergy at 1, 3 and 5 years. Logistic regression was used to assess the association between exposure to five phthalates and asthma diagnosis at 5 years, and recurrent wheeze between 2 and 5 years, with further stratification by wheeze subtypes (late onset, persistent, transient) based on the timing of onset and persistence of wheeze symptoms.