Positive Control Research Articles

Euphane and Tirucallane Triterpenes with Trypanocidal Activity from Euphorbia desmondii.

The phytochemical investigation of Euphorbia desmondii resulted in the isolation of 15 previously undescribed triterpenoids (desmondiins A, C-P) and 8 already described compounds. The structures of the isolated compounds were determined by extensive spectroscopic analyses. The compounds were identified as tirucallane and euphane triterpenes based on 7-keto-8-ene, 11-keto-8-ene, or 7,11-diketo-8-ene skeletons. Additionally, the selective trypanocidal activities of these compounds against Trypanosoma cruzi were evaluated. Desmondiins A, C, D, F, H, and M exhibited IC50 values in the range of 3-5 μM, and selectivity indices between 5-9, against T. cruzi epimastigotes over the host cell (RAW264.7 macrophages). Furthermore, desmondiin A efficiently inhibited amastigote replication in host cells (IC50 = 2.5 ± 0.3 μM), which was comparable to that of the positive control, benznidazole (3.6 ± 0.4 μM). Overall, the isolated euphane and tirucallane triterpenoids could act as antichagasic lead scaffolds.

Statherin-derived peptide protects against intrinsic erosive enamel wear in situ.

This in situ study investigated the protective effect of a solution containing statherin-derived peptide (StatpSpS) against enamel intrinsic erosion. Fifteen volunteers wore appliances containing 2 bovine specimens. The samples were subjected to erosion (ERO) with HCl, mimicking dental erosion by intrinsic acid. The volunteers participated in 3 phases (double-blind and crossover): 1) Deionized water (negative control); 2) Commercial solution containing SnCl2/NaF/AmF (800 ppm Sn+2, 500 ppm F-, pH 4.5) - (positive control); 3) Solution containing 1.88 X 10-5M StatpSpS. Four times a day, the volunteers administered one drop of the solutions (50 µl, 1 min) on each specimen. After the treatment, erosive challenges were performed extraorally with 0.01 M HCl (pH 2.0, 4 times/day, 1 min, 150 mL). Enamel wear was assessed by profilometry. Data was analyzed by one-way RM-ANOVA/Bonferroni's tests (p<0.05). In terms of the treatments, both the commercial solution - SnCl2/NaF/AmF and StatpSpS significantly reduced the wear when compared to the negative control (p<0.01), without significant differences between them (p>0.05). The solution containing StatpSpS demonstrated protection against enamel intrinsic erosive wear. This study marks a significant advancement in the prevention of intrinsic erosive wear, utilizing StatpSpS in acquired pellicle engineering procedures.

Effect of remimazolam on intra-operative hypotension: Systematic review and meta-analysis of randomised controlled trials.

Hypotension is common during anaesthesia. Increasing number of studies have reported that remimazolam may be associated with lower incidence of intra-operative hypotension compared with other anaesthetics. However, the results remain controversial. This study aimed to evaluate the influence of remimazolam on intra-operative hypotension and its related outcomes (hypoxaemia, bradycardia and time to awake). A systematic review of randomised controlled trials (RCTs) with meta-analyses. PubMed, Cocharane and Embase databases were searched to identify eligible RCTs published up to June 2024. RCTs published in English were eligible for inclusion. The study patients were 18 years or older who were administered with remimazolam and other positive control agents in either the pre-operative or intra-operative period. The incidence of intra-operative hypotension was identified in these studies. This study evaluated 34 trials including 4847 individuals. Basing on moderate-certainty evidence, we found that remimazolam administration reduced the incidence of intra-operative hypotension [risk ratio (RR) = 0.48, 95% confidence interval (95% CI): 0.41 to 0.57] and bradycardia (16 studies, n = 2869, RR = 0.40, 95% CI: 0.29 to 0.54). No difference was observed in the incidence of hypoxaemia (RR = 0.70, 95% CI: 0.48 to 1.01) and time to awake (MD = -0.91, 95% CI: -2.42 to 0.60). The remarkable association between remimazolam and hypotension remained robust and significant, regardless of general anaesthesia or procedural sedation (P < 0.01, I2 = 82%). No significant difference was found between different control drugs (P = 0.97, I2 = 82%). Moderate-quality evidence shows that remimazolam administration to patients undergoing general anaesthesia or procedural sedation decreases the incidence of intra-operative hypotension and bradycardia.

Flavonol-ruthenium complexes as antioxidant and anticancer agents.

Flavonol-metal complexes can enhance the biological activity of flavonols. Inspired by the potential of ruthenium-based drugs in pharmaceutical applications, seven flavonol-Ru (II) complexes were synthesized to evaluate their biological activities. Among these compounds, compounds 8, 11, and 12 showed potent antioxidant activities. Compound 12 exhibited superior anti-inflammatory activity to natural quercetin, which served as a positive control. This study is the first to report the free radical scavenging abilities and antioxidant activity of flavonol-Ru (II) complexes. Furthermore, compound 12 demonstrated comparable efficacy to 5-FU against human non-small-cell lung cancer cells (A549). These results strongly support the potential of flavonol-Ru (II) agents.

Use of a synthetic oligonucleotide to detect false positives caused by cross-contamination in nested PCR

Nested PCR is a useful tool for identifying low-abundance target sequences of pathogens and avoiding false negatives. However, it carries an increased risk of cross-contamination, especially with its positive control. Here, we propose using customized synthetic oligonucleotides to detect false positives due to cross-contamination.

Keeping quality of raw ground beef patties fortified with polyphenols extracted from Acacia mearnsii bark and leaves

Acacia mearnsii byproducts are naturally endowed with a plethora of diverse polyphenols that exhibit antioxidant properties indicating potential application in enhancing oxidative shelf-life of perishable foods. The current study evaluated the oxidative shelf-life of raw ground beef patties fortified with 450 μg/g of polyphenolic extracts from A. mearnsii bark (AMBE) or leaves (AMLE) compared to positive (sodium metabisulphite; SMB) and negative (no extract; CTL) controls for 9 d at 4 °C in a simulated retail display. The AMBE had higher (P ≤ 0.05) contents of proanthocyanidins, and total phenols, flavonoids and tannins, and consequently demonstrated greater (P ≤ 0.05) in vitro antioxidant activity than AMLE. The polyphenolic extracts increased (P ≤ 0.05) antioxidant activity in beef patties compared to the CTL though they were outperformed (P ≤ 0.05) by the SMB. Fortification of beef patties with the polyphenolic extracts, particularly AMBE, delayed colour deterioration and oxidation of myoglobin during retail display relative to the CTL but were less efficient than SMB (P ≤ 0.05). Beef patties fortified with the polyphenolic extracts and SMB had comparable (P > 0.05) peroxide values, TBARS and p-Anisidine values which were all lower (P ≤ 0.05) than those for the CTL patties. The order of protein thiol content in beef patties was as follows: CTL ≥ AMLE ≥ AMBE ≥ SMB (P ≤ 0.05). Findings suggest that A. mearnsii-derived polyphenolic antioxidants, particularly AMBE has great potential to extend oxidative shelf-life of raw beef patties.

Phyto-assisted synthesis of zinc oxide nanoparticles using Bauhinia variegata buds extract and evaluation of their multi-faceted biological potentials

Zinc oxide nanoparticles have wide range biological, biomedical and environmental applications. However, traditional nanofabrication of ZnONPs uses various toxic chemicals and organic solvents which limit their bio-applications. To overcome this hurdle, Bauhinia variegata derived buds extract was utilized to fabricate ZnONPs. The greenly generated ZnONPs were successfully prepared and extensively characterized using different analytical tools and the average crystalline size was calculated as 25.47 nm. Further, bioengineered ZnONPs were explored for multiple biological activities that revealed excellent therapeutic potentials. The antibacterial potential was determined using different bacterial strains. Pseudomonas aeruginosa (MIC: 137.5 µg/mL) was reported to be the most resistant variant while Bacillus subtilis (MIC: 34.38 µg/mL) was observed to be most susceptible bacterial strain. DPPH radical scavenging potential was measured to determine the antioxidant capacity of ZnONPs and the highest scavenging potential was observed as 82% at highest of 300 µg/mL. The fungicidal effect of green ZnONPs in comparison with Amphotericin B was assessed against five selected pathogenic fungal strains. The results revealed, Fusarium solani (MIC: 46.875 µg/mL) was least resistant and Aspergillus flavus (MIC: 187.5 µg/mL) was most resistant in fungicidal examination. Cytotoxicity potential of B.V@ZnONPs was analyzed against newly hatched nauplii of brine shrimps. The results for greenly produced ZnONPs was recorded as 39.78 µg/mL while 3.006 µg/mL was reported for positive control vincristine sulphate. The results confirmed the category of general cytotoxic for greenly synthesized nano sized B.V@ZnONPs.

The Impact of Silver Nanoparticles’ Size on Biofilm Eradication

IntroductionEfficient intracanal disinfection is required for a successful regenerative endodontic treatment. Thus, this study aimed to identify the silver nanoparticles’ (NPs) size (AgNPs) with the highest antibiofilm efficacy when mixed with calcium hydroxide [Ca(OH)2] to eradicate an in vitro endodontic biofilm. MethodsThe various sizes of AgNPs and mixtures were characterized by scanning electron microscopy, transmission electron microscopy, and ultraviolet-visible spectroscopy. A total of 168 dentin root segments were prepared, sterilized, and inoculated for 3 weeks with Actinomyces naeslundii and Fusobacterium nucleatum. Samples were randomly allocated to 4 experimental groups (n = 28/group): 2 nm AgNPs + 35% Ca(OH)2, 5 nm AgNPs + 35% Ca(OH)2, 10 nm AgNPs + 35% Ca(OH)2, and 35% Ca(OH)2 alone. Samples exposed to saline and triple antibiotic paste (TAP) acted as negative and positive control groups, respectively. After 1 and 2 weeks, samples were stained with LIVE/DEAD BacLight dye and examined under a confocal laser scanning microscope to determine the proportion of dead bacteria. ResultsThe characterization procedure revealed a spherical NP's structure with minor aggregations. Except for Ca(OH)2 group, all groups had significantly higher antibiofilm efficacy at 2 weeks. Both the 10 nm mixture (99.5%) and TAP (99.2%) exhibited the highest antibiofilm efficacy at 2 weeks and were not significantly different from one another (P > .05). No significant difference was noted between the 2 and 5 nm mixtures at 1 week (81% and 84%) and 2 weeks (89% and 91%). ConclusionThe 10 nm AgNPs (0.02%) + 35% Ca(OH)2 mixture exhibited the highest antibiofilm efficacy at 2 weeks compared to all other mixtures at both observation periods. Interestingly, the 10 nm mixture performed similarly to TAP at 2 weeks. Excluding Ca(OH)2 group, longer application significantly improved the antibiofilm efficacy of all tested medicaments. Clinical RelevanceThe 10 nm AgNPs + 35% Ca(OH)2 mixture revealed promising results as an intracanal medicament in the regenerative endodontic treatment protocol.

The effect of some vegetable origin oils used in different clove varieties against Meloidogyne incognita

Alternative control methods are needed against plant parasitic nematodes in Gerbera (Gerbera jamesonii L.) and Carnation (Dianthus caryophyllus L.) plants and one of these methods is the use of plant-based extracts against nematodes. Plant parasitic nematodes cause economic damage in cut flower production areas, so in order to reduce this damage, it is aimed to use different non-synthetic plant-based extracts as an alternative to chemical control methods within the scope of cultural control of nematodes. For this purpose, garlic, thyme, and terminator (70% thyme + 30% different plant mixture formation) were used to determine the resistance against M. incognita in two different clove cultivars, Turbo with standard flower type and Harnet with spray flower type. While the egg pack index was 1.40 ± 0.70 in the Harnet cultivar with garlic application, this rate was 16.00 ± 9.66 in the positive control. While the egg pack index was 1.20 ± 0.42 in the Turbo variety, in which garlic was applied, this value was 3.70 ± 0.48 in the control. When evaluated based on varieties, the egg package index was lower in the Turbo variety with garlic application compared to the Harnet variety.

Deoxynivalenol Induces Local Inflammation and Lesions in Tissues at Doses Recommended by the EU

The mycotoxin deoxynivalenol (DON) is frequently present in cereals at low levels, resulting in its occurrence in food and feed. DON has been proven to alter the immune response and induce inflammation in all species, with pigs exhibiting heightened sensitivity and exposure. However, no study has yet evaluated the effects of exposure to DON at the recommended levels in pig feed. In two separate trials, piglets were subjected to control feed or feed contaminated with a low level of purified DON (0.83 mg/kg feed in trial 1 and 0.85 mg/kg feed in trial 2) for either three weeks (trial 1) or two weeks (trial 2). Additionally, a group of animals exposed to 2.85 mg/kg feed of DON was included as a positive control in Trial 1. The impact of DON on porcine tissues (intestine, liver, and spleen) was evaluated through histological and qPCR analyses of immune-related genes. Additionally, biochemical analyses and acute-phase proteins were examined in plasma samples. Lesions were identified in the intestine (jejunum and ileum), the liver, and the spleen of pigs receiving diets contaminated with low and high concentrations of DON. The low level of DON also resulted in impaired expression of genes associated with intestinal barrier integrity, intestinal immune responses, and liver function. In conclusion, the results of the two trials demonstrate the impact of DON exposure even at doses below the recommended level of 0.9 mg/kg feed set by the European Union. This suggests that the current recommended level should be reconsidered to ensure the optimal health and well-being of pigs.

Application of Asteraceae biomass and biofertilizers to improve potato crop health by controlling black scurf disease

Potato (Solanum tuberosum L.) cultivation in Pakistan faces challenges, with black scurf disease caused by Rhizoctonia solani Kühn being a significant concern. Conventional methods like chemical fungicides partially control it, but an effective solution is lacking. This study explores the potential of biofertilizers and soil amendments from Asteraceae weed biomass to manage the disease. Two potato varieties, Karoda and Sante, were chosen, and two biofertilizers, Fertibio and Feng Shou, were tested alone or with Xanthium strumarium biomass. Disease pressure was highest in the positive control, with significant reduction by chemical fungicide. X. strumarium biomass also decreased disease incidence significantly. Fertibio showed better efficacy than Feng Shou. Physiological and biochemical attributes of plants improved with biofertilizer and biomass application. Tuber weight, photosynthetic pigments, total protein content, and antioxidant enzymes (CAT, POX, and PPO) were positively correlated. Combined application of Fertibio and S. marianum biomass effectively managed black scurf disease. These eco-friendly alternatives could enhance disease management and yield. Future research should explore their cost-effectiveness, commercialization, and safety.

Anti-obesity and immunomodulatory effects of Allium hookeri leaves cultivated with artificial light of different intensities on immune-depressed obese mice

This study was conducted to evaluate the effects of Allium hookeri (AH) leaves cultivated with different light-emitting diode (LED) intensities (L: low, 100 μmol/m2/s; M: medium, 150 μmol/m2/s; H: high, 200 μmol/m2/s). Alliin concentration increased as light intensity increased in AH and showed the highest level at LED-H condition. The anti-obesity and immunomodulatory properties of AH were evaluated in a cyclophosphamide (CPA)-induced immunosuppressed obese animal model. C57BL/6 J mice were randomly divided into control (CON), high-fat diet (HFD) control (CON-H), negative control (NC), positive control (PC, β-glucan, 50 mg/kg body weight (BW)), AH L, M, and H groups. The three kinds of AH extracts were orally administered to the mice at 300 mg/kg BW for 2 weeks. Except for CON and CON-H, all the other groups were intraperitoneally treated with CPA. Epididymal and abdominal fat weight decreased as LED intensity increased while spleen weight increased in the AH groups. Serum glucose decreased as LED intensity increased in the AH groups and H group showed the lowest level. Triglycerides, total, and LDL-cholesterol levels decreased while HDL-cholesterol level increased in the AH groups compared to the NC group. Moreover, AH effectively reduced serum ALT and AST levels and increased the total white blood cell count, particularly elevating lymphocyte and monocyte levels. Furthermore, NK cell activity was higher in the AH groups. These findings suggest that AH cultivated at optimal LED intensity could be used as a novel biomedicine and in pharmacotherapy to treat related diseases to improve public health without any toxicity.

Kefir recovered depressive-like behaviour in CantonS lineage of Drosophila melanogaster exposed to chronic unpredictable mild stress protocol.

Chronic unpredictable mild stress (CUMS) is a widely accepted method for inducing depressive-like states in animal models. We decided to explore the effects of CUMS on the CantonS lineage of Drosophila melanogaster, which differs from the OregonR lineage in various ways. Additionally, we wanted to investigate the potential benefits of kefir in treating these chronically stressed flies, as previous research has shown promising results in using kefir components for depression treatment. To begin, we exposed male CantonS flies to a 10-day CUMS protocol and compared them to non-stressed flies. Within the stressed group, we had two subgroups: one treated with kefir (CUMS+ Kefir group) and the other treated with sertraline (positive control). We then analysed various factors including serotonin levels, brain structure, markers of oxidative damage in lipids and proteins, and behavioural manifestations such as sociability, locomotor function, and anhedonic-like behaviour. Our results showed that flies exposed to CUMS experienced a decrease in serotonin levels without any signs of degeneration. They also exhibited reduced sociability, increased motor agitation, and decreased sucrose consumption, which are all indicative of stress-induced depressive-like behaviour. However, treatment with sertraline partially reversed these effects. Interestingly, treatment with kefir not only restored serotonin levels but also improved sociability and anhedonic-like behaviours. Additionally, flies in the CUMS+ Kefir group had a longer lifespan compared to their untreated counterparts. These findings suggest that kefir has multiple advantageous effects on flies subjected to the 10-day CUMS protocol. In conclusion, our study demonstrates that the CantonS lineage of D. melanogaster displays depressive-like manifestations after exposure to CUMS. Furthermore, kefir emerges as a powerful nutritional tool capable of reversing these effects and promoting beneficial outcomes in chronically stressed flies.

The effects of positive psychology and physical activity on depression, anxiety, and stress among students with premenstrual syndrome: a single-blind, randomized controlled trial

BackgroundPremenstrual syndrome affects many women in their reproductive years and often disrupts their social connections and work. This study aimed to compare the effects of positive psychology and physical activity on depression, anxiety, and stress among students with premenstrual syndrome.MethodsIn this four-group parallel clinical trial with blinded data analysis, 120 eligible students who experienced premenstrual syndrome were recruited based on inclusion/exclusion criteria and randomly allocated to four groups (n = 30) including three experiment groups as positive psychology, physical activity, and positive psychology, physical activity, and control group, using a simple randomization method. All four groups completed premenstrual syndrome screening and the DASS-21 questionnaire before the intervention. Then, the positive psychology intervention group received eight sessions of 70–90 min weekly intervention, the second group received eight weeks of aerobic physical activity intervention, and the third group received positive psychology and physical activity intervention for eight weeks. The control group did not receive any interventions. The DASS-21 was completed immediately after the intervention and two months later by all four groups. In this study, the participants and investigators were not blinded; however, the analysts were. The recruitment process took place from September 2018 to March 2019. One hundred twenty participants fulfilled the study. The Data were collected and analyzed using SPSS (v18).ResultsBefore and immediately after the intervention, there was no statistically significant difference in depression, anxiety, and stress mean scores among the positive psychology, physical activity, positive psychology, and physical activity and control groups (p ≥ 0.05). However, two months after the intervention, a significant difference was observed between the four groups so there was a difference between the scores of the three intervention groups and the control group (p < 0.05). There was no significant difference between positive psychology, and physical activity groups. No significant adverse events or side effects were observed.ConclusionOur findings supported the use of aerobic physical activity and educational interventions based on positive psychology as non-pharmacologic interventions to reduce anxiety, depression, and stress. This research should be replicated in different settings.Trial registration clinical trialsIranian Registry of Clinical Trials; https://irct.behdasht.gov.ir/trial/32363 (IRCT20130812014333N97), registered (11/08/2018).

Novel insights into the association between genetically proxied inhibition of proprotein convertase subtilisin/kexin type 9 and risk of sarcopenia.

The effects of lipid-lowering drugs [including statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors] on hyperlipidaemia have been established. Some may have treatment effects beyond their reported properties, offering potential opportunities for drug repurposing. Epidemiological studies have reported conflicting findings on the relationship between lipid-lowering medication use and sarcopenia risk. We performed a two-sample Mendelian randomization (MR) study to investigate the causal association between the use of genetically proxied lipid-lowering drugs (including statins, ezetimibe, and PCSK9 inhibitors, which use low-density lipoprotein as a biomarker), and sarcopenia risk. The inverse-variance weighting method was used with pleiotropy-robust methods (MR-Egger regression and weighted median) and colocalization as sensitivity analyses. According to the positive control analysis, genetically proxied inhibition in lipid-lowering drug targets was associated with a lower risk of coronary heart disease [PCSK9 (OR, 0.67; 95% CI, 0.61 to 0.72; P=7.7E-21); 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR; OR, 0.68; 95% CI, 0.57 to 0.82; P=4.6E-05), and Niemann-Pick C1-like 1 (NPC1L1; OR, 0.53; 95% CI, 0.40 to 0.69; P=3.3E-06)], consistent with drug mechanistic actions and previous trial evidence. Genetically proxied inhibition of PCSK9 (beta, -0.040; 95% CI, -0.068 to -0.012; P=0.005) and circulating PCSK9 levels (beta, -0.019; 95% CI, -0.033 to -0.005; P=0.006) were associated with reduced appendicular lean mass (ALM) with concordant estimates in terms of direction and magnitude. Validation analyses using a second instrument for PCSK9 yielded consistent results in terms of direction and magnitude [(PCSK9 to ALM; beta, -0.052; 95% CI, -0.074 to -0.032; P=7.1E-7); (PCSK9 protein to ALM; beta, -0.060; 95% CI, -0.106 to -0.014; P=0.010)]. Genetically proxied inhibition of PCSK9 gene expression in the liver may be associated with reduced ALM (beta, -0.013; 95% CI, -0.035 to 0.009; P=0.25), consistent with the results of PCSK9 drug-target and PCSK9 protein MR analyses, but the magnitude was less precise. No robust association was found between HMGCR inhibition (beta, 0.048; 95% CI, -0.015 to 0.110; P=0.14) or NPC1L1 (beta, 0.035; 95% CI, -0.074 to 0.144; P=0.53) inhibition and ALM, and validation and sensitivity MR analyses showed consistent estimates. This MR study suggested that PCSK9 is involved in sarcopenia pathogenesis and that its inhibition is associated with reduced ALM. These findings potentially pave the way for future studies that may allow personalized selection of lipid-lowering drugs for those at risk of sarcopenia.

Tantalum granules with hierarchical pore structure for bone regeneration porous tantalum granules repair bone

Tantalum (Ta) has good potential for bone tissue engineering due to its excellent corrosion resistance and biocompatibility. However, the customization of Ta-based bone repair materials for irregularly shaped bone defects has been challenging due to their high melting point and hardness. In this work, porous tantalum granules (PTaG) were developed for the first time to repair irregularly shaped bone defects, inspired by the natural phenomenon of sand flow. PTaG were designed as a hierarchical porous structure to regulate the mechanical properties and provide a favorable space for inward growth of cells and tissues. Commercial porous titanium granules (PTiG) and Bio-Oss were used as positive controls to explore the potential of PTaG as bone substitute. The morphology, three-dimensional structure, composition, and mechanical properties of PTaG and PTiG were evaluated by SEM, X-Ray 3D imaging system, 3D laser confocal microscope, EDS, XRD, XPS, and nanoindentation. In vitro, cell compatibility and mineralization ability were evaluated for both materials. Furthermore, PTaG, PTiG, and Bio-Oss were filled in the rabbit femoral defect, and micro-CT and histological analysis were performed after 8 weeks. The results showed that the PTaG had the best bone healing effect due to the hierarchical porous structure, excellent three-dimensional connectivity and chemical stability, suitable mechanical properties and surface roughness, good biocompatibility and mineralization osteogenic activity. This work indicates that PTaG may have a positive potential for filling and repairing irregularly shaped bone defects.

Structural characterization and hypolipidemic activity of a natural polysaccharide from Suaeda salsa L.

Herein, the identification and analysis of a newly discovered hypolipidemic polysaccharide extracted from Suaeda salsa L., SS3-N1, is reported. The weight-average molecular weight (Mw), number-average molecular weight (Mn), and dispersity (Ð) of SS3-N1 were determined to be 45.50 kDa, 34.21 kDa, and 1.33, respectively. This polysaccharide primarily consists of galactose (50.80 %) and arabinose (30.70 %), with lower proportions of xylose, mannose, guluronic acid, rhamnose, glucuronic acid, ribose, and fucose. Methylation and NMR analyses indicated that its backbone was primarily composed of R → 3,6)-β-D-Galp-(1 → R and R → 5)-α-L-Araf-(1→ residues. The sugar units at the reducing and nonreducing ends were identified as R → 4)-β-D-Xylp-(1 → R and R → 3)-β-D-Galp-(1 → R, respectively. In addition, α-L-Araf (1 → R side branches were incorporated at the C-3 position of R → 3,6)-β-D-Galp-(1 → R. At 100 μg/mL, SS3-N1 surpassed the lipid-lowering efficacy of the positive control, atorvastatin (0.4 μM), in an egg yolk powder (EYP)-induced hyperlipidemic zebrafish model. This effect may be attributed to the modulation of cholesterol metabolism due to the upregulation of nrf2, ho-1, ampk, ppara, and cyp7a1 gene expression and the downregulation of acaca and hmgcr gene expression. Such dual gene regulation inhibits fatty acid and cholesterol synthesis, suggesting potential applications for the natural hypolipidemic polysaccharide derived from S. salsa L.

Terpenoids and steroids from aerial parts of Achillea alpina L. as PTP1B inhibitors: kinetic analysis and molecular docking studies

Achillea alpina L. (Alpine yarrow) is a noteworthy herb in the genus Achillea with many uses in vegetables and traditionally used to treat stomach disorders. In our continuous research on the chemical constituents and biological activities of medicinal plants, ten previously undescribed terpenoids including eight eudesmane-type sesquiterpenes (1‒8), one nor-eudesmane-type sesquiterpene (9), one cyclo-geraniol derivative (10), and twenty-one known compounds were isolated and structurally elucidated from the aerial parts of A. alpina. Structures and absolute configurations of the undescribed terpenoids were identified using comprehensive spectroscopic analysis (NMR, HRESI-MS, and CD data) and computational methods (ECD and NMR calculation). Enzyme inhibitory assays showed that the isolated sesquiterpene (19), triterpene (22), and sterol (26) were protein tyrosine phosphatase 1B (PTP1B) inhibitors with IC50 values ranging from 14.87 to 23.09 μM in comparison with positive control - ursolic acid, showing IC50 value of 5.93 ± 0.16 μM. Further enzyme kinetics and molecular docking studies were performed to provide valuable insights into their mechanism of action.

The Effect of Rent Control Status on Eviction Filing Rates: Causal Evidence From San Francisco

This paper presents causal evidence of a significant positive effect of rent control status on eviction filing rates in San Francisco, CA. Two datasets of eviction notices (n = 13,887) and property tax records (n = 1,978,687) are combined using a regression discontinuity design to estimate a local average treatment effect of ∼0.3% evictions per residential unit per year conditioned on positive rent control status. Compared to the baseline rate of eviction notices over this same time period, the findings suggest that for a given tenant, positive rent control status (i.e., living in a rent-controlled unit) increases the likelihood of eviction by approximately 127% per year. This finding is best understood not as an inherent characteristic of rent control policy in general, but rather as the result of specific state-wide laws, passed in the years following the adoption of rent control in San Francisco, which granted rent-controlled property owners an economic incentive to evict and the legal means to do so.

Epigenetic Changes in the HTR8 and 3A-sub E placental Cell Lines Exposed to Bisphenol A and Benzyl Butyl Phthalate

Objective: Bisphenol A and phthalate are known endocrine disruptors and capable of inducing epigenetic changes in the human population. However, their impact on the placenta is less well studied. Our objective was to measure the effect of exposure to bisphenol A and benzyl butyl phthalate in first-trimester HTR8-SVneo and third-trimester 3A-sub E trophoblast cells by profiling the DNA methylation pattern of the imprinting control region of the IGF2 (insulin-like growth factor) and H19 genes. Methods: Human placental HTR8-SVneo and 3A-sub E cell lines were treated with two sub-lethal concentrations of bisphenol A and benzyl butyl phthalate. Demethylating agent, 5-azacytidine, was used as a positive control. Cells were harvested on post-treatment days 1 and 4. The methylation profile of six CpG dinucleotide sites, part of the CTCF 6 binding site of the IGF2/H19 imprinting control region, was determined by pyrosequencing. Results: In the first-trimester HTR8-SVneo cell line, we observed a significant increased methylation of the CpG sites 3, 4 when treated with a high concentration of bisphenol A or benzyl butyl phthalate while increased methylation at site 6 for both high and low dose treatment on day 4. Demethylation of the CpG sites 1, 4, and 6 was observed when treated with 5-azacytidine on day 4. In the third-trimester 3A-sub E cell line, no significant changes in the methylation profile were observed under any treatment conditions. Conclusions: The results of this study demonstrate the capability of epigenetic changes in human placenta cells induced by bisphenol A and benzyl butyl phthalate. The observed methylation changes only in the first-trimester HTR8-SVneo cells phthalate may reflect a window of epigenetic susceptibility related to these environmental toxicants.