Miracle-dz/UniFAR-FTUs huggingface dataset:
Radix Polygoni Multiflori and Its Main Component Emodin Attenuate Non-Alcoholic Fatty Liver Disease in Zebrafish by Regulation of AMPK Signaling Pathway

Purpose Nonalcoholic fatty liver disease (NAFLD) has become a predictor of death in many diseases. This study was carried out to investigate the therapeutic effect of Radix Polygoni Multiflori Preparata (RPMP) and its main component emodin on egg yolk powder-induced NAFLD in zebrafish. Further investigation was performed to explore whether emodin was the main component of RPMP for the treatment of NAFLD as well as the underlying therapeutic mechanism of RPMP and emodin. Methods Zebrafish were divided into control group, egg yolk powder group, RPMP group and emodin group. The obesity of zebrafish was evaluated by body weight, body length and BMI. The content of lipid was detected by triglyceride (TG), total cholesterol (TC) reagent kit and the fatty acid was detected by nonesterified free fatty acids (NEFA) reagent kit. HE staining was used to detect the histological structure of liver. Whole-mount Oil red O staining and Frozen oil red O staining were carried out to investigate the lipid accumulation in liver. KEGG and STRING databases were performed to analyze the potential role of AMPK between insulin resistance (IR) and fatty acid oxidation. Western blot and RT-qPCR were carried out for mechanism research. Results RPMP and emodin significantly reduced zebrafish weight, body length and BMI. Both RPMP and emodin treatment could reduce the lipid deposition in zebrafish liver. RPMP significantly reduced the content of TG. However, emodin significantly reduced the contents of TG, TC and NEFA in zebrafish with NAFLD. The protein interaction network indicated that AMPK participated in both IR and fatty acid oxidation. Further investigation indicated that RPMP and emodin reduced hepatic lipogenesis via up-regulating the expressions of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT2), amp-activated protein kinase alpha (AMPKα), proliferator-activated receptor alpha (PPARα), carnitine palmitoyl transferase 1a (CPT-1a) and acyl-coenzyme A oxidase 1 (ACOX1). Conclusion These findings suggest that emodin is the main component of RPMP for the treatment of NAFLD, which is closely related to the regulation of AMPK signaling pathway which increases IR and fatty acid oxidation.
Pumpkin Oil–Based Nanostructured Lipid Carrier System for Antiulcer Effect in NSAID-Induced Gastric Ulcer Model in Rats

Background Peptic ulcer disease, a painful lesion of the gastric mucosa, is considered one of the most common gastrointestinal disorders. This study aims to investigate the formulation of pumpkin seed oil (PSO)-based nanostructured lipid carriers (NLCs) to utilize PSO as the liquid lipid component of NLCs and to achieve oil dispersion in the nano-range in the stomach. Methods Box–Behnken design was utilized to deduce the optimum formula with minimum particle size. The optimized PSO-NLCs formula was investigated for gastric ulcer protective effects in Wistar rats by evaluating ulcer index and determination of gastric mucosa oxidative stress parameters. Results PSO was successfully incorporated as the liquid lipid (LL) component of NLCs. The prepared optimum PSO-NLCs formula showed a size of 64.3 nm. Pretreatment of animals using the optimized PSO-NLCs formula showed significantly (p< 0.001) lower ulcer index compared to indomethacin alone group and significantly (p<0.05) less mucosal lesions compared to the raw oil. Conclusion These results indicated great potential for future application of optimized PSO-NLCs formula for antiulcer effect in non-steroidal anti-inflammatory drug (NSAID)-induced gastric ulcer.
Prevalence of Metabolic Syndrome and Its Association with Sociodemographic Characteristics in Participants of a Public Chronic Disease Control Program in Medellin, Colombia, in 2018

Background Metabolic syndrome has increased to epidemic levels in low- and middle-income countries. The knowledge on metabolic syndrome and its related diseases constitutes a clinical, epidemiological, and economic challenge of great relevance. The frequency of metabolic syndrome may vary between populations depending on age, sex, lifestyle, and culture; however, in Colombia, there is only little research, and the available studies focus on small populations that do not allow estimating their prevalence and distribution in different sociodemographic groups. We aimed to estimate the prevalence of metabolic syndrome and its association with sociodemographic characteristics in participants attending public chronic disease control programs in Medellin, Colombia, in the year 2018. Methods We conducted a cross-sectional study in all patients who participated in a public chronic disease control program. Involved in this study were 68,288 individuals who attended at 10 hospital units and were strategically distributed in the city. The diagnostic criteria of the metabolic syndrome and its components were based on the consensus of the Latin American Diabetes Association. The data on age, sex, blood pressure, weight, height, physical activity, medications, lipid profile, and glycemic and glycosylated hemoglobin levels were obtained for clinical records. The prevalence, Pearson’s chi-square test, prevalence ratios (Kato-Katz method), and odds ratios (Woolf method) were estimated with 95% confidence intervals. A multivariate adjustment model was used with a logistic regression model to identify potential confounders using Epidat 4.2 and SPSS® 25.0. Results The prevalence of the syndrome was 35.4%, with abdominal obesity in 82.3% individuals, hypertension in 48.6%, glucose intolerance in 25.5%, and hypertriglyceridemia in 22%. The prevalence of the syndrome exhibited statistical differences according to the area of residence. It was 15% higher in women; 31% and 59% higher in young and older adults, respectively, than in individuals aged <25 years; 11% and 13% higher in the illiterate population and population with primary studies than in individuals with higher education; and approximately 200 times higher than those who are sedentary. Conclusion A high prevalence of the syndrome and its constitutive factors in the study population demonstrated the importance of controlling it and increasing community-based prevention strategies, prioritizing the identified groups that are at the highest risk.
Novel Drug Delivery Systems for Loading of Natural Plant Extracts and Their Biomedical Applications

Abstract Many types of research have distinctly addressed the efficacy of natural plant metabolites used for human consumption both in cell culture and preclinical animal model systems. However, these in vitro and in vivo effects have not been able to be translated for clinical use because of several factors such as inefficient systemic delivery and bioavailability of promising agents that significantly contribute to this disconnection. Over the past decades, extraordinary advances have been made successfully on the development of novel drug delivery systems for encapsulation of plant active metabolites including organic, inorganic and hybrid nanoparticles. The advanced formulas are confirmed to have extraordinary benefits over conventional and previously used systems in the manner of solubility, bioavailability, toxicity, pharmacological activity, stability, distribution, sustained delivery, and both physical and chemical degradation. The current review highlights the development of novel nanocarrier for plant active compounds, their method of preparation, type of active ingredients, and their biomedical applications.
Diabetes and Risk of Post-Fragility Hip Fracture Outcomes in Elderly Patients

Objective To explore the effect of diabetes on short-term (30 days after fracture) and 1-year outcomes for fragility hip fracture patients. Methods We conducted a retrospective cohort study involving 161 diabetic hip fracture patients (older than 60 years) and 483 nondiabetic hip fracture patients. Patients were followed up on day 30 and 1 year after fracture. The short-term outcome was complications that occurred within 30 days after hip fracture and length of stay. The 1-year outcomes were postfracture functional outcomes and reduced activity level and mortality rate within 1 year after fracture. The clinical characteristics and outcomes of patients were analyzed. Results Compared with nondiabetic patients, diabetic patients had a longer length of awaiting surgery (6.0 vs. 5.0 days, P=0.031) and a longer length of total hospital stay (17 vs. 15 days, P < 0.001). Furthermore, compared with nondiabetic patients, diabetic patients have higher costs (P=0.011), in addition to being more prone to developing urinary tract infections (6.2% vs. 1.7%, P=0.002) and deep vein thrombosis (4.3% vs. 1.4%, P=0.029) complications. However, at one-year follow-up, no differences in recovery of function and mortality were observed between the two groups. Conclusions Diabetic patients are at an increased risk of urinary tract infections and deep vein thrombosis complications but have similar recovery of function and 1-year mortality compared to nondiabetic patients.
Land use and soil organic matter in South Africa 1 : a review on spatial variability and the influence of rangeland stock production : review article

Degradation of soil as a consequence of land use poses a threat to sustainable agriculture in South Africa, resulting in the need for a soil protection strategy and policy. Development of such a strategy and policy require cognisance of the extent and impact of soil degradation processes. One of the identified processes is the decline of soil organic matter, which also plays a central role in soil health or quality. The spatial variability of organic matter and the impact of grazing and burning under rangeland stock production are addressed in this first part of the review. Data from uncoordinated studies showed that South African soils have low organic matter levels. About 58% of soils contain less than 0.5% organic carbon and only 4% contain more than 2% organic carbon. Furthermore, there are large differences in organic matter content within and between soil forms, depending on climatic conditions, vegetative cover, topographical position and soil texture. A countrywide baseline study to quantify organic matter contents within and between soil forms is suggested for future reference. Degradation of rangeland because of overgrazing has resulted in significant losses of soil organic matter, mainly as a result of lower biomass production. The use of fire in rangeland management decreases soil organic matter because litter is destroyed by burning. Maintaining or increasing organic matter levels in degraded rangeland soils by preventing overgrazing and restricting burning could contribute to the restoration of degraded rangelands. This restoration is of the utmost importance because stock farming uses the majority of land in South Africa.
THE USE OF β-BLOCKERS IN HYPERTENSION

The compelling reason for treating hypertension is to prevent the associated cardiovascular mortality and morbidity: in particular stroke, myocardial infarction and heart failure (HF). The treatment of elevated arterial pressure with antihypertensive agents results in significant reductions in cardiovascular morbidity and mortality (1). In a meta-analysis of 13 major intervention trials in hypertensive subjects, a reduction in diastolic blood pressure of just 5–6 mm Hg was associated with a 42% reduction in the incidence of stroke and a 14% reduction in coronary heart disease (CHD) (1). Similar results were found in three subsequent intervention trials in elderly patients: the Systolic Hypertension in the Elderly Program (SHEP) (2), the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) (3), and the Medical Research Council (MRC) Trial in Older Adults (4). When the data from trials in the elderly (SHEP, STOP-Hypertension, and MRC) were included in an update of the meta-analysis, the preventive effect of antihypertensive treatment on CHD morbidity and mortality was 16%, compared with 38% for stroke (5). Although the relative risk reduction is similar in young and old hypertensive subjects, the absolute risk reduction and the number of events is much greater in the elderly because of their higher baseline risk (6). Many of the major intervention studies were planned and conducted in the 1970s and 1980s, which explains the prominent role of diuretics and β-blockers in many trials, since these were the drugs used most widely during this time, even if treatment with multiple drugs was Journal of Cardiovascular PharmacologyTM 38 (Suppl. 3):S25–S31 © 2001 Lippincott Williams & Wilkins, London
REPLY: Key factors affecting the efficacy of NSAIDs are ocular penetration, potency in inhibiting COX ac- tivity, and maintenance of COX inhibition throughout the dosing cycle. For the following reasons, bromfenac

REPLY: Key factors affecting the efficacy of NSAIDs are ocular penetration, potency in inhibiting COX activity, and maintenance of COX inhibition throughout the dosing cycle. For the following reasons, bromfenac 0.09% twice a day does not appear to fulfill these criteria as well as ketorolac 0.4% 4 times a day. First, the over 20-fold higher ketorolac concentrations in the aqueous cannot be explained by a 4-fold difference in the initial concentrations of ophthalmic ketorolac and bromfenac formulations. A difference of this magnitude is a robust indication of a significantly higher partition coefficient of ketorolac and strongly suggests that ketorolac 0.4% penetrates into the aqueous more effectively than bromfenac 0.09%. In a similar study, we demonstrated that a 2-day dosing regimen of ketorolac 0.4% 4 times a day maintained significantly higher aqueous concentrations and lowered aqueous PGE2 levels significantly more than a 2-day regimen of bromfenac 0.09% twice a day at trough levels (LD Waterbury, MD, FA Bucci Jr, MD, ‘‘Aqueous PGE2 Levels at Trough Ketorolac and Bromfenac Concentrations Following a 2-Day Preoperative Dosing in Patients Undergoing Cataract Surgery,’’ presented at the Association for Research in Vision and Ophthalmology Summer Eye Research Conference, Monterey, California, USA, July 2008). The mean aqueous PGE2 level was 285.6 pg/mL G 141.9 (SD) in ketorolac patients and 386.2 G 131.0 pg/mL in bromfenac patients (P Z .006) The mean aqueous concentration of ketorolac and bromfenac was 83.6 G 73.8 ng/mL and 9.2 G 6.6 ng/mL, respectively (P! .001) Second, the higher potency of bromfenac 0.09% in inhibiting COX-2 isoenzyme does not appear to compensate for its lower aqueous levels because COX-1, not COX-2, is the isoenzyme implicated in the inflammatory response to mechanical injury occurring during cataract surgery (Waterbury L, Galindo D. IOVS 2008; 49:ARVO E-Abstract 2618; Ogawa T, et al. IOVS 2007; 48:ARVO E-Abstract 5834). Ketorolac 0.4% is 10 times more potent than bromfenac 0.09% in suppressingCOX-1 activity.Certainly, the combination of anterior chamber concentration and COX inhibition is the key to therapeutic effect. In this context, our findings are proof of the concept by showing that ketorolac 0.4% (with a higher aqueous concentration and potency for COX-1 inhibition) was more effective than bromfenac 0.09% in lowering aqueous PGE2 levels. Third, the pharmacokinetics and pharmacodynamics of bromfenac 0.09% during the entire 12-hour dosing period are not known. Ogawa et al. measured aqueous bromfenac concentrations for only 5.5 hours (Ogawa T, et al. IOVS 2006; 47:ARVO E-Abstract 687). Using a computer simulation, they predicted that aqueous bromfenac concentration at 12 hours
Seasonal periodicity of plankton and benthic fauna community structure and diversity in a small North African reservoir

Aquatic biota in terms of phytoplankton, zooplankton and benthic fauna were qualitatively and quantitatively followed seasonally during 2007 in a North African small reservoir, Aswan Reservoir. Simultaneously, seasonal variations in water quality were investigated in order to determine how far the aquatic biota could be altered by physicochemical and biotic factors. In phytoplankton of the investigated reservoir, 75 species belonging to four systematic groups were recorded, comprising 11 Cyanoprokaryota, 24 Bacillariophyceae, 2 Dinophyceae and 38 Chlorophyceae. Most numerous zooplankton were Rotifera (23 species). Cladocera and Copepoda were less numerous, with only seven and three species, respectively. Early development stages of copepods, nauplii and copepodites were sometimes recorded in considerable numbers. Twenty‐two invertebrate species related to five animal groups were exclusively benthic fauna: three Oligochaeta, nine Mollusca, seven larvae of Chironomidae, one Platyhelminthes, one Hirudinea and one Decapoda. Generally, the estimated values of phytoplankton species richness were relatively higher than those of zooplankton or benthic fauna. In particular, phytoplankton was influenced by physicochemical factors – water transparency, salinity and soluble reactive silica contents – as well as biotic factors – zooplankton and benthic fauna. Levels of pH value, Mg+2, NO3‐N and chlorophyll‐a contents appeared to be the most influential parameters dictating the pattern of seasonal periodicity of benthic fauna. Numerically, the phytoplankton was somewhat more abundant in winter and autumn than in spring or summer. The peak of zooplankton population densities was observed in spring season. Benthic fauna tended to be abundant in summer and autumn seasons, showing a reverse seasonal trend from that of zooplankton. Cyanoprokaryota and Bacillariophyceae were the most important groups that determined the seasonal fluctuation pattern of phytoplankton. Rotifera and Copepoda were the most predominant groups influencing the seasonal periodicity of zooplankton. Oligochaeta and Mollusca alternated the dominancy of benthic fauna community in Aswan Reservoir.
Ripple (∼200-Hz) Oscillations in Temporal Structures

Summary Spontaneous network oscillations near 200 Hz have been described in the hippocampus and parahippocampal regions of rodents and humans. During the last decade the characteristics and the mechanisms behind these field “ripples” have been studied extensively, mainly in rodents. They occur during rest or slow-wave sleep and provide a very fast, short-lasting (approximately 50 msec) rhythmic and synchronous activation of specific projection cells and interneurons. Ripples are frequently triggered by a massive synaptic activation from the hippocampal CA3 subfield, which is called a sharp wave. Recent evidence suggests that ripples have a specific task in memory processing—namely, that they convey information stored in the hippocampus to the cortex where it can be preserved permanently. Network mechanisms involved in ripple oscillations may be relevant for understanding pathologic synchronization processes in temporal lobe epilepsy.
Regulation of signal transduction by RGS4.

In the present study, the function and the mechanism of action of RGS4, a member of a family of proteins called Regulators of G protein Signalling (RGS) was investigated. A C-terminal fluorescent tag on RGS4 confirmed that transiently transfected RGS4 was predominantly cytosolic and underwent translocation to the plasma membrane of HEK293T cells following co-expression of Gi1, the 2A-adrenoceptor, or agonist activated 2A-adrenoceptor. This translocation of RGS4 to the plasma membrane was most pronounced with the co-expression of the constitutively active GTPase deficient Gi1 Q204L. High-affinity GTPase experiments indicated that RGS4S30C had enhanced GAP activity towards Go1 compared to wild type RGS4. This approach also demonstrated a simultaneous significant decrease in potency of both adrenaline and UK14304 to increase 2A-arenoceptor-activated high-affinity GTPase activity of Go1 in the presence of RGS4 and a further significant decrease in potency of both ligands in the presence of RGS4S30C. This enhanced GAP activity and observed decrease in agonist potency was also transferable to RGS16, an RGS protein closely related to RGS4. The selectivity of the G subunit was also investigated. The enhanced GAP activity and simultaneous significant decrease in potency of adrenaline and UK14304 to increase 2A-arenoceptor-activated high-affinity GTPase activity of RGS4S30C and RGS16S30C was selective for Go1 over Gi1. RGS4S30K and RGS4S30F also demonstrated higher GAP activity than wild type RGS4 but no consensus side chain could be identified that conferred a specific enhancement or loss of GAP activity. The ability to inhibit intracellular calcium release by an activated 1b-adrenoceptor-G11 fusion protein was used in order to investigate the GAP activity of RGS4N88S, RGS4N128A and RGS4N88S,N128A. All three mutants had ablated GAP activity towards G11 and therefore failed to inhibit intracellular calcium release. A novel role for the RGS insensitive mutation G188S was also observed when despite similar expression, G11 G188S significantly reduced agonist-stimulated [35S]GTPS binding compared to wild type G11. RGS4 represents a novel target for pharmaceutical drug development and the study of its regulation of signal transduction is an important area of investigation. These results highlight specific areas of RGS4 research with great pharmaceutical potential.
DIGESTIÓN DE LOS LÍPIDOS EN LOS RUMIANTES: UNA REVISIÓN

Las cualidades saludables de la carne y la leche de los rumiantes para el ser humano dependen, entre otros factores, del tipo y las proporciones de los acidos grasos que contienen, que a su vez estan estrechamente relacionadas con la digestion de los lipidos en dichas especies. Debido a las bacterias del rumen, los lipidos incluidos en la dieta que no estan protegidos en alguna forma sufren un proceso de lipolisis y biohidrogenacion que resulta en la saturacion de la mayoria de los acidos grasos insaturados consumidos. La extension del proceso depende de las caracteristicas de los lipidos (tipo y cantidad) y la dieta (efecto en el pH ruminal). Cuando se reduce la eficacia de la biohidrogenacion, se acumulan productos intermedios caracteristicos en el rumen, tales como el acido vaccenico e isomeros del acido linoleico conjugado, entre los que destaca el acido rumenico. A pesar de la ausencia de monogliceridos en la digesta duodenal, la digestibilidad intestinal de la grasa es elevada por la presencia de abundantes lisolecitinas biliares y microbianas. No obstante, distintos estudios sugieren que la digestibilidad intestinal disminuye, probablemente debido a la limitada produccion de bilis, al aumentar la cantidad de grasa consumida. Claramente, la digestion microbiana ruminal de los lipidos tiene la maxima influencia en la cantidad de los distintos tipos de acidos grasos que pasa al intestino delgado, en tanto que la digestion intestinal determina el valor energetico de la grasa extra incluida en la dieta