Standardized Extract Research Articles

Management of Bleeding and Thrombotic Complications During Pediatric Extracorporeal Membrane Oxygenation: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

To derive systematic-review informed, modified Delphi consensus regarding the management of bleeding and thrombotic complications during pediatric extracorporeal membrane oxygenation (ECMO) for the Pediatric ECMO Anticoagulation CollaborativE Consensus Conference. A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021. The management of bleeding and thrombotic complications of ECMO. Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Twelve references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form. Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements for the management of bleeding and thrombotic complications in pediatric ECMO patients. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. Two good practice statements, 5 weak recommendations, and 18 consensus statements are presented. Although bleeding and thrombotic complications during pediatric ECMO remain common, limited definitive data exist to support an evidence-based approach to treating these complications. Research is needed to improve hemostatic management of children supported with ECMO.

Anticoagulation Monitoring and Targets: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

To derive systematic-review informed, modified Delphi consensus regarding anticoagulation monitoring assays and target levels in pediatric extracorporeal membrane oxygenation (ECMO) for the Pediatric ECMO Anticoagulation CollaborativE. A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021. Anticoagulation monitoring of pediatric patients on ECMO. Two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. Evidence tables were constructed using a standardized data extraction form. Risk of bias was assessed using the Quality in Prognosis Studies tool or the revised Cochrane risk of bias for randomized trials, as appropriate and the evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements for clinical recommendations focused on anticoagulation monitoring and targets, using a web-based modified Delphi process to build consensus (defined as > 80% agreement). One weak recommendation, two consensus statements, and three good practice statements were developed and, in all, agreement greater than 80% was reached. We also derived some resources for anticoagulation monitoring for ECMO clinician use at the bedside. There is insufficient evidence to formulate optimal anticoagulation monitoring during pediatric ECMO, but we propose one recommendation, two consensus and three good practice statements. Overall, the available pediatric evidence is poor and significant gaps exist in the literature.

Antifibrinolytic and Adjunct Hemostatic Agents: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

To derive systematic-review informed, modified Delphi consensus regarding antifibrinolytic and adjunct hemostatic agents in neonates and children supported with extracorporeal membrane oxygenation (ECMO) for the Pediatric ECMO Anticoagulation CollaborativE consensus conference. A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021. Use of antifibrinolytics (epsilon-aminocaproic acid [EACA] or tranexamic acid), recombinant factor VII activated (rFVIIa), or topical hemostatic agents (THAs). Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Eleven references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form. Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements for the management of bleeding and thrombotic complications in pediatric ECMO patients. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. One weak recommendation and three consensus statements are presented. Evidence supporting recommendations for administration of antifibrinolytics (EACA or tranexamic acid), rFVIIa, and THAs were sparse and inconclusive. Much work remains to determine effective and safe usage strategies.

The Influence of the Extracorporeal Membrane Oxygenation Circuit and Components on Anticoagulation Management: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

To derive systematic-review informed, modified Delphi consensus regarding the influence of extracorporeal membrane oxygenation (ECMO) circuit components on anticoagulation practices for pediatric ECMO for the Pediatric ECMO Anticoagulation CollaborativE. A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021. Management of ECMO anticoagulation in the setting of different ECMO circuit components. Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Twenty-nine references were used for data extraction and informed recommendations, evidence-based consensus statements, and good practice statements. Evidence tables were constructed using a standardized data extraction form. Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements or good practice statements for the influence of ECMO circuit and components on anticoagulation management. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. One good practice statement, 2 weak recommendations, and 2 consensus statements are presented. The incorporation of new component technologies into clinical practice has outpaced clinical investigations of anticoagulation strategies for pediatric ECMO. Future investigations should leverage academic and industrial collaborations, translational platforms, and modern biostatistical methods to improve patient outcomes.

Recommendations on Monitoring and Replacement of Antithrombin, Fibrinogen, and Von Willebrand Factor in Pediatric Patients on Extracorporeal Membrane Oxygenation: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

To derive systematic review informed, modified Delphi consensus regarding monitoring and replacement of specific coagulation factors during pediatric extracorporeal membrane oxygenation (ECMO) support for the Pediatric ECMO Anticoagulation CollaborativE. A structured literature search was performed using PubMed, Embase, and Cochrane Library (CENTRAL) databases from January 1988 to May 2020, with an update in May 2021. Included studies assessed monitoring and replacement of antithrombin, fibrinogen, and von Willebrand factor in pediatric ECMO support. Two authors reviewed all citations independently, with conflicts resolved by a third reviewer if required. Twenty-nine references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form. Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. A panel of 48 experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. We developed one weak recommendation and four expert consensus statements. There is insufficient evidence to formulate recommendations on monitoring and replacement of antithrombin, fibrinogen, and von Willebrand factor in pediatric patients on ECMO. Optimal monitoring and parameters for replacement of key hemostasis parameters is largely unknown.

Effectiveness of Injection of Ginkgo biloba Leaf Extract Combined with Early Rehabilitation on Functional Recovery in Patients Following Ischemic Stroke

The interest in the development of traditional Chinese medicine for the treatment of ischemic stroke (IS) is growing. In this study, we aim to examine the therapeutic effects of the standardized extract of Ginkgo biloba leaf EGb-761 on neurological behavioral outcomes and brain infarction in rats following cerebral ischemia. Additionally, we evaluated the effectiveness of combining EGb-761 injection with early rehabilitation in improving the functional status of patients with IS. The rats were induced with focal transient cerebral ischemia by means of middle cerebral artery occlusion (MCAO). The rats undergoing MCAO/reperfusion were given an intraperitoneal injection of different doses of EGb-761. A total of 65 patients with IS were recruited and assigned into receiving conventional treatments and intravenous drips of Ginaton injection, followed by early rehabilitation. The results showed that neurological deficit scores, brain infarct volume, neuronal apoptosis, and oxidative stress injury were reduced in the MCAO/reperfusion rats treated with different doses of EGb-761 compared to those without EGb-761 treatment. These reductions were more significant in the high-dose EGb-761 treatment group (P <0.05). Both EGb-761 treatment and conventional treatment combined with early rehabilitation resulted in increased muscle strength and higher total BI scores in the patients. However, these increases were more pronounced in the group receiving Ginaton injection (P <0.05). In conclusion, our study demonstrates that acute administration of EGb-761 may contribute to better neurological behavioral outcomes and reduced area of brain infarction in rats following cerebral ischemia and EGb-761 treatment integrated with early rehabilitation could improve the muscle strength and functional recovery of patients with IS.

Lanctos 75™ is A Novel Retino-Protective and Neovascular Inhibitor for Diabetic Retinopathy

Diabetic retinopathy (DR) is a significant neurovascular complication driven by abnormal angiogenesis. This study evaluated the efficacy and safety of Lanctos 75™, a proprietary standardized extract of Orthosiphon stamineus leaves (code name C5OSEW5050ESA), as a retinal-protective and anti-neovascular agent in streptozotocin-induced diabetic retinopathy in rats. The safety and neuroprotective properties of Lanctos 75™ were assessed in various in vitro and in vivo models of ischemia-induced neuronal injury. In vitro studies using RGC-5 cells showed that Lanctos 75™ significantly suppressed apoptosis, demonstrating strong cytoprotective effects. In vivo, PanOptic ophthalmoscopic imaging in diabetic rats revealed that Lanctos 75™ protected against retinal damage, inhibiting the development of microaneurysms, hemorrhages, vascular leakage, venous beading, and retinal inflammation. Fluorescence molecular tomography (FMT) imaging further confirmed its protective effect against ischemia-reperfusion injury and related inflammation. Overall, the results suggest that Lanctos 75™, with an effective dose of O. stamineus, holds promise as an adjunct therapy for diabetic retinopathy and other neovascular-related eye conditions.

Targeting senescence induced by age or chemotherapy with a polyphenol-rich natural extract improves longevity and healthspan in mice

Accumulating senescent cells within tissues contribute to the progression of aging and age-related diseases. Botanical extracts, rich in phytoconstituents, present a useful resource for discovering therapies that could target senescence and thus improve healthspan. Here, we show that daily oral administration of a standardized extract of Salvia haenkei (Haenkenium (HK)) extended lifespan and healthspan of naturally aged mice. HK treatment inhibited age-induced inflammation, fibrosis and senescence markers across several tissues, as well as increased muscle strength and fur thickness compared with age-matched controls. We also found that HK treatment reduced acutely induced senescence by the chemotherapeutic agent doxorubicin, using p16LUC reporter mice. We profiled the constituent components of HK by mass spectrometry, and identified luteolin—the most concentrated flavonoid in HK—as a senomorphic compound. Mechanistically, by performing surface plasmon resonance and in situ proximity ligation assay, we found that luteolin disrupted the p16–CDK6 interaction. This work demonstrates that administration of HK promotes longevity in mice, possibly by modulating cellular senescence and by disrupting the p16–CDK6 interaction.

Chromatographic Profiling of Ziziphus mauritiana Lam. Extracts for Phytochemical Characterization

Ziziphus mauritiana, commonly known as Chinese date, Ber, and Indian jujube, belongs to the Rhamnaceae family and is native to Southeast Asia. Although it has been naturalized in tropical regions from South Africa to the Middle East and the Indian subcontinent, its phytochemical profile remains underexplored. A comprehensive phytochemical profiling and standardization of extract can be achieved by TLC and HPLC analysis. The study involves the development of improved chromatographic methods for the analysis of local Z. mauritiana leaves, including selection of the mobile phase type, gradient elution method and temperature, which are all potential HPLC parameters that may affect the result of analysis. The leaves were subjected to extraction through maceration utilizing methanol and hexane. The results indicated a percentage yield of 7.28% for hexane and 18.98% for methanol. TLC investigations were conducted using the crude extracts obtained, employing a dual mobile phase system (ethyl acetate: chloroform = 6:4) for the methanol extract and hexane:acetone (6:4) for the hexane extract, respectively. Both systems exhibited successful separation of phytochemicals. The methanol extract was subjected to HPLC profiling in accordance with the established protocols. Naringin was determined to be present through qualitative HPLC screening. Phytochemicals present in the leaves of Z. mauritiana are identified as a result of this research, which also sheds light on the optimal parameters for TLC and HPLC analyses. This research may also provide valuable insight regarding the importance of quality control and formulation of herbal medicines from the standardized extract.

Anti-wrinkle efficacy of standardized phenolic acids polymer extract (PAPE)from propolis: Implications for antiaging and skin health.

The increasing quest for effective and safe antiaging skincare solutions has led to a surge in the exploration of natural compounds such as phenolic acids. Despite the proven efficacy of traditional antiaging ingredients like retinol, their associated side effects have necessitated the search for alternatives. This study aimed to assess the anti-wrinkle efficacy of a standardized phenolic acids polymer extract (PAPE) from propolis, employing both invitro and clinical methodologies to explore its suitability as a novel antiaging skincare ingredient for sensitive and nonsensitive skin types. The study comprised of evaluating PAPE effects on key skin health biomarkers in dermal fibroblasts and keratinocytes. A double-blind, randomized clinical trial involving female participants aged 30-70 years assessed the wrinkle-reducing effectiveness of face creams formulated with two concentrations of PAPE (1.5% and 3%) over a 28-day period. In vitro studies indicated that PAPE could modulate inflammation and tissue remodeling biomarkers. The clinical trial demonstrated that applying PAPE-enriched cream resulted in significant wrinkle reduction, with 25% and 34% improvements for the 1.5% and 3% PAPE formulations, respectively. Subjective feedback from participants further validated the antiaging efficacy and overall satisfaction with the product. Incorporating PAPE offers a compelling antiaging solution, significantly reducing wrinkle depth with a favorable safety profile. The study substantiates PAPE's potential as an effective and safe alternative to conventional antiaging ingredients, aligning with the cosmetic industry's shift toward natural, evidence-based formulations.

LOW TEMPERATURE ANALYTICAL CLOUD POINT EXTRACTION. 2: PRECONCENTRATION AND SPECTROPHOTOMETRIC DETERMINATION OF GE(IV)

Cloud point extraction is a powerful tool for the analytical preconcentration of trace amounts of analytes. The standard cloud point extraction procedure requires prolonged heating of the solution, which is not always appropriate in the case of thermally unstable analytes or analytical forms and significantly limits the capabilities of the method. One of the ways to modify cloud point extraction is to find approaches to intensifying the process of analytical concentration. The main disadvantage of cloud point extraction is the need for thermal, ultrasonic, infrared or any other initiation of the formation of the surfactant rich phase. It has been shown that salts of aromatic carboxylic acids can cause instantaneous formation of a surfactant-rich phase. In this work, the conditions of micellar extraction concentration of Ge(IV) in the form of a complex with 6,7-dihydroxy-2-phenyl-4-methylbenzopyrylium bromide into the micellar phase of the nonionic surfactant triton X-100 were studied and optimized. It is shown that the introduction of ammonium benzoate into the system at a pH of 1.0 and a triton X-100 concentration of 0.5 vol.% leads to the initiation of the formation of a micellar phase at room temperature. The method of spectrophotometric determination of Ge(IV) with 6,7-dihydroxy-2-phenyl-4-methylbenzopyrylium bromide after its micellar- extraction concentration has been developed. The calibration graph is linear in the concentration range of 4.36–472 μg/L, and the limits of detection and determination are 1.31 and 4.36 μg/L, respectively. The proposed method was tested in the analysis of model solutions and biologically active additives, and the relative standard deviation does not exceed 5.1%.

Anti-obesity effect of standardized ethanol extract from the leaves of Adenocaulon himalaicum Edgew. via regulation of adipogenesis and lipid accumulation in 3T3-L1 cells and high-fat diet-induced obese mice

Obesity causes various complications like type 2 diabetes and fatty liver, and as the proportion of obese patients increases worldwide, the discovery of new treatments has become necessary. Here, we evaluated the in vitro and in vivo anti-obesity effects of 30% ethanol extract of Adenocaulon himalaicum Edgew. (EEAH). Treatment with EEAH suppressed adipogenesis and lipogenesis via the AMP-activated protein kinase (AMPK) pathway. EEAH altered the expression of adipogenic and lipogenic proteins and impeded mitotic clonal expansion during adipocyte differentiation. Oral administration of EEAH significantly mitigated body weight gain and fat accumulation in high-fat diet-induced obese mice. EEAH regulated adipogenesis and lipid accumulation in white adipose and liver tissues. EEAH modulated plasma levels of insulin and leptin. In brown adipose tissue, EEAH induced expression of thermogenic factors. EEAH shows potential for treating obesity by reducing body weight, inhibiting lipid accumulation, and suppressing adipogenesis through the AMPK pathway.

Integrating network pharmacology and experimental verification to reveal the anti-inflammatory ingredients and molecular mechanism of pycnogenol.

Introduction: Pycnogenol (PYC), a standardized extract from French maritime pine, has traditionally been used to treat inflammation. However, its primary active components and their mechanisms of action have not yet been determined. Methods: This study employed UPLC-MS/MS (Ultra-high performance liquid chromatography-tandem mass spectrometry) and network pharmacology to identify the potential active components of PYC and elucidate their anti-inflammatory mechanisms by cell experiments. Results: 768 PYC compounds were identified and 19 anti-inflammatory compounds were screened with 85 target proteins directly involved in the inflammation. PPI (protein-protein interaction) analysis identified IL6, TNF, MMP9, IL1B, AKT1, IFNG, CXCL8, NFKB1, CCL2, IL10, and PTGS2 as core targets. KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis suggested that the compound in PYC might exert anti-inflammatory effects through the IL17 and TNF signal pathways. Cell experiments determined that PYC treatment can reduce the expression of IL6 and IL1β to relieve inflammation in LPS (lipopolysaccharide)-induced BV2 cells. Conclusion: PYC could affect inflammation via multi-components, -targets, and -mechanisms.

Evaluation of the acute and sub-acute toxicity of the standardized extract of Avicennia officinalis L. in mice

Avicennia officinalis L. (AOL) has shown promise for its anti-inflammatory, anti-cancer, and antioxidant properties. However, there is no research on the toxicity of this plant in Vietnam. The acute and sub-acute toxicology study proved that AOL leaf extracts are practically non-toxic in normal mice. Acute toxicity assessment was conducted with single oral doses of AOL extract (2500, 3100, 4100, and 5000 mg/kg). In sub-acute toxicity, mice were administered daily oral doses of AOL extract (200 and 400 mg/kg) for 28 days. Blood was collected from the heart, liver, and kidneys for further analysis. The comprehensive results revealed an oral median lethal dose (LD50) exceeding 5000 mg/kg, indicating low acute toxicity. A sub-acute study (200 and 400 mg/kg/day) showed no deaths or weight gain. At both doses, the standardized AOL extracts decreased serum aspartate transaminase activity. Administration of the 200 mg/kg group significantly increased blood urea levels; however, histological examination of mouse kidneys in this group revealed no signal of damage. Histological examination of mouse livers revealed mild degeneration, possibly due to the use of adult mice and potentially unrelated to the extract. This study emphasizes AOL's potential for further pharmacological testing based on its low acute toxicity and promising results.

Feeding modalities, HIV transmission and its predictors among HIV-exposed infants visited Gamo and Gofa zones public health facilities, Southern Ethiopia: a retrospective follow up study

BackgroundDespite the highest (88%) Prevention of Mother-To-Child Transmission (PMTCT) of HIV coverage in Eastern Africa, 50% of new HIV infections in children aged 0–14 years occur in the region.ObjectiveThe aim of this study was to assess the feeding modalities, the rate of HIV transmission and its predictors among HIV exposed infants (HIV-EIs) visited Gamo and Gofa Zones public health facilities, Southern Ethiopia from January 2013 to February 2019.Method and materialsInstitution-based retrospective follow up study was employed among 450 HIV-EIs having DNA/PCR test results. All infant-mother pair records in selected health facilities were reviewed using a standard data extraction tool from March to July 2019. HIV transmission probabilities were assessed by Kaplan–Meier time-to-event analysis method and log-rank tests were used to compare the risk among different groups. The Cox-proportional hazards model, adjusted on infant feeding modalities and other co-variants was used to identify predictors of HIV transmission, and statistical significance was declared at a p-value of < 0.05.ResultsIn total, 383 complete records were analyzed. In the study, 85.6% (95%CI: 81.6%, 89.1%) of HIV-EIs were exclusively breastfed in the first six months. The 18 months probability of infant HIV transmission was 64 (16.7%) (95%CI: 13.1%–20.8%). The risk of HIV-transmission was higher among infants who were delivered at the hospital than health centers/health posts (AHR = 3.07; 95%CI: 1.19, 7.95); discontinued Cotrimoxazole prophylaxis in at least one visit (AHR = 6.32; 95%CI: 3.35, 11.94); did not exclusively breastfeed (AHR = 3.07; 95%CI: 1.72, 5.47) and came from urban areas (AHR = 5.90; 95%CI: 1.40, 24.85).ConclusionsThe study showed that HIV-EIs had a greater rate of 18 months HIV transmission than the national pooled prevalence. The risk of transmission is higher among infants who do not breastfeed exclusively for the first 6 months, and the risk increases with the number of months spent by breastfeeding. Therefore, strengthening counselling on safer feeding options and Cotrimoxazole prophylaxis use; provision of quality PMTCT service with special focus in hospitals and urban residents were recommended.

Magnitude and determinants of undernutrition among tuberculosis patients in Ethiopia: systematic review and meta-analysis

BackgroundUndernutrition increases the risk of TB infection to be active TB, death and relapse of the disease. Undernutrition also disturbs the management process of tuberculosis. Therefore, this study aimed to estimate the pooled magnitude and determinants of undernutrition among TB patients in Ethiopia.MethodsFrom August 20, 2022 to January 6, 2023, the research articles were identified via the search engines Google Scholar, Medline, Pub Med, Cochrane Library, and Web of Science. Stata version 14 was used for analysis, along with a standardized data extraction checklist. The Cochrane Q test statistic and I2 statistics were used to determine heterogeneity. A random-effect model was used to assess the extent of undernutrition among TB patients. OR with a 95% CI was used to report the relationship between undernutrition and independent factors. A funnel plot and Egger’s test were used to examine publication bias.ResultsA total of 720 research articles were identified via several databases and 21 studies were included in the systematic review and meta-analysis. The pooled magnitude of undernutrition among TB patients was 48.23% (95% CI 42.84, 53.62). The current meta-analysis revealed that patients who had no formal education (OR = 2.11(95%CI: 1.09, 4.06), average monthly income < 1800 ETB (OR = 2.32 (95CI: 1.33, 4.04), unable to work (OR = 2.61(95CI:1.99, 3.43), patients who had eating disorder (OR = 2.73 (95CI: 2.09, 3.56), patients who had intestinal parasite (OR = 3.77 (95CI: 2.39, 5.94), patients of > 5 family size (OR = 3.79 (95CI: 1.06, 14.93), and patients who drank alcohol (OR = 1.47(95CI: 1.06, 2.05) were significantly associated with undernutrition.ConclusionThis meta-analysis examined the high magnitude of undernutrition among TB patients in Ethiopia. Strategic and police-oriented intervention to prevent factors contributing to the problem is mandatory.

Preanalytical considerations in quantifying circulating miRNAs that predict end-stage kidney disease in diabetes.

Our previous study identified 8 risk and 9 protective plasma miRNAs associated with progression to end-stage kidney disease (ESKD) in diabetes. This study aimed to elucidate preanalytical factors that influence the quantification of circulating miRNAs. Using the EdgeSeq platform, which quantifies 2,002 miRNAs in plasma, including ESKD-associated miRNAs, we compared miRNA profiles in whole plasma versus miRNA profiles in RNA extracted from the same plasma specimens. Less than half of the miRNAs were detected in standard RNA extraction from plasma. Detection of individual and concentrations of miRNAs were much lower when RNA extracted from plasma was quantified by RNA sequencing (RNA-Seq) or quantitative reverse transcription PCR (qRT-PCR) platforms compared with EdgeSeq. Plasma profiles of miRNAs determined by the EdgeSeq platform had excellent reproducibility in assessment and had no variation with age, sex, hemoglobin A1c, BMI, and cryostorage time. The risk ESKD-associated miRNAs were detected and measured accurately only in whole plasma and using the EdgeSeq platform. Protective ESKD-associated miRNAs were detected by all platforms except qRT-PCR; however, correlations among concentrations obtained with different platforms were weak or nonexistent. In conclusion, preanalytical factors have a profound effect on detection and quantification of circulating miRNAs in ESKD in diabetes. Quantification of miRNAs in whole plasma and using the EdgeSeq platform may be the preferable method to study profiles of circulating cell-free miRNAs associated with ESKD and possibly other diseases.

Double-blind randomized placebo-controlled supplementation of a standardized Terminalia chebula fruit extract alters the gut microbiome, phageome, and increases short chain fatty acids in High-BMI, borderline diabetic females

Terminalia chebula (TC) is an Ayurvedic herb containing polyphenolic compounds that interact with gut microbiota to modulate bioactivity. To examine how TC supplementation modulates the gut microbiome and associated metabolic pathways, a double-blind, randomized, placebo-controlled study that screened 58 and enrolled 43 females aged 25–55 with a BMI of 25–35 kg/m2 and HbA1C between 5.5–7. Subjects were randomized to standardized preparation of TC (250 mg, Synastol® TC) capsules or oral placebo twice daily for 8 weeks. Stool sample collections and venipuncture were performed. Α-diversity of the gut microbiome increased in the TC group at week 8 versus placebo (p < 0.05). Akkermansia muciniphila, Alistipes_putredinis, Bacteroides_u_s, Ruminococcaceae_u_s, Waltera_intestinalis, Lachnospira_eligens, Parabacteroides phage YZ-2015b and Uncultured_crAssphage increased at week 8 versus baseline following TC supplementation. Circulating acetic acid (p < 0.05), propionic acid (p < 0.01), and butyric acid (p = 0.12) increased at week 8 in the TC group versus placebo. Chenodeoxycholate and tauro-beta-muricholate increased following TC supplementation (p < 0.05). TC supplementation increases beneficial gut bacteria, phages, and circulating SCFAs, which may modulate bile acid synthesis. Future studies on how TC extract supplementation influences the metabolome in an expanded population are warranted.

UP165, standardized corn leaf extract and its active component 6-methoxybenzoxazolinone induce non-rapid eye movement sleep through melatonergic and GABAergic mechanisms

The aim of this study was to investigate the sleep-promoting effects of corn leaf extract (UP165) and its active component 6-methoxybenzoxazolinone (6-MBOA), along with the underlying mechanisms in rodent models. Sleep activity in UP165 was measured by measuring sleep duration in the pentobarbital induced sleep model, and sleep quality was evaluated through electroencephalogram (EEG) analysis. In addition, the sleep mechanism was analyzed through an in vivo sleep study co-administrated with receptor antagonists. The administrations of both UP165 and 6-MBOA effectively increased sleep duration, demonstrating a 3-fold increase sleep time at 100 mg/kg UP165 and a 2.3-fold increase at 280 μg/kg 6-MBOA compared to those of the control group. The sleep-promoting effect of UP165 was also observed in the caffeine-induced insomnia model, resulting in a 71.6% increase in sleep duration. The UP165-mediated increase in sleep time was attributed to enhanced non-rapid eye movement (NREM) sleep, specifically an increase in the δ-wave sleep measured by EEG. Mechanism analysis with co-administration of competitive antagonists in vivo revealed that UP165 and 6-MBOA enhanced sleep duration through binding to gamma-aminobutyric acid type A (GABAA) and melatonin receptors. Oral administration of UP165 for 4 weeks effectively increased both gene expression and protein levels of GABAA, melatonin 1A, and melatonin 1B receptors. High-dose administration of UP165 significantly decreased the blood level of corticosterone, while concurrently increased GABA, serotonin, and melatonin levels in brain. This study highlights the potential of UP165 and 6-MBOA as edible-grade natural ingredients for sleep promotion.

Red Oranges and Olive Leaf Waste-Derived Bioactive Extracts Promote Adipocyte Functionality In Vitro.

Obesity is increasingly prevalent worldwide and is linked to metabolic diseases, such as insulin resistance (IR) and type 2 diabetes mellitus (T2DM), due to excessive free fatty acids (FFAs). Although lifestyle changes are effective, they often prove to be insufficient as initial treatments for obesity. Additionally, while surgical and pharmacological interventions are available, they are not entirely safe or effective. Recently, interest has grown in utilizing food waste and plant-derived phenolic compounds for their health benefits, presenting a promising avenue for managing obesity and its related disorders. Indeed, many studies have examined the potential inhibitory effects of the natural extract on adipocyte differentiation and lipid accumulation. This study focused on the evaluation of the effects of standardized extracts obtained from red oranges and olive leaf waste on 3T3-L1 murine pre-adipocyte and adipocyte functionality. Red orange extract (ROE) and olive leaf extract (OLE), alone and in combination, were tested to assess their anti-obesity and anti-inflammatory effects, as well as their potential therapeutic benefits. Three in vitro models were established to investigate the effects of the extracts on (I) adipocyte differentiation; (II) mature and hypertrophic adipocytes challenged with palmitic acid (PA) and erastin (ER), respectively; and (III) erastin-induced cytotoxicity on pre-adipocytes.