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During the routine postmortem inspection from carcasses and offal of slaughtered ewes in an abattoir in Isfahan (Iran), an ovine heart was discovered with a firm nodule in the myocard on palpation. In closer examination, a liquid containing cyst (1x1 cm) was recognized on left part of the heart. The cyst had thick fibrotic capsule in outer surface and a thin inner layer containing few white clusters of scolices. White clusters contained scolices that adhered to the inner transparent layer, like white beads. Based on the gross and microscopical characteristics, the cyst was diagnosed as non-cerebral coenurus cyst. This is a rare report of heart coenurosis in a sheep.

Accumulating evidence suggests an association between autism spectrum disorders (ASD) and inflammation in brain regions related to cognitive function. The natural flavonoid luteolin has antioxidant, anti-inflammatory, mast cell–blocking, and neuroprotective effects. It was shown to improve cognitive performance in a mouse model of ASD, but its effect in humans has not been adequately studied. The goal of this study was to assess the effectiveness and tolerability in white children with ASD of a dietary supplement containing 2 flavonoids (>95% pure), luteolin (100 mg/capsule, from chamomile) and quercetin (70 mg/capsule), and the quercetin glycoside rutin (30 mg/capsule) from the Sophora japonica leaf, formulated in olive kernel oil to increase oral absorption. Fifty children (4–10 years old; 42 boys and 8 girls) with ASD were enrolled in a 26-week, prospective, open-label trial at the 2nd University Department of Psychiatry at “Attikon” General Hospital, Athens, Greece. Children were referred for the study by their respective physicians or came from the practice of the senior author. ASD diagnosis by clinical assessment was based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, symptom list and corroborated by using the Autism Diagnostic Observation Schedule. The dose of the study formulation used was 1 capsule per 10 kg weight per day with food. The primary outcome measures were the age-equivalent scores in the Vineland Adaptive Behavior Scales domains. Secondary outcomes included the Aberrant Behavior Checklist, the Autism Treatment Evaluation Checklist, and the Clinical Global Impression–Improvement score. Data were measured at baseline, week 18, and week 26. Parents were interviewed for any possible improvements they noticed and instructed to report any unusual adverse events. A total of 40 children completed the protocol. There was a significant improvement in adaptive functioning as measured by using the VABS age-equivalent scores (8.43 months in the communication domain, 7.17 months in daily living skills, and 8 months in the social domain; P < 0.005), as well as in overall behavior as indicated by the reduction (26.6%–34.8%) in Aberrant Behavior Checklist subscale scores. Age, sex, and history of allergies had no effect on the results, whereas the initial level of functioning or difficulty did predict the final outcome in most of the measures used. There was a transient (1–8 weeks) increased irritability in 27 of the 50 participants. These results are encouraging in that the combination of the flavonoids luteolin and quercetin seemed to be effective in reducing ASD symptoms, with no major adverse effects. ClinicalTrials.gov identifier: NCT01847521.

Age-related sarcopenia is a progressive and generalized skeletal muscle disorder associated with adverse outcomes. Herein, we evaluate the effects of a combination of electrical muscle stimulation (EMS) and a whey-based nutritional supplement (with or without polyphenols and fish oil-derived omega-3 fatty acids) on muscle function and size. Free-living elderly participants with mobility limitations were included in this study. They received 2 sessions of EMS per week and were randomly assigned to ingest an isocaloric beverage and capsules for 12 weeks: (1) carbohydrate + placebo capsules (CHO, n = 12), (2) whey protein isolate + placebo capsules (WPI, n = 15) and (3) whey protein isolate + bioactives (BIO) capsules containing omega-3 fatty acids, rutin, and curcumin (WPI + BIO, n = 10). The change in knee extension strength was significantly improved by 13% in the WPI + BIO group versus CHO on top of EMS, while WPI alone did not provide a significant benefit over CHO. On top of this, there was the largest improvement in gait speed (8%). The combination of EMS and this specific nutritional intervention could be considered as a new approach for the prevention of sarcopenia but more work is needed before this approach should be recommended. This trial was registered at the Japanese University Hospital Medical Information Network (UMIN) clinical trial registry (UMIN000008382).

Background Tau pathology is a hallmark of Alzheimer’s disease (AD) and other tauopathies. During disease progression, abnormally phosphorylated forms of tau aggregate and accumulate into neurofibrillary tangles, leading to synapse loss, neuroinflammation, and neurodegeneration. Thus, targeting of tau pathology is expected to be a promising strategy for AD treatment. Methods The effect of rutin on tau aggregation was detected by thioflavin T fluorescence and transmission electron microscope imaging. The effect of rutin on tau oligomer-induced cytotoxicity was assessed by MTT assay. The effect of rutin on tau oligomer-mediated the production of IL-1β and TNF-α in vitro was measured by ELISA. The uptake of extracellular tau by microglia was determined by immunocytochemistry. Six-month-old male Tau-P301S mice were treated with rutin or vehicle by oral administration daily for 30 days. The cognitive performance was determined using the Morris water maze test, Y-maze test, and novel object recognition test. The levels of pathological tau, gliosis, NF-kB activation, proinflammatory cytokines such as IL-1β and TNF-α, and synaptic proteins including synaptophysin and PSD95 in the brains of the mice were evaluated by immunolabeling, immunoblotting, or ELISA. Results We showed that rutin, a natural flavonoid glycoside, inhibited tau aggregation and tau oligomer-induced cytotoxicity, lowered the production of proinflammatory cytokines, protected neuronal morphology from toxic tau oligomers, and promoted microglial uptake of extracellular tau oligomers in vitro. When applied to Tau-P301S mouse model of tauopathy, rutin reduced pathological tau levels, regulated tau hyperphosphorylation by increasing PP2A level, suppressed gliosis and neuroinflammation by downregulating NF-kB pathway, prevented microglial synapse engulfment, and rescued synapse loss in mouse brains, resulting in a significant improvement of cognition. Conclusion In combination with the previously reported therapeutic effects of rutin on Aβ pathology, rutin is a promising drug candidate for AD treatment based its combinatorial targeting of tau and Aβ.

Supplementation with prebiotic polyphenol rutin is a potential dietary therapy for type 2 diabetes prevention in adults with obesity, based on previous glycaemic improvement in transgenic mouse models. Gut microbiota are hypothesised to underpin these effects. We investigated the effect of rutin supplementation on pancreatic β-cell function measured as C-peptide/glucose ratio, and 16S rRNA gene-based gut microbiota profiles, in a cohort of individuals with overweight plus normoglycaemia or prediabetes. Eighty-seven participants were enrolled, aged 18–65 years with BMI of 23–35 kg/m2. This was a 12-week double-blind randomised controlled trial (RCT), with 3 treatments comprising (i) placebo control, (ii) 500 mg/day encapsulated rutin, and (iii) 500 mg/day rutin-supplemented yoghurt. A 2-h oral glucose tolerance test (OGTT) was performed at baseline and at the end of the trial, with faecal samples also collected. Compliance with treatment was high (~90%), but rutin in both capsule and dietary format did not alter pancreatic β-cell response to OGTT over 12 weeks. Gut bacterial community composition also did not significantly change, with Firmicutes dominating irrespective of treatment. Fasting plasma glucose negatively correlated with the abundance of the butyrate producer Roseburia inulinivorans, known for its anti-inflammatory capacity. This is the first RCT to investigate postprandial pancreatic β-cell function in response to rutin supplementation.

Rutin is a flavonoid compound with potential for treating Alzheimer’s disease, preventing brain damage, mitigating cerebral ischemia–reperfusion injury, and exhibiting anti-glioblastoma activity. However, its efficacy is limited by its low solubility, poor bioavailability, and limited permeability across the blood–brain barrier (BBB). To enhance the bioavailability and brain-targeting ability of Rutin, transferrin-modified Rutin liposome (Tf-Rutin-Lip) was developed using liposomes as a delivery system. Rutin liposomes were prepared using the thin-film dispersion method, and the preparation conditions were optimized using the response surface methodology. Then, transferrin (Tf) was incorporated into the liposomes through covalent modification, yielding Tf-Rutin liposomes. The toxicity of these liposomes on bEnd.3 cells, as well as their impact on the tight junctions of these cells, was rigorously evaluated. Additionally, in vitro and in vivo experiments were conducted to validate the brain-targeting efficacy of the Tf-Rutin liposomes. A susceptible detection method was developed to characterize the pharmacokinetics of Tf-Rutin-Lip further. The optimized conditions for the preparation of Tf-Rutin-Lip were determined as follows: a lipid-to-cholesterol ratio of 4.63:1, a drug-to-lipid ratio of 1:45.84, a preparation temperature of 42.7 °C, a hydration volume of 20 mL, a sonication time of 10 min, a surfactant concentration of 80 mg/mL, a DSPE-MPEG-2000 concentration of 5%, and a DSPE-PEG2000-COOH to DSPE-MPEG-2000 molar ratio of 10%. The liposomes did not affect the cell activity of bEnd.3 cells at 24 h and did not disrupt the tight junction of the blood–brain barrier. Tf-modified liposomes were taken up by bEnd.3 cells, which, in turn, passed through the BBB, thus improving liposomal brain targeting. Furthermore, the results of pharmacokinetic experiments showed that the Cmax, AUC0-∞, AUC0-t, MRT0-∞, and t1/2 of Tf-Rutin-Lip increased 1.99-fold, 2.77-fold, 2.58-fold, 1.26-fold, and 1.19-fold compared to those of free Rutin solution, respectively. These findings suggest that Tf-Rutin-Lip is brain-targeted and may enhance the efficacy of Rutin in the treatment of brain disorders.

Quercetin is a flavonoid with a wide range of biological activities. It mainly occurs in plants as glycosides, such as rutin (quercetin rutinoside) in tea. Quercetin and rutin are used in many countries as vasoprotectants and are ingredients of numerous multivitamin preparations and herbal remedies. The primary objective was to characterise and compare the absorption and the pharmacokinetics of quercetin from quercetin aglycone and rutin. A secondary objective was to investigate which forms of quercetin are present in plasma. In this double blind, diet-controlled, two-period cross-over study, 16 healthy volunteers received three different doses of quercetin and rutin orally. The doses corresponded to 8 mg, 20 mg and 50 mg quercetin aglycone. Blood samples were obtained between 0 h and 32 h post-dose. The overall kinetic behaviour of quercetin differed remarkably after ingestion of quercetin aglycone or rutin. The mean area under the plasma concentration-time curve from 0 h to 32 h [AUC(0-32)] and maximum plasma concentration (Cmax) values of the two treatments were similar. However, time to reach Cmax (tmax) was significantly shorter after the quercetin aglycone treatment than after the rutin treatment (1.9, 2.7 and 4.8 versus 6.5, 7.4 and 7.5 h, for doses 1, 2 and 3, respectively). Also, the absorption of quercetin from quercetin aglycone was predictable and inter-individual variation was small. In contrast, after ingestion of rutin, inter-individual variations in AUC(0-32) and Cmax values were considerable and seemed to be associated with gender and use of oral contraceptives. Quercetin and rutin were found in plasma as glucuronides and/or sulfates of quercetin and as unconjugated quercetin aglycone, but no rutin was detected. In clinical trials, studying the effects of quercetin from rutin, bioavailability must be taken into consideration and plasma quercetin concentrations monitored. Whether our results apply to other glycosidic drugs as well, especially other rutosides, should be investigated.

Amaç: Sarkosistozis, dünya çapında yaygın bir dağılıma sahip ve çok çeşitli konakları olan önemli bir zoonotik protozoal hastalıktır. Bu çalışmanın amacı; Zabol-İran’da kesilen sığırlarda Sarkosistis spp. enfeksiyonunun yoğunluğunu belirlemek ve sarkosistis kistik lezyonlarının histopatolojik özellikleri göstermektir. Yöntemler: Nisan-Eylül 2018 tarihleri arasında kesilen 100 sığırın özofagus, kalp, diyafram, dil ve çiğneme kaslarından 500 doku örneği hazırlanmıştır. Tüm numuneler %10 nötr tamponlu formalin ile sabitlenmiştir ve tüm numunelere rutin doku işleme protokolü uygulanmıştır. Bulgular: Mikroskobik sonuçlar, örneklerin %92,2’sinde S. cruzi’nin ince duvarlı kistleri, %14’ünde kalın duvarlı Sarkosistis (S. hirsuta ve S. hominis) olduğunu, ancak makrokistin sadece bir sığırda görüldüğünü göstermiştir. İnce duvarlı kistlerin pozitiflik oranı kalp için %58,8, çiğneme kasları için %13,9, dil için %10,2, özofagus için %9,3 ve diyafram için %7,8 idi. S. hominis ve S. hirsuta’yı temsil edecek şekilde kalın duvarlı kistlerin pozitiflik oranı özofagus için %32,8, dil için %28,6, kalp için %22,9, çiğneme kasları için %15,7 ve diyafram için %0 idi. En çok enfekte olan doku kalp ve en az enfekte olan doku diyaframdı. İnce duvarlı kistler (S. cruzi) çoğunlukla kalpte bulundu ve diyaframda en az bulundu. Ancak, özofagusta kalın duvarlı kistler (S. hirsuta ve S. hominis) tespit edildi. Diyafram kasında kalın duvarlı kist bulunmadı. Sonuç: Zabol mezbahasında kesilen sığırlarda sarkosistosisin yüksek pozitiflik oranı, Sistan bölgesinin bu önemli paraziter hastalıkla ağır çevresel kontaminasyonunu ortaya çıkarmaktadır.

The current study was aimed to develop an amphiphilic drug-lipid nano-complex of rutin:egg phosphatidylcholine (EPC) to enhance its poor absorption and bioavailability, and investigated the impact of the complex on hepatoprotective and antioxidant activity. Rutin nano-complexes were prepared by solvent evaporation, salting out and lyophilisation methods and compared for the complex formation. For the selected lyophilisation method, principal solvent DMSO, co-solvent ( t -butyl alcohol) and rutin:EPC ratios (1:1, 1:2 and 1:3) were selected after optimisation. The properties of the nano-complexes such as complexation, thermal behaviour, surface morphology, molecular crystallinity, particle size, zeta potential, drug content, solubility, in vitro stability study, in vitro drug release, in vitro and in vivo antioxidant study, in vivo hepatoprotective activity and oral bioavailability/pharmacokinetic studies were investigated. Rutin nano-complexes were developed successfully via the lyophilisation method and found to be in nanometric range. Rutin nano-complexes significantly improved the solubility and in vitro drug release, and kinetic studies confirmed the diffusion-controlled release of the drug from the formulation. The nano-complex showed better antioxidant activity in vitro and exhibited well in vitro stability in different pH media . The in vivo study showed better hepatoprotective activity of the formulation compared to pure rutin at the same dose levels with improved oral bioavailability. Carbon tetrachloride (CCl 4 )-treated animals (group II) failed to restore the normal levels of serum hepatic marker enzymes and liver antioxidant enzyme compared to the nano-complex-treated animals. The results obtained from solubility, hepatoprotective activity and oral bioavailability studies proved the better efficacy of the nano-complex compared to the pure drug.

The renal cell carcinoma (RCC) is the most common type of kidney cancer. Identifying novel and more effective therapies, while minimizing toxicity, continues to be fundamental in curtailing RCC. Rutin, a bioflavonoid widely found in nature, has shown promising anticancer properties, but with limited applicability due to its poor water solubility and pharmacokinetics. Thus, the potential anticancer effects of rutin toward a human renal cancer cell line (786-O), while considering its safety in Vero kidney cells, was assessed, as well as the applicability of ionic liquids (ILs) to improve drug delivery. Rutin (up to 50 µM) did not show relevant cytotoxic effects in Vero cells. However, in 786-O cells, a significant decrease in cell viability was already observed at 50 µM. Moreover, exposure to rutin caused a significant increase in the sub-G1 population of 786-O cells, reinforcing the possible anticancer activity of this biomolecule. Two choline-amino acid ILs, at non-toxic concentrations, enhanced rutin’s solubility/loading while allowing the maintenance of rutin’s anticancer effects. Globally, our findings suggest that rutin may have a beneficial impact against RCC and that its combination with ILs ensures that this poorly soluble drug is successfully incorporated into ILs–nanoparticles hybrid systems, allowing controlled drug delivery.