Pycnogenol® supplementation to relieve symptoms after hemorrhoidectomy.

BACKGROUND: Hemorrhoids are a common problem associated with symptoms, like swelling, local thrombosis and generally with a decreased quality of life, often in otherwise healthy subjects. Hemorrhoids can be classified by grades (I to IV) according to their severity. In this registry study subjects treated with excisional hemorrhoidectomy (EH) for the first time, were included. After surgery, edema tends to complicate surgical areas causing relevant symptoms. Most hemorrhoids symptoms are related to alterations in bowel habits. Increase in diet fibers to avoid constipation, exercise, and limiting straining reduce recurrence after surgery. METHODS: The aim of the registry study was to evaluate the effects of Pycnogenol® (Horphag Research, Geneva, Switzerland) on relieving postoperative symptoms following hemorrhoidectomy. Pycnogenol® 150 mg/day was used between one month before surgery up to one month after surgery. The main postoperative symptoms were scored. RESULTS: Thirty-eight subjects completed the 60-day supplement registry study. Eighteen subjects were supplemented with Pycnogenol® in addition to the standard management (SM) and 20 subjects only received SM and were considered as controls. The two groups were comparable for age, sex and main symptoms distribution and for their clinical characteristics at inclusion. No other disease was present. The scores for pain, discomfort, and constipation were significantly lower with the supplement compared to controls (P<0.05) 10 and 30 days after surgery. In addition, the quality-of-life score was higher with Pycnogenol® (P<0.05) while bleeding (minimal, not clinically evaluable) and a possible residual anal stenosis (requiring a longer period of observation) were barely observed. A satisfactory return to activity was observed 30 days after surgery in the 18 subjects using Pycnogenol®, and in only 15 out of 20 patients (75%) in the control group (P<0.05). All Pycnogenol® subjects were able to drive and perform daily tasks in comparison with 14 out of 20 subjects in the control group. The proportion of patients that took pain medication from day 10 to 30 post-surgery was significantly lower in the Pycnogenol® group than in controls (P<0.05). CONCLUSIONS: In this post-surgical pilot, registry study, Pycnogenol® was effective in preventing and controlling postoperative symptoms after hemorrhoidectomy. To confirm the results, more cases are needed, including different surgical methods and clinical conditions. Mucosal and cutaneous edema and perianal swelling - generally seen after surgery - seem to be clearly reduced with Pycnogenol® and the supplement intake was associated with a more regular and pain-controlled convalescence and healing.

Higher habitual intakes of flavonoids and flavonoid-rich foods are associated with a lower incidence of type 2 diabetes in the UK Biobank cohort.

AIM: To examine the associations of a diet high in flavonoid-rich foods, as reflected by a "Flavodiet Score" (FDS), the major individual food contributors to flavonoid intake, and flavonoid subclasses with type 2 diabetes (T2D) risk in the UK Biobank cohort. MATERIALS AND METHODS: Flavonoid intakes were estimated from ≥2 dietary assessments among 113,097 study participants [age at enrolment: 56 ± 8 years; 57% female] using the U.S Department of Agriculture (USDA) databases. Multivariable Cox proportional hazards models were used to investigate associations between dietary exposures and T2D. RESULTS: During 12 years of follow-up, 2628 incident cases of T2D were identified. A higher FDS (compared to lower [Q4 vs. Q1]), characterised by an average of 6 servings of flavonoid-rich foods per day, was associated with a 26% lower T2D risk [HR: 0.74 (95% CI: 0.66-0.84), ptrend = <0.001]. Mediation analyses showed that lower body fatness and basal inflammation, as well as better kidney and liver function partially explain this association. In food-based analyses, higher intakes of black or green tea, berries, and apples were significantly associated with 21%, 15%, and 12% lower T2D risk. Among individual flavonoid subclasses, 19-28% lower risks of T2D were observed among those with the highest, compared to lowest intakes. CONCLUSIONS: A higher consumption of flavonoid-rich foods was associated with lower T2D risk, potentially mediated by benefits to obesity/sugar metabolism, inflammation, kidney and liver function. Achievable increases in intakes of specific flavonoid-rich foods have the potential to reduce T2D risk.

Association between Flavonoid Intake and Cognitive Executive Function among African American and White Adults in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) Study.

Healthy dietary patterns rich in flavonoids may benefit cognitive performance over time. Among socioeconomically disadvantaged groups, the association between flavonoid intake and measures of cognition is unclear. This study sought to identify associations between flavonoid intake and cognitive performance among Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study participants (n = 1947) across three study visits. Flavonoid intakes were assessed via two 24-h dietary recalls. Cognitive performance was assessed via the Trail Making Test (TMT)-A and TMT-B, which provide measures of attention and executive function, respectively. Mixed effects linear regression was used to model TMT scores over three study visits against visit 1 (v1) flavonoid intake, time (years from v1), and the interaction between v1 flavonoid intake and time, capturing both the cross-sectional association between flavonoid intake and time at v1 as well as the longitudinal association between v1 flavonoid intake and the change in TMT scores over time. Prior to adjustment, inverse cross-sectional associations at v1 were observed between (1) anthocyanidin intake and TMT-A scores for the overall sample and (2) total flavonoid, anthocyanidin, flavan-3-ol, flavone, and flavonol intake and TMT-B scores for the overall sample and among White adults. Only the association between anthocyanidin intake and TMT-B at v1 among White adults persisted after adjustment (for demographic characteristics such as age). One possible explanation for the few significant associations is universally low flavonoid intakes resulting from the consumption of an unhealthy dietary pattern.

Integrated Analysis of Genomic and Genome-Wide Association Studies Identified Candidate Genes for Nutrigenetic Studies in Flavonoids and Vascular Health: Path to Precision Nutrition for (Poly)phenols.

Flavonoids exert vasculoprotective effects in humans, but interindividual variability in their action has also been reported. This study aims to identify genes that are associated with vascular health effects of flavonoids and whose polymorphisms could explain interindividual variability in response to their intake. Applying the predetermined literature search criteria, we identified five human intervention studies reporting positive effects of flavonoids on vascular function together with global genomic changes analyzed using microarray methods. Genes involved in vascular dysfunction were identified from genome-wide association studies (GWAS). By extracting data from the eligible human intervention studies, we obtained 5807 differentially expressed genes (DEGs). The number of identified upstream regulators (URs) varied across the studies, from 227 to 1407. The search of the GWAS Catalog revealed 493 genes associated with vascular dysfunction. An integrative analysis of transcriptomic data with GWAS genes identified 106 candidate DEGs and 42 candidate URs, while subsequent functional analyses and a search of the literature identified 20 top priority candidate genes: ALDH2, APOE, CAPZA1, CYP11B2, GNA13, IL6, IRF5, LDLR, LPL, LSP1, MKNK1, MMP3, MTHFR, MYO6, NCR3, PPARG, SARM1, TCF20, TCF7L2, and TNF. In conclusion, this integrated analysis identifies important genes to design future nutrigenetic studies for development of precision nutrition for polyphenols.

The relationship between dietary total flavonoids and thyroid function in U.S.adults, NHANES 2007-2010.

BACKGROUND: Although small studies have shown that flavonoids can affect thyroid disease, few epidemiological studies have explored the relationship between dietary total flavonoids (TFs) intake and serum thyroid function. The aim of this research was to evaluate the relationship between TFs and serum thyroid function. METHODS: Our study included 4,949 adults from the National Health and Nutrition Examination Survey (NHANES) 2007-2010. Multivariable linear regression, subgroup analyses, and interaction terms were used to explore the relationships between TFs and thyroid function. And we also used restricted cubic splines (RCS) to investigate possible nonlinear relationships. RESULTS: After adjusting for covariates, we found that log10-transformated dietary total flavonoids intake (LgTFs) was negatively associated with total thyroxine (TT4) (ß = -0.153, 95% CI = -0.222 to -0.084, P<0.001). Subgroup analyses revealed a stronger and statistically supported association in subjects with high annual family income (ß = -0.367, P<0.001, P for interaction = 0.026) and subjects with high poverty to income ratio (PIR) (ß = -0.622, P<0.001, P for interaction = 0.042). And we found a U-shaped curve association between LgTFs and free triiodothyronine (FT3) (inflection point for LgTFs: 2.063). CONCLUSION: The results of our study demonstrated that a higher intake of total flavonoids in the diet was negatively associated with a lower TT4. Furthermore, the associations were more pronounced in high annual family income and high PIR adults. And we found a U-shaped relationship between LgTFs and FT3. These findings provided guidance for future thyroid dysfunction diet guidelines.

Improving physicochemical characteristics and cytotoxicity of baicalin esters by liposome encapsulation.

The instability of ester bonds, low water solubility, and increased cytotoxicity of flavonoid glycoside esters significantly limit their application in the food industry. Therefore, the present study attempted to resolve these issues through liposome encapsulation. The results showed that baicalin butyl ester (BEC4) and octyl ester (BEC8) have higher encapsulation and loading efficiencies and lower leakage rate from liposomes than baicalin. FTIR results revealed the location of BEC4 and BEC8 in the hydrophobic layer of liposomes, which was different from baicalin. Additionally, liposome encapsulation improved the water solubility and stability of BEC4 and BEC8 in the digestive system and PBS but significantly reduced their cytotoxicity. Furthermore, the release rate of BEC4 and BEC8 from liposomes was lower than that of baicalin during gastrointestinal digestion. These results indicate that liposome encapsulation alleviated the negative effects of fatty chain introduction into flavonoid glycosides.

Associations of Flavonoid Intakes with Mortality among Populations with Hypertension: A Prospective Cohort Study.

BACKGROUND: The effect of flavonoid consumption on all-cause and special-cause mortality remains unclear among populations with hypertension. METHODS: A total of 6110 people with hypertension from three NHANES survey cycles (2007-2008, 2009-2010, and 2017-2018) were enrolled in this study. Cox proportional hazard models were conducted to estimate the association between the intake of total flavonoids and flavonoid subclasses and all-cause, cancer-related, and cardiovascular disease (CVD)-related mortality. Nonlinear relationships were identified using restricted cubic splines (RCS). RESULTS: During 43,977 person-years of follow-up, 1155 participants died from any cause, 282 participants died from CVD, and 265 participants died from cancer. After adjusting for relevant confounders, including demographic, lifestyle, and dietary intake, a higher intake of total flavonoids was significantly associated with lower all-cause mortality but not CVD-related and cancer-related mortality among the population with hypertension. Compared with extreme quartiles, the hazard ratio (HR) and 95% confidence interval (CI) were 0.74 (0.56-0.97) for all-cause mortality, 0.77 (0.40-1.46) for CVD-related mortality, and 0.62 (0.35-1.08) for cancer-related mortality. In terms of all-cause mortality, this inverse association was optimized at total flavonoid consumption of approximately 375 mg/day. In addition, the negative association between total flavonoid consumption and all-cause mortality was more pronounced in non-obese (BMI < 30 kg/m2) compared to obese (BMI ≥ 30 kg/m2) populations. Higher intakes of anthocyanidin, flavan-3-ol, flavonol, and isoflavone were significantly associated with lower all-cause mortality (HR (95%CI): 0.70 (0.55-0.89); 0.76 (0.59-0.96); 0.66 (0.46-0.94); 0.79 (0.67-0.93), respectively). Higher intakes of anthocyanidin, flavan-3-ol, and flavonol were significantly associated with lower cancer-related mortality (HR (95%CI): 0.55 (0.32-0.93); 0.51 (0.31-0.82); 0.52 (0.28-0.96), respectively). CONCLUSION: This study suggests that a heightened consumption of total flavonoids and some flavonoid subclasses was linked to lower mortality, which supports the proposal of increasing flavonoid intake as part of healthy diets in patients with hypertension.

Integrated Janus nanofibers enabled by a co-shell solvent for enhancing icariin delivery efficiency.

During the past several decades, nanostructures have played their increasing influences on the developments of novel nano drug delivery systems, among which, double-chamber Janus nanostructure is a popular one. In this study, a new tri-channel spinneret was developed, in which two parallel metal capillaries were nested into another metal capillary in a core-shell manner. A tri-fluid electrospinning was conducted with a solvent mixture as the shell working fluid for ensuring the formation of an integrated Janus nanostructure. The scanning electronic microscopic results demonstrated that the resultant nanofibers had a linear morphology and two distinct compartments within them, as indicated by the image of a cross-section. Fourier Transformation Infra-Red spectra and X-Ray Diffraction patterns verified that the loaded poorly water-soluble drug, i.e. icariin, presented in the Janus medicated nanofibers in an amorphous state, which should be attributed to the favorable secondary interactions between icariin and the two soluble polymeric matrices, i.e. hydroxypropyl methyl cellulose (HPMC) and polyvinylpyrrolidone (PVP). The in vitro dissolution tests revealed that icariin, when encapsulated within the Janus nanofibers, exhibited complete release within a duration of 5 min, which was over 11 times faster compared to the raw drug particles. Furthermore, the ex vivo permeation tests demonstrated that the permeation rate of icariin was 16.2 times higher than that of the drug powders. This improvement was attributed to both the rapid dissolution of the drug and the pre-release of the trans-membrane enhancer sodium lauryl sulfate from the PVP side of the nanofibers. Mechanisms for microformation, drug release, and permeation were proposed. Based on the methodologies outlined in this study, numerous novel Janus nanostructure-based nano drug delivery systems can be developed for poorly water-soluble drugs in the future.

Association between dietary flavonoid intake and hypertension among U.S. adults.

Background: Hypertension is one of the major risk factors for cardiovascular disease. Dietary flavonoids have been reported to reduce inflammation, protect against oxidative stress, protect the vascular endothelium, and improve vascular health. However, the relationship between dietary flavonoid intake and the prevalence of hypertension remains controversial. Methods: This study included 8010 adults from the 2007-2010 and 2017-2018 National Health and Nutrition Examination Surveys (NHANES). The relationship between dietary flavonoid intake and the prevalence of hypertension was explored by weighted logistic regression and weighted restricted cubic spline. Results: We found an inverse relationship between total anthocyanin intake and the prevalence of hypertension in the fourth quartile compared with the first quartile [0.81(0.66,0.99), p = 0.04]. Moreover, the prevalence of hypertension tended to decrease with increasing total anthocyanin intake in participants over 60 years of age. In addition, we found a U-shaped relationship between the prevalence of hypertension and total flavan-3-ol intake. Total flavan-3-ol intake was inversely associated with hypertension prevalence in the third quartile compared with the first quartile [0.79 (0.63,0.99), p = 0.04]. Moreover, there was a significant negative association between the prevalence of hypertension and total flavan-3-ol intake when total flavan-3-ol intake was below 48.26 mg/day. Conclusion: Our study found a negative association between the prevalence of hypertension and moderate total anthocyanins intake and total flavan-3-ols intake. Our study provides evidence from a population-based study for a negative association between dietary flavonoid intake and the prevalence of hypertension.

Dietary Flavonoid Intakes in France Are Linked to Brewed Tea Consumption and to Socioeconomic Status: Analyses of the Third French Individual and National Food Consumption (INCA3) Survey for Children and Adults.

Flavonoids from green and black tea may benefit cardiovascular health. Brewed tea consumption and flavonoid intake in France have not been previously explored. This study assessed the dietary intake of flavonoids among French children and adults, using 3 days' dietary recall for 3896 persons aged >4 y in the Third French Individual and National Food Consumption Survey (INCA3). Foods consumed by INCA 3 participants were manually matched with the flavonoid content of foods from the French PhenolExplorer database and the US Department of Agriculture expanded flavonoid database (2018 version). The six subclasses of flavonoids were flavan-3-ols, flavanones, anthocyanidins, flavonols, flavones, and isoflavones. Flavonoid intake was stratified by age subgroups (children and adults separately) and examined using socio-demographics and tea consumption patterns. Mean flavonoid intake was 210 mg/d. Flavonoids in the French diet were predominantly flavan-3-ols (147 mg/d), of which tea is the main source. The effects of age, education, income, and socio-professional category (SPC) on flavonoid intake were all significant (p < 0.0001). Brewed tea consumers were 31.88% of French adults and 3.79% of children. Brewed tea consumption and flavonoid intake were highly correlated. The highest brewed tea and flavonoid intakes were found among individuals with the highest SPC and education levels. Flavonoid intake in France was associated with brewed tea consumption and with higher education and income.

Tannic acid coated nanosuspension for oral delivery of chrysin intended for anti-schizophrenic effect in mice.

Chrysin is a flavonoid drug with numerous therapeutic activities. It suffers from low intestinal absorption owing to its hydrophobicity. Therefore, the aim of this study is to exploit the efficient technique of nanosuspension (NSP) to formulate chrysin-NSP coated with tannic acid (TA) to improve the solubility and anti-schizophrenic activity of chrysin. A 23 full factorial design was constructed where the independent factors were type of polymer, surfactant concentration (0.5 or 1 %) and the aqueous phase volume (5 or 15 mL), while the dependent responses were the particle size (PS) of the obtained formulation as well as the % chrysin dissolved after 2 h (Q2h). The optimum formulation (NSP-4) composed of 1 % PEG 400 and 1 % Cremophor RH40 in 15 mL aqueous phase. It achieved a PS and Q2h values of 108.00 nm and 38.77 %, respectively. NSP-4 was then coated with TA (TA-coated NSP-4) for further enhancement of chrysin solubility. TA-coated NSP-4 revealed PS and zeta potential values of 150 ± 14 nm and -32.54 ± 2.45 mV, respectively. After 6 h, chrysin dissolved % were 53.97 and 80.22 for uncoated NSP-4 and TA-coated NSP-4, respectively, compared with only 9.47 for free chrysin. The developed formulations and free chrysin were assessed regarding their effect on schizophrenia induced in mice by cuprizone (CPZ). Treatment with the developed formulations and free chrysin ameliorated demyelination and behavioral deficit induced by CPZ via elevating MBP and PI3K/PKC activities as well as reducing GFAP expression levels. The developed formulations and free chrysin inhibited Galactin-3 and TGF-ß expressions and stimulated GST antioxidant enzyme. Furthermore, they maintained the balances in glutamatergic and dopaminergic neurotransmission via modulation on neuregulin-1 and alleviated nuclear pyknosis and degeneration in the neurons. The order of activity was: TA-coated NSP-4 > NSP-4 > free chrysin.

Novel fast dissolving freeze dried sublingual baicalin tablets for enhanced hepatoprotective effect: in-vitro characterization, cell viability, and in-vivo evaluation.

Baicalin (BG), a natural product, has been used in the prevention and treatment of drug-induced liver injury (DILI); however, its poor solubility and extensive liver metabolism limit its pharmacological use. The aim of the present study was the formulation of fast-dissolving freeze-dried sublingual tablets (FFSTs) to increase BG dissolution, avoid first-pass metabolism, and overcome swallowing difficulties. FFSTs were prepared following a 23 factorial design. The effect of three independent variables namely matrix former, Maltodextrin, concentration (4%, and 6%), binder concentration (2%, and 3%), and binder type (Methocel E5, and Methocel E15) on the FFSTs' in-vitro disintegration time and percentage dissolution was studied along with other tablet characteristics. Differential scanning calorimetry, scanning electron microscopy, in-vitro HepG2 cell viability assay, and in-vivo characterization were also performed. F8 (6% Maltodextrin, 2% Mannitol, 2% Methocel E5), with desirability of 0.852, has been furtherly enhanced using 1%PEG (F10). F10 has achieved an in-vitro disintegration time of 41 secs, and 60.83% in-vitro dissolution after 2 min. Cell viability assay, in-vivo study in rats, and histopathological studies confirmed that pretreatment with F10 has achieved a significant hepatoprotective effect against acetaminophen-induced hepatotoxicity. The outcome of this study demonstrated that FFSTs may present a patient-friendly dosage form against DILI.

Preparation, characterisation, and pharmacodynamic study of myricetin pH-sensitive liposomes.

AIMS: Myricetin (MYR) was incorporated into pH-sensitive liposomes in order to improve its bioavailability and anti-hyperuricemic activity. METHODS: The MYR pH-sensitive liposomes (MYR liposomes) were prepared using thin film dispersion method, and assessed by particle size (PS), polydispersed index (PDI), zeta potential (ZP), encapsulation efficiency, drug loading, and in vitro release rate. Pharmacokinetics and anti-hyperuricemic activities were also evaluated. RESULTS: The PS, PDI, ZP, encapsulation efficiency, and drug loading of MYR liposomes were 184.34 ± 1.05 nm, 0.215 ± 0.005, -38.46 ± 0.30 mV, 83.42 ± 1.07%w/w, and 6.20 ± 0.31%w/w, respectively. The release rate of MYR liposomes was higher than free MYR, wherein the cumulative value responded to pH. Besides, the Cmax of MYR liposomes was 4.92 ± 0.20 µg/mL. The level of uric acid in the M-L-H group (200 mg/kg) was reduced by 54.74%w/v in comparison with the model group. CONCLUSION: MYR liposomes exhibited pH sensitivity and could potentially enhance the oral bioavailability and anti-hyperuricemic efficacy of MYR.

High-strength double-network silk fibroin based hydrogel loaded with Icariin and BMSCs to inhibit osteoclasts and promote osteogenic differentiation to enhance bone repair.

Large bone defects cause significant clinical challenges due to the lack of optimal grafts for effective regeneration. The tissue engineering way that requires the combination of biomaterials scaffold, stem cells and proper bioactive factors is a prospective method for large bone repair. Here, we synthesized a three-arm host-guest supramolecule (HGSM) to covalently crosslinking with the naturally derived polymer methacrylated silk fibroin (SFMA). The combination of HGSM and SFMA can form a high strength double-crosslinked hydrogel HGSFMA, that serve as the hydrogel scaffold for bone marrow mesenchymal stem cells (BMSCs) growing. Icariin (ICA) loaded in the HGSFMA hydrogel can promote the osteogenesis efficiency of BMSCs and inhibit the osteoclasts differentiation. Our findings demonstrated that the HGSFMA/ICA hydrogel effectively promoted the in vitro adhesion, proliferation, and osteogenic differentiation of BMSCs. Rat femoral defects model show that this hydrogel can completely repair femoral damage within 4 weeks and significantly promote the secretion of osteogenesis-related proteins. In summary, we have prepared an effective biomimetic bone carrier, offering a novel strategy for bone regeneration and the treatment of large-scale bone defects.

The association between flavonoids intake and hypertension in U.S. adults: A cross-sectional study from The National Health and Nutrition Examination Survey.

Although in vitro experiments have demonstrated the potential of flavonoid compounds in regulating blood pressure, there is still a lack of evidence from large population studies. We conducted a cross-sectional study using the National Health and Nutrition Examination Survey to investigate the relationship between flavonoid intake levels (natural log transformation) and hypertension events. A total of 15 752 participants aged over 20 years were included, and a weighted multivariable logistic regression analysis was performed to explore the relationship between total flavonoids, five sub types intake, and hypertension events. Smooth curve fitting was used to explore potential nonlinear relationships. Higher total flavonoids intake was associated with a lower risk of hypertension than the lowest group. The adjusted odds ratios (95% CIs) were 0.79 (0.70-0.88) for total flavonoids intake. Elevated total flavonoids intake levels were significantly and linearly associated with a lower risk of hypertension. For each unit increase in the total flavonoids intake level, the adjusted ORs for risk of hypertension decrease by 5% (OR 0.95; 95% CI, 0.92-0.98). In addition, in restricted cubic spline regression, we found that flavan-3-ols, anthocyanidins, and flavonols intake were linearly and negatively related to prevalence of hypertension. Flavones intake showed nonlinear associations with prevalence of hypertension with inflection points of -1.90. Within a certain range, a negative correlation exists between flavonoids intake and hypertension events. This finding provides insights into dietary modifications in the prevention of hypertension.

Dietary supplementation of osthole and icariin improves the production performance of laying hens by promoting follicular development.

Osthole (Ost) and icariin (Ica) are extracted from traditional Chinese medicine Cnidium monnieri and Epimedii Folium, respectively, and both exhibit estrogen-like biological activity. This study aimed to determine the efficacy and safety of combining Ost with Ica on the production performance of laying hens and to explore their possible mechanisms. The production performance, egg quality, residues of Ost and Ica in eggs, serum reproductive hormone levels, expression of ovarian reproductive hormone receptor, proliferation of granulosa cells in small yellow follicles (SYF), and progesterone secretion in large yellow follicles (LYF) related genes and proteins expression were detected. The results showed that adding 2 mg/kg Ost + 2 mg/kg Ica to the feed increased the laying rate, average egg weight, Haugh unit, and protein height of laying hens. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and progesterone (P4) levels increased, and the expression of ovarian estrogen receptor (ER), follicle-stimulating hormone receptor (FSHR), and progesterone receptor (PGR) mRNA was up-regulated. Additionally, the mRNA and protein levels of steroidogenesis acute regulatory protein (StAR), cytochrome P450 side-chain cleavage (P450scc), and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) increased in LYF. Furthermore, mRNA and protein levels of proliferating cell nuclear antigen (PCNA), cyclin E1, and cyclin A2 were up-regulated in SYF. The residues of Ost and Ica in egg samples were not detected by high-performance liquid chromatography (HPLC). In conclusion, dietary supplementation of Ost and Ica increased granulosa cells proliferation in SYF and increased P4 secretion in granulosa cells of LYF, ultimately improving the production performance of laying hens.

Binary Nano-inhalant Formulation of Icariin Enhances Cognitive Function in Vascular Dementia via BDNF/TrkB Signaling and Anti-inflammatory Effects.

Vascular dementia (VaD) has a serious impact on the patients' quality of life. Icariin (Ica) possesses neuroprotective potential for treating VaD, yet its oral bioavailability and blood-brain barrier (BBB) permeability remain challenges. This research introduced a PEG-PLGA-loaded chitosan hydrogel-based binary formulation tailored for intranasal delivery, enhancing the intracerebral delivery efficacy of neuroprotective agents. The formulation underwent optimization to facilitate BBB crossing, with examinations conducted on its particle size, morphology, drug-loading capacity, in vitro release, and biodistribution. Using the bilateral common carotid artery occlusion (BCCAO) rat model, the therapeutic efficacy of this binary formulation was assessed against chitosan hydrogel and PEG-PLGA nanoparticles loaded with Ica. Post-intranasal administration, enhanced cognitive function was evident in chronic cerebral hypoperfusion (CCH) rats. Further mechanistic evaluations, utilizing immunohistochemistry (IHC), RT-PCR, and ELISA, revealed augmented transcription of synaptic plasticity-associated proteins like SYP and PSD-95, and a marked reduction in hippocampal inflammatory markers such as IL-1ß and TNF-α, highlighting the formulation's promise in alleviating cognitive impairment. The brain-derived neurotrophic factor (BDNF)/tropomyosin related kinase B (TrkB) pathway was activated significantly in the binary formulation compared with the other two. Our study demonstrates that the intranasal application of chitosan hydrogel loaded with Ica-encapsulated PEG-PLGA could effectively deliver Ica into the brain and enhance its neuroprotective effect.

Efficacy of Micronized Purified Flavonoid Fraction in the Posthemorrhoidectomy Period Trial: Open-Label Randomized Controlled Trial.

BACKGROUND: Frequent early postoperative complications of hemorrhoidectomy are thrombosis and edema of mucocutaneous "bridges." OBJECTIVE: This study aimed to investigate the efficacy of micronized purified flavonoid fraction in preventing complications after elective hemorrhoidectomy. DESIGN: Prospective unicentral open-label randomized controlled trial. SETTINGS: 2021-2022 at the Clinic of Colorectal and Minimally Invasive Surgery at Sechenov University (Moscow, Russia). PATIENTS: Patients who underwent hemorrhoidectomy for grade III and IV hemorrhoids. INTERVENTIONS: After hemorrhoidectomy, patients were randomly assigned either to standard treatment (peroral nonsteroid anti-inflammatory drugs and local anesthetics, topical steroids, psyllium, warm sitz baths, and nifedipine gel), referred to as the control group, or to standard treatment with micronized purified flavonoid fraction, referred to as the study group, and followed up for 60 days. MAIN OUTCOME MEASURES: Thrombosis or edema of mucocutaneous bridges and pain intensity on a visual analog scale оn postoperative days 1-7, 14, 21, and 30; quality of life and patient-assessed treatment effect оn postoperative days 1, 3, 7, 21, and 30; and perianal skin tags оn postoperative day 60. RESULTS: The data from 50 patients were analyzed (25 in each group). The visual analog scale demonstrated no differences between groups in each follow-up point. Compared to the control group, the patients in the study group had a significantly higher patient-assessed treatment effect оn postoperative days 1, 3, 7, 21, and 30 and a significantly lower rate of thrombosis or edema of mucocutaneous bridges оn postoperative days 1-7 and 14. Patients in the study group had significantly lower rates of perianal skin tags. LIMITATIONS: Unicenter open-label design. CONCLUSIONS: Micronized purified flavonoid fraction in the posthemorrhoidectomy period is an effective adjunct to standard treatment that helps reduce the rate of thrombosis and edema of mucocutaneous bridges, improves patient-assessed treatment effect, and prevents postoperative perianal skin tags formation. Micronized purified flavonoid fraction in the posthemorrhoidectomy period is not associated with additional pain relief in comparison with nonmicronized purified flavonoid fraction standard treatment. See Video Abstract . EFICACIA DE LA FRACCIN DE FLAVONOIDES PURIFICADA MICRONIZADA EN EL PERODO POSTERIOR A LA HEMORROIDECTOMA ENSAYO MOST ENSAYO CONTROLADO, ALEATORIZADO, ABIERTO: ANTECEDENTES:Una complicación postoperatoria temprana frecuente de la hemorroidectomía es la trombosis y el edema de los "puentes" mucocutáneos.OBJETIVO:Investigamos la eficacia de la fracción de flavonoides purificada micronizada en la prevención de complicaciones después de una hemorroidectomía electiva.DISEÑO:Ensayo controlado aleatorio, prospectivo, unicentral, abierto.AJUSTES:2021-2022 Clínica de Cirugía Colorrectal y Mínimamente Invasiva Universidad Sechenov (Moscú, Rusia).PACIENTES:Pacientes después de hemorroidectomía, que se realizó para hemorroides de grado III-IV.INTERVENCIONES:Después de la hemorroidectomía, los pacientes fueron asignados aleatoriamente al tratamiento estándar (antiinflamatorios no esteroides perorales y anestésicos locales, esteroides tópicos, psyllium, baños de asiento tibios, gel de nifedipina) - grupo de control, o al tratamiento estándar con flavonoide purificado micronizado. fracción (grupo de estudio) y seguido durante 60 días.RESULTADOS DE MEDIDAS PRINCIPALES:Trombosis o edema de puentes mucocutáneos e intensidad del dolor en una escala analógica visual entre el 1.º, 7.º, 14.º, 21.º y 30.º día postoperatorio; calidad de vida y efecto del tratamiento evaluado por el paciente el día 1, 3, 7, 21 y 30 del postoperatorio; Marcas cutáneas perianales en el día 60 del postoperatorio.RESULTADOS:Se analizaron los datos de 50 pacientes (25 en cada grupo). La escala analógica visual no demostró diferencias entre grupos en cada punto de seguimiento. En comparación con el grupo de control, los pacientes en el grupo de estudio tuvieron un efecto del tratamiento evaluado por el paciente significativamente mayor en los días 1, 3, 7, 21 y 30 después de la operación, una tasa significativamente menor de trombosis o edema de los puentes mucocutáneos en los días 1, 7 y 14.. Los pacientes del grupo de estudio tuvieron tasas significativamente más bajas de marcas en la piel perianal.LIMITACIONES:Diseño Unicenter de etiqueta abierta.CONCLUSIONES:La fracción de flavonoides purificada micronizada en el período posterior a la hemorroidectomía es un complemento eficaz del tratamiento estándar que ayuda a reducir la tasa de trombosis y edema de los puentes mucocutáneos, mejora el efecto del tratamiento evaluado por el paciente y previene la formación de marcas cutáneas perianales posoperatorias. La fracción de flavonoides purificados micronizados en el período posterior a la hemorroidectomía no se asocia con un alivio adicional del dolor en comparación con el tratamiento estándar con la fracción de flavonoides purificados no micronizados. (Traducción-Yesenia Rojas-Khalil ).

The association of dietary total flavonoids and their subclasses with the risk of type 2 diabetes: a prospective cohort study.

BACKGROUND: Data from mechanistic studies suggest flavonoids may benefit glucose metabolism, but their associations with type 2 diabetes (T2D) remain unclear. This study examined the prospective associations of dietary intake of total, classes, and individual flavonoids, as well as their source foods, with T2D in the CArdioVascular disease Association Study (CAVAS). METHODS: A total of 16,666 Korean men and women were enrolled at baseline, and 953 were newly diagnosed with T2D over a median follow-up of 5.96 years. Intake of flavonoids was cumulatively averaged using all food frequency questionnaires before the censoring events. A Poisson regression model was used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs). RESULTS: Women with higher total flavonoid, flavonol, isoflavone, and proanthocyanidin intake had a lower risk of T2D (fourth vs. first quartile, IRR 0.62; 95% CI 0.44-0.89; P for linearity and non-linearity < 0.05 for total flavonoids), while in men, flavanones, anthocyanins, and proanthocyanidins, but not total flavonoids, were inversely associated with T2D risk (all P interaction for sex > 0.05). The key source foods contributing to flavonoid intake were also different between men and women, except for apples: tangerines and strawberries in men and green leafy vegetables and soy products in women. CONCLUSIONS: A higher intake of total flavonoids, particularly from vegetables, soybeans, and apples, may be associated with lower risk of T2D in women. However, flavonoids from fruits, rather than total flavonoids, may be inversely associated in men. The association between flavonoid intake and the risk of T2D may be contingent upon the dietary sources of flavonoids consumed.

Prevention and control of jet lag symptoms and temporary impairment of cognitive function with Pycnogenol® in healthy individuals and in hypertensives.

BACKGROUND: The aim of this registry study was to evaluate the efficacy of Pycnogenol® in controlling signs/symptoms and temporary impairment of cognitive function (COFU) associated with jet lag. Previous flight studies have shown a decrease in the level of jet lag symptoms with Pycnogenol®. The control of jet lag signs/symptoms appeared to be correlated with flight-related microangiopathy and peripheral edema. Pycnogenol® - a standardized extract from the bark of French maritime pine - has significant antiedema, anti-inflammatory and antioxidant properties. METHODS: A group of subjects flying east in economy class for 10-12 hours used Pycnogenol® 150 mg/day and a similar group without supplementation served as controls. A subgroup of mild hypertensive subjects using a single ACE inhibitor was also included. RESULTS: One hundred twenty-seven subjects completed the study. Of the participants, 48 were aviation professionals like pilots, flight attendants or air company staff - 24 of them took Pycnogenol® and 24 served as controls. Forty-seven study participants were frequent flyers and non-staff professionals, 25 of which took Pycnogenol® and 22 served as controls. In addition, a group of 32 subjects with mild hypertension was included, 16 took Pycnogenol® and 16 served as controls. No side effects and a good tolerability were observed. The registry groups were comparable for baseline characteristics. Eastbound flights' duration was 11.22±0.4 hours in supplemented subjects and 11.14±0.32 in controls. Dropouts were due to logistical problems. Post flight Visual Analogue Scale (VAS) scores were significantly lower in all Pycnogenol® groups, including hypertensives for all signs and symptoms of jet lag compared to controls, showing prevention and improvement of jet lag symptoms. The duration of any sign/symptom of jet lag with Pycnogenol® intake was significantly shorter (P<0.05) post-flight compared to controls (P<0.05). The number of nights of altered/disturbed sleep was also lower in the Pycnogenol® groups compared to controls. Leg edema was present in almost all subjects with different degrees especially in the hypertensive group. The increase in ankle circumference before and after flight was significantly lower with Pycnogenol® compared to controls (P<0.05). After the flight, average scores of the single COFU tasks were significantly higher in the Pycnogenol® groups compared to controls, showing preserved cognitive function. CONCLUSIONS: In conclusion, in this registry study Pycnogenol® was effective in preventing jet lag-related symptoms and preserving cognitive functions without tolerability problems. These observations should be tested in a larger group of subjects including complex individuals prone to edema (i.e. diabetics, hypertensive or older patients).