Polyphenol- and Glucuronoxylan-Rich Fiber Extract from Birch (Betula sp.) Wood Regulates Colonic Barrier Function and Cell Proliferation in Healthy Rats.

Birch wood-derived fiber extracts containing glucuronoxylans (GX) and polyphenols show potential for various food technological applications. This study investigated the effect of two extracts, GXpoly and pureGX, differing in lignin content on colonic barrier function. Healthy rats were fed diets containing 10% GXpoly, pureGX, or cellulose for 4 weeks. Colon crypt depth was lower in the GX groups than in the control group, but in the proximal colon, the result was significant only in GXpoly. An artificial intelligence approach was established to measure the mucus content and goblet cells. In the distal colon, their amounts were higher in the control group than in the GX groups. All diets had a similar effect on the expression of the tight junction proteins occludin, claudin-1, and claudin-7. GXpoly enhanced the fecal IgA production. Our results suggest that GX-rich extracts could support the colonic barrier and work as functional food ingredients in the future.

Silver Nanoparticles (AgNPs) as Enhancers of Everolimus and Radiotherapy Sensitivity on Clear Cell Renal Cell Carcinoma.

Nanomedicine's advent has promised to revolutionize different biomedical fields, including oncology. Silver Nanoparticles (AgNPs) showed promising results in different tumor models. Clear cell Renal Cell Carcinoma (ccRCC) is especially challenging due to its late diagnosis, poor prognosis and treatment resistance. Therefore, defining new therapeutic targets and regimens could improve patient management. This study intends to evaluate AgNPs' effect in ccRCC cells and explore their potential combinatory effect with Everolimus and Radiotherapy. AgNPs were synthesized, and their effect was evaluated regarding their entering pathway, cellular proliferation capacity, ROS production, mitochondrial membrane depolarization, cell cycle analysis and apoptosis assessment. AgNPs were combined with Everolimus or used to sensitize cells to radiotherapy. AgNPs are cytotoxic to 786-O cells, a ccRCC cell line, entering through endocytosis, increasing ROS, depolarizing mitochondrial membrane, and blocking the cell cycle, leading to a reduction of proliferation capacity and apoptosis. Combined with Everolimus, AgNPs reduce cell viability and inhibit proliferation capacity. Moreover, 786-O is intrinsically resistant to radiation, but after AgNPs' administration, radiation induces cytotoxicity through mitochondrial membrane depolarization and S phase blockage. These results demonstrate AgNPs' cytotoxic potential against ccRCC and seem promising regarding the combination with Everolimus and sensitization to radiotherapy, which can, in the future, benefit ccRCC patients' management.

Metabolic Fate of Lignin in Birch Glucuronoxylan Extracts as Dietary Fiber Studied in a Rat Model.

SCOPE: While previously considered inert, recent studies suggest lignin metabolism with unknown metabolic fates is occurring in the gastrointestinal tract of several animal models. This study focuses on analyzing the potential metabolites of lignin. METHODS AND RESULTS: The diets of rats include relatively pure birch glucuronoxylan (pureGX) with residual lignin or lignin-rich GX (GXpoly) in their diet. Nuclear magnetic spectroscopy of the lignin isolated from the GXpoly-fed rats fecal sample shows high alteration in chemical structure, whereas lignin-carbohydrate complexes (LCCs) are enriched in fecal samples from the pureGX group. Moreover, the increased syringyl-to-guaiacyl (S/G) ratio suggests that lignin G-units are predominantly metabolized based on pyrolysis gas chromatography-mass spectrometry (pyr-GC/MS). The presence of small phenolic metabolites identified in urine samples of the GXpoly group, for example, ferulic and sinapic acids, their sulfate and glucuronide derivatives, and 4-sulfobenzylalcohol, suggests that the small fragmented lignin metabolites in the large intestine enter the plasma, and are further processed in the liver. Finally, the relative abundances of polyphenol-degrading Enterorhabdus and Akkermansia in the gut microbiota are associated with lignin metabolism. CONCLUSION: These findings give further evidence to lignin metabolism in the gut of nonruminants and provide insight to the potential microbes and metabolic routes.

Glucose-Functionalized Silver Nanoparticles as a Potential New Therapy Agent Targeting Hormone-Resistant Prostate Cancer cells.

Purpose: Silver nanoparticles (AgNPs) have shown great potential as anticancer agents, namely in therapies' resistant forms of cancer. The progression of prostate cancer (PCa) to resistant forms of the disease (castration-resistant PCa, CRPC) is associated with poor prognosis and life quality, with current limited therapeutic options. CRPC is characterized by a high glucose consumption, which poses as an opportunity to direct AgNPs to these cancer cells. Thus, this study explores the effect of glucose functionalization of AgNPs in PCa and CRPC cell lines (LNCaP, Du-145 and PC-3). Methods: AgNPs were synthesized, further functionalized, and their physical and chemical composition was characterized both in water and in culture medium, through UV-visible spectrum, dynamic light scattering (DLS), transmission electron microscopy (TEM) and Fourier-transform infrared spectroscopy (FTIR). Their effect was assessed in the cell lines regarding AgNPs' entering pathway, cellular proliferation capacity, ROS production, mitochondrial membrane depolarization, cell cycle analysis and apoptosis evaluation. Results: AgNPs displayed an average size of 61nm and moderate monodispersity with a slight increase after functionalization, and a round shape. These characteristics remained stable when redispersed in culture medium. Both AgNPs and G-AgNPs were cytotoxic only to CRPC cells and not to hormone-sensitive ones and their effect was higher after functionalization showing the potential of glucose to favor AgNPs' uptake by cancer cells. Entering through endocytosis and being encapsulated in lysosomes, the NPs increased the ROS, inducing mitochondrial damage, and arresting cell cycle in S Phase, therefore blocking proliferation, and inducing apoptosis. Conclusion: The nanoparticles synthesized in the present study revealed good characteristics and stability for administration to cancer cells. Their uptake through endocytosis leads to promising cytotoxic effects towards CRPC cells, revealing the potential of G-AgNPs as a future therapeutic approach to improve the management of patients with PCa resistant to hormone therapy or metastatic disease.

Gut microbiota can utilize prebiotic birch glucuronoxylan in production of short-chain fatty acids in rats.

Birch-derived glucuronoxylan (GX)-rich hemicellulose extract is an abundantly available by-product of the forest industry. It has multifunctional food stabilizing properties, and is rich in fiber and polyphenols. Here, we studied its effects on colonic metabolism and gut microbiota in healthy rats. Male and female Wistar rats (n = 42) were fed AIN-93G-based diets with 10% (w/w) of either cellulose (control), a polyphenol and GX-rich extract (GXpoly), or a highly purified GX-rich extract (pureGX) for four weeks. Both the GXpoly and pureGX diets resulted in changes on the gut microbiota, especially in a higher abundance of Bifidobacteriaceae than the cellulose containing diet (p < 0.001). This coincided with higher concentrations of microbial metabolites in the luminal contents of the GX-fed than control rats, such as total short-chain fatty acids (SCFAs) (p < 0.001), acetate (p < 0.001), and N-nitroso compounds (NOCs) (p = 0.001). The difference in the concentration of NOCs was not seen when adjusted with fecal weight. GX supplementation supported the normal growth of the rats. Our results indicate that GXpoly and pureGX can favorably affect colonic metabolism and the gut microbiota. They have high potential to be used as prebiotic stabilizers to support more ecologically sustainable food production.

Respiratory viruses and febrile response in children with febrile seizures: A cohort study and embedded case-control study.

OBJECTIVE: There are limited data on the pathogen-related and host-related factors in the pathogenesis of febrile seizures (FS). We designed a controlled study to compare the role of different respiratory viruses and febrile response in FS. METHODS: In a prospective cohort study of 1899 pediatric emergency room patients aged 6 months-6 years with a positive respiratory virus multiplex PCR, we identified 225 patients with FSs. We first compared the distribution of respiratory viruses in age-stratified patients with FSs with that in other patients. In an embedded case-control study, we compared the febrile response in patients with FSs with that in the controls matched for age, season and the same respiratory virus. RESULTS: The relative risk for FS was the highest for coronavirus OC43, 229E, and NL63 infections [RR: 3.2, 95 % confidence interval (CI): 1.4-7.2) and influenza A and B [RR: 2.5, 95 % CI: 1.4-4.7] as compared to those with other respiratory viral infections. The patients with FSs had a stronger febrile response of 39.2 °C (difference: 0.8 °C, 95 % CI: 0.5-1.2) later during hospitalization after acute care than the controls matched for the same respiratory virus. CONCLUSIONS: Influenza and coronaviruses caused relatively more FS-related emergency room visits than other respiratory viruses. Furthermore, the febrile response was stronger in the patients with FSs than in the controls matched for the same respiratory virus. The results suggest that the pathomechanism of FSs includes modifiable pathogen-related and host-related factors with possible potential in the prevention of FSs.

Effects of Enzymatic Hydrolysis of Fava Bean Protein Isolate by Alcalase on the Physical and Oxidative Stability of Oil-in-Water Emulsions.

Fava bean protein isolate (FBPI) was hydrolyzed by Alcalase with different degrees of hydrolysis (DHs), and the role of hydrolysates in oil-in-water (O/W) emulsion stability was investigated. Four emulsions, DH0, DH4, DH9, and DH15, were prepared by 1% (w/v) FBPI hydrolysates with different DHs (0% as the control and 4, 9, and 15%) and 5% (w/v) purified rapeseed oil. The emulsions were monitored for physical and oxidative stability at 37 °C for 7 days. DH4 and DH0 exhibited better physical stability than DH9 and DH15, indicated by droplet size, morphology, and Turbiscan stability index. More importantly, FBPI hydrolysates with DH of 4% most effectively inhibited lipid oxidation (i.e., formation of conjugated dienes and hexanal) while maintaining protein oxidative stability compared to the native and extensively hydrolyzed FBPI. Higher DHs (9 and 15%) induced unduly decreased surface hydrophobicity and increased surface load, which might negatively affect the emulsifying activity. FBPI hydrolysates with DH of 4% had suitable molecular weight for better interfacial layer stability, increased surface net charge for more repulsive electrostatic force, and increased hydrophobicity for better adsorption at the interface and, therefore, may serve as potential natural emulsifiers to maintain both physical and oxidative stability of O/W emulsions.

Biocomposites of nanofibrillated cellulose, polypyrrole, and silver nanoparticles with electroconductive and antimicrobial properties.

In this work, flexible and free-standing composite films of nanofibrillated cellulose/polypyrrole (NFC/PPy) and NFC/PPy-silver nanoparticles (NFC/PPy-Ag) have been synthesized for the first time via in situ one-step chemical polymerization and applied in potential biomedical applications. Incorporation of NFC into PPy significantly improved its film formation ability resulting in composite materials with good mechanical and electrical properties. It is shown that the NFC/PPy-Ag composite films have strong inhibition effect against the growth of Gram-positive bacteria, e.g., Staphylococcus aureus. The electrical conductivity and strong antimicrobial activity makes it possible to use the silver composites in various applications aimed at biomedical treatments and diagnostics. Additionally, we report here the structural and morphological characterization of the composite materials with Fourier-transform infrared spectroscopy, atomic force microscopy, and scanning and transmission electron microscopy techniques.

Reproductive endocrine function in women with epilepsy: the role of epilepsy type and medication.

The purpose of the analysis described here was to assess reproductive endocrine disorders in 148 women with epilepsy (WWE) by epilepsy type and antiepileptic drug use. Women with idiopathic generalized epilepsy had a higher prevalence of reproductive endocrine disorders than control subjects. In addition, hyperandrogenism, polycystic ovaries, and polycystic ovary syndrome were more prevalent in WWE on valproate than in WWE taking other drugs or control women. The use of VPA was a predictor of the development of polycystic ovaries and polycystic ovary syndrome, and the use of valproate and younger age predicted the development of hyperandrogenism. In conclusion, both idiopathic generalized epilepsy and valproate were associated with an increased risk of reproductive endocrine disorders in WWE in this post hoc reanalysis of data on a large number of WWE. This was especially evident if the epilepsy was active and required treatment early in life.

Frostbite injuries treated in the Helsinki area from 1995 to 2002.

BACKGROUND: : Exposure to cold results in frostbite, superficial or deeper tissue damage. In severe frostbites, amputations are life-saving but diminish quality of life (QOL). METHODS: : Retrospective study was performed. RAND 36- questionnaire was administered to assess QOL. Our aim was to investigate risk factors and adjustment to everyday life of hospitalized patients. RESULTS: : 92 frostbites in 42 patients were recorded. One third of the patients were chronic alcoholics. Age and temperature were statistically significant factors for unfavorable outcome. 20% of patients required secondary reconstructive procedures. One-third reported their emotional well-being very poor. Half had limitations in social life. CONCLUSIONS: : Hospitalized cases of frostbite are rare. Anti-social behavior increases the risk in general, and patients present with complicated problems similar to those encountered in burns victims. We recommend that frostbite patients requiring hospital attendance are treated in specialized units, where sufficient expertise for acute as well as reconstructive surgery is available.

Serum androgen levels and testicular structure during pubertal maturation in male subjects with epilepsy.

PURPOSE: To evaluate reproductive endocrine function in boys and young men with epilepsy taking an antiepileptic drug in a population-based, controlled study. METHODS: Seventy patients and 70 controls matched for age and pubertal stage participated in this study. Twenty-eight patients were taking carbamazepine (CBZ); five, lamotrigine (LTG); 12, oxcarbazepine (OXC); and 25, valproate (VPA) as monotherapy for epilepsy. All subjects were examined clinically, and their medical histories were obtained. Serum reproductive hormone and sex hormone-binding globulin concentrations were measured, and testicular ultrasonography was performed. RESULTS: Serum testosterone levels were within the normal range in young male patients with epilepsy. However, the patients taking VPA had high serum androstenedione levels at all pubertal stages. In prepuberty, their serum androstenedione values were already approximately fivefold compared with the values of the controls (8.7 nM; SD, 4.0 vs. 1.8 nM, SD, 1.0; p < 0.0003), and they were elevated in 64% of the VPA-treated patients compared with none of the other patients, p = 0.0006. Serum sex hormone-binding globulin levels were increased, and serum dehydroepiandrosterone sulfate concentrations decreased in the pubertal patients taking CBZ. The mean testicular volumes did not differ between the patients and the controls. CONCLUSIONS: CBZ and VPA, but not LTG and OXC, are associated with changes in serum sex-hormone levels in boys and young men with epilepsy. However, the long-term health consequences of these reproductive endocrine changes during pubertal development remain to be established.