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Aging can lead to the occurrence of many degenerative diseases, and the most intuitive consequences are mainly manifested on the skin, which is affected by both endogenous and exogenous aging factors and can be used as an ideal model organ for studying aging. 4,4'-Dimethoxychalcone (DMC), a natural flavonoid compound from

7,8-dihydroxyflavone (7,8-DHF), a tyrosine kinase B (TrkB) receptor agonist, can mimick physiological actions of brain-derived neurotrophic factor (BDNF) to attenuate neurogenic disease. However, its use as a functional food, is limited by its low-water solubility, chemical instability, and poor bioavailability. The purpose of this work is to fabricate stable 7,8-DHF loaded zein/lactoferrin (LF) composite nanoparticles (zein/LF-DHF) to overcome these challenges. Results showed that mean particle size of zein/LF nanoparticles was about 74 nm with low polydispersity index (0.200) and turbidity (0.300) values. Zein/LF nanoparticles had good stability against pH (3.0-9.0), ionic strengths (0-500 mM NaCl at neutral pH) and long-term storage. Zein/LF nanoparticles showed spherical structures formed by hydrogen bonding and hydrophobic interactions, however, LF changed surface morphology of zein nanoparticles as observed by scanning electron microscope. X-ray diffraction indicated 7,8-DHF was presented in an amorphous state inside zein/LF nanoparticles. Most importantly, zein/LF-DHF had good redispersibility, and increased the encapsulation efficiency, chemical stability, water solubility and bioaccessibility of 7,8-DHF. Collectively, zein/LF nanoparticles are promising delivery systems for 7,8-DHF in functional foods.

Anti-solvent co-precipitation (ASCP) is the most commonly used method of fabricating food-grade nanoparticles, while the impact of the blending sequence on the formation of nanoparticles lacks research. In this study, 7,8-dihydroxyflavone (7,8-DHF) loaded zein-/sophorolipid nanoparticles with two blending sequences (DHF-Z-S and DHF-Z/S) were successfully fabricated by the ASCP method and used to improve the storage stability and the in vitro bioaccessibility of 7,8-DHF. The results showed that blending sequences significantly affect the physicochemical properties of nanoparticles. DHF-Z-S nanoparticles had smaller particle size, lower polydispersity index and turbidity, and higher negative charge, entrapment efficiency and loading capacity compared to DHF-Z/S nanoparticles. Transmission electron microscopy and scanning electron microscopy revealed that DHF-Z-S and DHF-Z/S nanoparticles have core-shell spherical shape at the nanoscale and sophorolipid changed the surface morphology of zein nanoparticles. Fourier transform infrared spectroscopy and fluorescence spectrum analysis confirmed the presence of effective hydrogen bonding, electrostatic interactions and hydrophobic effects between 7,8-DHF, zein and sophorolipid and the presence of stronger hydrogen bonding and hydrophobic effects in DHF-Z-S nanoparticles. The encapsulated 7,8-DHF was in an amorphous state rather than a crystalline form as determined by X-ray diffraction analysis. Circular dichroism revealed that 7,8-DHF and sophorolipid were capable of changing the secondary structure of zein remarkably. More importantly, compared to DHF-Z/S nanoparticles, the DHF-Z-S nanoparticles possessed higher storage stability and in vitro bioaccessibility. Collectively, DHF-Z-S nanoparticles developed in this study might be a promising means of encapsulating, protecting and delivering hydrophobic nutraceuticals for applications in functional foods.

Advances in understanding the biological effects of dietary flavonoids and flavonoid-rich foods have been reported. Improving knowledge about their beneficial effects, and mechanisms of action, is crucial for better utilization. However, mechanisms responsible for their health benefits are still unclear. Previous research considered has suggested that gut microbiota might be linked to the metabolism of dietary flavonoids. To understand the bioactivities of dietary flavonoids/flavonoid-rich foods better, and the role of microbiota, we explored systematically 1) types of dietary flavonoids and associated health benefits, 2) low bioaccessibilities and metabolic characteristics, 3) gut microbiota role in regulation, and 4) crosstalk between regulation mechanisms. Current challenges and future perspectives were also considered, offering new research directions and identifying trends in the development of flavonoid-rich food products.

Background: A novel pyrrolo indole alkaloids, named Robustanoids A, was isolated from Coffea canephora beans, and it inhibits proliferation of prostate cancer (PCa) cells. However, the molecular mechanism linking Robustanoids A to the tumorigenesis of PCa is not yet clear. Methods: We investigated the expression of lncRNAs in PCa cells with Robustanoids A and control group by microarray analysis. The expression level of TCONS_00027385 in PCa tissues and cell lines was detected by qRT-PCR. Additionally, we conducted functional experiments to investigate the biological effects of TCONS_00027385 on the development of PCa both in vitro and in vivo. Furthermore, bioinformatic analysis, luciferase reporter experiment, RIP assay, pulldown assay, and protein chip were performed to investigate the oncogenic molecular mechanisms of TCONS_00027385.Results: In our current study, we focused on TCONS_00027385, which was up-regulated in PCa tissues and cell lines. The high expression of TCONS_00027385 was related to the progression of PCa. Function assays revealed that silencing TCONS_00027385 inhibited PCa cell proliferation and induced apoptosis, while over-expression of TCONS_00027385 remarkably played an opposite role. A deeper investigation showed that TCONS_00027385 acted as a sponge for hsa-miR-874-5p in PCa, and ASCC2 was a target of miR-874-5p in the downstream. Moreover, a positive association between TCONS_00027385 with ASCC2 and a negative relationship between miR-874-5p and TCONS_00027385 (or ASCC2) were also founded. According to the rescue assay, inhibiting ASCC2 could partially suppress the oncogenic effect on cell proliferation and apoptosis in PCa caused by the overexpression of TCONS_00027385.Conclusion: TCONS_00027385 acted as a competing endogenous RNA (ceRNA) for miR-874-5p to regulate the expression of ASCC2. TCONS_00027385 regulated the miR-874-5p/ASCC2 axis to promote PCa progression.

7,8-Dihydroxyflavone (7,8-DHF), as a high-affinity TrkB receptor agonist, has been extensively explored in many human disorders involving brain-derived neurotrophic factor (BDNF) such as Alzheimer's disease, Parkinson's disease, depression, and obesity. However, to date, the transepithelial transport mechanisms of 7,8-DHF in the intestines remain unclear. The aim of our work was to quantify and to characterize in vitro transport of naturally occurring 7,8-DHF distinguished by its physicochemical and pharmacological properties. We discussed the transport mechanisms of 7,8-DHF using the Caco-2 cell model to determine the bi-directional permeability with different environmental factors (time, concentration, pH, metabolic inhibitors etc.). The influx and efflux characteristics of 7,8-DHF were also clarified. 7,8-DHF was poorly transported across Caco-2 cell monolayers by mainly passive diffusion via a transcellular pathway and not a paracellular pathway. The transport of 7,8-DHF was time and concentration-dependent in both the apical (AP) to basolateral (BL) side and the reverse direction. Interestingly, decreasing the pH from 7.4 to 6.0 markedly enhanced 7,8-DHF transport. It is noteworthy that 7,8-DHF transport was strongly inhibited by metabolic inhibitors and was highly dependent on temperature. The efflux ratio (ER) values at different concentrations were all above 1.5, indicating the existence of the efflux transporter. We found that breast cancer resistance protein (BCRP) was not involved in 7,8-DHF secretion and that the transport mechanism of 7,8-DHF was passive transport with an active efflux mediated by P-glycoprotein (P-gp) and multidrug resistance associated proteins (MRPs), particularly MRP 2. Moreover, the use of various influx transporter inhibitors in Caco-2 cells showed that organic cation transporters (OCTs) and organic anion-transporting polypeptides (OATPs) participated in 7,8-DHF transport. Taken together, the elucidated transport characteristics of 7,8-DHF provide useful information for designing novel and efficient delivery systems and avoiding food-food or food-drug interactions.

Objective 7,8-Dihydroxyflavone (7,8-DHF), a small molecular mimetic of brain-derived neurotrophic factor (BDNF), alleviates high-fat diet-induced obesity in female mice in a sex-specific manner by activating muscular tropomyosin-related kinase B (TrkB). However, the underlying molecular mechanism for this sex difference is unknown. Moreover, muscular estrogen receptor α (ERα) plays a critical role in metabolic diseases. Impaired ERα action is often accompanied by metabolic syndrome (MetS) in postmenopausal women. This study investigated whether muscular ERα is involved in the metabolic effects of 7,8-DHF. Methods For the in vivo studies, 72 female C57BL/6J mice were given a low-fat diet or high-fat diet, and both received daily intragastric administration of vehicle or 7,8-DHF for 24 weeks. The hypothalamic-pituitary-ovarian (HPO) axis function was assessed by investigating typical sex-related serum hormones and the ovarian reserve. Indicators of menopausal MetS, including lipid metabolism, insulin sensitivity, bone density, and serum inflammatory cytokines, were also evaluated. The expression levels of ERα and other relevant signaling molecules were also examined. In vitro, the molecular mechanism involved in the interplay of ERα and TrkB receptors was verified in differentiated C2C12 myotubes using several inhibitors and a lentivirus short hairpin RNA-knockdown strategy. Results Long-term oral administration of 7,8-DHF acted as a protective factor for the female HPO axis function, protecting against ovarian failure, earlier menopause, and sex hormone disorders, which was paralleled by the alleviation of MetS coupled with the production of ERα-rich, TrkB-activated, and uncoupling protein 1 (UCP1) high thermogenic skeletal muscle tissues. 7,8-DHF-stimulated transactivation of ERα at serine 118 (S118) and tyrosine 537 (Y537), which was crucial to activate the BDNF/TrkB signaling cascades. In turn, activation of BDNF/TrkB signaling was also required for the ligand-independent activation of ERα, especially at the Y537 phosphorylation site. In addition, Src family kinases played a core role in the interplay of ERα and TrkB, synergistically activating the signaling pathways related to energy metabolism. Conclusions These findings revealed a novel role of 7,8-DHF in protecting the function of the female HPO axis and activating tissue-specific ERα, which improves our understanding of this sex difference in 7,8-DHF-mediated maintenance of metabolic homeostasis and provides new therapeutic strategies for managing MetS in women., Graphical abstract Image 1, Highlights • 7,8-DHF improves hypothalamic-pituitary-ovarian axis function in mature adult female mice. • 7,8-DHF protects against ovarian failure and onset of earlier menopause. • 7,8-DHF-induced transactivation of ERα is crucial to activate BDNF/TrkB signaling cascades. • 7,8-DHF-induced activations of ERα and BDNF/TrkB signaling are interdependent. • Src family kinases play a core role in the crosstalk of ERα and BDNF/TrkB signaling pathways.

Imbalances in bone formation and resorption cause osteoporosis. Mounting evidence supports that brain-derived neurotrophic factor (BDNF) implicates in this process. 7,8-Dihydroxyflavone (7,8-DHF), a plant-derived small molecular TrkB agonist, mimics the functions of BDNF. We show that both BDNF and 7,8-DHF promoted the proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells. These effects might be attributed to the activation of the Wnt/β-catenin signaling pathway as the expression of cyclin D1, phosphorylated-glycogen synthase kinase-3β (p-GSK3β), β-catenin, Runx2, Osterix, and osteoprotegerin (OPG) was all significantly up-regulated. Knockdown of β-catenin restrained the up-regulation of Runx2 and Osterix stimulated by 7,8-DHF. In particular, blocking TrkB by its specific inhibitor K252a suppressed 7,8-DHF-induced osteoblastic proliferation, differentiation, and expression of osteoblastogenic genes. Moreover, BDNF and 7,8-DHF repressed osteoclastic differentiation of RAW264.7 cells. The transcription factor c-fos and osteoclastic genes such as tartrate-resistant acid phosphatase (TRAP), matrix metalloprotein-9 (MMP-9), Adamts5 were inhibited by 7,8-DHF. More importantly, 7,8-DHF attenuated bone loss, improved trabecular microarchitecture, tibial biomechanical properties, and bone biochemical indexes in an ovariectomy (OVX) rat model. The current work highlights the dual regulatory effects that 7,8-DHF exerts on bone remodeling.

A case-control study was conducted in Shandong from January to December 2017 to explore the relationship between sleep quality and the risk of active pulmonary tuberculosis (PTB). Seventy-nine patients with type 2 diabetes mellitus coincident with newly diagnosed pulmonary tuberculosis (DM-PTB) and 169 age, sex, and DM course frequency-matched controls (DM alone) were enrolled. Univariate and multivariable unconditional logistic regression analyses were conducted. We further conducted subgroup analyses to explore the relationship between sleep quality and PTB risk, including DM course (≤5 and ＞5 years), age, sex, and the presence of overweight or obesity (body mass index (BMI) ＞ 24 kg/m2). Multivariate logistic regression demonstrated that poor sleep quality had a borderline negative association with the odds of PTB (P ＝ 0.065). Subgroup multivariate analyses showed that poor sleep quality increased the risk of PTB to more than 3 times among patients with a DM course ＞ 5 years (odds ratio 3.31, 95% confidence interval: 1.08-10.13; P ＝ 0.036) after adjusting for potential confounding factors including residential area, educational level, BMI, history of contact with tuberculosis patients, smoking, alcohol consumption, physical exercise, immune status, and frequency of blood glucose monitoring. In conclusion, poor sleep quality is an independent risk factor of PTB among DM patients with a course of ＞ 5 years, which indicates significant epidemiological implications for PTB control.

Adsorption of black peanut skin anthocyanins, a natural pigment, onto various macroporous resins was optimized to develop a potential approach for large-scale production of black peanut skin anthocyanins. Seven different macroporous resins (AB-8, SP-207, LS-305A, HP-20, LS-305, DM-21 and LS-610B) were evaluated for the adsorption properties of the anthocyanins extracted from the black peanut skins of Arachis hypogaea L. The adsorption experiment proved that compared to AB-8, SP-207 and LS-305A, four resins, i.e., LS-610B, DM-21, LS-305 and HP-20 have relatively higher capacity of adsorbing black peanut skin anthocyanins from the aqueous solution, which are verified by the related adsorption experiments. The adsorption isotherm data was successfully described by Langmuir isotherm model and the pseudo-second-order rate model simulates the kinetic process well. Column adsorption and desorption tests further proved DM-21 is a promising adsorbent for field applications to recover black peanut skin anthocyanins from aqueous solution. The overall yield of pigment product was 14% based on dried black peanut skin, and anthocyanins purity is at about 5.7% in the pigment product.

Low bioavailability and stability of 7,8-dihydroxyflavone (7,8-DHF) hinder its potential application in prevention of humans’ disease. 7,8-DHF loaded nanoliposomes decorated by original, crosslinked and glycosylated lactoferrin (LF) were fabricated. The mean particle size of spherical crosslinked and glycosylated LF coating liposomes were larger than uncoated liposomes with a low polydispersity index, and the former had higher encapsulation efficiency (Above 98%). Crosslinked and glycosylated LF coating liposomes had higher antioxidant activity, storage stability, slow-release ability, bioaccessibility and transepithelial transport compared to free 7,8-DHF and 7,8-DHF loaded liposome. Effective hydrogen bonding between phospholipid and 7,8-DHF, while electrostatic interaction and hydrogen bonding between LF proteins and phospholipid existed. The encapsulated 7,8-DHF was in an amorphous state rather than a crystalline form as detected by differential scanning calorimetry. Collectively, crosslinked or glycosylated LF coating liposomes are promising delivery systems for protecting and transporting 7,8-DHF or other relative bioactive components.

Background: Patients with type 2 diabetes (DM) have a higher risk of developing pulmonary tuberculosis (PTB); moreover, DM co-morbidity in PTB is associated with poor PTB treatment outcomes. Community based prevalence data on DM and prediabetes (pre-DM) among TB patients is lacking, particularly from the developing world. Therefore we conducted a prospective study to investigate the prevalence of DM and pre-DM and evaluated the risk factors for the presence of DM among newly detected PTB patients in rural areas of China. Methods and Findings: In a prospective community based study carried out from 2010 to 2012, a representative sample of 6382 newly detected PTB patients from 7 TB clinics in Linyi were tested for DM. A population of 6674 non-TB controls from the same community was similarly tested as well. The prevalence of DM in TB patients (6.3%) was higher than that in non-TB controls (4.7%, p = 10000 RMB yuan) were positively associated and frequent outdoor activity was negatively associated with DM in PTB patients. Conclusions: The prevalence of DM in PTB patients was higher than in non-TB controls with a 3 fold higher adjusted odds ratio of having DM. Given the increasing DM prevalence and still high burden of TB in China, this association may represent a new public health challenge concerning the prevention and treatment of both diseases.

A modified multiframe image restoration algorithm of degraded images is described in this paper, which is based on the method developed by V. Katkovnik. The projection gradient algorithm based on anisotropic LPA-ICI filtering, being proposed by V. Katkovnik, could only restore images contaminated by Gaussian noisy, also it was too complicated and time consuming. By improving Katkovnik's cost function and applying constraints on image intensity value in iteration, we reached a new multiframe recursive iteration restoration scheme in frequency domain. This method is suitable for reconstruction of images degenerated by both Gaussian noise and Poissonian noise, as well by mixed noise. Experimental results demonstrated that this method works efficiently, and could well restore images blurred heavily by multi-noise.