Protective effects of Quercus acuta Thunb. fruit extract against UVB-induced photoaging through ERK/AP-1 signaling modulation in human keratinocytes

Background Quercus acuta Thunb. (Fagaceae) or Japanese evergreen oak is cultivated as an ornamental plant in South Korea, China, Japan, and Taiwan and used in traditional medicine. The acorn or fruit of Quercus acuta Thunb. (QAF) is the main ingredient of acorn jelly, a traditional food in Korea. Its leaf was recently shown to have potent xanthine oxidase inhibitory and anti-hyperuricemic activities; however, there have been no studies on the biological activity of QAF extracts. Solar ultraviolet light triggers photoaging of the skin, which increases the production of reactive oxygen species (ROS) and expression of matrix metalloproteinase (MMPs), and destroys collagen fibers, consequently inducing wrinkle formation. The aim of this study was to investigate the effect of water extracts of QAF against UVB-induced skin photoaging and to elucidate the underlying molecular mechanisms in human keratinocytes (HaCaT). Methods In this study, we used HPLC to identify the major active components of QAF water extracts. Anti-photoaging effects of QAF extracts were evaluated by analyzing ROS procollagen type I in UVB-irradiated HaCaT keratinocytes. Antiradical activity was determined using 2,2-diphenyl-1-picrylhydrazyl and 2,20-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) assays. The expression of MMP-1 was tested by western blotting and ELISA kits. QAF effects on phosphorylation of the MAPK (p38, JNK, and ERK) pathway and transcription factor AP-1, which enhances the expression of MMPs, were analyzed by western blots. Results We identified two major active components in QAF water extracts, gallotannic acid and ellagic acid. The QAF aqueous extracts recovered UVB-induced cell toxicity and reduced oxidative stress by inhibiting intracellular ROS generation in HaCaT cells. QAF rescued UVB-induced collagen degradation by suppressing MMP-1 expression. The anti-photoaging activities of QAF were associated with the inhibition of UVB-induced phosphorylation of extracellular signal-regulated kinase (ERK) and activator protein 1 (AP-1). Our findings indicated that QAF prevents UVB-induced skin damage due to collagen degradation and MMP-1 activation via inactivation of the ERK/AP-1 signaling pathway. Overall, this study strongly suggests that QAF exerts anti-skin-aging effects and is a potential natural biomaterial that inhibits UVB-induced photoaging. Conclusion These results show that QAF water extract effectively prevents skin photoaging by enhancing collagen deposition and inhibiting MMP-1 via the ERK/AP-1 signaling pathway.

Impaired LAIR-1-mediated immune control due to collagen degradation in fibrosis

SummaryTissue repair is disturbed in fibrotic diseases like systemic sclerosis (SSc), where the deposition of large amounts of extracellular matrix components such as collagen interferes with organ function. LAIR-1 is an inhibitory collagen receptor highly expressed on tissue immune cells. We questioned whether in SSc, impaired LAIR-1-collagen interaction is contributing to the ongoing inflammation and fibrosis.We found that SSc patients do not have an intrinsic defect in LAIR-1 expression or function. Instead, fibroblasts from SSc patients deposit disorganized collagen products in vitro, which are dysfunctional LAIR-1 ligands. This can be mimicked in healthy fibroblast stimulated by soluble factors that drive inflammation and fibrosis in SSc and is dependent of matrix metalloproteinases and platelet-derived growth factor receptor signaling.In support of a non-redundant role of LAIR-1 in the control of fibrosis, we found that LAIR-1-deficient mice have increased skin fibrosis in the bleomycin mouse model for SSc. Thus, LAIR-1 represents an essential control mechanism for tissue repair. In fibrotic disease, excessive collagen degradation may lead to a disturbed feedback loop. The presence of functional LAIR-1 in patients provides a therapeutic opportunity to reactivate this intrinsic negative feedback mechanism in fibrotic diseases.Abstract Figure

INFLUENCE OF CHRONIC NON-GASEOUS ACIDOSIS ON BONE TISSUE

The urgency of the problem is due to the high prevalence among the population in all countries of the world and socio-economic losses associated with serious complications of osteoporosis. Chronic non-gaseous acidosis leads to disruption of many metabolic processes, which causes dysfunction of some organs, namely, can lead to decreased kidney function, exacerbate cardiovascular disease, the development of osteoporosis. Different types of non-gaseous acidosis are accompanied by changes in protein metabolism, which lead to the development of osteoporosis. Aim: to study the structural features of the bone tissue of the femur in chronic non-gaseous acidosis. Methods. The experiments were carried out on 60 intact white outbred male rats weighing 120-180 g, which were kept on a balanced diet of vivarium. Chronic non-gaseous acidosis was simulated by daily intragastric administration with a probe for 60 days 20 mmol/kg NH4CL. The control animals were injected with the same amount of tap water. Histological examination and osteometry were used to study the structure, length and thickness of the rat femur. Free, bound, and total oxyproline in rat urine was determined by biochemical method. Results. In chronic non-gaseous acidosis after 6 months there is a tendency to reduce the length and thickness of the femur, but does not differ significantly from the control group. In the urine of rats of the experimental group, the total oxyproline increases mainly due to an increase in free oxyproline, which indicates the predominance of collagen degradation over repair. The histological structure of the bone is disturbed due to the thinning of the bone beams, the intercellular matrix is disorganized, in some places there is its "defibering" with the formation of foci of destruction and cylindrical "lumens". There is a violation of the crystalline structure of bone tissue, its uneven calcification, the formation of cracks in the bone beams. Studied literature sources and our research indicate that chronic non-gaseous acidosis has a pathogenic effect on the histological structure of bone. Acidosis is a stress factor that increases the level of glucocorticoids. Glucocorticoids inhibit type I collagen synthesis and increase the expression of collagenase 3, which promotes collagen degradation. Collagen is a source of amino acids that are the substrate for renal ammoniogenesis. Renal ammoniogenesis is a compensatory mechanism in chronic non-gaseous acidosis, which required for restores the normal ratio between fixed cations and anions blood plasma. Thus, the violation of the organic basis of bones is the body's adaptation to chronic non-gaseous acidosis. Conclusions. Chronic non-gaseous acidosis simultaneously leads to thinning and disorganization of the intercellular matrix, disruption of the crystal structure of bone tissue, which indicates its important role in the development of osteoporosis. In chronic non-gaseous acidosis, the concentration of oxyproline in the urine increases, which is a marker of the destruction of collagen in the organic matrix of bone.

Echinochrome A Protects against Ultraviolet B-induced Photoaging by Lowering Collagen Degradation and Inflammatory Cell Infiltration in Hairless Mice

Echinochrome A (Ech A, 7-ethyl-2,3,5,6,8-pentahydroxy-1,4-naphthoquinone) has been known to exhibit anti-oxidative and anti-inflammatory effects. However, no study has been carried out on the efficacy of Ech A against skin photoaging; this process is largely mediated by oxidative stress. Six-week-old male SKH-1 hairless mice (n = 36) were divided into five groups. Except for a group that were not treated (n = 4), all mice underwent ultraviolet-B (UVB) exposure for 8 weeks while applying phosphate-buffered saline or Ech A through intraperitoneal injection. UVB impaired skin barrier function, showing increased transepidermal water loss and decreased stratum corneum hydration. UVB induced dermal collagen degeneration and mast cell infiltration. Ech A injection was found to significantly lower transepidermal water loss while attenuating tissue inflammatory changes and collagen degeneration compared to the control. Furthermore, Ech A was found to decrease the relative expression of matrix metalloproteinase, tryptase, and chymase. Taken together, these results suggest that Ech A protects against UVB-induced photoaging in both functional and histologic aspects, causing a lowering of collagen degradation and inflammatory cell infiltration.

An Adipose-Derived Injectable Sustained-Release Collagen Scaffold of Adipokines Prepared Through a Fast Mechanical Processing Technique for Preventing Skin Photoaging in Mice

Ultraviolet A (UVA) radiation is the major contributor to skin photoaging, associated with increased collagen degradation and reactive oxygen species (ROS) expression. Adipokines have been proven as promising therapeutic agents for skin photoaging. However, adipokine therapy is generally limited by the short in vivo release duration and biological instability. Therefore, developing a treatment that provides a sustained release of adipokines and enhanced therapeutic effects is desirable. In this study, we developed a novel mechanical processing technique to extract adipose tissue-derived ECM components, named the “adipose collagen fragment” (ACF). The physical characterization, injectability, collagen components, residual DNA/RNA and adipokine release pattern of ACF were identified in vitro. L929 cells were treated with ACF or phosphate-buffered saline for 24 h after UVA irradiation in vitro. The expression of senescence-associated xβ-galactosidase (SA-β-gal), ROS and antioxidase were investigated. Then, we evaluated its therapeutic efficacy by injecting ACF and phosphate-buffered saline, as a control, into the dermis of photoaging nude mice and harvesting skin samples at weeks 1, 2, and 4 after treatment for assessment. The content of adipokines released from ACF was identified in vivo. The collagen synthesis and collagen degradation in ACF implants were evaluated by immune staining. Dermal thickness, fibroblast expression, collagen synthesis, ROS level, antioxidase expression, capillary density, and apoptotic cell number were evaluated by histological assessment, immune staining, and polymerase chain reaction in the skin samples. We demonstrated that ACF is the concentrated adipose extracellular matrix collagen fragment without viable cells and can be injected through fine needles. The lower expression of SA-β-gal, ROS and higher expression of antioxidase were observed in the ACF-treated group. ACF undergoes collagen degradation and promotes neocollagen synthesis in ACF implants. Meanwhile, ACF serves as a sustained-release system of adipokines and exhibits a significantly higher therapeutic effect on mouse skin photoaging by enhancing angiogenesis, antioxidant abilities, antiapoptotic activities, and collagen synthesis through sustainedly releasing adipokines. To sum up, ACF is an adipokines-enriched, sustained-release extracellular matrix collagen scaffold that can prevent UVA-induced skin photoaging in mice. ACF may serve as a novel autologous skin filler for skin rejuvenation applications in the clinic.

Diagnostic Significance of β-Collagen Degradation Products and Osteocalcin in Chronic Obstructive Pulmonary Disease Complicated with Osteoporosis

Chronic obstructive pulmonary disease is a pulmonary dysfunction common to the middle-aged and elderly population. About 20–60% of patients with moderate or severe chronic obstructive pulmonary disease suffer from different degrees of osteoporosis. A strong relationship between β-collagen degradation products and osteocalcin has been shown in several bone diseases, but their roles in chronic obstructive pulmonary disease remain to be investigated. This study was designed to explore such a relationship in patients with chronic obstructive pulmonary disease complicated with osteoporosis. The β-collagen degradation products were the highest in the serum of patients diagnosed with both chronic obstructive pulmonary disease and osteoporosis followed by those with chronic obstructive pulmonary disease only and osteoporosis only. According to the receiver operating characteristic analysis curves, both β-collagen degradation products and osteocalcin had favorable predictive values for patients with chronic obstructive pulmonary disease, osteoporosis or both. In addition, β-collagen degradation products were negatively correlated with forced expiratory volume in 1 s and bone mineral density, while osteocalcin was positively correlated with them. β-collagen degradation products increase, and osteocalcin decreases in patients with both chronic obstructive pulmonary disease and osteoporosis.