Ethanol extract of Chrysanthemum zawadskii inhibits the NLRP3 inflammasome by suppressing ASC oligomerization in macrophages.

Chrysanthemum zawadskii (C. zawadskii) is used in traditional East Asian medicine for the treatment of various diseases, including inflammatory disease. However, it has remained unclear whether extracts of C. zawadskii inhibit inflammasome activation in macrophages. The present study assessed the inhibitory effect of an ethanol extract of C. zawadskii (CZE) on the activation of the inflammasome in macrophages and the underlying mechanism. Bone marrow-derived macrophages were obtained from wild-type C57BL/6 mice. The release of IL-1ß and lactate dehydrogenase in response to nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome activators, such as ATP, nigericin and monosodium urate (MSU) crystals, was significantly decreased by CZE in lipopolysaccharide (LPS)-primed BMDMs. Western blotting revealed that CZE inhibited ATP-induced caspase-1 cleavage and IL-1ß maturation. To investigate whether CZE inhibits the priming step of the NLRP3 inflammasome, we confirmed the role of CZE at the gene level using RT-qPCR. CZE also downregulated the gene expression of NLRP3 and pro-IL-1ß as well as NF-κB activation in BMDMs in response to LPS. Apoptosis-associated speck-like protein containing a caspase-recruitment domain (CARD) oligomerization and speck formation by NLRP3 inflammasome activators were suppressed by CZE. By contrast, CZE did not affect NLR family CARD domain-containing protein 4 or absent in melanoma 2 inflammasome activation in response to Salmonella typhimurium and poly(dA:dT) in LPS-primed BMDMs, respectively. The results revealed that three key components of CZE, namely linarin, 3,5-dicaffeoylquinic acid and chlorogenic acid, decreased IL-1ß secretion in response to ATP, nigericin and MSU. These findings suggest that CZE effectively inhibited activation of the NLRP3 inflammasome.

Torilis japonica Extract Suppresses the Induction of Atopic Inflammation.

As one of the major intractable allergic disorders, atopic inflammation is commonly accompanied by itching, dry skin, and inflammation. Atopic inflammation deteriorates the quality of life and has no fundamental cure, so it is crucial to urgently explore and develop natural resources for long-term treatment without any side effects. This study aimed to verify Torilis japonica extract (TJE)'s relieving effect and mechanism against atopic inflammation using skin cells and skin equivalent models, as well as to investigate torilin's effect (obtained from TJE) and other unknown components as marker compounds. Torilin concentration was verified in TJE using high-performance liquid chromatography and analyzed the unknown components using nuclear magnetic resonance spectroscopy. Furthermore, TJE's cytotoxicity, regenerative effect, and cell cycle regulation effects were confirmed using skin cells with atopic inflammation (human dermal fibroblasts and HaCaT keratinocytes) by using TNF-α and IFN-γ treatments. Consequently, TJE was demonstrated to regulate TARC and CTACK expressions as chemokines and those of interleukin-4, -5, and -13 as cytokines related to atopic inflammation. TJE was further confirmed to affect the matrix metalloproteinase-1, -2, and -9 expressions, which are essential in skin damage. Lastly, this study confirmed TJE's relieving effect against atopic inflammation through a 3D skin model and RhCE model using human dermal fibroblasts and HaCaT keratinocytes. These findings on atopic inflammation verified torilin's relieving effects and TJE's other components.

Salicornia herbacea Aqueous Extracts Regulate NLRP3 Inflammasome Activation in Macrophages and Trophoblasts.

Salicornia herbacea L. (Chenopodiaceae), an edible salt marsh plant with anti-inflammatory effects, was examined in macrophages and trophoblasts whether it modulates NLRP3 inflammasome activity. Pretreatment and delayed treatment of S. herbacea extract (SHE) in bone marrow-derived macrophages (BMDMs) reduced the activity of NLRP3 inflammasome induced by lipopolysaccharide (LPS) and adenosine triphosphate stimulation and downregulated interleukin (IL)-1ß production. SHE also inhibited pyroptotic cell death, the adaptor molecule apoptosis-associated speck-like protein containing a CARD (ASC), oligomerization, and speck by NLRP3 inflammasome activity in BMDM. Similarly, SHE decreased the mRNA expression of NLRP3, ASC, IL-1ß, and IL-6 in the LPS-stimulated human trophoblast cell line, Swan 71 cells. In addition, SHE inhibited the production of IL-6 and IL-1ß and decreased the expression of cyclooxygenase-2 and prostaglandin E2 in stimulated Swan 71 cells. Finally, 3,5-dicaffeoylquinic acid (3,5-DCQA), one of the components of S. herbacea, inhibited IL-1ß produced by NLRP3 inflammasome activity. In conclusion, SHE downregulated the activity of the NLRP3 inflammasome in macrophages and trophoblasts.

The p53-Driven Anticancer Effect of Ribes fasciculatum Extract on AGS Gastric Cancer Cells.

Cancer metastasis is directly related to the survival rate of cancer patients. Although cancer metastasis proceeds by the movement of cancer cells, it is fundamentally caused by its resistance to anoikis, a mechanism of apoptosis caused by the loss of adhesion of cancer cells. Therefore, it was found that inhibiting cancer migration and reducing anoikis resistance are important for cancer suppression, and natural compounds can effectively control it. Among them, Ribes fasciculatum, which has been used as a medicinal plant, was confirmed to have anticancer potential, and experiments were conducted to prove various anticancer effects by extracting Ribes fasciculatum (RFE). Through various experiments, it was observed that RFE induces apoptosis of AGS gastric cancer cells, arrests the cell cycle, induces oxidative stress, and reduces mobility. It was also demonstrated that anoikis resistance was attenuated through the downregulation of proteins, such as epidermal growth factor receptor (EGFR). Moreover, the anticancer effect of RFE depends upon the increase in p53 expression, suggesting that RFE is suitable for the development of p53-targeted anticancer materials. Moreover, through xenotransplantation, it was found that the anticancer effect of RFE confirmed in vitro was continued in vivo.

Enhanced biotransformation of the minor ginsenosides in red ginseng extract by Penicillium decumbens ß-glucosidase.

Compound K (C-K) and Rh2, which are present at low levels in ginseng and ginseng extracts, have higher intestinal absorption rates than other ginsenosides. Here, we attempted to convert ginsenoside Rb1 to C-K using a ß-glucosidase from Penicillium decumbens. Ten commercially available enzymes were screened to identify enzymes that can convert ginsenoside Rb1 to C-K, resulting in the selection of a P. decumbens-derived ß-glucosidase. ß-Glucosidase showed maximum activity at pH 4.0 and 60 °C; its substrate specificity for ginsenoside Rb1 was investigated. The main glucoside-hydrolyzing pathways were as follows: ginsenoside Rb1 or Rd → gypenoside XVII → F2 → C-K and ginsenoside Rg3 → Rh2. The P. decumbens-derived ß-glucosidase was used to generate C-K and Rh2 using protopanaxadiol-type ginsenosides as substrates. Additionally, to apply this enzyme to the commercialized red ginseng extract products, the contents of C-K and Rh2 in the total ginsenosides significantly (p < 0.05) increased up to 36-fold and 8.9-fold, respectively, higher than prior to subjecting to biotransformation. To the best of our knowledge, this is the first report of the dual biotransformation of C-K and Rh2 by a food-grade commercial enzyme. This study demonstrates that the use of a specific ß-glucosidase may increase C-K and Rh2 contents in the ginseng extract through a simple biotransformation process and, thus, enhance its health benefits.

Extract from Zanthoxylum piperitum Induces Apoptosis of AGS Gastric Cancer Cells Through Akt/MDM2/p53 Signaling Pathway.

OBJECTIVE: To determine the effect of Zanthoxylum piperitum extracet (ZPE) on apoptosis and analyze anticancer substances in ZPE, changes in proteins related to apoptosis, and pathological changes in tumors in mouse. METHODS: Fifteen 4-week-old female BALB/c nu/nu mice were divided into 3 groups depending on ZPE dose, with 5 in each group. AGS gastric carcinoma cells (1 × 106 cells/200 µL) were subcutaneously injected into the flank of each mouse. One week after the injection of AGS cells, ZPE was administered to the skin tissue [10 or 50 mg/(kg·d)] in the low- and high-dose groups, respectively for 20 days. Control animals were injected with vehicle only. After 3 weeks, the tumor was extracted and carried out for immunohistochemistry, the tendency of apoptosis and p53 in the body was checked using TdT-mediated dUTP nick-end labeling (TUNEL) assay. For 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, annexin V dead cell staining, cell cycle arrest and Western blotting, AGS gastric carcinoma cells were incubated with various concentrations of ZPE for 24 h. Cell survival rates were analyzed by MTT assays. Apoptosis was analyzed using annexin V dead cell staining and cell cycle arrest and measured using Muse cell analyzer. RESULTS: High performance liquid chromatography (HPLC) analysis showed that ZPE contained organic sulfur compounds such as alliin and S-allylcysteine. MTT assay results revealed that ZPE (10-85 µ g/mL) could effectively inhibit the growth of AGS gastric cancer cells at higher concentrations (P<0.05, P<0.01). The annexin V & dead cell staining assay and cell cycle arrest assay confirmed a dose-dependent increase in the apoptosis rate and G1 phase in ZPE (10-70 µ g/mL) groups. ZPE decreased the expression of anti-apoptotic proteins (p-Akt, p-MDM2, Bcl-2), while increased pro-apoptotic proteins (cleaved PARP, p53, pro-Caspase 3, Bax). TUNEL assays revealed an increase in cell apoptosis. Immunohistochemistry staining confirmed the involvement of p53. CONCLUSION: ZPE decreases AGS cell proliferation and induces apoptosis by inhibiting Akt and MDM2 expression.

Combination of vegetable soup and glucan demonstrates synergistic effects on macrophage-mediated immune responses.

Vegetable soup (VS), a plant-based functional food, has been used as a traditional folk medicine and is attracting attention for its ability to enhance the immune response. ß-Glucan, a well-established and effective immunomodulator, has synergistic effects when used in combination with some bioactive compounds. In the present study, we aimed to evaluate the synergistic immunomodulatory effects of the combination of VS and ß-glucan on macrophage-mediated immune responses. ß-Glucan was demonstrated to synergistically enhance the VS-stimulated immune response, including the production of interleukin-6, tumor necrosis factor-α, and nitric oxide, mainly through the mitogen-activated protein kinase pathway in macrophages. In addition, this combination has the potential for further development in functional foods with immune-enhancing activity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-00888-x.

Aqueous green tea infusion extracted by ultra-sonication method, but not by conventional method, facilitates GLUT4 membrane translocation in adipocytes which potently ameliorates high-fat diet-induced obesity.

Green tea contains bioactive compounds, such as polyphenols, responsible for its health-promoting effects, including antiobesity and antidiabetic effects. We previously reported that ultra-sonication extraction (UE) could efficiently increase the extraction yield of green tea compounds. In the present study, we found that the extract obtained using UE contained higher phenolic and flavonoid contents than that obtained using the conventional method. We therefore considered the extract as a bioactive metabolite-rich functional green tea extract (BMF-GTE), and tested its glucose-lowering effect by generating an adipocyte cell line stably expressing 7myc-GLUT4-GFP. We found that BMF-GTE treatment increased GLUT4 translocation to the plasma membrane. Moreover, BMF-GTE administration attenuated weight gain in mice fed a high-fat diet (HFD). Importantly, HFD-induced glucose tolerance was ameliorated in the mice receiving BMF-GTE. Therefore, we conclude that BMF-GTE worked against obesity and diabetes, at least partially, by enhancing GLUT4 translocation in adipocytes. PRACTICAL APPLICATIONS: As green tea is one of the most consumed beverages worldwide, its health effects have been widely tested. In our previous studies, we found that ultra-sonication extraction (UE) has the potential to increase the aqueous extraction yield of green tea compounds compared to conventional extraction techniques. In this study, we examined the biological effect of bioactive metabolite-rich functional green tea extract (BMF-GTE) obtained using UE; we observed that administering BMF-GTE lowered the body weight and increased insulin sensitivity in mice fed a high-fat diet, potentially by facilitating the membrane translocation of GLUT4 in adipocytes. Therefore, this study suggests that the extract obtained with UE had antiobesity and antidiabetic properties, indicative of a potential application of UE in maximizing the beneficial effects of green tea on human health.

Anti-Obesity Effect of an Ethanol Extract of Cheongchunchal In Vitro and In Vivo.

Cheongchunchal (CE) is a developed crop more highly enriched in cyanidin-3-O-glucoside chloride (anthocyanin) than conventional waxy corn. Anthocyanin has been proven to have anti-oxidant, anti-inflammatory, anti-obesity, and anti-cancer effects. In this study, using high-performance liquid chromatography (HPLC), Cheongchunchal was confirmed to contain 8.99 mg/g anthocyanin. The inhibitory effect of an ethanol extract of Cheongchunchal (CE) on adipocyte differentiation was demonstrated using Oil Red O staining and a triglyceride assay. By conducting Western blotting, we also confirmed the regulatory effect of CE on adipocyte differentiation factors by assessing changes in the levels of factors that play a significant role in the differentiation of 3T3-L1 preadipocytes. A C57BL/6N mouse model of obesity was induced with a high-fat diet, and CE (400, 600, and 800 mg/kg/day) or Garcinia (245 mg/kg/day) was orally administered to verify the anti-obesity effect of CE. As a result of CE administration, the food efficiency ratio (FER), weight gain, and weight of tissues decreased. Additionally, blood biochemical changes were observed. Furthermore, the inhibitory effect of CE on adipocytes was confirmed through morphological observation and the expression of adipocyte differentiation-related factors in the liver and fat tissues. Therefore, in this study, we verified the anti-obesity effects of anthocyanin-rich CE both in vitro and in vivo.

Antiaging Activity of Peptide Identified from Fermented Trapa Japonica Fruit Extract in Human Dermal Fibroblasts.

We have previously shown that Trapa japonica fruit extract (TJE) as well as its fermented extract (FTJ) can be potentially used to treat alopecia. In the current study, a newly synthesized peptide (PEP) was detected in an active compound isolated from FTJ. Several biological assays were conducted to verify the antiaging effects of TJE, FTJ, and PEP on the skin. We examined the effects of TJE, FTJ, and PEP on cell viability, collagen synthesis, and inhibition of mRNA expression of matrix metalloproteinases (MMPs), induced by tumor necrosis factor alpha (TNF-α), in human dermal fibroblasts (HDFs). In addition, a wound-healing assay of the human keratinocyte cell line (HaCaT) and a clinical study of antiaging activity were conducted. The findings confirmed that PEP exerted an effect on cell proliferation in a dose-dependent manner. Treatment with TJE, FTJ, and PEP increased collagen synthesis but inhibited TNF-α-induced mRNA expression of MMPs. Compared with TJE and FTJ, PEP promoted a significant level of wound recovery in HaCaT cells and also exhibited antiaging effect, as demonstrated by a clinical study. These results suggest that PEP shows potential as a skin antiaging cosmetic product.

Kinetic analysis and catalytic pyrolysis of spent medicinal herb over HZSM-5 and HY.

In this study, the kinetic analysis on the pyrolysis of a spent medicinal herb, namely spent Achyranthes root, is performed using a thermogravimetric analyzer and a model-free kinetic analysis method, allowing the calculation of activation energy values without the assumption of kinetic model. Owing to the structural change of lignin and elimination of hemicellulose during the decoction of raw Achyranthes root, the thermogravimetric analysis results show a large difference between the derivative thermogravimetry curves of spent and raw Achyranthes roots. The average apparent activation energy value of spent Achyranthes root, obtained from the non-isothermal thermogravimetric analysis, are found to be lower than those of raw Achyranthes root. This comes as a result of the much lower content of hemicellulose in spent Achyranthes root caused by the hemicellulose elimination from raw Achyranthes root during the decoction process. The catalytic fast pyrolysis of spent Achyranthes root over HZSM5-30 (HZSM-5 with SiO2/Al2O3 = 30) and HY30 (HY with SiO2/Al2O3 = 30) was performed using a two-stage fixed-bed reactor system. The catalytic fast pyrolysis of spent Achyranthes root over both HY30 and HZSM5-30 produced the much larger amount of aromatic hydrocarbons, compared to the non-catalytic fast pyrolysis, with a parallel decrease of oxygen-containing pyrolyzates. Owing to its robust pore structure and high acidity, it was the HZSM5-30 that produced the highest quality oil during the catalytic fast pyrolysis of spent Achyranthes root, having higher selectivity of mono-aromatic hydrocarbons compared to HY30.

New 8-C-p-Hydroxylbenzylflavonol Glycosides from Pumpkin (Cucurbita moschata Duch.) Tendril and Their Osteoclast Differentiation Inhibitory Activities.

Six new 8-C-p-hydroxybenzylflavonol glycosides were isolated from a hot water extract of pumpkin (Cucurbita moschata Duch.) tendril and elucidated as 8-C-p-hydroxybenzylquercetin 3-O-rutinoside, 8-C-p-hydroxybenzoylquercetin 3-O-ß-D-glucopyranoside, 8-C-p-hydroxybenzylkaempferol 3-O-(α-L-rhamnopyranosyl(1→6)-ß-D-galactopyranoside, 8-C-p-hydroxybenzoylkaempferol 3-O-rutinoside, 8-C-p-hydroxybenzylisorhamnetin 3-O-rutinoside, and 8-C-p-hydroxybenzylisorhamnetin 3-O-(α-L-rhamnopyranosyl(1→6)-ß-D-galactopyranoside. Their chemical structures were determined using nuclear magnetic resonance (NMR) and electrospray ionization-mass spectrometer (ESIMS) analyses. The 8-C-p-hydroxybenzylflavonol glycosides were found to inhibit the receptor activator of nuclear factor-κB (RANKL)-induced osteoclast differentiation of bone marrow derived macrophage (BMDM), an osteoclast progenitor. Additionally, 8-C-p-hydroxybenzylflavonol glycosides effectively reduced the expression of osteoclast-related genes, such as tartrate-resistant acid phosphatase, cathepsin K, nuclear factor activated T-cell cytoplasmic 1, and dendritic cell specific transmembrane protein in RANKL-treated BMDMs. These results indicate that the 8-C-p-hydroxybenzylflavonol glycosides may be the main components responsible for the osteoclast differentiation inhibitory effect of pumpkin tendril.

Tendril extract of Cucurbita moschata suppresses NLRP3 inflammasome activation in murine macrophages and human trophoblast cells.

Inflammation is the root cause of many diseases that pose a serious threat to human health. Excessive inflammation can also result in preterm birth or miscarriage in pregnant women. Pumpkin (Cucurbita moschata Duchesne, CMD) is a well-known traditional health food and medicinal herb used in many countries to treat diabetes, obesity, osteoporosis, cancer and other diseases. In this study, we investigated the effects of hot water extract derived from the tendrils of C. moschata Duchesne (TCMD) on NLRP3 inflammasome activation in murine macrophages and human trophoblast cells. The TCMD treatment of LPS-primed bone marrow-derived macrophages (BMDMs) and human trophoblast cells attenuated NLRP3 inflammasome activation induced by inflammasome activators such as ATP, nigericin, and monosodium urate (MSU). TCMD treatment suppressed IL-1ß secretion in a dose-dependent manner, without affecting IL-6 secretion. In addition, TCMD inhibited NLRP3-dependent pyroptosis in BMDMs. TCMD also suppressed the release of mature IL-1ß and activation of cleaved-caspase-1 via limited ASC oligomerization. Furthermore, TCMD significantly inhibited IL-1ß secretion and pyroptotic cell death in human trophoblast cells. These results suggest that TCMD exhibits anti-inflammatory effects mediated via inhibition of NLRP3 inflammasome activation suggesting therapeutic potential against inflammatory diseases, preterm birth, and miscarriage.

Water extract of tendril of Cucurbita Moschata Duch. suppresses RANKL-induced osteoclastogenesis by down-regulating p38 and ERK signaling.

Background: Pumpkin (Curcubita sp.) is a natural product that is commonly used in folk medicine. However, the inhibitory effect and molecular mechanisms of tendril of Cucurbita Moschata Duch. (TCMD) on osteoclast differentiation have yet to be clearly elucidated. Thus, the present study aimed to investigate the effect and underlying mechanism of water extract of TCMD on osteoclast differentiation. Methods: Bone marrow-derived macrophages (BMDMs), osteoclast precursors, were cultured with macrophage colony stimulating factor (M-CSF) 30 ng/ml and receptor activator of nuclear factor-kappa B ligand (RANKL) 100 ng/ml for four days. We investigated the effect of TCMD on RANKL-induced osteoclast differentiation, tartrate-resistant acid phosphatase (TRAP) staining, F-actin ring formation, and bone resorption assay. RANKL signaling pathways were determined through Western blotting, and osteoclast differentiation marker genes were confirmed by Real-time PCR. Results: TCMD inhibited the RANKL-induced osteoclast differentiation in a dose-dependent manner without cytotoxicity. Further, F-actin ring formation and bone resorption were reduced by TCMD in RANKL-treated BMDMs. In addition, TCMD decreased the phosphorylation of p38 and ERK as well as the expression of osteoclast-related genes in BMDMs treated with RANKL. Conclusion: These findings suggest that TCMD may have preventive and therapeutic effects for destructive bone diseases.

Bio-transformation of green tea infusion with tannase and its improvement on adipocyte metabolism.

Catechins in green tea possess various health benefits. Enzymatic treatment improves physiological activities by inducing bioconversion of catechins. Here, we investigated the effect of green tea infusion (GT) after tannase treatment, which transforms (-)-epigallocatechin gallate (EGCG) to gallic acid (GA) and (-)-epigallocatechin (EGC), on adipocyte differentiation and mature adipocyte metabolism. The optimal conditions for tannase-mediated improvement in GA and EGC yields in GT were investigated using response surface methodology. Yields of GA and EGC were 43-fold (0.43 mg/mL) and 1.66-fold higher (1.11 mg/mL), respectively, compared to GT without tannase treatment. The optimal reaction conditions for tannase-mediated biotransformation were observed on 0.54 mg mL-1 of tannase, reaction time (86.79 min), and reaction temperature at 22.59 °C. GT and tannase-treated GT (TANs) upregulated adiponectin, uncoupling protein 1, adipose triglyceride lipase, and hormone-sensitive lipase gene expression in differentiated 3T3-L1 adipocytes, with TAN inducing better effects than GT, which implies that tannase treatment improved the beneficial effect of GT on adipocyte metabolism. Thus, tannase-mediated bio-transformation is an attractive candidate for preparing GT with enhanced anti-obesity properties.

Solvent fractions of fermented Trapa japonica fruit extract stimulate collagen synthesis through TGF-ß1/GSK-3ß/ß-catenin pathway in human dermal fibroblasts.

BACKGROUND: The dermis, composed predominantly of dermal fibroblasts and extracellular matrix (ECM), consists of fibrous proteins such as collagen and elastin and is associated with wrinkle formation and dermal elasticity. As the major constituent of the dermal matrix, collagen strengthens the skin, enhances its elasticity and protects it from external factors, such as ultraviolet (UV) rays, skin inflammation, intracellular metabolites, and aging. AIMS: Economic growth and long-life expectancy have increased the interest in beauty, with extensive studies conducted to evaluate the anti-aging and health-promoting benefits of bioactive substances. METHODS: In this study, we used natural ingredients, Trapa japonica fruit is a hard, aquatic plant that grows in ponds or marshes and contains protein and starch. To develop the ingredients for comprehensive skin improvement, this study investigated the effects of the trapa japonica fruit extract on the improvement of skin cells. CONCLUSION: We investigated the role of the fermented hot-water trapa japonica fruit extract to isolate the active ingredients with antiwrinkle effects in vitro and ex vivo situation through human dermal fibroblast cell proliferation via activating TGF-ß1/GSK-3ß/ß-catenin pathway.

The peptide AC 2 isolated from Bacillus-treated Trapa japonica fruit extract rescues DHT (dihydrotestosterone)-treated human dermal papilla cells and mediates mTORC1 signaling for autophagy and apoptosis suppression.

The Trapa japonica fruit is a natural plant growing in ponds with its roots in the mud. It has long been used as a home remedy for many diseases; however, a major problem with this kind of natural extract is the multicomponents-multitargets for diseases. Such problems make it difficult to identify the mechanism of action. Another problem is quality control and consistency. The aim of this research was to isolate a single bioactive compound (peptide) derived from the Trapa japonica fruit. The research was conducted with various experimental techniques, such as fermentation and liquid chromatography, to isolate a peptide. We isolated the AC 2 peptide from Trapa japonica fruit and found it to be promising on human dermal papilla cells. Dihydrotestosterone (DHT) stresses human dermal papilla cells and is a major cause of hair loss resulting from hormones and environmental factors. The purpose of this research was to develop an understanding of the mechanism by which the AC 2 peptide rescues dihydrotestosterone (DHT)-treated human dermal papilla cells. We explored the effects of the AC 2 peptide on the cell biological functions of human dermal papilla cells (HDPs). HDPs were treated with the AC 2 peptide and DHT. Then, a cytotoxicity assay, flow cytometry, Western blot, immunoprecipitation, and 3D cell culture for immunohistochemistry were conducted to investigate the mTORC1 pathway and suppression of autophagy and apoptosis. In addition, we also synthesized the AC2 peptide as an alternative to the expensive and difficult isolation and purification procedures and confirmed its potential in biomedical applications. We also validated the effects of the synthetic AC2 peptide as well as the isolated and purified AC2 peptide and established their similarity. Although extensive research has been carried out on natural extracts, few single studies have isolated and separated a bioactive peptide (single compound).

Epigallocatechin Exerts Anti-Obesity Effect in Brown Adipose Tissue.

Catechins in green tea are well-known to be effective in reducing the risk of obesity. The purpose of this study was to elucidate the effects of catechins present in green tea on adipocyte differentiation and mature adipocyte metabolism. Treatment of 3T3-L1 mouse adipocyte during differentiation adipocytes with (-)-epigallocatechin (EGC) and gallic acid (GA) resulted in dose-dependent inhibition of adipogenesis. Specifically, EGC increased adiponectin and uncoupling protein 1 (UCP1) transcription in mature adipocytes. Transcription levels of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) were not significantly impacted by either of the compounds. These results suggest that the EGC is the most effective catechin having anti-obesity activity. Finally, EGC is an attractive candidate component for remodeling obesity.

Injectable and Quadruple-Functional Hydrogel as an Alternative to Intravenous Delivery for Enhanced Tumor Targeting.

Intravenous (IV) route is the most commonly used drug-delivery approach. However, the targeting efficiency to tumor through IV delivery is usually less than 10%. To address this limitation, we report a new systemic delivery method utilizing injectable and quadruple-functional hydrogels to improve targeting efficiency through passive, active, and magnetic targeting, and hydrogel-controlled sustained release. The hydrogels consist of a folate/polyethylenimine-conjugated poly(organophosphazene) polymer, which encapsulates small interfering RNA (siRNA) and Au-Fe3O4 nanoparticles to form a nanocapsule (NC) structure by a simple mixing. The hydrogels are localized as a long-term "drug-release depot" after a single subcutaneous injection and sol-gel phase transition. NCs released from the hydrogels enter the circulatory systems and then target the tumor through enhanced permeability and retention/folate/magnetism triple-targeting, over the course of circulation, itself prolonged by the controlled release. In vivo experiments show that 12% of NCs are successfully delivered to the tumor, which is a considerable improvement compared to most results through IV delivery. The sustained targeting of gold to tumor enables two cycles of photothermal therapy, resulting in an enhanced silencing effect of siRNA and considerable reduction of tumor volume, which we are unable to achieve via simple intravenous injection.

Self-selective van der Waals heterostructures for large scale memory array.

The large-scale crossbar array is a promising architecture for hardware-amenable energy efficient three-dimensional memory and neuromorphic computing systems. While accessing a memory cell with negligible sneak currents remains a fundamental issue in the crossbar array architecture, up-to-date memory cells for large-scale crossbar arrays suffer from process and device integration (one selector one resistor) or destructive read operation (complementary resistive switching). Here, we introduce a self-selective memory cell based on hexagonal boron nitride and graphene in a vertical heterostructure. Combining non-volatile and volatile memory operations in the two hexagonal boron nitride layers, we demonstrate a self-selectivity of 1010 with an on/off resistance ratio larger than 103. The graphene layer efficiently blocks the diffusion of volatile silver filaments to integrate the volatile and non-volatile kinetics in a novel way. Our self-selective memory minimizes sneak currents on large-scale memory operation, thereby achieving a practical readout margin for terabit-scale and energy-efficient memory integration.