Ferric- and calcium-loaded red soil assist colonization of submerged macrophyte for the in-situ remediation of eutrophic shallow lake: From mesocosm experiment to field enclosure application.

Eutrophication and its resulting harmful algal blooms greatly reduce the ecosystem services of natural waters. The use of modified clay materials to assist the phytoremediation of eutrophic water is a promising technique. In this study, ferric chloride and calcium hydroxide were respectively loaded on red soil for algal flocculation and phosphorus inactivation. A two-by-two factorial mesocosm experiment with and without the application of ferric- and calcium- loaded red soil (FA), and with and without planting the submerged macrophyte Vallisneria natans was conducted for the in-situ repair of eutrophic water and sediment. Furthermore, field enclosure application was carried out to verify the feasibility of the technology. At the end of the mesocosm experiment, the total phosphorus, total nitrogen, and ammonia nitrogen concentrations in water were reduced by 81.8 %, 63.3 %, and 62.0 %, respectively, and orthophosphate phosphorus concentration in the sediment-water interface decreased by 90.2 % in the FA + V. natans group compared with those in the control group. The concentration and proportion of chlorophyll-a in cyanobacteria decreased by 89.8 % and 71.2 %, respectively, in the FA + V. natans group. The content of active phosphorus in V. natans decreased and that of inert phosphorus increased in the FA + V. natans group, compared with those in the V. natans alone group, thus may reducing the risk of phosphorus release after decomposing of V. natans. The sediment bacterial diversity index did not change significantly among treatments. Field enclosure application have also been successful, with chlorophyll-a concentration in the water of treated enclosure decreased from above 200 µg/L to below 10 µg/L, and phosphorus concentration in the water decreased from >0.6 mg/L to <0.02 mg/L. These results demonstrated that the FA in combination with submerged macrophyte planting had great potential for the in-situ remediation of eutrophic water, especially those with severe algal blooms.

Selenium-dependent glutathione peroxidase 1 regulates transcription of elongase 3 in murine tissues.

We have previously shown dysregulated lipid metabolism in tissues of glutathione peroxidase 1 (GPX1) overexpressing (OE) or deficient (KO) mice. This study explored underlying mechanisms of GPX1 in regulating tissue fatty acid (FA) biosynthesis. GPX1 OE, KO, and wild-type (WT) mice (n = 5, male, 3-6 months old) were fed a Se-adequate diet (0.3 mg/kg) and assayed for liver and adipose tissue FA profiles and mRNA levels of key enzymes of FA biosynthesis and redox-responsive transcriptional factors (TFs). These three genotypes of mice (n = 5) were injected intraperitoneally with diquat, ebselen, and N-acetylcysteine (NAC) at 10, 50, and 50 mg/kg of body weight, respectively, and killed at 0 and 12 h after the injections to detect mRNA levels of FA elongases and desaturases and the TFs in the liver and adipose tissue. A luciferase reporter assay with targeted deletions of mouse Elovl3 promoter was performed to determine transcriptional regulations of the gene by GPX1 mimic ebselen in HEK293T cells. Compared with WT, GPX1 OE and KO mice had 9-42% lower (p < 0.05) and 36-161% higher (p < 0.05) concentrations of C20:0, C22:0, and C24:0 in these two tissues, respectively, along with reciprocal increases and decreases (p < 0.05) of Elovl3 transcripts. Ebselen and NAC decreased (p < 0.05), whereas diquat decreased (p < 0.05), Elovl3 transcripts in the two tissues. Overexpression and knockout of GPX1 decreased (p < 0.05) and increased (p < 0.05) ELOVL3 levels in the two tissues, respectively. Three TFs (GABP, SP1, and DBP) were identified to bind the Elovl3 promoter (-1164/+33 base pairs). Deletion of DBP (-98/-86 base pairs) binding domain in the promoter attenuated (13%, p < 0.05) inhibition of ebselen on Elovl3 promoter activation. In summary, GPX1 overexpression down-regulated very long-chain FA biosynthesis via transcriptional inhibition of the Elovl3 promoter activation.

Baicalin Antagonizes Prostate Cancer Stemness via Inhibiting Notch1/NF-κB Signaling Pathway.

OBJECTIVE: To investigate the molecular mechanisms underlying the effect of baicalin on prostate cancer (PCa) progression both in vivo and in vitro. METHODS: The in situ PCa stem cells (PCSCs)-injected xenograft tumor models were established in BALB/c nude mice. Tumor volume and weight were respectively checked after baicalin (100 mg/kg) treatment. Hematoxylin-eosin (HE) staining was used to observe the growth arrest and cell necrosis. mRNA expression levels of acetaldehyde dehydrogenase 1 (ALDH1), CD44, CD133 and Notch1 were determined by reverse transcription-polymerase chain reaction. Protein expression levels of ALDH1, CD44, CD133, Notch1, nuclear factor κB (NF-κB) P65 and NF-κB p-P65 were detected by Western blot. Expression and subcellular location of ALDH1, CD44, CD133, Notch1 and NF-κB p65 were detected by immunofluorescence analysis. In vitro, cell cycle distribution and cell apoptosis of PC3 PCSCs was assessed by flow cytometry after baicalin (125 µmol/L) treatment. The migration and invasion abilities of PCSCs were assessed using Transwell assays. Transmission electron microscopy scanning was utilized to observe the structure and autophagosome formation of baicalin-treated PCSCs. In addition, PCSCs were infected with lentiviruses expressing human Notch1. RESULTS: Compared with the control group, the tumor volume and weight were notably reduced in mice treated with 100 mg/kg baicalin (P<0.05 or P<0.01). Histopathological analysis showed that baicalin treatment significantly inhibited cell proliferation and promoted cell apoptosis. Furthermore, baicalin treatment reduced mRNA and protein expression levels of CD44, CD133, ALDH1, and Notch1 as well as the protein expression of NF-κB p-P65 in the xenograft tumor (P<0.01). In vitro, the cell proliferation of PCSCs was significantly attenuated after treatment with 125 µmol/L baicalin for 72 h (P<0.01). The cell migration and invasion rates were decreased following treatment with baicalin for 48 and 72 h (P<0.01). Baicalin notably induced cell apoptosis and seriously damaged the structure of PCSCs. The mRNA and protein expressions of CD133, CD44, ALDH1 and Notch1 in PCSCs were significantly downregulated following baicalin treatment (P<0.01). Importantly, the inhibitory effects of baicalin on PCa progression and stemness were reversed by Notch1 overexpression (P<0.05 or P<0.01). CONCLUSION: Mechanistically, baicalin exhibited a potential therapeutic effect on PCa via inhibiting the Notch1/NF-κB signaling pathway and its mediated cancer stemness.

Crosslinked albumin-manganese nanoaggregates with sensitized T1 relaxivity and indocyanine green loading for multimodal imaging and cancer phototherapy.

Albumin-manganese-based nanocomposites (AMNs) characterized by simple preparation and good biocompatibility have been widely used for in vivo T1-weighted magnetic resonance imaging (MRI) and cancer theranostics. Herein, an aggregation and crosslinking assembly strategy was proposed to achieve the sensitization to T1 relaxivity of the albumin-manganese nanocomposite. At a relatively low Mn content (0.35%), the aggregation and crosslinking of bovine serum albumin-MnO2 (BM) resulted in a dramatic increase of T1 relaxivity from 5.49 to 67.2 mM-1 s-1. Upon the loading of indocyanine green (ICG) into the crosslinked BM nanoaggregates (C-BM), the T1 relaxivity of the C-BM/ICG nanocomposite (C-BM/I) was further increased to 97.3 mM-1 s-1, which was much higher than those reported previously even at high Mn contents. Moreover, the presence of C-BM greatly enhanced the photoacoustic (PA) and photothermal effects of ICG at 830 and 808 nm, respectively, and the second near infrared fluorescence (NIR-II FL) of ICG also showed better stability. Therefore, the synthesized C-BM/ICG nanocomposite exhibited remarkable performance in in vivo multimodal imaging of tumors, such as T1-weighted MRI, NIR-II FL imaging and PA imaging, and cancer phototherapy with little side effects. This work provided a highly efficient and promising multifunctional nanoprobe for breaking through the limits of cancer theranostics, and opened a new avenue for the development of high-relaxivity AMNs and multimodal imaging methodology.

Total coumarins of Pileostegia tomentella induces cell death in SCLC by reprogramming metabolic patterns, possibly through attenuating ß-catenin/AMPK/SIRT1.

BACKGROUND: Small-cell lung cancer (SCLC) is a high malignant and high energy-consuming type of lung cancer. Total coumarins of Pileostegia tomentella (TCPT) from a traditional folk medicine of Yao minority, is a potential anti-cancer mixture against SCLC, but the pharmacological and molecular mechanism of TCPT remains largely unknown. METHODS: Screening of viability inhibition of TCPT among 7 cell lines were conducted by using CCK-8 assays. Anti-proliferative activities of TCPT in SCLC were observed by using colony formation and flow cytometry assays. Morphological changes were observed by transmission electron microscope and Mito-Tracker staining. High Throughput RNA-seq analysis and bio-informatics analysis were applied to find potential targeted biological and signaling pathways affected by TCPT. The mRNA expression of DEGs and protein expression of signalling proteins and metabolic enzymes were verified by qPCR and Western blot assays. Activity of rate-limiting enzymes and metabolite level were detected by corresponding enzyme activity and metabolites kits. Xenograft nude mice model of SCLC was established to observe the in vivo inhibition, metabolism reprogramming and mechanism of TCPT. RESULTS: TCPT treatment shows the best inhibition in SCLC cell line H1688 rather than other 5 lung cancer cell lines. Ultrastructural investigation indicates TCPT induces mitochondria damage such as cytoplasm shrinkage, ridges concentration and early sight of autolysosome, as well as decrease of membrane potential. Results of RNA-seq combined bio-informatics analysis find out changes of metabolism progression affected the most by TCPT in SCLC cells, and these changes might be regulated by ß-catenin/AMPK/SIRT1 axis. TCPT might mainly decline the activity and expression of rate-limiting enzymes, OGDH, PDHE1, and LDHA/B to reprogram aerobic oxidation pattern, resulting in reduction of ATP production in SCLC cells. Xenograft nude mice model demonstrates TCPT could induce cell death and inhibit growth in vivo. Assimilate to the results of in vitro model, TCPT reprograms metabolism by decreasing the activity and expression of rate-limiting enzymes (OGDH, PDHE1, and LDHA/B), and attenuates the expression of ß-catenin, p-ß-catenin, AMPK and SIRT1 accordance with in vitro data. CONCLUSION: Our results demonstrated TCPT induces cell death of SCLC by reprograming metabolic patterns, possibly through attenuating master metabolic pathway axis ß-catenin/AMPK/SIRT1.

Transcription Factor YY1 Ameliorates Liver Ischemia-reperfusion Injury Through Modulating the miR-181a-5p/ESR1/ERBB2 Axis.

BACKGROUND: Liver ischemia/reperfusion injury (I/RI) is characterized by inflammatory actions. Understanding the mechanistic insights underpinning inflammation is critical to developing treatment strategies. In this study, we illustrated the mechanistic insights of transcription factor Yin-Yang 1 (YY1)-mediated microRNA (miR)-181a-5p/estrogen receptor alpha (ESR1)/epidermal growth factor receptor 2 (ERBB2) axis in liver I/RI. METHODS: First, we established liver I/RI models in mice and hypoxia-reperfusion (H/R) cell models in mouse hepatocytes (AML12). Subsequently, the expression of YY1, miR-181a-5p, and ESR1 was determined in the 2 models. I/RI mouse models were further injected with lentivirus carrying oe-YY1' and H/R-exposed AML12 cells were subjected to a series of inhibitors, mimics, and shRNAs to validate the mechanisms of YY1 in controlling miR-181a-5p and ESR1 in liver I/RI. RESULTS: Upregulated expression of miR-181a-5p and downregulated expression of YY1 were identified in the liver tissues of liver I/RI mice and H/R-exposed hepatocytes. Moreover, overexpression of YY1 inhibited the miR-181a-5p expression and thus repressed the H/R-induced hepatocyte apoptosis and inflammation. ESR1 was further validated as a target gene of miR-181a-5p and could be negatively regulated by miR-181a-5p. miR-181a-5p inhibition elevated ESR1 expression, which consequently enhanced the ERBB2 expression and reduced H/R-induced hepatocyte apoptosis and inflammation. CONCLUSIONS: Overall, these findings highlighted that YY1 repressed the miR-181a-5p expression and stimulated ESR1-mediated activation of ERBB2, thereby ameliorating liver I/RI. This study provides insight into the development of novel targets for liver I/RI.

Orthogonal excitations of lanthanide nanoparticle up/down conversion emissions via switching NIR lights for in-vivo theranostics.

With multiple emissions ranging from NIR-IIb to visible lights, near-infrared light-excited lanthanide nanoparticle (LnNP) is an ideal in-vivo theranostic platform to achieve imaging guided phototherapy. However, current reported LnNPs typically demonstrate simultaneous up and downconversion emissions with fixed single excitation light, which impairs therapeutic efficiency and generates side effect during navigation. Here we develop a lanthanide-based conversion switching nanoparticle (CSNP) with independent activation of 1550 nm NIR-IIb downconversion emission under 808 nm excitation and 345/450 nm upconversion emission under 980 nm excitation. CSNP is modified with Cy-GSH to quench NIR-IIb emission and photosensitizer hypocrellin A. In vivo delivery of CSNP is traced via 808 nm irradiation, and Cy-GSH changes structure in response to glutathione to activate NIR-IIb imaging. This indicates the tumor position and timing to switch for 980 nm irradiation to activate hypocrellin A for photodynamic therapy. Orthogonal activation of CSNP up/down conversion emissions demonstrates high tumor-to-normal tissue ratio in vivo and good therapeutic result, would have promising potential as a theranostics platform.

The Role of Vitamin D in SARS-CoV-2 Infection and Acute Kidney Injury.

Vitamin D has been described as an essential nutrient and hormone, which can cause nuclear, non-genomic, and mitochondrial effects. Vitamin D not only controls the transcription of thousands of genes, directly or indirectly through the modulation of calcium fluxes, but it also influences the cell metabolism and maintenance specific nuclear programs. Given its broad spectrum of activity and multiple molecular targets, a deficiency of vitamin D can be involved in many pathologies. Vitamin D deficiency also influences mortality and multiple outcomes in chronic kidney disease (CKD). Active and native vitamin D serum levels are also decreased in critically ill patients and are associated with acute kidney injury (AKI) and in-hospital mortality. In addition to regulating calcium and phosphate homeostasis, vitamin D-related mechanisms regulate adaptive and innate immunity. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have a role in excessive proinflammatory cell recruitment and cytokine release, which contribute to alveolar and full-body endothelial damage. AKI is one of the most common extrapulmonary manifestations of severe coronavirus disease 2019 (COVID-19). There are also some correlations between the vitamin D level and COVID-19 severity via several pathways. Proper vitamin D supplementation may be an attractive therapeutic strategy for AKI and has the benefits of low cost and low risk of toxicity and side effects.

Development of a traditional Chinese medicine-based agent for the treatment of cancer cachexia.

BACKGROUND: Despite recent advances in understanding the pathophysiology of cancer cachexia, prevention/treatment of this debilitating disease remains an unmet medical need. METHODS: We developed an integrated, multi-tiered strategy involving both in vitro and in vivo muscle atrophy platforms to identify traditional Chinese medicine (TCM)-based anti-cachectic agents. In the initial screening, we used inflammatory cytokine-induced atrophy of C2C12 myotubes as a phenotypic screening platform to assess the protective effects of TCMs. The selected TCMs were then evaluated for their abilities to protect Caenorhabditis elegans from age-related reduction of mobility and contractility, followed by the C-26 colon adenocarcinoma mouse model of cachexia to confirm the anti-muscle atrophy effects (body/skeletal muscle weights, fibre size distribution, grip strengths, and serum IL-6). Transcriptome analysis, quantitative real-time polymerase chain reaction, and immunoblotting were performed to gain understanding of the potential mechanism(s) by which effective TCM protected against C26 tumour-induced muscle atrophy. RESULTS: Of 29 widely used TCMs, Dioscorea radix (DR) and Mu Dan Pi (MDP) showed a complete protection (all P values, 0.0002) vis-à-vis C26 conditioned medium control in the myotube atrophy platform. MDP exhibited a unique ability to ameliorate age-associated decreases in worm mobility, accompanied by improved total body contractions, relative to control (P < 0.0001 and <0.01, respectively), which, however, was not noted with DR. This differential in vivo protective effect between MDP and DR was also confirmed in the C-26 mouse model. MDP at 1000 mg/kg (MDP-H) was effective in protecting body weight loss (P < 0.05) in C-26 tumour-bearing mice without changing food or water intake, accompanied by the restoration of the fibre size distribution of hindleg skeletal muscles (P < 0.0001) and the forelimb grip strength (P < 0.05). MDP-treated C-26-tumour-bearing mice were alert, showed normal posture and better body conditions, and exhibited lower serum IL-6 levels (P = 0.06) relative to vehicle control. This decreased serum IL-6 was associated with the in vitro suppressive effect of MDP (25 and 50 µg/mL) on IL-6 secretion into culture medium by C26 cells. RNA-seq analysis, followed by quantitative real-time polymerase chain reaction and/or immunoblotting, shows that MDP's anti-cachectic effect was attributable to its ability to reverse the C-26 tumour-induced re-programming of muscle homoeostasis-associated gene expression, including that of two cachexia drivers (MuRF1 and Atrogin-1), in skeletal muscles. CONCLUSIONS: All these findings suggest the translational potential of MDP to foster new strategies for the prevention and/or treatment of cachexia. The protective effect of MDP on other types of muscle atrophy such as sarcopenia might warrant investigations.

The enhanced removal of arsenite from water by double-shell CuOx@MnOy hollow spheres (DCMHS): behavior and mechanisms.

To facilitate removing As(III) from water through an "oxidation-adsorption" process, the double-shell CuOx@MnOy hollow spheres (DCMHS) have been fabricated via a two-step co-precipitation route combined with the soft-template method. The surface characterization results showed that Mn oxides were formed without segregation and uniformly distributed on the surface of CuOx hollow spheres. DCMHS could achieve outstanding performance to remove As(III) with an As maximum adsorption capacity of 32.15 mg/g. Meanwhile, the kinetics results illustrated that the oxidative activity of DCMHS was strengthened due to its specific structure, and part of As(III) was converted to As(V) during the adsorption process. Also, air aeration could further enhance As(III) oxidation and thus improving As removal. The As(III) removal performance could be maintained under neutral and weak alkaline conditions. Phosphate, silicate, and carbonate anions could depress the removal performance, while chloride ions and sulfate anions barely influenced As removal. Moreover, DCMHS could be regenerated using NaOH and KMnO4 solutions without breaking the hollow sphere structure. Based on the spectroscopic analysis results, As(III) molecules were converted to As(V) via two pathways, including the oxidation by Mn oxides or superoxide radicals. The Cu-Mn synergistic effect could not only enhance the oxidative activity of Mn oxides but also produce superoxide radicals via the activation of surface-adsorbed oxygen molecules. Afterwards, the newly formed As(V) could be attached to the hydroxyl groups through surface complexation. Therefore, this work has provided insights into the morphology design of Mn-oxide-containing adsorbents and supplemented the interface reaction mechanisms for enhancing As(III) removal.

Association of Dietary Fish and n-3 Unsaturated Fatty Acid Consumption with Diabetic Nephropathy from a District Hospital in Northern Taiwan.

Nephropathy caused by diabetes mellitus (DM) is the main cause of end-stage renal disease (ESRD). To understand the association of dietary intake with renal function indicators among patients with diabetic nephropathy (DN), this cross-sectional study was conducted at the dietetic consultation clinic of the Taoyuan Armed Forces General Hospital in Taiwan. In total, 317 participants were recruited for this study. Patients with diabetes who had a urinary albumin-creatinine ratio (UACR) of ≥30 mg/g were defined as having DN. The anthropometric characteristics, blood biochemistry, and renal function of the participants were assessed. Furthermore, a semiquantitative food frequency questionnaire (SQFFQ) was administered to investigate the dietary intake of the participants in the DM and DN groups. The result showed that participants in the DN group were older, had longer diabetes duration and poorer glycemic control and renal function than those in the DM group. Logistic regression models revealed that intake of high-fat marine fishes had the lowest odds ratio (OR) for DN risk compared with other fishes (OR: 0.868; 95% CI: 0.781-0.965, p = 0.009). Shellfish, soybean products, and skim milk also provided better protective effects to decrease the risk of DN. A further analysis of polyunsaturated fatty acids revealed that Σn-3 PUFAs significantly reduced DN risk, while Σn-6 PUFAs did not, especially EPA (OR: 0.821; 95% CI: 0.688-0.979, p = 0.029) and DHA (OR: 0.903; 95% CI: 0.823-0.992, p = 0.033) regardless of whether the variables were adjusted, including diabetes duration, age, and HbA1c. Our findings suggest that a diet that incorporates high-fat fish, shellfish, soybean products, and a lower Σn-6/Σn-3 ratio can mitigate DN risk.

General Use of Chinese Herbal Products among Female Patients with Mastitis in Taiwan.

Objectives: Little information is available regarding the use of Chinese herbal medicine to treat mastitis. This study evaluated the prescription patterns of Chinese herbal medicine products in women with mastitis in Taiwan. Design: This is a population-based cross-sectional study. Setting. 8,531 women aged 20-49 years, who received a diagnosis of mastitis between 2004 and 2013, were identified from the Longitudinal Health Insurance Database in Taiwan. We collected data on demographic characteristics, including age, monthly insurance premium, and urbanization level. The ten most Chinese herbal medicines prescribed for mastitis were assessed, including frequency, percentage, average daily dose, and average duration of prescription. Main outcome measures. We analysed the ten most single Chinese herbs and Chinese herbal formulae prescribed for mastitis. Results: Overall, 437 (5.1%) women received Chinese herbal medicine to treat mastitis. Mai Men Dong (Ophiopogon japonicus (Thunb.) Ker Gawl.; 22.3%), Pu Gong Yin (Taraxacum mongolicum Hand.-Mazz.; 7.8%), and Wang Bu Liu Xing (Vaccaria hispanica (Mill.) Rauschert; 3.5%) were three of the most commonly prescribed single Chinese herbs for mastitis. Xian-Fang-Huo-Ming-Yin (18.2%), Jia-Wei-Xiao-Yao-San (9.1%), and Chai-Hu-Shu-Gan-San (8.4%) were three of the most commonly prescribed Chinese herbal formulae. Conclusion: Xian-Fang-Huo-Ming-Yin can clear heat, detoxify body, alleviate swelling, activate blood, and relieve pain. It was the most frequently prescribed Chinese herbal formula in patients with mastitis.

Yin Yang 1-stimulated long noncoding RNA bladder cancer-associated transcript 1 upregulation facilitates esophageal carcinoma progression via the microRNA-5590-3p/programmed cell death-ligand 1 pathway.

Esophageal carcinoma (EC) is a common gastrointestinal malignancy that poses a threat to public health worldwide. Long noncoding RNA (lncRNA) bladder cancer-associated transcript 1 (BLACAT1) exerts a tumorigenic role in several malignant tumors; nevertheless, its function in EC remains largely unknown. Besides, programmed cell death-ligand 1 (PD-L1), an oncogene in numerous human cancers, has been identified as a therapeutic target for EC. Therefore, we intended to explore the potential regulatory network involving BLACAT1 and PD-L1 in EC. In this study, we observed increased BLACAT1 and PD-L1 levels in EC tissues and EC cell lines. Moreover, YY1 could activate BLACAT1 transcription in EC cells (TE-1 and EC9706). In addition, in vitro and in vivo experiments demonstrated that BLACAT1 facilitated EC cell proliferation and metastasis and EC tumor growth. Also, the effects of BLACAT1 silencing on EC cell functions were partially reversed by PD-L1 overexpression. Besides, it was identified that BLACAT1 competed with PD-L1 to bind to miR-5590-3p in EC cells. Furthermore, miR-5590-3p suppression could abrogate the functional effects of BLACAT1 knockdown on EC cells; while PD-L1 silencing partly abolished the promoting effects of miR-5590-3p suppression on the biological functions of EC cells. To sum up, YY1-induced BLACAT1 accelerated EC progression via regulating the miR-5590-3p/PD-L1 axis.

Calycosin, a Common Dietary Isoflavonoid, Suppresses Melanogenesis through the Downregulation of PKA/CREB and p38 MAPK Signaling Pathways.

Calycosin, a bioactive isoflavonoid isolated from root extracts of Astragalus membranaceus, has been reported to inhibit melanogenesis, the mechanism of which remains undefined. In this study, we interrogated the mechanistic basis by which calycosin inhibits melanin production in two model systems, i.e., B16F10 melanoma cells and zebrafish embryos. Calycosin was effective in protecting B16F10 cells from α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis and tyrosinase activity. This anti-melanogenic effect was accompanied by decreased expression levels of microphthalmia-associated transcription factor (MITF), a key protein controlling melanin synthesis, and its target genes tyrosinase and tyrosinase-related protein-2 (TRP-2) in calycosin-treated cells. Mechanistically, we obtained the first evidence that calycosin-mediated MITF downregulation was attributable to its ability to block signaling pathways mediated by cAMP response element-binding protein (CREB) and p38 MAP kinase. The protein kinase A (PKA) inhibitor H-89 and p38 inhibitor SB203580 validated the premise that calycosin inhibits melanin synthesis and tyrosinase activity by regulating the PKA/CREB and p38 MAPK signaling pathways. Moreover, the in vivo anti-melanogenic efficacy of calycosin was manifested by its ability to suppress body pigmentation and tyrosinase activity in zebrafish embryos. Together, these data suggested the translational potential of calycosin to be developed as skin-lightening cosmeceuticals.

Evaluations and Mechanistic Interrogation of Natural Products Isolated From Paeonia suffruticosa for the Treatment of Inflammatory Bowel Disease.

Mu Dan Pi (MDP), a traditional Chinese medicine derived from the root bark of Paeonia suffruticosa Andrews, is used to treat autoimmune diseases due to its anti-inflammatory properties. However, the impact of MDP on inflammatory bowel disease (IBD) and its principal active compounds that contribute to the anti-inflammatory properties are uncertain. Thus, this study systemically evaluated the anti-inflammatory effects of fractionated MDP, which has therapeutic potential for IBD. MDP fractions were prepared by multistep fractionation, among which the ethyl acetate-fraction MDP5 exhibited the highest potency, with anti-inflammatory activity screened by the Toll-like receptor (TLR)-2 agonist, Pam3CSK4, in a cell-based model. MDP5 (at 50 µg/ml, p < 0.001) significantly inhibited nuclear factor kappa-B (NF-κB) reporters triggered by Pam3CSK4, without significant cell toxicity. Moreover, MDP5 (at 10 µg/ml) alleviated proinflammatory signaling triggered by Pam3CSK4 in a dose-dependent manner and reduced downstream IL-6 and TNF-α production (p < 0.001) in primary macrophages. MDP5 also mitigated weight loss, clinical inflammation, colonic infiltration of immune cells and cytokine production in a murine colitis model. Index compounds including paeoniflorin derivatives (ranging from 0.1 to 3.4%), gallic acid (1.8%), and 1,2,3,4,6-penta-O-galloyl-ß-D-glucose (1.1%) in MDP5 fractions were identified by LC-MS/MS and could be used as anti-inflammatory markers for MDP preparation. Collectively, these data suggest that MDP5 is a promising treatment for IBD patients.

Effect of modified bamboo lignin replacing part of C5 petroleum resin on properties of polyurethane/polysiloxane pressure-sensitive adhesive and its application on the wood substrate.

This paper reports a fresh and robust strategy to develop polyurethane/polysiloxane pressure-sensitive adhesives (PSAs) with excellent properties by replacing part of C5 petroleum resin with modified lignin. A unique aspect of this work is the use of renewable lignin to obtain modified monomers. The phenolic hydroxyl group of lignin is increased by 21.4% after demethylation, which will help to introduce 6-bromo-1-hexene into the lignin structure through Williamson method. The L3 lignin and C5 petroleum resin are mixed with polyurethane/polysiloxane prepolymer, and furthermore a series of PSAs are obtained under ultraviolet light. It turns out that L3 lignin can not only replace part of C5 petroleum resin, but also obtain attractive and controllable features. Especially when the mass ratio of C5 petroleum resin to L3 lignin is 6:4, compared with pure C5 petroleum resin, the 180° peel strength and the shear strength of PU46 are increased by 24.1% and 91.5% respectively. Additionally, the shear strength on the wood substrate is increased by 320.6%. This study provides an effective method for the preparation of high value-added lignin PSA, and expands the application fields of PSA.

Hypokalemic paralysis in hyperthyroidism: Not all that glitter are gold.

Abnormal acid-base status (metabolic acidosis or alkalosis), inappropriate urine electrolytes excretion (high or low Na+ and Cl-), and higher required dose of potassium supplement (4-5 mmol/kg) are suggestive of non-TPP causes of hypokalemia.

Replacing fish oil and astaxanthin by microalgal sources produced different metabolic responses in juvenile rainbow trout fed 2 types of practical diets.

Dietary fish oil supplementation provides n-3 long-chained polyunsaturated fatty acids for supporting fish growth and metabolism and enriching fillet with eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; c22:6n-3). Two experiments were performed as a 3 × 2 factorial arrangement of dietary treatments for 16 wk to determine effects and mechanisms of replacing 0%, 50%, and 100% fish oil with DHA-rich microalgae in combination with synthetic vs. microalgal source of astaxanthin in plant protein meal (PM)- or fishmeal (FM)- based diets for juvenile rainbow trout (Oncorhynchus mykiss). Fish (22 ± 0.26 g) were stocked at 17/tank and 3 tanks/diet. The 100% fish oil replacement impaired (P < 0.0001) growth performance, dietary protein and energy utilization, body indices, and tissue accumulation of DHA and EPA in both diet series. The impairments were associated (P < 0.05) with upregulation of hepatic gene expression related to growth (ghr1and igf1) and biosynthesis of DHA and EPA (fads6 and evol5) that was more dramatic in the FM than PM diet-fed fish, and more pronounced on tissue EPA than DHA concentrations. The source of astaxanthin exerted interaction effects with the fish oil replacement on several measures including muscle total cholesterol concentrations. In conclusion, replacing fish oil by the DHA-rich microalgae produced more negative metabolic responses than the substitution of synthetic astaxanthin by the microalgal source in juvenile rainbow trout fed 2 types of practical diets.

Supplemental Microalgal DHA and Astaxanthin Affect Astaxanthin Metabolism and Redox Status of Juvenile Rainbow Trout.

Microalgal docosahexaenoic acid (DHA) and astaxanthin (AST) may substitute for fish oil and synthetic AST in aquafeeds. This study explored the effects and mechanisms of those substitutions on AST metabolism and redox status of rainbow trout fed plant protein meal (PM)- or fishmeal (FM)-based diets. Two parallel experiments (PM vs. FM) were performed with 612 juvenile rainbow trout for 16 weeks as a 2 × 3 factorial arrangement of treatments with two AST sources (synthetic (SA) vs. microalgal (AA), at 80 mg/kg) and three levels (0, 50, and 100%) of fish oil substitutions with DHA-rich microalgae. The fish oil substitutions exhibit main effects (p < 0.05) and/or interactive effects (p < 0.05) with the source of AST on AST deposition, malondialdehyde and glutathione concentrations, and mRNA levels and activities of major redox enzymes (glutathione reductase (GR), glutathione peroxidase (GPX), glutathione S-transferase (GST), and superoxide dismutase (SOD)) in the muscle and liver of trout fed both diet series. The AST source produced only differences in tissue AST deposition (p < 0.05) and number of metabolites. In conclusion, the substitutions of fish oil by the DHA-rich microalgae exerted more impacts than those of SA by AA on redox status and functional expression of antioxidant enzymes in the tissues of rainbow trout.

Ziyin Bushen Decoction Alleviates Perimenopausal Syndrome in Rats by Enhancing Estradiol Production.

Perimenopausal syndrome (PMS) has a high incidence rate and affects the physical and mental health of middle-aged and elderly women. The blockage of PMS is significant in improving the health of perimenopausal women. Currently, for PMS prevention and treatment, traditional Chinese medicine (TCM) has become an ideal choice because of its safety and effectiveness. This study aimed to explore the anti-PMS effects of Ziyin Bushen Decoction (DKTP) and the underlying mechanism. Thirty female Wistar rats were divided into 5 groups (n = 6): control group, low-dose DKTP group, medium-dose DKTP group, high-dose DKTP group, and nilestriol group. The estradiol (E2) level in rat peripheral blood was analyzed using an E2 Radioimmunoassay Kit, and uterine morphologic changes were examined by hematoxylin-eosin staining. Learning and memory ability of rats was assessed by Morris water maze (MWM) and novel object recognition (NOR) task. E2 synthesis, metabolism, and transport associated estrogen receptor-alpha (ERα), GnRHR, CYP17, CYP11A1, CYP19, 17ßHSD, STS, and SHGB were assessed to explore the E2-promoting mechanism of DKTP during PMS treatment. The loss of learning and memory, the decreased estrous and uterine coefficient, and the presence of histopathological changes suggests a successful establishment of rat PMS model. Following DKTP or nilestriol treatment, the above results were reversed. E2 level in serum, uterine, and ovarian tissues was upregulated upon different concentrations of DKTP treatment, indicating that DKTP promotes the E2 level in a dose-dependent manner. DKTP also increased the expression of ERα, CYP17, CYP11A1, CYP19, 17ßHSD, STS, and SHGB while decreased the GnRHR expression in uterine and ovarian tissues, revealing that these key molecules involved in estrogen synthesis, metabolism, and transport in PMS rats. We confirmed the anti-PMS effect of DKTP through enhancing E2 production. Exploring a novel drug based on improving E2 synthesis, metabolism, and transport may represent a novel strategy for PMS prevention and treatment.