Precursor Heterogeneity Driven Mo-Te Nanoparticle Structural Diversification for Cancer Photo-Theranostics.

Chemical reactions between homogeneous precursors are typically used to synthesize monodisperse nanoparticles with well-controlled size and morphology. It is difficult to predict the evolved nanostructures when using two heterogeneous precursors. In this study, three types of Mo-Te nanoparticles shaped like leaves, spindles, and rice grains (denoted respectively as nanoleaf, nanospindle, and nanorice) were obtained from dextrose-mediated proton-coupled electron transfer reaction between the solid polyoxomolybdate (POM) and the ionic tellurite anion as precursors. All produced nanoparticles had excellent optical absorption in the ultraviolet(UV)-visible(Vis)-near-infrared(NIR) regions, with only slight deviations among them. After confirming nanoparticles' photothermal conversion and photocatalytic activity at multiple wavelengths, the Mo-Te nanorice was tested as a potential agent for cancer treatment due to its minimum toxicity, excellent colloidal stability, and intrinsic anticancer effect. Excellent treatment efficacy and clearance were confirmed in vitro and in vivo. Due to their photoacoustic imaging capability, the injection of pristine nanoparticles could also realize phototheranostics without using additional drugs, probes, or photosensitizers.

Protective Effects of Ethanolic Extract from Rhizome of Polygoni avicularis against Renal Fibrosis and Inflammation in a Diabetic Nephropathy Model.

Progressive diabetic nephropathy (DN) in diabetes leads to major morbidity and mortality. The major pathological alterations of DN include mesangial expansion, extracellular matrix alterations, tubulointerstitial fibrosis, and glomerular sclerosis. Polygoni avicularis is widely used in traditional oriental medicine and has long been used as a diuretic, astringent, insecticide and antihypertensive. However, to the best of the authors' knowledge, the effects of the ethanolic extract from rhizome of Polygoni avicularis (ER-PA) on DN have not yet been assessed. The present study aimed to identify the effect of ER-PA on renal dysfunction, which has been implicated in DN in human renal mesangial cells and db/db mice and investigate its mechanism of action. The in vivo experiment was performed using Polygoni avicularis-ethanol soluble fraction (ER-PA) and was administrated to db/db mice at 10 and 50 mg/kg dose. For the in vitro experiments, the human renal mesangial cells were induced by high glucose (HG, 25 mM). The ER-PA group showed significant amelioration in oral glucose tolerance, and insulin resistance index. ER-PA significantly improved the albumin excretion and markedly reduced plasma creatinine, kidney injury molecule-1 and C-reactive protein. In addition, ER-PA significantly suppressed inflammatory cytokines. Histopathologically, ER-PA attenuated glomerular expansion and tubular fibrosis in db/db mice. Furthermore, ER-PA suppressed the expression of renal fibrosis biomarkers (TGF and Collagen IV). ER-PA also reduced the NLR family pyrin domain containing 3 inflammatory factor level. These results suggest that ER-PA has a protective effect against renal dysfunction through improved insulin resistance as well as the inhibition of nephritis and fibrosis in DN.

Development of evidence-based consensus on critical issues in the management of patients with vitiligo: A modified Delphi study.

BACKGROUND/PURPOSE: Vitiligo remains a major challenge in dermatology. However, much of the treatment remains unclear, because little evidence is available. We sought to answer some critical questions pertaining to management of vitiligo patients. METHODS: A modified Delphi process among 31 vitiligo experts was conducted. A total of 12 clinical vitiligo treatment questions without clear answers were collected via a vote. To address each question, two members performed systematic literature reviews and prepared draft statements along with the levels of evidence and strength of recommendation. After reviewing the draft, all expressed their extent of agreement from 1 (strong disagreement) to 9 (strong agreement) for each item. The drafts were revised to reflect suggested comments. Discussion continued until all members agreed with the ultimate decision. RESULTS: The consensus process was completed after five rounds. We identified the best answers to 12 key questions, including issues on long-term phototherapy, systemic and topical corticosteroids, topical calcineurin inhibitors, immunosuppressants, excimer laser treatment, and surgical interventions. CONCLUSION: This consensus would complement current guidelines and aid both physician and patient decision-making in the treatment of vitiligo.

Evaluation for Skin Cancer and Precancer in Patients With Vitiligo Treated With Long-term Narrowband UV-B Phototherapy.

Importance: Narrowband UV-B (NBUVB) phototherapy has been the mainstay in the treatment of vitiligo, but its long-term safety in terms of photocarcinogenesis has not been established. Objectives: To investigate the risks of skin cancer and precancerous lesions among patients with vitiligo undergoing NBUVB phototherapy, based on the number of NBUVB phototherapy sessions. Design, Setting, and Participants: This nationwide population-based retrospective cohort study enrolled 60 321 patients with vitiligo 20 years or older between January 1, 2007, and December 31, 2017. Patients and outcomes were identified through nationwide cohort data from the Korean national health insurance claims database, and frequency matching by age and sex was performed. Exposures: The number of phototherapy sessions each patient received between 2008 and 2017. Patients were classified into 5 groups according to the number of phototherapy sessions (0 sessions, 20 105 patients; 1-49 sessions, 20 106 patients; 50-99 sessions, 9702 patients; 100-199 sessions, 6226 patients; and ≥200 sessions, 4182 patients). We also identifed patients who underwent at least 500 phototherapy sessions (717 patients). Main Outcomes and Measures: Primary outcomes were the development of actinic keratosis, Bowen disease, nonmelanoma skin cancer, or melanoma after enrollment. Results: Among the 60 321 patients with vitiligo in this study (33 617 women; mean [SD] age, 50.2 [14.9] years), the risks of Bowen disease (<50 sessions of phototherapy: hazard ratio [HR], 0.289 [95% CI, 0.060-1.392]; 50-99 sessions: HR, 0.603 [95% CI, 0.125-2.904]; 100-199 sessions: HR, 1.273 [95% CI, 0.329-4.924]; ≥200 sessions: HR, 1.021 [95% CI, 0.212-4.919]), nonmelanoma skin cancer (<50 sessions: HR, 0.914 [95% CI, 0.533-1.567]; 50-99 sessions: HR, 0.765 [95% CI, 0.372-1.576]; 100-199 sessions: HR, 0.960 [95% CI, 0.453-2.034]; ≥200 sessions: HR, 0.905 [95% CI, 0.395-2.073]), and melanoma (<50 sessions: HR, 0.660 [95% CI, 0.286-1.526]; 50-99 sessions: HR, 0.907 [95% CI, 0.348-2.362]; 100-199 sessions: HR, 0.648 [95% CI, 0.186-2.255]; ≥200 sessions: HR, 0.539 [95% CI, 0.122-2.374]) did not increase after phototherapy. The risk of actinic keratosis increased significantly for those who had undergone 200 or more NBUVB phototherapy sessions (HR, 2.269 [95% CI, 1.530-3.365]). A total of 717 patients with vitiligo underwent at least 500 sessions of NBUVB phototherapy; their risks of nonmelanoma skin cancer and melanoma were no greater than those of the patients who did not undergo NBUVB phototherapy (nonmelanoma skin cancer: HR, 0.563 [95% CI, 0.076-4.142]; melanoma: HR, not applicable). Conclusions and Relevance: Our results suggest that long-term NBUVB phototherapy is not associated with an increased risk of skin cancer in patients with vitiligo and that NBUVB phototherapy may be considered a safe treatment.

Dianthus superbus Improves Glomerular Fibrosis and Renal Dysfunction in Diabetic Nephropathy Model.

Glomerular fibrosis is caused by an accumulation of intercellular spaces containing mesangial matrix proteins through either diffused or nodular changes. Dianthus superbus has been used in traditional medicine as a diuretic, a contraceptive, and an anti-inflammatory agent. The aim of this study was to investigate the effects of Dianthus superbus-EtOAc soluble fraction (DS-EA) on glomerular fibrosis and renal dysfunction, which has been implicated in diabetic nephropathy in human renal mesangial cells and db/db mice. DS-EA was administered to db/db mice at 10 or 50 mg/kg/day for 8 weeks. DS-EA treatment significantly ameliorated blood glucose, insulin, the homeostasis model assessment of insulin resistance (HOMA-IR) index, and HbA1c in diabetic mice. DS-EA decreased albumin excretion, creatinine clearance (Ccr), and plasma creatinine levels. DS-EA also ameliorated the levels of kidney injury molecules-1 (KIM-1) and C-reactive protein. DS-EA reduced the periodic acid-Schiff (PAS) staining intensity and basement membrane thickening in glomeruli of the diabetic nephropathy model. In addition, DS-EA suppressed transforming growth factor-ß (TGF-ß)/Smad signaling. Collagen type IV, a glomerular fibrosis biomarker, was significantly decreased upon DS-EA administration. DS-EA pretreatment attenuated levels of inflammation factors such as intracellular cell adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1). DS-EA inhibited the translocation of nuclear factor kappa B (NF-κB) in Angiotensin II (Ang II)-stimulated mesangial cells. These findings suggest that DS-EA has a protective effect against renal inflammation and fibrosis. Therefore, DS-EA may serve as a potential therapeutic agent targeting glomerulonephritis and glomerulosclerosis, which lead to diabetic nephropathy.

1,[Formula: see text]2,[Formula: see text]3,[Formula: see text]4,[Formula: see text]6-Penta-O-Galloyl-ß-D-Glucose from Galla rhois Ameliorates Renal Tubular Injury and Microvascular Inflammation in Acute Kidney Injury Rats.

Renal ischemia-reperfusion injury (IRI), an important cause of acute kidney injury (AKI), causes increased renal tubular injury and microvascular inflammation. 1,[Formula: see text]2,[Formula: see text]3,[Formula: see text]4,[Formula: see text]6-penta-O-galloyl-[Formula: see text]-D-glucose (PGG) from Galla rhois has anticancer, anti-oxidation and angiogenesis effects. We examined protective effects of PGG on IRI-induced acute AKI. Clamping both renal arteries for 45[Formula: see text]min induced isechemia and then reperfusion. Treatment with PGG (10[Formula: see text]mg/kg/day and 50[Formula: see text]mg/kg/day for four days) significantly ameliorated urine volume, urine osmolality, creatinine clearance (Ccr) and blood urea nitrogen (BUN). In addition, PGG increased aquaporine 1/2/3, Na[Formula: see text]-K[Formula: see text]-ATPase and urea transporter (UT-B) and decreased ICAM-1, MCP-1, and HMGB-1 expression. In this histopathologic study, PGG improved glomerular and tubular damage. Immunohistochemistry results showed that PGG increased aquaporine 1/2, and Na[Formula: see text]-K[Formula: see text] ATPase and decreased ICAM-1 expression. These findings suggest that PGG ameliorates tubular injury including tubular dysfunction and microvascular inflammation in IRI-induced AKI rats.

Classification of facial vitiligo: A cluster analysis of 473 patients.

Vitiligo has a substantial negative impact on quality of life in affected patients, especially those with the involvement of the face. However, the current system can barely distinguish between specific patterns of facial involvement except for the segmental type when focusing only on facial lesions. We classified facial vitiligo into three distinct subtypes using cluster analysis based on facial topography (n = 473): centrofacial vitiligo (72.9%), panfacial vitiligo (18.0%), and hairline vitiligo (9.1%). Centrofacial vitiligo was the most common type and is thought to comprise the typical facial involvement of generalized vitiligo. Panfacial vitiligo was a distinct subtype with onset in old age and less involvement of other body parts. Hairline vitiligo was another distinct subtype with onset in old age and a poor response to conventional phototherapy. A relevant classification system could help us to explore the causes, anticipate the prognosis, and manage the condition in patients with vitiligo.

Systems-level mechanisms of action of Panax ginseng: a network pharmacological approach.

Panax ginseng has been used since ancient times based on the traditional Asian medicine theory and clinical experiences, and currently, is one of the most popular herbs in the world. To date, most of the studies concerning P. ginseng have focused on specific mechanisms of action of individual constituents. However, in spite of many studies on the molecular mechanisms of P. ginseng, it still remains unclear how multiple active ingredients of P. ginseng interact with multiple targets simultaneously, giving the multidimensional effects on various conditions and diseases. In order to decipher the systems-level mechanism of multiple ingredients of P. ginseng, a novel approach is needed beyond conventional reductive analysis. We aim to review the systems-level mechanism of P. ginseng by adopting novel analytical framework-network pharmacology. Here, we constructed a compound-target network of P. ginseng using experimentally validated and machine learning-based prediction results. The targets of the network were analyzed in terms of related biological process, pathways, and diseases. The majority of targets were found to be related with primary metabolic process, signal transduction, nitrogen compound metabolic process, blood circulation, immune system process, cell-cell signaling, biosynthetic process, and neurological system process. In pathway enrichment analysis of targets, mainly the terms related with neural activity showed significant enrichment and formed a cluster. Finally, relative degrees analysis for the target-disease association of P. ginseng revealed several categories of related diseases, including respiratory, psychiatric, and cardiovascular diseases.

Plantago asiatica L. Ameliorates Puromycin Aminonucleoside-Induced Nephrotic Syndrome by Suppressing Inflammation and Apoptosis.

OBJECTIVE: Nephrotic syndrome, a kidney disease with a variety of causes, is mainly characterized by heavy proteinuria, hypoproteinemia, and ascites. This study was designed to evaluate the underlying mechanism of action of Plantago asiatica L. (PAL) in treating nephrotic syndrome induced by puromycin aminonucleoside. METHODS: PAL has been used in Asia as a traditional medicine and dietary health supplement. Sprague-Dawley (SD) rats were intravenously injected with puromycin aminonucleoside (75 mg/kg/day), then treated with either Losartan (30 mg/kg/day) or PAL (200 mg/kg/day) by oral gavage for seven days. RESULTS: PAL significantly decreased ascites, proteinuria level, and plasma lipid parameters. In addition, treatment with PAL attenuated histological damage and hypoalbuminemia. Treatment with PAL also restored podocin expression and reduced inflammation markers such as intracellular adhesion molecules (ICAM-1), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor alpha (TNF-α) and high-mobility group box-1 (HMGB1). Lower expression levels of the apoptosis markers Bax, caspase-3 and capase-9 were documented in SD rats receiving PAL. PAL also significantly decreased the phosphorylation levels of MAPKs such as ERK, JNK and p38. CONCLUSION: As a multifunctional agent, PAL has a renoprotective effect in nephrotic syndrome rat models. The anti-inflammatory and anti-apoptotic properties, along with reductions in hyperlipidemia and ascites, represent important therapeutic effects. These results indicate that Plantago asiatica is likely to be a promising agent in the treatment of nephrotic syndrome.

Fermented Red Ginseng Potentiates Improvement of Metabolic Dysfunction in Metabolic Syndrome Rat Models.

Metabolic syndrome including obesity, dyslipidemia and hypertension is a cluster of risk factors of cardiovascular disease. Fermentation of medicinal herbs improves their pharmacological efficacy. Red ginseng (RG), a widely used traditional herbal medicine, was reported with anti-inflammatory and anti-oxidant activity. Aim in the present study was to investigate that the effects of fermented red ginseng (FRG) on a high-fructose (HF) diet induced metabolic disorders, and those effects were compared to RG and losartan. Animals were divided into four groups: a control group fed a regular diet and tap water, and fructose groups that were fed a 60% high-fructose (HF) diet with/without RG 250 mg/kg/day or FRG 250 mg/kg/day for eight weeks, respectively. Treatment with FRG significantly suppressed the increments of body weight, liver weight, epididymal fat weight and adipocyte size. Moreover, FRG significantly prevented the development of metabolic disturbances such as hyperlipidemia and hypertension. Staining with Oil-red-o demonstrated a marked increase of hepatic accumulation of triglycerides, and this increase was prevented by FRG. FRG ameliorated endothelial dysfunction by downregulation of endothelin-1 (ET-1) and adhesion molecules in the aorta. In addition, FRG induced markedly upregulation of Insulin receptor substrate 1 (IRS-1) and glucose transporter type 4 (Glut4) in the muscle. These results indicate that FRG ameliorates obesity, dyslipidemia, hypertension and fatty liver in HF diet rats. More favorable pharmacological effects on HF diet induced metabolic disorders were observed with FRG, compared to an equal dose of RG. These results showed that the pharmacological activity of RG was enhanced by fermentation. Taken together, fermentated red ginseng might be a beneficial therapeutic approach for metabolic syndrome.

Combination with Red ginseng and Polygoni Multiflori ameliorates highfructose diet induced metabolic syndrome.

BACKGROUND: Metabolic syndrome such as dyslipidemia, hypertension, obesity, impaired glucose tolerance and fatty liver, can be caused by modification of diet by means of overconsumption of high fructose diet. This study was designed to investigate whether combination with Red ginseng and Polygoni Multiflori Radix (RGPM), widely used traditional herbal medicine, ameliorates on highfructose (HF) diet-induced metabolic syndrome. METHODS: SD rats were fed the 60% HF diet with/without rosiglitazone, and RGPM 100, 300 mg/kg/day, respectively. All groups received regular diet or HF diet, respectively, for 8 weeks. The last three groups treatment of rosiglitazone and RPGM orally for a period of 6 weeks. RESULTS: Chronic treatment with RGPM significantly decreased body weight, fat weight and adipocyte size. RGPM significantly prevented the development of the metabolic disturbances such as hypertension, hyperlipidemia and impaired glucose tolerance. RGPM also led to increase in high density lipoprotein level in the HF group. RGPM suppressed high-fructose diet induced vascular inflammation marker expression such as adhesion molecules and ET-1 in aorta as well as increasing of C-reactive protein (CRP) levels in plasma. Similarly, RGPM attenuated hepatic lipid accumulation by inhibition of monocyte chemoattractant protein-1 (MCP-1) expression. CONCLUSION: An administration of RGPM may be a beneficial therapy for the treatment of metabolic syndrome through the improvement of hypertension, obesity, hyperlipidemia, vascular inflammation and insulin resistance.

Blackcurrant Suppresses Metabolic Syndrome Induced by High-Fructose Diet in Rats.

Increased fructose ingestion has been linked to obesity, hyperglycemia, dyslipidemia, and hypertension associated with metabolic syndrome. Blackcurrant (Ribes nigrum; BC) is a horticultural crop in Europe. To induce metabolic syndrome, Sprague-Dawley rats were fed 60% high-fructose diet. Treatment with BC (100 or 300 mg/kg/day for 8 weeks) significantly suppressed increased liver weight, epididymal fat weight, C-reactive protein (CRP), total bilirubin, leptin, and insulin in rats with induced metabolic syndrome. BC markedly prevented increased adipocyte size and hepatic triglyceride accumulation in rats with induced metabolic syndrome. BC suppressed oral glucose tolerance and protein expression of insulin receptor substrate-1 (IRS-1) and phosphorylated AMP-activated protein kinase (p-AMPK) in muscle. BC significantly suppressed plasma total cholesterol, triglyceride, and LDL content. BC suppressed endothelial dysfunction by inducing downregulation of endothelin-1 and adhesion molecules in the aorta. Vascular relaxation of thoracic aortic rings by sodium nitroprusside and acetylcholine was improved by BC. The present study provides evidence of the potential protective effect of BC against metabolic syndrome by demonstrating improvements in dyslipidemia, hypertension, insulin resistance, and obesity in vivo.

Rice mitogen-activated protein kinase interactome analysis using the yeast two-hybrid system.

Mitogen-activated protein kinase (MAPK) cascades support the flow of extracellular signals to intracellular target molecules and ultimately drive a diverse array of physiological functions in cells, tissues, and organisms by interacting with other proteins. Yet, our knowledge of the global physical MAPK interactome in plants remains largely fragmented. Here, we utilized the yeast two-hybrid system and coimmunoprecipitation, pull-down, bimolecular fluorescence complementation, subcellular localization, and kinase assay experiments in the model crop rice (Oryza sativa) to systematically map what is to our knowledge the first plant MAPK-interacting proteins. We identified 80 nonredundant interacting protein pairs (74 nonredundant interactors) for rice MAPKs and elucidated the novel proteome-wide network of MAPK interactors. The established interactome contains four membrane-associated proteins, seven MAP2Ks (for MAPK kinase), four MAPKs, and 59 putative substrates, including 18 transcription factors. Several interactors were also validated by experimental approaches (in vivo and in vitro) and literature survey. Our results highlight the importance of OsMPK1, an ortholog of tobacco (Nicotiana benthamiana) salicyclic acid-induced protein kinase and Arabidopsis (Arabidopsis thaliana) AtMPK6, among the rice MAPKs, as it alone interacts with 41 unique proteins (51.2% of the mapped MAPK interaction network). Additionally, Gene Ontology classification of interacting proteins into 34 functional categories suggested MAPK participation in diverse physiological functions. Together, the results obtained essentially enhance our knowledge of the MAPK-interacting protein network and provide a valuable research resource for developing a nearly complete map of the rice MAPK interactome.