Dynamic bond crosslinked maca polysaccharide hydrogels with reactive oxygen species scavenging and antibacterial effects on infected wound healing.

In this study, a polysaccharide fragment with antioxidant and reactive oxygen species (ROS) scavenging activities was extracted from Maca (Lepidium meyenii Walp.) and subjected to structural analyses. The fragment, characterized by the α-D-Glcp-(1 → terminal group of the main chain linked to the →4)-Glcp-(1 → end unit through an O-6 bond and the O-3 bond of 1-3-4Glcp, was modified by introducing dialdehyde structures on its glucose units. It was then crosslinked with N-carboxymethyl chitosan via the Schiff base reaction to create a multifunctional hydrogel with antibacterial and ROS scavenging properties. Polyvinyl alcohol was incorporated to form a double crosslinked gel network, and the addition of silver nanoparticles enhanced its antibacterial efficacy. This gel system can scavenge excess ROS, mitigate wound inflammation, eradicate harmful bacteria, and aid in the restoration of skin microecology. The multifunctional maca polysaccharide hydrogel shows significant potential as a medical dressing for the treatment of infected wounds.

Establishment and validation of a nomogram model for predicting the specific mortality risk of melanoma in upper limbs based on the SEER database.

For patients with upper limb melanoma, the significance of specific death is more important than that of all-cause death, and traditional survival analysis may overestimate the mortality rate of patients. Therefore, the nomogram model for predicting the specific mortality risk of melanoma in the upper limbs was developed. A population with melanoma in the upper limbs, diagnosed from 2010 to 2015, were selected from the National Cancer Institute database of Surveillance, Epidemiology, and End Results (SEER). The independent predictive factors of specific death were confirmed by the competing risk model of one-factor analysis and multi-factor analysis, and the nomogram was constructed according to the independent predictive factors. 17,200 patients with upper limb melanoma were enrolled in the study (training cohort: n = 12,040; validation cohort: n = 5160). Multi-factor analysis of the competing risk model showed that age, marital status, gender, tumor stage, T stage, M stage, regional lymph node surgery information, radiotherapy, chemotherapy, mitotic cell count, ulcer and whether there were multiple primary cancers, were independent factors affecting the specific death of upper limb melanoma patients (P < 0.05). The nomogram has good predictive ability regarding the specific mortality risk of melanoma in the upper limbs, and could be of great help to formulate prognostic treatment strategies and follow-up strategies that are conducive to survival.

Deep eutectic solvents-Hydrogels for the topical management of rheumatoid arthritis.

Deep eutectic solvents (DES) have demonstrated their ability to facilitate skin penetrability of rigid nanoparticles (NPs). Here, we reported a feasible and simple transdermal delivery strategy using mesoporous silica nanoparticles impregnated in DES hydrogels for topical management of rheumatoid arthritis (RA). To achieve this goal, nanoceria was immobilized within a silica nanoparticle matrix (MSN) and encapsulated with methotrexate (MTX). The functionalized nanoparticles were first engineered in an Arginine (Arg)-citric acid (CA) DES and then transferred to the carbomer hydrogel matrix. Due to the strong affinity of DES hydrogels to the skin, combined with solvent-driven "Drag" effects, the prepared DES-MSNs hydrogels produced dynamic mobility of MSNs through skin layers, resulting in high skin penetrability. After application to the skin, the hydrogel solvent drove the rigid NPs across the skin barrier in a nonintrusive manner, resulting in sustained penetration and accumulation of MSNs at subcutaneous inflammation sites. Subsequently, the MTX payload exerted a direct therapeutic effect, while nanoceria moderated the inflammatory microenvironment by initiating reactive oxygen species (ROS) scavenging and transformation of the macrophage phenotype. In this way, the synergistic action of the combination of immuno- and chemotherapy of the drug and its carrier on RA was achieved. Our work provides a novel strategy for multisite regulation and controlled management of RA in a noninvasive way.

De novo and comparative transcriptomic analysis explain morphological differences in Panax notoginseng taproots.

BACKGROUND: Panax notoginseng (Burk.) F. H. Chen (PN) belonging to the genus Panax of family Araliaceae is widely used in traditional Chinese medicine to treat various diseases. PN taproot, as the most vital organ for the accumulation of bioactive components, presents a variable morphology (oval or long), even within the same environment. However, no related studies have yet explained the molecular mechanism of phenotypic differences. To investigate the cause of differences in the taproot phenotype, de novo and comparative transcriptomic analysis on PN taproot was performed. RESULTS: A total of 133,730,886 and 114,761,595 paired-end clean reads were obtained based on high-throughput sequencing from oval and long taproot samples, respectively. 121,955 unigenes with contig N50 = 1,774 bp were generated by using the de novo assembly transcriptome, 63,133 annotations were obtained with the BLAST. And then, 42 genes belong to class III peroxidase (PRX) gene family, 8 genes belong to L-Ascorbate peroxidase (APX) gene family, and 55 genes belong to a series of mitogen-activated protein kinase (MAPK) gene family were identified based on integrated annotation results. Differentially expressed genes analysis indicated substantial up-regulation of PnAPX3 and PnPRX45, which are related to reactive oxygen species metabolism, and the PnMPK3 gene, which is related to cell proliferation and plant root development, in long taproots compared with that in oval taproots. Furthermore, the determination results of real-time quantitative PCR, enzyme activity, and H2O2 content verified transcriptomic analysis results. CONCLUSION: These results collectively demonstrate that reactive oxygen species (ROS) metabolism and the PnMPK3 gene may play vital roles in regulating the taproot phenotype of PN. This study provides further insights into the genetic mechanisms of phenotypic differences in other species of the genus Panax.

Dissolvable microneedles based on Panax notoginseng polysaccharide for transdermal drug delivery and skin dendritic cell activation.

This work explored the feasibility of using biological polysaccharide to fabricate dissolvable microneedles (MNs) for the purpose of transdermal drug delivery and skin dendritic cell (DC) activation. Panax notoginseng polysaccharide (PNPS), a naturally derived immunoactive macromolecule, was used to fabricate dissolvable MNs. The prepared PNPS MNs showed a satisfactory mechanical strength and a skin penetration depth. By Franz diffusion cell assay, the PNPS MNs demonstrated a high transdermal delivery amount of model drugs. Furthermore, with the assistance of MNs, PNPS easily penetrated across the stratum corneum and target ear skin DCs, activating the maturation and migration of immunocytes by increasing the expressions of CD40, CD80, CD86, and MHC II of skin DCs. Consequently, the matured DCs migrated to the auricular draining lymph nodes and increased the proportions of CD4+ T and CD8+ T cells. Thus, PNPS might be a promising biomaterial for transdermal drug delivery, with adjuvant potential.

Lepidium meyenii Walpers polysaccharide and its cationic derivative re-educate tumor-associated macrophages for synergistic tumor immunotherapy.

In the current study, we developed a synergistic chemo-immunotherapy using doxorubicin (Dox) and a natural polysaccharide as immunomodulator. First, we isolated a polysaccharide (MPW) from the root of Lepidium meyenii Walp. (maca) and characterized its chemical properties. MPW contains → 4) -α-D-Glcp- (1 → glycosidic bonds, while the terminal α-D-Glcp- (1 → group is connected to the main chain through an O-6 bond. This polysaccharide was then modified by cationization (C-MPW) to enhance immunoregulatory activity. MPW and C-MPW were combined with Dox and their chemo-immunotherapy effects on 4T1 tumor-bearing mice were assessed. Results indicated that the combination of MPW/C-MPW exerted a stronger anti-tumor effect than Dox alone, while reducing systemic toxicity and inhibiting tumor metastasis. In addition, MPW and C-MPW exerted tumor immunotherapy effects through the NF-κB, STAT1, and STAT3 signaling pathways, redirecting TAMs to the M1 phenotype that facilitates immunological responses against tumors. As a result, the immunosuppressive tumor microenvironment was remodeled into an immune-activated state due to enhanced secretion of IL-12, TNF-α, and INF-γ. Moreover, C-MPW exerted a stronger immunomodulatory effect than MPW. In conclusion, MPW and its cationic derivative are promising tools for cancer immunotherapy.

A novel acidic polysaccharide from the residue of Panax notoginseng and its hepatoprotective effect on alcoholic liver damage in mice.

This study presented the first purification and characterization of a hepatoprotective polysaccharide (PNPS-0.5 M) from the residue of Panax notoginseng (Burk.) F.H. Chen. This polysaccharide included a backbone of (4 â†’ 1)-linked GalA and branches of (1→)-linked Araf, (1→)-linked Rhap, and (5 â†’ 1)-linked Araf and had an extremely high molecular weight (2600 kDa). We investigated the hepatoprotective effects of PNPS-0.5 M on mice with alcoholic liver damage (ALD). After administration of PNPS-0.5 M, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), and hepatic malondialdehyde (MDA) were reduced to normal. In contrast, hepatic levels of alcohol dehydrogenase (ADH) and the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were elevated to normal. Further investigations indicated that PNPS-0.5 M activated Nrf2 signaling as a protective mechanism against Cyp2e1 toxicity in ALD mice. Meanwhile, it strengthened the ADH pathway and suppressed the CAT pathway of alcohol metabolism to prevent peroxide accumulation, thereby ameliorating ALD. In the present study, we describe a novel acidic polysaccharide from P. notoginseng with hepatoprotective activity that facilitates the development and utilization of P. notoginseng resources.

Rapid discrimination of Notoginseng powder adulteration of different grades using FT-MIR spectroscopy combined with chemometrics.

Panax Notoginseng is a kind of herb material with high medicinal value, which requires adaptive planting environment, and not can be continuously cultivated in the same ground. Those reasons lead to a large number of low-grade Notoginseng appears in the market. The objective of this study is to discriminate adulterant of Notoginseng of different grades by FT-MIR spectroscopy couple with chemometrics. In the experiment, high-grade Notoginseng was adulterated with 14 blend ratios: 0%, 1%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, and 100% of low-grade Notoginseng. All samples were scanned in the range of 4000-400 cm-1 by FT-MIR spectra instrument in absorption mode. Baseline, standard normal variate (SNV), multiplicative scatter correction (MSC), orthogonal signal correction (OSC), first derivative (D1) with 11-points smoothing and second derivative (D2) with 11-points smoothing were used to preprocess the spectral data, in which Baseline combined with SNV and D1 with 11-points performed best. The spectral data in the range of 1485-405 cm-1 were selected by interval partial least squares (iPLS) for modeling. Then, Support vector machine (SVM) and linear discriminant analysis (LDA) were applied for modeling analysis. The best result was achieved by SVM, as the classification accuracy was 100%, which indicated that FT-MIR spectroscopy combined with chemometrics was an effective approach to identify Notoginseng powder adulteration. It could detect the blend ratio of 5% (w/w) as well as the blend ratio of over 5%.

Macrophage migration inhibitory factor in the regulation of myoblast proliferation and differentiation.

Obesity is documented to be a state of chronic mild inflammation associated with increased macrophage infiltration into adipose tissue and liver and skeletal muscle. As a pleiotropic inflammatory mediator, macrophage migration inhibitory factor (MIF) is associated with metabolic disease, so MIF may signal molecular links between adipocytes and myocytes. MIF expression was modified during myoblast differentiation, but the role of MIF during this process is unclear. C2C12 cells were transfected with MIF to investigate their role during differentiation. MIF expression attenuated C2C12 differentiation. It did not change proliferation, but downregulated cyclin D1 and CDK4, causing cell accumulation in the G1 phase. p21 protein was increased significantly and MyoD, MyoG, and p21 mRNA also increased significantly in the C2C12 cells treated with ISO-1, suggesting that inhibition of MIF promotes differentiation. MIF inhibits the myoblast differentiation by affecting the cell cycle progression, but does not affect proliferation.

Molecular cloning and characterization of the anti-obesity gene adipose in pig.

Obesity has become an epidemic health problem characterized by aberrant energy metabolism. As the major player in energy homeostasis, adipose tissue has a decisive role in the development of obesity. Many genes involved in adipogenesis are also correlated with obesity. Adipose (Adp) has been established as an anti-obesity gene to repress adipogenesis and fat accumulation in mice, which inhibits the transcriptional activity of PPARγ by forming a chromatin remodeling complex with histones and HDAC3. Here, we reported the cloning and characterization of the pig Adp gene. Pig Adp cDNA had an ORF of 2034 nucleotides and was highly conserved among various species. Genomic sequence analysis indicated that pig Adp gene contains 16 exons and 15 introns, spanning more than 60kb on chromosome 6q21-24. The expression of pig Adp was high in testis, lung, kidney and adipose tissues, and relatively low in skeletal muscle. Bioinformatic analysis of 5'-flanking region of Adp has identified several potential binding sites for pivotal transcriptional factors related to both adipocyte differentiation and inflammation, highlighting the significance of Adp in energy metabolism. We have confirmed that KLF6, a positive regulator of adipogenesis, can enhance the promoter activity of Adp and up-regulate its mRNA expression. Taken together, our results would be helpful for further study of Adp regulation in the process of fat accumulation.