Construction of a dual-component hydrogel matrix for 3D biomimetic skin based on photo-crosslinked chondroitin sulfate/collagen.

The main challenge in the field of 3D biomimetic skin is to search for a suitable hydrogel matrix with good biocompatibility, appropriate mechanical property and inner porosity that can support the adhesion and proliferation of skin cells. In this study, photocurable chondroitin sulfate methacrylate (CSMA) and collagen methacrylate (CoLMA) synthesized from chondroitin sulfate (CS) and type I collagen I (CoL) in the dermal matrix were used to construct a photo-crosslinked dual-component CSMA-CoLMA hydrogel matrix. Due to the toughening effect of the dual-component, the CSMA-CoLMA hydrogel improved the intrinsic brittleness of the single-component CSMA hydrogel, presented good mechanical tunability. The average storage and elasticity modulus could reach 3.3 KPa and 30.3 KPa, respectively, which were close to those of natural skin. The CSMA-CoLMA hydrogel with a ratio of 8/6 showed suitable porous structure and good biocompatibility, supporting the adhesion and proliferation of skin cells. Furthermore, the expression of characteristic marker proteins was detected in the epidermal and dermal bi-layered models constructed with the hydrogel containing keratinocytes and fibroblasts. These results suggest that the dual-component CSMA-CoLMA hydrogel has promising potential as a matrix to construct 3D biomimetic skin.

Explorating the mechanism of Huangqin Tang against skin lipid accumulation through network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Tang (HQT), a famous prescription with the effect of clearing pathogenic heat and detoxifying, was first recorded in "Treatise on Typhoid and Miscellaneous Diseases". It has proved that HQT has good anti-inflammatory and antioxidant effects and can improve acne symptoms clinically. However, the study on the regulation of HQT on sebum secretion which is one of the inducements of acne is not enough. AIM OF THE STUDY: This paper aimed to investigate the mechanisms of HQT in the treatment of skin lipid accumulation by network pharmacology and validating the results via in vitro experiments. MATERIALS AND METHODS: Network pharmacology was employed to predict the potential targets of HQT against sebum accumulation. Then, the palmitic acid (PA)-induced SZ95 cell model was established to evaluate the effect of HQT on lipid accumulation and anti-inflammation, and the core pathways predicted by network pharmacology were verified in cell studies. RESULTS: 336 chemical compounds and 368 targets in HQT were obtained by network pharmacology, of which 65 targets were related to sebum synthesis. 12 core genes were revealed by protein-protein interaction (PPI) network analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results suggested that AMP-activated protein kinase (AMPK) signaling pathway might play a crucial role in regulating lipogenesis. In vitro experiments, HQT suppressed lipid accumulation, downregulated the expressions of sterol-regulatory element binding protein-1 (SREBP-1) and fatty acid synthase (FAS), and upregulated AMPK phosphorylation. Furthermore, AMPK inhibitor reversed HQT-mediated sebosuppressive effect. CONCLUSION: The results disclosed that HQT ameliorates lipogenesis in PA-induced SZ95 sebocytes partially through the AMPK signaling pathway.

An integrated transcriptomics and network pharmacology approach to exploring the mechanism of adriamycin-induced kidney injury.

BACKGROUND AND AIMS: Adriamycin nephropathy model (AN), a rodent model of nephrotic syndrome disease that was caused by the nephrotoxicity of adriamycin, has been widely used for pharmacodynamic evaluation of traditional Chinese medicine (TCM) in the treatment of kidney injury. Although some studies have clearly shown the pathological process of AN, the mechanism of kidney injury have not been systematically investigated. METHODS: The reliability of AN was evaluated by weight, urinary protein quantitation, serum biochemical and histopathological examination. Transcriptomic sequencing combined with network pharmacology were used to elucidate the molecular mechanism of AN, and cell experiment combined with real-time quantitative PCR (RT-qPCR) and was used to validate the accuracy of transcriptomic sequencing result and KEGG pathways. RESULTS: Network analysis result showed that Mapk10 and Ptgs2 played important roles in the development of adriamycin-induced kidney injury. KEGG pathway analysis showed that the mechanism of kidney injury may be related to the regulation of biosynthesis of unsaturated fatty acids, complement and coagulation cascades, PPAR signaling pathway and PI3K-AKT signaling pathway. CONCLUSION: These results provide a new insight into the deep research on the mechanism of kidney injury, and provide an experimental basis for finding drug targets for the treatment of AN.

Exploration the active compounds of Astragali Radix in treatment of adriamycin nephropathy by network pharmacology combined with transcriptomic approach.

PURPOSE: This paper aimed to study the active compounds of Astragali Radix (AR) in the treatment of adriamycin nephropathy (AN) by a combination of network pharmacology and transcriptomics. METHODS: The chemical compounds of AR were screened out by text mining and database searching. Pharm Mapper was used to predict the targets of these chemical compounds. Potential targets of AN were screened by integrating the data from network pharmacology with known transcriptomics analysis results of kidney tissue. Compound-active target-potential target interactions networks were constructed so as to illustrate the relationship between compounds and targets, and obtain the chemical compounds directly related to potential targets of AN. The formula of compound contribution index (CI) based on algorithm was used to screen the active compounds of AR in the treatment of AN. In addition, we established an adriamycin-induced cell damage model with MPC5 cell, and used MTT assay, trypan blue dyeing and western blot analyses to validate the pharmacodynamic effect of the active compounds. RESULTS: 27 chemical compounds and 376 targets in AR were obtained by network pharmacology. Through Compound-active target-potential target interactions networks analysis, 22 compounds and 9 active targets as well as 130 potential targets were linked through 282 edges. The CI of every chemical compounds was further calculated by formula, the first four chemical compounds, including astragaloside IV, formononetin, quercetin and calycosin, whose cumulative contribution rate reached 87.28%, were considered to be active compounds. The results of MTT and trypan blue staining indicate that four active compounds had the significant protective effect on adriamycin-induced cell damage with MPC5 cell. Western blot result showed that four active compounds could significantly increase the expression of podocin protein in MPC5 cell. CONCLUSION: The active compounds of AR in the treatment of AN were successfully identified by using a network pharmacology and transcriptomics approach. This approach is expected to be beneficial to the study of the pharmacodynamic material basis of traditional Chinese medicine (TCM) in treating specific diseases.

Evaluation of Injury Degree of Adriamycin-Induced Nephropathy in Rats Based on Serum Metabolomics Combined with Proline Marker.

Nephrotic syndrome (NS) is one of the leading causes of end-stage renal failure. Unfortunately, reliable surrogate markers for early diagnosing and monitoring the entire progression of NS are as yet absent. A method using UPLC-Q exactive HR-MS was established for the serum metabolomic study of adriamycin-induced nephropathy in rats. Two rat nephropathy models induced by adriamycin were adopted to reflect different degrees of renal damage of early and advanced stages. Then two MPC5 cell models were used to verify the role of proline in the progression of kidney injury. The results showed that seven metabolites such as 14S-HDHA, DPA, and DHA were associated with early renal injury, while 12 metabolites such as tryptophan, linoleyl carnitine, and LysoPC (18:3) reflected the advanced renal disease. At the same time, metabolites including LPE (22:6), LysoPC (22:5), and proline that changed during the whole process of NS were defined as progressive markers. Pathway analysis results showed that fatty acid metabolism, glycerophospholipid metabolism, and amino acids metabolism participated in the occurrence and development of NS. In addition, the change trend of intracellular proline content was consistent with that in serum, and the results were further supported by the detection of the crucial gene PYCRL. This study provides an important basis for searching for diagnostic markers of NS and also provides a methodological reference for early diagnosing and monitoring the pathogenesis of other progressive diseases.

Metabolomics coupled with integrative pharmacology reveal the protective effect of FangjiHuangqi Decoction against adriamycin-induced rat nephropathy model.

With the development of the society, the number of people who got the nephrotic syndrome (NS) is going up roughly. Therefore, finding a better way to treat NS is becoming a major global public health issue. As we all know, traditional Chinese medicine (TCM), especially Fangji Huangqi Decoction (FHD), has a long history and has good curative effects on NS. However, the mechanism of FHD treating NS has not been clearly elucidated. To address this problem, a feasible system was developed by metabolomics and integrative pharmacology approach. To study the mechanisms of Chinese medical formula FHD treating NS based on metabolomics and integrative pharmacology. In this study, a NMR based metabolomics approach coupled with biochemical assay and Western Blot had been employed to study the protective effect of FHD against adriamycin-induced nephropathy using rat model. And we proposed a integrative pharmacology-based method, which combined chemical ingredients database building, target identification and network analysis. These were aimed to decipher the mechanisms of action for the FHD in NS treatment. Multivariate analysis revealed that 13 of 16 perturbed metabolites could be reversed by FHD, and the MetaboAnalyst analysis revealed that the anti-nephrotic syndrome effect of FHD was probably related with regulation of alanine, aspartate and glutamate metabolism, citrate cycle, pyruvate metabolism, cysteine and methionine metabolism and glyoxylate and dicarboxylate metabolism. The integrative pharmacology analysis revealed 93 potential targets for FHD, and suggested that the protective effect of FHD on the nephrotic syndrome was probably related with the regulation of immune, and energy metabolic and fatty acid metabolic. In addition, both the metabolomics and the integrative pharmacology are focus together on the alanine, aspartate and glutamate metabolism pathway. These metabolites changes and the core targets changes, as well as the metabolite-target pathway network provide insights into the mechanisms of FHD treating nephrotic syndrome, and further studies are needed to validate the bioactive compounds responsible for the anti-nephrotic syndrome effect of FHD.

A Short Progress Report on High-Efficiency Perovskite Solar Cells.

Faced with the increasingly serious energy and environmental crisis in the world nowadays, the development of renewable energy has attracted increasingly more attention of all countries. Solar energy as an abundant and cheap energy is one of the most promising renewable energy sources. While high-performance solar cells have been well developed in the last couple of decades, the high module cost largely hinders wide deployment of photovoltaic devices. In the last 10 years, this urgent demand for cost-effective solar cells greatly facilitates the research of solar cells. This paper reviews the recent development of cost-effective and high-efficient solar cell technologies. This report paper covers low-cost and high-efficiency perovskite solar cells. The development and the state-of-the-art results of perovskite solar cell technologies are also introduced.