Chemical constituents of Rubia tibetica Hook. f. from Tibetan medicine and cytotoxic activity evaluation.

Two unprecedented quinone compounds Rubiaxylm A (1) and Rubiaxylm B (2), along with fifteen known anthraquinones (3-17) were isolated and characterized from the roots of Rubia tibetica in Tibetan medicine. Their structures were identified through comprehensive analyses of 1D/2D NMR as well as HR-ESIMS data. Furthermore, all separated compounds were evaluated for their cytotoxic activity on A549, Caco-2, MDA-MB-231 and Skov-3 cell lines. In particular, compound 2 effectively inhibited MDA-MB-231 cells with an IC50 value of 8.15 ± 0.20 µM. Subsequently, the anti-tumor mechanism of 2 was investigated by flow cytometry, JC-1 staining, cell scratching and cell colony. These results indicated that compound 2 could inhibit the proliferation of MDA-MB-231 cells by arresting cells in the G1 phase.

Potential application of Nardostachyos Radix et Rhizoma-Rhubarb for the treatment of diabetic kidney disease based on network pharmacology and cell culture experimental verification.

BACKGROUND: Diabetic kidney disease (DKD) is one of the serious complications of diabetes mellitus, and the existing treatments cannot meet the needs of today's patients. Traditional Chinese medicine has been validated for its efficacy in DKD after many years of clinical application. However, the specific mechanism by which it works is still unclear. Elucidating the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair (NRDP) for the treatment of DKD will provide a new way of thinking for the research and development of new drugs. AIM: To investigate the mechanism of the NRDP in DKD by network pharmacology combined with molecular docking, and then verify the initial findings by in vitro experiments. METHODS: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to screen active ingredient targets of NRDP. Targets for DKD were obtained based on the Genecards, OMIM, and TTD databases. The VENNY 2.1 database was used to obtain DKD and NRDP intersection targets and their Venn diagram, and Cytoscape 3.9.0 was used to build a "drug-component-target-disease" network. The String database was used to construct protein interaction networks. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Gene Ontology analysis were performed based on the DAVID database. After selecting the targets and the active ingredients, Autodock software was used to perform molecular docking. In experimental validation using renal tubular epithelial cells (TCMK-1), we used the Cell Counting Kit-8 assay to detect the effect of NRDP on cell viability, with glucose solution used to mimic a hyperglycemic environment. Flow cytometry was used to detect the cell cycle progression and apoptosis. Western blot was used to detect the protein expression of STAT3, p-STAT3, BAX, BCL-2, Caspase9, and Caspase3. RESULTS: A total of 10 active ingredients and 85 targets with 111 disease-related signaling pathways were obtained for NRDP. Enrichment analysis of KEGG pathways was performed to determine advanced glycation end products (AGEs)-receptor for AGEs (RAGE) signaling as the core pathway. Molecular docking showed good binding between each active ingredient and its core targets. In vitro experiments showed that NRDP inhibited the viability of TCMK-1 cells, blocked cell cycle progression in the G0/G1 phase, and reduced apoptosis in a concentration-dependent manner. Based on the results of Western blot analysis, NRDP differentially downregulated p-STAT3, BAX, Caspase3, and Caspase9 protein levels (P < 0.01 or P < 0.05). In addition, BAX/BCL-2 and p-STAT3/STAT3 ratios were reduced, while BCL-2 and STAT3 protein expression was upregulated (P < 0.01). CONCLUSION: NRDP may upregulate BCL-2 and STAT3 protein expression, and downregulate BAX, Caspase3, and Caspase9 protein expression, thus activating the AGE-RAGE signaling pathway, inhibiting the vitality of TCMK-1 cells, reducing their apoptosis. and arresting them in the G0/G1 phase to protect them from damage by high glucose.

The Role and Mechanism of Paeoniae Radix Alba in Tumor Therapy.

Tumors have a huge impact on human life and are now the main cause of disease-related deaths. The main means of treatment are surgery and radiotherapy, but they are more damaging to the organism and have a poor postoperative prognosis. Therefore, we urgently need safe and effective drugs to treat tumors. In recent years, Chinese herbal medicines have been widely used in tumor therapy as complementary and alternative therapies. Medicinal and edible herbs are popular and have become a hot topic of research, which not only have excellent pharmacological effects and activities, but also have almost no side effects. Therefore, as a typical medicine and food homology, some components of Paeoniae Radix Alba (PRA, called Baishao in China) have been shown to have good efficacy and safety against cancer. Numerous studies have also shown that Paeoniae Radix Alba and its active ingredients treat cancer through various pathways and are also one of the important components of many antitumor herbal compound formulas. In this paper, we reviewed the literature on the intervention of Paeoniae Radix Alba in tumors and its mechanism of action in recent years and found that there is a large amount of literature on its effect on total glucosides of paeony (TGP) and paeoniflorin (PF), as well as an in-depth discussion of the mechanism of action of Paeoniae Radix Alba and its main constituents, with a view to promote the clinical development and application of Paeoniae Radix Alba in the field of antitumor management.

A Cotyledon-based Virus-Induced Gene Silencing (Cotyledon-VIGS) approach to study specialized metabolism in medicinal plants.

BACKGROUND: Virus-induced gene silencing (VIGS) is widely used in plant functional genomics. However, the efficiency of VIGS in young plantlets varies across plant species. Additionally, VIGS is not optimized for many plant species, especially medicinal plants that produce valuable specialized metabolites. RESULTS: We evaluated the efficacy of five-day-old, etiolated seedlings of Catharanthus roseus (periwinkle) for VIGS. The seedlings were vacuum-infiltrated with Agrobacterium tumefaciens GV3101 cells carrying the tobacco rattle virus (TRV) vectors. The protoporphyrin IX magnesium chelatase subunit H (ChlH) gene, a key gene in chlorophyll biosynthesis, was used as the target for VIGS, and we observed yellow cotyledons 6 days after infiltration. As expected, the expression of CrChlH and the chlorophyll contents of the cotyledons were significantly decreased after VIGS. To validate the cotyledon based-VIGS method, we silenced the genes encoding several transcriptional regulators of the terpenoid indole alkaloid (TIA) biosynthesis in C. roseus, including two activators (CrGATA1 and CrMYC2) and two repressors (CrGBF1 and CrGBF2). Silencing CrGATA1 led to downregulation of the vindoline pathway genes (T3O, T3R, and DAT) and decreased vindoline contents in cotyledons. Silencing CrMYC2, followed by elicitation with methyl jasmonate (MeJA), resulted in the downregulation of ORCA2 and ORCA3. We also co-infiltrated C. roseus seedlings with TRV vectors that silence both CrGBF1 and CrGBF2 and overexpress CrMYC2, aiming to simultaneous silencing two repressors while overexpressing an activator. The simultaneous manipulation of repressors and activator resulted in significant upregulation of the TIA pathway genes. To demonstrate the broad application of the cotyledon-based VIGS method, we optimized the method for two other valuable medicinal plants, Glycyrrhiza inflata (licorice) and Artemisia annua (sweet wormwood). When TRV vectors carrying the fragments of the ChlH genes were infiltrated into the seedlings of these plants, we observed yellow cotyledons with decreased chlorophyll contents. CONCLUSIONS: The widely applicable cotyledon-based VIGS method is faster, more efficient, and easily accessible to additional treatments than the traditional VIGS method. It can be combined with transient gene overexpression to achieve simultaneous up- and down-regulation of desired genes in non-model plants. This method provides a powerful tool for functional genomics of medicinal plants, facilitating the discovery and production of valuable therapeutic compounds.

Molecular mechanism of Gan-song Yin inhibiting the proliferation of renal tubular epithelial cells by regulating miR-21-5p in adipocyte exosomes.

ETHNOPHARMACOLOGICAL RELEVANCE: Gan-song Yin is derived from the classic ancient prescription " Gan-song pill " for the treatment of wasting-thirst in Ningxia combined with the characteristic "fragrant medicine". It is clinically used for the treatment of early renal fibrosis caused by diabetic nephropathy. Previous studies have shown that it has a good effect and great potential in the prevention and treatment of diabetic nephropathy, but its mechanism research is still limited. AIM OF THE STUDY: To investigate the mechanism of GSY to improve DN by interfering with miR-21-5p and glycolipid metabolism in adipocyte exosomes using 3T3-L1 and TCMK-1 co-culture system. MATERIALS AND METHODS: The co-culture system of 3T3-L3 and TCMK-1 was established, the IR model was established, and the stability, lipid drop change, glucose consumption, triglyceride content, cell viability, cell cycle and apoptosis level, protein content and mRNA expression of the IR model were detected. RESULTS: GSY inhibited 3T3-L1 activity, increased glucose consumption and decreased TG content. Decreased TCMK-1 cell viability, inhibited apoptosis, cell cycle arrest occurred in G0/G1 phase and S phase. Adipocyte IR model and co-culture system were stable within 48 h. After GSY intervention, lipid droplet decomposition and glucose consumption increased. The TG content of adipocytes increased, while the TG content of co-culture system decreased. GSY can regulate the expression of TGF-ß1/SMAD signaling pathway protein in IR state. After GSY intervention, the expression of miR-21-5p was increased in 3T3-L1 and Exo cells, and decreased in TCMK-1 cells. CONCLUSIONS: GSY can regulate TGF-ß1/SMAD signaling pathway through the secretion of miR-21-5p from adipocytes, protect IR TCMK-1, regulate the protein and mRNA expression levels of PPARγ, GLUT4, FABP4, and improve glucose and lipid metabolism.

The Potential of Glycyrrhiza from "Medicine Food Homology" in the Fight against Digestive System Tumors.

Glycyrrhiza has a long history of applications and a wide range of pharmacological effects. It is known as the "king of all herbs". Glycyrrhiza is effective in clearing heat, detoxifying, relieving cough, and tonifying qi and has good bioactivity in multiple inflammatory, immune, and tumor diseases. This review aims to summarize the origin, distribution, and anti-digestive system tumor mechanism of glycyrrhiza and its homologous applications in medicine and food. The active compounds include triterpenoids, flavonoids, and coumarins, which are widely used in clinical treatments, disease prevention, and daily foods because of their "enhancement of efficacy" and "reduction of toxicity" against digestive system tumors. This paper reviews the use of glycyrrhiza in digestive system tumors and provides an outlook on future research and clinical applications.

Research progress of ginger in the treatment of gastrointestinal tumors.

Cancer seriously endangers human health. Gastrointestinal cancer is the most common and major malignant tumor, and its morbidity and mortality are gradually increasing. Although there are effective treatments such as radiotherapy and chemotherapy for gastrointestinal tumors, they are often accompanied by serious side effects. According to the traditional Chinese medicine and food homology theory, many materials are both food and medicine. Moreover, food is just as capable of preventing and treating diseases as medicine. Medicine and food homologous herbs not only have excellent pharmacological effects and activities but also have few side effects. As a typical medicinal herb with both medicinal and edible uses, some components of ginger have been shown to have good efficacy and safety against cancer. A mass of evidence has also shown that ginger has anti-tumor effects on digestive tract cancers (such as gastric cancer, colorectal cancer, liver cancer, laryngeal cancer, and pancreatic cancer) through a variety of pathways. The aim of this study is to investigate the mechanisms of action of the main components of ginger and their potential clinical applications in treating gastrointestinal tumors.

Exploring the mechanism of Dahuang-Tusizi drug pair in the treatment of diabetes nephropathy based on network pharmacology and immune infiltration analysis.

The study aimed to explore the key targets and molecular mechanisms of Dahuang-Tusizi drug pair (DTDP) in the treatment of diabetes nephropathy (DN) based on the GEO database by using network pharmacology combined with molecular docking and immune infiltration. The active components of the DTDP were screened using the Traditional Chinese Medicine Systems Pharmacology database and the Swiss Target Prediction database. The differential genes of DN were retrieved from GEO databases. Next, the intersecting targets of drug and disease were imported into the String database for protein-protein interactions network analysis, and the core targets were identified through topological analysis. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed with the help of the Metascape database and gene set enrichment analysis database. Subsequently, molecular docking was performed to verify the binding activity of the key component and the key target. The Nephroseq V5 database was used to verify the clinical relevance of DN and core genes. Finally, the Using CIBERSORT Algorithm to analyze the immune Infiltration of DN Gene Chip. The network analysis showed that 25 active ingredients of DTDP were associated with 22 targets in DN. The key active ingredients (Sesamin, quercetin, EUPATIN, matrine, beta-sitosterol, isorhamnetin, etc.) and the core targets (JUN, EGF, CD44, FOS, KDR, CCL2, PTGS2, and MMP2) were further identified. Enrichment analysis revealed signaling pathways including TNF, MAPK, and IL-17 signaling pathway. Molecular docking results showed that there was a strong affinity between the key components and core targets. The results of immune infiltration found that the proportion of macrophages in DN tissues was significantly increased. Our findings demonstrated that the characteristics of DTDP in treating DN are "multiple components, multiple targets and multiple pathways." We predicted that DTDP may inhibit inflammation related pathways by regulating key genes, reducing macrophage infiltration. Thus, inhibiting inflammatory response to reduce glomerular damage and delay the development of DN.

Pharmacological Mechanisms and Adjuvant Properties of Licorice Glycyrrhiza in Treating Gastric Cancer.

Licorice is a remarkable traditional Chinese medicine obtained from the dried root and rhizomes of the Glycyrrhiza genus, and t has been utilized in China for many centuries. It consists of more than 300 compounds that are mainly divided into triterpene saponins, flavonoids, polysaccharides, and phenolic components. The active compounds of licorice have been found to possess multiple biological activities, including antitumor, anti-inflammatory, antiviral, antimicrobial, immunoregulatory, cardioprotective, and neuroprotective functions. In addition to providing a brief overview of licorice's adjuvant properties, this review describes and analyzes the pharmacological mechanisms by which licorice components function to treat gastric cancer. Furthermore, licorice compounds are also found to be potent adjuvant chemotherapy agents, as they can improve the quality of life of cancer patients and alleviate chemotherapy-induced adverse effects.

Vascular wall microenvironment: exosomes secreted by adventitial fibroblasts induced vascular calcification.

Vascular calcification often occurs in patients with chronic renal failure (CRF), which significantly increases the incidence of cardiovascular events in CRF patients. Our previous studies identified the crosstalk between the endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), and the paracrine effect of VSMCs, which regulate the calcification of VSMCs. Herein, we aim to investigate the effects of exosomes secreted by high phosphorus (HPi) -induced adventitial fibroblasts (AFs) on the calcification of VSMCs and the underlying mechanism, which will further elucidate the important role of AFs in high phosphorus vascular wall microenvironment. The conditioned medium of HPi-induced AFs promotes the calcification of VSMCs, which is partially abrogated by GW4869, a blocker of exosomes biogenesis or release. Exosomes secreted by high phosphorus-induced AFs (AFsHPi-Exos) show similar effects on VSMCs. miR-21-5p is enriched in AFsHPi-Exos, and miR-21-5p enhances osteoblast-like differentiation of VSMCs by downregulating cysteine-rich motor neuron 1 (Crim1) expression. AFsHPi-Exos and exosomes secreted by AFs with overexpression of miR-21-5p (AFsmiR21M-Exos) significantly accelerate vascular calcification in CRF mice. In general, AFsHPi-Exos promote the calcification of VSMCs and vascular calcification by delivering miR-21-5p to VSMCs and subsequently inhibiting the expression of Crim1. Combined with our previous studies, the present experiment supports the theory of vascular wall microenvironment.

The Role and Mechanism of Perilla frutescens in Cancer Treatment.

Perilla frutescens is an annual herb of the Labiatae family and is widely grown in several countries in Asia. Perilla frutescens is a plant that is used medicinally in its entirety, as seen in its subdivision into perilla seeds, perilla stalks, and perilla leaves, which vary more markedly in their chemical composition. Several studies have shown that Perilla frutescens has a variety of pharmacological effects, including anti-inflammatory, antibacterial, detoxifying, antioxidant, and hepatoprotective. In the absence of a review of Perilla frutescens for the treatment of cancer. This review provides an overview of the chemical composition and molecular mechanisms of Perilla frutescens for cancer treatment. It was found that the main active components of Perilla frutescens producing cancer therapeutic effects were perilla aldehyde (PAH), rosmarinic acid (Ros A), lignan, and isoestrogen (IK). In addition to these, extracts of the leaves and fruits of Perilla frutescens are also included. Among these, perilla seed oil (PSO) has a preventive effect against colorectal cancer due to the presence of omega-3 polyunsaturated fatty acids. This review also provides new ideas and thoughts for scientific innovation and clinical applications related to Perilla frutescens.

Enzymatic activity of 38 CYP2C9 genotypes on ibuprofen.

BACKGROUND AND OBJECTIVE: Ibuprofen, a common non-steroidal anti-inflammatory drug, is used clinically for pain relief and antipyretic treatment worldwide. However, regular or long-term use of ibuprofen may lead to a series of adverse reactions, including gastrointestinal bleeding, hypertension and kidney injury. Previous studies have shown that CYP2C9 gene polymorphism plays an important role in the elimination of various drugs, which leads to the variation in drug efficacy. This study aimed to evaluate the effect of 38 CYP2C9 genotypes on ibuprofen metabolism. METHODS: Thirty-eight recombinant human CYP2C9 microsomal enzymes were obtained using a frugiperda 21 insect expression system according to a previously described method. Assessment of the catalytic function of these variants was completed via a mature incubation system: 5 pmol CYP2C9*1 and 38 CYP2C9 variants recombinant human microsomes, 5 µL cytochrome B5, ibuprofen (5-1000 µM), and Tris-HCl buffer (pH 7.4). The ibuprofen metabolite contents were determined using HPLC analysis. HPLC analysis included a UV detector, Plus-C18 column, and mobile phase [50% acetonitrile and 50% water (containing 0.05% trifluoroacetic acid)]. The kinetic parameters of the CYP2C9 genotypes were obtained by Michaelis-Menten curve fitting. RESULTS: The intrinsic clearance (CLint) of eight variants was not significantly different from CYP2C9*1; four CYP2C9 variants (CYP2C9*38, *44, *53 and *59) showed significantly higher CLint (increase by 35%-230%) than that of the wild-type; the remaining twenty-six variants exhibited significantly reduced CLint (reduced by 30%-99%) compared to that of the wild-type. CONCLUSION: This is the first systematic evaluation of the catalytic characteristics of 38 CYP2C9 genotypes involved ibuprofen metabolism. Our results provide a corresponding supplement to studies on CYP2C9 gene polymorphisms and kinetic characteristics of different variants. We need to focus on poor metabolizers (PMs) with severely abnormal metabolic functions, because they are more susceptible to drug exposure.

Transcription factor bZIP52 modulates Arabidopsis seed oil biosynthesis through interaction with WRINKLED1.

Transcriptional regulation mediated by combinatorial interaction of transcription factors (TFs) is a key molecular mechanism modulating plant development and metabolism. Basic leucine zipper (bZIP) TFs play important roles in various plant developmental and physiological processes. However, their involvement in fatty acid biosynthesis is largely unknown. Arabidopsis (Arabidopsis thaliana) WRINKLED1 (WRI1) is a pivotal TF in regulation of plant oil biosynthesis and interacts with other positive and negative regulators. In this study, we identified two bZIP TFs, bZIP21 and bZIP52, as interacting partners of AtWRI1 by yeast-two-hybrid (Y2H)-based screening of an Arabidopsis TF library. We found that coexpression of bZIP52, but not bZIP21, with AtWRI1 reduced AtWRI1-mediated oil biosynthesis in Nicotiana benthamiana leaves. The AtWRI1-bZIP52 interaction was further verified by Y2H, in vitro pull-down, and bimolecular fluorescence complementation assays. Transgenic Arabidopsis plants overexpressing bZIP52 showed reduced seed oil accumulation, while the CRISPR/Cas9-edited bzip52 knockout mutant exhibited increased seed oil accumulation. Further analysis revealed that bZIP52 represses the transcriptional activity of AtWRI1 on the fatty acid biosynthetic gene promoters. Together, our findings suggest that bZIP52 represses fatty acid biosynthesis genes through interaction with AtWRI1, resulting in a reduction of oil production. Our work reports a previously uncharacterized regulatory mechanism that enables fine-tuning of seed oil biosynthesis.

Integrated metabolic and transcriptional analysis reveals the role of carotenoid cleavage dioxygenase 4 (IbCCD4) in carotenoid accumulation in sweetpotato tuberous roots.

BACKGROUND: Plant carotenoids are essential for human health, having wide uses in dietary supplements, food colorants, animal feed additives, and cosmetics. With the increasing demand for natural carotenoids, plant carotenoids have gained great interest in both academic and industry research worldwide. Orange-fleshed sweetpotato (Ipomoea batatas) enriched with carotenoids is an ideal feedstock for producing natural carotenoids. However, limited information is available regarding the molecular mechanism responsible for carotenoid metabolism in sweetpotato tuberous roots. RESULTS: In this study, metabolic profiling of carotenoids and gene expression analysis were conducted at six tuberous root developmental stages of three sweetpotato varieties with different flesh colors. The correlations between the expression of carotenoid metabolic genes and carotenoid levels suggested that the carotenoid cleavage dioxygenase 4 (IbCCD4) and 9-cis-epoxycarotenoid cleavage dioxygenases 3 (IbNCED3) play important roles in the regulation of carotenoid contents in sweetpotato. Transgenic experiments confirmed that the total carotenoid content decreased in the tuberous roots of IbCCD4-overexpressing sweetpotato. In addition, IbCCD4 may be regulated by two stress-related transcription factors, IbWRKY20 and IbCBF2, implying that the carotenoid accumulation in sweeetpotato is possibly fine-tuned in responses to stress signals. CONCLUSIONS: A set of key genes were revealed to be responsible for carotenoid accumulation in sweetpotato, with IbCCD4 acts as a crucial player. Our findings provided new insights into carotenoid metabolism in sweetpotato tuberous roots and insinuated IbCCD4 to be a target gene in the development of new sweetpotato varieties with high carotenoid production.

Rheum officinale and Salvia miltiorrhiza inhibit renal fibrosis via miR-21/PTEN/Akt signaling pathway in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: As one of the main components of many famous Chinese herbal formulas, Rheum palmatum L. and Salvia miltiorhiza Bunge (RS) are extensively used to treat chronic kidney disease (CKD). RS has been proved to improve renal function and relieve renal fibrosis (RF), but the potential mechanism remains a mystery. AIM OF THE STUDY: The purpose of this study is to determine whether microRNA-21 (miR-21) is associated with RF progression, as well as whether RS protects against RF through miR-21/PTEN/AKT signaling. MATERIALS AND METHODS: (1) The rat model of RF was established using unilateral ureteral obstruction (UUO). After UUO surgery, miR-21 levels in plasma were detected by RT-PCR and RF scores were assessed by Masson's trichrome stain at days 3, 7, 14 and 21. The correlation analysis of the above two indexes was carried out by Spearman correlation analysis. (2) Human proximal tubular epithelial cells (HK-2) was transfected with miR-21 mimic and inhibitor, and then the levels of phosphatase and tensin homolog (PTEN) protein and mRNA were measured with Western blotting and RT-PCR, respectively. (3) TGF-ß (10 ng/mL) was added into HK-2 cells to induce fibrosis, followed by the intervention of RS-containing rat serum. PTEN and protein kinase-B (Akt) phosphorylation, as well as the expression of PTEN protein in HK-2 cells, were assessed by RT-PCR, Western blotting and immunofluorescence. (4) The rat models of RF were prepared by UUO and treated with RS. Serum creatinine and urea nitrogen levels were measured. RF score was determined by Masson's trichrome stain. RT-PCR was used to determine the expression of miR-21, PTEN, and Akt mRNA. Western blotting was used to determine the expression of PTEN and Akt proteins. RESULTS: A positive correlation was found between plasma miR-21 levels and RF scores of rats after UUO surgery at Days 3, 7, 14 and 21. It was confirmed that miR-21 targeted PTEN. RS drug-containing serum could rise the expression of PTEN and reduce Akt phosphorylation of HK-2 cells induced by TGF-ß. Moreover, RS drug-containing serum could increase PTEN expression and reduce Akt phosphorylation induced by miR-21 mimic in HK-2 cells. The rats treated with RS had significantly decreased serum creatinine and urea nitrogen levels and a lower RF score. RS also decreased miR-21 and Akt expressions, increased PTEN expression of UUO rats. CONCLUSION: There was a positive correlation between plasma miR-21 levels and RF scores. The inhibitory effect of RS on RF might be mediated by miR-21/PTEN/AKT signaling.

Injectable methacrylated gelatin/thiolated pectin hydrogels carrying melatonin/tideglusib-loaded core/shell PMMA/silk fibroin electrospun fibers for vital pulp regeneration.

Use of injectable hydrogels attract attention in the regeneration of dental pulp due to their ability to fill non-uniform voids such as pulp cavities. Here, gelatin methacrylate/thiolated pectin hydrogels (GelMA/PecTH) carrying electrospun core/shell fibers of melatonin (Mel)-polymethylmethacrylate (PMMA)/Tideglusib (Td)-silk fibroin (SF) were designed as an injectable hydrogel for vital pulp regeneration, through prolonged release of Td and Mel to induce proliferation and odontoblastic differentiation of dental pulp stem cells (DPSC). H NMR and FTIR confirmed methacrylation of Gel and thiolation of Pec. Addition of PMMA/SF increased degradation and water retention capacities of GelMA/PecTH. Rheological analyses and syringe tests proved the injectability of the hydrogel systems. Release studies indicated that Td and Mel were released from the fibers inside the hydrogels sequentially due to their specific locations. This release pattern from the hydrogels resulted in DPSC proliferation and odontogenic differentiation in vitro. Gene expression studies showed that the upregulation of DMP1, DSPP, and Axin-2 genes was promoted by GelMA/PecTH carrying PMMA/SF loaded with Mel (50 µg/mL) and Td (200 nM), respectively. Our results suggest that this hydrogel system holds promise for use in the regeneration of pulp tissue.

Exploring the Role of Lycium barbarum Polysaccharide in Corneal Injury Repair and Investigating the Relevant Mechanisms through In Vivo and In Vitro Experiments.

Lycium barbarum polysaccharide (LBP) is the main active component of Fructus Lycii, exhibiting various biological activities. This study aims to explore the protective effects of LBP on human corneal epithelial cells (HCEC) and a rat corneal injury model. Potential target points for LBP improving corneal injury repair were screened from public databases, and functional and pathway enrichment analyses of core targets were conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Rat corneal alkali burns and HCEC oxidative stress injury models were established, and the results were validated through slit lamp examination, HE staining, TUNEL assay, immunofluorescence, CCK-8 assay, flow cytometry, scratch assay, and qRT-PCR methods. In the context of database retrieval, identification of 10 LBP monosaccharide components and 50 corneal injury repair-related targets was achieved. KEGG pathway analysis suggested that LBP might regulate the IL-17 and TNF signaling pathways through targets such as JUN, CASP3, and MMP9, thereby improving corneal damage. In vivo and in vitro experimental results indicated that LBP could reduce the increase of inflammation index scores (p < 0.05), inflammatory cell density (p < 0.01), TUNEL-positive cells (p < 0.01), corneal opacity scores (p < 0.01), and expression of corneal stromal fibrosis-related proteins α-SMA, FN, and COL (p < 0.01) caused by chemical damage to rat corneas. LBP inhibited oxidative stress-induced decreases in cell viability (p < 0.001) and migration healing ability (p < 0.01) in HCECs, reducing apoptosis rates (p < 0.001), ROS levels (p < 0.001), and the expression of inflammatory factors TNF-α and IL-6 (p < 0.01). qRT-PCR results demonstrated that LBP intervention decreased the mRNA levels of JUN, CASP3, and MMP9 in H2O2-induced alkaline-burned corneas and HCECs (p < 0.01).The integrated results from network pharmacology and validation experiments suggest that the inhibitory effects of LBP on apoptosis, inflammation, and fibrosis after corneal injury may be achieved through the suppression of the TNF and IL-17 signaling pathways mediated by JUN, CASP3, and MMP9.

Anti-tumor effect of coix seed based on the theory of medicinal and food homology.

Coix seed is a dry and mature seed of Coix lacryma-jobi L.var.ma-yuen (Roman.) Stapf in the Gramineae family. Coix seed has a sweet, light taste, and a cool nature. Coix seed enters the spleen, stomach, and lung meridians. It has the effects of promoting diuresis and dampness, strengthening the spleen to prevent diarrhea, removing arthralgia, expelling pus, and detoxifying and dispersing nodules. It is used for the treatment of edema, athlete's foot, poor urination, spleen deficiency and diarrhea, dampness and obstruction, lung carbuncle, intestinal carbuncle, verruca, and cancer. The medicinal and health value is high, and it has been included in the list of medicinal and food sources in China, which has a large development and application space. This article reviews the current research achievements in the processing methods and anti-tumor activities of Coix seed and provides examples of its clinical application in ancient and modern times, aiming to provide reference for further research on Coix seed and contribute to its clinical application and development. Through the analysis of the traditional Chinese patent medicines, and simple preparations and related health food of Coix seed queried by Yaozhi.com, the source, function, and dosage form of Coix seed were comprehensively analyzed, with a view of providing a reference for the development of Coix seed medicine and food.

The clinical diagnostic value of plasma miR-592 and miR-217-3p levels in retinoblastoma.

Background: This study was designed to investigate the abnormal expression of plasma miR-592 and miR-217-3p in retinoblastoma (Rb) and explore the clinical diagnostic value of their expression levels for Rb. Methods: The 100 Rb patients who came to Nanchang Hongdu Hospital of Traditional Chinese Medicine from January 2018 to January 2019 were selected as the Rb group, and 100 healthy patients who came to the physical examination centre during the same period were selected as the control group. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the expression levels of plasma miR-592 and miR-217-3p in all subjects; analyse the relationship between plasma miR-592 and miR-217-3p levels and the clinicopathological characteristics of Rb. Pearson correlation analysis evaluated the relationship between plasma miR-592 and miR-217-3p levels and overall survival. Results: Plasma levels of miR-592 and miR-217-3p in the Rb group were significantly higher than those in the control group (p<0.0001), and the expression of miR-592 was significantly correlated with family genetic history (p 0.0001), tumour bias (p=0.0081), lymph node metastasis (p=0.0048) and pathological grade (p=0.0025), and the expression of miR-217-3p was significantly related to family genetic history (p 0.0001), optic nerve infiltration (p 0.0001), lymph node metastasis (p=0.0090), and pathological grade (p 0.0001). The high expression of miR-592 and miR-217-3p presents a more serious pathological manifestation of Rb, and the overall survival of patients is significantly shortened with the increase of miR-592 (r=-0.2276, p=0.0052) and miR-217-3p levels (r=-0.6461, p 0.0001). Conclusions: and miR-217-3p are highly expressed in the plasma of Rb patients, and their elevated levels present severe pathological manifestations of Rb and shortened overall survival, which is expected to become biomarkers for clinical diagnosis of Rb.