Anti-cancer activity and mechanism of flurbiprofen organoselenium compound RY-1-92 in non-small cell lung cancer.

Lung cancer is one of the malignancies with the highest incidence and mortality rates worldwide, and non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer types. In this study, the anti-cancer activities of a novel flurbiprofen organic selenium compound, RY-1-92, on NSCLC cells and a mouse model and the underlying molecular mechanisms were explored. We found that compound RY-1-92 can significantly inhibit the viability, colony formation and migration of A549, NCI-H460 lung cancer cells. Flow cytometry analysis showed that RY-1-92 also can lead to G2/M cell cycle arrest and apoptosis induced in lung cancer cells. Further, RY-1-92 can decrease the tumor size in the Lewis lung cancer tumor-bearing mouse model. The protein levels of cell cycle-related proteins CDK1/cyclinB1 were decreased, while the apoptosis-related protein BAX was increased dramatically after RY-1-92 treatment in vitro and in vivo. Impressively, it was found that TRPV1 might act as a potential molecular target of RY-1-92 using the SEA search server. Furthermore, down-regulation on TRPV1 and its downstream associated factors including p-AKT protein and MAPK signaling pathway-related proteins after RY-1-92 treatment was observed in A549, NCI-H460 lung cancer cells. Taken together, our findings shed light on the potential of RY-1-92 as a novel small molecular drug for NSCLC, and it is of great significance for its further in-depth research and development.

CTNet: Contrastive Transformer Network for Polyp Segmentation.

Segmenting polyps from colonoscopy images is very important in clinical practice since it provides valuable information for colorectal cancer. However, polyp segmentation remains a challenging task as polyps have camouflage properties and vary greatly in size. Although many polyp segmentation methods have been recently proposed and produced remarkable results, most of them cannot yield stable results due to the lack of features with distinguishing properties and those with high-level semantic details. Therefore, we proposed a novel polyp segmentation framework called contrastive Transformer network (CTNet), with three key components of contrastive Transformer backbone, self-multiscale interaction module (SMIM), and collection information module (CIM), which has excellent learning and generalization abilities. The long-range dependence and highly structured feature map space obtained by CTNet through contrastive Transformer can effectively localize polyps with camouflage properties. CTNet benefits from the multiscale information and high-resolution feature maps with high-level semantic obtained by SMIM and CIM, respectively, and thus can obtain accurate segmentation results for polyps of different sizes. Without bells and whistles, CTNet yields significant gains of 2.3%, 3.7%, 3.7%, 18.2%, and 10.1% over classical method PraNet on Kvasir-SEG, CVC-ClinicDB, Endoscene, ETIS-LaribPolypDB, and CVC-ColonDB respectively. In addition, CTNet has advantages in camouflaged object detection and defect detection. The code is available at https://github.com/Fhujinwu/CTNet.

Inhibition of Gpx4-mediated ferroptosis alleviates cisplatin-induced hearing loss in C57BL/6 mice.

Cisplatin-induced hearing loss is a common side effect of cancer chemotherapy in clinics; however, the mechanism of cisplatin-induced ototoxicity is still not completely clarified. Cisplatin-induced ototoxicity is mainly associated with the production of reactive oxygen species, activation of apoptosis, and accumulation of intracellular lipid peroxidation, which also is involved in ferroptosis induction. In this study, the expression of TfR1, a ferroptosis biomarker, was upregulated in the outer hair cells of cisplatin-treated mice. Moreover, several key ferroptosis regulator genes were altered in cisplatin-damaged cochlear explants based on RNA sequencing, implying the induction of ferroptosis. Ferroptosis-related Gpx4 and Fsp1 knockout mice were established to investigate the specific mechanisms associated with ferroptosis in cochleae. Severe outer hair cell loss and progressive damage of synapses in inner hair cells were observed in Atoh1-Gpx4-/- mice. However, Fsp1-/- mice showed no significant hearing phenotype, demonstrating that Gpx4, but not Fsp1, may play an important role in the functional maintenance of HCs. Moreover, findings showed that FDA-approved luteolin could specifically inhibit ferroptosis and alleviate cisplatin-induced ototoxicity through decreased expression of transferrin and intracellular concentration of ferrous ions. This study indicated that ferroptosis inhibition through the reduction of intracellular ferrous ions might be a potential strategy to prevent cisplatin-induced hearing loss.

Research Progress on the Synergistic Anti-Tumor Effect of Natural Anti-Tumor Components of Chinese Herbal Medicine Combined with Chemotherapy Drugs.

The application of chemotherapy drugs in tumor treatment has a long history, but the lack of selectivity of drugs often leads to serious side effects during chemotherapy. The natural anti-tumor ingredients derived from Chinese herbal medicine are attracting increased attention due to their diverse anti-tumor effects, abundant resources, and minimal side effects. An effective anti-tumor strategy may lie in the combination of these naturally derived anti-tumor ingredients with conventional chemotherapy drugs. This approach could potentially inhibit tumor growth and the development of drug resistance in tumor cells while reducing the adverse effects of chemotherapy drugs. This review provides a comprehensive overview of the combined therapy strategies integrating natural anti-tumor components from Chinese herbal medicine with chemotherapy drugs in current research. We primarily summarize various compounds in Chinese herbal medicine exhibiting natural anti-tumor activities and the relevant mechanisms in synergistic anti-tumor combination therapy. The focus of this paper is on underlining that this integrative approach, combining natural anti-tumor components of Chinese herbal medicine with chemotherapy drugs, presents a novel cancer treatment methodology, thereby providing new insights for future oncological research.

The plant nuclear lamina disassembles to regulate genome folding in stress conditions.

The nuclear lamina is a complex network of nuclear lamins and lamin-associated nuclear membrane proteins, which scaffold the nucleus to maintain structural integrity. In Arabidopsis thaliana, nuclear matrix constituent proteins (NMCPs) are essential components of the nuclear lamina and are required to maintain the structural integrity of the nucleus and specific perinuclear chromatin anchoring. At the nuclear periphery, suppressed chromatin overlapping with repetitive sequences and inactive protein-coding genes are enriched. At a chromosomal level, plant chromatin organization in interphase nuclei is flexible and responds to various developmental cues and environmental stimuli. On the basis of these observations in Arabidopsis, and given the role of NMCP genes (CRWN1 and CRWN4) in organizing chromatin positioning at the nuclear periphery, one can expect considerable changes in chromatin-nuclear lamina interactions when the global chromatin organization patterns are being altered in plants. Here we report the highly flexible nature of the plant nuclear lamina, which disassembles substantially under various stress conditions. Focusing on heat stress, we reveal that chromatin domains, initially tethered to the nuclear envelope, remain largely associated with CRWN1 and become scattered in the inner nuclear space. By investigating the three-dimensional chromatin contact network, we further reveal that CRWN1 proteins play a structural role in shaping the changes in genome folding under heat stress. Also, CRWN1 acts as a negative transcriptional coregulator to modulate the shift of the plant transcriptome profile in response to heat stress.

Gender-Specific Association Between Perceived Stigma Toward Tuberculosis and Acceptance of Preventive Treatment Among College Students With Latent Tuberculosis Infection: Cross-Sectional Analysis.

BACKGROUND: With the increasing enrollment scale of colleges, the number of students on campus has risen sharply in China. The number of students with tuberculosis (TB) and rifampicin-resistant TB in colleges has increased significantly. Preventive treatment of latent tuberculosis infection (LTBI) is an important means for TB prevention and control in colleges. At present, the acceptance of LTBI treatment among college students remains unclear. In addition, evidence shows stigma may be one of the key factors affecting acceptance of LTBI treatment. To date, there is little direct evidence on the gender-specific association between perceived stigma toward TB and acceptance of LTBI treatment among college students. OBJECTIVE: This study aimed to describe the acceptance of LTBI treatment among college students in an eastern province of China to explore the association between perceived stigma toward TB and acceptance of LTBI treatment and to examine the moderating effect of gender on the association. METHODS: Data were derived from the project on the evaluation of LTBI treatment and its effectiveness among college students in Shandong, China. In total, 1547 college students were included in the analysis. We considered covariates at the individual and family levels. Multilevel mixed-effects logistic regression was used to examine the moderating role of gender and also explore the association between perceived stigma toward TB and acceptance of LTBI treatment. RESULTS: The acceptance rate of LTBI treatment among the diagnosed college students was 46.7% (n=723). The proportion of female students (n=361, 51.5%) accepting LTBI treatment was higher than that of male students (n=362, 42.8%; P=.001). There was an interaction between perceived stigma toward TB and gender (OR 0.93, 95% CI 0.87-1.00; P=.06). Among college students with LTBI, perceived stigma toward TB was positively associated with acceptance of preventive treatment (OR 1.03, 95% CI 1.00-1.08, P=.05). Perceived stigma toward TB was positively associated with accepting LTBI treatment only among male students (OR 1.07, 95% CI 1.02-1.12; P=.005). CONCLUSIONS: The acceptance rate of preventive treatment among college students with LTBI was low. Contrary to our expectations, perceived stigma toward TB was positively associated with acceptance of preventive treatment. Gender moderated this association; high perceived stigma toward TB was associated with acceptance of preventive treatment only in male gender. Gender-specific strategies are effective in improving the acceptability of LTBI treatment in colleges.

Peroxisome Deficiency in Cochlear Hair Cells Causes Hearing Loss by Deregulating BK Channels.

The peroxisome is a ubiquitous organelle in rodent cells and plays important roles in a variety of cell types and tissues. It is previously indicated that peroxisomes are associated with auditory function, and patients with peroxisome biogenesis disorders (PBDs) are found to have hearing dysfunction, but the specific role of peroxisomes in hearing remains unclear. In this study, two peroxisome-deficient mouse models (Atoh1-Pex5-/- and Pax2-Pex5-/- ) are established and it is found that peroxisomes mainly function in the hair cells of cochleae. Furthermore, peroxisome deficiency-mediated negative effects on hearing do not involve mitochondrial dysfunction and oxidative damage. Although the mammalian target of rapamycin complex 1 (mTORC1) signaling is shown to function through peroxisomes, no changes are observed in the mTORC1 signaling in Atoh1-Pex5-/- mice when compared to wild-type (WT) mice. However, the expression of large-conductance, voltage-, and Ca2+ -activated K+ (BK) channels is less in Atoh1-Pex5-/- mice as compared to the WT mice, and the administration of activators of BK channels (NS-1619 and NS-11021) restores the auditory function in knockout mice. These results suggest that peroxisomes play an essential role in cochlear hair cells by regulating BK channels. Hence, BK channels appear as the probable target for treating peroxisome-related hearing diseases such as PBDs.

Dyslexia-Related Hearing Loss Occurs Mainly through the Abnormal Spontaneous Electrical Activity of Spiral Ganglion Neurons.

Dyslexia is a reading and spelling disorder due to neurodevelopmental abnormalities and is occasionally found to be accompanied by hearing loss, but the reason for the associated deafness remains unclear. This study finds that knockout of the dyslexia susceptibility 1 candidate 1 gene (Dyx1c1-/- ) in mice, the best gene for studying dyslexia, causes severe hearing loss, and thus it is a good model for studying the mechanism of dyslexia-related hearing loss (DRHL). This work finds that the Dyx1c1 gene is highly expressed in the mouse cochlea and that the spontaneous electrical activity of inner hair cells and type I spiral ganglion neurons is altered in the cochleae of Dyx1c1-/- mice. In addition, primary ciliary dyskinesia-related phenotypes such as situs inversus and disrupted ciliary structure are seen in Dyx1c1-/- mice. In conclusion, this study gives new insights into the mechanism of DRHL in detail and suggests that Dyx1c1 may serve as a potential target for the clinical diagnosis of DRHL.

Natural Products and Gastric Cancer: Cellular Mechanisms and Effects to Change Cancer Progression.

Gastric cancer is a severe malignant tumor with high morbidity and mortality, which seriously affects people's health. At present, the most common treatment for gastric cancer is chemotherapy. However, chemotherapy is very harmful to the human body, and some of the injuries caused by chemotherapy are irreversible. Natural products have low toxicity and anti-cancer activity, so they are currently widely studied at present. Natural products are a large variety of compounds naturally found in fruits, vegetables, spices, and medicinal plants. It is reported that natural products have different anti-cancer properties. This review has summarized the study of natural products in inducing gastric cancer cell apoptosis, inhibiting gastric cancer cell metastasis, and inhibiting gastric cancer cell proliferation. The relevant references on gastric cancer and natural products were obtained from scientific databases, including Pub- Med, Web of Science, and Science Direct. This paper records dozens of natural products with anti-gastric tumor activity and describes the potential living anti-cancer chemical compounds, their element targets, and their underlying mechanism. This review may lay the foundation for future researchers to treat gastric cancer.

Factors associated with refusal of preventive therapy after initial willingness to accept treatment among college students with latent tuberculosis infection in Shandong, China.

BACKGROUND: Preventive therapy of latent tuberculosis infection (LTBI) is an important component of tuberculosis (TB) control. Research on acceptance of TB preventive therapy (TPT) is an important topic. Current studies focus on acceptability and compliance. However, it is unclear whether LTBI patients will start TPT after accepting treatment. The study assessed the factors associated with TPT refusal after initial willingness to accept treatment. METHODS: Data were derived from a baseline survey of prospective study of LTBI treatment among college students in Shandong Province, China. A total of 723 students initially willing to accept TPT were included in the analysis. Stepwise logistic regression was used to explore the individual- and family-level characteristic variables that factors associated with TPT refusal after initial willingness to accept treatment. RESULTS: Of the 723 LTBI college students who initially had acceptance willingness, 436 (60.3%) finally refused TPT. At the individual level, non-medical students were more likely to refuse TPT [odds ratio (OR) = 4.87, 95% confidence interval (CI): 3.10-7.67)], as were students with moderate physical activity (OR = 1.45, 95% CI: 1.04-2.04). Students with boarding experience (OR = 0.49, 95% CI: 0.31-0.78) and a high level of knowledge about TB (OR = 0.97, 95% CI: 0.95-0.99) were less likely to refuse TPT. At the family level, those with high father's educational level (OR = 1.50, 95% CI: 1.07-2.10) or high household income (OR = 1.80, 95% CI: 1.20-2.71) were more likely to refuse TPT after initially accepting treatment. CONCLUSIONS: Factors associated with TPT refusal after initial willingness to accept treatment, such as personal (type of students, physical activity, boarding experiences, knowledge of TB) and family characteristics (father's education level, household income) among college student with LTBI, might help identify persons for whom tailored interventions could improve the start of LTBI treatment.

Macrophage-mediated immune response aggravates hearing disfunction caused by the disorder of mitochondrial dynamics in cochlear hair cells.

Mitochondrial dynamics is essential for maintaining the physiological function of the mitochondrial network, and its disorders lead to a variety of diseases. Our previous study identified mitochondrial dynamics controlled anti-tumor immune responses and anxiety symptoms. However, how mitochondrial dynamics affects auditory function in the inner ear remains unclear. Here, we show that the deficiency of FAM73a or FAM73b, two mitochondrial outer membrane proteins that mediate mitochondrial fusion, leads to outer hair cells (HCs) damage and progressive hearing loss in FVB/N mice. Abnormal mitochondrial fusion causes elevated oxidative stress and apoptosis of HCs in the early stage. Thereafter, the activation of macrophages and CD4+ T cell is found in the mutant mice with the increased expression of the inflammatory cytokines IL-12 and IFN-γ compared with control mice. Strikingly, a dramatically decreased number of macrophages by Clophosome®-A-Clodronate Liposomes treatment alleviates the hearing loss of mutant mice. Collectively, our finding highlights that FAM73a or FAM73b deficiency affects HCs survival by disturbing the mitochondrial function, and the subsequent immune response in the cochleae worsens the damage of HCs.

Sirtuin1 (SIRT1) is involved in the anticancer effect of black raspberry anthocyanins in colorectal cancer.

PURPOSE: Abnormal acetylation modification is a common epigenetic change in tumorigenesis and is closely related to the progression of colorectal cancer (CRC). Our previous studies have suggested that black raspberry (BRB) anthocyanins have a significant chemopreventive effect against CRC. This study investigated whether protein acetylation plays an important role in BRB anthocyanins-mediated regulation of CRC progression. METHODS: We used the AOM-induced CRC mouse model and the CRC cell lines SW480 and Caco-2 to explore the potential role of acetylation of histone H4 and NF-κB signaling pathway-related proteins (non-histone proteins) in the antitumor process mediated by BRB anthocyanins. The expression of related proteins was detected by western blot. ROS level was detected by immunofluorescence. RESULTS: BRB anthocyanins affected the acetylation level by down-regulating the expression of Sirtuin1 (SIRT1) and up-regulating the expression of MOF and EP300. The acetylation level of lysine sites on histone H4 (H4K5, H4K12 and H4K16) was increased. Furthermore, following BRB anthocyanins treatment, the expression of ac-p65 was significantly up-regulated and the NF-κB signal pathway was activated, which in turn up-regulated Bax expression and inhibited Bcl-2, cyclin-D1, c-myc and NLRP3 expression to promote CRC cell cycle arrest, apoptosis and relieve inflammation. CONCLUSION: The findings suggested that protein acetylation could play a critical role in BRB anthocyanins-regulated CRC development.

Study on the awareness and its influencing factors of patients with pulmonary tuberculosis on preferential policies for tuberculosis prevention and treatment in Shandong, China.

We investigated the awareness and its influencing factors of patients with pulmonary tuberculosis on preferential policies for tuberculosis prevention and treatment in Shandong, China. A total of 858 patients with pulmonary tuberculosis between January 1, 2018 and September 30, 2019 were surveyed with questionnaires. The basic information (age, sex, education level, family financial situation, disease and diagnosis and treatment, etc), policy awareness, and satisfaction survey status, etc of these 858 tuberculosis patients were collected and analyzed with SPSS software (Chicago, IL) The awareness of tuberculosis patients on preferential policies for tuberculosis prevention and treatment was acceptable with awareness rate of 75.17% (645/858), but their satisfaction with the current policies was not ideal. Debt status and total household assets were the influencing factors of awareness (P < .01). Patients with pulmonary tuberculosis expected to get more free items and lower-cost auxiliary drugs. Patients with pulmonary tuberculosis have different levels of awareness on preferential policies for tuberculosis prevention and treatment. Therefore, targeted promotion of preferential policies for tuberculosis prevention and treatment and different management methods for different patients are of great significance to the treatment of tuberculosis epidemics.

Gstm1/Gstt1 is essential for reducing cisplatin ototoxicity in CBA/CaJ mice.

Cisplatin is a widely used chemotherapeutic agent. However, its clinical utility is limited because of cisplatin-induced ototoxicity. Glutathione S-transferase (GST) was found to play a vital role in reducing cisplatin ototoxicity in mice. Deletion polymorphisms of GSTM1 and GSTT1, members of the GST family, are common in humans and are presumed to be associated with cisplatin-induced hearing impairment. However, the specific roles of GSTM1 and GSTT1 in cisplatin ototoxicity are not completely clear. Here, under cisplatin treatment, simultaneous deletion of Gstm1 and Gstt1 lead to a more profound hearing loss in CBA/CaJ mice (Gstm1/Gstt1-DKO) than in wild-type mice. The Gstm1/Gstt1-DKO mice, in which phase II detoxification genes were upregulated, exhibited more severe oxidative stress and higher outer hair cell apoptosis in the cochleae than the control mice. Thus, our study revealed that Gstm1 and Gstt1 protect auditory hair cells from cisplatin-induced ototoxicity in the CBA/CaJ mice, and genetic screening for GSTM1 and GSTT1 polymorphisms could help determine a standard cisplatin dose for cancer patients undergoing chemotherapy.

HS-Vectors: Heart Sound Embeddings for Abnormal Heart Sound Detection Based on Time-Compressed and Frequency-Expanded TDNN With Dynamic Mask Encoder.

In recent years, auxiliary diagnosis technology for cardiovascular disease based on abnormal heart sound detection has become a research hotspot. Heart sound signals are promising in the preliminary diagnosis of cardiovascular diseases. Previous studies have focused on capturing the local characteristics of heart sounds. In this paper, we investigate a method for mapping heart sound signals with complex patterns to fixed-length feature embedding called HS-Vectors for abnormal heart sound detection. To get the full embedding of the complex heart sound, HS-Vectors are obtained through the Time-Compressed and Frequency-Expanded Time-Delay Neural Network(TCFE-TDNN) and the Dynamic Masked-Attention (DMA) module. HS-Vectors extract and utilize the global and critical heart sound characteristics by masking out irreverent information. Based on the TCFE-TDNN module, the heart sound signal within a certain time is projected into fixed-length embedding. Then, with a learnable mask attention matrix, DMA stats pooling aggregates multi-scale hidden features from different TCFE-TDNN layers and masks out irrelevant frame-level features. Experimental evaluations are performed on a 10-fold cross-validation task using the 2016 PhysioNet/CinC Challenge dataset and the new publicly available pediatric heart sound dataset we collected. Experimental results demonstrate that the proposed method excels the state-of-the-art models in abnormality detection.

Novel organoselenides (NSAIDs-Se derivatives) protect against LPS-induced inflammation in microglia by targeting the NOX2/NLRP3 signaling pathway.

Neuro-inflammation is an immune response of the central nervous system (CNS) to pathogens, and it is associated with a variety of neurodegenerative diseases. Microglial cells are the main category of macrophages in the CNS parenchyma, and they represent one of the most important cellular drivers and regulators of neuroinflammation. In this study, nine new organoselenium compounds based on the hybridization of nonsteroidal anti-inflammatory drugs (NSAIDs) skeleton and organoselenium motif (-SeCN and -SeCF3) were synthesized and their potential anti-neuroinflammatory effects were evaluated using LPS-induced BV2 mouse microglia. The cells were first treated with the organoselenium compounds and the extent of oxidative stress and inflammatory response of the cells was determined by measuring the levels of NO, ROS, IL-1ß, and IL-18. Among the nine compounds, 1-39 and 1A-38 exhibited the most significant effect on oxidative stress and inflammatory response. Subsequent studies carried out with 1-39 and 1A-38 showed that both compounds could reduce the production of ROS in the cells, probably through down-regulating NOX2 and its downstream targets, including TXNIP (thioredoxin-interacting protein) and NLRP3 (NOD-like receptor protein 3). In addition, 1-39 and 1A-38 also suppressed the ability of the cells to secret IL-18 and IL-1ß, which greatly dampened the response of the cells to LPS-induced inflammation. Our finding demonstrated that organoselenium compounds derived from NSAID might play an important role in the protection of brain microglia against inflammation-related neurodegenerative disease by potentially down-regulating the NOX2/NLRP3 signaling axis.

2D-LCoLBP: A Learning Two-Dimensional Co-Occurrence Local Binary Pattern for Image Recognition.

The rotation, scale and translation invariance of extracted features have a high significance in image recognition. Local binary pattern (LBP) and LBP-based descriptors have been widely used in image recognition due to feature discrimination and computational efficiency. However, most of the existing LBP-based descriptors have been designed to achieve rotation invariance while fail to achieve scale invariance. Moreover, it is usually difficult to achieve a good trade-off between the feature discrimination and the feature dimension. In this work, a learning 2D co-occurrence LBP termed 2D-LCoLBP is proposed to address these issues. Firstly, a weighted joint histogram is constructed in different neighborhoods and scales of an image to represent the multi-neighborhood and multi-scale LBP (2D-MLBP) and achieve the rotation invariance. A feature learning strategy is then designed to learn the compact and robust descriptor (2D-LCoLBP) from LBP pattern pairs across different scales in the extracted 2D-MLBP to characterize the most stable local structures and achieve the scale invariance, as well as decrease the feature dimension and improve the noise robustness. Finally, a linear SVM classifier is employed for recognition. We applied the proposed 2D-LCoLBP on four image recognition tasks-texture, object, face and food recognition with ten image databases. Experimental results show that 2D-LCoLBP has obviously low feature dimension but outperforms the state-of-the-art LBP-based descriptors in terms of recognition accuracy under noise-free, Gaussian noise and JPEG compression conditions.

The protective role of protocatechuic acid against chemically induced liver fibrosis in vitro and in vivo.

Liver fibrosis is the result of long-term liver injury and has a high incidence worldwide. Protocatechuic acid (PCA) is ubiquitous in vegetables, nuts, brown rice and herbal medicines, which is reported to possess anti-asthmatic, anti-cancer, and anti-oxidation properties. Our research aimed to investigate the effect of PCA on liver fibrosis. In vitro, TNF-α-induced hepatic stellate cell (HSC) model was used to assess the anti-fibrosis effects of PCA. In vivo, mice were treated with thioacetamide (TAA) to develop liver fibrosis. Body weight, organ index, histological changes, and proteins alteration of factors associated with TGF-ß signaling pathway were used to assess the anti-fibrosis effects of PCA. Our results showed that PCA not only inhibited cell viability in TNF-α activated HSC-T6 cells in vitro, but also efficiently mitigated TAA-induced liver damage and fibrosis in vivo. Further experiments indicated that PCA played a protective role in liver fibrosis through regulation of the TGF-ß signaling pathway downregulating the protein expression of p-Smad2, p-ERK, c-Jun. In summary, our findings provide a pharmacological justification for the clinical application of PCA in preventing or treating liver fibrosis.

Purification of ginseng rare sapogenins 25-OH-PPT and its hypoglycemic, antiinflammatory and lipid-lowering mechanisms.

BACKGROUND: Panax ginseng Meyer has been used as a nourishing edible herb in East Asia for thousands of years. 25-OH-PPT was first discovered as a natural rare triterpenoid saponin in ginseng stems and leaves by our group. Research found that it showed strong inhibitory effects on α-glucosidase and protein tyrosine phosphatase 1B, and protected cardiocytes (H9c2) through PI3K/Akt pathway. METHODS: In the research, in order to optimize the 25-OH-PPT enrichment process, optimal macroporous resins and optimal purification conditions were studied. Meanwhile, the hypoglycemic effect and mechanism of 25-OH-PPT were evaluated by using STZ to establish insulin-dependent diabetic mice and the spontaneous type 2 diabetes DB/DB mice. RESULTS AND CONCLUSION: Research found that 25-OH-PPT can reduce blood glucose and enhance glucose tolerance in STZ model mice. It increases insulin sensitivity by upregulating GLUT4 and AMPK in skeletal muscle, and activating insulin signaling pathways. In DB/DB mice, 25-OH-PPT achieves hypoglycemic effects mainly by activating the insulin signaling pathway. Meanwhile, through the influence of liver inflammatory factors and lipids in serum, it can be seen that 25-OH-PPT has obvious anti-inflammatory and lipid-lowering effects. These results provide new insights into the study of ginseng as a functional food.

Decorin deficiency promotes epithelial-mesenchymal transition and colon cancer metastasis.

The tumor microenvironment encompasses a complex cellular network that includes cancer-associated fibroblasts, inflammatory cells, neo-vessels, and an extracellular matrix enriched in angiogenic growth factors. Decorin is one of the main components of the tumor stroma, but it is not expressed by cancer cells. Lack of this proteoglycan correlates with down-regulation of E-cadherin and induction of ß-catenin signaling. In this study, we investigated the role of a decorin-deficient tumor microenvironment in colon carcinoma progression and metastasis. We utilized an established model of colitis-associated cancer by administering Azoxymethane/Dextran sodium sulfate to adult wild-type and Dcn-/- mice. We discovered that after 12 weeks, all the animals developed intestinal tumors independently of their genotype. However, the number of intestinal neoplasms was significantly higher in the Dcn-/- microenvironment vis-à-vis wild-type mice. Mechanistically, we found that under unchallenged basal conditions, the intestinal epithelium of the Dcn-/- mice showed a significant increase in the protein levels of epithelial-mesenchymal transition associated factors including Snail, Slug, Twist, and MMP2. In comparison, in the colitis-associated cancer evoked in the Dcn-/- mice, we found that intercellular adhesion molecule 1 (ICAM-1) was also significantly increased, in parallel with epithelial-mesenchymal transition signaling pathway-related factors. Furthermore, a combined Celecoxib/decorin treatment revealed a promising therapeutic efficacy in treating human colorectal cancer cells, in decorin-deficient animals. Collectively, our results shed light on colorectal cancer progression and provide a protein-based therapy, i.e., treatment using recombinant decorin, to target the tumor microenvironment.