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The association between capsaicin, the major natural pungent compound of chili peppers, and gastric cancer progression has engendered conflicting findings. In this work, we sought to explore the character of a high capsaicin diet in gastric cancer metastasis and its possible mechanism. The impact of high capsaicin consumption on gastric cancer metastasis was investigated in vivo (xenograft mouse and zebrafish models) and in vitro (biochemical and molecular assays). It was demonstrated that high diet of capsaicin gave rise to accelerate tumor metastasis, which was partially mediated by elevating the expression of transient receptor potential vanilloid 1 (TRPV1) in gastric cancer cells. Importantly, we found that genetic depletion of TRPV1 could reduce gastric cancer metastasis by diminishing the motility of tumor cells in vitro, but acted poorly in xenograft mouse model. Considering the distribution of capsaicin in vivo, 16S rRNA sequencing and fecal microbiota transplantation (FMT) were used to appraise whether the gut microbiota involved in the high capsaicin diet induced metastasis. It was demonstrated that the level of Firmicutes and Clostridiales was expressively boosted following the high consumption of capsaicin. This microbial shift contributed to the increased peripheral 5-hydroxytryptamine (5-HT) levels, yielding the aggravated metastatic burden. Collectively, our findings highlighted the potential risk of high capsaicin diet in promoting gastric cancer metastasis by virtue of modulating TRPV1 expression and gut microbiota composition, indicating the importance of controlled consumption of chili peppers for patients with gastric cancer. CLQ_5di4C7NjAvrz19eKZi Video Abstract [ABSTRACT FROM AUTHOR]

The abnormal expression of Transient Receptor Potential cation channel subfamily V member 4 (TRPV4) is closely related to the progression of multiple tumors. In addition, TRPV4 is increasingly being considered a potential target for cancer therapy, especially in tumor metastasis prevention. However, the biological correlation between TRPV4 and tumor metastasis, as well as the specific role of TRPV4 in malignant melanoma metastasis, is poorly understood. In this study, we aimed to examine the role of TRPV4 in melanoma metastasis through experiments and clinical data analysis, and the underlying anticancer mechanism of Baicalin, a natural compound, and its inhibitory effect on TRPV4 with in vivo and in vitro experiments. Our findings suggested that TRPV4 promotes metastasis in melanoma by regulating cell motility via rearranging the cytoskeletal, and Baicalin can inhibit cancer metastasis, whose mechanisms reverse the recruitment of activated cofilin to leading-edge protrusion and the increasing phosphorylation level of cortactin, which is provoked by TRPV4 activation. [ABSTRACT FROM AUTHOR]

Background. Patients with stable chronic obstructive pulmonary disease (COPD) have been observed to benefit from tiotropium bromide. However, there are few studies of tiotropium bromide on sputum and sputum viscosity. To evaluate the effect of tiotropium bromide on mucus hypersecretion, a randomized, double-blind controlled trial was performed. Methods. 120 cases of patients with pulmonary function grade II were divided into two groups, which include the treatment group given tiotropium bromide powder inhalation (18 μg, inhalation, QD) and the control group given formoterol fumarate powder inhalation (12 μg, inhalation, BID) plus ambroxol hydrochloride tablets (60 mg, oral, TID). After 3 months of treatment, the pulmonary function and α1-acid glycoprotein (α1-AGP) in sputum were detected, and the changes of glycoprotein and Ca2+ content were evaluated by Miller classification. Results. Three patients (2 cases in the treatment group and 1 case in the control group) were dropped due to loss of follow-up, and 117 cases of patients were enrolled in this study. After 3 months of treatment, the sputum character score, α1-acid glycoprotein, Ca2+ content, and lung function of the two groups were significantly improved; group comparison analyses revealed that there was no significant difference in the content of α1-AGP, Ca2+ in sputum, and lung function between the two groups (P > 0.05), but the improvement of sputum properties was significant (P < 0.05), and the treatment group was better than the control group (t = − 2.77 ; P = 0.007). Conclusions. Inhaled tiotropium bromide can effectively inhibit the mucus hypersecretion in stable COPD patients, improve the sputum properties and lung function of patients, and improve the quality of life of patients. [ABSTRACT FROM AUTHOR]

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is becoming a common respiratory disease, leading to increased morbidity and mortality worldwide. Tumor necrosis factor-alpha (TNF-α) is a powerful proinflammatory cytokine involved in the pathogenesis of AECOPD. Therefore, we proposed a close correlation between the TNF-α polymorphism [-308G/A (rs1800629), +489G/A (rs1800610)] and the disease progress of patients with AECOPD. Comparison of the TNF-α genotypes between the 198 AECOPD diagnosed patients groups and 195 healthy peoples suggested their significant differences of the three genotypes (AA, GA, GG) distribution for TNF-α -308 (P < 0.05), but no differences of that for TNF-α +489. We found that patients with TNF-α -308 GA/AA genotypes showed smaller adjacent arterial diameter, thicker bronchial wall, higher bronchial artery ratio, higher bronchial wall grading, and higher frequency of acute exacerbations than those with TNF-α -308 GG genotype. Patients with TNF-α +489 GA/AA genotypes showed the same AECOPD properties as patients with TNF-α -308 except for the high frequency of acute exacerbations. Further experiment showed that the TNF-α -308 and+489 gene polymorphisms could affect the expression level of TNF-α in macrophages, suggesting the involvement of the macrophage population in disease regulation of AECOPD patients with TNF-α -308G/A and+489G/A genotype heterogeneity. In conclusion, the TNF-α -308 G/A genotype was related to AECOPD susceptibility and progress, while the TNF-α +489G/A genotype was related to AECOPD progress, but not AECOPD susceptibility. [ABSTRACT FROM AUTHOR]

It is common sense that chewing a mint leaf can cause a cooling feeling, while chewing ginger root will produce a burning feeling. In Traditional Chinese Medicine (TCM), this phenomenon is referred to as 'cold/hot' properties of herbs. Herein, it is reported that TCM with different "cold/hot" properties have different effects on the variation of cells. To explore the intrinsic 'cold/hot' properties of TCM from the perspective of cellular and molecular biology. A375 cells were selected using Cancer Cell Line Encyclopaedia (CCLE) analysis and western blots. Hypaconitine and baicalin were selected by structural similarity analysis from 56 and 140 compounds, respectively. A wireless thermometry system was used to measure cellular temperature change induced by different compounds. Alteration of intracellular calcium influx was investigated by means of calcium imaging. The IC50 values of GSK1016790A, HC067047, hypaconitine, and baicalin for A375 cells are 8.363 nM, 816.4 μM, 286.4 μM and 29.84 μM, respectively. And, 8 μM hypaconitine induced obvious calcium influx while 8 μM baicalin inhibited calcium influx induced by TRPV4 activation. Cellular temperature elevated significantly when treated with GSK1016790A or hypaconitine, while the results were reversed when cells were treated with HC067047 or baicalin. The changes in cellular temperature are speculated to be caused by the alteration of intracellular calcium influx mediated by TRPV4. In addition, the 'cold/hot' properties of compounds in TCM can be classified by using cellular temperature detection. [ABSTRACT FROM AUTHOR]

The incidence and mortality of lung cancer were extremely high. The present study showed that SRCIN1 was an oncogene in non-small-cell lung cancer (NSCLC). Public dataset analysis showed SRCIN1 was significantly overexpressed in NSCLC samples. Also, we found that NSCLC patients with higher SRCIN1 expression had shorter OS time by analyzing TCGA, Kaplan-Meier Plotter, GSE30219, GSE50081, and GSE19188 databases. Overexpression or knockdown of SRCIN1 significantly induced or reduced A549 and H1299 cell proliferation. Furthermore, we found SRCIN1 was directly targeted by miR-211. Overexpression or knockdown of miR-211 suppressed or induced SRCIN1 levels in NSCLC. Moreover, we found that miR-211 affected NSCLC cell proliferation through SRCIN1. Previous studies demonstrated that circRNAs could act as miRNA sponges in cancer cells. In this study, we showed that knockdown of circCCDC66 induced expression of miR-211. Luciferase assay demonstrated that miR-211 suppressed the activity of luciferase reporter-contained circCCDC66 sequences. Moreover, knockdown of circCCDC66 significantly inhibited SRCIN1 levels in both A549 and H1299 cells. These results showed that circCCDC66 acted as a miRNA sponge to affect the miR-211/SRCIN1 axis. Of note, we for the first time revealed that circCCDC66 suppression reduced cell proliferation by about 65% in A549 and by about 40% in H1299 cells. We thought this study could provide novel potential biomarkers for NSCLC. [ABSTRACT FROM AUTHOR]

Relieving Sore Throat Formula (RSTF) is a formula approved by the China Food and Drug Administration and has been used for the treatment of pharyngitis in clinic for many years. However, the potential pharmacological mechanism still remains unknown. We combined multiple methods including bioinformatics data digging, network pharmacology analysis, and pathway analysis to predict the potential target of RSTF. We verified our in silico prediction results with an in vivo/vitro antibacterial effect test, mouse phagocytic index test, proliferation, transformation, and migration of mouse spleen lymphocytes. Alteration of NF-κB pathway was determined by Western blotting, immunofluorescence, and PCR. The in vivo experiments demonstrated that the RSTF could significantly relieve the symptoms of pharyngitis. A rat saliva secretion test showed that RSTF can effectively relieve the xerostomia symptom. A phenol red excretion test showed that RSTF has an eliminating phlegm effect. A hot plate method and granuloma experiment proved that RSTF also have analgesic and anti-inflammatory effects. In silico prediction demonstrates that 70 active compounds of RSTF were filtered out through ADME screening and 84 putative targets correlated with different diseases. Pathway enrichment analysis showed that the candidate targets were mostly related to the response to bacteria and immunity signalling pathways, which are known contributors to pharyngitis. Experimental results confirmed that RSTF exerted therapeutic effects on pharyngitis mainly by antibacterial effect and downregulation of NF-κB activities. It is demonstrated both in silico and in vivo/vitro that RSTF exerted therapeutic effects on pharyngitis mainly through an antibiotic effect and downregulation of NF-κB signalling pathway. [ABSTRACT FROM AUTHOR]

Though it has been widely accepted that infections of the respiratory tract is associated with aetiology of acute exacerbation of chronic obstructive pulmonary disease (AECOPD), more recent techniques have shown emerging evidence on the importance of alterations of diversity and composition of microbiota itself in the disease process. Specifically, these alterations is widely present in COPD patients from a variety of populations, and is associated with severity of disease, frequency of acute exacerbation, as well as prediction of exacerbation. In addition, the microbiota from respiratory tract contributes to disease mechanisms, and more recently have been shown to interact with gut microbiota in a bidirectional way. Therefore, updating progress in the field is crucial as it not only reveals potential underlying mechanisms of the disease, but also highlights the potential utilisation of microbiota as a biomarker for disease prediction and as a target for treatment. In this narrative review, we summarize current updates on microbiota dysbiosis in COPD, including techniques for sampling and analysis of microbiota, recent findings on the presence of microbiota dysbiosis and its correlation with clinical prediction and prognosis of the disease, as well as its potential roles in disease mechanisms. In addition, how gut-lung axis contributes to COPD progression is also discussed. Finally, we addressed the utilisation of prebiotic and probiotic treatment for COPD. Together, we hope to provide useful information to advocate the use of microbial parameters as important tools for diagnosis, treatment and long-term follow-up for COPD patients. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Fufang Xueshuantong Capsule, an herbal formula licensed for clinical use in China, which is composed of Panax notoginseng (Burkill) F.H. Chen, Salvia miltiorrhiza Bunge, Astragalus membranaceus (Fisch.) Bunge, and Scrophularia ningpoensis Hemsl, has proven effective for the treatment of diabetic retinopathy. However, its bioactive constituents are still ambiguous. In this study, the therapeutic effects of a combination of the main constituents of Fufang Xueshuantong Capsule (cFXT) were evaluated in streptozotocin (STZ)-induced retinal lesions to identify the bioactive constituents. Methods Sprague-Dawley rats, except for those in the control group (vehicle+vehicle), were administered a single injection of 60 mg/kg STZ. One-week later, STZ-treated rats were randomly divided into three groups—one STZ group (STZ+vehicle) and two cFXT treatment groups (STZ+cFXT). The rats in the latter two groups received cFXT 44.8 mg/kg or cFXT 22.4 mg/kg by intragastric gavage once per day, for 24 consecutive weeks. The rats in the control and STZ groups received the vehicle in the same way. Body weights and fasting blood glucose levels were recorded every four weeks. After treatment, hemorheological tests were performed to record the erythrocyte aggregation indexes, blood viscosity, and plasma viscosity. The trypsin digestion method was used to observe pericyte and acellular capillary counts in the retina. Ultraviolet spectrophotometry was utilized to measure the activity of aldose reductase (AR) by measuring the nicotinamide adenine dinucleotide phosphate (NADPH) consumption at 340 nm. An immunohistochemical assay was used to observe the expressions of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in the retina. The expression levels of intercellular adhesion molecule-1 (ICAM-1), endothelin-1 (RT-1),and occludin in the retina were tested by the western blot assay. Results cFXT is composed of 991.44 mg/g saponins of Panax notoginseng , 1.62 mg/g harpagoside, 0.70 mg/g cryptotanshinone, 0.74 mg/g tanshinone I, and 5.50 mg/g astragaloside A. Although it showed no effects on the increased body weight and blood glucose levels induced by STZ in rats. However, it showed a tendency to attenuate the increase in erythrocyte aggregation, plasma viscosity, and acellular vessel and pericyte loss, paralleled with a reversal of the hyper-activation of AR, the hyper-expression of VEGF, ICAM-1, and ET-1, and the hypo-expression of PEDF and occludin in the retinas of STZ-treated rats. Conclusion The saponins of Panax notoginseng , harpagoside, cryptotanshinone, tanshinone I, and astragaloside A are the main bioactive constituents of Fufang Xueshuantong Capsule and contribute to the attenuation of STZ-induced retinal lesions in rats. These constituents can be used as the base to optimize a new drug for the treatment of diabetic retinopathy, and can be selected for quality control of Fufang Xueshuantong Capsules. [ABSTRACT FROM AUTHOR]

Background: Circulating tumor cell (CTC) clusters play a critical role in carcinoma metastasis. However, the rarity of CTC clusters and the limitations of capture techniques have retarded the research progress. In vitro CTC clusters model can help to further understand the biological properties of CTC clusters and their clinical significance. Therefore, it is necessary to establish reliable in vitro methodological models to form CTC clusters whose biological characteristics are very similar to clinical CTC clusters. Methods: The assays of immunofluorescence, transmission electron microscopy, EdU incorporation, cell adhension and microfluidic chips were used. The experimental metastasis model in mice was used. Results: We systematically optimized the culture methods to form in vitro CTC clusters model, and more importantly, evaluated it with reference to the biological capabilities of reported clinical CTC clusters. In vitro CTC clusters exhibited a high degree of similarity to the reported pathological characteristics of CTC clusters isolated from patients at different stages of tumor metastasis, including the appearance morphology, size, adhesive and tight junctions-associated proteins, and other indicators of CTC clusters. Furthermore, in vivo experiments also demonstrated that the CTC clusters had an enhanced ability to grow and metastasize compared to single CTC. Conclusions: The study provides a reliable model to help to obtain comparatively stable and qualified CTC clusters in vitro, propelling the studies on tumor metastasis. [ABSTRACT FROM AUTHOR]

Programmed cell death protein‐1 (PD‐1)/programmed death ligand‐1 (PD‐L1) immune checkpoint blockade as a breakthrough in cancer immunotherapy has shown unprecedented positive outcomes in the clinic. However, the overall effectiveness of PD‐L1 antibody is less than expected. An increasing number of studies have demonstrated that PD‐L1 is widely distributed and expressed not only on the cell membrane but also on the inside of the cells as well as on the extracellular vesicles secreted by tumour cells. Both endogenous and exogenous PD‐L1 play significant roles in influencing the therapeutic effect of anti‐tumour immunity. Herein, we mainly focused on the distribution and function of PD‐L1 and further summarized the potential targeted therapeutic strategies. More importantly, in addition to taking the overall expression abundance of PD‐L1 as a predictive indicator for selecting corresponding PD‐1/PD‐L1 monoclonal antibodies (mAbs), we also proposed that personalized combination therapies based on the different distribution of PD‐L1 are worth attention to achieve more efficient and effective therapeutic outcomes in cancer patients. LINKED ARTICLES: This article is part of a themed issue on Cancer Microenvironment and Pharmacological Interventions. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.2/issuetoc [ABSTRACT FROM AUTHOR]

Tumor cell extravasation across endothelial barrier has been recognized as a pivotal event in orchestrating metastasis formation. This event is initiated by the interactions of extravasating tumor cells with endothelial cells (ECs). Therefore, targeting the crosstalk between tumor cells and ECs might be a promising therapeutic strategy to prevent metastasis. In this study, we demonstrated that Rh1, one of the main ingredients of ginseng, hindered the invasion of breast cancer (BC) cells as well as diminished the permeability of ECs both in vitro and in vivo, which was responsible for the attenuated tumor cell extravasation across endothelium. Noteworthily, we showed that ECs were capable of inducing the epithelial-mesenchymal transition (EMT) and invadopodia of BC cells that are essential for tumor cell migration and invasion through limiting the nuclear translocation of hematopoietically expressed homeobox (HHEX). The decreased nuclear HHEX paved the way for initiating the CCL20/CCR6 signaling axis, which in turn contributed to damaged endothelial junctions, uncovering a new crosstalk mode between tumor cells and ECs. Intriguingly, Rh1 inhibited the kinase activity of casein kinase II subunit alpha (CK2α) and further promoted the nuclear translocation of HHEX in the BC cells, which resulted in the disrupted crosstalk between chemokine (C-C motif) ligand 20 (CCL20) in the BC cells and chemokine (C-C motif) receptor 6 (CCR6) in the ECs. The prohibited CCL20-CCR6 axis by Rh1 enhanced vascular integrity and diminished tumor cell motility. Taken together, our data suggest that Rh1 serves as an effective natural CK2α inhibitor that can be further optimized to be a therapeutic agent for reducing tumor cell extravasation. [Display omitted] Inhibition of CK2α by Rh1 retarded the metastasis with restraining extravasation of BC cells across endothelial barrier via disrupting the HHEX/CCL20 signaling cascade. [ABSTRACT FROM AUTHOR]

Previous studies had shown that xanthatin, a natural xanthanolide sesquiterpene lactone, could induce mitotic arrest and apoptosis in non-small cell lung cancer (NSCLC) cells. Here, we examined whether the DNA damage response (DDR) could be a primary cytotoxic event underlying xanthatin-mediated anti-tumor activity. Using EdU incorporation assay in combination with novel imaging flow cytometry, our data indicated that xanthatin suppressed DNA replication, prevented cells from G 2 /M entry and increased the spot count of γH2AX nuclear foci. Given that checkpoint kinase 1 (Chk1) represents a core component in DDR-mediated cell cycle transition and the phosphorylation on Ser-345 is essential for kinase activation and function, we surprisingly found xanthatin distinctly modulated Ser-345 phosphorylation of Chk1 in A549 and H1299 cells. Further investigation on Cdc25C/CDK1/CyclinB1 signaling cascade in the absence or presence of pharmacological DDR inhibitors showed that xanthatin directly destabilized the protein levels of Cdc25C, and recovery of p53 expression in p53-deficient H1299 cells further intensified xanthatin-mediated inhibition of Cdc25C, suggesting p53-dependent regulation of Cdc25C in a DDR machinery. Moreover, exogenous expression of Cdc25C was also substantially repressed by xanthatin and partially impaired xanthatin-induced G 2 arrest. In addition, xanthatin could induce accumulation of ubiquitinated Cdc25C without undergoing further proteasomal degradation. However, an alternative lysosomal proteolysis of Cdc25C was observed. Interestingly, lysosome-like vesicles were produced upon xanthatin treatment, accompanied by rapid accumulation of lysosomal associated membrane protein LAPM-1. Furthermore, vacuolar proton (V)-ATPases inhibitor bafilomycin A1 and lysosomal proteases inhibitor leupeptin could remarkably overturn the levels of Cdc25C in xanthatin-treated H1299 cells. Altogether, these data provide insight into how xanthatin can be effectively targeted DDR molecules towards certain tumors. [ABSTRACT FROM AUTHOR]

• Reciprocal regulation between tumor vascular normalization and immune reprogramming enables the formation of a positive feedback loop. • Endothelial cell metabolism drives blood vessel sprouting in parallel with the control of genetic signals in cancer. • Combination of vascular normalization and immunotherapy is one of the strategies in cancer treatment. In solid tumors, the vasculature is highly abnormal in structure and function, resulting in the formation of an immunosuppressive tumor microenvironment by limiting immune cells infiltration into tumors. Vascular normalization is receiving much attention as an alternative strategy to anti-angiogenic therapy, and its potential therapeutic targets include signaling pathways, angiogenesis-related genes, and metabolic pathways. Endothelial cells play an important role in the formation of blood vessel structure and function, and their metabolic processes drive blood vessel sprouting in parallel with the control of genetic signals in cancer. The feedback loop between vascular normalization and immunotherapy has been discussed extensively in many reviews. In this review, we summarize the impact of aberrant tumor vascular structure and function on drug delivery, metastasis, and anti-tumor immune responses. In addition, we present evidences for the mutual regulation of immune vasculature. Based on the importance of endothelial metabolism in controlling angiogenesis, we elucidate the crosstalk between endothelial cells and immune cells from the perspective of metabolic pathways and propose that targeting abnormal endothelial metabolism to achieve vascular normalization can be an alternative strategy for cancer treatment, which provides a new theoretical basis for future research on the combination of vascular normalization and immunotherapy. [ABSTRACT FROM AUTHOR]

Metastasis is the leading cause of death in melanoma patients. Aerobic glycolysis is a common metabolic feature in tumor and is closely related to cell growth and metastasis. Kaempferol (KAM) is one of the active ingredients in the total flavonoids of Chinese traditional medicine Sparganii Rhizoma. Studies have shown that it interferes with the cell cycle, apoptosis, angiogenesis and metastasis of tumor cells, but whether it can affect the aerobic glycolysis of melanoma is still unclear. Here, we explored the effects and mechanisms of KAM on melanoma metastasis and aerobic glycolysis. KAM inhibited the migration and invasion of A375 and B16F10 cells, and reduced the lung metastasis of melanoma cells. Extracellular acidification rates (ECAR) and glucose consumption were obviously suppressed by KAM, as well as the production of ATP, pyruvate and lactate. Mechanistically, the activity of hexokinase (HK), the first key kinase of aerobic glycolysis, was significantly inhibited by KAM. Although the total protein expression of HK2 was not significantly changed, the binding of HK2 and voltage-dependent anion channel 1 (VDAC1) on mitochondria was inhibited by KAM through AKT/GSK-3β signal pathway. In conclusion, KAM inhibits melanoma metastasis via blocking aerobic glycolysis of melanoma cells, in which the binding of HK2 and VDAC1 on mitochondria was broken. [Display omitted] [ABSTRACT FROM AUTHOR]

A pebble-bed high-temperature gas-cooled reactor (pebble-bed HTR) uses a helium coolant, graphite core structure, and spherical fuel elements. The pebble-bed design enables on-line refueling, avoiding refueling shutdowns. During circulation process, the pebbles are lifted pneumatically via a stainless steel lifting pipe and reinserted into the reactor. Inevitably, the movement of the fuel elements as they recirculate in the reactor produces graphite dust. Mechanical wear is the primary source of graphite dust production. Specifically, the sources are mechanisms of pebble–pebble contact, pebble–wall (structural graphite) contact, and fuel handling (pebble–metal abrasion). The key contribution to graphite dust production is from the fuel handling system, particularly from the lifting pipe. During pneumatic lift, graphite pebbles undergo multiple collisions with the stainless steel lifting pipe, thereby causing abrasion of the graphite pebbles and producing graphite dust. The present work explored the abrasion behavior of graphite pebble in the lifting pipe by measuring the abrasion rate at different lifting velocities. The abrasion rate of the graphite pebble in helium was found much higher than those in air and nitrogen. This gas environment effect could be explained by either tribology behavior or dynamic behavior. Friction testing excluded the possibility of tribology reason. The dynamic behavior of the graphite pebble was captured by analysis of the audio waveforms during pneumatic lift. The analysis results revealed unique dynamic behavior of the graphite pebble in helium. Oscillation and consequently intensive collisions occur during pneumatic lift, causing significant abrasion of the graphite pebble. This study provides an excellent explanation for the abrasion behavior of graphite pebbles in the lifting pipe of the pebble-bed HTR. [ABSTRACT FROM AUTHOR]

Skin toxicities induced by epidermal growth factor receptor inhibitors such as Erlotinib plagues clinical challenges. Chinese formulas have a unique advantage in reducing side effects. Here, we aim to investigate the skin protecting function of XiaoZhenFang (XZF), a clinical adjuvant prescription made up of Lonicerae Japonicae Flos, Lithospermum Erythrorhizon, Smilacis Glabrae Rhizoma, Forsythiae Fructus, Spirodelae Herba, Cortex Moutan and Prunellae Spica. Our data showed that XZF aqueous extract effectively reduced skin toxicities induced by Erlotinib in vivo using established mice model. Next, we used a systems pharmacology approach to investigate the pharmacological mechanism of XZF with the goal of understanding its effects at the system, organ, and molecular levels. 44 candidate compounds and 103 potential targets were identified by network pharmacology. Inflammation, cell stress and the EGFR-related signal pathways, which may participate in the skin protection afforded by XZF, were analyzed by gene enrichment. Importantly, our in vivo experimental results largely validated XZF's mechanism of action, as predicted by the system pharmacology analysis. Our study uncovered the effect and mechanism of XZF in attenuating skin toxicities induced by EGFRI, providing a basis for the development of in-hospital preparations and new drugs for the prevention of skin toxicities. [ABSTRACT FROM AUTHOR]

Major depressive disorder is now becoming a common disease in daily life, and most patients do not have satisfactory treatment outcomes. We herein evaluated the therapeutic effects of Zhile capsule and clarified the molecular mechanism. A rat model of chronic unpredictable mild stress-induced depression was established to assess the antidepressant-like effects of Zhile by using the sucrose preference test, open field test, forced swim test, tail suspension test and HPLC. Systems pharmacology was then performed to unravel the underlying mechanism which was confirmed by western blot, enzyme-linked immunosorbent assay, and qPCR. Zhile alleviated depression-like behaviors by upregulating the cAMP-CREB-BDNF (brain-derived neurotrophic factor) axis to exert neuroprotective effects. It may be beneficial to depressive patients in clinical practice. [ABSTRACT FROM AUTHOR]