Exploring the Effect of Polyphyllin I on Hepatitis B Virus-related Liver Cancer through Network Pharmacology and in vitro Experiments.

AIM AND OBJECTIVE: To investigate the effect of Polyphyllin I (PPI) on HBV-related liver cancer through network pharmacology and in vitro experiments, and to explore its mechanism of action. MATERIALS AND METHODS: Use bioinformatics software to predict the active ingredient target of PPI and the disease target of liver cancer, and perform active ingredient-disease target analysis. The results of network pharmacology through molecular docking and in vitro experiments can be further verified. The HepG2 receptor cells (HepG2. 2. 15) were transfected with HBV plasmid for observation, with the human liver cancer HepG2 being used as the control. RESULTS: Bioinformatics analysis found that PPI had a total of 161 protein targets, and the predicted target and liver cancer targets were combined to obtain 13 intersection targets. The results of molecular docking demonstrated that PPI had a good affinity with STAT3, PTP1B, IL2, and BCL2L1. The results of the in vitro experiments indicated that the PPI inhibited cell proliferation and metastasis in a concentration-dependent manner (P<0.01). Compared with the vehicle group, the PPI group of 1.5, 3, and 6 µmol/L can promote the apoptosis of liver cancer to different degrees (P<0.01). CONCLUSION: The present study revealed the mechanism of PPI against liver cancer through network pharmacology and in vitro experiments. Its mechanism of action is related to the inhibition of PPI on the proliferation of HBV-related liver cancer through promoting the apoptosis of liver cancer cells. Additionally, in vitro experiments have also verified that PPI can promote the apoptosis of HepG2 and HepG2.2.15 cells.

Exploring the effect of Gupi Xiaoji Prescription on hepatitis B virus-related liver cancer through network pharmacology and in vitro experiments.

AIM AND OBJECTIVE: To study the effect of Gupi Xiaoji Prescription (GXP) on hepatitis B virus(HBV)-related liver cancer through network pharmacology coupled with in vitro experiments and explore their related mechanisms. MATERIALS AND METHODS: Gupi Xiaoji Prescription's chemical constituents and the action targets of its six medicinal components were identified using several databases. These included the Traditional Chinese Medicine Systems Pharmacology Database （TCMSP), the Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM), and the Traditional Chinese Medicine Integrated Database (TCMID), while GeneCards and OMIM were used to compile relevant liver cancer disease targets. Pathway enrichment of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), analysis of potential targets, and analysis of the enriched pathways in literature were executed in R. The Hepatocellular carcinoma (HCC)-derived HepG2.2.15 cell line stably expresses and replicates HBV. In vitro experiments with HepG2.2.15 were used to verify GXP's effects on HBV-related liver cancer, while the human liver cancer cell line HepG2 was used as the control. RESULTS: 171 active ingredients and 259 potential drug targets were screened from GXP, involving 181 pathways in vitro. These assays identified Polyphyllin I as an effective GXP component. Notably, GXP inhibited cell proliferation and metastasis in a concentration-dependent manner (P < 0.01). In comparison with the vehicle group, the fluorescence intensity of each drug group was significantly weakened (P < 0.01), while the drug group Mitofusins 1(MFN1) and protein expression level of Mitofusins 2 (MFN2) increased significantly. The protein expression level of Mitochondrial fission protein 1 (FIS1) and Optic Atrophy 1 (OPA1) also showed significant decreases (P < 0.01). Molecular docking revealed Fructus saponins I's high affinity with FIS1, MFN1, MFN2, and OPA1. CONCLUSION: The network pharmacology results indicate that Gupi Xiaoji Prescription may treat liver cancer by regulating mitochondrial division and fusion of key genes to disrupt liver cancer cells' energy metabolism. In vitro experiments also verified that GXP could inhibit the proliferation and migration of HepG2.2.15 cells by up-regulating MFN1 and MFN2, down-regulating the expression of FIS1 and OPA1 in addition to damaging mitochondria. Consistent with network pharmacology and molecular docking results, Polyphyllin I may be the most active compound of the formula's components. It also shows that Traditional Chinese medicine (TCM) plays a significant, targeted role in the treatment of HBV-related liver cancer.

The role of tumor-associated macrophages in osteosarcoma progression - therapeutic implications.

BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumor. Compared with previous treatment modalities, such as amputation, more recent comprehensive treatment modalities based on neoadjuvant chemotherapy combined with limb salvage surgery have improved the survival rates of patients. Osteosarcoma treatment has, however, not further improved in recent years. Therefore, attention has shifted to the tumor microenvironment (TME) in which osteosarcoma cells are embedded. Therapeutic targets in the TME may be key to improving osteosarcoma treatment. Tumor-associated macrophages (TAMs) are the most common immune cells within the TME. TAMs in osteosarcoma may account for over 50% of the immune cells, and may play important roles in tumorigenesis, angiogenesis, immunosuppression, drug resistance and metastasis. Knowledge on the role of TAMs in the development, progression and treatment of osteosarcoma is gradually improving, although different or even opposing opinions still remain. CONCLUSIONS: TAMs may participate in the malignant progression of osteosarcoma through self-polarization, the promotion of blood vessel and lymphatic vessel formation, immunosuppression, and drug resistance. Besides, various immune checkpoint proteins expressed on the surface of TAMs, such as PD-1 and CD47, provide the possibility of the application of immune checkpoint inhibitors. Several clinical trials have been carried out and/or are in progress. Mifamotide and the immune checkpoint inhibitor Camrelizumab were both found to be effective in prolonging progression-free survival. Thus, TAMs may serve as attractive therapeutic targets. Targeting TAMs as a complementary therapy is expected to improve the prognosis of osteosarcoma. Further efforts may be made to identify potential beneficiaries of TAM-targeted therapies.

The effectiveness of combination therapies for androgenetic alopecia: A systematic review and meta-analysis.

Androgenetic alopecia (AGA) is the most common type of baldness affecting both men and women. Studies investigating combination therapies for AGA reported greater efficacy than monotherapy but without rigorous examination. The authors performed a meta-analysis and systemic review to further verify the evidence. To evaluate the effectiveness of three common combination therapies of minoxidil with finasteride, low-level laser light therapy (LLLT) or microneedling versus minoxidil monotherapy. We conducted a systematic review of randomized controlled trials (RCTs) of combination therapies consisting of topical minoxidil for AGA through April 2020. Quality assessment and data analysis were performed by Review Manager 5.3. Fifteen studies met the inclusion criteria involving a total of 1172 AGA patients. We conducted meta-analysis for three groups of combined treatment separately, and all were superior to monotherapy in terms of global photographic assessment (P < .05). Combination of LLLT or microneedling with minoxidil also showed significant increase in hair count (P < .05) compared to monotherapy. The present study suggests that combination therapy could be an effective, safe and promising option for the treatment of AGA. However, more RCTs are needed to further investigate and confirm the efficacy of combined treatment.

[Influence of Spatial Pattern of Paddy Field on the Losses of Nitrogen and Phosphorus in Three Gorges Reservoir Area].

This paper used three plots of paddy field in Wangjiagou small catchment in Fuling District, Chongqing Municipality as a case study. Wangjiagou, located in Three Gorges Reservoir Area, provided a good case in terms of its closeness of surface runoff. The samples of individual rainfall of twelve times and process of two typical individual rainfalls on three plots of sloping paddy field were collected from 2014 to 2015. These samples were used to analyze the influence of spatial pattern of sloping paddy field on the concentration of nitrogen and phosphorus in the surface runoff. The samples of daily runoff in subcatchments in 2010 and 2015 were used to analyze the influence of spatial pattern change of subcatchments' paddy field on the concentration of nitrogen and phosphorus in the surface runoff. The results indicated that the removal rates of TN, NO3--N and TP of paddy field at the valley bottom were higher than those in the mid-slopes. The removal rate of TP would be higher if plot size of paddy field at the bottom got bigger. During individual rainfall event, the losses concentration of TN, NO3--N and TP in the paddy fields was significantly different among three different spatial patterns during the previous period of heavy rain event, but it became different during the next period of moderate rain event. The two subcatchments' spatial pattern change of paddy field had weakened the intercepting purification ability of nitrogen and phosphorus losses of paddy field in 2015, compared with that in 2010. TN's losses concentration increased significantly during the periods of light and moderate rain event and base flow. TP's losses concentration fluctuated during the event from moderate rain to heavy rain. Hence, increasing the area of paddy field of catchment and optimizing its spatial pattern reasonably were found as effective measures to control agricultural non-point source pollution in the Three Gorges Reservoir Region.

[Nitrogen Losses Under the Action of Different Land Use Types of Small Catchment in Three Gorges Region].

As an independent water-collecting area, small catchment is the source of non-point source pollution in Three Gorges Region. Choosing 3 kinds of the most representative land-use types and using them to lay monitoring points of overland runoff within the small catchment of Wangjiagou in Fuling of Three Gorges Region, the author used the samples of surface runoff collected through the twelve natural rainfalls from May to December to analyze the feature of spatial-temporal change of Nitrogen's losses concentrations under the influence of different land use types and the hillslopes and small catchments composed by those land use types, revealing the relation between different land-use types and Nitrogen's losses of small catchments in Three Gorges Region. The result showed: the average losses concentration of TN showed the biggest difference for different land use types during the period of spring crops, and the average value of dry land was 1. 61 times and 6.73 times of the values of interplanting field of mulberry and paddy field, respectively; the change of the losses concentration of TN was most conspicuous in the 3 periods of paddy field. The main element was NO3⁻-N, and the relation between TN and NO3⁻-N showed a significant linear correlation. TN's and NO3⁻-N's losses concentrations were significantly and positively correlated with the area ratio of corn and mustard, but got a significant negative correlation with the area ratio of paddy and mulberry; NH4⁺-N's losses concentrations got a significant positive correlation with the area ratio of mustard. Among all the hillslopes composed by different land use types, TN's average losses concentration of surface runoff of the hillslope composed by interplantating field of mulberry and paddy land during the three periods was the lowest, and the values were 2.55, 11.52, 8.58 mg · L⁻¹, respectively; the hillslope of rotation plough land of corn and mustard had the maximum value, and the values were 27.51, 25.11, 27.11 mg · L⁻¹, respectively; different land use types and spatial combination ways of subcatchment had a greater influence on TN's losses concentrations, so using a reasonable way to adjust land use structure and spatial arrangement of whole catchment was an effective measure to control the source of non-point source pollution of Three Gorges Region.

Spatial and temporal variations in non-point source losses of nitrogen and phosphorus in a small agricultural catchment in the Three Gorges Region.

Losses of agricultural pollutants from small catchments are a major issue for water quality in the Three Gorges Region. Solutions are urgently needed. However, before pollutant losses can be controlled, information about spatial and temporal variations in pollutant losses is needed. The study was carried out in the Wangjiagou catchment, a small agricultural catchment in Fuling District, Chongqing, and the data about non-point source losses of nitrogen and phosphorus was collected here. Water samples were collected daily by an automatic water sampler at the outlets of two subcatchments from 2012 to 2014. Also, samples of surface runoff from 28 sampling sites distributed through the subcatchments were collected during 12 rainfall events in 2014. A range of water quality variables were analyzed for all samples and were used to demonstrate the variation in non-point losses of nitrogen and phosphorus over a range of temporal and spatial scales and in different types of rainfall in the catchment. Results showed that there was a significant linear correlation between the mass concentrations of total nitrogen (TN) and nitrate (NO3-N) in surface runoff and that the relationship was maintained with changes in time. Concentrations of TN and NO3-N peaked after fertilizer was applied to crops in spring and autumn; concentrations decreased rapidly after the peak values in spring but declined slowly in autumn. N and P concentrations fluctuated more and showed a greater degree of dispersion during the spring crop cultivation period than those in autumn. Concentrations of TN and NO3-N in surface runoff were significantly and positively correlated with the proportion of the area that was planted with corn and mustard tubers, but were negatively correlated with the proportion of the area taken up with rice and mulberry plantations. The average concentrations of TN and NO3-N in surface runoff reached the highest level from the sampling points at the bottom of the land used for corn only, but lowest in rice fields. Slope gradient had a significant positive correlation with TN's and total phosphorus (TP)'s concentration losses. Concentrations of TN, NO3-N, and total phosphorus were significantly correlated with rainfall. Peak concentrations of ammoniacal nitrogen occurred during the fertilizer application period in spring and autumn. Different structures of land use types had a significant influence on the concentration losses of nitrogen and phosphorus; thus, using a reasonable way to adjust land use structure and spatial arrangement of whole catchment was an effective solution to control non-point source pollution of the Three Gorges Region.