Cannabidiol Inhibits Epithelial Ovarian Cancer: Role of Gut Microbiome.

Epithelial ovarian cancer is among the deadliest gynecological tumors worldwide. Clinical treatment usually consists of surgery and adjuvant chemo- and radiotherapies. Due to the high rate of recurrence and rapid development of drug resistance, the current focus of research is on finding effective natural products with minimal toxic side effects for treating epithelial ovarian tumors. Cannabidiol is among the most abundant cannabinoids and has a non-psychoactive effect compared to tetrahydrocannabinol, which is a key advantage for clinical application. Studies have shown that cannabidiol has antiproliferative, pro-apoptotic, cytotoxic, antiangiogenic, anti-inflammatory, and immunomodulatory properties. However, its therapeutic value for epithelial ovarian tumors remains unclear. This study aims to investigate the effects of cannabidiol on epithelial ovarian tumors and to elucidate the underlying mechanisms. The results showed that cannabidiol has a significant inhibitory effect on epithelial ovarian tumors. In vivo experiments demonstrated that cannabidiol could inhibit tumor growth by modulating the intestinal microbiome and increasing the abundance of beneficial bacteria. Western blot assays showed that cannabidiol bound to EGFR/AKT/MMPs proteins and suppressed EGFR/AKT/MMPs expression in a dose-dependent manner. Network pharmacology and molecular docking results suggested that cannabidiol could affect the EGFR/AKT/MMPs signaling pathway.

Enterolactone and trabectedin suppress epithelial ovarian cancer synergistically via upregulating THBS1.

Epithelial ovarian cancer (EOC) is the most common and fatal subtype of ovarian malignancies, with no effective therapeutics available. Our previous studies have demonstrated extraordinary suppressive efficacy of enterolactone (ENL) on EOC. A chemotherapeutic agent, trabectedin (Trabe), is shown to be effective on ovarian cancer, especially when combined with other therapeutics, such as pegylated liposomal doxorubicin or oxaliplatin. Thrombospondin 1 (THBS1), a kind of matrix glycoprotein, plays important roles against cancer development through inhibiting angiogenesis but whether it is involved in the suppression of EOC by ENL or Trabe remains unknown. To test combined suppressive effects of ENL and Trabe on EOC and possible involvement of THBS1 in the anticancer activities of ENL and Trabe. The EOC cell line ES-2 was transfected with overexpressed THBS1 by lentivirus vector. We employed tube formation assay to evaluate the anti-angiogenesis activity of ENL and of its combined use with Trabe after THBS1 overexpression and established drug intervention and xenograft nude mouse cancer models to assess the in vivo effects of the hypothesized synergistic suppression between the agents and the involvement of THBS1. Mouse fecal samples were collected for 16S rDNA sequencing and microbiota analysis. We detected strong inhibitory activities of ENL and Trabe against the proliferation and migration of cancer cells and observed synergistic effects between ENL and Trabe in suppressing EOC. ENL and Trabe, given either separately or in combination, could suppress the tube formation capability of human microvascular endothelial cells, and this inhibitory effect became even stronger with THBS1 overexpression. In the ENL plus Trabe combination group, the expression of tissue inhibitor of metalloproteinases 3 and cluster of differentiation 36 was both upregulated, whereas matrix metalloproteinase 9, vascular endothelial growth factor, and cluster of differentiation 47 were all decreased. With the overexpression of THBS1, the results became even more pronounced. In animal experiments, combined use of ENL and Trabe showed superior inhibitory effects to either single agent and significantly suppressed tumor growth, and the overexpression of THBS1 further enhanced the anti-cancer activities of the drug combination group. ENL and Trabe synergistically suppress EOC and THBS1 could remarkably facilitate the synergistic anticancer effects of ENL and Trabe.

Regional Differences, Dynamic Evolution and Convergence of Public Health Level in China.

People's health is a necessary condition for the country's prosperity. Under the background of the COVID-19 pandemic and frequent natural disasters, exploring the spatial and temporal distribution, regional differences and convergence of China's provincial public health level is of great significance to promoting the coordinated development of China's regional public health and achieving the strategic goal of a "healthy China". Based on China's provincial panel data from 2009 to 2020, this paper constructs an evaluation index system for China's public health level from five dimensions: the popularization of a healthy life, optimization of health services, improvement of health insurance, construction of a healthy environment, and development of a health industry. In this paper, the entropy method, Dagum Gini coefficient, Kernel density function and spatial econometric model are used to analyze the spatiotemporal distribution, regional differences, dynamic evolution and convergence of China's public health level since the new medical reform. The study found that, first, China's public health level is generally low, structural contradictions are prominent and the construction of a healthy environment has become a shortcoming hindering the improvement of China's public health level since the new medical reform. The public health level of the four major regions showed a spatial distribution pattern of "high in the eastern, low in the northeastern, central and western" areas. Second, the overall Gini coefficient of China's public health level showed a "V-shaped" trend of first decreasing and then rising, but the overall decrease was greater than the increase, among which the regional difference was the main source of regional differences in China's public health level, but its contribution rate showed a downward trend. Third, except for the basic maintenance of a healthy environment, the Kernel density curves of China's public health level and its sub-dimensions have shifted to the right to a certain extent, and there is no polarization phenomenon. Finally, the level of public health in China has a significant spatial correlation. Except for the northeast region, the growth rate of low-level public health provinces in China and the other three major regions is higher than that of high-level public health provinces, showing a certain convergence trend. In addition, the impact of economic development, financial pressure, and urbanization on the convergence of public health levels in the four major regions is significantly heterogeneous.

Combined Use of Immune Checkpoint Inhibitors and Phytochemicals as a Novel Therapeutic Strategy against Cancer.

Immune checkpoint inhibitor (ICI) therapy has dramatically changed cancer treatment, opening novel opportunities to cure malignant diseases. To date, most prevalently targeted immune checkpoints are programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), with many others being under extensive investigations. However, according to available data, only a fraction of patients may respond to ICI therapy. Additionally, this therapy may cause severe adverse immune-related side effects, such as diarrhea, headache, muscle weakness, rash, hepatitis and leucopenia, although most of them are not fatal, they can affect the patient's treatment outcome and quality of life. On the other hand, growing evidence has shown that phytochemicals with anticancer effects may combine ICI therapy to augment the safety and effectiveness of the treatment against cancer while reducing the adverse side effects. In this review, we summarize the state of art in the various experiments and clinical application of ICIs plus phytochemicals, with a focus on their combined use as a novel therapeutic strategy to cure cancer.

The Spatiotemporal Evolution and Influencing Factors of the Chinese Cities' Ecological Welfare Performance.

In the "full world" where natural capital is scarce, within the limits of the ecological environment, the improvement of welfare is a fundamental requirement for sustainable development. The ecological wellbeing performance (EWP) of 284 cities in China from 2007 to 2020 was measured by the superefficient SBM-DEA model, considering undesirable output, and analyzing the evolutionary trends of overall comprehensive technical efficiency, pure technical efficiency, and scale efficiency. The Theil index was used to explore the source and distribution of the Chinese cities' EWP differences. Exploratory spatial data analysis (ESDA) and the spatial Durbin model (SDM) were applied to analyze the spatial distribution characteristics and driving factors of cities' EWP. The results showed the following: (1) Regarding spatial and temporal distribution, the EWP of Chinese cities showed a fluctuating upward trend, in which pure technical efficiency > scale efficiency. (2) Considering regional differences, the differences in cities' EWP were mainly intraregional rather than interregional. The contribution rates of distinct regions to the differences in EWP varied, i.e., western region > eastern region > central region > northeastern region. (3) In terms of spatial correlation, China's EWP showed positive spatial correlation, i.e., high-high agglomeration and low-low agglomeration. (4) Concerning influencing factors, the level of financial development, the structure of secondary industries, the level of opening-up, and the degree of urbanization significantly improved EWP. Decentralization of fiscal revenue significantly inhibited improvement of EWP. Decentralization of fiscal expenditure and technological progress had no significant impact on the EWP. In the future, to improve cities' EWP, China should focus on reducing differences in intraregional EWP, overcoming administrative regional limitations, encouraging regions with similar locations to formulate coordinated development plans, promoting economic growth, reducing levels of environmental pollution, and paying attention to the improvement of social welfare.

Metabolomics analysis in rats after administration of Datura stramonium.

This study aimed to evaluate the effect of Datura stramonium on rats by examining the differences in urine and serum metabolites between Datura stramonium groups and control group. SIMCA-P+12.0.1.0 software was used for partial least-squares discriminant analysis (PLS-DA) to screen for the differential metabolites. Fifteen metabolites in urine including malonic acid, pentanedioic acid, D-xylose, D-ribose, xylulose, azelaic acid, threitol, glycine, butanoic acid, D-mannose, D-gluconic acid, galactonic acid, myo-inositol, octadecanoic acid, pseudouridine and ten metabolites in serum including alanine, butanedioic acid, L-methionine, propanedioic acid, hexadecanoic acid, D-fructose, tetradecanoic acid, D-glucose, D-galactose, oleic acid were selected as the characteristic metabolites. The PLS-DA scores plot indicated that serum and urine metabolites have a variety of changes among low dose group, high dose group and control group. These metabolites were related with amino metabolism, lipid metabolism and energy metabolism. The result reflected the relationship between metabolites in rat fluid and Datura stramonium spectra. Potential differences in metabolites and metabolic pathway analysis showed that the establishment of urine and serum metabolomics methods for further evaluating drug has great significance.

Seasonal skin darkening in Chinese women: the Shanghaiese experience of daily sun protection.

The facial skin tone of two groups of Chinese women from Shanghai was compared using standard colorimetric space techniques during a 6-month interval between January and July 2011. During the study period, one group of women (n = 40) applied a potent sun-protective cosmetic product daily, while the other group (n = 40) did not use any sun protection. The results, based on images taken using a standardized digital camera coupled to a spectroradiometer, showed that sun protection largely mitigated changes in the components of skin tone, ie, lightness, melanization, and individual typology angle parameters. The skin darkening process appeared to be reduced or prevented in the sun-protected group when compared with the control group. The sun-protected women had participated in an earlier study in 2008, which confirmed that seasonal skin darkening occurs from winter through summer in Shanghaiese women. Comparing the data obtained in the winters of 2008 and 2011, we were able to identify better the impact of 3 years of aging on the components of skin tone. Comparing data between seasons on the same women with (2011 study) and without (2008 study) sun protection highlights the role of the test product in preventing skin darkening.