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Hypercholesterolemia is frequently diagnosed in patients with primary biliary cholangitis (PBC). However, its association with the prognosis and lipid metabolism is unknown. In this study, we aimed to investigate the prognostic value of baseline total cholesterol (TC) levels in PBC and characterized the associated lipid metabolism. Five hundred and thirty-one patients with PBC without prior cirrhosis-related complications were randomly divided into the derivation and validation cohorts at a ratio of 7:3. Complete clinical data were obtained and analyzed. The endpoints were defined as liver-related death, liver transplantation, and cirrhosis-related complications. Lipidomics was performed in 89 patients and 28 healthy controls. Baseline TC was independently associated with poor liver-related outcomes, and adjusted C-statistics were 0.80 (95% confidence interval [CI]: 0.74–0.85) and 0.88 (95% CI: 0.78–0.91) in the derivation and validation cohorts, respectively. The predictive ability of TC for disease outcomes was stable over time and comparable with the Globe score. The 200 mg/dL cut-off optimally divided patients into low- and high-TC groups. A combination of TC and Globe score provided a more accurate stratification of patients into risk subgroups. Lipidomics indicated an up-regulation of lipid families in high-TC patients. Pathway analysis of 66 up-regulated lipids revealed the dysregulation of glycerophospholipid and sphingolipid metabolism in high-TC patients, which were associated with poor liver-related outcomes. Our results indicate that patients with PBC having baseline TC levels above 200 mg/dL have unique lipidome characteristics and are at a higher risk of poor liver-related outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]

One critical component of the immune system that prevents breast cancer cells from forming distant metastasis is natural killer (NK) cells participating in immune responses to tumors. Ginsenoside Rh2 (GRh2) as one of the major active ingredients of ginseng has been employed in treatment of cancers, but the function of GRh2 in modulating the development of breast cancer remains elusive. This study was to dissect the effect of GRh2 against breast cancer and its potential mechanisms associated with NK cells, both in vitro and in vivo. MDA-MB-231 and 4T1 cells were used to establish in situ and hematogenous mouse models. MDA-MB-231 and MCF-7 were respectively co-cultured with NK92MI cells or primary NK cells in vitro. Anti-tumor efficacy of GRh2 was verified by immunohistochemistry (IHC), Cell Counting Kit-8 (CCK8), high resolution micro-computed tomography (micro-CT) scanning of lungs and hematoxylin and eosin (H&E) staining. Lactate dehydrogenase (LDH) cytotoxicity assay, flow cytometry, in vivo depletion of NK cells, enzyme-linked immunosorbent assay (ELISA), western blot, quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunofluorescence and cell transfection were performed for investigating the anti-tumor mechanisms of GRh2. Molecular docking, microscale thermophoresis (MST) and cellular thermal shift assay (CETSA) were employed to determine the binding between endoplasmic reticulum protein 5 (ERp5) and GRh2. We demonstrated that GRh2 exerted prominent impacts on retarding the growth and metastasis of breast cancer through boosting the cytotoxic function of NK cells, as validated by the elevated release of perforin, granzyme B and interferon- γ (IFN- γ). Mechanistical studies revealed that GRh2 was capable of diminishing the expression of ERp5 and GRh2 directly bound to ERp5 in MDA-MB-231 cells as well as on a recombinant protein level. GRh2 prevented the formation of soluble MICA (sMICA) and upregulated the expression level of MICA in vivo and in vitro. Importantly, the reduced lung metastasis of breast cancer by GRh2 was almost abolished upon the depletion of NK cells. Moreover, GRh2 was able to insert into the binding pocket of ERp5 directly. We firstly demonstrated that GRh2 played a pivotal role in augmenting NK cell activity by virtue of modulating the NKG2D-MICA signaling axis via directly binding to ERp5, and may be further optimized to a therapeutic agent for the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

[Display omitted] • Acacetin weakens the proliferation, migration and invasion of osteosarcoma cells. • Acacetin promotes the apoptosis of osteosarcoma cells. • Xenograft mouse osteosarcoma model confirms the inhibitory effect in vivo. • The signal pathway is predicted by network pharmacology and confirmed by the experiments. Osteosarcoma (OS) is the most common primary malignant bone tumor with high lung metastasis and mortality rate. Neo-adjuvant chemotherapy combined with limb salvage is the main treatment strategy for OS. However, because of the tolerance to conventional chemotherapy and the cell toxicity of chemotherapy drugs, new drugs with lower toxicity for OS are urgently needed. Acacetin is a natural flavonoid compound that has inhibitory effects on many kinds of tumors. Herein, we explored the impact of acacetin on OS cell growth in vitro and in vivo. We discovered that acacetin suppressed the proliferation, migration and invasion, while promoted the apoptosis of OS cells. Notably, acacetin had little impact on proliferation and apoptosis of human normal cells. Furthermore, we confirmed that acacetin repressed the growth and metastasis of OS in xenograft mouse model in vivo. Mechanically, we discovered that acacetin activated JNK pathway and inactivated Wnt/β-catenin pathway. β-catenin over-expression or JNK inhibitor SP600125 was able to partially neutralize acacetin-induced inhibitory effect on OS cells. To sum up, our study implies that acacetin may inhibit tumor growth of human OS cells through regulating Wnt/β-catenin and JNK signaling pathways. [ABSTRACT FROM AUTHOR]

Abstract: In this study, the preparation and trophic characterization of perilla chewable tablet were investigated. Perilla chewable tablet was prepared according to the following process: mixing perilla raw materials with excipients, making wet granules, drying, tabletting and coating. The optimal formula was determined as follows: 8% perilla powder, 2.5% perilla extract powder, 20% isomaltooligosaccharide, 20% microcrystalline cellulose, 44.4% lactose, 0.5% essence of perilla, 0.1% sucralose, 2% erythritol, 2% vitamin C, 0.5% magnesium stearate. Results from nutrient analysis showed that perilla chewable tablet was rich in essential vitamins and mineral substances, which are good for human health. [Copyright &y& Elsevier]

Abstract: The objective of this study was to investigate the enzymatic preparation method of soybean oligosaccharides (S0S) from okara by using Viscozyme L, characterize the physicochemical properties as well as antioxidant activity of S0S. The effect of Viscozyme L treatment on the preparation of S0S from okara was researched by orthogonal test. Under the fixed extraction time of 2.5 h and the ratio of okara to water of 1:15 (w/v), the optimal enzymatic preparation conditions of S0S by using Viscozyme L were identified as pH of 3.5, temperature of 45 °C, enzyme dosage of 3% (w/v) with a maximum yield of 10% (w/w). S0S were found to be crude oligosaccharides containing 56.5% neutral sugar, having a low molecular weight distribution range between 860 and 9380 Da, composing of galactose, xylose, rhamnose, arabinose, mannose and glucose. Furthermore, S0S showed the free radical scavenging activity with IC50 value of 1.81 mg/mL. These results suggest that S0S are novel oligosaccharides derived from okara, and could be improve value-added utilization of okara as antioxidants in functional foods and nutraceuticals. [Copyright &y& Elsevier]

• This article first discovered that CAR can inhibit the growth of osteosarcoma. • In this article, while studying the effect of CAR on osteosarcoma, it also studies its toxic and side effects on normal cells. • This article also studies the role of CAR in vitro and in vivo. • This study confirmed the mechanism of CAR inhibiting osteosarcoma through P 38 and JNK signaling pathway inhibitors. Osteosarcoma (OS) is the most common type of bone malignant tumors. Clinical commonly used therapeutic drugs of OS treatment are prone to toxic and side effects, so it is very urgent to develop new drugs with low toxicity and low side effects. As a Chinese herbal medicine, Cardamonin (CAR) (C 16 H 14 O 4) has inhibitory effects in various tumors. In the present study, we investigated the effects of CAR on OS cells in vitro and in vivo. We found that CAR inhibited cell proliferation, reduced migration, decreased invasion, and induced G2 / M arrest of OS cells. Notably, we demonstrated that CAR had no obvious effect on proliferation and apoptosis of normal cells. Besides, CAR repressed tumor growth of OS cells in xenograft mouse model. Mechanically, we found that CAR increased the phosphorylation level of P38 and JNK. In summary, our research validates that CAR may inhibit the proliferation, migration, and invasion of OS and promote apoptosis possibly by activating P38 and JNK Mitogen-activated protein kinase (MAPK) signaling pathway. [ABSTRACT FROM AUTHOR]

• The Markov, FLUS, and InVEST models were combined for their respective strengths. • The cultivated land occupation by construction land leads to the reduction of carbon storage. • 200 m is the optimal grid scale in carbon storage prediction. • The NTS, FSS, HUS, and ESS were used to predict future changes in carbon storage. • ESS increases carbon storage by 1.51 Tg between 2020 and 2035. Carbon storage services play an important role in maintaining ecosystem stability. Land use/cover change (LUCC) is the dominant factor generating changes in the ecosystem carbon storage. Demonstrating the impact of LUCC on regional carbon storage changes and predicting future carbon storage under different land use scenarios is of great significance for promoting regional carbon peak and carbon neutrality goals. Taking the main urban area of Chongqing as an example, this study analyzes carbon storage changes from 2000 to 2020 and the response to LUCC. The Markov-FLUS model is employed to predict the land use pattern of the main urban area in 2035 under four scenarios, and the InVEST model is used to assess carbon storage in 2035 under different scenarios. The results can be summarized as follows: 1) In the past 20 years, the area of cultivated land in the main urban areas of Chongqing decreased by 743.29 km2, and the area of construction land increased by 773.48 km2. About 18.8 % of the main urban area of Chongqing was transferred, the conversion of cultivated land to construction land being the most important type of transfer. 2) In 2000, 2005, 2010, 2015, and 2020, the carbon storage in the main urban area was 59.85, 59.29, 57.90, 56.95, and 54.07 Tg, respectively, showing an annually decreasing trend with a cumulative decrease of 5.78 Tg. The cultivated land occupation by construction land is the leading factor for the rapid decrease of carbon storage. The spatial distribution of carbon storage in the main urban area differs significantly, exhibiting a low in the middle and high in the surrounding areas. 3) In 2035, the carbon storage in the main urban area shows different degrees of decline in the Natural Trend Scenario (NTS), the Food Security Scenario (FSS) and the High Urbanization Scenario (HUS), decreasing by 3.37, 0.59, and 5.25 Tg, respectively. The only increase by 1.51 Tg is found in the Ecological Security Scenario (ESS). Therefore, under the background of the "Dual Carbon" targets and the important positioning of Chongqing as an important ecological barrier in the Yangtze River Basin, the ESS can be considered in the future development planning of the main urban area of Chongqing, which can both increase carbon sink and ensure ecological security. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is a common disease, and patients often do not have satisfactory treatments. We investigated therapeutic effects of Fuxin Granules(FX) on DN and potential molecular mechanisms. We orally administered doses of FX to db/db mice for 10 weeks and measured total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol. H&E, PAS, Masson, and Oil Red O staining were used to observe the structure of kidneys and calculate indices of kidney function. We used pharmacological analysis to investigate potential mechanisms of FX. Relative mRNA and protein levels in the TGF-β1/Smad, TGF-β1/Smad, and VEGF/VEGFR2 pathways were examined. TC, TG, and LDL-C were markedly reduced, lipid accumulation was low, fibrosis reduced, kidney atrophy improved, kidney lipid droplet number significantly reduced, and glomerular filtration function improved by FX treatment. Multi-channel therapeutic effects in DN through the TGF-β1/Smad and VEGF/VEGFR2 signaling pathways occurred, and FX substantially reduced expression of TGF-β1 in the glomeruli. FX significantly inhibited TGF-β1, Smad2/3 total protein levels, Smad2/3 phosphorylation mRNA levels of TGF-β1, Smad2, and Smad3. eNOS, VEGFA, and VEGFR2 expression was regulated, levels of VEGFA and VEGFR2 were decreased, and FX increased eNOS. FX ameliorated symptoms of DN, resulting in marked improvement in hyperglycemia and hyperlipidemia and optimized structure and function of kidneys in db/db mice. FX efficacy was associated with the TGF-β1/Smad and VEGF/VEGFR2 signaling pathways. We verified this potential mechanism and hope that this study will provide benefits for the clinical treatment of DN. [Display omitted] • Fuxin Granules attenuate symptoms of hyperglycemia and hyperlipidemia in db/db mice. • Fuxin Granules aid kidney lipid droplet deposition and renal function in db/db mice. • Fuxin Granules play a multi-channel regulatory and therapeutic role. • Fuxin Granules inhibit ECM storage in db/db mice by TGF-β1/Smad pathway activation. • Fuxin Granules protect renal function in db/db mice through the VEGF/VEGFR2 pathway. [ABSTRACT FROM AUTHOR]