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Background and ObjectivesDiets containing red or processed meat are associated with a growing risk of digestive system cancers. Whether a plant-based diet is protective against cancer needs a high level of statistical evidence.MethodsWe performed a meta-analysis of five English databases, including PubMed, Medline, Embase, Web of Science databases, and Scopus, on October 24, 2021 to identify published papers. Cohort studies or case-control studies that reported a relationship between plant-based diets and cancers of the digestive system were included. Summary effect-size estimates are expressed as Risk ratios (RRs) or Odds ratios (ORs) with 95% confidence intervals and were evaluated using random-effect models. The inconsistency index (I2) and τ2 (Tau2) index were used to quantify the magnitude of heterogeneity derived from the random-effects Mantel-Haenszel model.ResultsThe same results were found in cohort (adjusted RR = 0.82, 95% CI: 0.78–0.86, P < 0.001, I2 = 46.4%, Tau2 = 0.017) and case-control (adjusted OR = 0.70, 95% CI: 0.64–0.77, P < 0.001, I2 = 83.8%, Tau2 = 0.160) studies. The overall analysis concluded that plant-based diets played a protective role in the risk of digestive system neoplasms. Subgroup analyses demonstrated that the plant-based diets reduced the risk of cancers, especially pancreatic (adjusted RR = 0.71, 95% CI: 0.59–0.86, P < 0.001, I2 = 55.1%, Tau2 = 0.028), colorectal (adjusted RR = 0.76, 95% CI: 0.69–0.83, P < 0.001, I2 = 53.4%, Tau2 = 0.023), rectal (adjusted RR = 0.84, 95% CI: 0.78–0.91, P < 0.001, I2 = 1.6%, Tau2 = 0.005) and colon (adjusted RR = 0.88, 95% CI: 0.82–0.95, P < 0.001, I2 = 0.0%, Tau2 = 0.000) cancers, in cohort studies. The correlation between vegan and other plant-based diets was compared using Z-tests, and the results showed no difference.ConclusionsPlant-based diets were protective against cancers of the digestive system, with no significant differences between different types of cancer.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022322276, Identifier: CRD42022322276.

Cisplatin-based chemotherapy and radiotherapy are the main first-line treatment strategies for nasopharyngeal carcinoma (NPC) patients. Unfortunately, resistance is a major obstacle in the clinical management of NPC patients. We prove that the expression level of high-mobility group box 1 (HMGB1) is dramatically increased in resistant NPC cells than that in sensitive cells. HMGB1 induces the expression and secretion of IL6, which leads to constitutive autocrine activation of the JAK2/STAT3 pathway and eventually contributes to chemoresistance in NPC cells. Long non-coding RNAs (lncRNAs) have been identified as key regulators involved in drug resistance. In this study, using GO analysis of the biological process and differential expression analysis, we find 12 significantly altered IncRNAs in NPC cell lines, which may be involved in regulating gene expression. Furthermore, we determine that elevated lncRNA MIAT level upregulates HMGB1 expression, contributing to cisplatin resistance in NPC cells. We find that the deficiency of the lncRNA MIAT/HMGB1 axis, inhibition of JAK2/STAT3, or neutralization of IL6 by antibodies significantly re-sensitizes resistant NPC cells to cisplatin in resistant NPC cells. Moreover, we provide the in vivo evidence that the deficiency of HMGB1 reduces cisplatin-resistant tumor growth. Most importantly, we provide clinical evidence showing that the expression level of the lncRNA MIAT/HMGB1/IL6 axis is elevated in resistant NPC tumors, which is highly correlated with poor clinical outcome. Our findings identify a novel chemoresistance mechanism regulated by the lncRNA MIAT/HMGB1/IL6 axis, which indicates the possibilities for lncRNA MIAT, HMGB1, and IL6 as biomarkers for chemoresistance and targets for developing novel strategies to overcome resistance in NPC patients.

Protein tyrosine phosphatase 1B (PTP1B) is an established therapeutic target for type 2 diabetes mellitus (T2DM) and obesity. The aim of this study was to investigate the inhibitory activity of Magnolia officinalis extract (ME) on PTP1B and its anti-T2DM effects. Inhibition assays and inhibition kinetics of ME were performed in vitro. 3T3-L1 adipocytes and C2C12 myotubes were stimulated with ME to explore its bioavailability in cell level. The in vivo studies were performed on db/db mice to probe its anti-T2DM effects. In the present study, ME inhibited PTP1B in a reversible competitive manner and displayed good selectivity against PTPs in vitro. Furthermore, ME enhanced tyrosine phosphorylation levels of cellular proteins, especially the insulin-induced tyrosine phosphorylations of insulin receptor β-subunit (IRβ) and ERK1/2 in a dose-dependent manner in stimulated 3T3-L1 adipocytes and C2C12 myotubes. Meanwhile, ME enhanced insulin-stimulated GLUT4 translocation. More importantly, there was a significant decrease in fasting plasma glucose level of db/db diabetic mice treated orally with 0.5 g/kg ME for 4 weeks. These findings indicated that improvement of insulin sensitivity and hypoglycemic effects of ME may be attributed to the inhibition of PTP1B. Thereby, we pioneered the inhibitory potential of ME targeted on PTP1B as anti-T2DM drug discovery.

BackgroundBreast cancer is one of the most frequently occurring cancers in women. In recent years, Dendrobium candidum has played a part in antihyperthyroidism and anticancer drugs. This study aims to examine the antitumor effect of D. candidum on breast cancer.MethodsHuman breast cancer cell line MCF-7 and normal breast epithelial cell line MCF10A were used to observe the effects of D. candidum treatment on human breast cancer. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was employed to examine the cell proliferation of the MCF-7 and MCF10A cells. Western blot analysis and reverse transcription polymerase chain reaction were used to detect the key molecules and biomarkers in breast cancer pathology. Cell cycle was analyzed by using Becton Dickinson FACScan cytofluorometer.ResultsThe results indicated that D. candidum significantly decreased cell viability at different concentrations compared to the control group (P<0.05). D. candidum-treated MCF-7 cells in the G2/M phase was significantly increased compared to the control group (P<0.05). The messenger RNA levels of estrogen receptor alpha, IGFBP2, IGFBP4, and GATA3 were significantly decreased, and the messenger RNA and protein levels of ELF5, p53, p21, p18, CDH1, CDH2, and p12 were significantly increased, compared to the control group (P<0.05). The protein levels of estrogen receptor alpha, PGR, GATA3, and Ki67 were significantly decreased and the protein levels of p53 and ELF5 were significantly increased compared to the control group (P<0.05). The general apoptosis biomarker, Bcl-2, was significantly decreased and the Bax was significantly increased compared to the control group (P<0.05). In contrast to that in MCF-7, D. candidum does not affect cell proliferation at any concentration and any time points in normal breast epithelial cells, MCF10A cells.ConclusionD. candidum could decrease the cell viability of MCF-7 cells by inducing cell cycle arrest at the G2/M phase and regulating the key biomarkers in breast cancer cells.

BackgroundHonokiol is one of the main bioactive constituents of the traditional Chinese herbal drug Magnolia bark (Cortex Magnoliae officinalis, Hou Po). The aim of this study was to probe its anti-type 2 diabetes mellitus effects and the underlying mechanism.MethodsType 2 diabetic mouse model was established by intraperitoneally injecting with streptozotocin. Fasting blood glucose, body weight, and lipid profile were measured. The subcutaneous adipose tissue, skeletal muscle, and liver were isolated as well as homogenized. The phospho-insulin receptor β-subunit (IRβ), IRβ, phospho-AKT, AKT, phospho-ERK1/2, ERK1/2, phosphotyrosine, and actin were examined by Western blot assay. Cell viability or cytotoxicity was analyzed by using MTT method. The inhibitory potencies of honokiol on the protein tyrosine phosphatase 1B (PTP1B) activity were performed in reaction buffer. Molecular docking and dynamic simulation were also analyzed.ResultsIn in vivo studies, oral treatment with 200 mg/kg honokiol for 8 weeks significantly decreases the fasting blood glucose in type 2 diabetes mellitus mice. The phosphorylations of the IRβ and the downstream insulin signaling factors including AKT and ERK1/2 significantly increase in adipose, skeletal muscle, and liver tissue of the honokiol-treated mice. Moreover, honokiol enhanced the insulin-stimulated phosphorylations of IRβ, AKT, and ERK1/2 in a dose-dependent manner in C2C12 myotube cells. Meanwhile, honokiol enhanced insulin-stimulated GLUT4 translocation. Importantly, honokiol exhibited reversible competitive inhibitory activity against PTP1B with good selectivity in vitro and in vivo. Furthermore, using molecular docking and dynamic simulation approaches, we determined the potential binding mode of honokiol to PTP1B at an atomic level.ConclusionThese findings indicated the hypoglycemic effects of honokiol and its mechanism that honokiol improved the insulin sensitivity by targeting PTP1B. Therefore, our study may highlight honokiol as a promising insulin sensitizer for the therapy of type 2 diabetes.

Manganese (Mn) plays an essential role in plant growth; however, excessive Mn is toxic to plants. Polygonum lapathifolium Linn. was tested as a novel Mn-hyperaccumulating species in our previous study, but the underlying mechanisms of this hyperaccumulation are poorly understood. A hydroponic experiment with (8 mmol L−1) and without additional Mn (CK) was established to explore the possible mechanisms through the effects on photosynthesis-related physiological characteristics and metabolomics. The results showed that additional Mn increased plant biomass, photosynthesis, and stomatal conductance related to increases in the effective photochemical quantum yield of photosystem II and relative electron transport rate (P < 0.05). The results from liquid chromatography–mass spectrometry revealed 56 metabolites differentially accumulated between the plants composing these two groups. Metabolites were enriched in 20 metabolic pathways at three levels (environmental information processing, genetic information processing, and metabolism), of which five metabolic pathways were associated with significant or extremely significant changes (P < 0.05). These five enriched pathways were ABC transporters (environmental information processing), aminoacyl-tRNA biosynthesis (genetic information processing), biosynthesis of amino acids, d-arginine and d-ornithine metabolism, and arginine biosynthesis (metabolism). Flavonoids may play a key role in Mn tolerance, as they accumulated more than 490-fold, and the relationship between flavonoids and Mn tolerance needs to be studied in the future.

The polycomb repressive complex 2 (PRC2) maintains the transcriptional repression of target genes through its catalytic component enhancer of zeste homolog 2 (EZH2). Through modulating critical gene expression, EZH2 also plays a role in cancer development and progression by promoting cancer cell survival and invasion. Mutations in EZH2 are prevalent in certain B-cell lymphoma subtypes such as diffuse large cell lymphoma and follicular lymphoma; while no EZH2 mutation has been reported in the mantle cell lymphoma (MCL). Here we demonstrate that the PRC2 components EZH2, EED and SUZ12 are upregulated in the MCL cells as compared to normal B-cells. Moreover, stably transfected cells with wild-type EZH2 or-EED showed increased cell growth and H3K27-trimehtylation. However, unlike wild-type EZH2, ectopic expression of a deletion construct of EZH2 (EZH2 550−738 lacking SET domain) had no growth advantage over control cells. Pharmacological inhibition of EZH2 suppressed H3K27me3 and had significant inhibitory effect on cell growth and colony forming capacity (p < 0.05) of MCL cells, and this effect was more or less comparable to the anti-proliferative effects of EZH2 inhibition in cells harboring EZH2-mutation. Mechanistically, EZH2 appears to downregulate expression of cdkn2b gene via enhanced H3K27me3, a well-known suppressive epigenetic mark, at the cdkn2b promoter region. Overall, these results highlight that deregulation of PRC2/EZH2 is associated with epigenetic suppression of cdkn2b in MCL, and in part responsible for increased cell growth, thus the EZH2 inhibitors may have therapeutic potential in the patients with MCL.