Therapeutic effects of epigallocatechin-3-gallate for inflammatory bowel disease: A preclinical meta-analysis.

BACKGROUND: Epigallocatechin-3-gallate (EGCG), the primary active compound in green tea, is recognized for its significant anti-inflammatory properties and potential pharmacological effects on inflammatory bowel disease (IBD). However, comprehensive preclinical evidence supporting the use of EGCG in treating IBD is currently insufficient. PURPOSE: To evaluate the efficacy of EGCG in animal models of IBD and explore potential underlying mechanisms, serving as a groundwork for future clinical investigations. METHODS: A systematic review of pertinent preclinical studies published until September 1, 2023, in databases such as PubMed, Embase, Web of Science, and Cochrane Library was conducted, adhering to stringent quality criteria. The potential mechanisms via which EGCG may address IBD were summarized. STATA v16.0 was used to perform a meta-analysis to assess IBD pathology, inflammation, and indicators of oxidative stress. Additionally, dose-response analysis and machine learning models were utilized to evaluate the dose-effect relationship and determine the optimal dosage of EGCG for IBD treatment. RESULTS: The analysis included 19 studies involving 309 animals. The findings suggest that EGCG can ameliorate IBD-related pathology in animals, with a reduction in inflammatory and oxidative stress indicators. These effects were observed through significant changes in histological scores, Disease Activity Index, Colitis Macroscopic Damage Index and colon length; a decrease in markers such as interleukin (IL)-1ß, IL-6 and interferon-γ; and alterations in malondialdehyde, superoxide dismutase, glutathione, and catalase levels. Subgroup analysis indicated that the oral administration route of EGCG exhibited superior efficacy over other administration routes. Dose-response analysis and machine learning outcomes highlighted an optimal EGCG dosage range of 32-62 mg/kg/day, with an intervention duration of 4.8-13.6 days. CONCLUSIONS: EGCG exhibits positive effects on IBD, particularly when administered at the dose range of 32 - 62 mg/kg/day, primarily attributed to its ability to regulate inflammation and oxidative stress levels.

Differential structure and function of phosphorus-mineralizing microbial communities in organic and upper mineral soil horizons across a temperate rainforest chronosequence.

Microbial community structure and function were assessed in the organic and upper mineral soil across a ~4000-year dune-based chronosequence at Big Bay, New Zealand, where total P declined and the proportional contribution of organic soil in the profile increased with time. We hypothesized that the organic and mineral soils would show divergent community evolution over time with a greater dependency on the functionality of phosphatase genes in the organic soil layer as it developed. The structure of bacterial, fungal, and phosphatase-harbouring communities was examined in both horizons across 3 dunes using amplicon sequencing, network analysis, and qPCR. The soils showed a decline in pH and total phosphorus (P) over time with an increase in phosphatase activity. The organic horizon had a wider diversity of Class A (phoN/phoC) and phoD-harbouring communities and a more complex microbiome, with hub taxa that correlated with P. Bacterial diversity declined in both horizons over time, with enrichment of Planctomycetes and Acidobacteria. More complex fungal communities were evident in the youngest dune, transitioning to a dominance of Ascomycota in both soil horizons. Higher phosphatase activity in older dunes was driven by less diverse P-mineralizing communities, especially in the organic horizon.

Dietary supplementation of magnolol alleviates fatty liver hemorrhage syndrome in postpeak Xinhua laying hens via regulation of liver lipid metabolism.

As a metabolic disease, fatty liver hemorrhagic syndrome (FLHS) has emerged as a major cause of noninfectious mortality in laying hens, resulting in substantial economic losses to the poultry industry. This study aimed to investigate the therapeutic effects of magnolol on FLHS in postpeak laying hen model, focusing on lipid metabolism, antioxidative capacity, and potential molecular mechanisms of action. We selected 150 Xinhua laying hens aged 50 wk and divided them into normal diet group (ND), high-fat diet group (HFD), 100 mg/kg magnolol group (MG100), 300 mg/kg magnolol group (MG300), 500 mg/kg magnolol group (MG500) on average. The experiment lasted for 6 wk, and liver samples were collected from the hens at the end of the experiment. The results demonstrated that the inclusion of magnolol in the diet had a significant impact on various factors. It led to a reduction in weight, an increase in egg production rate, a decrease in blood lipid levels, and an improvement in abnormal liver function, liver steatosis, and oxidative stress. These effects were particularly prominent in the MG500 group. The RNA-Seq analysis demonstrated that in the MG500 group, there was a down-regulation of genes associated with fatty acid synthesis (Acc, Fasn, Scd, Srebf1, Elovl6) compared to the HFD group. Moreover, genes related to fatty acid oxidation (CPT1A and PGC1α) were found to be up-regulated. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of these differentially expressed genes indicated their enrichment in the PPAR signaling pathway. These findings demonstrate that magnolol can mitigate FLHS by inhibiting fatty acid synthesis and promoting fatty acid oxidation. This discovery offers a novel approach for treating FLHS in laying hens, reducing the economic losses associate with FLHS.

An autocatalytic multicomponent DNAzyme nanomachine for tumor-specific photothermal therapy sensitization in pancreatic cancer.

Multicomponent deoxyribozymes (MNAzymes) have great potential in gene therapy, but their ability to recognize disease tissue and further achieve synergistic gene regulation has rarely been studied. Herein, Arginylglycylaspartic acid (RGD)-modified Distearyl acylphosphatidyl ethanolamine (DSPE)-polyethylene glycol (PEG) (DSPE-PEG-RGD) micelle is prepared with a DSPE hydrophobic core to load the photothermal therapy (PTT) dye IR780 and the calcium efflux pump inhibitor curcumin. Then, the MNAzyme is distributed into the hydrophilic PEG layer and sealed with calcium phosphate through biomineralization. Moreover, RGD is attached to the outer tail of PEG for tumor targeting. The constructed nanomachine can release MNAzyme and the cofactor Ca2+ under acidic conditions and self-assemble into an active mode to cleave heat shock protein (HSP) mRNA by consuming the oncogene miRNA-21. Silencing miRNA-21 enhances the expression of the tumor suppressor gene PTEN, leading to PTT sensitization. Meanwhile, curcumin maintains high intracellular Ca2+ to further suppress HSP-chaperone ATP by disrupting mitochondrial Ca2+ homeostasis. Therefore, pancreatic cancer is triple-sensitized to IR780-mediated PTT. The in vitro and in vivo results show that the MNAzyme-based nanomachine can strongly regulate HSP and PTEN expression and lead to significant pancreatic tumor inhibition under laser irradiation.

Cumulative Sum Chart as Complement to Objective Assessment of Graduating Surgical Resident Competency: An Exploratory Study.

BACKGROUND: Rater-based assessment and objective assessment play an important role in evaluating residents' clinical competencies. We hypothesize that a cumulative sum (CUSUM) chart of operative time is a complement to the assessment of chief general surgery residents' competencies with ACGME Milestones, aiding residency programs' determination of graduating residents' practice readiness. STUDY DESIGN: We extracted ACGME Milestone evaluations of performance of operations and procedures (POP) and 3 objective metrics (operative time, case type, and case complexity) from 3 procedures (cholecystectomy, colectomy, and inguinal hernia) performed by 3 cohorts of residents (N = 15) during their PGY4-5. CUSUM charts were computed for each resident on each procedure type. A learning plateau was defined as at least 4 cases consistently locating around the centerline (target performance) at the end of a CUSUM chart with minimal deviations (range 0 to 1). RESULTS: All residents reached the ACGME graduation targets for the overall POP by the end of chief year. A total of 2,446 cases were included (cholecystectomy N = 1234, colectomy N = 507, and inguinal hernia N = 705), and 3 CUSUM chart patterns emerged: skewed distribution, bimodal distribution, and peaks and valleys distribution. Analysis of CUSUM charts revealed surgery residents' development processes in the operating room towards a learning plateau vary, and only 46.7% residents reach a learning plateau in all 3 procedures upon graduation. CONCLUSIONS: CUSUM charts of operative time complement the ACGME Milestones evaluations. The use of both may enable residency programs to holistically determine graduating residents' practice readiness and provide recommendations for their upcoming career/practice transition.

The effectiveness of photobiomodulation therapy on inferior alveolar nerve injury: A systematic review and META-analysis.

OBJECTIVE: The aim of this META-analysis was to evaluate the efficacy of photobiomodulation (PBM) therapy in the treatment of inferior alveolar nerve (IAN) injury due to orthognathic surgeries, extraction of impacted third molars and mandibular fractures. METHODS AND MATERIALS: A electric search was conducted by a combination of manual search and four electric databases including Pubmed, Embase, Cochrane library and Web of Science, with no limitation on language and publication date. Gray literature was searched in ClinicalTrials.gov and googlescholar. All retrieved articles were imported into ENDNOTE software (version X9) and screened by two independent reviewers. All analysis was performed using the REVMAN software (version 5.3). RESULTS: Finally, 15 randomized controlled trials met the inclusion criteria for qualitative analysis and 14 for META-analysis from 219 articles. The results showed that PBM therapy had no effect on nerve injury in a short period of time (0-48h, 14 days), but had significant effect over 30 days. However, the effect of photobiomodulation therapy on thermal discrimination was still controversial, most authors supported no significant improvement. By calculating the effective rate of PBM, it was found that there was no significant difference in the onset time of treatment, whether within or over 6 months. CONCLUSIONS: The results of this META-analysis show that PBM therapy is effective in the treatment of IAN injures no matter it begins early or later. However, due to the limited number of well-designed RCTs and small number of patients in each study, it would be necessary to conduct randomized controlled trials with large sample size, long follow-up time and more standardized treatment and evaluation methods in the future to provide more accurate and clinically meaningful results.

Renal transporter OAT1 and PPAR-α pathway co-contribute to icaritin-induced nephrotoxicity.

This study aimed to investigate the potential nephrotoxicity of icaritin and the underlying mechanism by in vitro-in vivo experiment technology combined with proteomics technology. First, icaritin showed a significant cytotoxic effect on HK-2 cells, which was accompanied by increased LDH and TNF-α in the supernatant, decreased protein expressions of Bcl-2 and increased Bax and enhanced apoptosis of HK-2 cells as measured by TUNEL staining. Moreover, icaritin induced obvious tubular damage and up-regulation of BUN and CRE levels in plasma in mice. Second, intracellular uptake of icaritin was considerably higher in hOAT1-HEK293 cells than in mock-HEK293 cells, suggesting that icaritin might accumulate in renal cells via OAT1 uptake. Importantly, icaritin caused significant changes in the PPAR signaling pathway in HK2 cells through proteomic analysis. Then, in vitro and in vivo results verified that icaritin significantly downregulated the protein expression of PPAR-α as well as downregulated APOB, ACSL3, ACSL4, and upregulated 5/12/15-HETE, implying that a lipid metabolism disorder was involved in the icaritin-induced nephrotoxicity. Finally, icaritin was found to increase the accumulation of iron and LPO levels while reducing the activity of GPX4, suggesting that ferroptosis was involved in the nephrotoxicity induced by icaritin.

Comparative Inhibitory Effects of Natural Biflavones from Ginkgo against Human CYP1B1 in Recombinant Enzymes and MCF-7 Cells.

Human cytochrome P450 1B1 (CYP1B1) is an extrahepatic enzyme overexpressed in many tumors and associated with angiogenesis. Ginkgetin, isoginkgetin, sciadopitysin, and amentoflavone, the primary biflavones found in Ginkgo biloba, have excellent anti-inflammatory and anti-tumor effects. However, the effect of biflavones on CYP1B1 activities remains unknown. In this study, 7-ethoxyresorufin O-deethylation (EROD) was used to characterize the activities of CYP1 families. The impacts of four ginkgo biflavones on CYP1B1 activity and the cellular protein expression of CYP1B1 were systematically investigated. The results showed that amentoflavone with six hydroxyl substituents exhibited the most potent selective inhibitory effect on CYP1B1 activity with IC50 of 0.054 µM in four biflavones. Sciadopitysin, with three hydroxyl and three methoxy substituents, had the weakest inhibitory activity against CYP1B1. Ginkgetin and isoginkgetin, both with four hydroxyl and two methoxy substituents, showed similar inhibitory intensity towards CYP1B1 with IC50 values of 0.289 and 0.211 µM, respectively. Kinetic analysis showed that ginkgetin and amentoflavone inhibited CYP1B1 in a non-competitive mode, whereas sciadopitysin and isoginkgetin induced competitive or mixed types of inhibition. Notably, four ginkgo biflavones were also confirmed to suppress the protein expressions of CYP1B1 and AhR in MCF-7. Furthermore, molecular docking studies indicated more hydrogen bonds formed between amentoflavone and CYP1B1, which might explain the strongest inhibitory action towards CYP1B1. In summary, these findings suggested that biflavones remarkably inhibited both the activity and protein expression of CYP1B1 and the inhibitory activities enhanced with the increasing hydroxyl substitution, providing new insights into the anti-tumor potentials of biflavones.

Unraveling the Structure-Dependent Inhibitory Effects of Ginsenoside Series Compounds on Human Cytochrome P450 1B1.

BACKGROUND: Cytochrome P450 1B1(CYP1B1) is an extrahepatic P450 isoenzyme that can participate in processes of undermining the effectiveness and safety of anti-cancer therapy. Ginsenosides are the main active ingredients in ginseng, which possesses rich pharmacological activities, including anti-cancer activity and organ protection. However, the effect of ginsenosides on the activity of CYP1B1 remains unclear. OBJECTIVE: The present study aimed to investigate the inhibitory effect of ginsenosides on CYP1B1 and reveal the structure-inhibitory activity relationship. METHODS: Firstly, recombinant CYP1B1 and EROD reactions were used to evaluate the inhibitory effect of ginsenosides. Secondly, molecular docking was used to simulate the interactions between ginsenosides and CYP1B1. Finally, the structure-inhibitory activity relationship was analyzed. RESULTS: The ginsenosides, Rb2, Rd, and Rg3, significantly inhibited CYP1B1; the ginsenoside Rd showed the strongest inhibition effect, with a Ki value of 47.37 µM in non-competitive mode. Notably, ginsenoside Rd formed hydrogen bonds with two key amino acid residues of CYP1B1, and one bond was between the glycosyl in position 20 and ALA330, which also made ginsenoside Rd close to the heme iron of CYP1B1. In contrast, ginsenosides, Rb2 and Rg3, which showed weaker inhibition, interacted with only one CYP1B1 residue by the hydrogen bond, which was far away from the heme iron. Finally, the structure-inhibitory activity relationship analysis demonstrated that the number of glycosyls in position 20 and the type of sapogenins in the ginsenoside structure are the key factors determining inhibitory activity. Meanwhile, ALA330 was a vital amino acid in the potent inhibition of CYP1B1 by ginsenosides. CONCLUSION: A structure-dependent inhibitory effect on CYP1B1 was revealed for ginsenosides, among which ginsenoside Rd showed the strongest inhibition due to its mono-glycosyl in position 20 of the ginsenoside parent structure. These findings would provide evidence for the synthesis of novel CYP1B1 inhibitors to augment the anti-cancer therapeutic effect.

Effect of hyperthermic intraperitoneal chemotherapy in combination with cytoreductive surgery on the prognosis of patients with colorectal cancer peritoneal metastasis: a systematic review and meta-analysis.

BACKGROUND: Peritoneal metastasis often occurs in patients with colorectal cancer peritoneal metastasis, and the prognosis is poor. A large body of evidence highlights the beneficial effects of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on survival, but to date, there is little consensus on the optimal treatment strategy for patients with colorectal cancer peritoneal metastasis. The purpose of this study is to evaluate the impact of CRS + HIPEC on survival and provide reference for the treatment of patients with colorectal cancer peritoneal metastasis. METHODS: This systematic review and meta-analysis is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The PubMed, Embase, Cochrane, Web of Knowledge, and ClinicalTrials.gov databases were screened from inception of the review to March 11, 2022. Ten studies were included in qualitative and quantitative analysis. RESULTS: A total of 3200 patients were enrolled in the study, including 788 patients in the CRS and HIPEC groups and 2412 patients in the control group, of which 3 were randomized controlled trials and 7 were cohort studies. The 3 randomized controlled studies were of high quality, and the quality scores of the 7 cohort studies were all 7 or above, indicating high quality. The results showed that the OS of CRS + HIPEC group was higher than that of control group (HR: 0.53, 95% CI: 0.38-0.73; P < 0.00001, I2 = 82.9%); the heterogeneity of the studies was large. The subgroup analysis showed that the OS of CRS and HIPEC group was higher than that of PC group (HR: 0.37, 95% CI: 0.30-0.47; P = 0.215, I2 = 31%) and higher than that in CRS group (HR: 0.73, 95% CI: 0.49-1.07; P = 0.163, I2 = 44.8%); the heterogeneity of the studies was low. In the OPEN group, the OS of THE CRS and HIPEC groups was higher than that in the control group (HR: 0.51, 95% CI: 0.38-0.70; P = 0.353, I2 = 3.9%); OPEN group showed lower heterogeneity. The OS of 60-100-min group was higher than that in the control group (HR: 0.65, 95% CI: 0.49-0.88; P = 0.172, I2 = 37.4%); the heterogeneity of the studies was low. Sensitivity analysis showed that there was no significant difference in the results of the combined analysis after each study was deleted. The results of publication bias showed that the P-value of Egger and Begg tests was 0.078 > 0.05, indicating that there is no publication bias. CONCLUSIONS: CRS + HIPEC can improve the survival rate of patients with colorectal cancer peritoneal metastasis.

Dietary Selenium Alleviated Mouse Liver Oxidative Stress and NAFLD Induced by Obesity by Regulating the KEAP1/NRF2 Pathway.

Nonalcoholic fatty liver disease (NAFLD) occurs when excess fat is stored in the liver and it is strongly linked with metabolic syndrome and oxidative stress. Selenium (Se) is an essential micronutrient in animals, which has a variety of biological functions, including antioxidant and anti-inflammatory. However, the exact effect of dietary selenium on NAFLD and the underlying molecular mechanism are not yet clear. Herein, we fed a high-fat diet (HFD) to C57BL/6 mice to construct an in vivo NAFLD model, treated AML-12 cells with palmitic acid (PA) to construct an in vitro NAFLD model, and AML-12 cells were stimulated with H2O2 to induce hepatocyte oxidative stress and then treated with adequate selenium. We observed that adequate selenium significantly improved the hepatic injury and insulin resistance in HFD mice, and decreased the fat accumulation and the expression of lipogenic genes in PA-induced AML-12 cells. Meanwhile, selenium significantly inhibited the production of reactive oxygen species (ROS), inhibited apoptosis, and restored mitochondrial number and membrane potential in PA- induced AML-12 cells. In addition, selenium can promote selenoproteinP1 (SEPP1) synthesis to regulate the Kelch-like ECH-associated protein 1 (KEAP1)/NF-E2-related factor 2 (NRF2) pathway, so as to defend against hepatocyte oxidative stress. These findings suggest that dietary selenium supplementation can effectively resist hepatic injury and insulin resistance during NAFLD development, and regulate the KEAP1/NRF2 pathway to resist oxidative stress by promoting SEPP1 synthesis.

Hedyotis diffusae Herba-Andrographis Herba inhibits the cellular proliferation of nasopharyngeal carcinoma and triggers DNA damage through activation of p53 and p21.

Dysregulation of the cell cycle and the resulting aberrant cellular proliferation has been highlighted as a hallmark of cancer. Certain traditional Chinese medicines can inhibit cancer growth by inducing cell cycle arrest. In this study we explore the effect of Hedyotis diffusae Herba-Andrographis Herba on the cell cycle of nasopharyngeal carcinoma (NPC). Hedyotis diffusae Herba-Andrographis Herba-containing serum was prepared and then added to the cell culture medium. BrdU, comet, and FUCCI assays, western blot analysis and flow cytometry analysis revealed that Hedyotis diffusae Herba-Andrographis Herba treatment significantly alters cell proliferation, DNA damage, and cell cycle distribution. Xenograft mouse model experiments were performed, confirming these in vitro findings in vivo. Treatment with Hedyotis diffusae Herba-Andrographis Herba inhibited cell proliferation, promoted DNA damage, and arrested NPC cells progression from G1 to S phase. Further examination of the underlying molecular mechanisms revealed that treatment with Hedyotis diffusae Herba-Andrographis Herba increased the expression of p53 and p21, while reducing that of CCND1, Phospho-Rb, E2F1, γH2AX, and Ki-67 both in vivo and in vitro. Conversely, the inhibition of p53 and p21 could abolish the promoting effect of Hedyotis diffusae Herba-Andrographis Herba on the NPC cell cycle arrest at the G1 phase, contributing to the proliferation of NPC cells. Hedyotis diffusae Herba-Andrographis Herba suppressed the tumor growth in vivo. Overall, these findings suggest that Hedyotis Diffusae Herba-Andrographis prevent the progression of NPC by inducing NPC cell cycle arrest at the G1 phase through a p53/p21-dependent mechanism, providing a novel potential therapeutic treatment against NPC.

Perioperative nutrition management for gastric cancer.

Gastric cancer is one of the most frequently diagnosed and the leading cause of cancer death worldwide. Malnutrition is a substantial problem in patients with gastric cancer, associated with poor treatment tolerance and increased morbidity. It has also been recognized as an independent prognostic factor in individuals with cancer. Early detection of malnutrition and effective perioperative nutrition intervention play an important role in the treatment of gastric cancer. Nutrition screening and assessment are the first steps in nutrition management and provide a basis for further nutrition support. Several tools, including the Nutrition Risk Screening-2002 and Patient-Generated Subjective Global Assessment, have been developed for nutrition screening and assessment. Effective nutrition support can significantly improve nutritional and immune status, reduce the incidence of postoperative complications, and accelerate recovery. The aim of this review was to focus on preoperative nutrition risk screening and assessment, and perioperative nutrition support, which may serve as a framework of perioperative nutrition management for gastric cancer.

Application of Machine Learning in Intelligent Medical Image Diagnosis and Construction of Intelligent Service Process.

The introduction of digital technology in the healthcare industry is marked by ongoing difficulties with implementation and use. Slow progress has been made in unifying different healthcare systems, and much of the globe still lacks a fully integrated healthcare system. As a result, it is critical and advantageous for healthcare providers to comprehend the fundamental ideas of AI in order to design and deliver their own AI-powered technology. AI is commonly defined as the capacity of machines to mimic human cognitive functions. It can tackle jobs with equivalent or superior performance to humans by combining computer science, algorithms, machine learning, and data science. The healthcare system is a dynamic and evolving environment, and medical experts are constantly confronted with new issues, shifting duties, and frequent interruptions. Because of this variation, illness diagnosis frequently becomes a secondary concern for healthcare professionals. Furthermore, clinical interpretation of medical information is a cognitively demanding endeavor. This applies not just to seasoned experts, but also to individuals with varying or limited skills, such as young assistant doctors. In this paper, we proposed the comparative analysis of various state-of-the-art methods of deep learning for medical imaging diagnosis and evaluated various important characteristics. The methodology is to evaluate various important factors such as interpretability, visualization, semantic data, and quantification of logical relationships in medical data. Furthermore, the glaucoma diagnosis system is discussed in detail via qualitative and quantitative approaches. Finally, the applications and future prospects were also discussed.

Analysis of Anesthesia Effect of Dexmedetomidine in Clinical Operation of Replantation of Severed Finger.

Brachial plexus block commonly used in finger replantation has the advantages of simple operation, small side effects, and stable circulation, but it has inherent problems such as imperfect block range, slow onset of anesthesia, and short maintenance time of anesthesia. In order to explore the reliable clinical anesthesia effect, this paper uses experimental investigation methods to study the effect of dexmedetomidine in clinical surgery of replantation of severed fingers. Moreover, this paper uses comparative test methods, uses statistical methods to process test data, and uses intuitive methods to display test results. Finally, this paper verifies the reliability of dexmedetomidine in replantation of severed finger through comparative analysis and verifies that the anesthesia method proposed in this paper has certain user satisfaction through parameter survey.

Curcumin Inhibits HGF-Induced EMT by Regulating c-MET-Dependent PI3K/Akt/mTOR Signaling Pathways in Meningioma.

Meningiomas, which are the most common primary intracranial tumors, have highly aggressive cells in malignant cases. Due to its extensive antitumor effects, curcumin is widely used in experimental and clinical studies. However, the role of curcumin during the epithelial-mesenchymal transition (EMT) in meningioma has not been established. We found that curcumin blocks hepatocyte growth factor- (HGF-) induced proliferation, migration, invasion, and EMT of human malignant meningioma cells by regulating the PI3K/Akt/mTOR signaling pathway. In addition, treatment of human malignant meningioma cells with the tyrosine protein kinase (c-MET) inhibitor (SU11274) or the phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) suppressed HGF-induced migration and EMT. Furthermore, we found that curcumin inhibited tumor growth and HGF-induced EMT in mice subjected to subcutaneous xenotransplantation. These findings indicate that HGF regulates EMT in human malignant meningioma cells through c-MET/PI3K/Akt/mTOR modulation. In conclusion, curcumin inhibits HGF-induced EMT by targeting c-MET and subsequently blocking the PI3K/Akt/mTOR pathway.

Effects of Mindfulness-Based Cognitive Therapy on Stigma in Female Patients With Schizophrenia.

Mindfulness-based cognitive therapy (MBCT) has been increasingly recognized as effective in different mental illnesses, but these effects are limited in schizophrenia. For patients with schizophrenia, stigma is one of the most negative factors that affects treatment, rehabilitation and social function. This research aimed to determine the effects of MBCT on stigma in patients with schizophrenia. In total, 62 inpatients with schizophrenia were recruited and randomly assigned to the experimental group or control group. The experimental group received an 8-week MBCT intervention, and the control group were treated as usual. Link's Stigma Scales (with three subscales, including perceived devaluation-discrimination (PDD), stigma-coping orientation, and stigma-related feeling), Five Facet Mindfulness Questionnaire (FFMQ), and Insight and Treatment Attitudes Questionnaire (ITAQ) were used to collect data before and after intervention. After intervention, the post-test score of PDD, stigma-coping orientation, FFMQ, and ITAQ were significantly different between the experimental group and the control group. In the experimental group, the PDD and stigma-coping orientation scores significantly decreased, and FFMQ and ITAQ scores increased remarkably (P < 0.05). In addition, correlation analysis revealed a significant negative correlation between mindfulness and stigma. MBCT was effective in reducing stigma in patients with schizophrenia, which mainly manifested as changes in the patients' perception of stigma as well as the withdrawal and avoidance caused by schizophrenia. Enhancing mindfulness will help reduce the stigma level. MBCT is worthy of promotion and application in patients with schizophrenia.

Biochar application under low phosphorus input promotes soil organic phosphorus mineralization by shifting bacterial phoD gene community composition.

Biochar has the potential to enhance microbial-mediated phosphorus (P) cycling in soils, but the underlying mechanisms remain largely unknown. We hypothesized that biochar amendment could enhance the production of acid and alkaline phosphomonoesterase, phosphodiesterase and P mineralization, which may vary depending on the P input. To test this hypothesis, we assessed the impacts of rice straw biochar application (0 and 4%) under different P-input rates (0, 30 and 90 kg P ha-1) on the relationships among P fractions, phosphatase activities and alkaline phosphomonoesterase-encoding bacterial (phoD gene) communities in an acidic soil. Biochar application under low P input (< 30 kg P ha-1) significantly increased the activities of phosphodiesterase and alkaline phosphomonoesterase but not that of acid phosphomonoesterase and depleted organic P. The results from the structural equation model revealed a dominant role of alkaline phosphomonoesterase in P mineralization. The increase in alkaline phosphomonoesterase activity was not related to an increase in phoD gene abundance but was due to a shift in community composition, which was primarily driven by the soil C:P ratio. Microbial network analysis demonstrated a more complex phoD gene community with more functionally interrelated groups as a result of biochar application under low P input than under high P input. Moreover, the specific enrichment of Micromonosporaceae under C-rich and P-poor conditions may play a critical role in alkaline phosphomonoesterase production and potential P mineralization. In conclusion, we demonstrated that biochar application under low P input supports a more organized phoD gene community and preferentially enriches taxa in terms of their capacity for P mineralization, which in turn may enhance P bioavailability and plant P acquisition.

Gut microbiota from patients with arteriosclerotic CSVD induces higher IL-17A production in neutrophils via activating RORγt.

The intestinal microbiota shape the host immune system and influence the outcomes of various neurological disorders. Arteriosclerotic cerebral small vessel disease (aCSVD) is highly prevalent among the elderly with its pathological mechanisms yet is incompletely understood. The current study investigated the ecology of gut microbiota in patients with aCSVD, particularly its impact on the host immune system. We reported that the altered composition of gut microbiota was associated with undesirable disease outcomes and exacerbated inflammaging status. When exposed to the fecal bacterial extracts from a patient with aCSVD, human and mouse neutrophils were activated, and capacity of interleukin-17A (IL-17A) production was increased. Mechanistically, RORγt signaling in neutrophils was activated by aCSVD-associated gut bacterial extracts to up-regulate IL-17A production. Our findings revealed a previously unrecognized implication of the gut-immune-brain axis in aCSVD pathophysiology, with therapeutic implications.