Dose-Response Meta-Analysis on Risk of Diabetes in Relation to Red and Processed Meat Consumption - Asian Populations, 2006-2021.

What is already known about this topic?: Red and processed meat consumption has been positively related to an increased risk of diabetes in Western populations. However, the results remain inconclusive within Asian populations. What is added by this report?: This dose-response meta-analysis of prospective cohort studies conducted in East Asian populations reveals a positive relation between the consumption of processed meat and increased risk of diabetes. Furthermore, a U-shaped association was identified between the consumption of unprocessed red meat and the risk of diabetes. What are the implications for public health practice?: This research presents substantive evidence advocating for the reduction of processed and unprocessed red meat consumption as a viable strategy for mitigating the risk of diabetes in East Asian populations.

Viral lysing can alleviate microbial nutrient limitations and accumulate recalcitrant dissolved organic matter components in soil.

Viruses are critical for regulating microbial communities and biogeochemical processes affecting carbon/nutrient cycling. However, the role of soil phages in controlling microbial physiological traits and intrinsic dissolved organic matter (DOM) properties remains largely unknown. Herein, microcosm experiments with different soil phage concentrates (including no-added phages, inactive phages, and three dilutions of active phages) at two temperatures (15 °C and 25 °C) were conducted to disclose the nutrient and DOM dynamics associated with viral lysing. Results demonstrated three different phases of viral impacts on CO2 emission at both temperatures, and phages played a role in maintaining Q10 within bounds. At both temperatures, microbial nutrient limitations (especially P limitation) were alleviated by viral lysing as determined by extracellular enzyme activity (decreased Vangle with active phages). Additionally, the re-utilization of lysate-derived DOM by surviving microbes stimulated an increase of microbial metabolic efficiency and recalcitrant DOM components (e.g., SUV254, SUV260 and HIX). This research provides direct experimental evidence that the "viral shuttle" exists in soils, whereby soil phages increase recalcitrant DOM components. Our findings advance the understanding of viral controls on soil biogeochemical processes, and provide a new perspective for assessing whether soil phages provide a net "carbon sink" vs. "carbon source" in soils.

Enhanced soil function and health by soybean root microbial communities during in situ remediation of Cd-contaminated soil with the application of soil amendments.

The interactions between soil microbiomes at various trophic levels are essential for restoring soil functions. Legumes are considered as "pioneer crops" in degraded or contaminated soils because they can fix nitrogen through symbiotic relationships with rhizobacteria, which promotes soil fertility. However, little is known about the abilities of legumes to contribute to the health of soil contaminated with cadmium (Cd). In this research, we applied a soil amendment (commercial Mg-Ca-Si conditioner, CMC) at two rates (1,500 and 3,000 kg/ha) in a Cd-contaminated soybean field. Bulk and rhizosphere soil samples were collected to assess the amendment-induced effects on four microbial lineages (bacteria, fungi, arbuscular mycorrhizal fungi [AMF], and nematodes) and their functions including Cd stabilization, nutrient cycling, and pathogen control. Compared with the control, both CMC application rates increased the pH and reduced labile Cd fraction in the bulk and rhizosphere soils. Although the total Cd concentrations in the soil were similar, the Cd accumulation in the grains was significantly reduced in treatments of soil amendments. It was observed that the application of CMC can significantly reduce the AMF diversity but increased the diversity of the other three communities. Moreover, the biodiversity within keystone modules (identified by co-occurrence network analysis) played key roles in driving soil multifunctionality. Specifically, key beneficial groups in module 2 such as Aggregicoccus (bacteria), Sordariomycetes (fungi), Glomus (AMF), and Bursaphelenchus (nematode) were strongly associated with soil multifunctionality. By co-culturing bacterial suspensions with the soybean root rot pathogen Fusarium solani in the in vitro assays, we experimentally validated that the application of CMC promoted the suppression of soil bacterial community on pathogens by inhibiting the mycelium growth and spore germination. Also, the bacterial community was more resistant to Cd stress in soils receiving CMC amendment. Our findings provide valuable theoretical references for enhancing soil functions and health via applying a soil amendment (CMC) during Cd-contaminated soil remediation. IMPORTANCE Restoration of microbiome-driven soil functions and health is of great importance during Cd-contaminated soil remediation via soil amendment. Soybean and its symbiotic mutualism can provide abundant nitrogen and phosphorus to relieve the nutrient deficiency of Cd-contaminated soil. This study provides a novel perspective on the potential role of applying a soil amendment (CMC) in enhancing the functions and health of Cd-contaminated soils. Our results showed the distinct differences in soil microbial community responding to amendment-induced changes in edaphic properties. The biodiversity within keystone modules had major contributions to the maintenance of the soil's multifunctionality and health. Additionally, a higher CMC application rate showed more beneficial effects. Collectively, our results enhance our understanding about the effects of applying CMC, together with soybean rotation, to enhance and maintain soil functions and health during the field Cd stabilization process.

Resveratrol-Loaded TPGS-Resveratrol-Solid Lipid Nanoparticles for Multidrug-Resistant Therapy of Breast Cancer: In Vivo and In Vitro Study.

Multidrug resistance (MDR) is a serious problem during cancer therapy. The purpose of the present study was to formulate D-α-Tocopheryl polyethylene glycol 1000 succinate-resveratrol-solid lipid nanoparticles (TPGS-Res-SLNs) to improve its therapeutic efficacy against breast cancer. In this study, the solvent injection method was used to prepare the TPGS-Res-SLNs. It was found that the TPGS-Res-SLNs exhibited zeta potential and drug-loading of -25.6 ± 1.3 mV and 32.4 ± 2.6%, respectively. Therefore, it was evident that the TPGS-Res-SLNs can increase cellular uptake of chemotherapeutic drugs, induce mitochondrial dysfunction, and augment tumor treatment efficiency by inducing apoptosis. Moreover, it was found that SKBR3/PR cells treated with TPGS-Res-SLNs exhibited significant inhibition of cell migration and invasion, as compared with free resveratrol. In addition, results from in vivo SKBR3/PR xenograft tumor models revealed that TPGS-Res-SLNs has better efficacy in promoting apoptosis of tumor cells owing to high therapeutic outcomes on tumors when compared with the efficacy of free resveratrol. In conclusion, the findings of the present study indicate significant potential for use of TPGS-Res-SLNs as an efficient drug delivery vehicle to overcome drug resistance in breast cancer therapy.

Advances in the research of nanodrug delivery system for targeted treatment of liver fibrosis.

Liver fibrosis is one of the major threats to human health. At present, anti-liver fibrosis drugs exist some problems，such as, lack of targeting, limited treatment effect and more or less toxic side effects. In order to improve the efficacy of targeted therapy for liver fibrosis, the development of a large number of nanocarriers and strategies of targeted therapy for liver fibrosis have been widely studied. In this paper, the research progress of nano-delivery vectors targeting cells related to the process of liver fibrosis in recent years was reviewed in terms of targeting vectors and the types of modified ligands, providing a new strategy for targeted cell therapy and theoretical reference for the realization of high efficient targeted therapy of liver fibrosis.

Removal and tolerance mechanism of Pb by a filamentous fungus: A case study.

Currently, Pb pollution has become a severe environmental problem and filamentous fungi hold a promising potential for the treatment of Pb-containing wastewater. The present study showed that the strain Pleurotus ostreatus ISS-1 had a strong ability to tolerate Pb at high concentration and reached a removal rate of 53.7% in liquid media. Pb was removed by extracellular biosorption, intracellular bioaccumulation by mycelia, or precipitation with extracellular oxalic acids. On the cellular level, Pb was mainly distributed in the cell wall, followed by vacuoles and organelles. Fourier transform infrared spectroscopy (FTIR) analysis indicated that hydroxyl, amides, carboxyl, and sulfhydryl groups provided binding sites for Pb. Furthermore, Pb was found on the cell surface in the form of PbS and PbCO3 through X-ray diffraction (XRD). Intracellular chelates such as thiol compounds and oxalic acid, as well as extracellular oxalic acid, might play an important role in the tolerance of Pb. In addition, isobaric tags for relative and absolute quantitation (iTRAQ) analysis showed that ATP-binding cassette (ABC) transporter, cytochrome P450, peroxisome, and the calcium signaling pathway might participate in both accumulation and detoxification of Pb. These results have successfully provided a basis for further developing Pb polluted water treatment technology by fungi.

miR­16­2­3p inhibits cell proliferation and migration and induces apoptosis by targeting PDPK1 in maxillary primordium mesenchymal cells.

MicroRNAs (miRNAs) post­transcriptionally regulate gene expression by targeting the 3' untranslated region (UTR) of target genes, and serve diverse roles in cell proliferation, differentiation and apoptosis. However, the association between miR­16­2­3p and 3­phosphoinositide­dependent protein kinase­1 (PDPK1) in nonsyndromic cleft lip (NSCL) remains unclear. In the present study, a luciferase activity assay indicated that miR­16­2­3p negatively regulated PDPK1 in maxillary primordium mesenchymal cells (MPMCs). In addition, it was confirmed that the expression levels of miR­16­2­3p was markedly increased in cleft lip tissues compared with those in adjacent normal lip tissues. A negative correlation between miR­16­2­3p and PDPK1 in cleft lip tissues was observed. Furthermore, miR­16­2­3p inhibited cell proliferation and migration, and induced apoptosis of MPMCs via repressing PDPK1. Finally, miR­16­2­3p exerted its suppressive role in MPMCs by inhibiting the PDPK1/protein kinase B signaling pathway. These results indicate that miR­16­2­3p may inhibit cell proliferation and migration, and promote apoptosis in MPMCs through repression of PDPK1 and may be a potential target for future clinical prevention and treatment of NSCL.

Overexpression of the alfalfa WRKY11 gene enhances salt tolerance in soybean.

The WRKY transcription factors play an important role in the regulation of transcriptional reprogramming associated with plant abiotic stress responses. In this study, the WRKY transcription factor MsWRKY11, containing the plant-specific WRKY zinc finger DNA-binding motif, was isolated from alfalfa. The MsWRKY11 gene was detected in all plant tissues (root, stem, leaf, flower, and fruit), with high expression in root and leaf tissues. MsWRKY11 was upregulated in response to a variety of abiotic stresses, including salinity, alkalinity, cold, abscisic acid, and drought. Overexpression of MsWRKY11 in soybean enhanced the salt tolerance at the seedling stage. Transgenic soybean had a better salt-tolerant phenotype, and the hypocotyls were significantly longer than those of wild-type seeds after salt treatment. Furthermore, MsWRKY11 overexpression increased the contents of chlorophyll, proline, soluble sugar, superoxide dismutase, and catalase, but reduced the relative electrical conductivity and the contents of malonaldehyde, H2O2, and O2-. Plant height, pods per plant, seeds per plant, and 100-seed weight of transgenic MsWRKY11 soybean were higher than those of wild-type soybean, especially OX2. Results of the salt experiment showed that MsWRKY11 is involved in salt stress responses, and its overexpression improves salt tolerance in soybean.

Genome-wide analysis and expression patterns of the NAC transcription factor family in Medicago truncatula.

NAC transcription factor (TF) family proteins are expressed in various developmental stages and following various stresses. NAC TFs are involved in mediating various physiological functions of plants and participate in various signaling pathways under biotic or abiotic stress. The present study provided a comprehensive functional analysis of members of the MtNAC TF family. Via screening of Medicago truncatula genome information, we identified 97 MtNAC TFs in M. truncatula and compared the phylogenetic analysis of 14 conserved groups with their Arabidopsis and rice counterparts. The NAC TFs were categorized into 14 groups based on their conserved motifs and gene structure. The predicted M. truncatula NAC genes were distributed among eight chromosomes, and in addition, we found that these genes showed mass gene duplication. Through expression profiling of RNA-seq data analysis, we determined that NAC family members were expressed significantly under different abiotic stresses. This indicates that the NAC TF shows different functions in M. truncatula. Together, this genome-wide analysis of the NAC gene family in M. truncatula, could be applied to improving stress tolerance in plants.

Mechanisms of Cd and Cr removal and tolerance by macrofungus Pleurotus ostreatus HAU-2.

Fungi bioaccumulation is a novel and highly promising approach to remediate polluted soil. The present study revealed a high ability to tolerate Cd and Cr in the fungus Pleurotus ostreatus HAU-2. However, high concentrations of Cd and Cr can suppress fungal growth and result in a variation of hypha micromorphology. Batch experiments were performed to investigate Cd and Cr stress effects on the amount of active oxygen in fungi, activity of antioxidant enzyme, as well as the removal efficiency of Cd and Cr. The results revealed that Cd and Cr caused increasing active oxygen and malonaldehyde (MDA) concentrations. Antioxidant enzymes play a central role in removing active oxygen, while glutathione (GSH) aids the Cd detoxification within cells. In fluid culture, fungal removal rates of Cd and Cr ranged from 44.85% to 80.36% and 14.49% to 45.55%, respectively. Intracellular accumulation and extracellular adsorption were the major removal approaches. Bag cultivation testing indicated that the fungus absorbed Cd and Cr contained within soil. In particular, the accumulation ability of Cd (15.6mgkg-1) was higher compared to that of Cr (8.9mgkg-1). These results successfully establish P. ostreatus HAU-2 as promising candidate for the remediation of heavy-metal polluted soils.

[Effects of Electroacupuncture Stimulation of "Neiguan" (PC 6) at Different Frequencies on Plasma Vasoactive Substance Levels in Myocardial Ischemic Reperfusion Rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of "Neiguan" (PC 6) at different frequencies on plasma vasoactive substance levels in myocardial ischemia-reperfusion (MIR) injury rats, so as to explore its mechanisms underlying improvement of acute myocardial ischemia. METHODS: A total of 40 Wistar rats were randomized into control, model, high frequency (HF, 120 Hz) and low frequency (LF, 20 Hz) groups (n = 10 in each group). The MIR model was established by occlusion of the anterior descending branch (ADB) of the left coronary artery for 30 min, followed by reperfusion for 40 min. EA (3 V, 120 Hz or 20 Hz) was applied to bilateral "Neiguan" (PC 6) for 50 min immediately after occlusion of ADB. Subsequently, the contents of plasma endothelin (ET), atrial natriuretic peptide (ANP), thromboxane B 2 (TXB2) and 6-Keto-PGF1, were assayed by radioimmunoassay, and the content of serum nitric oxide (NO) was detected by nitrate reductase method. RESULTS: Compared with the control group, the contents of plasma ET, ANP and TXB2 in the model group were significantly increased (P < 0.05), and that of plasma 6-Keto-PGF1α in the model group was notably decreased (P < 0.05), but no significant change was found in serum NO level (P > 0.05). Compared with the model group, the contents of plasma ET, ANP and TXB2 were considerably decreased, and plasma 6-Keto-PGF1α and serum NO contents were obviously increased in both HF and LF groups (P < 0.05). No significant differences were found between the HF and LF groups in plasma ET , ANP, TXB2 and 6-Keto-PGF1α contents (P > 0.05), but the HF EA was markedly superior to the LF EA in up-regulating the content of serum NO (P < 0.05). CONCLUSION: EA stimulation of "Neiguan" (PC 6) can down-regulate the contents of plasma ET, ANP and TXB2 and up-regulate contents of plasma 6-Keto-PGF1α and serum NO in MIR rats, which may contribute to its effect in relieving acute ischemic myocardial injury. The effect of HF EA is better than LF EA in raising blood NO level.

PTPRO-associated hepatic stellate cell activation plays a critical role in liver fibrosis.

BACKGROUND/AIMS: PTPRO (protein tyrosine phosphatase, receptor type O) is implicated in diverse physiological and pathological processes in cancer and hepatic ischemia/reperfusion injury, although little is known about its role in hepatic fibrosis. METHODS: Here, by using genetically deficient mice, we reported that PTPRO knockout (PTPRO(-/-)) significantly attenuated liver injury, release of inflammatory factors, tissue remodeling, and liver fibrosis in two experimental mouse models of fibrogenesis induced by bile-duct ligation or carbon tetrachloride administration. RESULTS: However, we proved that PTPRO expression was strongly downregulated in clinical and experimental liver fibrosis specimens. Further investigations revealed that stimulation of primary hepatic stellate cells (HSCs) and hepatocytes with specific activator platelet-derived growth factor (PDGF)-BB increased PTPRO transcription in HSCs but had the opposite effect in primary hepatocytes. More importantly, synthetic short hairpin RNA targeting PTPRO significantly neutralized PDGF-BB-induced HSC proliferation and myofibroblast marker expression through downregulated phosphorylation of extracellular signal-regulated kinase (ERK) and AKT. CONCLUSION: These observations confirm that PTPRO plays a critical role in liver fibrogenesis by affecting PDGF signaling in HSC activation and might be developed into a feasible therapeutic approach for the treatment of chronic fibrotic liver diseases.

Survival and inflammation promotion effect of PTPRO in fulminant hepatitis is associated with NF-κB activation.

Previous investigations demonstrated that protein tyrosine phosphatase, receptor type, O (PTPRO) acts as a tumor suppressor in liver cancer; however, little is known about its role in liver inflammation. Thus, we investigated the role of PTPRO in fulminant hepatitis (FH) using a Con A-induced mouse model. Significantly more severe liver damage, but attenuated inflammation, was detected in PTPRO-knockout (KO) mice, and PTPRO deficiency could confer this phenotype to wild-type mice in bone marrow transplantation. Moreover, hepatocytes with PTPRO depletion were more sensitive to TNF-α-induced apoptosis, and secretion of cytokines was significantly decreased in both T and NK/NKT cells and led to marked impairment of NF-κB activation. Intriguingly, wild-type and PTPRO-KO cells responded equally to TNF-α in activation of IKK, but NF-κB activation was clearly decreased in PTPRO-KO cells. PTPRO associated with ErbB2, and loss of PTPRO potentiated activation of the ErbB2/Akt/GSK-3ß/ß-catenin cascade. Increased ß-catenin formed a complex with NF-κB and attenuated its nuclear translocation and activation. Importantly, in humans, PTPRO was much decreased in FH, and this was associated with enhanced ß-catenin accumulation but reduced IFN-γ secretion. Taken together, our study identified a novel PTPRO/ErbB2/Akt/GSK-3ß/ß-catenin/NF-κB axis in FH, which suggests that PTPRO may have therapeutic potential in this liver disease.

IL-17A plays a critical role in the pathogenesis of liver fibrosis through hepatic stellate cell activation.

Liver fibrosis is a severe, life-threatening clinical condition resulting from nonresolving hepatitis of different origins. IL-17A is critical in inflammation, but its relation to liver fibrosis remains elusive. We find increased IL-17A expression in fibrotic livers from HBV-infected patients undergoing partial hepatectomy because of cirrhosis-related early-stage hepatocellular carcinoma in comparison with control nonfibrotic livers from uninfected patients with hepatic hemangioma. In fibrotic livers, IL-17A immunoreactivity localizes to the inflammatory infiltrate. In experimental carbon tetrachloride-induced liver fibrosis of IL-17RA-deficient mice, we observe reduced neutrophil influx, proinflammatory cytokines, hepatocellular necrosis, inflammation, and fibrosis as compared with control C57BL/6 mice. IL-17A is produced by neutrophils and T lymphocytes expressing the Th17 lineage-specific transcription factor Retinoic acid receptor-related orphan receptor γt. Furthermore, hepatic stellate cells (HSCs) isolated from naive C57BL/6 mice respond to IL-17A with increased IL-6, α-smooth muscle actin, collagen, and TGF-ß mRNA expression, suggesting an IL-17A-driven fibrotic process. Pharmacologic ERK1/2 or p38 inhibition significantly attenuated IL-17A-induced HSC activation and collagen expression. In conclusion, IL-17A(+) Retinoic acid receptor-related orphan receptor γt(+) neutrophils and T cells are recruited into the injured liver driving a chronic, fibrotic hepatitis. IL-17A-dependent HSC activation may be critical for liver fibrosis. Thus, blockade of IL-17A could potentially benefit patients with chronic hepatitis and liver fibrosis.

A bystander cell-based GM-CSF secreting vaccine synergized with a low dose of cyclophosphamide presents therapeutic immune responses against murine hepatocellular carcinoma.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) secreting cellular tumor vaccines contribute to the induction of potent antitumor immune responses in murine models and patients suffering from cancers. Hepatocellular carcinoma (HCC) is one of the most frequent and malignant cancers in China. We describe, for the first time, a GM-CSF releasing vaccine strategy that represents a step toward combating this type of cancer. In this study, a bystander cell-based GM-CSF secreting vaccine against murine HCC, Hepa1-6/B78H1-GM-CSF, was co-administered with a low dose of cyclophosphamide (CY). After challenging with tumor and vaccination, immunological assays demonstrated that the cellular antitumor immune responses were efficiently activated and that tumor development was significantly retarded, which was dependent on synergy with CY. The promising outcome of the anti-HCC vaccine in the murine model demonstrates the feasibility of a future clinical application for this treatment in HCC patients.

Estrogen-sensitive PTPRO expression represses hepatocellular carcinoma progression by control of STAT3.

UNLABELLED: Protein tyrosine phosphatase receptor type O (PTPRO), one of the receptor types of phosphotyrosine phosphatases (PTP), was recently described as a tumor suppressor in various kinds of cancers. We aimed to clarify the role of PTPRO in hepatocellular carcinoma (HCC). It was demonstrated in 180 pairs (120 male and 60 female) of clinical HCC specimens that the PTPRO level was significantly reduced, as compared with adjacent tissue, and the PTPRO level in male adjacent tissue was lower than in female. We further found that estrogen receptor alpha (ERα) could up-regulate PTPRO expression as a transcription factor. Moreover, an in vitro study showed that cell proliferation was inhibited and apoptosis was promoted in PTPRO-transduced HCC cell lines, whereas an in vivo study represented that tumor number and size was increased in ptpro(-/-) mice. As a result of its tumor-suppressive position, PTPRO was proved to down-regulate signal transducers and activators of transcription (STAT3) activity dependent on Janus kinase 2 (JAK2) and phosphoinositide 3-kinase (PI3K) dephosphorylation. CONCLUSIONS: PTPRO expression results in pathological deficiency and gender bias in HCC, which could be attributed to ERα regulation. The suppressive role of PTPRO in HCC could be ascribed to STAT3 inactivation.