Endosymbiotic Fungal Diversity and Dynamics of the Brown Planthopper across Developmental Stages, Tissues, and Sexes Revealed Using Circular Consensus Sequencing.

Endosymbiotic fungi play an important role in the growth and development of insects. Understanding the endosymbiont communities hosted by the brown planthopper (BPH; Nilaparvata lugens Stål), the most destructive pest in rice, is a prerequisite for controlling BPH rice infestations. However, the endosymbiont diversity and dynamics of the BPH remain poorly studied. Here, we used circular consensus sequencing (CCS) to obtain 87,131 OTUs (operational taxonomic units), which annotated 730 species of endosymbiotic fungi in the various developmental stages and tissues. We found that three yeast-like symbionts (YLSs), Polycephalomyces prolificus, Ophiocordyceps heteropoda, and Hirsutella proturicola, were dominant in almost all samples, which was especially pronounced in instar nymphs 4-5, female adults, and the fat bodies of female and male adult BPH. Interestingly, honeydew as the only in vitro sample had a unique community structure. Various diversity indices might indicate the different activity of endosymbionts in these stages and tissues. The biomarkers analyzed using LEfSe suggested some special functions of samples at different developmental stages of growth and the active functions of specific tissues in different sexes. Finally, we found that the incidence of occurrence of three species of Malassezia and Fusarium sp. was higher in males than in females in all comparison groups. In summary, our study provides a comprehensive survey of symbiotic fungi in the BPH, which complements the previous research on YLSs. These results offer new theoretical insights and practical implications for novel pest management strategies to understand the BPH-microbe symbiosis and devise effective pest control strategies.

Network pharmacology analysis and experimental verification of the antitumor effect and molecular mechanism of isocryptomerin on HepG2 cells.

Isocryptomerin (ISO) is a flavonoid isolated from the natural medicine Selaginellae Herba, which has various pharmacological activities. This study investigated the antitumor effect and underlying molecular mechanism of ISO on hepatocellular carcinoma (HCC) HepG2 cells. The cell viability assay revealed that ISO has a considerable killing effect on HCC cell lines. The apoptosis assay showed that ISO induced mitochondria-dependent apoptosis through the Bad/cyto-c/cleaved (cle)-caspase-3/cleaved (cle)-PARP pathway. The network pharmacological analysis found 13 key target genes, and epidermal growth factor receptor (EGFR), AKT, mitogen-activated protein kinase (MAPK), and reactive oxygen species (ROS) signaling pathways were strongly associated with ISO against HCC. Further verification of the results showed that ISO induced apoptosis by increasing p-p38 and p-JNK expression and decreasing p-EGFR, p-SRC, p-ERK, and p-STAT3 expression. Furthermore, ISO induced G0/G1 phase arrest by downregulating p-AKT, Cyclin D, and CDK 4 expression and upregulating p21 and p27 expression in HepG2 cells. Moreover, ISO inhibited HepG2 cell migration by decreasing p-GSK-3ß, ß-catenin, and N-cadherin expression and increasing E-cadherin expression. Additionally, ISO promoted ROS accumulation in HepG2 cells, and ISO-induced apoptosis, arrest cell cycle, and inhibition of migration were reversed by an ROS scavenger, N-acetyl- l-cysteine. Overall, ISO induced cell apoptosis and cell cycle arrest and inhibited cell migration by ROS-mediated EGFR, AKT, and MAPK signaling pathways in HepG2 cells.

The Elk-3 target Abhd10 ameliorates hepatotoxic injury and fibrosis in alcoholic liver disease.

Alcoholic liver disease (ALD) and other forms of chronic hepatotoxic injury can lead to transforming growth factor ß1 (TGFß1)-induced hepatic fibrosis and compromised liver function, underscoring the need to develop novel treatments for these conditions. Herein, our analyses of liver tissue samples from severe alcoholic hepatitis (SAH) patients and two murine models of ALD reveals that the ALD phenotype was associated with upregulation of the transcription factor ETS domain-containing protein (ELK-3) and ELK-3 signaling activity coupled with downregulation of α/ß hydrolase domain containing 10 (ABHD10) and upregulation of deactivating S-palmitoylation of the antioxidant protein Peroxiredoxin 5 (PRDX5). In vitro, we further demonstrate that ELK-3 can directly bind to the ABHD10 promoter to inhibit its transactivation. TGFß1 and epidermal growth factor (EGF) signaling induce ABHD10 downregulation and PRDX5 S-palmitoylation via ELK-3. This ELK-3-mediated ABHD10 downregulation drives oxidative stress and disrupts mature hepatocyte function via enhancing S-palmitoylation of PRDX5's Cys100 residue. In vivo, ectopic Abhd10 overexpression ameliorates liver damage in ALD model mice. Overall, these data suggest that the therapeutic targeting of the ABHD10-PRDX5 axis may represent a viable approach to treating ALD and other forms of hepatotoxicity.

Acanthopanax senticosus extract alleviates radiation-induced learning and memory impairment based on neurotransmitter-gut microbiota communication.

BACKGROUND: Acanthopanax senticosus (AS) is a medicinal and food plant with many physiological functions, especially nerve protection. Its extract has many functional components, including polysaccharides, flavonoids, saponins, and amino acids. Our previous study indicated that AS extract protected against nerve damage caused by radiation. However, little is known about the gut-brain axis mechanism of AS and its impact on radiation-induced learning and memory impairment. METHOD: In 60 Co-γ ray-irradiated mice, we investigated the changes in behavior, neurotransmitters and gut microbiota after different days of administration of AS extract as a dietary supplement. RESULTS: The AS extract improved learning and memory ability in mice, and the neurotransmitter levels in the hippocampus and colon started to change from the 7th day, which accompanied changes of the gut microbiota, a decreased abundance of Helicobacter on the 7th day and an increased abundance of Lactobacillus on the 28th day. Among the marker bacteria, Ruminococcus and Clostridiales were associated with 5-HT synthesis, and Streptococcus were associated with 5-HT and ACH synthesis. In addition, the AS extract increased the tight junction protein, inhibited inflammation levels in colon, and even increased the relative protein expression of BDNF and NF-κB and decreased the relative protein expression of IκBα in the hippocampus of irradiated mice. CONCLUSION: These results will lay the foundation for further study on the mechanism of the gut-brain axis of AS in preventing radiation-induced learning and memory impairment.

Combined effects of temperature and humidity on the interaction between tomato and Botrytis cinerea revealed by integration of histological characteristics and transcriptome sequencing.

The environment significantly impacts the interaction between plants and pathogens, thus remarkably affecting crop disease occurrence. However, the detailed combined mechanisms of temperature and humidity influencing this interaction remain unclear. In this study, the interaction between tomato and Botrytis cinerea in various temperature and humidity conditions was analyzed by histological observation and a dual RNA-seq approach. Results showed that low humidity was not favorable for mycelial growth, resulting in infection failure. Both high and low temperatures at high humidity successfully inhibited pathogenic infection and disease incidence in the tomato plants, thus enhancing their resistance to B. cinerea. The high temperature and high humidity (HH) treatment induced the upregulation of light reaction genes, increased the net photosynthetic rate, and expanded the chloroplast morphology of infected tomatoes. The HH treatment also inhibited the expression of cell cycle-related genes of B. cinerea, interfered with conidial germination and mycelial growth, and damaged mycelial cell structure. Low temperature and high humidity (LH) treatment induced the expression of cell wall modification genes and remodeled the cell wall morphology of tomatoes in response to B. cinerea. In addition, the downregulated fungal catabolic genes and the abnormal increase in electron density of mycelial cells under LH treatment subsequently reduced the infection ability of B. cinerea. These results further explain the coupled effects of temperature and humidity on plant defenses and pathogen virulence, and provide a potential means to control gray mold.

Enhanced viability of probiotics encapsulated within synthetic/natural biopolymers by the addition of gum arabic via electrohydrodynamic processing.

To enhance the probiotics' viability, novel vehicles consisting of synthetic/natural biopolymers, i.e., polyvinyl alcohol (PVOH), polyvinylpyrrolidone, whey protein concentrate and maltodextrin, encapsulated with L. plantarum KLDS 1.0328 and gum arabic (GA) as a prebiotic were fabricated by electrohydrodynamic techniques. Inclusion of cells into composites caused an increase in conductivity and viscosity. Morphological analysis showed that cells were distributed along the electrospun nanofibres or distributed randomly in the electrosprayed microcapsules. Both intramolecular and intermolecular hydrogen bond interactions exist between biopolymers and cells. Thermal analysis revealed that the degradation temperatures (>300 °C) of various encapsulation systems have potential applications in heat-treatment foods. Additionally, cells especially immobilized in PVOH/GA electrospun nanofibres showed the highest viability compared with free cells after exposure to simulated gastrointestinal stress. Furthermore, cells retained their antimicrobial ability after rehydration of the composite matrices. Therefore, electrohydrodynamic techniques have great potential in encapsulating probiotics.

Effects of Intermittent Temperature and Humidity Regulation on Tomato Gray Mold.

Temperature and humidity play an important role in plant-pathogen interactions. However, regulating the temperature and humidity specifically to inhibit the development of plant diseases remains unclear. In this study, we explored the influence of intermittent temperature and humidity variation on tomato gray mold. Intermittent regulation of temperature and humidity (increasing temperature with decreasing humidity for different periods within 24 h) inhibited the disease severity of plants and the infection process of Botrytis cinerea. The 4-h treatment (increasing temperature accompanied by decreasing humidity for 4 h and recovering for 4 h, and so on) effectively inhibited the development of tomato gray mold, reduced the biomass of B. cinerea, delayed the differentiation time of mycelia, and inhibited the accumulation of hydrogen peroxide in tomato leaves at the later stage of infection. The increased expressions of heat-shock protein (HSP) genes HSP20, HSP70, HSP90, BAG6, and BAG7 in tomato were mainly caused by environmental changes and environment-plant-pathogen interactions, and the increased expression of the latter was greater than that of the former in the 2-h (increasing temperature accompanied by decreasing humidity for 2 h and recovering for 2 h, and so on) and 4-h treatments. Pathogen infection induced the expression of defense-related genes in tomato, and the increase in the expressions of FLS2, FEI1, PI2, Pti5, and WRKY75 induced by B. cinerea in the 4-h treatment was greater than that under unregulated temperature and humidity conditions. In general, intermittent temperature and humidity variation can effectively inhibit the development of tomato gray mold, and the 4-h treatment had the best inhibitory effect.

Intermittent Changes in Temperature and Humidity Repress Gray Mold in Tomato.

Environmental temperature and humidity play a vital role in plant-pathogen interactions, which profoundly affect the occurrence of crop diseases. However, the specific methods and mechanisms through which intermittent changes in temperature and humidity mitigate plant diseases remain unclear. In this study, six temperature and humidity combinations were set, the disease severity of tomatoes and biomass of Botrytis cinerea were analyzed, and the infection process of pathogens was observed using an optical microscope. Furthermore, dual RNA-seq analysis was performed to explore the interactions between plants and pathogens. Results showed that the 24 hours postinoculation (hpi)-12 h day (regulation was performed at 24 hpi for 12 h after inoculation during the day) treatment reduced the gray mold severity and biomass of B. cinerea in plants by the greatest amount and effectively inhibited the growth of mycelia. The 24 hpi-12 h day treatment induced the upregulation of light reactions, photorespiration, and Calvin cycle-related genes in tomatoes, whereas fungal genes related to the biosynthesis of sesquiterpene botrydial and polyketide botcinic acid were downregulated. Overall, we identified the optimal combination of temperature and humidity changes to inhibit the development of tomato gray mold and preliminarily explored the interactions between tomato and B. cinerea under temperature and humidity changes. This work has practical importance and provides a theoretical basis for the ecological control of plant diseases.

Diagnosis, clustering, and immune cell infiltration analysis of m6A-related genes in patients with acute myocardial infarction-a bioinformatics analysis.

Background: Accurate myocardial infarction (AMI) is one of the leading causes of mortality worldwide. N6-methyladenosine (m6A) modification plays an important role in the development of cardiac remodeling and the cardiomyocyte contractile function. The aim of this study is to analyze the m6A-related molecular biological mechanisms of AMI in terms of accurate diagnosis and prognosis. Methods: The platform data and probe data of the GSE66360 data set were downloaded. The differential analysis was conducted by combining the m6A-related gene expression. Thereafter, a diagnostic model was established using the random-forest method. The diagnostic accuracy of the diagnostic models was assessed by using the area under the receiver operating characteristic (ROC) curve (AUC). Next, the patients with AMI were clustered by unsupervised machine learning using the R software. Finally, an immune cell clustering analysis for each cluster was conducted to determine the correlations between m6A-related gene expression and the infiltration amount of the immune cells. The case and control groups were not matched in terms of demographics. Results: The GSE6636 data set comprised 99 participants (49 patients with AMI and 50 without in control group). The differential analysis identified 10 m6A-related genes: 5 writers [Methyltransferase-like 3 (METTL3), Methyltransferase-like 14 (METTL14), Wilms tumor 1-associated protein (WTAP), Zinc Finger CCCH-Type Containing 13 (ZC3H13), and Casitas B-lineage proto-oncogene like 1 (CBLL1)], 4 readers [YT521-B homology domain-containing family 3 (YTHDF3), Fragile X mental retardation type 1 (FMR1), YT521-B homology-domain-containing protein 1 (YTHDC1), and insulin-like growth factor binding protein 3 (IGFBP3)] and 1 eraser [fat mass and obesity associated (FTO) gene]. The Mean Decrease Gini (MDG) values of these 10 genes were greater than 2. The FTO, WTAP, YTHDC1, IGFBP3, and CBLL1 were included in the model with a C index of 0.842. METTL3, ZC3H13, WTAP, and CBLL1 were highly expressed in Type A, and YTHDF3 was highly expressed in Type B. Conclusions: A diagnostic model of AMI was established based on the genes of FTO, WTAP, YTHDC1, IGFBP3, and CBLL1. Additionally, 2 molecular subtypes were successfully identified from the above-mentioned gene. Our findings could provide a novel method for the accurate diagnosis of AMI.

Agmatine mitigates palmitate (PA)-induced mitochondrial and metabolic dysfunction in microvascular endothelial cells.

Agmatine is an arginine metabolite that has neuroprotective capacity. Recently, it has been found to ameliorate atherosclerosis progression in rabbits. However, further molecular mechanisms of its anti-atherosclerotic properties remain unclear. High plasma levels of free fatty acids (FFAs) are an important risk factor for atherosclerosis due to their detrimental effects on vascular endothelial cells (ECs). Here, we used palmitate (PA), a kind of FFA, to induce endothelial dysfunction in human microvascular endothelial cells (HMECs) to determine the possible biological functions of agmatine. We found that PA caused ECs dysfunction in HMEC-1 cells, decreased cell viability, and elevated lactate dehydrogenase (LDH) release which could be reversed by agmatine treatment. Agmatine also improved the nitric oxide (NO) production and endothelial nitric oxide synthase (eNOS) activity in PA-induced HMEC-1 cells. The PA-caused mitochondrial dysfunction of HMEC-1 cells was diminished after agmatine treatment, as proven by the increased intracellular Adenosine Triphosphate (ATP) level, decreased mitochondrial reactive oxygen species (ROS) level, and increased mitochondrial oxygen consumption rate (OCR). Further, agmatine could alleviate PA-caused lipid accumulation with increased levels of Triglyceride (TG) and total cholesterol (TC) in HMEC-1 cells. Furthermore, Western blot analysis revealed that agmatine administration markedly decreased the expression levels of phosphorylated-AMP-activated protein kinase α (p-AMPKα), p-protein kinase B (p-AKT), and p-eNOS in PA-induced HMEC-1 cells. Inhibition of AMPK by compound C reversed the protective effects of agmatine on PA-induced HMEC-1 cells. Taken together, we hypothesize that agmatine mitigated PA-induced HMEC-1 cell dysfunction by alleviating mitochondrial and metabolic dysfunction via the AMPK/PI3K/Akt/eNOS signaling pathway.

Transcriptome and Metabolome Profiling Reveal the Resistance Mechanisms of Rice against Brown Planthopper.

Brown planthopper (Nilaparvata lugens Stål, BPH) is one of the most destructive insects affecting rice production. To better understand the physiological mechanisms of how rice responds to BPH feeding, we analyzed BPH-induced transcriptomic and metabolic changes in leaf sheaths of both BPH-susceptible and -resistant rice varieties. Our results demonstrated that the resistant rice reduced the settling, feeding and growth of BPH. Metabolic analyses indicated that BPH infestation caused more drastic overall metabolic changes in the susceptible variety than the resistant rice. Differently accumulated metabolites (DAMs) belonging to flavonoids were downregulated in the susceptible rice but upregulated in resistant variety. Transcriptomic analyses revealed more differentially expressed genes (DEGs) in susceptible rice than resistant rice, and DEGs related to stimulus were significantly upregulated in resistant rice but downregulated in susceptible rice. Combined analyses of transcriptome and metabolome showed that many DEGs and DAMs were enriched in phenylpropane biosynthesis, flavonoid biosynthesis, and plant hormone signal transduction. We conducted correlation analyses of DEGs and DAMs in these pathways and found a high correlation between DEGs and DAMs. Then, we found that the contents of endogenous indole 3-acetic acid (IAA) in resistant rice was lower than that of susceptible rice after BPH feeding, while the salicylic acid (SA) content was the opposite. For functional analysis, an exogenous application of IAA decreased rice resistance to BPH, but the exogenous application of SA increased resistance. In addition, biochemical assessment and quantitative PCR analysis showed that the lignin content of resistant accession was constitutively higher than in susceptible accession. By adding epigallocatechin, the substrate of anthocyanidin reductase (ANR), to the artificial diet decreased the performance of BPH. We first combined a transcriptome-metabolome-wide association study (TMWAS) on rice resistance to BPH in this study. We demonstrated that rice promoted resistance to BPH by inducing epigallocatechin and decreasing IAA. These findings provided useful transcriptomic and metabolic information for understanding the rice-BPH interactions.

Reminiscence therapy involved care programs as an option to improve psychological disorders and patient satisfaction in elderly lung cancer patients: A randomized, controlled study.

Objective: Reminiscence therapy (RT) is frequently used with elderly patients to improve their psychological status, but a few studies have examined its application in lung cancer patients. This study explored whether a reminiscence therapy-involved care program (RTICP) could improve cognitive functions, anxiety, depression, patient satisfaction, and survival in elderly lung cancer patients. Materials and Methods: This randomized, controlled study enrolled 138 elderly post-operative lung cancer patients into two groups, an RTICP group (n = 69) and a usual care program (UCP) group (n = 69), for a 12-month intervention period and a follow-up period. During the 12-month intervention, the Mini-Mental State Examination (MMSE) score, the Hospital Anxiety and Depression Scale for anxiety (HADS-A) and depression (HADS-D), patient satisfaction, disease-free survival (DFS), and overall survival (OS) were evaluated. Results: MMSE and patient satisfaction were elevated in the RTICP group compared to the UCP group at month (M) 12. Additionally, RTICP reduced HADS-A at M6, M9, and M12 and the anxiety rate at M9, HADS-D at M9, and M12 compared to UCP, whereas the depression rate was no different between the two groups at any time (all P > 0.050). Moreover, DFS and OS were no different between the two groups (all P > 0.050). Conclusion: RTICP, considered as an optional psychological intervention, enhances cognitive functions, alleviates anxiety and depression feelings, and elevates satisfaction among elderly lung cancer patients.

Flavonoids derived from buckwheat hull can break advanced glycation end-products and improve diabetic nephropathy.

Diabetic nephropathy (DN) is the most important complication in patients with diabetes. The accumulation of advanced glycation end-products (AGEs) is the main reason for the development of DN. In this study, we investigated the mechanism of buckwheat hull flavonoids to break AGEs in vitro by measuring fluorescence analysis, three-dimensional fluorescence, protein molecular weight, free amino groups, and the sulfhydryl group content. Proteomics analysis was used to determine the effect of total buckwheat hull flavonoids (TBHF) intervention on protein differential expression in the kidney of db/db mice. The results showed that buckwheat hull flavonoids were potent in breaking AGEs in vitro, and they protected mice kidneys by regulating the renal AGE-RAGE pathway. This study lays a strong experimental and theoretical foundation for the development of new lysing agents to break AGEs. The findings should make an important contribution to the field of flavonoids in improving the application of diabetic nephropathy in the diet.

PD-1 Immune Checkpoint Inhibitor Therapy Malignant Tumor Based on Monotherapy and Combined Treatment Research.

Recently, immunotherapy has become the fourth pillar of cancer treatment in addition to surgery therapy, chemotherapy, and radiation therapy. The inhibitors of programed cell death protein 1 (PD-1) and its ligand PD-L1 are the new stars in immunotherapy, as they can overcome tumor immunosuppression. However, the efficacy of PD-1 inhibitors still needs to be further developed for clinical treatment. Therefore, research into treatment with anti-PD-1 drugs has emerged as a new development field. This review provides novel insights into the role and mechanism of PD-1 combination anti-tumor therapy, thereby promoting its clinical application in anti-tumor immunotherapy.

Role of psychrotrophic fungal strains in accelerating and enhancing the maturity of pig manure composting under low-temperature conditions.

This study investigatedthe effects of applying psychrotrophic cellulose-degrading fungion cellulase production, fungal community structure, and maturity of pig manure (PM) compost under low-temperature conditions. Three psychrotrophic fungal strains were isolated and identified, and after the cold-active cellulase production conditions were optimized, they were inoculated into PM compost. While the control (CK) compost temperature failed to reachthe thermophilic stage, the inoculated compost temperature reached it within 3 days and was maintained for up to 17 days. Fungal inoculants improved fungal community structure at the end of composting, as suggested by network analysis. Principal component analysis revealed that the germination index (GI), total phosphorus (TP), total potassium (TK), and total nitrogen (TN) were the most influential physicochemical parameters affecting compost maturity. The results of the compost products reflected the suitability of the compost as a fertilizer. This study indicated that newly identified strains positively impacted composting at low temperatures.

In Situ Formation of Prussian Blue Analogue Nanoparticles Decorated with Three-Dimensional Carbon Nanosheet Networks for Superior Hybrid Capacitive Deionization Performance.

Capacitive deionization (CDI) is considered to be an alternative water purification technology because of its low cost and low driven energy. However, the desalination performance of traditional CDI still cannot meet the requirement of actual operations, which is the limited adsorption capacity of carbon electrodes. Here, we report a feasible and simple strategy for the synthesis of a three-dimensional hierarchical composite with homogeneous Prussian blue analogue nanoparticles, decorating hierarchical porous carbon nanosheet networks (NiHCF@3DC-2) as a redox-active intercalation electrode material for hybrid capacitive deionization (HCDI). The interconnected network structure, accompanied by its unique porous characteristic and uniform NiHCF nanoparticles, endows the prepared NiHCF@3DC-2 with enough straining space for alleviating the effect of volume change upon the regeneration process and guarantees fast transmission kinetics for both electrons and salt ions. As a consequence, an HCDI cell with NiHCF@3DC-2 and activated carbon showed superior desalination ability with a high ion removal capacity of 47.8 mg g-1 (107.5 mg g-1 NiHCF@3DC-2) and good cyclic regenerative performance. Moreover, the Na+ ions storage mechanism and the interfacial synergy of the NiHCF@3DC-2 were also explored by structure and electrochemistry analyses during the CDI process. Our work provides a promising redox-active intercalation electrode material to highly efficient hybrid capacitive deionization for brine.

Isoorientin induces the apoptosis and cell cycle arrest of A549 human lung cancer cells via the ROS­regulated MAPK, STAT3 and NF­κB signaling pathways.

Isoorientin (ISO) is a naturally occurring C­glycosyl flavone that has various pharmacological properties, such as anti­bacterial and anti­inflammatory effects. However, its underlying molecular mechanisms in human lung cancer cells remain unknown. In the present study, the effects of ISO on the induction of apoptosis and relative molecular mechanisms in A549 human lung cancer cells were investigated. The results of Cell Counting Kit­8 assay (CCK­8) indicated that ISO exerted significant cytotoxic effects on 3 lung cancer cell lines, but had no obvious side­effects on normal cells. Moreover, flow cytometry and western blot analysis revealed that ISO induced mitochondrial­dependent apoptosis by reducing mitochondrial membrane potential. ISO also increased the expression levels of Bax, cleaved­caspase­3 (cle­cas­3) and poly(ADP­ribose) polymerase (PARP; cle­PARP), and decreased the expression levels of Bcl­2 in A549 cells. Furthermore, ISO induced G2/M cell cycle arrest by decreasing the expression levels of cyclin B1 and CDK1/2, and increasing the expression levels of p21 and p27 in A549 cells. As the duration of ISO treatment increased, intracellular reactive oxygen species (ROS) levels in A549 cells also increased. However, pre­treatment of the cells with the ROS scavenger, N­acetylcysteine (NAC), inhibited ISO­induced apoptosis. In addition, ISO increased the expression levels of p­p38, p­JNK and IκB­α; and decreased the expression levels of p­extracellular signal­regulated kinase (ERK), p­signal transducer and activator of transcription (STAT)3, p­nuclear factor (NF)­κB, NF­κB and p­IκB; these effects were induced by mitogen­activated protein kinase (MAPK) inhibitors and blocked by NAC. Taken together, the results of the present study indicate that ISO induces the apoptosis of A549 lung cancer cells via the ROS­mediated MAPK/STAT3/NF­κB signaling pathway, and thus may be a potential drug for use in the treatment of lung cancer.

An enhancement strategy for the biodegradation of high-concentration aliphatic nitriles: Utilizing the glucose-mediated carbon catabolite repression mechanism.

Wastewater containing high concentrations of nitriles, if discharged without an appropriate nonhazardous disposal strategy, will cause serious environmental pollution. During secondary sewage biological treatment, most existing bacteria cannot endure high-concentration nitriles due to poor tolerance and low degradation ability. The Rhodococcus rhodochrous strain BX2 screened by our laboratory shows high resistance to nitriles and can efficiently degrade these compounds. Compared with sole high-concentration nitriles present in the biodegradation process, the addition of glucose at a suitable concentration can effectively increase the biomass of BX2, promote the expression of nitrile-degrading enzyme genes, improve the activities of these enzymes and enhance the pollutant removal efficiency via carbon catabolite repression (CCR) mechanisms. Whole-genome sequencing revealed that the four key regulators of CCR identified in gram-negative and gram-positive bacteria are concomitant in BX2. This study provides an economically feasible strategy for the microbial remediation of high-concentration nitriles and other organic pollutants.

IL-22 produced by Th22 cells aggravates atherosclerosis development in ApoE-/- mice by enhancing DC-induced Th17 cell proliferation.

Th22 cells are a novel subset of CD4+ T cells that primarily mediate biological effects through IL-22, with both Th22 cells and IL-22 being closely associated with multiple autoimmune and chronic inflammatory diseases. In this study, we investigated whether and how Th22 cells affect atherosclerosis. ApoE-/- mice and age-matched C57BL/6J mice were fed a Western diet for 0, 4, 8 or 12 weeks. The results of dynamic analyses showed that Th22 cells, which secrete the majority of IL-22 among the known CD4+ cells, play a major role in atherosclerosis. ApoE-/- mice fed a Western diet for 12 weeks and administered recombinant mouse IL-22 (rIL-22) developed substantially larger plaques in both the aorta and aortic root and higher levels of CD3+ T cells, CD68+ macrophages, collagen, IL-6, Th17 cells, dendritic cells (DCs) and pSTAT3 but lower smooth muscle cell (SMC) α-actin expression than the control mice. Treatment with a neutralizing anti-IL-22 monoclonal antibody (IL-22 mAb) reversed the above effects. Bone marrow-derived DCs exhibited increased differentiation into mature DCs following rIL-22 and ox-LDL stimulation. IL-17 and pSTAT3 were up-regulated after stimulation with IL-22 and ox-LDL in cells cocultured with CD4+ T cells and mature DC supernatant, but this up-regulation was significantly inhibited by IL-6mAb or the cell-permeable STAT3 inhibitor S31-201. Thus, Th22 cell-derived IL-22 aggravates atherosclerosis development through a mechanism that is associated with IL-6/STAT3 activation, DC-induced Th17 cell proliferation and IL-22-stimulated SMC dedifferentiation into a synthetic phenotype.

Liquiritin inhibits proliferation and induces apoptosis in HepG2 hepatocellular carcinoma cells via the ROS-mediated MAPK/AKT/NF-κB signaling pathway.

Liquiritin (LIQ), a major constituent of Glycyrrhiza Radix, exhibits various pharmacological activities. In this study, to explore the potential anti-cancer effects and its underlying molecular mechanisms of LIQ in hepatocellular carcinoma (HCC) cells. LIQ significantly decreased viability and induced apoptosis in HepG2 cells by decreasing mitochondrial membrane potential and regulating Bcl-2 family proteins, cytochrome c, cle-caspase-3, and cle-PARP. The cell cycle analysis and western blot analysis revealed that LIQ induced G2/M phase arrest through increased expression of p21 and decreased levels of p27, cyclin B, and CDK1/2. The flow cytometry and western blot analysis also suggested that LIQ promoted the accumulation of ROS in HepG2 cells and up-regulated the phosphorylation expression levels of p38 kinase, c-Jun N-terminal kinase (JNK), and inhibitor of NF-κB (IκB-α); the phosphorylation levels of extracellular signal-regulated kinase (ERK), protein kinase B (AKT), signal transducer activator of transcription 3 (STAT3), and nuclear factor kappa B (NF-κB) were down-regulated. However, these effects were reversed by N-acetyl-L-cysteine (NAC), MAPK, and AKT inhibitors. The findings demonstrated that LIQ induced cell cycle arrest and apoptosis via the ROS-mediated MAPK/AKT/NF-κB signaling pathway in HepG2 cells, and the LIQ may serve as a potential therapeutic agent for the treatment of human HCC.