PRDX1 negatively regulates bleomycin-induced pulmonary fibrosis via inhibiting the epithelial-mesenchymal transition and lung fibroblast proliferation in vitro and in vivo.

BACKGROUND: Pulmonary fibrosis is a major category of end-stage changes in lung diseases, characterized by lung epithelial cell damage, proliferation of fibroblasts, and accumulation of extracellular matrix. Peroxiredoxin 1 (PRDX1), a member of the peroxiredoxin protein family, participates in the regulation of the levels of reactive oxygen species in cells and various other physiological activities, as well as the occurrence and development of diseases by functioning as a chaperonin. METHODS: Experimental methods including MTT assay, morphological observation of fibrosis, wound healing assay, fluorescence microscopy, flow cytometry, ELISA, western blot, transcriptome sequencing, and histopathological analysis were used in this study. RESULTS: PRDX1 knockdown increased ROS levels in lung epithelial cells and promoted epithelial-mesenchymal transition (EMT) through the PI3K/Akt and JNK/Smad signalling pathways. PRDX1 knockout significantly increased TGF-ß secretion, ROS production, and cell migration in primary lung fibroblasts. PRDX1 deficiency also increased cell proliferation, cell cycle circulation, and fibrosis progression through the PI3K/Akt and JNK/Smad signalling pathways. BLM treatment induced more severe pulmonary fibrosis in PRDX1-knockout mice, mainly through the PI3K/Akt and JNK/Smad signalling pathways. CONCLUSIONS: Our findings strongly suggest that PRDX1 is a key molecule in BLM-induced lung fibrosis progression and acts through modulating EMT and lung fibroblast proliferation; therefore, it may be a therapeutic target for the treatment of BLM-induced lung fibrosis.

The Status Quo and Influencing Factors of Care Activities and Support Behaviors of the Main Caregivers of Stroke Patients During the Transition Period from Discharge.

Objective: This study investigated stroke patients and their primary caregivers, examining the impact of stroke events on caregivers and families, identifying factors affecting burden levels, and proposing measures to improve caregivers' quality of life and reduce family burden. Methods: This study adopted a questionnaire method, which includes a general information questionnaire, a patient self-care ability evaluation scale (Barthel index), a caregiver needs evaluation scale, and a social support evaluation scale (SSRS). Results: A total of 163 primary caregivers, mostly spouses or children of the patients, participated with an average age of 55.99 ± 11.92 years. A significant portion (36.81%) provided care alone for an average of 6.06 years. Social support received by caregivers was generally low, with only 1.84% reporting high support. 90.13% of caregivers experienced varying levels of burden, with 61.35% experiencing mild burden, 25.15% moderate burden, and 3.68% severe burden. Conclusion: The study concluded that China's nursing system for stroke patients is inadequate, relying heavily on family members for rehabilitation.

Low calf circumference can predict nutritional risk and mortality in adults with metabolic syndrome aged over 80 years.

BACKGROUND: Metabolic disorders and malnutrition are a double burden worldwide. The aim was to determine whether low calf circumference (CC) could predict nutritional risk and the cut-off values of CC for predicting nutritional risk in metabolic syndrome (MetS) patients aged over 80 years. We aimed to evaluate the risk factors for predicting mortality in MetS. METHODS: A total of 514 patients aged over 80 years with MetS were enrolled and followed for 2.5 years. On admission, demographic data, CC, and laboratory parameters were obtained. Patients with a Nutritional Risk Screening 2002 (NRS 2002) total score ≥ 3 were considered to have nutritional risk. RESULTS: The CC level was significantly lower in the nutritional risk group than in the non-nutritional risk with MetS group (27.1 ± 4.0 cm vs. 30.8 ± 3.9 cm). Logistic regression analysis of nutritional risk revealed that increasing CC (adjusted OR, 0.81; 95% CI, 0.74-0.88) was an independent protective factor against nutrition risk. The best CC cut-off value for predicting nutritional risk according to the NRS 2002 was 28.8 cm. Cox regression multivariate models showed nutritional risk (HR, 2.48; 95% CI, 1.22-5.04) and decreased CC (HR, 2.78; 95% CI, 1.27-5.98) remained independent risk factors for mortality. CONCLUSION: Decreased CC could predict not only nutritional risk but also mortality in MetS patients aged over 80 years. The elderly who had MetS with nutritional risk should be discovered early, early intervention and early treatment. CC may be a valuable index to screen out this population.

Artificially designed routes for the conversion of starch to value-added mannosyl compounds through coupling in vitro and in vivo metabolic engineering strategies.

Starch/cellulose has become the major feedstock for manufacturing biofuels and biochemicals because of their abundance and sustainability. In this study, we presented an artificially designed "starch-mannose-fermentation" biotransformation process through coupling the advantages of in vivo and in vitro metabolic engineering strategies together. Starch was initially converted into mannose via an in vitro metabolic engineering biosystem, and then mannose was fermented by engineered microorganisms for biomanufacturing valuable mannosyl compounds. The in vitro metabolic engineering biosystem based on phosphorylation/dephosphorylation reactions was thermodynamically favorable and the conversion rate reached 81%. The mannose production using whole-cell biocatalysts reached 75.4 g/L in a 30-L reactor, indicating the potential industrial application. Furthermore, the produced mannose in the reactor was directly served as feedstock for the fermentation process to bottom-up produced 19.2 g/L mannosyl-oligosaccharides (MOS) and 7.2 g/L mannosylglycerate (MG) using recombinant Corynebacterium glutamicum strains. Notably, such a mannose fermentation process facilitated the synthesis of MOS, which has not been achieved under glucose fermentation and improved MG production by 2.6-fold than that using the same C-mole of glucose. This approach also allowed access to produce other kinds of mannosyl derivatives from starch.

Low calf circumference is associated with frailty in diabetic adults aged over 80 years.

BACKGROUND: Frailty is now seen as a significant factor in older people with diabetes, whose mortality and disability increased. This study aims to investigate the association between calf circumference (CC) with frailty in diabetic adults aged over 80 years. METHODS: A cross-sectional analysis was performed on the data of 426 diabetic adults aged over 80 years. On admission, demographic data and laboratory parameters were recorded. CC was measured on the lower right leg at the point of the maximal circumference. All participants accepted frailty assessments. Frailty was mainly defined using the Fried frailty phenotype criteria. RESULTS: The CC levels were significantly lower in the frail than the non-frail (26.7 ± 4.0 vs. 31.2 ± 4.0, P < 0.001). CC was negatively correlated with the Fried frailty phenotype index (P < 0.001). Logistic regression analysis of frailty revealed that age (Odds Ratio (OR), 1.368; 95% Confidential Interval (CI) 1.002-1.869; P = 0.049), CC (OR, 0.756; 95%CI 0.598-0.956; P = 0.019) were independent impact factors of frailty after adjusting all the potential confounders. Participants with low CC tertile had a significantly higher Fried frailty phenotype index than those with high CC tertiles. The best CC cut-off value for predicting frailty was 29.3 cm, its sensitivity was 75.0%, and the specificity was 78.6%, and areas under the curve (AUC) was 0.786 (P < 0.001). CONCLUSIONS: CC was strongly related to frailty in diabetic adults aged over 80 years, suggesting that CC may be helpful for monitoring physical frailty in older adults in clinical and research settings.

Development of food-grade expression system for d-allulose 3-epimerase preparation with tandem isoenzyme genes in Corynebacterium glutamicum and its application in conversion of cane molasses to D-allulose.

D-Allulose 3-epimerase (DAE) has been applied to produce D-allulose, a low-calorie and functional sweetener. In this study, a new DAE from Paenibacillus senegalensis was characterized in Escherichia coli. Furthermore, we presented a tandem isoenzyme gene expression strategy to express multiple DAEs in one cell and construct food-grade expression systems based on Corynebacterium glutamicum. Seventeen expression cassettes based on three DAE genes from different organisms were constructed. Among all recombinant strains, DAE16 harboring three DAE genes in an expression vector exhibited the highest enzyme activity with 22.7 U/mg. Whole-cell transformation of DAE16 produced 225 g/L D-allulose with a volumetric productivity of 353 g·g -1 ·hr -1 . The catalytic efficiency of strain C-DAE9 integrating total 11 DAE genes in chromosome was 16.4-fold higher than strains carrying one DAE. Fed-batch culture of C-DAE9 gave enzyme activity of 44,700 U/L. We also expressed a thermostable invertase in C. glutamicum and obtained enzyme activity of 29 U/mg. Immobilized cells expressing DAE or invertase exhibited 80% of retained activity after 30 cycles of catalytic reactions. Those immobilized cells were coupled to produce 61.2 g/L D-allulose from cane molasses in a two-step reaction process. This study provided an efficient approach for enzyme preparation and allowed access to produce D-allulose from other abundant and low-cost feedstock enriched with sucrose.

Low serum potassium level is associated with nonalcoholic fatty liver disease and its related metabolic disorders.

CONTEXT: Subjects with nonalcoholic fatty liver disease (NAFLD) have a high risk of developing type 2 diabetes and cardiovascular diseases. Low serum potassium concentration or low dietary potassium intake can result in metabolic disorders. OBJECTIVE: Our objective was to evaluate the association between low serum potassium level and prevalence of NAFLD in a Chinese population. DESIGN: A population-based cross-sectional study. PATIENTS: We conducted a community-based study in 8592 subjects to investigate the association of serum potassium with the risk of prevalent NAFLD. NAFLD was diagnosed by hepatic ultrasonography. RESULTS: The prevalence rate of NAFLD was 30·3% in this population and gradually decreased across serum potassium quartiles. With the reduction in serum potassium level, participants have larger waist circumference (WC) and more severe insulin resistance. The correlations hold also in multivariate linear regression analysis. In logistic regression analysis, compared with subjects in the highest quartile of serum potassium level, the adjusted odds ratios (ORs) in the lowest quartile was 1·33 [95% confidence interval (CI), 1·11-1·60] for NAFLD, 1·81 (95% CI, 1·49-2·19) for insulin resistance and 1·58 (95% CI, 1·30-1·93) for central obesity. In subgroup analysis after multiple adjustments, significant relation between serum potassium level and prevalent NAFLD was detected in women, younger subjects, those with insulin resistance and those with central obesity, respectively. CONCLUSION: Low serum potassium level significantly associated with prevalence of NAFLD in middle-aged and elderly Chinese.

Association between carotid intima-media thickness and index of central fat distribution in middle-aged and elderly Chinese.

BACKGROUND: Evidence has demonstrated that central fat distribution produces the most profound metabolic abnormalities and is associated with an increased risk of atherosclerotic cardiovascular diseases. We aimed to investigate whether the indexes of central fat distribution, including waist-to-height ratio (WHtR) and visceral fat area (VFA), were stronger risk factors of subclinical atherosclerosis than body mass index (BMI) in Chinese adults. METHODS: A total of 3381 participants aged 40 years or older without history of cardiovascular diseases (CVD) were enrolled in the present cross-sectional study from the Songnan community, Shanghai, China. Height, weight and waist circumference (WC) were measured by experienced physicians. High-resolution B-mode ultrasonography was performed to measure carotid intima-media thickness (CIMT). Regional adiposity was measured by a dual-source computed tomography (CT) scanner. RESULTS: Normal weight but central obesity group (BMI < 23 kg/m2 and WHtR > 0.5) had higher levels of systolic blood pressure (SBP), fasting plasma glucose (FPG), 2 h post-load glucose (2 h PG), Hemoglobin A1c (HbA1c), and CIMT, as well as an elevated prevalence of hypertension and diabetes compared with overweight/obesity but not central obesity group (BMI ≥ 23 kg/m2 and WHtR ≤ 0.5). In logistic regression analysis, WHtR > 0.5 was significantly and independently associated with elevated CIMT (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.01-1.68, p value = 0.044). Similar association was noted for each standard deviation (SD) increase of WHtR (OR 1.25, 95% CI 1.07-1.47, p value = 0.006). Stepwise multiple linear regression analysis revealed that both WHtR and VFA were important determinants of CIMT, independent of other well-recognized risk factors (both p values < 0.01). CONCLUSIONS: WHtR and VFA were associated with CIMT, independent of BMI and conventional CVD risk factors. Given the relatively high cost and complexness of VFA measurement, WHtR could be a more convenient and appropriate measure of abdominal obesity in clinical practice.

Biomimetic androgen receptor-based AIE biosensor for detecting bisphenol analogues: An integrating in silico topological analysis, molecular docking, and experimental validation study.

Bisphenol analogues are the typical class of endocrine disrupting chemicals (EDCs) that interfere with binding of endogenous hormones to androgen receptor (AR). With the expansion of industrial activities and the intensification of environmental pollution, an increasing array of bisphenol analogues is being released into the environment and food chain. This highlights the urgency to develop sensitive methods for the detection of bisphenol analogues. Here, we propose a biomimetic AR-based biosensor platform for detecting bisphenol analogues (BPF, TBBPA, and TBBPS) by binding with Aggregation-Induced Emission (AIE) probes. Following a comparison of the PROSS and ABACUS methods, biomimetic AR was designed using the ABACUS approach and subsequently expressed in vitro via the E. coli expression system. Through molecular docking and the observation of fluorescence changes upon binding with biomimetic AR, BS-46006 was selected as the AIE probe for the biosensor. The biomimetic AR-based biosensor showed sensitive detections of BPF, TBBPA, and TBBPS within a range of 0-50 mM. To further elucidate the multi-residue recognition mechanism, molecular orbitals, Electron Localization Function (ELF), and Localized Orbital Locator (LOL) were systematically calculated in this study. Lowest unoccupied molecular orbital and highest occupied molecular orbital indicated the energy gap of BPF, TBBPA, and TBBPS, which correspond to 0.12812, 0.19689, and 0.18711 eV, respectively. ELF and LOL offered clearer perspective through heat maps to visually represent the electron delocalization in BPF, TBBPA, and TBBPS. The matrix effect analysis suggested that the responses of bisphenol analogues in soil matrices could be effectively mitigated through sample pretreatment. The analysis of spiked soil samples showed the acceptable recoveries ranged from 91 % to 105 %. Additionally, the biomimetic AR-based AIE biosensor, which combines multi-residue detection with Tolerable Daily Intakes, shows great promise for the risk assessment of bisphenol analogues. This research may present a viable approach for the analysis of environmental pollutants.

Multiplex aptamer cluster detection platform and systems toxicology study for 17ß-estradiol, bisphenol A, and diethylstilbestrol.

Intake of 17ß-estradiol (E2), bisphenol A (BPA), and diethylstilbestrol (DES) from food can contribute to endocrine disorders. Therefore, developing a sensitive method for the simultaneous detection of E2, BPA, and DES and understanding their combined effects on endocrine disruption are crucial. We developed a fluorescence aptasensing platform utilizing DNase I-assisted cyclic enzymatic signal amplification in conjunction with an aptamer/graphene oxide complex. Using PEG 20000 as a surface-blocking agent, the aptasensor achieved ultralow detection limits of 2.643, 0.3039, and 0.6996 for E2, BPA, and DES, respectively. The sensor demonstrated accurate detection in plastic bottled water at spiked levels of 10 and 100 ng/mL. Systems toxicology revealed 30 potential targets for mixture-induced endocrine disruption. Molecular docking showed binding affinities of E2, BPA, and DES for ESR1 of -9.94, -8.29, and - 8.98 kcal/mol, respectively. These results highlight the effectiveness of the aptasensor and provide valuable insights into endocrine disruption mechanisms.

The association of subjective sleep characteristics and plasma biomarkers of Alzheimer's disease pathology in older cognitively unimpaired adults with higher amyloid-ß burden.

We aimed to investigate the association of subjective sleep characteristics and plasma Alzheimer's disease (AD) biomarkers in older cognitively unimpaired adults with higher amyloid-ß (Aß) burden. Unimpaired cognition was determined by education-adjusted performance for the Mini-Mental State Examination and exclusion of dementia and mild cognitive impairment via standardized neuropsychological tests. We used Pittsburgh Sleep Quality Index (PSQI) to assess subjective sleep quality. The participants also underwent examination of plasma AD biomarkers and 18F-florbetapir PET scan. Correlation and multiple linear regression analyses were used to investigate the association between subjective sleep characteristics and AD biomarkers. A total of 335 participants were included and 114 were Aß-PET positive. Multivariable regression analysis showed sleep duration > 8 h and sleep disturbance were associated with Aß deposition in total participants. Two multiple linear regression models were applied and the results revealed in participants with Aß-PET (+), falling asleep at ≥ 22:00 to ≤ 23:00 was associated with higher levels of Aß42 and Aß42/40. Other associations with higher Aß42/40 and standard uptake value ratio contained sleep efficiency value, sleep efficiency ≥ 75%, no/mild daytime dysfunction and PSQI score ≤ 5. Higher p-Tau-181 level was associated with sleep latency > 30 min in Aß-PET (+) group and moderate/severe sleep disturbance in Aß-PET (-) group. Our data suggests sleep duration ≤ 8 h and no/mild sleep disturbance may be related to less Aß burden. In participants with Aß deposition, falling asleep at 22:00 to 23:00, higher sleep efficiency (at least ≥ 75%), no/mild daytime dysfunction, sleep latency ≤ 30 min, and good sleep quality may help improve AD pathology.

Underwater acoustic target recognition method based on a joint neural network.

To improve the recognition accuracy of underwater acoustic targets by artificial neural network, this study presents a new recognition method that integrates a one-dimensional convolutional neural network and a long short-term memory network. This new network framework is constructed and applied to underwater acoustic target recognition for the first time. Ship acoustic data are used as input to evaluate the network performance. A visual analysis of the recognition results is performed. The results show that this method can realize the recognition and classification of underwater acoustic targets. Compared with a single neural network, the relevant indices, such as the recognition accuracy of the joint network are considerably higher. This provides a new direction for the application of deep learning in the field of underwater acoustic target recognition.

Effects of Intestinal Microorganisms on Metabolism and Toxicity Mitigation of Zearalenone in Broilers.

Zearalenone (ZEN) is an estrogenic mycotoxin, and chickens are relatively insensitive to it. In this study, the effects of intestinal microorganisms on ZEN metabolism and toxicity mitigation in broilers were studied by two experiments. Firstly, in vitro, ZEN was incubated anaerobically with chyme from each part of the chicken intestine to study its intestinal microbial metabolism. Then, in vivo, we explored the effects of intestinal microbiota on ZEN by inhibiting intestinal microorganisms. Broilers were fed a control diet, 2.5 mg/kg ZEN diet, microbial inhibition diet or 'microbial inhibition +2.5 mg/kg ZEN' diet. In vitro, the results showed that the rates of ZEN degradation by microorganisms in the duodenum, ileum, caecum, and colon were 56%, 12%, 15%, and 17%, respectively, and the microorganisms could convert ZEN into Zearalenol (ZOL). After microbial inhibition in vivo, the content of ZEN and its metabolites in excreta of broilers increased significantly, and antioxidant damage and liver damage were aggravated. 16S rRNA sequencing results showed that antioxidant indices and the content of ZEN and its metabolites in excreta were significantly correlated with the relative abundance of Streptococcus, Lactococcus and Enterococcus, etc. In conclusion, the intestinal microorganisms of broilers play an important role in ZEN metabolism and ZEN-induced antioxidant and liver injury mitigation, among which the key bacteria include Streptococcus, Lactococcus and Enterococcus, etc.

Sarcopenia Index Based on Serum Creatinine and Cystatin C is Associated with Mortality, Nutritional Risk/Malnutrition and Sarcopenia in Older Patients.

Purpose: To investigate the association of sarcopenia index (SI) [(serum creatinine/serum cystatin C) × 100] with mortality, nutritional risk/malnutrition and sarcopenia among hospitalized older adults. Subjects and Methods: A prospective analysis was performed in 758 hospitalized older adults. Anthropometric measures and biochemical parameters were carried out for each patient. Sarcopenia was defined according to the Asian Working Group for Sarcopenia (AWGS) 2019 algorithm. Nutritional risk/malnutrition was defined according to the European Society of Clinical Nutrition and Metabolism (ESPEN) criteria. The logistic regression analysis was employed for the analysis of correlation between the SI and other variables. Cox regression analysis was employed to analyze correlation between the SI and mortality. Results: A total of 758 participants agreed to participate in this study (589 men and 169 women; mean age: 85.6±6.1 years). The median of the follow-up period was 212 days. A total of 112 patients died. A high SI (per 1-SD was 22.1) was independently associated with all-cause mortality (HR per 1-SD = 0.61, 95% CI: 0.47-0.79), nutritional risk/malnutrition (OR per 1-SD = 0.38, 95% CI: 0.29-0.49) and sarcopenia (OR per 1-SD = 0.58, 95% CI: 0.45-0.74). High SI was positively correlated with albumin (r = 0.32, P < 0.001), hemoglobin (r = 0.24, P < 0.001), body mass index (BMI) (r = 0.12, P = 0.001), waist circumference (WC) (r = 0.08, P = 0.046), calf circumference (CC) (r = 0.45, P < 0.001), hand grip strength (HGS) (r = 0.52, P < 0.001) and negatively correlated with triglyceride glucose (TyG) (r = -0.11, P = 0.007). Conclusion: The SI based on serum cystatin C and creatinine is associated with long-term mortality, nutritional risk/malnutrition and sarcopenia in hospitalized older Chinese patients.

Effects of Zearalenone on Production Performance, Egg Quality, Ovarian Function and Gut Microbiota of Laying Hens.

Zearalenone (ZEN) is a ubiquitous contaminant in poultry feed, since ZEN and its metabolites can interfere with estrogen function and affect the reproductive ability of animals. The estrogen-like effect of ZEN on mammal is widely reported, while little information is available, regarding the effect of relatively low dose of ZEN on estrogen function and production performance of laying hens, and the relationship between them. This work was aimed to investigate the effects of ZEN on the production performance, egg quality, ovarian function and gut microbiota of laying hens. A total of 96 Hy-line brown laying hens aged 25-week were randomly divided into 3 groups including basal diet group (BD group), basal diet supplemented with 250 µg/kg (250 µg/kg ZEN group) and 750 µg/kg (750 µg/kg ZEN group) ZEN group. Here, 750 µg/kg ZEN resulted in a significant increase in the feed conversion ratio (FCR) (g feed/g egg) (p < 0.05), a decrease in the egg production (p > 0.05), albumen height and Haugh unit (p > 0.05), compared to the BD group. The serum Follicle-stimulating hormone (FSH) levels significantly decreased in ZEN supplemented groups (p < 0.05). Serum Luteinizing hormone (LH) and Progesterone (P) levels in the 750 µg/kg ZEN group were significantly lower than those in the BD group (p < 0.05). 16S rRNA sequencing indicated that ZEN reduced cecum microbial diversity (p < 0.05) and altered gut microbiota composition. In contrast to 250 µg/kg ZEN, 750 µg/kg ZEN had more dramatic effects on the gut microbiota function. Spearman's correlation analysis revealed negative correlations between the dominant bacteria of the 750 µg/kg ZEN group and the production performance, egg quality and ovarian function of hens. Overall, ZEN was shown to exert a detrimental effect on production performance, egg quality and ovarian function of laying hens in this study. Moreover, alterations in the composition and function of the gut microbiota induced by ZEN may be involved in the adverse effects of ZEN on laying hens.

Knockdown of Peroxiredoxin V increased the cytotoxicity of non-thermal plasma-treated culture medium to A549 cells.

Administration of non-thermal plasma therapy via the use of plasma-activated medium (PAM) might be a novel strategy for cancer treatment, as it induces apoptosis by increasing reactive oxygen species (ROS) levels. Peroxiredoxin V (PRDX5) scavenges ROS and reactive nitrogen species and is known to regulate several physiological and pathological reactions. However, its role in lung cancer cells exposed to PAM is unknown. Here, we investigated the effect of PRDX5 in PAM-treated A549 lung cancer cells and determined the mechanism underlying its cytotoxicity. Cell culture medium was treated with low temperature plasma at 16.4 kV for 0, 60, 120, or 180 s to develop PAM. PRDX5 was knocked down in A549 cells via transfection with short hairpin RNA targeting PRDX5. Colony formation and wound healing assays, flow cytometry, fluorescence microscopy, and western blotting were performed to detect the effect of PRDX5 knockdown on PAM-treated A549 cells. PAM showed higher cytotoxicity in lung cancer cells than in control cells, downregulated the mitogen-activated protein kinase signaling pathway, and induced apoptosis. PRDX5 knockdown significantly inhibited cell colony formation and migration, increased ROS accumulation, and reduced mitochondrial membrane potential in lung cancer cells. Hence, PRDX5 knockdown combined with PAM treatment represents an effective option for lung cancer treatment.

Ethyl ß-Carboline-3-Carboxylate Increases Cervical Cancer Cell Apoptosis Through ROS-p38 MAPK Signaling Pathway.

BACKGROUND/AIM: Ethyl ß-carboline-3-carboxylate (ß-CCE) is one of the effective ingredients of Picrasma quassioides (P. quassioides). As a ß-carboline alkaloid, it can antagonize the pharmacological effects of benzodiazepines by regulating neurotransmitter secretion through receptors, thus affecting anxiety and physiology. However, its efficacy in cancer treatment is still unclear. MATERIALS AND METHODS: We explored the effect of b-CCE on SiHa cells using MTT assay, western blot, flow cytometry, LDH release, T-AOC, SOD, and MDA assays. RESULTS: We investigated the cytotoxicity of ß-CCE in SiHa cells and verified that ß-CCE could induce cell apoptosis in a time- and concentration-dependent manner. In this process, treatment with ß-CCE significantly increased the levels of cytoplasmic and mitochondrial reactive oxygen species (ROS), which disturb the oxidation homeostasis by regulating the total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, and malondialdehyde (MDA) production. Notably, the addition of N-acetylcysteine (NAC) (ROS scavenger) effectively alleviated ß-CCE-induced apoptosis in SiHa cells. In addition, ß-CCE might activate the p38/MAPK signaling pathway, as the pre-treatment with SB203580 (p38 inhibitor) significantly reduced ß-CCE-induced apoptosis in SiHa cells. CONCLUSION: ß-CCE has an anti-tumor activity. It activates the p38/MAPK signaling pathway by increasing intracellular ROS levels, which subsequently induce SiHa cell apoptosis. Our results provide a novel therapeutic target for treatment of cervical cancer.

Peroxiredoxin 5 protects HepG2 cells from ethyl ß-carboline-3-carboxylate-induced cell death via ROS-dependent MAPK signalling pathways.

Peroxiredoxin 5 (PRDX5) is the member of Prxs family, widely reported to be involved in various types of cell death. We previously found that PRDX5 knockdown increases the susceptibility of cell death upon oxidative stress treatment. Ethyl ß-carboline-3-carboxylate (ß-CCE), an alkaloid extracted from Picrasma quassioides, has been reported to play a role in neuronal disease, but its anti-cancer potential on liver cancers remains unknown. Here, we studied the effect of PRDX5 on ethyl ß-carboline-3-carboxylate (ß-CCE)-induced apoptosis of hepatomas. High expression level of PRDX5 was deeply related with the postoperative survival of patients with liver cancer, indicating that PRDX5 may be a biomarker of live cancer processing. Moreover, PRDX5 over-expression in HepG2 cells significantly inhibited ß-CCE-induced cell apoptosis and cellular ROS levels as well as mitochondrial dysfunction. Signalling pathway analysis showed that ß-CCE could significantly up-regulate the ROS-dependent MAPK signalling, which were in turn boosts the mitochondria-dependent cell apoptosis. Moreover, PRDX5 over-expression could reverse the anti-cancer effects induced by ß-CCE in HepG2 cells. Our findings suggest that PRDX5 has a protective role on ß-CCE-induced liver cancer cell death and provides new insights for using its anti-cancer properties for liver cancer treatment.

The insensitive mechanism of poultry to zearalenone: A review.

Zearalenone (ZEN) is one of the most common contaminating mycotoxins and is mainly produced by Fusarium graminearum. ZEN and its metabolites can interfere with estrogen function and affect animals' reproductive ability. Pigs are most susceptible to ZEN, and ZEN is less harmful to poultry than to pigs. The exact mechanism for the difference in susceptibility remains unclear. In this review, we summarized some possible reasons for the relative insensitivity of poultry to ZEN, such as the lower total amount of α-zearalenol (α-ZOL) and the α-ZOL-to-ß-ZOL ratio which reduce the toxicity of ZEN to poultry. The faster hepatic and enteric circulation, and excretion capacity in poultry can excrete more ZEN and its metabolites. There are other possible factors such as the transformation of intestinal microorganisms, differences in hydroxysteroid dehydrogenases' activity, high estrogen levels, and low estrogen receptors affinity which can also cause poultry to be relatively insensitive to ZEN. In this review, we summarized the hazards, pollution status, metabolic pathways, and some measures to mitigate ZEN's harmfulness. Specifically, we discussed the possible mechanisms of low reproductive toxicity by ZEN in poultry.

Regulatory function of peroxiredoxin I on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung cancer development.

Smoking is a major cause of lung cancer, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the most important carcinogens in cigarette smoke. NNK modulates the expression of peroxiredoxin (Prdx) I in lung cancer. Prdx1 is upregulated in lung squamous cell carcinoma and lung adenocarcinoma, and considered a potential biomarker for lung cancer. The current article reviewed the role and regulatory mechanisms of Prdx1 in NNK-induced lung cancer cells. Prdx1 protects erythrocytes and DNA from NNK-induced oxidative damage, prevents malignant transformation of cells and promotes cytotoxicity of natural killer cells, hence suppressing tumor formation. In addition, Prdx1 has the ability to prevent NNK-induced lung tumor metabolic activity and generation of large amount of reactive oxygen species (ROS) and ROS-induced apoptosis, thus promoting tumor cell survival. In contrast to this, Prdx1, together with NNK, can promote the epithelial-mesenchymal transition and migration of lung tumor cells. The signaling pathways associated with NNK and Prdx1 in lung cancer cells have been discussed in present review; however, numerous potential pathways are yet to be studied. To develop novel methods for treating NNK-induced lung cancer, and improve the survival rate of patients with lung cancer, further research is needed to understand the complete mechanism associated with NNK.