Altered vaginal cervical microbiota diversity contributes to HPV-induced cervical cancer via inflammation regulation.

Background: Cancer has surpassed infectious diseases and heart ailments, taking the top spot in the disease hierarchy. Cervical cancer is a significant concern for women due to high incidence and mortality rates, linked to the human papillomavirus (HPV). HPV infection leads to precancerous lesions progressing to cervical cancer. The cervix's external os, near the vagina, hosts various microorganisms. Evidence points to the link between vaginal microbiota and HPV-induced cervical cancer. Cervical cancer onset aligns with an imbalanced Th1/Th2 immune response, but the role of vaginal microbiota in modulating this imbalance is unclear. Methods: In this study, we collected vaginal samples from 99 HPV-infected patients across varying degrees of lesions, alongside control groups. These samples underwent bacterial DNA sequencing. Additionally, we employed Elisa kits to quantify the protein expression levels of Th1/Th2 cytokines IL2, IL12, IL5, IL13, and TNFa within the centrifuged supernatant of vaginal-cervical secretions from diverse research subjects. Subsequently, correlation analyses were conducted between inflammatory factors and vaginal microbiota. Results: Our findings highlighted a correlation between decreased Lactobacillus and increased Gardenerella presence with HPV-induced cervical cancer. Functionally, our predictive analysis revealed the predominant enrichment of the ABC transporter within the vaginal microbiota of cervical cancer patients. Notably, these microbiota alterations exhibited correlations with the production of Th1/Th2 cytokines, which are intimately tied to tumor immunity. Conclusions: This study suggests the potential involvement of vaginal microbiota in the progression of HPV-induced cervical cancer through Th1/Th2 cytokine regulation. This novel insight offers a fresh perspective for early cervical cancer diagnosis and future prevention strategies.

Exploring the Mechanism of Brucea Javanica against Ovarian Cancer based on Network Pharmacology and the Influence of Luteolin on the PI3K/AKT Pathway.

BACKGROUND: Ovarian cancer (OC) is a commonly diagnosed female cancer around the world. The Chinese herbal medicine Brucea Javanica has an anti-cancer effect. However, there is no relevant report on whether Brucea Javanica is effective in treating OC, and the corresponding mechanism is also unknown. OBJECTIVE: This study was projected to excavate the active components and underpinned molecular mechanisms of Brucea Javanica in treating ovarian cancer (OC) through network pharmacology combined with in vitro experiments. METHODS: The essential active components of Brucea Javanica were selected using the TCMSP database. The OC-related targets were selected by GeneCards, intersecting targets were obtained by Venn Diagram. The core targets were obtained through the PPI network and Cytoscape, and the key pathway was gained through GO and KEGG enrichment analyses. Meanwhile, docking conformation was observed as reflected by molecular docking. MTT, colony formation assay and flow cytometer (FCM) analysis were performed to determine cell proliferation and apoptosis, respectively. Finally, Levels of various signaling proteins were evaluated by western blotting. RESULTS: Luteolin, ß-sitosterol and their corresponding targets were selected as the essential active components of Brucea Javanica. 76 intersecting targets were obtained by Venn Diagram. TP53, AKT1, and TNF were obtained through the PPI network and Cytoscape, and the key pathway PI3K/AKT was gained through GO and KEGG enrichment analyses. A good docking conformation was observed between luteolin and AKT1. Luteolin could hinder A2780 cell proliferation, induce cell apoptosis and enhance the inhibition of the PI3K/AKT pathway. CONCLUSION: It was verified in vitro that luteolin could hinder OC cell proliferation and activate the PI3K/AKT pathway to lead to apoptosis.

Effects of peripheral blood neutrophil/lymphocyte ratio levels and their changes on the prognosis of patients with early cervical cancer.

Although some studies have reported on the levels and clinical significance of peripheral blood neutrophil/lymphocyte ratio (NLR) in cervical cancer, the role of NLR levels and their changes preoperatively and postoperatively in early cervical cancer remain unclear. Our analyses explored the preoperative and postoperative NLR in 203 patients with stage I-IIA cervical cancer and evaluated the relationship between NLR changes, clinicopathological characteristics, and patient prognosis. The cut-off preoperative and postoperative NLR values were determined using receiver operating characteristic curve analysis. Preoperative NLR correlated with age, menopausal status, tumor size, and vascular infiltration, whereas postoperative NLR correlated with tumor differentiation. Patients with cervical cancer with a high preoperative NLR had significantly shorter overall survival (OS) and progression-free survival (PFS) than other patients, whereas PFS was significantly lower in the high postoperative NLR group. When comparing postoperative and preoperative NLR values, we observed a significantly higher rate of increase in postmenopausal patients and those without vascular infiltration than that among premenopausal patients and those with vascular infiltration. However, no clear difference in prognosis was observed between the groups with increased and decreased NLR. Therefore, a high peripheral blood NLR may predict a poor prognosis in patients with early cervical cancer. The effect of NLR changes on the prognosis of patients with cervical cancer requires further verification in multicenter studies.

The detection of self-group conflicts in exercise behaviors differs with social network centrality: ERP evidence.

BACKGROUND: The influence of social norms on exercise behaviors has been explored in studies over the years. However, little is known about whether an individual's role (central or peripheral) in his or her social network, which is associated with social skills, could shift his or her susceptibility to normative effects on exercise behaviors. To that end, event-related potentials (ERPs) were recorded to examine the underlying cognitive mechanism of the effects of network centrality on normative social influence. METHODS: We manipulated network centrality by assigning participants to exercise support groups, with group members who were their nominated friends (high centrality) or nonnominated classmates (low centrality). Participants were asked to evaluate their willingness to engage in various exercises, after viewing discrepant group ratings (peer influence) or not viewing (no-influence). RESULTS: Peer influence evoked a larger negative-going feedback-related negativity (FRN) wave, which was linked to automatic social conflict detection, and a larger positive-going P3 wave, which was linked to subsequent conformity behavioral changes. However, effects on the FRN, not the P3, were observed only in the high-centrality group. CONCLUSION: Our results highlight the important roles of network centrality in encoding self-group exercise attitude discrepancy rather than in decision-making regarding exercise attitude adjustments. Interventions aimed at promoting exercise behaviors should be considered in a broader social environmental framework.

Microbial community evolution and functional trade-offs of biofilm in odor treatment biofilters.

Biofilters inoculated with activated sludge are widely used for odor control in WWTP. In this process, biofilm community evolution plays an important role in the function of reactor and is closely related to reactor performance. However, the trade-offs in biofilm community and bioreactor function during the operation are still unclear. Herein, an artificially constructed biofilter for odorous gas treatment was operated for 105 days to study the trade-offs in the biofilm community and function. Biofilm colonization was found to drive community evolution during the start-up phase (phase 1, days 0-25). Although the removal efficiency of the biofilter was unsatisfactory at this phase, the microbial genera related to quorum sensing and extracellular polymeric substance secretion led to the rapid accumulation of the biofilm (2.3 kg biomass/m3 filter bed /day). During the stable operation phase (phase 2, days 26-80), genera related to target-pollutant degradation showed increases in relative abundance, which accompanied a high removal efficiency and a stable accumulation of biofilm (1.1 kg biomass/m3 filter bed/day). At the clogging phase (phase 3, days 81-105), a sharp decline in the biofilm accumulation rate (0.5 kg biomass/m3 filter bed /day) and fluctuating removal efficiency were observed. The quorum quenching-related genera and quenching genes of signal molecules increased, and competition for resources among species drove the evolution of the community in this phase. The results of this study highlight the trade-offs in biofilm community and functions during the operation of bioreactors, which could help improve bioreactor performance from a biofilm community perspective.

Degradation of trichloroethylene by double dielectric barrier discharge (DDBD) plasma technology: Performance, product analysis and acute biotoxicity assessment.

Trichloroethylene is carcinogenic and poorly degraded by microorganisms in the environment. Advanced Oxidation Technology is considered to be an effective treatment technology for TCE degradation. In this study, a double dielectric barrier discharge (DDBD) reactor was established to decompose TCE. The influence of different condition parameters on DDBD treatment of TCE was investigated to determine the appropriate working conditions. The chemical composition and biotoxicity of TCE degradation products were also investigated. Results showed that when SIE was 300 J L-1, the removal efficiency could reach more than 90%. The energy yield could reach 72.99 g kWh-1 at low SIE and gradually decreased with the increase of SIE. The k of the Non-thermal plasma (NTP) treatment of TCE was about 0.01 L J-1. DDBD degradation products were mainly polychlorinated organic compounds and produced more than 373 mg m-3 ozone. Moreover, a plausible TCE degradation mechanism in the DDBD reactors was proposed. Lastly, the ecological safety and biotoxicity were evaluated, indicating that the generation of chlorinated organic products was the main cause of elevated acute biotoxicity.

Bruceine D and afatinib combination inhibits ovarian cancer cells proliferation and migration through DNA damage repair and EGFR pathway.

Owing to the high rates of relapse and migration, ovarian cancer (OC) has been recognized as the most lethal gynecological malignancy worldwide. The activity of the epidermal growth factor receptor (EGFR) signaling pathway is frequently associated with OC cell proliferation and migration. Despite this knowledge, inhibition of EGFR signaling in OC patients failed to achieve satisfactory therapeutic effects. In this study, we identified that bruceine D (BD) and EGFR inhibitor, afatinib, combination resulted in synergistic anti-OC effects. The results indicated that compared with one of both drugs alone, the combination of BD and afatinib slowed the DNA replication rate, inhibition of cell viability, and proliferation and clone formation. This resulted in cell cycle arrest and cell apoptosis. In addition, the combination of BD and afatinib possessed a stronger ability to inhibit the OC cell adhesion and migration than treatment with BD or afatinib alone. Mechanistically, the combined treatment triggered intense DNA damage, suppressed DNA damage repair, and enhanced the inhibition of the EGFR pathway. These results demonstrated that compared with each pathway inhibition, combined blocking of both DNA damage repair and the EGFR pathway appears to more effective against OC treatment. The results support the potential of BD and afatinib combination as a therapeutic strategy for OC patients.

Microbial community regulation and performance enhancement in gas biofilters by interrupting bacterial communication.

BACKGROUND: Controlling excess biomass accumulation and clogging is important for maintaining the performance of gas biofilters and reducing energy consumption. Interruption of bacterial communication (quorum quenching) can modulate gene expression and alter biofilm properties. However, whether the problem of excess biomass accumulation in gas biofilters can be addressed by interrupting bacterial communication remains unknown. RESULTS: In this study, parallel laboratory-scale gas biofilters were operated with Rhodococcus sp. BH4 (QQBF) and without Rhodococcus sp. BH4 (BF) to explore the effects of quorum quenching (QQ) bacteria on biomass accumulation and clogging. QQBF showed lower biomass accumulation (109 kg/m3) and superior operational stability (85-96%) than BF (170 kg/m3; 63-92%) at the end of the operation. Compared to BF, the QQBF biofilm had lower adhesion strength and decreased extracellular polymeric substance production, leading to easier detachment of biomass from filler surface into the leachate. Meanwhile, the relative abundance of quorum sensing (QS)-related species was found to decrease from 67 (BF) to 56% (QQBF). The QS function genes were also found a lower relative abundance in QQBF, compared with BF. Moreover, although both biofilters presented aromatic compounds removal performance, the keystone species in QQBF played an important role in maintaining biofilm stability, while the keystone species in BF exhibited great potential for biofilm formation. Finally, the possible influencing mechanism of Rhodococcus sp. BH4 on biofilm adhesion was demonstrated. Overall, the results of this study achieved excess biomass control while maintaining stable biofiltration performance (without interrupting operation) and greatly promoted the use of QQ technology in bioreactors. Video Abstract.

Acute Sleep Deprivation Impairs Motor Inhibition in Table Tennis Athletes: An ERP Study.

Excellent response inhibition is the basis for outstanding competitive athletic performance, and sleep may be an important factor affecting athletes' response inhibition. This study investigates the effect of sleep deprivation on athletes' response inhibition, and its differentiating effect on non-athlete controls' performance, with the aim of helping athletes effectively improve their response inhibition ability through sleep pattern manipulation. Behavioral and event-related potential (ERP) data were collected from 36 participants (16 table tennis athletes and 20 general college students) after 36 h of sleep deprivation using ERP techniques and a stop-signal task. Sleep deprivation's different effects on response inhibition in the two groups were explored through repeated-measures ANOVA. Behavioral data showed that in a baseline state, stop-signal response time was significantly faster in table tennis athletes than in non-athlete controls, and appeared significantly longer after sleep deprivation in both groups. ERP results showed that at baseline state, N2, ERN, and P3 amplitudes were lower in table tennis athletes than in non-athlete controls, and corresponding significant decreases were observed in non-athlete controls after 36 h of sleep deprivation. Table tennis athletes showed a decrease in P3 amplitude and no significant difference in N2 and ERN amplitudes, after 36 h of sleep deprivation compared to the baseline state. Compared to non-athlete controls, table tennis athletes had better response inhibition, and the adverse effects of sleep deprivation on response inhibition occurred mainly in the later top-down motor inhibition process rather than in earlier automated conflict detection and monitoring.

Reduction of biofilm adhesion strength by adjusting the characteristics of biofilms through enzymatic quorum quenching.

Biofilm adhesion to the surface of a carrier plays an essential role during biofilm formation. Quorum quenching (QQ) has been shown to have great potential for delaying biofouling. However, little is known about whether QQ reduces the adhesion strength of biofilms during the formation process to inhibit biomass accumulation. In this study, we explored the effect of enzymatic QQ on the adhesion strength during biofilm development. In addition, a quantitative method was used to measure the adhesion strength of biofilms based on the shear force of water flow. Experimental results showed that QQ enzyme could reduce the adhesion strength of biofilms by at least 37% compared with the control. Furthermore, the biofilm accumulation rates were 0.05673 and 0.08762 h-1 with and without the QQ enzyme, illustrating a negative effect of QQ enzyme on biofilm accumulation. Specifically, QQ was confirmed to reduce extracellular polymeric substances, decrease the relative hydrophobicity, change the zeta potential by degrading signal molecules, and weaken the adhesion strength of biofilms. The successful reduction of the adhesion strength of the biofilm through QQ could provide a new strategy for the management and regulation of biofilm adhesion in the bioreactor.

Neurobiological Bases of Social Networks.

A social network is a web that integrates multiple levels of interindividual social relationships and has direct associations with an individual's health and well-being. Previous research has mainly focused on how brain and social network structures (structural properties) act on each other and on how the brain supports the spread of ideas and behaviors within social networks (functional properties). The structure of the social network is correlated with activity in the amygdala, which links decoding and interpreting social signals and social values. The structure also relies on the mentalizing network, which is central to an individual's ability to infer the mental states of others. Network functional properties depend on multilayer brain-social networks, indicating that information transmission is supported by the default mode system, the valuation system, and the mentalizing system. From the perspective of neuroendocrinology, overwhelming evidence shows that variations in oxytocin, ß-endorphin and dopamine receptor genes, including oxytocin receptor (OXTR), mu opioid receptor 1 (OPRM1) and dopamine receptor 2 (DRD2), predict an individual's social network structure, whereas oxytocin also contributes to improved transmission of emotional and behavioral information from person to person. Overall, previous studies have comprehensively revealed the effects of the brain, endocrine system, and genes on social networks. Future studies are required to determine the effects of cognitive abilities, such as memory, on social networks, the characteristics and neural mechanism of social networks in mental illness and how social networks change over time through the use of longitudinal methods.

Emissions, measurement, and control of odor in livestock farms: A review.

Odor emissions from intensive livestock farms have attracted increased attention due to their adverse impacts on the environment and human health. Nevertheless, a systematic summary regarding the characteristics, sampling detection, and control technology for odor emissions from livestock farms is currently lacking. This paper compares the development of odor standards in different countries and summarizes the odor emission characteristics of livestock farms. Ammonia, the most common odor substance, can reach as high as 4100 ppm in the compost area. Sampling methods for point and area source odor emissions are introduced in this paper, and odor analysis methods are compared. Olfactometers, odorometers, and the triangle odor bag method are usually used to measure odor concentration. Odor control technologies are divided into three categories: physical (activated carbon adsorption, masking, and dilution diffusion), chemical (plant extract spraying, wet scrubbing, combustion, non-thermal plasma, and photocatalytic oxidation), and biological (biofiltration, biotrickling, and bioscrubbing). Each technology is elucidated, and the performance in the removal of different pollutants is summarized. The application scopes, costs, operational stability, and secondary pollution of the technologies are compared. The generation of secondary pollution and long-term operation stability are issues that should be considered in future technological development. Lastly, a case analysis for engineering application is conducted.

Improving Broadband White-Light Emission Performances of 2D Perovskites by Subtly Regulating Organic Cations.

Recently, 2D organic-inorganic hybrid lead halide perovskites have attracted intensive attention in solid-state luminescence fields such as single-component white-light emitters, and rational optimization of the photoluminescence (PL) performance through accurate structural-design strategies is still significant. Herein, by carefully choosing homologous aliphatic amines as templates, isotypical perovskites [DMEDA]PbCl4 (1, DMEDA=N,N-dimethylethylenediamine) and [DMPDA]PbCl4 (2, DMPDA=N,N-dimethyl-1,3-diaminopropane) having tunable and stable broadband bluish white emission properties were rationally designed. The subtle regulation of organic cations leads to a higher degree of distortion of the 2D [PbCl4 ]2- layers and enhanced photoluminescence quantum efficiencies (<1 % for 1 and 4.9 % for 2). The broadband light emissions could be ascribed to self-trapped excitons on the basis of structural characterization, time-resolved PL, temperature-dependent PL emission, and theoretical calculations. This work gives a new guidance to rationally optimize the PL properties of low-dimensional halide perovskites and affords a platform to probe the structure-property relationship.

A short review of bioaerosol emissions from gas bioreactors: Health threats, influencing factors and control technologies.

Bioaerosols have widely been a concern due to their potential harm to human health caused by the carrying and spreading of harmful microorganisms. Biofiltration has been generally used as a green and effective technology for processing VOCs. However, bioaerosols can be emitted into the atmosphere as secondary pollutants from the biofiltration process. This review presents an overview of bioaerosol emissions from gas bioreactors. The mechanism of bioaerosols production and the effect of biofiltration on bioaerosol emissions were analyzed. The results showed that the bioaerosol emission concentrations were generally exceeded 104 CFU m-3, which would damage to human health. Biomass, inlet gas velocity, moisture content, temperature, and some other factors have significant influences on bioaerosol emissions. Moreover, as a result of the analysis done herein, different inactivation technologies and microbial immobilization of bioaerosols were proposed and evaluated as a potential solution for reducing bioaerosols emissions. The purpose of this paper is to make more people realize the importance of controlling the emissions of bioaerosols in the biofiltration process and to make the treatment of VOCs by biotechnology more environmentally friendly. Additionally, the present work intends to increase people's awareness in regards to the control of bioaerosols, including microbial fragment present in bioaerosols.

Performance enhancement of a biofilter with pH buffering and filter bed supporting material in removal of chlorobenzene.

Acidic substances, which produced during chlorinated volatile organic compounds, will corrode the commonly used packing materials, and then affect the removal performance of biofiltration. In this study, three biofilters with different filter bed structure were established to treat gaseous chlorobenzene. CaCO3 and 3D matrix material was added in filter bed as pH buffering material and filter bed supporting material, respectively. A comprehensive investigation of removal performance, biomass accumulation, microbial community, filter bed height, voidage, pressure drops, and specific surface area of the three biofilters was compared. The biofilter with CaCO3 and 3D matrix material addition presented stable removal performance and microbial community, and greater biomass density (209.9 kg biomass/m3 filter bed) and growth rate (0.033 d-1) were obtained by using logistic equation. After 200 days operation, the height, voidage, pressure drop, specific surface area of the filter bed consisted of perlite was 27.4 cm, 0.39, 32.8 Pa/m, 974,89 m2/m3, while those of the filter bed with CaCO3 addition was 28.2 cm, 0.43, 21.3 Pa/m, and 1021.03 m2/m3, and those of the filter bed with CaCO3 and 3D matrix material addition was 28.7 cm, 0.55, 17.4 Pa/m, and 1041.60 m2/m3. All the results verified the biofilter with CaCO3 and 3D matrix material addition is capable of sustaining the long-term performance of biofilters. CaCO3 could limit the changes of removal efficiency, microbial community and filter bed structure by buffering the pH variation. And 3D matrix material could maintain the filter bed structure by supporting the filter bed, regardless of the buffering effect.

Gel-encapsulated microorganisms used as a strategy to rapidly recover biofilters after starvation interruption.

Biosystems used for volatile organic compound (VOC) control have slow re-acclimation after extended starvation. In this study, a gel-encapsuled microorganism biofilter (GEBF) for the treatment of VOCs was used for rapid recovery after starvation interruption. Another conventional perlite biofilter (BF) was used as a control. Results showed that GEBF and BF needed 3 and 6 days for fully recovery after short-term (6 days) starvation. For long-term (20 days) starvation, GEBF fully recovered the removal performance after 9 days, whereas BF recovered only 70% within the same period. Flow cytometry analysis indicated that GEBF presented better viability state of microbial population than that in BF under starvation. The average metabolic activity of microorganisms in GEBF remained a relatively high during and after starvation (0.0049 h-1). However, the average metabolic activity of microorganisms in BF decreased from 0.0042 h-1 before starvation to 0.0033 h-1 under starvation. Changes in the microbial community structure in GEBF and BF were investigated and compared by high-throughput sequencing and principal component analysis. Notably, the microbial community structure in the two biofilters showed different behavior. All these results demonstrated that the gel encapsulation of microorganisms is a promising strategy to resist starvation in biofiltration technologies.

The effect of traumatic-like stress exposure on alterations in the temporal social behavior of a rodent population.

Though the relationship between traumatic stress and social behavior, which has been explored for years, is dynamic and largely estimated between dyads, little is known about the causal effects of traumatic stress exposure on the time-dependent dynamic alterations in the social behaviors on a large-group level. We thus investigated the effect of a single prolonged stress (SPS) exposure, a classical animal model that recapitulates posttraumatic stress disorder (PTSD)-like symptoms in rodents, on the spatiotemporal, social behavior changes within a large group of cohabiting rats. One-half of thirty-two Sprague-Dawley rats were assigned to the experimental group and subjected to SPS treatment administered two weeks after baseline social behavior recording; the other half served as the controls. Each group of rats (n = 16) was housed in one of two large custom-made cylinders. We used an automatic tracking system to record the behavioral indices of social behavior of the rats before SPS exposure, on the SPS exposure day, during a 7-day-long quiescent period after SPS treatment, as well as during subsequent behavioral test days. In addition to SPS-induced PTSD-like behaviors, SPS induced a time-dependent, oscillating change in active/passive social behaviors that lasted for 3 weeks. SPS treatment decreased active social behaviors (especially affiliative behaviors) but increased passive social behaviors (e.g. huddling) immediately following stress exposure. Increased active social interactions were observed during the early phase after SPS treatment; while increased passive social behaviors were observed during the late phase after SPS treatment. These dynamic changes were repeatedly observed when the rats underwent subsequent stressful behavioral tests and challenges. SPS induced a long-term, time-dependent oscillating change in indices of the social behavior. These changes may serve as an adaptive mechanism, and their manifestations critically depended on the time course following the traumatic stress exposure.

Effect of Aerobic Exercise on Serum Metabolites in Mice with Hepatocellular Carcinoma After Surgery.

BACKGROUND Modern medicine has suggested exercise therapy is one of the main treatments for postoperative rehabilitation of tumors. It can influence the recovery of cancer patients by changing the body's material metabolism and energy metabolism. However, studies on metabolic changes of exercise therapy on hepatocellular carcinoma (HCC) patients after surgery are limited. The aim of this study was to explore the effect of aerobic exercise on mice after orthotopic HCC surgery by serum metabolomics test and explore the related mechanism. MATERIAL AND METHODS A total of 60 C57Bl/6 mice were used to establish an orthotopic xenograft model of H22 mouse hepatoma cells. Mice were randomly divided into 6 groups and it was found that the metabolic products of the early postoperative exercise group and sedentary group mainly included L-tryptophan, citric acid, and other energy-related metabolites. RESULTS Energy metabolites, such as succinic acid of the high-intensity exercise group were increased after surgery, whereas phospholipid metabolites, including phosphatidylethanolamine (18: 0/0: 0), were decreased. In the moderate-intensity exercise group, the change tendency was consistent, and the level of various metabolites decreased. CONCLUSIONS Thus, it is likely that aerobic exercise reduced the degree of postoperative stress responses and improved energy metabolism in mice. The underlying mechanism involves improving the tricarboxylic acid cycle, intervening in energy metabolism, reorganization caused by the tumor, reducing the abnormal increase of phospholipase activity caused by the stress of liver cancer, reducing the level of hemolytic phospholipids, thereby inhibiting mitochondrial pathway-initiated apoptosis.

The anti-tumour effect of Mel and its role in autophagy in human hepatocellular carcinoma cells.

Melittin (Mel), a major component of venom of honey bee (Apismellifera), has various biological effects. Recent researches have reported the anti-tumor activity of Mel in various human cancers, including hepatocellular carcinoma (HCC). In this study, we aimed to further discuss the role of Mel in HCC and investigate the correlation of autophagy with the effect of Mel in HCC cells. Methyl thiazolyl tetrazolium (MTT) assay and flow cytometry were used to detect the viability and apoptosis of HCC cells, respectively. To examine the changes of autophagy in HCC cells treated with Mel, transmission electronmicroscope (TEM) and immunofluorescence detection were adopted. Finally, we used western blot method to detect the changes of pivotal proteins in autophagy and mitochondrial apoptotic pathways. The results of MTT assay and flow cytometry revealed that Mel could suppress the cell viability and promote the apoptosis of HCC cells. Autophagy could be induced by the treatment with Mel in HCC cells. The inhibition of autophagy by chloroquine (CQ) contributed to the enhanced anti-tumor effect of Mel, but autophagy induction by RAPA decreased Mel effect in HCC cells. Mel was closely associated with the expression of proteins in mitochondrial apoptotic pathway. In summary, Mel could induce the autophagy of HCC cells, and the autophagy might offer protection against apoptosis in HCC. Mel might suppress the tumor through activating mitochondrial apoptotic pathway.