Rule-based omics mining reveals antimicrobial macrocyclic peptides against drug-resistant clinical isolates.

Antimicrobial resistance remains a significant global threat, driving up mortality rates worldwide. Ribosomally synthesized and post-translationally modified peptides have emerged as a promising source of novel peptide antibiotics due to their diverse chemical structures. Here, we report the discovery of new aminovinyl-(methyl)cysteine (Avi(Me)Cys)-containing peptide antibiotics through a synergistic approach combining biosynthetic rule-based omics mining and heterologous expression. We first bioinformatically identify 1172 RiPP biosynthetic gene clusters (BGCs) responsible for Avi(Me)Cys-containing peptides formation from a vast pool of over 50,000 bacterial genomes. Subsequently, we successfully establish the connection between three identified BGCs and the biosynthesis of five peptide antibiotics via biosynthetic rule-guided metabolic analysis. Notably, we discover a class V lanthipeptide, massatide A, which displays excellent activity against gram-positive pathogens, including drug-resistant clinical isolates like linezolid-resistant S. aureus and methicillin-resistant S. aureus, with a minimum inhibitory concentration of 0.25 µg/mL. The remarkable performance of massatide A in an animal infection model, coupled with a relatively low risk of resistance and favorable safety profile, positions it as a promising candidate for antibiotic development. Our study highlights the potential of Avi(Me)Cys-containing peptides in expanding the arsenal of antibiotics against multi-drug-resistant bacteria, offering promising drug leads in the ongoing battle against infectious diseases.

Exploring the roles of ribosomal peptides in prokaryote-phage interactions through deep learning-enabled metagenome mining.

BACKGROUND: Microbial secondary metabolites play a crucial role in the intricate interactions within the natural environment. Among these metabolites, ribosomally synthesized and post-translationally modified peptides (RiPPs) are becoming a promising source of therapeutic agents due to their structural diversity and functional versatility. However, their biosynthetic capacity and ecological functions remain largely underexplored. RESULTS: Here, we aim to explore the biosynthetic profile of RiPPs and their potential roles in the interactions between microbes and viruses in the ocean, which encompasses a vast diversity of unique biomes that are rich in interactions and remains chemically underexplored. We first developed TrRiPP to identify RiPPs from ocean metagenomes, a deep learning method that detects RiPP precursors in a hallmark gene-independent manner to overcome the limitations of classic methods in processing highly fragmented metagenomic data. Applying this method to metagenomes from the global ocean microbiome, we uncover a diverse array of previously uncharacterized putative RiPP families with great novelty and diversity. Through correlation analysis based on metatranscriptomic data, we observed a high prevalence of antiphage defense-related and phage-related protein families that were co-expressed with RiPP families. Based on this putative association between RiPPs and phage infection, we constructed an Ocean Virus Database (OVD) and established a RiPP-involving host-phage interaction network through host prediction and co-expression analysis, revealing complex connectivities linking RiPP-encoding prokaryotes, RiPP families, viral protein families, and phages. These findings highlight the potential of RiPP families involved in prokaryote-phage interactions and coevolution, providing insights into their ecological functions in the ocean microbiome. CONCLUSIONS: This study provides a systematic investigation of the biosynthetic potential of RiPPs from the ocean microbiome at a global scale, shedding light on the essential insights into the ecological functions of RiPPs in prokaryote-phage interactions through the integration of deep learning approaches, metatranscriptomic data, and host-phage connectivity. This study serves as a valuable example of exploring the ecological functions of bacterial secondary metabolites, particularly their associations with unexplored microbial interactions. Video Abstract.

Comparison of Deep and Moderate Neuromuscular Blockade for Major Laparoscopic Surgery in Children: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: Neuromuscular blocking agents are routinely used in laparoscopic surgery to optimize operative conditions. We compared the effect of a deep and moderate neuromuscular blockade (NMB) on surgical conditions and postoperative outcomes in children undergoing major laparoscopic surgery. METHODS: Sixty children aged 2-14 years scheduled to undergo major laparoscopic surgery were randomly allocated to deep (post-tetanic count 1-2 twitches) or moderate (train-of-four 1-2 twitches) NMB groups. The anesthesia was maintained with propofol and remifentanil, and the NMB was maintained with a rocuronium continuous infusion. At the end of the operation, the NMB were antagonized with sugammadex. The intra-abdominal pressure, airway pressure, Leiden Surgical Rating Scale, intraoperative hemodynamics, drug usages, duration of surgery, postoperative recovery time, pain, and complications were compared between the groups. RESULTS: The maximum and mean intra-abdominal pressure, the peak inspiratory pressure, and mean airway pressure were significantly lower in the deep NMB group than in the moderate NMB group (p < 0.001). The Leiden Surgical Rating Scale and the dosage of rocuronium were significantly higher in the deep NMB group than the moderate NMB group (p < 0.001). The intraoperative hemodynamics, duration of surgery, post-operative recovery time, pain, and the incidence rate of complications were not significantly different between the groups (p > 0.05). CONCLUSIONS: A deep NMB provided better operative conditions and similar recovery profiles compared with a moderate NMB as reversed with sugammadex in children undergoing major laparoscopic surgery. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, No. ChiCTR2100053821.

Identification of intratumor bacteria-associated prognostic risk score in adrenocortical carcinoma.

A landmark study by Poore et al. showed intratumor bacteria (ITBs) playing a critical role in most cancers by reproduction of The Cancer Genome Atlas (TCGA) transcriptome data. A recent study by Salzberg et al. argued that ITBs, being overstated as a methodology by Poore et al., were problematic. We previously reported that ITBs were prognostic in adrenocortical carcinoma (ACC), a highly aggressive rare disease using data by Poore et al., and here, we aimed to answer whether ITBs truly existed and were prognostic in ACC. ACC samples from our institutes underwent 16S rRNA sequencing [adrenocortical carcinoma blocks from Huashan Hospital and China Medical University (HS) cohort]. The ITB profile was compared to TCGA data processed by Poore et al. (TCGA-P) and TCGA data processed by Salzberg et al. (TCGA-S), respectively. The primary outcome was overall survival (OS). A total of 26 ACC cases (HS cohort) and 10 paraffin controls were sequenced. The TCGA cohort encompassed 77 cases. Two and four amid the top 10 abundant genera in HS cohort were not detected in TCGA-P and TCGA-S, respectively. Neither was alpha or beta diversity associated with survival nor could ACC be subtyped by ITB signature in the HS cohort. Notably, a five-genera ITB risk score (Corynebacterium, Mycoplasma, Achromobacter, Anaerococcus, and Streptococcus) for OS trained in the HS cohort was validated in both TCGA-P and TCGA-S cohorts and was independently prognostic. Whereas ITB signature on the whole may not be associated with ACC subtypes, certain ITB features are associated with prognosis, and a risk score could be generated and validated externally. IMPORTANCE: In this report, we looked at the role of ITBs in ACC in patients with different race and sequencing platforms. We found a five-genera ITB risk score consistently predicted overall survival in all cohorts. We conclude that certain ITB features are universally pathogenic to ACC.

Bacterial Cytochrome P450 Catalyzed Post-translational Macrocyclization of Ribosomal Peptides.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a fascinating group of natural products that exhibit diverse structural features and bioactivities. P450-catalyzed RiPPs stand out as a unique but underexplored family. Herein, we introduce a rule-based genome mining strategy that harnesses the intrinsic biosynthetic principles of RiPPs, including the co-occurrence and co-conservation of precursors and P450s and interactions between them, successfully facilitating the identification of diverse P450-catalyzed RiPPs. Intensive BGC characterization revealed four new P450s, KstB, ScnB, MciB, and SgrB, that can catalyze the formation of Trp-Trp-Tyr (one C-C and two C-N bonds), Tyr-Trp (C-C bond), Trp-Trp (C-N bond), and His-His (ether bond) crosslinks, respectively, within three or four residues. KstB, ScnB, and MciB could accept non-native precursors, suggesting they could be promising starting templates for bioengineering to construct macrocycles. Our study highlights the potential of P450s to expand the chemical diversity of strained macrocyclic peptides and the range of biocatalytic tools available for peptide macrocyclization.

Refactoring and Heterologous Expression of Class III Lanthipeptide Biosynthetic Gene Clusters Lead to the Discovery of N,N-Dimethylated Lantibiotics from Firmicutes.

Class III lanthipeptides are an emerging subclass of lanthipeptides, representing an underexplored trove of new natural products with potentially broad chemical diversity and important biological activity. Bioinformatic analysis of class III lanthipeptide biosynthetic gene cluster (BGC) distribution has revealed their high abundance in the phylum Firmicutes. Many of these clusters also feature methyltransferase (MT) genes, which likely encode uncommon class III lanthipeptides. However, two hurdles, silent BGCs and low-yielding pathways, have hindered the discovery of class III lanthipeptides from Firmicutes. Here, we report the design and construction of a biosynthetic pathway refactoring and heterologous overexpression strategy which seeks to overcome these hurdles, simultaneously activating and increasing the production of these Firmicutes class III lanthipeptides. Applying our strategy to MT-containing BGCs, we report the discovery of new class III lanthipeptides from Firmicutes bearing rare N,N-dimethylations. We reveal the importance of the first two amino acids in the N-terminus of the core peptide in controlling the MT dimethylation activity. Leveraging this feature, we engineer class III lanthipeptides to enable N,N-dimethylation, resulting in significantly increased antibacterial activity. Furthermore, the refactoring and heterologous overexpression strategy showcased in this study is potentially applicable to other ribosomally synthesized and post-translationally modified peptide BGCs from Firmicutes, unlocking the genetic potential of Firmicutes for producing peptide natural products.

Intratumoral microbiota is associated with prognosis in patients with adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy. Recent studies have discovered a pivotal role of the intratumoral microbiota in various cancers, yet it remains elusive in ACC. Here, we explored the intratumoral microbiome data derived from in silico identification, further validated in an in-house cohort by bacterial 16S rRNA fluorescence in situ hybridization and lipopolysaccharide staining. Unsupervised clustering determined two naturally distinct clusters of the intratumoral microbiome in ACC, which was associated with overall survival. The incorporation of microbial signatures enhanced the prognostic performance of the clinical stage in an immunity-dependent manner. Genetic and transcriptomic association analyses identified significant upregulation of the cell cycle and p53 signaling pathways associated with microbial signatures for worsened prognosis. Our study not only supports the presence of intratumoral bacteria but also implies a prognostic and biological role of intratumoral microbiota in ACC, which can advance a better understanding of the biology of ACC.

Expanded Sequence Space of Radical S-Adenosylmethionine-Dependent Enzymes Involved in Post-translational Macrocyclization.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) represent one of the largest but primarily underexplored natural product families in bacteria. The genetically encoded nature of RiPPs simplifies the prediction and prioritization of their biosynthetic gene clusters (BGCs). We report a small peptide and enzyme co-occurrence analysis workflow (SPECO), which allowed us to identify 32 220 prospective rSAM-catalyzed RiPP BGCs from 161 954 bacterial genomes and prioritize 25 families with new biosynthetic architectures or precursor patterns. We characterized three new enzymes that respectively catalyze cysteine-glycine (BlaB), histidine-aliphatic side chain (ScaB), and tyrosine/histidine-arginine (VguB) cross-links. The cyclophane-forming enzyme ScaB exhibits broad substrate selectivity, allowing it to catalyze diverse triceptide formation. These results demonstrate the strength of the SPECO workflow in discovering new enzymes for peptide macrocyclization.

Predicting mortality in acute ischaemic stroke treated with mechanical thrombectomy: analysis of a multicentre prospective registry.

OBJECTIVES: We aimed to determine predictors of mortality within 90 days and develop a simple score for patients with mechanical thrombectomy (MT). DESIGN: Analysis of a multicentre prospective registry. SETTING: In six participating centres, patients who had an acute ischaemic stroke (AIS) treated by MT between March 2017 and May 2018 were documented prospectively. PARTICIPANTS: 224 patients with AIS were treated by MT. RESULTS: Of 224 patients, 49 (21.9%) patients died, and 87 (38.8%) were independent. Variables associated with 90-day mortality were age, previous stroke, admission National Institutes of Health Stroke Scale (NIHSS), fasting blood glucose and occlusion site. Logistic regression identified four variables independently associated with 90-day mortality: age ≥80 years (OR 3.26, 95% CI 1.45 to 7.33), previous stroke (OR 2.33, 95% CI 1.04 to 5.21), admission NIHSS ≥18 (OR 2.37, 95% CI 1.13 to 4.99) and internal carotid artery or basilar artery occlusion (OR 2.92, 95% CI 1.34 to 6.40). Using these data, we developed predicting 90-day mortality of AIS with MT (PRACTICE) score ranging from 0 to 6 points. The receiver operator curve analysis found that PRACTICE score (area under the curve (AUC)=0.744, 95% CI 0.669 to 0.820) was numerically better than iScore (AUC=0.661, 95% CI 0.577 to 0.745) and Predicting Early Mortality of Ischemic Stroke score (AUC=0.638, 95% CI 0.551 to 0.725) for predicting 90-day mortality. CONCLUSIONS: We developed a simple score to estimate the 90-day mortality of patients who had an AIS treated with MT. But the score needs to be prospectively validated. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR-OOC-17013052).

Toxoplasma gondii infection in patients with lung diseases in Shandong province, eastern China.

Toxoplasma gondii, an intracellular protozoan parasite, can induce various clinical symptoms. T. gondii has been considered to play an important role in the pathogenesis of lung diseases. This survey was conducted to explore the correlation between T. gondii infection and lung diseases through a case-control study carried out in Shandong province, eastern China. In the present survey, T. gondii IgG antibodies were found in 76/398 (19.10%) of patients with lung diseases, which was significantly higher (P < 0.001) than the level found in the control subjects (35/398; 8.79%) through serological diagnosis. Patients with lung cancer have the highest T. gondii seroprevalence (26.19%), followed by Pulmonary cyst (25.00%), Tuberculosis (17.07%), Pneumonia (16.33%) and chronic obstructive pulmonary disease (COPD) (16.05%). Moreover, a semi-nest PCR targeted T. gondii B1 gene was employed to detect the T. gondii DNA in the blood samples. T. gondii DNA was detected in 5.53% blood samples of patients with lung diseases and 2.51% control subjects, respectively. The present study firstly shows that T. gondii has a high probability to infect the patients with lung diseases. Thus, the potential presence of T. gondii in patients with lung diseases should be appreciated during in the course of treatment and safeguard procedures should be implemented to protect vulnerable patients with lung diseases.

A Chemical-Intervention Strategy To Circumvent Peptide Hydrolysis by d-Stereoselective Peptidases.

d-Stereoselective peptidases that degrade nonribosomal peptides (NRPs) were recently discovered and could have serious implications for the future of NRPs as antibiotics. Herein, we report chemical modifications that can be used to impart resistance to the d-peptidases BogQ and TriF. New tridecaptin A analogues were synthesized that retain strong antimicrobial activity and have significantly enhanced d-peptidase stability. In vitro assays confirmed that synthetic analogues retain the ability to bind to their cellular receptor, peptidoglycan intermediate lipid II.

[Research progress on auditory neuropathy spectrum disorder and cochlear implantation in infants and young children].

Auditory neuropathy is a disorder characterized by absent or severely abnormal auditory brainstem response (ABR) with intact outer hair cell function, as evidenced by the presence of evoked otoacoustic emissions and/or cochlear microphonics. Unlike patients with sensory hearing loss who show clinical evidence of impaired outer hair cell function. For ANSD patients, clinical rehabilitation is mainly limited to hearing aid wearing and cochlear implantation. However, the effect of cochlear implantation for ANSD patients may be difference. The outcome of cochlear implantation is related to the lesion location, the age of implantation and the diameter of cochlear nerve.

[Long-term results of endolymphatic sac mastoid drainage for Ménière disease].

Objective:To investigate the long-term efficacy of endolymphatic sac mastoid drainage for Ménière disease.Method:Data from 26 patients diagnosed with MD strictly meeting the criteria issued by " Guideline of diagnosis and treatment of Meniere disease(2017)" from 2006 to 2015 were analyzed in this study.Endolymphatic sac mastoid shunt surgery was performed for each patient.The therapeutic effect was evaluated against the " Guideline of diagnosis and treatment of Meniere disease(2017)".Vertigo control and auditory function were measured after at least two years follow up.Result:In 26 cases,16 cases were male and 10 cases were femaleThe age ranged from 24 to 71 years old,with an average of 52.04 years.The disease duration ranged from 1 to 32 years.22 cases were diagnosed as unilateral Ménière disease,and bilateral involvement was identified in 4 cases,thus a total of 30 ears were included.According to the preoperative staging of hearing,there were 0 cases in stage one,5 cases in stage two,16 in stage three and 9 cases in stage four.15 cases(57.7%)achieved class A vertigo conrol(complete control),9 cases(34.6%)class B(substantial control)and 2 cases(7.7%)class D(no control).The severity of vertigo and its impact on daily life were improved in 24 cases(92.3%)with a score of 0 point,and 2 cases(7.7%)scored 2 points.Post-operative hearing was improved in 3 cases(11.5%),unchanged in 16 cases(61.6%)and worsened in 7 cases(26.9%).After operation,tinnitus disappeared in 5 cases(19.2%),reduced in 13 case(50%)and unchanged in 8 cases(30.8%).Conclusion:Endolymphatic sac mastoid drainage was an effective and safe management for intractable Ménière disease patients with pre-operative residual hearing.The occurrence of complication was unsual.The patients who are in stage four could gain benifits from the surgery.

[Clinical analysis of otogenic Mouret abscess: a case report].

Mouret abscess is a rare extracranial complication of suppurative otitis media. It is generally believed to be a deep neck abscess caused by inflammation leading to the rupture of the bony tip of the mastoid tip. The location of Mouret abscess is deep. The symptoms are insidious at the onset, but may eventually spread to the surrounding tissue, and even lead to mediastinal abscess, cavernous sinus thrombosis, meningitis, dyspnea and other serious complications. At present, with the popularization of antibiotics, the occurrence rate of Mouret abscess is very low, and only sporadic cases have been reported.In this paper, a case of Mouret abscess caused by cholesteatoma was analyzed to explore Mouret abscess in terms of the route of infection, clinical manifestations, imaging features, diagnosis and treatment.

Resistance to nonribosomal peptide antibiotics mediated by D-stereospecific peptidases.

Nonribosomal peptide antibiotics, including polymyxin, vancomycin, and teixobactin, most of which contain D-amino acids, are highly effective against multidrug-resistant bacteria. However, overusing antibiotics while ignoring the risk of resistance arising has inexorably led to widespread emergence of resistant bacteria. Therefore, elucidation of the emerging mechanisms of resistance to nonribosomal peptide antibiotics is critical to their implementation. Here we describe a networking-associated genome-mining platform for linking biosynthetic building blocks to resistance components associated with biosynthetic gene clusters. By applying this approach to 5,585 complete bacterial genomes spanning the entire domain of bacteria, with subsequent chemical and enzymatic analyses, we demonstrate a mechanism of resistance toward nonribosomal peptide antibiotics that is based on hydrolytic cleavage by D-stereospecific peptidases. Our finding reveals both the widespread distribution and broad-spectrum resistance potential of D-stereospecific peptidases, providing a potential early indicator of antibiotic resistance to nonribosomal peptide antibiotics.

Naringin protects myocardial cells from doxorubicin­induced apoptosis partially by inhibiting the p38MAPK pathway.

Doxorubicin (DOX) has been widely used to treat cancers as a first­line antitumor drug. However, it causes severe, irreversible, dose­dependent cardiotoxicity. To evaluate the protective effects of naringin (NRG) on cardiotoxicity, the authors investigated the molecular mechanism of the p38MAPK signaling pathway. H9c2 cells were treated for 24 h by using 5 µmol/l DOX without or with being pretreated by 1 µM NRG for 150 min or by 3 µM SB203580 for 60 min. Cell viability was detected by cell counting kit­8 assay. Intracellular reactive oxygen species (ROS) levels were detected based on the oxidative conversion of 2',7'­dichlorfluorescein­diacetate (cell­permeable) to dichlorofluorescein (fluorescent). The expression of p38MAPK was determined by western blotting. The expression level of p­p38MAPK in H9c2 cells, which was significantly increased by exposure to 5 µM DOX for 60 min (P<0.01), was significantly decreased by pretreatment with 1 µM NRG for 150 min beforehand (P<0.01). The viability of H9c2 cells pretreated for 150 min with 1 µM NRG was significantly enhanced compared with that using DOX directly (P<0.01). Intracellular ROS levels were significantly reduced by being pretreated with 1 µM NRG for 150 min or with 3 µM SB203580 for 60 min before the cells were exposed to 5 µM DOX. Collectively, NRG protected H9c2 cells against the cardiotoxicity induced by DOX through suppressing the expression and activity of the p38MAPK pathway. The findings provided valuable evidence for the possible use of NRG to relieve DOX­induced cardiotoxicity.

CTRP9 regulates hypoxia-mediated human pulmonary artery smooth muscle cell proliferation, apoptosis and migration via TGF-ß1/ERK1/2 signaling pathway.

Hypoxia is an important risk factor for pulmonary arterial remodeling in pulmonary arterial hypertension (PAH). Vascular remodeling in hypoxia-induced PAH is driven by excessive proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs). The purpose of the present study was to explore the expression of CTRP9 in rats model of hypoxia-induced PAH and investigate the effects of CTRP9 on HPASMCs function in vitro and determine the underlying mechanisms. We established a rat model of hypoxic PAH, which showed a downregulation of CTRP9 expression. In HPASMCs cultured under the condition of hypoxia, treatment with CTRP9 notably restrained cell proliferation responses to hypoxia accompanied with decreased two biomarkers of cell proliferation Ki-67 and PCNA. Meanwhile, CTRP9 strikingly promoted hypoxia-mediated cell apoptosis as reflected by upregulation of Bax and downregulation of Bcl-2, as well as enhanced Caspase 3 activity. Additionally, CTRP9 treatment dramatically prevented the migratory potential by declined the expression of MMP-2 and MMP-9. Moreover treatment with CTRP9 augmented hypoxia-mediated differentiation by elevating the expression level of differentiation markers α-SMA and SM22. Mechanistically, anti-proliferative effects conferred by CTRP9 are mediated through suppression of TGF-ß1/ERK1/2 pathway. Collectively, we identified CTRP9 as a novel mediator of PASMC growth in hypoxia-mediated PAH, indicating that CTRP9 in the pulmonary vasculature may be an underlying mechanism in the development of hypoxia-induced PAH. Our study, for the first time, established that CTRP9 plays a protective role of CTRP9 in pulmonary vascular remodeling, pointing to its potential clinical value for patients with PAH.

Silencing of NRAGE induces autophagy via AMPK/Ulk1/Atg13 signaling pathway in NSCLC cells.

NRAGE has been reported to be overexpressed in cancer cells, especially in lung cancer cells. To determine the role of NRAGE in non-small-cell lung cancer cells, we investigated the effects of NRAGE on autophagy in non-small-cell lung cancer cells. Human A549 and H1299 cells were transfected with NRAGE-specific small-interfering RNA. The Cell Counting Kit-8 and plate clone assay showed that downregulation of NRAGE could induce the proliferation in A549 and H1299 cells. In addition, our data suggested that downregulation of NRAGE enhances autophagosome formation by immunofluorescence. We found that knockdown of NRAGE induced autophagy, together with downregulation of P62 and upregulation of LC3-II protein. Furthermore, to elucidate the mechanism of NRAGE in suppressing autophagy, the protein expressions of AMPK, Ulk1, and Atg13 were assessed. Collectively, these results demonstrate the effective anti-autophagic of NRAGE in non-small-cell lung cancer cells through AMPK/Ulk1/Atg13 autophagy signaling pathways. Therefore, NRAGE could be used as a potential therapeutic target for lung cancer.

Divergent biosynthesis yields a cytotoxic aminomalonate-containing precolibactin.

Colibactin is an as-yet-uncharacterized genotoxic secondary metabolite produced by human gut bacteria. Here we report the biosynthetic discovery of two new precolibactin molecules from Escherichia coli, including precolibactin-886, which uniquely incorporates the highly sought genotoxicity-associated aminomalonate building block into its unprecedented macrocyclic structure. This work provides new insights into the biosynthetic logic and mode of action of this colorectal-cancer-linked microbial chemical.

Dioxinodehydroeckol protects human keratinocyte cells from UVB-induced apoptosis modulated by related genes Bax/Bcl-2 and caspase pathway.

Although ultraviolet B (UVB) has a low level of skin penetration, it readily results in epidermal sunburn of keratinocytes that are destined to apoptosis after sun expose, and leads to DNA damage. Dioxinodehydroeckol (DHE), a phlorotannin from Ecklonia cava has been explored for its preventive activity against UVB-induced apoptosis in human keratinocyte (HaCaT) cells; however, the protective effects of treatment with low doses of DHE on UVB-damaged cells post-UVB exposure and their underlying mechanisms still remain unclear. The HaCaT cells were exposed to 20 mJcm(-2) of UVB irradiation which is the minimal erythema dose (MED) for individuals to be able to tan, and the expression levels of Bax/Bcl-2 and caspase-3,-8, -9 which are associated genes with apoptosis were investigated when we either treated cells with DHE doses after UVB irradiation or exposed them to UVB only. Our results suggest insight into proposed mechanistic pathway of protective activity of DHE on the HaCaT cells from UVB-induced apoptosis, indicating the benefit of DHE as a repair agent for skin damage against UVB.