T3SS protein EsrC binds to the lacI-like operator of type 1 fimbrial operon to suppress adhesion of Edwardsiella piscicida.

Type 1 fimbria, the short hair-like appendage assembled on the bacterial surface, plays a pivotal role in adhesion and invasion in Edwardsiella piscicida. The type III secretion system (T3SS), another bacterial surface appendage, facilitates E. piscicida's replication in vivo by delivering effectors into host cells. Our previous research demonstrated that E. piscicida T3SS protein EseJ inhibits adhesion and invasion of E. piscicida by suppressing type 1 fimbria. However, how EseJ suppresses type 1 fimbria remains elusive. In this study, a lacI-like operator (nt -245 to -1 of fimA) upstream of type 1 fimbrial operon in E. piscicida was identified, and EseJ inhibits type 1 fimbria through the lacI-like operator. Moreover, through DNA pull-down and electrophoretic mobility shift assay, an AraC-type T3SS regulator, EsrC, was screened and verified to bind to nt -145 to -126 and nt -50 to -1 of fimA, suppressing type 1 fimbria. EseJ is almost abolished upon the depletion of EsrC. EsrC and EseJ impede type 1 fimbria expression. Intriguingly, nutrition and microbiota-derived indole activate type 1 fimbria through downregulating T3SS, alleviating EsrC or EseJ's inhibitory effect on lacI-like operator of type 1 fimbrial operon. By this study, it is revealed that upon entering the gastrointestinal tract, rich nutrients and indole downregulate T3SS and thereof upregulate type 1 fimbria, stimulating efficient adhesion and invasion; upon being internalized into epithelium, the limit in indole and nutrition switches on T3SS and thereof switches off type 1 fimbria, facilitating effector delivery to guarantee E. piscicida's survival/replication in vivo.IMPORTANCEIn this work, we identified the lacI-like operator of type 1 fimbrial operon in E. piscicida, which was suppressed by the repressors-T3SS protein EseJ and EsrC. We unveiled that E. piscicida upregulates type 1 fimbria upon sensing rich nutrition and the microbiota-derived indole, thereof promoting the adhesion of E. piscicida. The increase of indole and nutrition promotes type 1 fimbria by downregulating T3SS. The decrease in EseJ and EsrC alleviates their suppression on type 1 fimbria, and vice versa.

Graphene metamaterials-based plasmon-induced terahertz modulator for high-performance multiband filtering and slow light applications.

We proposed multilayered graphene (Gr)-based surface plasmon resonance-induced high-performance terahertz (THz) modulators with tunable resonance frequencies. Previously reported Gr metamaterials-based THz plasmonic modulators had small group delay, low extinction ratio (ER), and difficult-to-tune resonant frequency without changing structural parameters in the THz range. A comprehensive investigation employing the finite-difference time-domain (FDTD) simulation technique revealed high group delay, broad tunability independent of structural parameters, and large ER for our proposed quadband and pentaband plasmonic modulators. We obtained tunable group delays with a maximum of 1.02 ps and 1.41 ps for our proposed quadband and pentaband plasmonic modulators, respectively, which are substantially greater compared to previously reported Gr-based metamaterial structures. The maximum ER of 22.3 dB was obtained, which was substantially high compared to previous reports. Our proposed modulators were sensitive to the polarization angle of incident light; therefore, the transmittance at resonant frequencies was increased while the polarization angle varied from 0° to 180°. These high-performance plasmonic modulators have emerging potential for the design of optical buffers, slow light devices, multistop band filters, integrated photonic circuits, and various optoelectronic systems.

Titanium nitride-based hyperbolic metamaterial for near-infrared ultrasensitive sensing of microbes.

We demonstrate an ultrasensitive microbe sensor for the first time using a titanium nitride (TiN) nanowire-based hyperbolic metamaterial (HMM) structure. We detected the change in the resonance wavelength shift due to the inclusion of microbes in a freshwater environment employing the finite-difference time-domain (FDTD) method. Our proposed HMM sensor exhibits strong bulk plasmon polariton (BPP) modes in the anisotropic hyperbolic regime (λ ≥ 590 nm) and operates in the near-infrared (NIR) wavelength region. We studied the impact of structural parameters on the resonance wavelength shift, where our proposed HMM sensor structure exhibited an outstanding sensing capability of 11 nm per bacteria. A limit of detection of 0.00008 RIU was achieved for our proposed HMM sensor structure. Additionally, we verified our results theoretically to calculate mode frequency shift by solving the effective medium theory (EMT). Our study revealed that HMM is the origin of highly sensitive BPP modes. We obtained two BPP modes, where the BPP mode at a longer wavelength (q = 1) exhibited the highest resonance wavelength shift compared to the BPP mode at a shorter wavelength (q = 2). More importantly, we demonstrated numerically the point-detection capability of our proposed HMM microbe sensor structure, which was unattainable in previously reported sensor work. Moreover, this sensor can be adapted to detect different viruses and bacteria. Our proposed TiN-based HMM structure can potentially be an ultrasensitive and straightforward microbe sensor for label-free detection.

TUSC3, p53 and p21 genetic association with development of oral submucous fibrosis and oral squamous cell carcinoma among addictive tobacco chewers of Pakistan.

BACKGROUND: This study delves into the intricate landscape of oral cancer, a global concern with a high incidence in Asian countries. We focus on oral squamous cell carcinoma (OSCC), primarily driven by the consumption of betel nut and its derivatives. OSCC often arises from premalignant lesions like oral submucous fibrosis (OSF). In Pakistan, OSCC is prevalent among men due to various addictive substances, including smokeless tobacco and chewing materials. Mutations in tumor suppressor genes, such as TP53 and p21, play crucial roles in this malignancy's development. We also explore the involvement of TUSC3 gene deletion in OSCC and OSF. METHODS: In this study we investigated demographics, TUSC3 gene expression, deletion analysis, and TP53 and p21 genetic alterations in OSCC and OSF patients (blood and tissue of 50 samples in each condition) who had tobacco derivates usage history. The association analysis was carried out mainly through PCR based genotyping. RESULTS: The study's patient cohort (OSCC and OSF) displayed a wide age range from 13 to 65 years (Mean = 32.96 years). Both conditions were more prevalent in males, with a male-female ratio of approximately 2.5:1. Chewing habits analysis revealed high frequencies of gutka use in both OSF and OSCC patients. TUSC3 expression analysis in OSCC cell lines indicated significant downregulation. Genotyping showed no TUSC3 deletion in OSF cases, but a deletion rate of over 22% in OSCC tissue samples. Analysis supported a significant association of TUSC3 deletion with OSCC development but not with OSF. Polymorphism in p53 exon 4 and p21 (rs1801270) were significantly associated with both OSCC and OSF, adding to their pathogenesis. Our findings further revealed a strong correlation between TUSC3 deletion and the excessive use of tobacco and related products, shedding light on the genetic underpinnings of OSCC development. CONCLUSIONS: Notably, our study provides a crucial insight into genetic aspects underlying OSCC and OSF in response of addictive consumption of areca nut, betel quid, and tobacco derivatives. A significant association between TUSC3 deletion and OSCC development, along with polymorphisms in TP53 and p21, underscores the importance of further research into the molecular mechanisms driving oral cancer progression for improved diagnosis and treatment outcomes.

Preference of the patient's family for family-centred care in a paediatric hospital.

Objective: To explore the dimensions of family-centred care preferred by families of paediatric inpatients in a public healthcare setting. METHODS: The qualitative study was conducted at the National Institute of Child Health, Karachi, from October 2021 to August 2022, and comprised family members of the hospitalised children. Data was collected through three focus group discussions that were guided by a semi-structured questionnaire. Using the five-step Fereday and Muir-Cochrane guidelines, data was coded and subjected to thematic analysis. RESULTS: Of the 21 subjects, 13(62%) were males and 8(38%) were females. The overall mean age was 32.24±7.58 years (range: 18-50 years). In terms of relationship with the patient, 9(43%) were fathers and 6(28.6%) were mothers. Each focus group discussion had 7(33.3%) subjects. Thematic analysis showed that the participants perceived family-centred care positively. Eight categories emerged depicting family perception and experience of family-centred care in a tertiary-care setting. Conclusion: The participants perceived family-centred care respectful and empathic towards patients' families, making them integral care team members.

Frequency of C-peptide and antibody levels (anti GAD, Islet cell antibodies, insulin auto antibodies) in children of Pakistan with Type-1 diabetes.

Background and Objective: The autoimmune mechanism in T1DM causes gradual loss of pancreatic ß-cell, which progresses to hyperglycemia and ultimate reliance on consistent insulin therapy. T1DM has been the commonest type of diabetes in children and this study will help in refining indulgent towards the problem and its pathophysiology in our people. The objective was to find out the prevalence of C-peptide and antibody levels (anti GAD, ICA, IAA and IA2) in children and adolescents of Pakistan with T1DM. Methods: We conducted this cross-sectional study at Department of Pediatric Endocrinology, National Institute of Child Health, Karachi between August 2019 to February 2020 and included 98 children who had T1DM for more than one month. Subjects whose GFR was <30ml/min were omitted from the study. Among those registered subjects, C-peptide, human islet cell antibody (ICA), insulin auto antibodies (IAA) and anti-glutamic acid decarboxylase were assessed. Demographical and laboratorial facts were noted on a pre-constructed proforma. Results: There were 77(78.3%) cases who had level of C-peptide <0.8 and anti-GAD was found in 47(48%) subjects. 35(35.7%) cases found positive for IA2 .and 7(7.1%) patients had insulin auto antibodies positive while ICA was negative in total 98(100%) subjects. Conclusion: Children with T1 DM possessed increased levels of anti-GAD antibodies, insulin autoantibodies and anti (IA2) but islet cells antibodies were negligible in our population when checked at a point of time. C-peptide may be normal in some, but its level declines with long duration of diabetes in children.

Recent research trends in textile-based temperature sensors: a mini review.

In this review, the current state of research on textile-based temperature sensors is explored by focusing on their potential use in various applications. The textile-based sensors show various advantages including flexibility, conformability and seamlessness for the wearer. Integration of the textile-based sensors into clothes or fabric-based products enables continuous and sensitive monitoring of change in temperature, which can be used for various medical and fitness applications. However, there are lacks of comprehensive review on the textile-based temperature sensors. This review introduces various types of textile-based temperature sensors, including resistive, thermoelectric and fibre-optical sensors. In addition, the challenges that need to be addressed to fully realise their potential, which include improving sensitivity and accuracy, integrating wireless communication capabilities, and developing low-cost fabrication techniques. The technological advances in textile-based temperature sensors to overcome the limitations will revolutionize wearable devices requiring function of temperature monitoring.

Collection of smartphone and internet addiction.

The enigma of smartphone and internet addiction has plagued academics for the last decade, now scholars believe this behavior might have a substantial effect on human health and social issues. However, there are literature gaps. Thus, BMC Psychiatry works with us to launch the special collection "Smartphone and Internet Addiction".

Gender differences in social environmental factors of psychological distress among Indonesian adolescents: Findings from the 2015 Global School-based Student Health Survey.

BACKGROUND: This study aimed to investigate gender differences in social environmental factors of psychological distress among Indonesian adolescents. METHODS: This was a cross-sectional study using the data from the 2015 Indonesia Global School-based Student Health Survey. Binary logistic regression was used to assess the influences of main independent variables - social environmental factors (i.e., peer support, having close friends, bullying victimisation, physical fight, physical attack, parental supervision, connectedness, bonding), demographic characteristics, and health-related behaviours on the measures of psychological distress (loneliness, anxiety-induced sleep disturbance, and a combination of both measures as psychological distress). RESULTS: The prevalence of psychological distress measured as loneliness, anxiety-induced sleep disturbance, and combined psychological distress was 6.12%, 4.52%, and 8.04%, respectively. Findings from multivariate analyses indicated that bullying victimisation, physical attack, experience of hunger (a proxy of socioeconomic status), and sedentary behaviour were associated with all measures of psychological distress. Meanwhile, age, gender, drug use, parental connectedness and bonding, and having no close friends were correlates of one or two measures of psychological distress. Based on gender-stratified analyses, experience of hunger, sedentary behaviour, bullying victimisation, and having no close friends were consistently associated with measures of psychological distress among both girls and boys. In addition, the influence of some social environmental factors, such as parental connectedness, peer support, and physical attack, were more salient among girls. CONCLUSIONS: The findings suggest that social environmental factors, demographic characteristics, and health-related behaviours were associated with psychological distress, and the associations appeared to differ by gender. Interventions that include improving positive social environmental factors (e.g., reducing interpersonal violence, encouraging positive relationships with parents and peers) and promoting healthy behaviours (e.g., less sedentary behaviour, preventing substance use) might help reduce the risk of psychological distress among Indonesian adolescents.

Molecular and functional characterization of zinc finger aspartate-histidine-histidine-cysteine (DHHC)-type containing 1, ZDHHC1 in Chinese perch Siniperca chuatsi.

In the present study, the zinc finger aspartate-histidine-histidine-cysteine (DHHC)-type containing 1 (ZDHHC1) gene was identified in a commercial fish, the Chinese perch Siniperca chuatsi. The ZDHHC1 has five putative transmembrane motifs and conserved DHHC domain, showing high amino-acid identity with other teleost fish, and vertebrate ZDHHC1 loci are conserved from fish to human. In vivo expression analysis indicated that ZDHHC1 gene was constitutively transcribed in all the examined organs/tissues, and was induced following infectious spleen and kidney necrosis virus (ISKNV) infection. It is further observed that ZDHHC1 interacts with MITA and the overexpression of ZDHHC1 in cells resulted in the upregulated expression of ISGs, such as Mx, RSAD2, IRF3 and type I IFNs such as IFNh and IFNc, exhibiting its antiviral function in fish as reported in mammals.

Assessing environmental fate of hexavalent chromium as influenced by fractionation of ferrihydrite with dissolved organic matter.

The dynamic interactions among iron (Fe) oxides, dissolved organic matter (DOM) and toxic trace metals play crucial roles in risk assessment and environmental remediation. Although the inhibitory effects of DOM on the iron oxides transformation process have been studied previously, there is still a lack of mechanistic and quantitative understanding on the kinetics of Cr(VI) and ferrihydrite transformation in the present of DOM. In this study, we investigated the fractionation process of DOM on ferrihydrite and its influence on the fate of Cr(VI) and transformation of ferrihydrite. The result of three-dimension excitation emission matrix (3D-EEM), Q-Exactive LC-MS/MS, X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HR-TEM) indicated that fulvic acid-like compounds of DOM were the mainly fractionated compounds on the surface of ferrihydrite, which further inhibited the transformation of ferrihydrite. Besides, bracewellite (CrO(OH)) generated as an accompanied mineral during the transformation of ferrihydrite in the present of Cr(VI). Based on the DFT theoretical calculation, we concluded that Cr(VI) mainly in the form of HCr O4- was more inclined to be adsorbed on iron-oxide tetrahedron by inner-sphere monodentate mononuclear configurations. The findings on the dynamic coupling among Fe oxide transformation and Cr(VI) sequestration under the effect of DOM provided the basis for accurately predicting the fate of trace elements and iron mineral.

Effectiveness of case scenario-based teaching to transition international Master of Public Health students specialising in health promotion from memorization to critical thinking.

ISSUE ADDRESSED: Critical thinking is essential to health promotion to overcome increasingly complex health issues. International students from Middle East and Asia are however disadvantaged when required to demonstrate critical thinking mainly because of their previous training in memorisation. This study addresses this need by evaluating the effect of case scenario-based teaching on transition from memorisation to critical thinking among international students in an Australia university. METHODS: This was a pre and post intervention study and data were collected from a convenience sample of 79 international Master of Public Health students specialising in health promotion in 2019 at the University of Wollongong. RESULTS: Most of the participants were female (73.4%) and aged 25 years or older (64.6%), predominantly from India (40.5%), Nepal (31.6%) and Saudi Arabia (11.4%). A paired t-test analysis showed that the intervention - case scenario-based teaching - significantly improved the mean post-intervention critical thinking skills (P < 0.001). Case studies improved critical thinking among international students, irrespective of demographic attributes. Multiple regression analyses indicated that critical thinking predicted 78.6 of the total marks, after controlling for demographic attributes. In terms of assessment marks, improved multiple solutions skills yielded better marks for tutorial participations; while improved problem identification skills improved marks for report assessments and exams. Improved communication skills led to better marks for essay assessments. CONCLUSIONS: Case studies improved critical thinking and was a reliable predictor of student performance among the participants. SO WHAT?: This study makes a strong case for case scenario-based teaching to improve critical thinking among international students. However, given the limitations of this study, including the small, non-representative sample, further testing is required.

Cryo-FIB-lift-out: practically impossible to practical reality.

In this paper, we explore the development of the Cryo-Lift-Out (cryo-LO) technique as preparation tool for cryogenic transmission electron microscopy (cryo-TEM). What started in early work defying what was considered 'practically impossible' has developed into state-of-the-art practical reality. This paper presents the key hardware, basic principles and key considerations for the practical usage of cryogenic Lift-Out for those new to the field. Detailed protocols and in-depth description of considerations and points for further development are presented. The authors have attempted to formalise everything known about the technique gathered together from their expertise gained in the development of this approach. LAY DESCRIPTION: A major challenge in electron microscopy is the production of suitable samples from hydrated biological and soft-matter materials for subnanometre resolution imaging in a cryo-Transmission Electron Microscope (TEM). A well-known solution for room temperature materials is called (in situ) Lift-Out. It uses a fine needle that picks up a tiny section called a lamella. Lamellae are made by a Focused Ion Beam (FIB). In this paper, we seek to set out the beginnings of Lift-Out sample preparation conducted under cryogenic conditions and the development of this approach as applied to frozen, hydrated biological and soft-matter samples. We discuss the required basic hardware and provide a thorough description of developed protocols. We aim at those new to the field of cryo-Lift-Out to fully educate them in the finer points of hardware setup and practical considerations when attempting to perform cryo-Lift-Out and to demonstrate what has been achieved thus far. We also discuss areas of further improvement and talking points for the future direction of this promising sample preparation technique.

Clinical outcome of right ventricle outflow tract management for repair of Tetralogy of Fallot with three contemporary surgical strategies.

OBJECTIVE: To compare the early operative outcome of TOF repair with three contemporary repair strategies of RVOTO repair i.e. TAP, Mono-cusp construction (MC) in TAP and pulmonary valve repair. METHODS: Study is performed at Punjab Institute of Cardiology, Lahore from May 2016 to April 2020. Retrospective analysis of data was performed for patient who underwent TOF repair by three different strategies of RVOT repairs during TOF surgery based on z scoring for pulmonary valve annulus. Group-I underwent trans-annular patch repair, while Group-II and III underwent Mono-cusp repair with autologous pericardium and pulmonary valve repair respectively. Analysis of Variance (ANOVA) and Pearson Chi-Square (PCS) statistics were used to compare the three groups for numeric and categorical variables respectively. Post-hoc t-test and Bonferroni correction were performed for numeric data to compare two groups with each other. Chi-square test was used to perform comparison between groups for categorial variables. RESULTS: ANOVA for aortic cross clamp time, total CPB time, Post-operative mechanical ventilation time, ICU stay and hospital stay showed statistical difference among all three group with p-value less than 0.05 however post hoc T-test showed this variation is limited to post-operative mechanical ventilation only when groups compared with each other. PCS showed there was difference for incidence of difficult weaning from CPB when all three groups compared while there was no difference in operative mortality with p-value of 0.15. However, Group-II comparison with Group-I showed that weaning from CPB was superior in-Group-II with p-value of 0.016. Group-III showed the best statistics for all operative outcome variables among all three groups. Comparison of incidence of post-operative moderate pulmonary regurgitation before discharge between Group-II and Group-III showed significant difference with p-value of 0.0052. CONCLUSION: PV repair strategy should be employed for RVOT repair of TOF whenever feasible. MC repair showed fewer hours of postoperative mechanical ventilation and higher incidence of easy weaning from CPB when compared to TAP, however its impacts over ICU stay, Hospital stay and operative mortality is not profound in our TOF repair population.

A distinct molecular mutational profile and its clinical impact in essential thrombocythemia and primary myelofibrosis patients.

BACKGROUND: Classical MPNs including ET and PMF have a chronic course and potential for leukaemic transformation. Timely diagnosis is obligatory to ensure appropriate management and positive outcomes. The aim of this study was to determine the mutational profile, clinical characteristics and outcome of ET and PMF patients in Pakistani population. METHODS: This was a prospective observational study conducted between 2012 and 2017 at NIBD. Patients were diagnosed and risk stratified according to international recommendations. Response to treatment was assessed by IWG criteria. RESULTS: Of the total 137 patients analysed, 75 were ET and 62 were PMF. JAK2 positivity was seen in 51 cases (37.2%), CALR in 41 cases (29.9%), while triple-negative in 17 (12.4%) cases. None of the patients in the present study were MPL positive. Overall survival for patients with ET and PMF was 92.5 and 86.0% respectively and leukaemia free survival was 100 and 91.6% respectively, at a median follow-up of 12 months. Leukaemic transformation occurred in 6.5% of MF patients; among them, JAK2 mutation was frequently found. Molecular mutations did not influence the OS in ET whereas in PMF, OS was shortest in the triple-negative PMF group as compared to the JAK2 and CALR positive patient groups. CONCLUSION: This study shows a different spectrum of molecular mutations in ET and PMF patients in Pakistani population as compared to other Asian countries. Similarly, the risk of leukaemic transformation in ET and PMF is relatively lower in our population of patients. The factors responsible for these phenotypic and genotypic differences need to be analysed in large scale studies with longer follow-up of patients.

Functional characterization of a group II interferon, IFNc in the perciform fish, Nile tilapia (Oreochromis niloticus).

Interferons are a family of class II α-helical cytokines playing vital roles in antiviral immune response, and little information is available to date regarding the interferon system of tilapia. In this study, a type I IFN gene, named On-IFNc, was identified in Nile tilapia, Oreochromis niloticus. The predicted protein of On-IFNc contains several structural features known in type I IFNs, and On-IFNc was clustered together with the known IFNc in fish into a separated clade in the phylogenetic tree. On-IFNc gene was constitutively expressed in all tissues examined, with the highest expression level observed in liver, and was rapidly induced in all organs/tissues tested following the stimulation of poly(I:C). In addition, recombinant On-IFNc has been proven to markedly induce the expression of the antiviral effectors, Mx and viperin, the signalling components, STAT1, STAT2, and IRF9, and the transcription factors, IRF3 and IRF7, as well as the tyrosine phosphorylation of STAT1 and STAT2 in fish cells. Furthermore, recombinant On-IFNc has been proven to possess antiviral activity against ISKNV. The present study thus contributes to a better understanding of the functional properties of the type I IFN system in tilapia.

Unique Composition of Intronless and Intron-Containing Type I IFNs in the Tibetan Frog Nanorana parkeri Provides New Evidence To Support Independent Retroposition Hypothesis for Type I IFN Genes in Amphibians.

In vertebrates, intron-containing and intronless type I IFN genes have recently been reported in amphibian model species Xenopus tropicalis and X. laevis. However, whether intronless type I IFNs in amphibians are the ancestral genes of type I IFNs in amniotes or just represent the independent divergence in amphibians is unknown or even uninvestigated. In this study, both intron-containing and intronless type I IFN genes, as well as their receptor genes, were identified in the Tibetan frog Nanorana parkeri The evidence obtained from homology, synteny, phylogeny, and divergence time showed that intronless type I IFN genes in N. parkeri and in Xenopus might have arisen from two independent retroposition events occurred in these two lineages, and the retrotransposition causing the generation of intronless type I IFN genes in amniotes is another independent event beyond the two in amphibians. It can then be proposed that intronless type I IFNs in N. parkeri and Xenopus may not be the ancestral genes of intronless type I IFNs in amniotes but may just represent two independent bifurcations in the amphibian lineage. Furthermore, both intronless and intron-containing type I IFNs in N. parkeri showed strong ability in inducing the expression of IFN-stimulated genes and the strong antiviral activity against frog virus 3. The present study thus provides the evolutionary evidence to support the independent retroposition hypothesis for the occurrence of intronless type I IFN genes in amphibians and contributes to a functional understanding of type I IFNs in this group of vertebrates.

The Anti-Cancer Effect of Linusorb B3 from Flaxseed Oil through the Promotion of Apoptosis, Inhibition of Actin Polymerization, and Suppression of Src Activity in Glioblastoma Cells.

Linusorbs (LOs) are natural peptides found in flaxseed oil that exert various biological activities. Of LOs, LOB3 ([1-9-NαC]-linusorb B3) was reported to have antioxidative and anti-inflammatory activities; however, its anti-cancer activity has been poorly understood. Therefore, this study investigated the anti-cancer effect of LOB3 and its underlying mechanism in glioblastoma cells. LOB3 induced apoptosis and suppressed the proliferation of C6 cells by inhibiting the expression of anti-apoptotic genes, B cell lymphoma 2 (Bcl-2) and p53, as well as promoting the activation of pro-apoptotic caspases, caspase-3 and -9. LOB3 also retarded the migration of C6 cells, which was achieved by suppressing the formation of the actin cytoskeleton critical for the progression, invasion, and metastasis of cancer. Moreover, LOB3 inhibited the activation of the proto-oncogene, Src, and the downstream effector, signal transducer and activator of transcription 3 (STAT3), in C6 cells. Taken together, these results suggest that LOB3 plays an anti-cancer role by inducing apoptosis and inhibiting the migration of C6 cells through the regulation of apoptosis-related molecules, actin polymerization, and proto-oncogenes.

Cytoprotective Effect of Epigallocatechin Gallate (EGCG)-5'-O-α-Glucopyranoside, a Novel EGCG Derivative.

Epigallocatechin gallate (EGCG) is a well-studied polyphenol with antioxidant effects. Since EGCG has low solubility and stability, many researchers have modified EGCG residues to ameliorate these problems. A novel EGCG derivative, EGCG-5'-O-α-glucopyranoside (EGCG-5'Glu), was synthesized, and its characteristics were investigated. EGCG-5'Glu showed antioxidant effects in cell and cell-free systems. Under SNP-derived radical exposure, EGCG-5'Glu decreased nitric oxide (NO) production, and recovered ROS-mediated cell viability. Moreover, EGCG-5'Glu regulated apoptotic pathways (caspases) and cell survival molecules (phosphoinositide 3-kinase (PI3K) and phosphoinositide-dependent kinase 1 (PDK1)). In another radical-induced condition, ultraviolet B (UVB) irradiation, EGCG-5'Glu protected cells from UVB and regulated the PI3K/PDK1/AKT pathway. Next, the proliferative effect of EGCG-5'Glu was examined. EGCG-5'Glu increased cell proliferation by modulating nuclear factor (NF)-κB activity. EGCG-5'Glu protects and repairs cells from external damage via its antioxidant effects. These results suggest that EGCG-5'Glu could be used as a cosmetics ingredient or dietary supplement.

Two type II IFN members, IFN-γ and IFN-γ related (rel), regulate differentially IRF1 and IRF11 in zebrafish.

Two members of type II IFNs have been identified in fish, i.e. an IFN-γ gene as in other vertebrates and a unique IFN-γ related (IFN-γ rel) gene being solely present in fish. However, the signalling pathways involved in the down-stream signalling of type II IFNs in fish remains poorly described. In this study, the type II IFNs mediated IRF1 was investigated in zebrafish, and the true homologous gene of mammalian IRF1 in fish was revealed despite the report of so-called IRF1a and IRF1b in zebrafish. As revealed in overexpression analysis, zebrafish IFN-γ had a higher induction ability than IFN-γ rel in relation with the expression of IRF1. IFN-γ stimulated the expression level of STAT1a and also STAT1b, but they had opposite trends with the increase of time; enhancement of STAT1a waned after 12 h post injection of plasmids; whereas STAT1b expression increased continuously. Zebrafish IRF1 gene promoter contained several putative transcription factor binding sites, including GAS and NF-κB motifs. Luciferase assay revealed that the GAS site was essential in the IFN-γ triggered IRF1 expression. In contrast, IRF11 contained neither GAS nor NF-κB elements, and did not respond to IFN-γ induction. It is considered that STAT1a and STAT1b are structurally and functionally similar to STAT1α and STAT1ß in mammal respectively, and that IRF11, although used to be nominated as IRF1a, is not the orthologue of mammalian IRF1, but IRF1b in zebrafish should be the orthologue.