Biology of macrophage fate decision: Implication in inflammatory disorders.

The activation of immune cells in response to stimuli present in their microenvironment is regulated by their metabolic profile. Unlike the signal transduction events, which overlap to a huge degree in diverse cellular processes, the metabolome of a cell reflects a more precise picture of cell physiology and function. Different factors governing the cellular metabolome include receptor signaling, macro and micronutrients, normoxic and hypoxic conditions, energy needs, and biomass demand. Macrophages have enormous plasticity and can perform diverse functions depending upon their phenotypic state. This review presents recent updates on the cellular metabolome and molecular patterns associated with M1 and M2 macrophages, also termed "classically activated macrophages" and "alternatively activated macrophages," respectively. M1 macrophages are proinflammatory in nature and predominantly Th1-specific immune responses induce their polarization. On the contrary, M2 macrophages are anti-inflammatory in nature and primarily participate in Th2-specific responses. Interestingly, the same macrophage cell can adapt to the M1 or M2 phenotype depending upon the clues from its microenvironment. We elaborate on the various tissue niche-specific factors, which govern macrophage metabolism and heterogeneity. Furthermore, the current review provides an in-depth account of deregulated macrophage metabolism associated with pathological disorders such as cancer, obesity, and atherosclerosis. We further highlight significant differences in various metabolic pathways governing the cellular bioenergetics and their impact on macrophage effector functions and associated disorders.

Occurrence and toxicity of a fusarium mycotoxin, zearalenone.

Zearalenone (ZEA) is a mycotoxin produced by the fungi of Fusarium genera, which contaminates the cereals and food stuffs worldwide. Fusarium mycotoxins are considered as important metabolites related to animal and human health. Evidences indicate that ZEA has been found to be present in different food stuffs from developed countries like USA, Canada, France, Germany, Japan, etc. and developing nations like Egypt, Thailand, Iran, Croatia, Philippines, etc. The toxicokinetic studies reveal that following oral exposure of ZEA, the compound is absorbed through gastrointestinal tract (GIT), gets metabolized and distributed to different body parts. ZEA has been shown to cause reproductive disorders in laboratory animals. Although the toxicity of ZEA in humans have not been conclusively established nonetheless, limited evidences indicate that ZEA can cause hyper estrogenic syndrome. Though, ZEA causes low acute toxicity, but reports are available confirming the systemic toxicity caused by ZEA. There is no review available that addresses the occurrence, systemic toxicity and the probable mechanisms of ZEA toxicity. This review shall address the world-wide occurrence and in vivo & in vitro toxicity studies of ZEA over the past 20 years. The review shall also discuss the toxicokinetics of ZEA and metabolites; illustrates the systemic toxicity and probable mechanisms of action leading to the risk associated with ZEA.

Troponin 1 of human filarial parasite Brugia malayi: cDNA cloning, expression, purification, and its immunoprophylactic potential.

In the search for immunoprophylactics for the control of human lymphatic filariasis, we recently identified troponin 1 (Tn1) in Brugia malayi adult worms. The present study reports the cloning and expression of the B. malayi Tn1 (Tn1bm), its immunoprophylactic efficacy against B. malayi infection, and the immunological responses of the host. The Tn1bm gene was cloned (Acc no. JF912447) and expressed, and the purified recombinant Tn1bm (rTn1bm) presented a single ~ 27 kDa band. Parasite load in rTn1bm-immunized BALB/c mice challenged with B. malayi infective larvae (L3) was assessed. In rTn1bm-immunized animals, IgE, IgG, and IgG subclasses in the serum, cell proliferative response, Th1 and Th2 cytokine secretion (from splenocytes), and NO release (from peritoneal macrophages) were determined. Antibody-dependent cell-mediated cytotoxicity (ADCC) to L3 was assayed using rTn1bm-immune serum. The innate immune response markers MHC class-I, MHC class-II, TLR2, TLR4, and TLR6 expression in peritoneal macrophages and CD3+, CD4+, CD8+, and CD19+ in the splenocyte population were determined in Tn1bm-exposed cells from naïve mice. rTn1bm-immunized L3-challenged animals showed a 60% reduction in parasite burden. Immunization upregulated cellular proliferation, cytokine (IFN-γ, TNF-α, IL-1ß, IL-4, IL-6, and IL-10) secretion, NO release, and antigen-specific IgG, IgG1, and IgG2b antibody levels. rTn1bm-immune serum killed > 65% of L3 in the ADCC assay. Increased MHC class-II, TLR2, and TLR6 expression and the relative CD4+ and CD19+ cell populations of naïve animal cells indicated the ability of rTn1bm to mobilize innate immune responses. This is the first report of the immunoprophylactic potential of rTn1bm against B. malayi.

Activation of Autophagic Flux against Xenoestrogen Bisphenol-A-induced Hippocampal Neurodegeneration via AMP kinase (AMPK)/Mammalian Target of Rapamycin (mTOR) Pathways.

The human health hazards related to persisting use of bisphenol-A (BPA) are well documented. BPA-induced neurotoxicity occurs with the generation of oxidative stress, neurodegeneration, and cognitive dysfunctions. However, the cellular and molecular mechanism(s) of the effects of BPA on autophagy and association with oxidative stress and apoptosis are still elusive. We observed that BPA exposure during the early postnatal period enhanced the expression and the levels of autophagy genes/proteins. BPA treatment in the presence of bafilomycin A1 increased the levels of LC3-II and SQSTM1 and also potentiated GFP-LC3 puncta index in GFP-LC3-transfected hippocampal neural stem cell-derived neurons. BPA-induced generation of reactive oxygen species and apoptosis were mitigated by a pharmacological activator of autophagy (rapamycin). Pharmacological (wortmannin and bafilomycin A1) and genetic (beclin siRNA) inhibition of autophagy aggravated BPA neurotoxicity. Activation of autophagy against BPA resulted in intracellular energy sensor AMP kinase (AMPK) activation, increased phosphorylation of raptor and acetyl-CoA carboxylase, and decreased phosphorylation of ULK1 (Ser-757), and silencing of AMPK exacerbated BPA neurotoxicity. Conversely, BPA exposure down-regulated the mammalian target of rapamycin (mTOR) pathway by phosphorylation of raptor as a transient cell's compensatory mechanism to preserve cellular energy pool. Moreover, silencing of mTOR enhanced autophagy, which further alleviated BPA-induced reactive oxygen species generation and apoptosis. BPA-mediated neurotoxicity also resulted in mitochondrial loss, bioenergetic deficits, and increased PARKIN mitochondrial translocation, suggesting enhanced mitophagy. These results suggest implication of autophagy against BPA-mediated neurodegeneration through involvement of AMPK and mTOR pathways. Hence, autophagy, which arbitrates cell survival and demise during stress conditions, requires further assessment to be established as a biomarker of xenoestrogen exposure.

Zinc oxide nanoparticles provide an adjuvant effect to ovalbumin via a Th2 response in Balb/c mice.

Zinc oxide nanoparticles (ZNPs) have been used in dietary supplements and may cause an immunomodulatory effect. The present study investigated the effect of ZNPs on antigen-specific immune responses in mice sensitized with the T-cell-dependent antigen ovalbumin (OVA). BALB/c mice were intraperitoneally administered ZNPs (0.25, 0.5, 1 and 3mg) once, in combination with OVA, and the serum antibodies, splenocyte reactivity and activation of antigen-presenting cells were examined. The serum levels of OVA-specific IgG1 and IgE were found significantly enhanced by treatment with ZNPs over control. An increased level of IL-2, IL-4, IL-6, IL-17 and decreased level of IL-10 and TNF-α in splenocytes administered with ZNPs were observed in comparison with control. The ZNPs and OVA-stimulated T lymphocytes showed enhanced proliferation compared with control. Macrophages and B cells showed high expression of MHC class II, whereas higher expression of CD11b in macrophages of the ZNPs and ZNPs/OVA treated groups was observed. The lungs and spleen had increased eosinophils and mast cell numbers. Also, myeloperoxidase activity in lungs was found to be increased by 2.5-fold in the case of ZNPs and 3.75-fold increase in ZNPs/OVA, whereas in intestine, there was significant increase in both the groups. Increased expression of the genes for GATA-3, SOCS-3, TLR-4, IL-13 and IL-5 in the intestine was observed. Collectively, these data indicate that systemic exposure to a single administration of ZNPs could enhance subsequent antigen-specific immune reactions, including the serum production of antigen-specific antibodies, and the functionality of T cells.

Mechanism of rhein-induced apoptosis in rat primary hepatocytes: beneficial effect of cyclosporine A.

Past observational and toxicity studies have established an association between the deaths of children and consumption of Cassia occidentalis (CO) seeds. We recently reported chemical evidence of this association following the identification of toxic anthraquinones (AQs), viz. aloe-emodin, chrysophanol, emodin, physcion, and rhein, in CO seeds (Panigrahi, G. K. et al. (2015), Chem. Res. Toxicol. DOI: 10.1021/acs.chemrestox.5b00056 ). Of these five AQs, earlier studies have shown rhein to be the most cytotoxic AQ in hepatocytes. Therefore, the present study was designed to investigate the effect of rhein on rat primary hepatocytes. Results indicated that rhein (50 µM) causes apoptosis in rat primary hepatocytes by generating reactive oxygen species (ROS), increasing intracellular Ca(2+), decreasing the mitochondrial membrane potential, and depleting intracellular glutathione content. At the molecular level, rhein-induced DNA damage results in overexpression of γ-H2AX protein (2.5-fold), thereby causing enhancement of p53 (4.5-fold) and p21 (3.6-fold), leading to intrinsic pathway-mediated apoptosis involving Bax, bcl2, cytochrome c, caspases 3 and 9, and poly-ADP ribose polymerase. Further, it was observed that rhein-induced ROS generation is also involved in the modulation of signaling molecules like MAPK kinases, including ERK1/2, p38, and JNK, and mitochondrial energetics proteins, including complexes II-V, p-AMPK, and Sirt-1. It was shown that 100 nM cyclosporine A was the most effective among the different protective agents at preventing apoptosis in hepatocytes by interfering in various metabolic pathways which were found to be altered by rhein.

Simultaneous Determination of Acetaminophen and Synthetic Color(s) by Derivative Spectroscopy in Syrup Formulations and Validation by HPLC: Exposure Risk of Colors to Children.

Color additives are used in pediatric syrup formulations as an excipient; though not pre-requisite, but pediatric syrup formulations are normally colored. An attempt has been made to measure simultaneously the single drug, acetaminophen (AT), along with the colors, carmoisine (CA), erythrosine (ET), and sunset yellow FCF (SSY) added in it by three derivative spectroscopy methods namely, 1st order, ratio, and differential derivative methods. Moreover, evaluation has been made for the exposure assessment of the colors added as excipient because some colors have been reported to cause allergic reactions and hypersensitivity in children. The present methods provide simple, accurate, and reproducible quantitative determination of the drug, AT, along with the color in synthetic mixtures and commercial drug formulations without any interference. The limit of detection varied from 0.0001-0.31 µg/ml while limit of quantification ranged from 0.002-1.04 µg/ml in all the three methods. The calibration curve of all the three derivative methods exhibited good linear relationship with excellent regression coefficients (0.9986-1.000). Both intra-day and inter-day precisions showed %RSD value less than 2% while the percentage recovery was found between 96.8-103.8%. The sensitivity of the proposed methods is almost comparable to HPLC and thus, can be used for determination of drug AT, and color simultaneously in pharmaceutical formulation on routine basis. The present methods also showed that colors like SSY and ET are saturating more than 50% of acceptable daily intake (ADI) value which is alarming and needs to be considered for modification by regulatory authorities to safeguard the health of children.

Toll-like receptor 6 mediated inflammatory and functional responses of zinc oxide nanoparticles primed macrophages.

Macrophages are among the most sensitive immune cells because of their phagocytic activity and are prone to become dysfunctional or not able to perform properly if nanoparticle load increases. We have previously reported that zinc oxide nanoparticles (ZNPs) induce inflammatory responses in macrophages that contribute to their death. Recognition of ZNPs by pattern recognition receptors such as toll-like receptors (TLRs) might be a factor in the initiation of these responses in macrophages. Therefore, in this study we explored the role played by TLR6 and mitogen-activated protein kinase (MAPKs) pathways in the inflammatory responses of macrophages during ZNPs exposure. ZNPs-activated macrophages showed enhanced expression of activation and maturation markers (CD1d, MHC-II, CD86 and CD71). Among various TLRs screened, TLR6 emerged as the most potent activator for ZNPs-induced inflammatory responses. Downstream signalling proteins myeloid differentiation 88, interleukin-1 receptor associated kinase and tumour necrosis factor receptor-associated factor were also enhanced. On inhibiting MAPKs pathways individually, the inflammatory responses such as interleukin-1ß, interleukin-6, tumour necrosis factor-α, cyclooxygenase-2 and inducible nitric oxide synthase were suppressed. TLR6 silencing significantly inhibited the pro-inflammatory cytokine levels, reactive nitrogen species generation and inducible nitric oxide synthase expression. Also, inhibition of MAPKs in the absence of TLR6 signalling validated the link between TLR6 and MAPKs in ZNPs-induced inflammatory responses. TLR6 was found to be co-localized with autophagosomes. Macrophages lacking TLR6 inhibited the autophagosome marker protein-microtubule-associated protein1 light chain 3-isoform II formation and phagocytosis. These results demonstrate that inflammatory responses caused by ZNPs-activated macrophages strongly depend on TLR6-mediated MAPK signalling.

Deoxynivalenol induced mouse skin cell proliferation and inflammation via MAPK pathway.

Several toxicological manifestations of deoxynivalenol (DON), a mycotoxin, are well documented; however, dermal toxicity is not yet explored. The effect of topical application of DON to mice was studied using markers of skin proliferation, inflammation and tumor promotion. Single topical application of DON (84-672nmol/mouse) significantly enhanced dermal hyperplasia and skin edema. DON (336 and 672nmol) caused significant enhancement in [(3)H]-thymidine uptake in DNA along with increased myeloperoxidase and ornithine decarboxylase activities, suggesting tissue inflammation and cell proliferation. Furthermore, DON (168nmol) caused enhanced expression of RAS, and phosphorylation of PI3K/Akt, ERK, JNK and p38 MAPKs. DON exposure also showed activation of transcription factors, c-fos, c-jun and NF-κB along with phosphorylation of IkBα. Enhanced phosphorylation of NF-κB by DON caused over expression of target proteins, COX-2, cyclin D1 and iNOS in skin. Though a single topical application of DMBA followed by twice weekly application of DON (84 and 168nmol) showed no tumorigenesis after 24weeks, however, histopathological studies suggested hyperplasia of the epidermis and hypertrophy of hair follicles. Interestingly, intestine was also found to be affected as enlarged Peyer's patches were observed, suggesting inflammatory effects which were supported by elevation of inflammatory cytokines after 24weeks of topical application of DON. These results suggest that DON induced cell proliferation in mouse skin is through the activation of MAPK signaling pathway involving transcription factors NFκB and AP-1, further leading to transcriptional activation of downstream target proteins c-fos, c-jun, cyclin D1, iNOS and COX-2 which might be responsible for its inflammatory potential.

Fluid-driven motion of passive cilia enables the layer to expel sticky particles.

Inspired by marine organisms that utilize active cilia to prevent the biofouling of their surfaces, we use computational and theoretical modeling to determine if passive cilia, which are driven to undulate by an oscillatory shear flow, can be harnessed for antifouling applications. By modeling the oscillating shear flow near a ciliated wall within a channel, we show that the fluid-driven motion of cilia enables the layer to repel adhesive particles away from the surface. Compared to the behavior of the system in a non-oscillating shear, the oscillations also help transport the particles more rapidly along the flow direction. Moreover, the oscillations allow "stickier" particles to be conveyed by the flow relative to the case involving non-oscillatory flow. A simple theoretical model that considers the motion of an adhesive particle interacting with an oscillating, elastic layer captures the behavior observed in the simulations and indicates that the adhesive particle can be repelled away for a wide range of oscillation frequencies. The findings suggest that passive cilia can be used to create self-cleaning surfaces, utilizing oscillations in the flow to prevent the attachment of microparticles and biological cells.

SARS-CoV-2 JN.1 variant: a short review.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded, positive-sense RNA virus. The SARS-CoV-2 virus is evolving continuously, and many variants have been detected over the last few years. SARS-CoV-2, as an RNA virus, is more prone to mutating. The continuous evolution of the SARS-CoV-2 virus is due to genetic mutation and recombination during the genomic replication process. Recombination is a naturally occurring phenomenon in which two distinct viral lineages simultaneously infect the same cellular entity in an individual. The evolution rate depends on the rate of mutation. The rate of mutation is variable among the RNA viruses, with the SARS-CoV-2 virus exhibiting a lower rate of mutation than other RNA viruses. The novel 3'-to-5' exoribonuclease proofreading machinery is responsible for a lower rate of mutation. Infection due to the SARS-CoV-2, influenza, and respiratory syncytial virus has been reported from around the world during the same period of fall and winter, resulting in a "tripledemic." The JN.1 variant, which evolved from the predecessor, the omicron variant BA.2.86, is currently the most dominant globally. The impact of the JN.1 variant on transmissibility, disease severity, immune evasion, and diagnostic and therapeutic escape will be discussed.

Role of thoracoscopy in diagnosis of tubercular pleural effusion in low ADA setting- A prospective, observational study.

BACKGROUND: Tubercular Pleural effusion (TBPE) is one of most common extrapulmonary tuberculosis. It can be difficult to diagnose due to low sensitivity of pleural fluid smear, culture and CBNAAT. Diagnosis of TBPE is then dependent on the level of pleural fluid Adenosine Deaminase (ADA). Thoracoscopic pleural biopsy gives definite diagnosis specially in Low Pleural fluid ADA setting. AIMS AND OBJECTIVE: This study was planned to find out the prevalence of tubercular etiology in patients of exudative pleural effusion with low ADA (ADA <40 IU/L). MATERIAL AND METHODS: A Prospective, observational study was carried out in a tertiary teaching institute in north India. Total 142 patients of pleural effusion with low ADA were enrolled. All patients underwent rigid thoracoscopy for confirmation of their diagnosis. RESULTS: Out of 142 patients, male were 78 (55%) and female were 64 (45%). Mean age of patients were 57.4 years. Tuberculosis was diagnosed as a cause of effusion in 22 (15.5%) out of 142 patients. Majority of TBPE patients had pleural thickening as thoracoscopic finding. Mean ADA level in TBPE was 27.36 ± 11.6 as compared to 18.55 ± 9.02 in non tubercular pleural effusion patients and this difference was significant statistically (P- 0.002). CONCLUSION: The diagnosis of patients having exudative, low ADA pleural effusion can be very easily confirmed by thoracoscopy guided pleural biopsy which has a very high diagnostic yield.

Salivary and serum estrogen level assessment in oral lichen planus patients and its correlative analysis with OLP and stress.

Background: Lichen planus is a chronic inflammatory disease of the skin and mucous membrane with higher predilection seen in the female population. Oral lichen planus (OLP) has been associated with various etiological factors, such as stress, hormonal imbalance, and immunological variation. The purpose of this study was to assess serum and salivary estrogen (E2) levels in OLP patients and correlate them with stress levels. Objectives: This study aimed to evaluate serum and salivary estrogen levels in female patients with OLP, along with the assessment of stress and its correlation with estrogen levels. Methods: A total of 78 females, 39 clinically diagnosed with OLP and 39 healthy females, were included in the study as the case and control groups, respectively. 2 ml each of salivary and serum samples was obtained from each participant to measure the estrogen levels. Stress levels in the study group patients were assessed using the Depression Anxiety Stress Scale (DASS-21) and the Perceived Stress Scale (PSS). The nonparametric Mann-Whitney test was used for intergroup comparisons. Results: Significantly higher serum estrogen levels with higher DASS-21 and PSS scores were noted in patients with OLP. Overall, significant positive correlations were observed between salivary E2 and serum E2 (r = 0.361, P = 0.001). There was a positive correlation between salivary and serum E2 and DASS score (r = 0.410, P < 0.001, and r = 0.768, P < 0.001, respectively), serum/salivary E2 and PSS score (r = 0.745, P < 0.001, and r = 0.410, P < 0.001, respectively), and DASS score and PSS score (r = 0.878, P < 0.001). Conclusion: Estrogen can be used as a useful biomarker for OLP in the future. Salivary samples can prove to be an accurate and feasible alternative to serum estrogen level determination. We also suggest that OLP patients must be given supportive psychological treatment for improved life quality and disease management.

Photoprotective efficacy of Sunset Yellow via inhibition of type-I and type-II pathway under exposure of sunlight.

Exposure to phototoxicants and photosensitizers can result in the generation of reactive oxygen species (ROS), leading to oxidative stress, DNA damage, and various skin-related issues such as aging, allergies, and cancer. While several photo-protectants offer defense against ultraviolet radiation (UV-R), their effectiveness is often limited by photo-instability. Sunset Yellow (SY), an FDA-approved food dye, possesses significant UV-R and visible light absorption properties. However, its photoprotective potential has remained unexplored. Our investigation reveals that SY exhibits remarkable photostability for up to 8 h under both UV-R and sunlight. Notably, SY demonstrates the ability to quench ROS, including singlet oxygen (1O2), superoxide radicals ( O 2 · - $$ {\mathrm{O}}_2^{\cdotp -} $$ ), and hydroxyl radicals (·OH) induced by rose bengal, riboflavin and levofloxacin, respectively. Moreover, SY proves effective in protecting against the apoptotic and necrotic cell death induced by the phototoxicant chlorpromazine (CPZ) in HaCaT cells. Further, it was observed that SY imparts photoprotection by inhibiting intracellular ROS generation and calcium release. Genotoxicity evaluation provides additional evidence supporting SY's photoprotective effects against CPZ-induced DNA damage. In conclusion, these findings underscore the potential of SY as a promising photoprotective agent against the toxic hazards induced by phototoxicants, suggesting its prospective application in the formulation of broad-spectrum sunscreens.

Serum and salivary interleukin-1ß level in oral precancer: An observational study.

BACKGROUND AND AIM: Precancer biomarkers help in early detection and management of oral potentially malignant disorders (OPMDs). Interleukin-1ß (IL-1ß), a biomarker, is known to be altered in oral submucous fibrosis (OSMF) and oral leukoplakia (OL). Therefore, we evaluated and compared the serum and salivary IL-1ß levels in patients with OSMF/oral leukoplakia and in gender- and age-matched healthy individuals. MATERIALS AND METHODS: An in vivo, prospective, observational study was conducted on 40 subjects. Subjects were divided into two groups with 20 individuals in each group, that is, Group I: OSMF/oral leukoplakia and Group II: control group. Salivary and serum IL-1ß levels were quantitatively estimated using enzyme-linked immunosorbent assay (ELISA). The statistical tests used were unpaired t-test and Chi-square test. RESULTS: The serum IL-1ß levels were significantly (P 0.001) lesser in Group I in comparison to Group II. The salivary IL-1ß levels remained insignificant between both the groups. However, in both the groups, the salivary IL-1ß levels were significantly higher compared to the serum IL-1ß levels. CONCLUSION: We found that the serum IL-1ß level can be considered as a prospective biomarker for dysplasia, whereas salivary IL-1ß alone needs more elaborated studies to account for its application as a potential biomarker in OPMD.

Sunset Yellow protects against oxidative damage and exhibits chemoprevention in chemically induced skin cancer model.

Skin cancer and other skin-related inflammatory pathologies are rising due to heightened exposure to environmental pollutants and carcinogens. In this context, natural products and repurposed compounds hold promise as novel therapeutic and preventive agents. Strengthening the skin's antioxidant defense mechanisms is pivotal in neutralizing reactive oxygen species (ROS) and mitigating oxidative stress. Sunset Yellow (SY) exhibits immunomodulatory characteristics, evidenced by its capacity to partially inhibit the secretion of proinflammatory cytokines, regulate immune cell populations, and modulate the activation of lymphocytes. This study aimed to investigate the antioxidant and anti-genotoxic properties of SY using in-silico, in vitro, and physiochemical test systems, and to further explore its potential role in 7,12-dimethylbenz(a) anthracene (DMBA)/ 12-o-tetradecanoylphorbol-13-acetate (TPA)-induced two-stage skin carcinogenesis. In vitro experiments showed that pre-treatment of SY significantly enhanced the cell viability of HaCaT cells when exposed to tertiary-Butyl Hydrogen Peroxide (tBHP). This increase was accompanied by reduced ROS levels, restoration of mitochondrial membrane potential, and notable reduction in DNA damage in (SY + tBHP) treated cells. Mechanistic investigations using DPPH chemical antioxidant activity test and potentiometric titrations confirmed SY's antioxidant properties, with a standard reduction potential ( E o ) of 0.211 V. Remarkably, evaluating the effect of topical application of SY in DMBA/TPA-induced two-step skin carcinogenesis model revealed dose-dependent decreases in tumor latency, incidence, yield, and burden over 21-weeks. Furthermore, computational analysis and experimental validations identified GSK3ß, KEAP1 and EGFR as putative molecular targets of SY. Collectively, our findings reveal that SY enhances cellular antioxidant defenses, exhibits anti-genotoxic effects, and functions as a promising chemopreventive agent.

Size selectivity in artificial cilia-particle interactions: mimicking the behavior of suspension feeders.

Inspired by the ability of marine suspension feeders to selectively capture small particles by their hairlike cilia, we simulate the interaction between artificial cilia and microscopic particles of different sizes to determine if a purely synthetic system can display analogous size-selective behavior. Our computational approach specifically models the capture of particles suspended in the surrounding fluid by adhesive filaments, which are anchored by one end to a surface. Via this model, we show that this size selectivity can arise as a result of adhesive and hydrodynamic interactions in the system. The substantial reduction in the mobility of the large particles near surfaces leads to a failure in capturing large particles. Using a simple analytical model, we show that the balance of hydrodynamic and adhesive forces favors capture of particles below a critical size for a given cilia-particle interaction. Our findings provide guidelines for designing artificial cilia that can be used for sorting and transporting particles within microfluidic devices.

Active ciliated surfaces expel model swimmers.

Continually moving cilia on the surface of marine organisms provide a natural defense against biofouling. To probe the physical mechanisms underlying this antifouling behavior, we integrate the lattice Boltzmann and immersed boundary methods and undertake the first computational studies of the interactions between actuated, biomimetic cilia and a model swimmer. We find that swimmers are effectively "knocked away" from the ciliated surface through a combination of steric repulsion and locally fluctuating flows. In addition, the net flow generated by the collective motion of the entire ciliary array was important for significantly reducing the times spent by relatively slow swimmers near the surface. The results reveal that active ciliated layers can offer a means to resist a wide range of species with a single surface.

A Biochip with a 3D microfluidic architecture for trapping white blood cells.

We present a microfluidic biochip for trapping single white blood cells (WBCs). The novel biochip, microfabricated using standard surface micromachining processes, consists of an array of precisely engineered microholes that confine single cells in a tight, three dimensional space and mechanically immobilize them. A high (> 87%) trapping efficiency was achieved when WBC-containing samples were delivered to the biochip at the optimal pressure of 3 psi. The biochip can efficiently trap up to 7,500 cells, maintaining a high trapping efficiency even when the number of cells is extremely low (~200 cells). We believe that the developed biochip can be used as a standalone unit in a biology/clinical lab for trapping WBCs as well as other cell types and imaging them using a standard fluorescent microscope at the single cell level. Furthermore, it can be integrated with other miniaturized optical modules to construct a portable platform for counting a wide variety of cells and therefore it can be an excellent tool for monitoring human diseases at the point-of-care.