Search
Filter Results
- Resource Type
- Article244
- Book1
- Book Print1
- Article Type
- Review7
- Clinical Trial3
- Systematic Review1
- Research Support, Non-U.S. Gov't111
- Result From
- PubMed244
- Lane Catalog1
-
Year
- Journal Title
- J Physiol34
- Proc SPIE Int Soc Opt Eng22
- FEBS Lett19
- Biochim Biophys Acta17
Search Results
Sort by
- ArticleZhang Y, Hu Y, Pan A, He L, Wang J, Zhou F, Lei Y, Wang Y.Bioengineered. 2021 12;12(2):11584-11596.Long non-coding (lncRNA) neuroblastoma highly expressed 1 (NHEG1) has been reorganized as a prognostic factor in neuroblastoma (NB), but the molecular mechanisms in the suppression of neuroblastoma remain to be elucidated. In our study, we explored the functional roles of lncRNA NHEG1 in neuroblastoma and the underlying molecular mechanism. We collected NB tumor samples and adjacent normal tissues to compare lncRNA NHEG1 expression. Through bioinformatic target prediction, we selected potential downstream effectors of lncRNA NHEG1 for functional validation in NB cell lines. We observed that lncRNA NHEG1 was significantly upregulated in NB tissues as compared to the normal tissues. In NB tissues, lncRNA NHEG1 expression showed an inverse correlation with hsa-miR-665 (miR-655), but a positive correlation with high mobility group box 1 (HMGB1). In NB cell lines, lncRNA NHEG1 knockdown caused the upregulation of miR-665 and the downregulation of HMGB1. Through a series of functional assays, we further demonstrated that lncRNA Nheg1 knockdown suppressed cell proliferation, migration and invasion of NB cells, which could be rescued by miR-665 inhibitor and HMGB1 overexpression. Together, our data demonstrated that lncRNA NHEG1 serves as a competitive partner to negatively regulate the activity of miR-665, which relieves the inhibition on HMGB1 expression and promotes the aggressive phenotype of neuroblastoma cells. Our study indicates that lncRNA NHEG1/miR-665/HMGB1 axis may play an important role in regulating the aggressiveness and the progression of neuroblastoma.
- ArticleEkong PS, Abdelfattah EM, Okello E, Williams DR, Lehenbauer TW, Karle BM, Rowe JD, Aly SS.PeerJ. 2021;9:e11596.BACKGROUND: Antimicrobial drugs (AMD) are critical for the treatment, control, and prevention of diseases in humans and food-animals. Good AMD stewardship practices and judicious use of AMD are beneficial to the preservation of animal and human health from antimicrobial resistance threat. This study reports on changes in AMD use and stewardship practices on California (CA) dairies, following the implementation of CA Senate Bill 27 (SB 27; codified as Food and Agricultural Code, FAC 14400-14408; here onward referred to as SB 27), by modeling the associations between management practices on CA conventional dairies and seven outcome variables relating to AMD use and stewardship practices following SB 27.
METHODS: A survey questionnaire was mailed to 1,282 grade A licensed dairies in CA in spring of 2018. Responses from 132 conventional dairies from 16 counties were included for analyses. Multivariate logistic regression models were specified to explore the associations between survey factors and six outcome variables: producers' familiarity with the Food and Drug Administration's (FDA), Silver Spring, WA, USA medically important antimicrobial drugs (MIAD) term; change in over-the-counter (OTC) AMD use; initiation or increased use of alternatives to AMD; changes to prevent disease outbreaks; changes in AMD costs; and better animal health post SB 27. We employed machine learning classification models to determine which of the survey factors were the most important predictors of good-excellent AMD stewardship practices of CA conventional dairy producers.
RESULTS: Having a valid veterinary-client-patient-relationship, involving a veterinarian in training employees on treatment protocols and decisions on AMDs used to treat sick cows, tracking milk and/or meat withdrawal intervals for treated cows, and participating in dairy quality assurance programs were positively associated with producers' familiarity with MIADs. Use or increased use of alternatives to AMDs since 2018 was associated with decreased use of AMDs that were previously available OTC prior to SB 27. Important variables associated with good-excellent AMD stewardship knowledge by CA conventional dairy producers included having written or computerized animal health protocols, keeping a drug inventory log, awareness that use of MIADs required a prescription following implementation of SB 27, involving a veterinarian in AMD treatment duration determination, and using selective dry cow treatment.
CONCLUSIONS: Our study identified management factors associated with reported AMD use and antimicrobial stewardship practices on conventional dairies in CA within a year from implementation of SB 27. Producers will benefit from extension outreach efforts that incorporate the findings of this survey by further highlighting the significance of these management practices and encouraging those that are associated with judicious AMD use and stewardship practices on CA conventional dairies. - ArticleEscriche-Tur L, Jover J, Font-Bardia M, Aullón G, Corbella M.Inorg Chem. 2015 Dec 21;54(24):11596-605.Two new heterometallic Mn(IV)-M(2+) compounds with formula [Mn6M2O9(4-(t)BuC6H4COO)10(4-(t)BuC6H4COOH)5] (M = Ca(2+) (1), Sr(2+) (2)) have been crystallized. The core of both compounds consists of a planar Mn6 ring, where the Mn(IV) ions are alternatively bridged by (μ3-O)2(μ-RCOO) and (μ4-O)(μ-RCOO)2 ligands, and the two alkaline earth ions are located to both sides of the wheel, linked to the oxo bridges, generating three fused [Mn2M2O4](4+) cuboids. These compounds show a net antiferromagnetic behavior, more important for 2 (Sr(2+)) than for 1 (Ca(2+)). The fitting of the experimental data was performed with the support of DFT calculations, considering four different exchange pathways: two between adjacent Mn(IV) ions (J1 and J2) and two between nonadjacent Mn(IV) ions (J3 and J4). The results of the analysis show that J1 and J2 are of the opposite sign, the ferromagnetic contribution corresponding to the [Mn2(μ4-O)(μ-RCOO)2](4+) unit (J2). The influence of the M(2+) ions in the magnetic behavior is analyzed for 1 and 2 and for three hypothetical models with the structural parameters of 1 containing Mg(2+), Sr(2+) or without the M(2+) ions. In spite of the diamagnetic character of the alkaline earth ions, their influence on the magnetic behavior has been evidenced and correlated with their polarizing effect. Moreover, the magnetic interactions between nonadjacent ions are non-negligible.
- ArticleBaudin PV, Sacksteder RE, Worthington AK, Voitiuk K, Ly VT, Hoffman RN, Elliott MAT, Parks DF, ... Show More Ward R, Torres-Montoya S, Amend F, Montellano Duran N, Vargas PA, Martinez G, Ramirez SM, Alvarado-Arnez LE, Ehrlich D, Rosen YM, Breevoort A, Schouten T, Kurniawan S, Haussler D, Teodorescu M, Mostajo-Radji MA.Heliyon. 2022 Nov;8(11):e11596.Project-based learning (PBL) has long been recognized as an effective way to teach complex biology concepts. However, not all institutions have the resources to facilitate effective project-based coursework for students. We have developed a framework for facilitating PBL using remote-controlled internet-connected microscopes. Through this approach, one lab facility can host an experiment for many students around the world simultaneously. Experiments on this platform can be run on long timescales and with materials that are typically unavailable to high school classrooms. This allows students to perform novel research projects rather than just repeating standard classroom experiments. To investigate the impact of this program, we designed and ran six user studies with students worldwide. All experiments were hosted in Santa Cruz and San Francisco, California, with observations and decisions made remotely by the students using their personal computers and cellphones. In surveys gathered after the experiments, students reported increased excitement for science and a greater desire to pursue a career in STEM. This framework represents a novel, scalable, and effective PBL approach that has the potential to democratize biology and STEM education around the world.
- ArticleZwingelberg SB, Lautwein B, Baar T, Heinzel-Gutenbrunner M, von Brandenstein M, Nobacht S, Matthaei M, Bachmann BO.Sci Rep. 2024 05 21;14(1):11596.To detect environmental factors, which may be possible risk factors in the disease course of Fuchs' endothelial corneal dystrophy (FECD). Evaluation of patients with FECD registered in the FECD genetics database of the Center for Ophthalmology, University Hospital Cologne. For the evaluation, disease onset, central corneal thickness, best spectacle corrected visual acuity (BSCVA, logMAR), and modified Krachmer grading (grades 1-6) were correlated with the presence of diabetes mellitus (DM), body mass index (BMI), and smoking behavior. To put the age-related increase in Krachmer grading into perspective, a correction of grading were formed. Depending on the variables studied, differences between groups were examined by Mann-Whitney U test and chi-square test. The significance level was 5%. 403 patients with FECD were included in the analysis. The mean age of the patients was 70.0 ± 10.32 (range 28-96) years. The mean age at diagnosis of those patients was 63.1 ± 13.2 years. The female-to-male ratio was 1.46:1. Patients with a BMI > 30.0 kg/m2 developed FECD significantly earlier than patients with a BMI < 30 kg/m2, p = 0.001. Patients with DM showed significantly more often an Krachmer grade of 5, p = 0.015. Smoking had a negative effect on Krachmer grading (p = 0.024). Using the mediation analysis, the presence of DM correlated Krachmer Grade 5 (p = 0.015), and the presence of DM correlated with BMI > 30.0 kg/m2 (p = 0.012). In addition to smoking and DM our study shows for the first time that obesity may have a negative impact on the development of FECD. Whether dietary interventions and hormones can influence the development or progression of the disease needs to be investigated in future studies.
- ArticleJaeger HK, Davis DA, Nair A, Shrestha P, Stream A, Yaparla A, Yarchoan R.Sci Rep. 2023 07 18;13(1):11596.Epstein-Barr virus (EBV) downregulates immune surface markers to avoid immune recognition. Pomalidomide (Pom) was previously shown to increase immune surface marker expression in EBV-infected tumor cells. We explored the mechanism by which Pom leads to these effects in EBV-infected cells. Pom increased B7-2/CD86 mRNA, protein, and surface expression in EBV-infected cells but this was virtually eliminated in EBV-infected cells made resistant to Pom-induced cytostatic effects. This indicates that Pom initiates the upregulation of these markers by interacting with its target, cereblon. Interestingly, Pom increased the proinflammatory cytokines IP-10 and MIP-1∝/β in EBV infected cells, supporting a possible role for the phosphoinositide 3-kinase (PI3K)/AKT pathway in Pom's effects. Idelalisib, an inhibitor of the delta subunit of PI3 Kinase, blocked AKT-Ser phosphorylation and Pom-induced B7-2 surface expression. PU.1 is a downstream target for AKT that is expressed in EBV-infected cells. Pom treatment led to an increase in PU.1 binding to the B7-2 promoter based on ChIP analysis. Thus, our data indicates Pom acts through cereblon leading to degradation of Ikaros and activation of the PI3K/AKT/PU.1 pathway resulting in upregulation of B7-2 mRNA and protein expression. The increased immune recognition in addition to the increases in proinflammatory cytokines upon Pom treatment suggests Pom may be useful in the treatment of EBV-positive lymphomas.
- ArticleGandhirajan RK, Jain M, Walla B, Johnsen M, Bartram MP, Huynh Anh M, Rinschen MM, Benzing T, Schermer B.J Biol Chem. 2016 May 27;291(22):11596-607.Transcriptional co-activator with PDZ-binding motif (TAZ) and Yes-associated protein (YAP) are critical transcriptional co-activators downstream of the Hippo pathway involved in the regulation of organ size, tissue regeneration, proliferation, and apoptosis. Recent studies suggested common and distinct functions of TAZ and YAP and their diverse impact under several pathological conditions. Here we report differential regulation of TAZ and YAP in response to oxidative stress. H2O2 exposure leads to increased stability and activation of TAZ but not of YAP. H2O2 induces reversible S-glutathionylation at conserved cysteine residues within TAZ. We further demonstrate that TAZ S-glutathionylation is critical for reactive oxygen species (ROS)-mediated, TAZ-dependent TEA domain transcription factor (TEAD) trans-activation. Lysophosphatidic acid, a physiological activator of YAP and TAZ, induces ROS elevation and, subsequently, TAZ S-glutathionylation, which promotes TAZ-mediated target gene expression. TAZ expression is essential for renal homeostasis in mice, and we identify basal TAZ S-glutathionylation in murine kidney lysates, which is elevated during ischemia/reperfusion injury in vivo This induced nuclear localization of TAZ and increased expression of connective tissue growth factor. These results describe a novel mechanism by which ROS sustains total cellular levels of TAZ. This preferential regulation suggests TAZ to be a redox sensor of the Hippo pathway.
- ArticleHarada KI, Furuita K, Yamashita E, Taoka KI, Tsuji H, Fujiwara T, Nakagawa A, Kojima C.Sci Rep. 2022 07 08;12(1):11596.In potato (Solanum tuberosum L.), 14-3-3 protein forms a protein complex with the FLOWERING LOCUS T (FT)-like protein StSP6A and the FD-like protein StFDL1 to activate potato tuber formation. Eleven 14-3-3 isoforms were reported in potato, designated as St14a-k. In this study, the crystal structure of the free form of St14f was determined at 2.5 Å resolution. Three chains were included in the asymmetric unit of the St14f free form crystal, and the structural deviation among the three chain structures was found on the C-terminal helix H and I. The St14f free form structure in solution was also investigated by nuclear magnetic resonance (NMR) residual dipolar coupling analysis, and the chain B in the crystal structure was consistent with NMR data. Compared to other crystal structures, St14f helix I exhibited a different conformation with larger B-factor values. Larger B-factor values on helix I were also found in the 14-3-3 free form structure with higher solvent contents. The mutation in St14f Helix I stabilized the complex with StFDL1. These data clearly showed that the flexibility of helix I of 14-3-3 protein plays an important role in the recognition of target protein.
- ArticleBi X, Yi S, Zhang A, Zhao Z, Liu Y, Zhang C, Ye Z.Sci Rep. 2021 07 05;11(1):11596.Hemorrhagic fever with renal syndrome (HFRS), a serious threat to human health, is mainly transmitted by rodents in Eurasia. The risk of disease differs according to sex, age, and occupation. Further, temperature and rainfall have some lagging effects on the occurrence of the disease. The quantitative data for these factors in the Tai'an region of China are still unknown. We used a forest map to calculate the risk of HFRS in different populations and used four different mathematical models to explain the relationship between time factors, meteorological factors, and the disease. The results showed that compared with the whole population, the relative risk in rural medical staff and farmers was 5.05 and 2.00, respectively (p < 0.05). Joinpoint models showed that the number of cases decreased by 33.32% per year from 2005 to 2008 (p < 0.05). The generalized additive model showed that air temperature was positively correlated with disease risk from January to June, and that relative humidity was negatively correlated with risk from July to December. From January to June, with an increase in temperature, after 15 lags, the cumulative risk of disease increased at low temperatures. From July to December, the cumulative risk decreased with an increase in the relative humidity. Rural medical staff, farmers, men, and middle-aged individuals were at a high risk of HFRS. Moreover, air temperature and relative humidity are important factors that affect disease occurrence. These associations show lagged and differing effects according to the season.
- ArticleChen Z, Andreev D, Oeser K, Krljanac B, Hueber A, Kleyer A, Voehringer D, Schett G, Bozec A.Nat Commun. 2016 06 07;7:11596.Th2-eosinophil immune responses are well known for mediating host defence against helminths. Herein we describe a function of Th2-eosinophil responses in counteracting the development of arthritis. In two independent models of arthritis, Nippostrongylus brasiliensis infection leads to Th2 and eosinophil accumulation in the joints associated with robust inhibition of arthritis and protection from bone loss. Mechanistically, this protective effect is dependent on IL-4/IL-13-induced STAT6 pathway. Furthermore, we show that eosinophils play a central role in the modulation of arthritis probably through the increase of anti-inflammatory macrophages into arthritic joints. The presence of these pathways in human disease is confirmed by detection of GATA3-positive cells and eosinophils in the joints of rheumatoid arthritis patients. Taken together, these results demonstrate that eosinophils and helminth-induced activation of the Th2 pathway axis effectively mitigate the course of inflammatory arthritis.
- ArticleMurei A, Ayinde WB, Gitari MW, Samie A.Sci Rep. 2020 07 14;10(1):11596.Some antibiotics have lost their efficacy over common infections and this has led to the search for new antibiotics and chemically altering existing ones for a better control of infectious diseases. In the present study, Pyrenacantha grandiflora tubers extracts were conjugated with ampicillin, penicillin, vancomycin and silver nanoparticles and their antimicrobial activity was evaluated against Escherichia coli, Staphylococcus aureus and Klebsiella Pneumoniae. The reactions were confirmed by formation of new functional groups that were identified by Fourier transmission infrared spectroscopy (FTIR). Minimum inhibitory concentrations were determined using the microdilution assay. Minimum bactericidal concentrations and the fractional inhibition concentration index were also determined. FTIR analysis indicated different functional group associated with conjugation. The activity of ampicillin was improved when conjugated with silver nanoparticles against K. pneumonia and E. coli. Vancomycin showed improvement of activity when conjugated to silver nanoparticles against K. pneumonia. Penicillin was improved by acetone extracts and vancomycin showed to be more effective when conjugated with silver nanoparticles and water extracts. The conjugation of P. grandiflora with penicillin, ampicillin and vancomycin in the presence of silver nanoparticles improved their biological activities. Therefore, the conjugates are medicinally important and can be used to improve the activity of existing antibiotics.
- ArticleIslam MR, Ihenacho K, Park JW, Islam IS.Sci Rep. 2019 08 12;9(1):11596.Protease inhibitors, such as trypsin inhibitor, serum alpha-1 antitrypsin, or liver aprotinin, are a class of proteins that competitively bind and block the catalytic activity of proteolytic enzymes with wide ranging biological functions. A significant number of protease inhibitors have also been shown to possess antimicrobial activity, presumed to contribute in defense against pathogenic microorganisms as plants with higher levels of protease inhibitors tend to exhibit increased resistance towards pathogens. Two proposed mechanisms for the antimicrobial activity are combating microbial proteases that play roles in disease development and disruption of microbial cell wall & membrane necessary for survival. Here we show for the first time a novel activity of soybean trypsin inhibitor and bovine aprotinin that they nick supercoiled, circular plasmid DNA. A number of experiments conducted to demonstrate the observed DNA nicking activity is inherent, rather than a co-purified, contaminating nuclease. The nicking of the plasmid results in markedly reduced efficiencies in transformation of E. coli and transfection of HEK293T cells. Thus, this work reveals yet a new mechanism for the antimicrobial activity by protease inhibitors.
- ArticleDeleglise B, Lassus B, Soubeyre V, Doulazmi M, Brugg B, Vanhoutte P, Peyrin JM.Sci Rep. 2018 08 02;8(1):11596.Increasing evidence suggests that pathological hallmarks of chronic degenerative syndromes progressively spread among interconnected brain areas in a disease-specific stereotyped pattern. Functional brain imaging from patients affected by various neurological syndromes such as traumatic brain injury and stroke indicates that the progression of such diseases follows functional connections, rather than simply spreading to structurally adjacent areas. Indeed, initial damage to a given brain area was shown to disrupt the communication in related brain networks. Using cortico-striatal neuronal networks reconstructed in a microfluidic environment, we investigated the role of glutamate signaling in activity-dependent neuronal survival and trans-synaptic degeneration processes. Using a variety of neuronal insults applied on cortical neurons, we demonstrate that acute injuries such as axonal trauma, focal ischemia, or alteration of neuronal rhythms, lead to glutamate-dependent striatal neuron dysfunction. Interestingly, focal pro-oxidant insults or chronic alteration of spontaneous cortical rhythms provoked dysfunction of distant striatal neurons through abnormal glutamate GluN2B-NMDAR-mediated signaling at cortico-striatal synapses. These results indicate that focal alteration of cortical functions can initiate spreading of dysfunction along neuronal pathways in the brain, reminiscent of diaschisis-like processes.
- ArticleVasireddy D, Atwi JE.Cureus. 2020 Nov 20;12(11):e11596.A nine-day-old male infant presents with his mother to the pediatric clinic with a concern of a white spot in his right eye. There was no history of antenatal or perinatal complications and the mother's serology was negative. Physical examination was remarkable only for leukocoria in the right eye. He was evaluated to have a Mittendorf dot. This is a benign clinical finding. Pupillary reflex check is an important part of a physical examination which can recognise pathological conditions such as cataract, retinoblastoma, metabolic errors with ocular manifestations and lead to early treatment before the child loses vision.
- ArticleDeng R, Bai Y, Liu Y, Lu Y, Zhao Z, Deng Y, Yang H.Chem Commun (Camb). 2024 Oct 08;60(81):11596.Correction for 'DNAzyme-activated CRISPR/Cas assay for sensitive and one-pot detection of lead contamination' by Ruijie Deng et al., Chem. Commun., 2024, 60, 5976-5979, https://doi.org/10.1039/D4CC01852D.
- ArticleUšaj M, Henn A.Sci Rep. 2017 09 14;7(1):11596.Myosins are actin-based molecular motors which are enzymatically adapted for their cellular functions such as transportation and membrane tethering. Human Myo19 affects mitochondrial motility, and promotes their localization to stress-induced filopodia. Therefore, studying Myo19 enzymology is essential to understand how this motor may facilitate mitochondrial motility. Towards this goal, we have purified Myo19 motor domain (Myo19-3IQ) from a human-cell expression system and utilized transient kinetics to study the Myo19-3IQ ATPase cycle. We found that Myo19-3IQ exhibits noticeable conformational changes (isomerization steps) preceding both ATP and ADP binding, which may contribute to nucleotide binding regulation. Notably, the ADP isomerization step and subsequent ADP release contribute significantly to the rate-limiting step of the Myo19-3IQ ATPase cycle. Both the slow ADP isomerization and ADP release prolong the time Myo19-3IQ spend in the strong actin binding state and hence contribute to its relatively high duty ratio. However, the predicted duty ratio is lower than required to support motility as a monomer. Therefore, it may be that several Myo19 motors are required to propel mitochondria movement on actin filaments efficiently. Finally, we provide a model explaining how Myo19 translocation may be regulated by the local ATP/ADP ratio, coupled to the mitochondria presence in the filopodia.
- ArticleZandieh M, Liu J.Langmuir. 2023 08 22;39(33):11596-11602.Nanodiamonds (NDs) have attracted considerable attention owing to their quantum properties and versatility in biological applications. In this study, we systematically investigated the adsorption of DNA oligonucleotides onto NDs with three types of surface groups: carboxylated (COOH-), hydroxylated (OH-), and hydrogenated (H-). Among them, only the H-NDs showed fluorescence quenching property that is useful for real-time DNA adsorption kinetic studies. The effect of common metal ions on DNA adsorption was studied. In the presence of Na+, the order of DNA adsorption efficiency was H- > OH- > COOH-, whereas all the NDs showed a similar DNA adsorption efficiency in the presence of divalent metal ions such as Ca2+ and Zn2+. Desorption studies revealed that hydrogen bonding and metal-mediated interactions were dominant for the adsorption of DNA, and the H-NDs exhibited extraordinarily tight DNA adsorption. Finally, a fluorescently labeled DNA was adsorbed on NDs for DNA detection, and the COOH-NDs had the highest target specificity, and a detection limit of 1.4 nM was achieved. This study indicates the feasibility of using metal ions to mediate the physical adsorption of DNA to NDs and compares various NDs with graphene oxide for fundamental understanding.
- ArticleBovay B, Descombes P, Chittaro Y, Glauser G, Nomoto H, Rasmann S.Ecol Evol. 2024 Jun;14(6):e11596.Asynchronous migration of insect herbivores and their host plants towards higher elevations following climate warming is expected to generate novel plant-insect interactions. While the disassociation of specialised interactions can challenge species' persistence, consequences for specialised low-elevation insect herbivores encountering novel high-elevation plants under climate change remain largely unknown. To explore the ability of two low-elevation Lepidoptera species, Melitaea celadussa and Zygaena filipendulae, to undergo shifts from low- to high-elevation host plants, we combined a translocation experiment performed at two elevations in the Swiss Alps with experiments conducted under controlled conditions. Specifically, we exposed M. celadussa and Z. filipendulae to current low- and congeneric high-elevation host plants, to test how shifts in host plant use impact oviposition probability, number of eggs clutches laid, caterpillar feeding preference and growth, pupation rate and wing size. While our study shows that both M. celadussa and Z. filipendulae can oviposit and feed on novel high-elevation host plants, we reveal strong preferences towards ovipositing and feeding on current low-elevation host plants. In addition, shifts from current low- to novel high-elevation host plants reduced pupation rates as well as wing size for M. celadussa, while caterpillar growth was unaffected by host plant identity for both species. Our study suggests that populations of M. celadussa and Z. filipendulae have the ability to undergo host plant shifts under climate change. However, these shifts may impact the ability of populations to respond to rapid climate change by altering developmental processes and morphology. Our study highlights the importance of considering altered biotic interactions when predicting consequences for natural populations facing novel abiotic and biotic environments.
- ArticleDeng R, Lu J, Liu X, Peng XH, Wang J, Li XP.Cancer Manag Res. 2020;12:11585-11596.PURPOSE: Tumour-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment and provide a barrier against the cytotoxic effector functions of T cells and natural killer (NK) cells. Recently, TAMs have become increasingly recognised as an attractive target in combination therapy with PD-1/PD-L1 immuno-checkpoint blockades (ICBs). However, the relationship between PD-L1 expression and TAMs remains unknown in nasopharyngeal carcinoma (NPC).
PATIENTS AND METHODS: A total of 212 NPC patients from Nanfang hospital were collected in this study. We evaluated the expression of PD-L1 in tumor cells, CD68 (pan-macrophages), and CD163 (M2-like macrophage) in NPC tissues using immunohistochemical (IHC) staining.
RESULTS: The positivity of PD-L1 on tumor cells was 61.3% (130/212). The infiltration densities of CD68+ cells and CD163+ cells in PD-L1-positive NPC tissues were significantly higher than those in PD-L1-negative NPC tissues (P=0.0012 for CD68; P<0.0001 for CD163). Logistic regression analysis showed that high densities of CD68+ macrophages and CD163+ TAMs were significantly associated with increased PD-L1 expression. Subgroup analyses demonstrated that a positive PD-L1 expression on tumor cells in combination with lower CD163+ TAMs density was significantly associated with favorable prognosis, whereas negative PD-L1 expression on tumor cells with higher CD163+ TAMs density was associated with worse prognosis.
CONCLUSION: The PD-L1 expression in tumor cells was positively correlated with TAMs density in tumor microenvironment of NPC, suggesting TAMs as a new target for combination therapy to improve the response rate of ICBs in NPC treatment. - ArticleÇolak A, Li B, Blass J, Koynov K, Del Campo A, Bennewitz R.Nanoscale. 2019 Jun 28;11(24):11596-11604.The response of cultured cells to the mechanical properties of hydrogel substrates depends ultimately on the response of single crosslinks to external forces exerted at cell attachment points. We prepared hydrogels by co-polymerization of poly(ethylene glycol diacrylate) (PEGDA) and carboxy poly(ethylene glycol) acrylate (ACPEG-COOH) and confirmed fibroblast spreading on the hydrogel after the ACPEG linker was functionalized with the RGD cell adhesive motif. We performed specific force spectroscopy experiments on the same ACPEG linkers in order to probe the mechanics of single cross-links which mediate the cell attachment and spreading. Measurements were performed with tips of an atomic force microscope (AFM) functionalized with streptavidin and ACPEG linkers functionalized with biotin. We compared hydrogels of varying elastic modulus between 4 and 41 kPa which exhibited significant differences in cell spreading. An effective spring constant for the displacement of single cross-links at the hydrogel surface was derived from the distributions of rupture force and molecular stiffness. A factor of ten in the elastic modulus E of the hydrogel corresponded to a factor of five in the effective spring constant k of single crosslinks, indicating a transition in scaling with the mesh size ξ from the macroscopic E∝ξ-3 to the molecular k∝ξ-2. The quantification of stiffness and deformation at the molecular length scale contributes to the discussion of mechanisms in force-regulated phenomena in cell biology.