Inhibition of TGF-B signaling in combination with TLR7 ligation re-programs a tumoricidal phenotype in tumor-associated macrophages

Inadequate immunity that occurs in a tumor environment is in part due to the presence of M2-type tumor-associated macrophages (TAMs). TGF-beta has a multi-functional role in tumor development including modulating the biological activity of both the tumor and TAMs. In this study, using an in vitro TAM/tumor cell co-culture system ligation of TLR7, which is expressed on TAMs but not the tumor cells, in the presence of TGF-beta receptor I inhibitor re-programmed the phenotype of the TAMs. In part they adopted the phenotype characteristic of M1-type macrophages, namely they had increased tumoricidal activity and elevated expression of iNOS, CD80 and MHC class II, while TGF-beta secretion was reduced. The reprogrammed phenotype was accompanied by enhanced NF-kappaB nuclear translocation. The pro-angiogenesis factor VEGF was down-regulated and in vivo the number of CD31-positive tumor capillaries was also reduced. Furthermore, in vivo we observed that TLR7 ligation/TGF-beta receptor I inhibition increased tumor apoptosis and elevated the number of CD4+, CD8+, and CD19+ cells as well as neutrophils infiltrating the tumor. Our data demonstrate that selective TLR stimulation with TGF-beta inhibition can reprogram TAMs towards an M1-like phenotype and thereby provides new perspectives in cancer therapy.postprin

Using Lycium Barbarum (Gouqizi) as an example to explain the holistic concept of anti-aging Chinese medical herbs

Session - Biological Activities and Mechanism Study II (Metabolic, Neural Diseases and Aging Process): abstract no. 11

Expression and electrophysiological studies of secretin in the rat hypothalamic paraventricular nucleus

Secretin, a 27-amino-acid brain-gut hormone, is a putative neuropeptide believed to have neuromodulatory effects in the central nervous system (CNS). Secretin and its receptor are widely distributed in the CNS, including the hypothalamus. By using double immunofluorosence, we discovered that secretin and its receptor are expressed and colocalized with vasopressin (VP) and less with oxytocin (OT), two neurosecretory hormones synthesized in the hypothalamic paraventricular nucleus magnocellular (mgPVN) neurons. This observation suggested that secretin may modulate the activity of mgPVN neurons. Using whole-cell patch clamp on rat hypothalamic slices, we examined the effects of secretin in the electrophysiologically identified magnocellular neurons. Voltage-clamp studies indicated that 100nM secretin did not significantly affect the frequency of miniature inhibitory postsynaptic currents (control:2.9±1.1Hz; secretin:3.3±1.2Hz, n=5, p>0.05) and miniature excitatory postsynaptic currents (control:1.3±0.4Hz; secretin:1.3±0.6Hz, n=3, p>0.05). Their amplitudes were also unaltered. Current-clamp studies showed that membrane potential was unaffected by 30nM (control:­43.4±1.6mV; secretin:­44.3±1.4mV, n=3, p>0.05) and 100nM secretin (control:­42.4±0.5mV; secretin:­42.5±0.5mV, n=11, p>0.05). Our data demonstrated that secretin has no observable pre- and postsynaptic effects on mgPVN neurons despite the expression of secretin and its receptor in VP and OT cells. These results suggested that secretin may be stored in the mgPVN neurons and co-release with VP or OT to the posterior pituitary. Further investigation is necessary to substantiate this hypothesis and to understand the function of secretin receptors in the PVN

Alzheimer-like pathology in rat receiving passive smoking

Program / Poster no. 626.13 / H26Although epidemiological studies shows that smoking could increase the risk of Alzheimer’s disease (AD), the molecular basis linking smoking with increased incidence of AD is still unclear. We have established a model of passive smoking (1 hour per day exposure to either sham air or 4% cigarette smoke) for 8 weeks in the ventilated smoking chamber on Sprague-Dawley rats and investigated the changes of β-amyloid (Aβ) in the model. It was found that smoke exposure resulted in increased accumulation of Aβ, up-regulation of β amyloid precursor protein (APP), its proteolytic product sAPPβ fragment as well as β-site APP-cleaving enzyme 1 (BACE1). In addition, the level of nitrotyrosine, a marker of oxidative stress, and 8-hydroxyguanosine, a marker of oxidative damage, was found to be significantly increased in the hippocampus of passive smoking rats. Taken together, our data suggest that passive smoking can induce Alzheimer-like Aβ pathology, and this pathological event may be associated with increased oxidative stress. Our study provides compelling evidence to support the findings from epidemiological studies

Folkbiology meets microbiology: A study of conceptual and behavioral change

Health education can offer a valuable window onto conceptual and behavioral change. In Study 1, we mapped out 3rd-grade Chinese children's beliefs about causes of colds and flu and ways they can be prevented. We also explored older adults' beliefs as a possible source of the children's ideas. In Study 2, we gave 3rd- and 4th-grade Chinese children either a conventional cold/flu education program or an experimental "Think Biology" program that focused on a biological causal mechanism for cold/flu transmission. The "Think Biology" program led children to reason about cold/flu causation and prevention more scientifically than the conventional program, and their reasoning abilities dovetailed with their mastery of the causal mechanism. Study 3, a modified replication of Study 2, found useful behavioral change as well as conceptual change among children who received the "Think Biology" program and documented coherence among knowledge enrichment, conceptual change, and behavioral change. © 2008 Elsevier Inc. All rights reserved.link_to_subscribed_fulltex

Semi-individualized acupuncture for insomnia disorder and oxidative stress : a randomized, double-blind, sham-controlled trial

202111 bchyVersion of RecordRGCPublishe

Renal stromal miRNAs are required for normal nephrogenesis and glomerular mesangial survival

MicroRNAs are small noncoding RNAs that post-transcriptionally regulate mRNA levels. While previous studies have demonstrated that miRNAs are indispensable in the nephron progenitor and ureteric bud lineage, little is understood about stromal miRNAs during kidney development. The renal stroma (marked by expression of FoxD1) gives rise to the renal interstitium, a subset of peritubular capillaries, and multiple supportive vascular cell types including pericytes and the glomerular mesangium. In this study, we generated FoxD1(GC);Dicer(fl/fl) transgenic mice that lack miRNA biogenesis in the FoxD1 lineage. Loss of Dicer activity resulted in multifaceted renal anomalies including perturbed nephrogenesis, expansion of nephron progenitors, decreased renin-expressing cells, fewer smooth muscle afferent arterioles, and progressive mesangial cell loss in mature glomeruli. Although the initial lineage specification of FoxD1(+) stroma was not perturbed, both the glomerular mesangium and renal interstitium exhibited ectopic apoptosis, which was associated with increased expression of Bcl2l11 (Bim) and p53 effector genes (Bax, Trp53inp1, Jun, Cdkn1a, Mmp2, and Arid3a). Using a combination of high-throughput miRNA profiling of the FoxD1(+)-derived cells and mRNA profiling of differentially expressed transcripts in FoxD1(GC);Dicer(fl/fl) kidneys, at least 72 miRNA:mRNA target interactions were identified to be suppressive of the apoptotic program. Together, the results support an indispensable role for stromal miRNAs in the regulation of apoptosis during kidney development

The acceptability of HPV vaccines and perceptions of vaccination against HPV among physicians and nurses in Hong Kong

201907 bcrcVersion of RecordPublishe