Higher dietary acid load is associated with the risk of hyperuricemia.

PURPOSE: Dietary acid load plays a key role in regulating serum uric acid levels. We hypothesized that dietary acid load indices would be positively associated with the odds of hyperuricemia. We aimed to test this hypothesis in a representative sample of Iranian adult population. METHODS: In this cross-sectional study, a total of 6145 participants aged 35-65 years were recruited from MASHAD cohort study. Dietary intakes were assessed using a 24-h dietary recall. Diet-based acid load was assessed as the potential renal acid load (PRAL), net endogenous acid production (NEAP), and dietary acid load (DAL). Hyperuricemia was defined as serum uric acid greater than the 75th percentile. Multivariable logistic regression models were applied to determine the association between diet-based acid load scores and hyperuricemia. RESULTS: The mean age of participants was 48.89 ± 8.09 years. Overall, 25.7% had hyperuricemia. According to the full-adjusted model, there was a significant association between higher tertile of PRAL, and DAL and hyperuricemia (Q3 PRAL; OR (95% CI): 1.23 (1.05-1.43), Q3 DAL; OR (95% CI): 1.22 (1.05-1.42)). Regarding NEAP, there was no significant association with hyperuricemia. We also found that dietary intake of total sugars, fiber, calcium, and magnesium was associated with the odds of hyperuricemia in our population. CONCLUSION: This study showed a significant positive association between two indicators of dietary acid load (PRAL, and DAL) and odds of hyperuricemia among Iranian adults.

Antimicrobial properties of green synthesized novel TiO2 nanoparticles using Iranian propolis extracts.

The oral antimicrobial and cytotoxic properties of green synthesized novel titanium dioxide nanoparticles (TiO2 NPs) using Iranian propolis extracts were investigated on oral bacteria and fibroblast cells. In this study, propolis was sampled, and alcoholic extracts were prepared. The TiO2 NPs were biosynthesized using propolis extracts. The synthesized TiO2 NPs were characterized by scanning electron microscope (SEM), X-ray diffraction analysis, energy-dispersive X-ray (EDX), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering, ultraviolet-visible (UV-Vis), transmission electron microscope, Brunauer-Emmett-Teller, and zeta potential. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide), minimal inhibitory concentration, minimum bactericidal concentration, minimum fungicidal concentration, biofilm formation, and degradation tests were studied to clarify the oral antimicrobial properties of green synthesized TiO2  NPs. According to the FTIR analysis, the propolis extract contained flavonoids and phenolic compounds in addition to TiO2 NPs. Additionally, UV-Vis revealed that intense bands had formed NPs. EDX spectra and SEM images revealed that the stabilizing agent was in perfect quasi-spherical shapes around 21 nm. An EDX spectrum was used to verify the presence of titanium and oxygen. There were no significant cytotoxicity effects. The antibacterial results showed that Pro1TiO2 (Khalkhal sample) had better effects than Pro2TiO2 (Gilan sample) and TiO2 NPs. The present study presents a new process for synthesizing TiO2 NPs from propolis extracts with less toxic effects and user-friendly, eco-friendly, and economical materials. Pro1TiO2 NPs may be considered the best candidate for clinical application.

A review of recent developments of metal-organic frameworks as combined biomedical platforms over the past decade.

Metal-organic frameworks (MOFs), also called porous coordination polymers, represent a class of crystalline porous materials made up of organic ligands and metal ions/metal clusters. Herein, an overview of the preparation of different metal-organic frameworks and the recent advances in MOF-based stimuli-responsive drug delivery systems (DDSs) with the drug release mechanisms including pH-, temperature-, ion-, magnetic-, pressure-, adenosine-triphosphate (ATP)-, H2S-, redox-, responsive, and photoresponsive MOF were rarely introduced. The combination therapy containing of two or more treatments can be enhanced treatment effectiveness through overcoming limitations of monotherapy. Photothermal therapy (PTT) combined with chemotherapy (CT), chemotherapy in combination with PTT or other combinations were explained to overcome drug resistance and side effects in normal cells as well as enhancing the therapeutic response. Integrated platforms containing of photothermal/drug-delivering functions with magnetic resonance imaging (MRI) properties exhibited great advantages in cancer therapy.

Development of venetoclax performance using its new derivatives on BCL-2 protein inhibition.

Cancer cells are resistant to apoptosis and this is one of the most obvious symptoms of cancer in humans. One of the most exciting strategies for treating cancer is to design regulators that increase cell death and stop cell growth. Members of the BCL-2 family of proteins play an important role in the regulation of apoptosis. In this study, an attempt was made to improve the performance of one of the anticancer drugs by designing new analogs of venetoclax (VNT). For this purpose, molecular docking studies were performed to determine the best binding state of VNT and its newly designed derivatives at the protein-binding site to estimate the binding energy. The best analog in terms of free energy was VNT-12 with the lowest energy (-12.15 kcal/mol). Finally, to investigate the inhibitory effect of the compounds on BCL-2 protein, molecular dynamics simulation was used, and by performing the relevant analyses during the simulation, it was observed that the newly designed ligand had better performance in inhibiting BCL-2 protein compared to VNT.

The current novel drug delivery system (natural and chemical composites) in dental infections for antibiotics resistance: a narrative review.

A mouth infection can also affect the teeth, the mouth tissues, and any other areas involved in the mouth. Biofilms formed by bacteria are the primary cause of mouth infections and other infectious diseases caused by bacteria. The most common dental problem is an infection or disease within the mouth. The term chronic infection is sometimes used to describe this type of problem. There is also the possibility that these discomforts may occur due to the presence of bacteria in plaque, which is responsible for causing inflammation throughout the body as a result of bacterial infection in the mouth. In many cases, antibiotics serve as a first-line treatment for mouth infections, especially those caused by bacteria, most commonly treated by antibiotics. It is common for antibiotics to be used orally, and they are absorbed into the body through their metabolism in the liver and kidneys. Antibiotic resistance, which is primarily caused by misuse and overuse of antibiotics, is also one of the most significant public health crises of the 21st century. With the help of new drug delivery systems, antibacterial resistance can be decreased in humans to maintain the effectiveness of antibiotics when they are used more frequently. By directly delivering antibiotics to damaged tissues and reducing undesirable side effects when administered systemically, antibiotic delivery systems enhance the efficiency of antibiotics in specific zones. Furthermore, several new delivery systems are being explored in an attempt to improve pharmacokinetics and pharmacodynamics, reduce bacterial resistance, and decrease dose times. As a result, antibiotics were delivered to tissues and biological fluids using an innovative delivery system. Research on some of the most prevalent dental diseases provides updates on antibiotic delivery systems that reduce antibiotic resistance. This review overviews oral infectious diseases, antibiotics effects, and the different delivery systems of these therapeutic approaches.

An outlook on coronavirus disease 2019 detection methods / 药物分析学报

Diagnostic testing plays a fundamental role in the mitigation and containment of coronavirus disease 2019(COVID-19),as it enables immediate quarantine of those who are infected and contagious and is essential for the epidemiological characterization of the virus and estimating the number of infected cases worldwide.Confirmation of viral infections,such as COVID-19,can be achieved through two general approaches:nucleic acid amplification tests(NAATs)or molecular tests,and serological or antibody-based tests.The genetic material of the pathogen is detected in NAAT,and in serological tests,host antibodies produced in response to the pathogen are identified.Other methods of diagnosing COVID-19 include radiological imaging of the lungs and in vitro detection of viral antigens.This review covers different approaches available to diagnosing COVID-19 by outlining their advantages and short-comings,as well as appropriate indications for more accurate testing.

A novel 3D nanofibre scaffold conserves the plasticity of glioblastoma stem cell invasion by regulating galectin-3 and integrin-ß1 expression.

Glioblastoma Multiforme (GBM) invasiveness renders complete surgical resection impossible and highly invasive Glioblastoma Initiating Cells (GICs) are responsible for tumour recurrence. Their dissemination occurs along pre-existing fibrillary brain structures comprising the aligned myelinated fibres of the corpus callosum (CC) and the laminin (LN)-rich basal lamina of blood vessels. The extracellular matrix (ECM) of these environments regulates GIC migration, but the underlying mechanisms remain largely unknown. In order to recapitulate the composition and the topographic properties of the cerebral ECM in the migration of GICs, we have set up a new aligned polyacrylonitrile (PAN)-derived nanofiber (NF) scaffold. This system is suitable for drug screening as well as discrimination of the migration potential of different glioblastoma stem cells. Functionalisation with LN increases the spatial anisotropy of migration and modulates its mode from collective to single cell migration. Mechanistically, equally similar to what has been observed for mesenchymal migration of GBM in vivo, is the upregulation of galectin-3 and integrin-ß1 in Gli4 cells migrating on our NF scaffold. Downregulation of Calpain-2 in GICs migrating in vivo along the CC and in vitro on LN-coated NF underlines a difference in the turnover of focal adhesion (FA) molecules between single-cell and collective types of migration.

Carbon quantum dots fluorescence quenching for potassium optode construction.

Photophysical phenomena associated with carbon nanoparticles in combination with biocompatibility and readily functionalizable properties have attracted significant interest for sensing and imaging applications. A potassium ion optode based on the fluorescence quenching of carbon quantum dots (CQDs) was constructed. The CQDs were synthesized using a microwave method, citric acid and 2,2'-(ethylene-dioxy)bis(ethylamine). A quantum yield of 7.1% was calculated for the synthesized CQDs. A linear dynamic range of about one-order of magnitude with a correlation coefficient of 0.99 was obtained. The optode was applied on real samples and a 0.60-1.60% error range was obtained relative to the ion-selective electrode.

Application of modified mesoporous boehmite (γ-AlOOH) with green synthesis carbon quantum dots for a fabrication biosensor to determine trace amounts of doxorubicin.

An important form of carbon nanoparticles that are used for a wide range of applications, are carbon dots (CDs). In this study, a very easy, in expensive and green process was described for the preparation of CDs by using hydrothermal treatment of Tragacanth Gum (TG). A rapid assay for the determination of trace amounts of an anticancer medication doxorubicin (DOX) was developed, based on the quenching of the CDs derived from their aggregation. Electrostatic interaction between CDs and DOX could lead to fluorescence quenching. The optimized biosensor showed a detection range from 1 to 400 ng mL-1 and a limit of detection of 0.4 ng mL-1 . In the following, the synthesized CDs modified the Boehmite (Boh) mesoporous surface based on hydrogen bonding. The Boh has been used as supports and ideal hosts in this method, in which the particle size distribution of CDs in the pores of Boh is limited and they have controlled pore sizes. Accordingly, the surface-to-volume ratio and the presence of high-volume pores increased the longevity and sustainability of CDs; also prevented the aggregation of the CDs and improved their photo stability. The advantages of Boh are large pore volume, high surface area, and narrow size distribution. Variable factors influencing optical sensor response in DOX measurement were evaluated and optimized. In optimal conditions, the linear range was calculated from 1 to 500 ngmL-1 and the detection limit was 0.2 ng mL-1 . The sensors were used for measuring DOX in human blood plasma.

Phostine PST3.1a Targets MGAT5 and Inhibits Glioblastoma-Initiating Cell Invasiveness and Proliferation.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor and accounts for a significant proportion of all primary brain tumors. Median survival after treatment is around 15 months. Remodeling of N-glycans by the N-acetylglucosamine glycosyltransferase (MGAT5) regulates tumoral development. Here, perturbation of MGAT5 enzymatic activity by the small-molecule inhibitor 3-hydroxy-4,5-bis-benzyloxy-6-benzyloxymethyl-2-phenyl2-oxo-2λ5-[1,2]oxaphosphinane (PST3.1a) restrains GBM growth. In cell-based assays, it is demonstrated that PST3.1a alters the ß1,6-GlcNAc N-glycans of GBM-initiating cells (GIC) by inhibiting MGAT5 enzymatic activity, resulting in the inhibition of TGFßR and FAK signaling associated with doublecortin (DCX) upregulation and increase oligodendrocyte lineage transcription factor 2 (OLIG2) expression. PST3.1a thus affects microtubule and microfilament integrity of GBM stem cells, leading to the inhibition of GIC proliferation, migration, invasiveness, and clonogenic capacities. Orthotopic graft models of GIC revealed that PST3.1a treatment leads to a drastic reduction of invasive and proliferative capacity and to an increase in overall survival relative to standard temozolomide therapy. Finally, bioinformatics analyses exposed that PST3.1a cytotoxic activity is positively correlated with the expression of genes of the epithelial-mesenchymal transition (EMT), while the expression of mitochondrial genes correlated negatively with cell sensitivity to the compound. These data demonstrate the relevance of targeting MGAT5, with a novel anti-invasive chemotherapy, to limit glioblastoma stem cell invasion. Mol Cancer Res; 15(10); 1376-87. ©2017 AACR.

Effect of Accelerated Aging on Color Change of Direct and Indirect Fiber-Reinforced Composite Restorations.

OBJECTIVES: The aim of this study was to assess the effect of artificial accelerated aging (AAA) on color change of direct and indirect fiber-reinforced composite (FRC) restorations. MATERIALS AND METHODS: Direct (Z250) and indirect (Gradia) composite resins were reinforced with glass (GF) and polyethylene fibers (PF) based on the manufacturers' instructions. Forty samples were fabricated and divided into eight groups (n=5). Four groups served as experimental groups and the remaining four served as controls. Color change (ΔE) and color parameters (ΔL*, Δa*, Δb*) were read at baseline and after AAA based on the CIELAB system. Three-way ANOVA and Tukey's test were used for statistical analysis. RESULTS: Significant differences were found in ΔE, ΔL*, Δa* and Δb* among the groups after AAA (P<0.05). Most of the studied samples demonstrated an increase in lightness and a red-yellow shift after AAA. CONCLUSIONS: The obtained ΔE values were unacceptable after AAA (ΔE≥ 3.3). All indirect samples showed a green-blue shift with a reduction in lightness except for Gradia/PF+ NuliteF.

A model based on equations of kinetics to study nitrogen dioxide behavior within a plasma discharge reactor.

In this work, a zero-dimensional kinetics model is used to study the temporal behavior of different species such as charged particles, radicals and excited states inside a Dielectric Barrier Discharge plasma reactor. It is shown that, the reactor significantly reduces the concentration of nitrogen monoxide as an environmental pollutant. After a drastic increase, a decrease in the concentration of the NO2 molecules inside the reactor is seen. Nitrogen monoxide molecules with a very low concentration are produced inside the reactor and its quick conversion to other products is proved. The obtained results are compared with the existing experimental and simulation findings, whenever possible.

Comparison of three methods in improving bag mask ventilation.

INTRODUCTION: Increasedlife expectancy in populations has brought along specific new scenarios in the fields of medicine for the elderly; prevalence of physical complications such as edentulism and patients with dentures is growing. Management of anesthesia and ventilation in this group of patients has turned into a great challenge. Some researchers suggest dentures to be left in place during bag-mask ventilation; yet, no unanimous agreement exists in this regard. METHODS: In a single blind randomized clinical trial, we studied 300 patients with ASA class I, II (American Society of Anesthesiologists), Mallampati class (I, II) and aged over 55 years in three groups. After induction of anesthesia, in group G dentures were removed and in each buccal space an eight-layer 10 × 10 cm gauze and an oral airway were placed. In group D, the dentures and an oral airway were left in place. In group C (control), after removing dentures just an appropriate oral airway was placed. Then, each three group underwent bag-mask ventilation. Success of bag-mask ventilation (BMV) was considered as increase in end-tidal carbon dioxide to more than 20 mmHg and back to baseline with fresh gas flow of 3 L/min and adjustable pressure limiting valve pressure of 20 cm H2O. Success rates were evaluated between groups. RESULTS: Effective BMV was possible in 91 (91%), 64 (64%) and 41 (41%) patients in groups G, D and C respectively. The differences were statistically significant. Successful BMV rate was significantly higher in female patients in group G compared to group C; 43/44 versus 25/46 individuals, P = 0.0001, odds ratio = 0.03, 95% confidence interval (0.00, 0.22). CONCLUSIONS: Leaving dentures in place in edentulous patients after inducing anesthesia improves bag-mask ventilation. However, placing folded compressed gauze in buccal space leads to more significant improvement in BMV compared to leaving dentures in place.

The use of silica gel modified with allyl 6-methyl-4-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate for selective separation and preconcentration of lead in environmental samples.

The aim of the present work is the assessment of a new sorbent, prepared using silica gel coated with a pyrimidine derivative (allyl 6-methyl-4-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate), for extraction and preconcentration trace amount of lead from different samples prior to determination by flame atomic absorption spectrometry. Common coexisting ions did not interfere with the separation and determination of lead at pH 6, so that lead ion completely adsorbed on the column. The limit of detection based on three times the standard deviation of the blank was found to be 0.53 ng mL(-1) in original solution. Obtained sorption capacity for 1 g sorbent was 5.0 mg Pb. The linearity was maintained in the concentration range of 0.1-30.0 ng mL(-1) for the concentrated solution. Eight replicate determinations of 2.0 µg mL(-1) of lead in the final solution gave relative standard deviation of ±2.6 %. The proposed method was successfully applied to the determination trace amounts of lead in the environmental samples such as carrot, rice, zardchoobe, and real water samples.

Human neural progenitor cell engraftment increases neurogenesis and microglial recruitment in the brain of rats with stroke.

MAIN OBJECTIVES: Stem cell transplantation is to date one of the most promising therapies for chronic ischemic stroke. The human conditionally immortalised neural stem cell line, CTX0E03, has demonstrable efficacy in a rodent model of stroke and is currently in clinical trials. Nonetheless, the mechanisms by which it promotes brain repair are not fully characterised. This study investigated the cellular events occurring after CTX0E03 transplantation in the brains of rats that underwent ischemic stroke. METHODS: We focused on the endogenous proliferative activity of the host brain in response to cell transplantation and determined the identity of the proliferating cells using markers for young neurons (doublecortin, Dcx) and microglia (CD11b). So as to determine the chronology of events occurring post-transplantation, we analysed the engrafted brains one week and four weeks post-transplantation. RESULTS: We observed a significantly greater endogenous proliferation in the striatum of ischemic brains receiving a CTX0E03 graft compared to vehicle-treated ischemic brains. A significant proportion of these proliferative cells were found to be Dcx+ striatal neuroblasts. Further, we describe an enhanced immune response after CTX0E03 engraftment, as shown by a significant increase of proliferating CD11b+ microglial cells. CONCLUSIONS: Our study demonstrates that few Dcx+ neuroblasts are proliferative in normal conditions, and that this population of proliferative neuroblasts is increased in response to stroke. We further show that CTX0E03 transplantation after stroke leads to the maintenance of this proliferative activity. Interestingly, the preservation of neuronal proliferative activity upon CTX0E03 transplantation is preceded and accompanied by a high rate of proliferating microglia. Our study suggests that microglia might mediate in part the effect of CTX0E03 transplantation on neuronal proliferation in ischemic stroke conditions.

Thyroid hormone signaling acts as a neurogenic switch by repressing Sox2 in the adult neural stem cell niche.

The subventricular zone (SVZ) neural stem cell niche contains mixed populations of stem cells, transit-amplifying cells, and migrating neuroblasts. Deciphering how endogenous signals, such as hormones, affect the balance between these cell types is essential for understanding the physiology of niche plasticity and homeostasis. We show that Thyroid Hormone (T(3)) and its receptor, TRα1, are directly involved in maintaining this balance. TRα1 is expressed in amplifying and migrating cells. In vivo gain- and loss-of-function experiments demonstrate first, that T(3)/TRα1 directly repress Sox2 expression, and second, that TRα1 overexpression in the niche favors the appearance of DCX+ migrating neuroblasts. Lack of TRα increases numbers of SOX2+ cells in the SVZ. Hypothyroidism increases proportions of cells in interphase. Thus, in the adult SVZ, T(3)/TRα1 together favor neural stem cell commitment and progression toward a migrating neuroblast phenotype; this transition correlates with T(3)/TRα1-dependent transcriptional repression of Sox2.

In vivo siRNA delivery to the mouse hypothalamus shows a role of the co-chaperone XAP2 in regulating TRH transcription.

RNA interference mediated by small interfering RNAs (siRNAs) is a powerful tool for evaluating gene function in vivo. In particular it should be able to provide tissue-specific and developmental stage-specific knockdown of target genes in physiological contexts. However, there are few demonstrations of its use on neuronal specific genes in vivo. We recently developed a cationic lipid-based approach to study gene function in a neuronal context. In particular, we applied it to study how the novel partner for TRbeta1, hepatitis virus B X-associated protein 2 (XAP2), a protein first identified as a co-chaperone protein, affects T3-transcriptional repression of the hypothalamic gene, TRH. The cationic lipid-based technique used, JetSI/DOPE, was previously shown to efficiently knockdown reporter gene mRNA in vivo. Using JetSI/DOPE to vectorize siRNA against XAP2 mRNA, we show that XAP2 is needed specifically for TRbeta1-mediated (but not TRbeta2) activation of hypothalamic TRH transcription. Thus, this cationic lipid-based siRNA strategy can effectively be used to reveal fine, tissue-specific and isoform-specific effects on neuronal gene transcription in vivo.

Cell division and apoptosis in the adult neural stem cell niche are differentially affected in transthyretin null mice.

Thyroid hormones (THs) are fundamental in regulation of growth and development, particularly of the brain. THs are required for full proliferative activity of neural stem cells in the subventricular zone (SVZ) of adult mouse brains, and also affect the normal fate of progenitor cells: apoptosis. Transthyretin (TTR) is a TH distributor protein in the blood and cerebrospinal fluid. TTR secretion by the choroid plexus is involved in transport of THs from blood into cerebrospinal fluid. We investigated the regulation of neural stem cell cycle in the SVZ of adult TTR null mice. Markers for neural stem cell mitosis that are reduced during hypothyroidism, did not differ between genotypes. However, in TTR null mice the level of apoptosis, the fate of most progenitor cells, was as low as that in brains of hypothyroid wildtype mice. Thus, lack of TTR results in reduced availability of TH to progenitor cells in the SVZ. We show that proliferation and apoptosis in the SVZ neural stem cell niche are differentially affected by the lack of TTR synthesis.

A hybrid CMV-H1 construct improves efficiency of PEI-delivered shRNA in the mouse brain.

RNA-interference-driven loss of function in specific tissues in vivo should permit analysis of gene function in temporally and spatially defined contexts. However, delivery of efficient short hairpin RNA (shRNA) to target tissues in vivo remains problematic. Here, we demonstrate that efficiency of polyethylenimine (PEI)-delivered shRNA depends on the regulatory sequences used, both in vivo and in vitro. When tested in vivo, silencing of a luciferase target gene by shRNA produced from a hybrid construct composed of the CMV enhancer/promoter placed immediately upstream of an H1 promoter (50%) exceeds that obtained with the H1 promoter alone (20%). In contrast, in NIH 3T3 cells, the H1 promoter was more efficient than the hybrid construct (75 versus 60% inhibition of target gene expression, respectively). To test CMV-H1 shRNA efficiency against an endogenous gene in vivo, we used shRNA against thyroid hormone receptor alpha1 (TRalpha1). When vectorized in the mouse brain, the hybrid construct strongly derepressed CyclinD1-luciferase reporter gene expression, CyclinD1 being a negatively regulated thyroid hormone target gene. We conclude that promoter choice affects shRNA efficiency distinctly in different in vitro and in vivo situations and that a hybrid CMV-H1 construct is optimal for shRNA delivery in the mouse brain.

In vivo siRNA delivery to the mouse hypothalamus confirms distinct roles of TR beta isoforms in regulating TRH transcription.

RNA interference mediated by small interfering RNAs (siRNAs) is a powerful tool for evaluating gene function in vivo. In particular it should be able to provide tissue-specific and developmental stage-specific knock-down of target genes in physiological contexts. However, demonstrations of its use on neuronal specific genes in vivo are lacking. We examined whether a recently developed cationic lipid based approach was applicable to study the differential effects of the two beta thyroid hormone receptor (TR) isoforms, TRbeta1 and TRbeta2, on T3-transcriptional repression of the hypothalamic gene, TRH. The cationic lipid based technique used, JetSI/DOPE, was previously shown to efficiently knock-down reporter gene mRNA in vivo. Here we now show that its use to vectorise siRNA against TRbeta1 and TRbeta2 mRNA abrogates T3-mediated repression of hypothalamic TRH transcription. In particular, when using siRNA against either TRbeta1 or TRbeta2 differential effects are revealed. siRNA directed against TRbeta1 blocks both T3 independent activation and T3 dependent modulation of TRH transcription. In contrast, siRNA directed against TRbeta2 abrogates only T3 repression of transcription. These results corroborate our previous findings obtained in mutant TRbeta(-/-) mice, showing that the TRbeta1 and TRbeta2 isoforms have differential effects on T3-TRH transcription. The data thus show that the cationic lipid-based siRNA strategy can effectively be used to reveal fine, tissue specific and isoform specific effects on neuronal gene transcription in vivo.