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Overview of psoriasis.

Psoriasis is a chronic disease that affects the skin and joints. Clinical hallmarks comprise erythematous plaques covered by silvery scaling and a chronic recurrent course. Histologically, psoriasis is characterized by the hyperproliferation of the epidermis, elongated and prominent blood vessels and a thick perivascular lymphocytic infiltrate. Psoriasis is now considered an auto-immune disease. Although many different therapies are available, there is clearly a need for new treatments. Our improvement of understanding of the pathogenesis of psoriasis together with the possibility to develop bioactive proteins ("biologicals") targeted at specific steps in the pathogenesis of psoriasis, have opened a new field of promising future treatments. In the development and assessment of new therapeutical modalities for psoriasis, a clear definition of a patient's psoriasis severity is essential. The impact of a given therapy can only then be evaluated, based on the changes in the severity score during and after application of the treatment.

Humans↗

Interleukin-12 gene expression in human monocyte-derived macrophages stimulated with Mycobacterium bovis BCG: cytokine regulation and effect of NK cells.

Macrophage-derived interleukin-12 (IL-12) is essential for the activation of a protective immune response against intracellular pathogens. In this study, we examined the regulation of IL-12 mRNA expression by monocyte-derived macrophages (MDM) in response to Mycobacterium bovis BCG stimulation. A reverse transcription-PCR assay detected p40 mRNA of IL-12 at 3 h and showed a peak at 6 to 12 h with a subsequent decline. Semiquantitation of mRNA levels by competitive PCR revealed that pretreatment with gamma interferon (IFN-gamma) amplified the expression approximately 100-fold, while pretreatment with tumor necrosis factor alpha (TNF-alpha) or granulocyte-macrophage colony-stimulating factor augmented this expression about 10-fold. In contrast, pretreatment with IL-10 and IL-4 inhibited IL-12 mRNA expression. These results were further confirmed by measuring the p70 bioactive protein level in each conditioned medium by an enzyme-linked immunosorbent assay. Since IL-12 mRNA expression was weak without cytokine pretreatment and IFN-gamma strongly augmented production, we speculated that IFN-gamma might have a role in BCG stimulation of IL-12 mRNA expression. Unexpectedly, the addition of three different kinds of anti-IFN-gamma antibodies and anti-IFN-gamma receptor antibody and the coaddition of anti-TNF-alpha antibody with anti-IFN-gamma receptor antibody all failed to inhibit IL-12 mRNA expression. However, the MiniMACS method used to remove NK cells from a mononuclear cell suspension inhibited the expression of p40 mRNA but not the expression of mRNA of TNF-alpha or IL-1beta. We concluded that the coexistence of NK cells was essential for the induction of IL-12 in MDM stimulated with BCG rather than through the secretion of IFN-gamma.

Cytokines↗

Basolateral sorting of furin in MDCK cells requires a phenylalanine-isoleucine motif together with an acidic amino acid cluster.

Furin is a subtilisin-related endoprotease which processes a wide range of bioactive proteins. Furin is concentrated in the trans-Golgi network (TGN), where proteolytic activation of many precursor proteins takes place. A significant fraction of furin, however, cycles among the TGN, the plasma membrane, and endosomes, indicating that the accumulation in the TGN reflects a dynamic localization process. The cytosolic domain of furin is necessary and sufficient for TGN localization, and two signals are responsible for retrieval of furin to the TGN. A tyrosine-based (YKGL) motif mediates internalization of furin from the cell surface into endosomes. An acidic cluster that is part of two casein kinase II phosphorylation sites (SDSEEDE) is then responsible for retrieval of furin from endosomes to the TGN. In addition, the acidic EEDE sequence also mediates endocytic activity. Here, we analyzed the sorting of furin in polarized epithelial cells. We show that furin is delivered to the basolateral surface of MDCK cells, from where a significant fraction of the protein can return to the TGN. A phenylalanine-isoleucine motif together with the acidic EEDE cluster is required for basolateral sorting and constitutes a novel signal regulating intracellular traffic of furin.

Amino Acid Sequence↗

Chronic recording of regenerating VIIIth nerve axons with a sieve electrode.

A micromachined silicon substrate sieve electrode was implanted within transected toadfish (Opsanus tau) otolith nerves. High fidelity, single unit neural activity was recorded from seven alert and unrestrained fish 30 to 60 days after implantation. Fibrous coatings of genetically engineered bioactive protein polymers and nerve guide tubes increased the number of axons regenerating through the electrode pores when compared with controls. Sieve electrodes have potential as permanent interfaces to the nervous system and to bridge missing connections between severed or damaged nerves and muscles. Recorded impulses might also be amplified and used to control prosthetic devices.

Animals↗

Agonist and antagonist of retinoic acid receptors cause similar changes in gene expression and induce senescence-like growth arrest in MCF-7 breast carcinoma cells.

Biological effects of retinoids are mediated via retinoic acid (RA) receptors (RAR) and retinoid X receptors (RXR). The best-characterized mechanism of retinoid action is stimulation of transcription from promoters containing RA response elements (RARE). Retinoids induce senescence-like growth arrest in MCF-7 breast carcinoma cells; this effect is associated with the induction of several growth-inhibitory genes. We have now found that these genes are induced by RAR-specific but not by RXR-specific ligands. Genome-scale microarray analysis of gene expression was used to compare the effects of two pan-RAR ligands, one of which is a strong agonist of RARE-dependent transcription, whereas the other induces such transcription only weakly and antagonizes the inducing effect of RAR agonists. Both RAR ligands, however, produced very similar effects on gene expression in MCF-7 cells, suggesting that RARE-dependent transcription is only a minor component of retinoid-induced changes in gene expression. The effects of RAR ligands on gene expression parallel changes associated with damage-induced senescence, and both ligands induced G(1) arrest and the senescent phenotype in MCF-7 cells. The RAR ligands up-regulated many tumor-suppressive genes and down-regulated multiple genes with oncogenic activities. Genes that are strongly induced by RAR ligands encode secreted bioactive proteins, including several tumor-suppressing factors. In agreement with these observations, retinoid-treated MCF-7 cells inhibited the growth of retinoid-insensitive MDA-MB-231 breast carcinoma cells in coculture. These results indicate that RARE-independent transcriptional effects of RAR ligands lead to senescence-like growth arrest and paracrine growth-inhibitory activity in MCF-7 breast carcinoma cells.

Actins↗

Positive correlation between estradiol and vascular endothelial growth factor but not fibroblast growth factor-2 in normal human breast tissue in vivo.

PURPOSE: Angiogenesis is crucial in tumor development and progression. Ovarian hormones regulate angiogenesis in the reproductive tract but very little is known about its regulation in the normal breast. Sex steroids play an important role in breast cancer development by poorly understood mechanisms. Vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) are potent stimulators of angiogenesis. Both VEGF and FGF-2 function in autocrine/paracrine pathways and there is a major contribution of bioactive proteins by a posttranslational activation of sequestered molecules in the extracellular space. A direct measurement of these molecules in the extracellular compartment is, therefore, needed. EXPERIMENTAL DESIGN: In this study, microdialysis was used to measure extracellular VEGF and FGF-2 in normal human breast tissue in situ in 11 premenopausal and 5 postmenopausal women. RESULTS: Significantly higher level of VEGF in breast tissue of premenopausal women was found. Plasma as well as local estradiol and breast tissue VEGF exhibited significant correlations, whereas progesterone had no correlation with breast VEGF. FGF-2 did not correlate with either estradiol or progesterone. CONCLUSION: The result suggests that estradiol is a more potent regulator of free VEGF levels than progesterone in the normal breast. The control of free FGF-2 seems to be independent of sex steroids in the breast. Estrogen induction of free extracellular VEGF may be one mechanism involved in sex steroid-dependent breast carcinogenesis.

Adult↗

Synthetic vascular prosthesis impregnated with mesenchymal stem cells overexpressing endothelial nitric oxide synthase.

BACKGROUND: Endothelial dysfunction is known to exaggerate coronary artery disease, sometimes leading to irreversible myocardial damage. In such cases, repetitive coronary revascularization including coronary artery bypass grafting is needed, which may cause a shortage of graft conduits. On the other hand, endothelial nitric oxide synthase (eNOS) is an attractive target of cardiovascular gene therapy. The vascular prostheses, of which the inner surfaces are covered with mesenchymal stem cells (MSCs) overexpressing eNOS, are expected to offer feasible effects of NO and angiogenic effects of MSCs on the native coronary arterial beds, as well as improvement of self-patency. Herein, we attempted to develop small caliber vascular prostheses generating the bioactive proteins. Also, we attempted to transduce eNOS cDNA into MSCs. METHODS AND RESULTS: The MSCs were isolated from rat bone marrow and transduced with each adenovirus harboring rat eNOS cDNA and beta-galactosidase (beta-gal) (eNOS/MSCs and beta-gal/MSCs). The beta-gal/MSCs were impregnated into vascular prostheses, then the expressions of beta-gal on the inner surfaces of them were evaluated by 5-bromo-4-chloro-3-indolyl beta-D-galactoside staining. The NOS activity of eNOS/MSCs was assayed by monitoring the conversion of 3H-arginine to 3H-citrulline. The inner surfaces of the vascular prostheses were covered with MSCs expressing beta-gal. The amount of the 3H-citrulline increased, and eNOS/MSCs were determined to generate enzymatic activity of eNOS. This activity was completely inhibited by N(G)-nitro-L-arginine methyl ester. CONCLUSIONS: The inner surface of expanded polytetrafluoroethylene vascular prostheses seeded with lacZ gene-transduced MSCs exhibited recombinant proteins. Development of eNOS/MSC-seeded vascular prostheses would promise much longer graft patency and vasculoprotective effects.

Adenoviridae↗

Single subcutaneous administration of chorionic gonadotropin to rats induces a rapid and transient increase in testicular expression of pro-inflammatory cytokines.

hCG has been reported to cause an inflammation-like effect in the testis, although the background and consequences of this phenomenon remain to be understood. This investigation reveals that a single injection of hCG (100 U) induces a transient surge in pro-inflammatory cytokine expression in the adult rat testis. Reverse transcriptase PCR analysis demonstrated onset of testicular expression of IL-1beta and IL-6 mRNA and increases in the levels of mRNA encoding the constitutively expressed cytokines IL-1alpha, IL-1 receptor antagonist, and tumor necrosis factor-alpha 4 h after hCG injection and a maximal response after 8-12 h. These increases were accompanied by a transient increase in testicular IL-1 bioactive protein. Twenty-four hours after administration of hCG, the levels of all cytokine mRNA had decreased, although most were still elevated above control. Immunohistochemical staining revealed that the IL-1beta protein was undetectable in normal testes but was seen to be localized to interstitial macrophages but not Leydig cells after hCG treatment. Testes devoid of Leydig cells after pretreatment with ethane dimethane sulphonate exhibited normal staining for interstitial macrophages but failed to respond to hCG with increases in IL-1beta mRNA and protein expression. We conclude that hCG induces testicular inflammation via local activation by Leydig cells of the production of pro-inflammatory cytokines by resident macrophages. It remains to be investigated whether the high-dose hCG regimens used for treatment of boys with cryptorchidism could induce similar increases of pro-inflammatory cytokines in the human testis and if such treatments could adversely affect future testicular function.

Animals↗

Isolation of a nontransforming bone-derived growth factor from medium conditioned by fetal rat calvariae.

Previous studies have indicated that medium conditioned by 21-day-old fetal rat calvariae contains bioactive proteins termed bone-derived growth factors (BDGF) I and II. In the present studies we have purified the nontransforming BDGF II by dialysis, molecular sieving, three reverse phase HPLC steps, and preparative polyacrylamide gel electrophoresis. The second HPLC step (HPLC-2) yielded a recovery of 22% of the biological activity and achieved a 1500-fold purification, resulting in 20 micrograms protein/liter calvarial conditioned medium; the third HPLC step was of limited value in the purification of BDGF. Analytical PAGE revealed that the majority of the protein in HPLC-2-purified BDGF migrated with a relative molecular mass (Mr) of 11,000 and two additional proteins were seen at a Mr of 22,000-23,000. On preparative PAGE, the material migrating with a Mr of 11,000 stimulated parameters of bone and fibroblast growth in vitro, whereas the material with a Mr of 22,000-23,000 had less biological activity. Isoelectric focusing revealed that BDGF had an isoelectric point (pI) of 5. BDGF enhanced the incorporation of [3H]thymidine into DNA in fibroblast and calvarial cultures and of [3H]proline into collagen and noncollagen protein in calvariae. In conclusion, fetal rat calvariae secrete a BDGF with an estimated Mr of 11,000 and a pI of 5; this material stimulates bone and fibroblast growth in vitro.

Animals↗

International collaborative study by in vitro bioassays of the first international standard for porcine inhibin.

A lyophilized preparation of inhibin from porcine ovarian follicular fluid, ampoule code 86/690, was made internationally available as a research standard for in vitro bioassays in 1987. A study involving ten participants in eight countries assessed the stability and suitability of this research standard to serve as an international standard. Each of the participants used in vitro assays, the majority of which depended upon the inhibition of release of follicle-stimulating hormone from dispersed rat anterior pituitary cells. The research standard 86/690 was compared with coded ampoules of 86/690 stored under conditions of accelerated thermal degradation and with inhibins from different species. Intra- and interlaboratory variation for estimates of potency of a coded duplicate ampoule of the research standard provided the basis for comparisons of non-identical inhibins, but the fourfold variability of potency estimates for identical ampoules was such that no conclusions about the differences seen for non-identical inhibins could be made. Predictions of stability from consensus estimates of potency of ampoules that have undergone accelerated thermal degradation indicated that the research standard had satisfactory stability. On the basis of this study, the research standard 86/690 was deemed sufficiently stable and suitable to serve as a standard for in vitro bioassays and was established by the World Health Organization Expert Committee on Biological Standardization as the First International Standard for Porcine Inhibin. The possible presence, in biological extracts (standard or sample), of other bioactive proteins, such as activin and follistatin, complicates the quantitative interpretation of bioassay data. A standard of highly purified human inhibin is now required as a standard for immunoassays used for clinical research purposes; sufficient quantities of recombinant human inhibins have recently been donated for ampouling and evaluation by bio- and immunoassay in the subsequent phase of the standardization of inhibins.

Animals↗

Nerve growth factor (NGF) and its receptor in rat olfactory epithelium.

Nerve Growth Factor (NGF) is a bioactive protein that plays an important role in the genesis, differentiation, growth, maintenance and aging of the central and peripheral nervous systems. The purpose of this study was to explore the significance of NGF in the turnover, regeneration and maintenance of the olfactory epithelium. We tried to detect NGF and NGF-receptor in the olfactory epithelium of young and mature rats with an immunohistochemical technique. Immunoreactivity to NGF and NGF-receptor was detected in all specimens of olfactory epithelium. Immunoreactivity to NGF was positive in the olfactory nerve cells, especially in the cytoplasm and dendrites, in the basal cell layer, and on fibers piercing the olfactory epithelium. Immunoreactivity to NGF-receptor was positive in the basal cell layer and on fibers piercing the olfactory epithelium. These results suggest that NGF plays a role in the maintenance of olfactory nerve cells, and in the differentiation from the basal cell to the mature olfactory nerve cell, in both the young and the mature rat. In addition, the differences in the density of immunoreactive cells between different parts of the olfactory epithelium support the concept of an active and a quiescent zone in olfactory epithelium turnover.

Aging↗

Comparative analysis of cytokines released by bone marrow stromal cells from normal donors and B-cell chronic lymphocytic leukemic patients.

We studied the production of cytokines (G-CSF, GM-CSF, IL-6, LIF and IL-10) by bone marrow stromal cells of five untreated patients with B-CLL, in Rai stage 0, I and II, and of 8 healthy subjects. The production of G-CSF, GM-CSF, LIF and IL-10 did not differ significantly between controls and B-CLL patients. However, the ability of stromal cells to release IL-6 in response to LPS was decreased in all patients: 36 +/- 5 ng/ml versus 123 +/- 47 ng/ml for normal controls (p < 0.004). Moreover, a soluble activity that inhibited hematopoietic colony formation was detected in B-CLL stromal cell conditioned media. Some potential inhibitors were envisaged and the results indicated an increased production of TGF-beta by B-CLL stromal cells compared to normal stromal cells (respectively 53 +/- 10 versus 15 +/- 4 ng/ml, p < 0.03). The reduced capacity of B-CLL stromal cells to produce IL-6 was associated with this excessive release of TGF-beta; indeed, addition of anti-TGF-beta neutralizing antibody to B-CLL stromal cells, before LPS stimulation, totally normalized the production of IL-6. TGF-beta and IL-6 were also measured in serum samples from normal subjects and B-CLL patients. No significant difference was seen in the production of total TGF-beta (bioactive and latent forms) between normal and B-CLL sera but the mean level of bioactive protein in B-CLL sera was increased in comparison with normal sera (1.74 +/- 0.44 versus 0.67 +/- 0.2 ng/ml, p < 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Transgenic dairy cattle: genetic engineering on a large scale.

Amid the explosion of fundamental knowledge generated from transgenic animal models, a small group of scientists has been producing transgenic livestock with goals of improving animal production efficiency and generating new products. The ability to modify mammary-specific genes provides an opportunity to pursue several distinctly different avenues of research. The objective of the emerging gene "pharming" industry is to produce pharmaceuticals for treating human diseases. It is argued that mammary glands are an ideal site for producing complex bioactive proteins that can be cost effectively harvested and purified. Consequently, during the past decade, approximately a dozen companies have been created to capture the US market for pharmaceuticals produced from transgenic bioreactors estimated at $3 billion annually. Several products produced in this way are now in human clinical trials. Another research direction, which has been widely discussed but has received less attention in the laboratory, is genetic engineering of the bovine mammary gland to alter the composition of milk destined for human consumption. Proposals include increasing or altering endogenous proteins, decreasing fat, and altering milk composition to resemble that of human milk. Initial studies using transgenic mice to investigate the feasibility of enhancing manufacturing properties of milk have been encouraging. The potential profitability of gene "pharming" seems clear, as do the benefits of transgenic cows producing milk that has been optimized for food products. To take full advantage of enhanced milk, it may be desirable to restructure the method by which dairy producers are compensated. However, the cost of producing functional transgenic cattle will remain a severe limitation to realizing the potential of transgenic cattle until inefficiencies of transgenic technology are overcome. These inefficiencies include low rates of gene integration, poor embryo survival, and unpredictable transgene behavior.

Animals↗

Evaluation of refolding conditions for a recombinant human interleukin-3 variant (daniplestim).

The refolding of daniplestim, a human interleukin-3 variant (SC-55494) from Escherichia coli inclusion bodies, was optimized using a reversed-phase HPLC method developed to permit quantification of the reduced and oxidized forms of daniplestim. The presence of cysteine or dithiothreitol accelerated refolding of daniplestim from E. coli inclusion body slurries dissolved in urea or guanidine solutions and was complete in 4-6 h. Regardless of the dissolution and refolding protocol used to renature daniplestim, equivalently bioactive protein was produced. Under refolding conditions, no covalent modification of daniplestim by cysteine or cyanate was observed. The folding process was characterized further by following the unfolding of purified daniplestim by far-UV CD and fluorescence spectroscopies under both oxidizing and reducing conditions at pH values between 7 and 11. Formation of the single disulphide bond had a large stabilizing effect on daniplestim structure ( approximately 4-5 kCal at pH 9.5). This thermodynamic stabilization drove the refolding process towards the native form, even under conditions where the reduced protein was largely unfolded. From these data, scaleable refolding conditions for daniplestim were established.

Cysteine↗

Vector-host interactions in disease transmission.

Tick-borne spirochetes include borreliae that cause Lyme disease and relapsing fever in humans. They survive in a triangle of parasitic interactions between the spirochete and its vertebrate host, the spirochete and its tick vector, and the host and the tick. Until recently, the significance of vector-host interactions in the transmission of arthropod-borne disease agents has been overlooked. However, there is now compelling evidence that the pharmacological activity of tick saliva can have a profound effect on pathogen transmission both from infected tick to uninfected host, and from infected host to uninfected tick. The salivary glands of ticks provide a pharmacopoeia of anti-inflammatory, anti-haemostatic and anti-immune molecules. These include bioactive proteins that control histamine, bind immunoglobulins, and inhibit the alternative complement cascade. The effect of these molecules is to provide a privileged site at the tick-host interface in which borreliae and other tick-borne pathogens are sheltered from the normal innate and acquired host immune mechanisms that combat infections. Understanding the key events at the tick vector-host interface, that promote spirochete infection and transmission, will provide a better understanding of the epidemiology and ecology of these important human pathogens.

Animals↗

Targeting of interferon to choroidal neovascularization by use of dextran and metal coordination.

PURPOSE: Bioactive proteins such as interferon (IFN) have been reported to be combined with water-soluble polymers, such as dextran, through metal coordination, without need for complicated procedures. In the current study, the targeting and inhibitory effects of IFN combined with dextran on experimental choroidal neovascularization (CNV) were studied in vivo. METHODS: Interferon (IFN)beta was conjugated to dextran, which has metal-chelating, diethylenetriaminepentaacetic acid (DTPA) residues. Based on metal coordination, conjugation of IFNbeta with DTPA-dextran resulted from simply mixing both substances in an aqueous solution containing Zn(2+). The effects of IFNbeta on the proliferation of human umbilical vein endothelial cells (HUVECs) and bovine retinal pigment epithelial cells (BRPECs) were evaluated. To evaluate the activity loss of IFNbeta by conjugation, the effect of the conjugate on HUVECs was compared with that of free IFNbeta. Experimental CNV was induced by subretinal injection of gelatin microspheres containing basic fibroblast growth factor in rabbits. The rabbits with CNV were intravenously treated twice weekly with 7.5 million international units (MIU)/kg per day free IFNbeta (for 4 weeks), with IFNbeta-DTPA-dextran conjugate containing 7.5 (for 2 weeks) or 0.75 (for 4 weeks) MIU/kg per day IFNbeta, or with saline. The effects of these substances were evaluated by fluorescein angiography and histology. To observe the accumulation of conjugate, the doses of IFNbeta in CNV tissues were measured by enzyme-linked immunosorbent assay. RESULTS: IFNbeta inhibited the growth of HUVECs and enhanced the proliferation of BRPECs. The conjugate seemed to preserve approximately 44% of IFNbeta activity. Although both doses of IFNbeta-DTPA-dextran inhibited progression of CNV in rabbits, longer term administration of a lower dose of IFNbeta-DTPA-dextran had a sustained inhibitory effect on progression of CNV (P < 0.05). Histologic studies revealed the inhibitory effect of IFNbeta-DTPA-dextran on progression of CNV. This conjugate prolonged the plasma half-life of IFNbeta and enabled IFNbeta to accumulate in the CNV in rabbits. CONCLUSIONS: In this study, human IFNbeta was successfully used to target CNV, an enhanced antiangiogenic effect was achieved by combining it with dextran, based on metal coordination. This targeted delivery of IFNbeta may have potential as a treatment modality for CNV.

Angiogenesis Inhibitors↗

[Reconsideration about fibroblast growth factor and soft tissue repair].

OBJECTIVE: To further explore the effects of fibroblast growth factor on soft tissue repair. METHODS: Based on the data from our experiments and clinical trial and data from other reports, a further reconsideration about fibroblast growth factor and soft tissue repair was demonstrated, including embryonic development, histology, animal experiments, clinical trial and prospect. RESULTS: Amounts of basic and clinical data showed that fibroblast growth factor was needed in embryonic development. Exogenous fibroblast growth factor could accelerate wound healing. CONCLUSION: Fibroblast growth factor is a bioactive protein which can obviously promote wound healing, it has broad prospects of clinical application.

Animals↗

[Effects of Fall-39 mRNA expression and antibacterial activity of human pulmonary gland epithelial cells induced by BCG].

OBJECTIVE: To disclose whether BCG can enhance Fall-39 gene expression in human pulmonary gland epithelial cells, and to isolate and identify the bioactive proteins that stimulate Fall-39 gene expression in human pulmonary gland epithelial cells. METHODS: Fall-39 mRNA expression in SPC-A-1 cells was detected by using RT-PCR. The cell wall proteins were isolated by sucrose density-gradient centrifugation and fractionated by Sephadex G-75 column chromatography. The antibacterial activity of the cell culture supernatant was determined by agarose radial diffusion assay. RESULTS: The enhanced expression of Fall-39 mRNA was dose- and time-dependent. BCG cell wall proteins fraction 4 had an activity that remarkably enhanced Fall-39 mRNA expression in SPC-A-1 cells and augmented antibacterial activity of the cell culture supernatant. CONCLUSION: These results indicated that BCG could stimulate Fall-39 mRNA expression in human pulmonary gland epithelial cells, thus providing an evidence base for shaping well a new strategy to enhance mucosa antibiotic peptide expression for the prevention and treatment of mucosal infections.

Anti-Bacterial Agents↗