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Chia-Li Yu

Publications and source records attributed to Chia-Li Yu.

At least 19 recordsLinked to original sources

Human kallikrein 8 protease confers a favorable clinical outcome in non-small cell lung cancer by suppressing tumor cell invasiveness.

The human kallikrein 8 (KLK8) gene, a member of the human tissue kallikrein gene family, encodes a serine protease. The KLK8 protein (hK8) is known to be a favorable prognostic marker in ovarian cancer, but the biological basis of this is not understood. We found that overexpressing the KLK8 gene in highly invasive lung cancer cell lines suppresses their invasiveness. This role in invasiveness was further confirmed by the fact that inhibition of endogenous KLK8 expression with a specific short hairpin RNA reduced cancer cell invasiveness. In situ degradation and cell adhesion assays showed that proteins produced from KLK8 splice variants modify the extracellular microenvironment by cleaving fibronectin. DNA microarray experiments and staining of cells for actin filaments revealed that the degradation of fibronectin by hK8 suppresses integrin signaling and retards cancer cell motility by inhibiting actin polymerization. In addition, studies in a mouse model coupled with the detection of circulating tumor cells by quantitative PCR for the human Alu sequence showed that KLK8 suppresses tumor growth and invasion in vivo. Finally, studies of clinical specimens from patients with non-small cell lung cancer showed that the time to postoperative recurrence was longer for early-stage patients (stages I and II) with high KLK8 expression (mean, 49.9 months) than for patients with low KLK8 expression (mean, 22.9 months). Collectively, these findings show that KLK8 expression confers a favorable clinical outcome in non-small cell lung cancer by suppressing tumor cell invasiveness.

Base Sequence↗

Hypernatremic myopathy caused by a hypothalamic mixed germ cell tumor mimicking polymyositis.

Hypernatremic myopathy was rarely reported in the literature and its clinical features have never been well-described. We present a 22-year-old man who had adipsic hypernatremia manifested with progressive proximal muscle weakness and remarkably high creatine kinase level that has never been reported in the cases of hypernatremic myopathy. His initial presentations were similar to that of polymyositis without the evidence of central nervous system dysfunction and hypopituitarism. The serum level of sodium at the beginning of myopathy is the lowest known in the literature. All the clinical presentations in this patient resulted from a hypothalamic mixed germ cell tumor with sub-acute intra-tumoral hemorrhage.

Adult↗

Release of surface-expressed lactoferrin from polymorphonuclear neutrophils after contact with CD4+ T cells and its modulation on Th1/Th2 cytokine production.

It is conceivable that a membrane component(s) is transferred from antigen-presenting cells to T cells after antigenic stimulation. However, it is not clear whether a certain membrane component(s) is transferred from polymorphonuclear neturophils (PMN) to T cells for immunomodulation. In the presence study, we cocultured two of the three autologous cells-PMN, CD4+ T, and red blood cells (RBC)-homotypically or heterotypically for 1 h. Spontaneous membrane exchange between autologous PMN-PMN and PMN-CD4+ T but not between CD4+ T-CD4+ T or RBC-CD4+ T was observed with a confocal microscope. Loss of membrane exchange between two paraformaldehyde-fixed cells suggests that mutual membrane exchange is via cell-cell contact. Different combinations of cellular enzyme-linked immunosorbent assay for measuring the binding between fixed cells and biotinylated cell lysates showed the same tendency. To identify the molecule(s) mediating PMN-CD4+ T binding, we compared the banding of biotinylated PMN lysates and the banding of plain PMN lysate probed by biotinylated CD4+ T lysate in 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis. We found that a 75- to 80-kDa surface-expressed molecule on PMN exists constantly to mediate PMN-CD4+ T binding. Peptide analysis disclosed that the molecule had 99.8% identity with lactoferrin (LF). The expression of LF on system lupus erythematosis (SLE)-PMN is less than normal PMN. PMN-CD4+ T coculture increased LF expression on CD4+ T. Normal PMN and human milk-derived LF suppressed interferon-gamma (IFN-gamma) but enhanced interleukin (IL)-10 production of anti-CD3+anti-CD28-activated, normal CD4+ T. In contrast, coculture of SLE-PMN and autologous CD4+ T suppressed IFN-gamma and IL-10 production. These results suggest that the surface-expressed LF released from PMN after contact with autologous CD4+ T modulated its T helper cell type 1 (Th1)/Th2 cytokine production. Decreased LF expression on SLE-PMN abnormally modulates Th1/Th2 production by CD4+ T cells.

Antigens, Surface↗

Skin denervation and cutaneous vasculitis in systemic lupus erythematosus.

To understand the clinical significance and mechanisms of cutaneous denervation in systemic lupus erythematosus (SLE), we assessed intraepidermal nerve fibre (IENF) density of the distal leg in 45 SLE patients (4 males and 41 females, aged 38.4 +/- 13.6 years) and analysed its correlations with pathology, lupus activity, sensory thresholds and electrophysiological parameters. Compared with age- and gender-matched control subjects, SLE patients had lower IENF densities (3.08 +/- 2.17 versus 11.27 +/- 3.96 fibres/mm, P < 0.0001); IENF densities were reduced in 38 patients (82.2%). Pathologically, 11 patients (24.4%) were found to have definite cutaneous vasculitis; the severity and extent of cutaneous vasculitis were correlated with IENF densities. Patients with active lupus had even lower IENF densities than those with quiescent lupus (1.86 +/- 1.37 versus 4.15 +/- 2.20 fibres/mm, P = 0.0002). By linear regression analysis, IENF densities were negatively correlated with the SLE disease activity index (r = 0.527, P = 0.0002) and cumulative episodes of lupus flare-up within 2 years before the skin biopsy (r = 0.616, P = 0.0014). Clinically, skin denervation was present not only in the patients with sensory neuropathy but also in the patients with neuropsychiatric syndrome involving the CNS. SLE patients had significantly elevated warm threshold temperatures (P = 0.003) and reduced cold threshold temperatures (P = 0.048); elevated warm threshold temperatures were associated with the reduced IENF densities (P = 0.032). In conclusion, cutaneous vasculitis and lupus activities underlie skin denervation with associated elevation of thermal thresholds as a major manifestation of sensory nerve injury in SLE.

Adult↗

Identification of forty-five novel and twenty-three known NF1 mutations in Chinese patients with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1), characterized by skin neurofibromas and an excess of café-au-lait spots, is due to mutations in the neurofibromin (NF1) gene. Identifying the genetic defect in individuals with the disease represents a significant challenge because the gene is extremely large with a high incidence of sporadic mutations across the entire gene ranging from single nucleotide substitutes to large deletions. In the present study, we have used a combination of techniques (heteroduplex analysis, sequencing, loss of heterozygosity and quantification of gene dosage) to define the genetic defect in 68 individuals from a cohort of 107 NF1 Taiwanese patients of Chinese origin. Fifty-eight were initially identified using heteroduplex analytical techniques and confirmed by sequence analysis. A further five were identified by direct sequence analysis alone. The reminders were shown to carry large deletions in the NF1 gene by demonstrating loss of heterozygosity that was confirmed by gene dosage measurements using quantitative-PCR techniques. Mis-sense, non-sense, frame-shift or splice-site mutations were identified across the entire gene of which the majority (45/68) were novel in nature. The detection rate with the various analytical techniques and the types of mutation detected are consistent with published data involving both individuals and large cohort studies from other ethnic backgrounds.

Adolescent↗

Spinal pseudoarthrosis: a rare complication in psoriatic arthritis.

Discovertebral erosion with pseudoarthrosis is a well-known complication in ankylosing spondylitis but it is seldom mentioned in psoriatic arthritis. We report a 53-year-old woman with an 8-year history of psoriatic arthritis who developed severe low back pain followed by sudden onset of numbness in the lower limbs, weakness and dysesthesia. Abnormal contour of L1 and L2 vertebrae and intervertebral disc space was noted during radiologic examination. Pseudoarthrosis was suspected based on extensive osseous resorption and reactive sclerosis about the discovertebral junction on magnetic resonance imaging study. She underwent emergency operation due to spinal instability with neurologic deficit. Pseudoarthrosis was confirmed intraoperatively. No evidence of infection or neoplasms was found. This case shows that pseudoarthrosis can be complicated in patients with psoriatic arthritis, and this possibility should be considered in patients with previously quiescent disease.

Arthritis, Psoriatic↗

Pilocarpine hydrochloride for the treatment of xerostomia in patients with Sjögren's syndrome in Taiwan--a double-blind, placebo-controlled trial.

BACKGROUND/PURPOSE: Sjögren's syndrome (SS) is characterized by diminished exocrine secretions with the resultant symptoms of dry mouth and dry eye. As genetic predisposition and ethnicity may alter the effectiveness of drug treatment, evaluation of the efficacy and safety of the secretagogue pilocarpine hydrochloride in the treatment of xerostomia in patients with SS in different populations is needed. METHODS: Forty-four patients with SS were enrolled in this double-blind, placebo-controlled trial. Patients were randomized to receive 5 mg pilocarpine (Salagen) or placebo tablet four times daily for 12 weeks. Global evaluation and subjective responses of patients were assessed by questionnaires with visual analog scales and categorical checkboxes. Saliva production was also measured by modified Saxon's test. RESULTS: Pilocarpine treatment significantly improved global assessment of dry mouth, symptoms associated with dry mouth (mouth comfort, ability to sleep and ability to speak), and saliva production compared to placebo. The drug was well tolerated and the most common adverse effect was sweating (5/23, 21.7%) resulting from the muscarinic agonist action of the drug. No serious drug-related adverse effect was found in this study. CONCLUSION: The results of this study suggest that therapy with 5 mg pilocarpine four times daily is effective, safe and well tolerated for the relief of oral symptoms in patients with SS in Taiwan.

Double-Blind Method↗

Lupus-related advanced liver involvement as the initial presentation of systemic lupus erythematosus.

BACKGROUND AND PURPOSE: Systemic lupus erythematosus (SLE), a prototype of systemic autoimmune disease characterized by multiorgan involvement with diverse clinical and serological manifestations, principally affects women in their child-bearing years. Clinically significant hepatic abnormality as the initial presentation of SLE has rarely been reported. METHODS: Eleven patients with lupus with initial presentation of lupus-related hepatitis were included in this retrospective review. Clinical manifestation, immunological profiles, and risk factors for poor prognosis were analyzed. RESULTS: The most commonly associated clinical manifestations were found to be thrombocytopenia, leukopenia, advancing age, and presence of anti-SSA/Ro antibody and anti-thyroid antibodies. The diagnosis of SLE was delayed due to dominant hepatic abnormalities. Age greater than 50 years and marked hepatic decompensation in accordance with Child classification B and C might suggest poor prognosis (p=0.06). However, the p value was not statistically significant because of the small sample size. CONCLUSIONS: Lupus-related hepatitis, particularly in late-onset lupus, is common. In addition, the presence of anti-SSA, anti-thyroglobulin, and anti-microsomal antibodies is indicative of hepatic involvement in patients with SLE.

Adult↗

Outcome and prognostic factors in critically ill patients with systemic lupus erythematosus: a retrospective study.

INTRODUCTION: Systemic lupus erythematosus (SLE) is an archetypal autoimmune disease, involving multiple organ systems with varying course and prognosis. However, there is a paucity of clinical data regarding prognostic factors in SLE patients admitted to the intensive care unit (ICU). METHODS: From January 1992 to December 2000, all patients admitted to the ICU with a diagnosis of SLE were included. Patients were excluded if the diagnosis of SLE was established at or after ICU admission. A multivariate logistic regression model was applied using Acute Physiology and Chronic Health Evaluation II scores and variables that were at least moderately associated (P < 0.2) with survival in the univariate analysis. RESULTS: A total of 51 patients meeting the criteria were included. The mortality rate was 47%. The most common cause of admission was pneumonia with acute respiratory distress syndrome. Multivariate logistic regression analysis showed that intracranial haemorrhage occurring while the patient was in the ICU (relative risk = 18.68), complicating gastrointestinal bleeding (relative risk = 6.97) and concurrent septic shock (relative risk = 77.06) were associated with greater risk of dying, whereas causes of ICU admission and Acute Physiology and Chronic Health Evaluation II score were not significantly associated with death. CONCLUSION: The mortality rate in critically ill SLE patients was high. Gastrointestinal bleeding, intracranial haemorrhage and septic shock were significant prognostic factors in SLE patients admitted to the ICU.

APACHE↗

Prognosis of non-small cell lung cancer patients by detecting circulating cancer cells in the peripheral blood with multiple marker genes.

PURPOSE: Current lung cancer staging and prognosis methods are based on imaging methods, which may not be sensitive enough for early and accurate detection of metastasis. This study aims to validate the use of a panel of markers for circulating cancer cell detection to improve the accuracy of cancer staging, prognosis, and as a rapid assessment of therapeutic response. EXPERIMENTAL DESIGN: We analyzed the National Cancer Institute-Cancer Genome Anatomy Project database to identify potential marker genes for the detection of circulating cancer cells in peripheral blood. Nested real-time quantitative PCR and a scoring method using cancer cell load Lc were employed to correlate the amount of circulating cancer cells with clinical outcomes in 54 non-small cell lung cancer (NSCLC) patients. The Kaplan-Meier method was employed for analysis of prognostic variables. RESULTS: A panel of four marker genes was identified and experimentally validated. With these marker genes, we achieved an overall positive detection rate of 72% for circulating cancer cells in the peripheral blood of NSCLC patients. Patients who had higher Lc values had worse outcomes and shorter survival times. Patients with poor therapeutic response were revealed by positive detection of circulating cancer cells after therapy. The results correlated well with the patients' survival time. CONCLUSION: Circulating cancer cell detection by a panel of markers and the Lc scoring method can supplement the current tumor, node, metastasis staging method for improved prognosis and for rapid assessment of therapeutic response. Together, they may facilitate the design of better therapeutic strategies for the treatment of NSCLC patients.

Aged↗

Quantitative analysis of SMN1 and SMN2 genes based on DHPLC: a highly efficient and reliable carrier-screening test.

Autosomal recessive spinal muscular atrophy (SMA) is a common, fatal neuromuscular disease caused by homozygous absence of the SMN1 gene in approximately 94% of patients. However, a highly homologous SMN2 gene exists in the same chromosome interval, centromeric to SMN1, and hampers detection of SMN1. We present a new, rapid, simple, and highly reliable method for detecting the SMN1 deletion/conversion and for determining the copy numbers of the SMN1 and SMN2 genes by DHPLC. We analyzed SMN1/SMN2 gene exon 7 deletion/conversion by DHPLC. A total of 25 patients with spinal muscular atrophy lacking the SMN1 gene as well as 309 control individuals from the general population and the family members of patients with SMA were analyzed. By DHPLC analysis, we could detect the SMA-affected cases efficiently just by recognizing an SMN2-only peak. Furthermore, after specific primer amplification and adjustment of the oven temperature, all of the SMA carriers with an SMN1/SMN2 ratio not equal to 1 could be identified unambiguously by this simple and efficient detection system. To calculate the total SMN1/SMN2 gene dosages further, we developed a specific multiplex competitive PCR protocol by simultaneously amplifying the CYBB gene (X-linked), the KRIT1 gene (on chromosome arm 7q), and the SMN1/SMN2 gene ratio by DHPLC. By applying this technique, we could successfully designate all of the genotypes with different SMN1/SMN2 gene copy numbers, including equal and unequal amounts of SMN1 and SMN2. We demonstrated that DHPLC is a fast and reliable tool for detection of carriers of SMA.

Chromatography, High Pressure Liquid↗

Monoclonal ribosomal P autoantibody inhibits the expression and release of IL-12, TNF-alpha and iNOS in activated RAW macrophage cell line.

Monoclonal ribosomal P protein antibody (anti-P mAb) may bind to the cell surface, penetrate into cells, and induce apoptosis of Jurkat T cells. Recently, modulation of cytokines has been considered to be important in the pathogenesis of systemic lupus erythematous (SLE). In this study, effects of anti-P mAbs (9B6) on gene expression of cytokines, apoptosis, and reactive oxygen species in murine macrophage RAW 264.7 were analyzed by RT-PCR and ELISA and those on IL-12 promoter activity was determined in an IL-12p40 promoter-reporter gene transfected cell line RAW (IL-12p40-SEAP). After treating LPS-activated RAW 264.7 with 9B6 for 6 or 24 h, the levels of mRNA and protein expression of IL-12, TNF-alpha, and iNOS were significantly inhibited by 25%, 16%, and 13%, respectively. The IL-12 promoter activity of RAW (IL-12p40-SEAP) was also inhibited by 13-22%. However, inhibitory effects were not observed in cells pre-treated with IgG1 for 1 h. The productions of IL-10 in LPS-activated RAW 264.7 and human macrophages were potentiated by 9B6 up to 65% and 51%, respectively. Since anti-P Abs inhibit productions of IL-12 and TNF-alpha and enhance IL-10 production in macrophages, these autoantibodies may augment Th2 responses and amplify lupus manifestations by causing immunological polarity and lymphocyte dysfunction.

Animals↗

Pigmentation in basal cell carcinoma involves enhanced endothelin-1 expression.

Basal cell carcinoma (BCC) is the most prevalent malignant skin tumor. In Asian patients, marked pigmentation in BCC lesions is often observed. Recently, endothelins (ETs) have been implicated to participate in the pigmentation process of BCC. Therefore, we set out to investigate the involvement of ET in the pigmentation process of BCC and the potential regulators in the pigmentation pathway. We explored the effects of an established BCC cell line on melanocytes. The growth factor profiles of BCC culture supernatant and effects of supernatant on melanocytes were documented. Potential regulators involved in the pigmentation pathway were also studied. The immunohistochemical staining of pigmented and non-pigmented BCC specimens was performed to confirm our in vitro findings. Our results showed that BCC supernatant contained significant amount of ET-1, basic fibroblast growth factor, and nerve growth factor. Furthermore, BCC supernatant stimulated melanin formation of cultured melanocytes. Addition of ET-receptor antagonist abrogated the melanogenic effect of BCC supernatant on melanocytes. Introduction of UVB irradiation decreased the ET-1 secretion by BCC cells. Immunohistochemical staining of the pigmented facial BCC specimens showed prominent expression of ET-1 on pigmented BCC, while the non-pigmented facial BCC specimens showed little ET-1 reactivity. Tumor necrosis factor-alpha (TNF-alpha) staining showed little expression on BCC specimens, regardless of pigmentation status. In summary, our results indicate that enhanced ET-1 expression in pigmented BCC plays an important role in the hyperpigmentation of this tumor. Moreover, this enhanced ET-1 cascade showed little correlation with UV irradiation and TNF-alpha expression in our study.

Basal Cell Carcinoma↗

An unusual case of ulcerative colitis with concurrent extraintestinal manifestations of primary sclerosing cholangitis, thromboembolism, hemolytic anemia, and hemochromatosis.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of intestines associated with a large number of extraintestinal manifestations (EIMs) which significantly contribute to its morbidity and mortality. A 32-year-old man presented with ulcerative colitis (UC) accompanied by the unusual coexisting clinical manifestations of primary sclerosing cholangitis, thromboembolism, and hemolytic anemia during the disease course. The incidental finding of hemochromatosis of the liver was attributed to chronic hemolysis. The full-blown EIMs and systemic complications in this patient did not appear to be attributable to drug treatment and/or infection but might have been related to both the underlying immune-mediated mechanism and the lack of early and adequate treatment for UC and its associated complications. This case emphasizes the need for early and aggressive treatment of IBD accompanied by EIMs to avoid morbidity and mortality.

Adult↗

Proinflammatory cytokines enhance COX-1 gene expression in cultured rat glomerular mesangial cells.

Glomerular mesangial cells (GMC) exert an essential maintaining effect on hemodynamic integrity and immune competence of the kidney through arachidonate metabolism. To clarify this, cultured rat GMC were measured for the expression and production of cyclooxygenase (COX) and excretion of prostaglandin (PG). The rat GMC spontaneously expressed type 1 cyclooxygenase (COX-1), but not COX-2. The PGE2 and thromboxane B2 (TXB2) were spontaneously produced by the cells. Interleukin (IL)-1beta (25 ng/ml), IL-8 (25 ng/ml), growth-related oncogene-alpha (GRO, 50 ng/ml) and tumor necrosis factor-alpha (TNF-alpha, 25 ng/ml) stimulated the COX-1 protein production as demonstrated by Western blot and enhanced PGE2 synthesis in GMC, beginning on 2 h of incubation, and steadily enhanced TXB2 synthesis over a 24-h period. Lipopolysaccharide (LPS, 100 ng/ml) enhanced both PGE2 and TXB2 syntheses from 2 h to at least 24 h of incubation. Collectively, the proinflammatory cytokines could enhance COX-1 but not COX-2 expression in GMC leading to increased PGE2 and TXB2 production. These biochemical events may be implicated in normal renal physiology as well as in pathogenesis of glomerular diseases.

Animals↗

Effects and interactions of low doses of arsenic and UVB on keratinocyte apoptosis.

Although arsenic and ultraviolet light B (UVB) are both causes for skin cancers, lesions of arsenic-induced Bowen's disease are often confined to sun-protected skin. UVB may play a modulatory role in skin carcinogenesis by arsenic. The purpose of this study was to evaluate the effects and interactions of arsenic and UVB on cell cycle progression and apoptosis. Cultured human keratinocytes were treated with sodium arsenite (1 microM) and/or UVB (50 mJ/cm(2)) irradiation in different combinations: (i) arsenic alone, (ii) UVB alone, (iii) arsenic followed by UVB (As-UVB), and (iv) UVB followed by arsenic (UVB-As) treatments. Cell cycle analysis and BrdU pulsing revealed S phase arrest in all treatment groups and growth arrest in As-UVB and UVB-As groups. The terminal deoxynucleotidyl transferase-mediated deoxyuridine nick-end labeling assay showed a higher apoptosis rate in the UVB-As group as compared to that of the As-UVB and UVB groups. UVB irradiation significantly decreased Bcl-2 expression. In either the As-UVB or the UVB-As group, the expression of Bcl-2 was further suppressed as compared to the UVB group. The caspase-3, -8, and -9 relative activities were all increased in the UVB group; however, arsenic significantly enhanced caspase-8 and -3 relative activities in UVB-irradiated keratinocytes (the UVB-As group). Pretreatment with the caspase inhibitor(s) rescued the keratinocytes viability to different degrees with the least in the UVB-As group. Our findings revealed that arsenic enhances UVB-induced keratinocyte apoptosis via suppression of Bcl-2 expression and stimulation of caspase-8 activity. Combined UVB and arsenic treatment resulted in the antiproliferative and proapoptotic effects in keratinocytes. Our results provide the explanation for the rare occurrences of arsenical cancers in the sun-exposed skin and the potential therapeutic role of UVB in arsenic-induced Bowen's disease.

Apoptosis↗

Narrow-band ultraviolet-B stimulates proliferation and migration of cultured melanocytes.

Narrow-band ultraviolet-B (UVB) radiation is an effective treatment for vitiligo vulgaris. However, the mechanisms of narrow-band UVB in inducing repigmentation of vitiligo lesions are not thoroughly clarified. The purpose of our study was to investigate the effects of narrow-band UVB irradiation on melanocyte proliferation and migration in vitro. Our results showed that the cell counts as well as [3H]thymidine uptake of melanocytes were significantly enhanced by narrow-band UVB-irradiated keratinocyte supernatants. In these supernatants, a significant increase in basic fibroblast growth factor (bFGF) and in endothelin-1 (ET-1) release was observed. bFGF is a natural mitogen for melanocytes, whereas ET-1 can stimulate DNA synthesis in melanocytes. This stimulatory effect of melanocyte proliferation by supernatants derived from narrow-band UVB-irradiated keratinocytes was significantly reduced by a selective endothelin-B (ET-B) receptor antagonist (BQ788), suggesting an essential role of ET-1 on melanocyte proliferation. Our results of time-lapse microphotography revealed a stimulatory effect of narrow-band UVB irradiation on melanocyte migration. Focal adhesion kinase (FAK) plays a pivotal role in cell migration. Phosphorylated FAK (p125(FAK)) expression on melanocyte was enhanced by narrow-band UVB irradiation. In this study, narrow-band UVB irradiation stimulated a significant increase in matrix metalloproteinase-2 (MMP-2) activity in melanocyte supernatants. Narrow-band UVB-irradiation-induced migration of melanocytes was significantly annihilated by the addition of p125(FAK) inhibitor (herbimycin-A) or MMP-2 inhibitor (GM6001). These results suggest that p125(FAK) and MMP-2 activity play important roles in narrow-band UVB-induced migration of melanocytes. Our results provide a theoretical basis for the effectiveness of narrow-band UVB irradiation in treating vitiligo.

Cell Movement↗

Effects of gallium on immune stimulation and apoptosis induction in human peripheral blood mononuclear cells.

Gallium is commonly used in the semiconductor industry and medical field. Biologically, gallium is able to interrupt iron metabolism. Exposure to gallium has been shown to affect the human immune system. The purpose of this study was to investigate the in vitro biological effects of different gallium concentrations on cultured human peripheral blood mononuclear cells (PBMCs) in terms of cell growth, cytokine release, and apoptosis induction. In addition, the in vivo effects of gallium were analyzed by Wistar rat model. Our results revealed that low concentrations (1-10 microg/ml) of gallium promoted cells to enter the S phase of cell cycle and enhanced cellular release of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma, both in vitro and in vivo. In contrast, high concentrations of gallium (50-100 microg/ml) induced apoptosis. Furthermore, gallium-induced cytokine release and apoptosis could be inhibited by iron-saturated transferrin (Tf-Fe). These results suggest that the concentration-dependent effects of gallium on PBMCs are related to iron metabolism.

Adjuvants, Immunologic↗