OBJECTIVE: Radiotherapy showed the potential to effectively kill the cysts of pulmonary cystic echinococcosis (CE). However, little is known about its safety. This study was designed to investigate the safety of three-dimensional conformal radiotherapy (3D-CRT) on the normal lung tissue adjacent to the cyst and blood of sheep naturally infected with pulmonary CE.
METHODS: Twenty pulmonary CE sheep were randomly divided into control group (n = 5) and radiation groups with a dose of 30 Gray (Gy) (n = 5), 45 Gy (n = 5), and 60 Gy (n = 5), respectively. Animals in control group received no radiation. Heat shock protein 70 (Hsp70), tumor growth factor-β (TGF-β), matrix metalloproteinase-2 (MMP-2) and MMP-9 in the lung tissues adjacent to the cysts, which were considered to be closely related to the pathogenesis of CE, were evaluated after 3D-CRT. A routine blood test was conducted.
RESULTS: The results showed that there were multiple cysts of various sizes with protoscoleces in the lung tissues of sheep, and necrotic cysts were found after 3D-CRT. 3D-CRT significantly increased the mRNA level of Hsp70, enhanced the protein level of TGF-β and slightly increased the expression of MMP-2 and MMP-9 in lung tissues adjacent to the cysts. 3D-CRT did not significantly alter the amount of WBC, HB and PLT in sheep blood.
CONCLUSIONS: The results suggested that 3D-CRT may suppress the inflammation and induce less damage of the normal lung tissues and blood. We preliminarily showed that 3D-CRT under a safe dose may be used to treat pulmonary CE.

UNASSIGNED: Behcet\'s disease (BD) is a complex, inflammatory, immune-mediated multi-systemic disease of unknown etiology. Cytokines play major roles in the pathophysiology of BD, and its production may be affected by polymorphism in cytokine genes. Hence, the present study was planned to investigate any possible association between the polymorphism in TGF-β, IFN-γ, and IL-6 genes and BD in the Saudi population.
UNASSIGNED: The present study includes 79 BD cases and 117 age-matched controls. Polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation systems (ARMS) PCR methods were used for polymorphic analysis.
UNASSIGNED: The heterozygous (CT) and (CT+TT) combined genotypes of TGF-β (509-C/T), heterozygous (AT), variant (TT), and (AT+TT) combined genotypes of IFN-γ (874-A/T) were significantly (P<0.05) associated with BD in the Saudi population. No significant differences were observed for IL-6 (174-G/C) genotypes and alleles between BD cases and controls. Gender does not reflect any significant genotypic and allelic association with males and females.
UNASSIGNED: CT genotype of TGF-β, and AT and TT genotypes of IFN-γ could be associative genetic risk factors for BD in Saudis. Regulatory region polymorphism in cytokines gene can increase inflammation and deregulated immune response, which could be risk factor for BD.

OBJECTIVE: MicroRNA-590-5p (miR-590-5p) has been reported to stimulate osteoblast differentiation; however, its effect in diabetic osteoporosis remains unknown. This study investigated the effect of miR-590-5p on high glucose (HG)-suppressed osteoblast differentiation.
METHODS: The effect of HG on MC3T3-E1 cell survival was assessed using the MTT assay. The expression levels and activities of osteoblastic proteins were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR), alkaline phosphatase (ALP) assay, and immunoblotting assay. Tumor growth factor-β (TGF-β) signaling in MC3T3-E1 cells was assessed using luciferase assay, qRT-PCR, and immunoblotting. Mineralized nodule formation in MC3T3-E1 cells was examined by using the mineralization assay.
RESULTS: When MC3T3-E1 cells were exposed to HG conditions, there was significant downregulation of miR-590-5p and osteoblastic proteins (e.g., collagen I, Runx2, and ALP); in contrast, Smad7 was upregulated. Furthermore, miR-590-5p targeted Smad7 and inhibited its expression. Additionally, overexpression of miR-590-5p significantly promoted osteoblast growth and differentiation by upregulating TGF-β signaling in HG-treated MC3T3-E1 cells.
CONCLUSIONS: Collectively, the results showed that miR-590-5p was involved in osteogenesis; moreover, miR-590-5p may represent a potential target for the treatment of diabetic osteoporosis.

Dietary garlic has been suggested to possess anticancer properties, and several attempts have been made to isolate the anticancer compounds. In this study, we efficiently synthesized N-benzyl-N-methyl-dodecan-1-amine (BMDA) by the reductive amination method. We evaluated the potential anticancer activities of BMDA against A549 lung cancer cells with cancer stem cell-like phenotypes due to the overexpression of cancer upregulated gene (CUG)2. N-Benzyl-N-methyl-dodecan-1-amine treatment sensitized A549 cells overexpressing CUG2 (A549-CUG2) to apoptosis and autophagy compared with those of the control cells. The treatment with BMDA also reduced tumor development in xenografted nude mice. Furthermore, BMDA inhibited cell migration, invasion, and sphere formation in A549-CUG2 cells, in which TGF-β signaling is involved. Further analysis showed that BMDA hindered TGF-β promoter activity, protein synthesis, and phosphorylation of Smad2, thus decreasing the expression of TGF-β-targeted proteins, including Snail and Twist. N-Benzyl-N-methyl-dodecan-1-amine also decreased Twist expression in vivo. In addition, BMDA inhibited Akt-ERK activities, β-catenin expression, and its transcriptional activity. These results suggest that BMDA can be a promising anticancer agent against cancer cells overexpressing CUG2.

We report a case of bilateral annular breast keloids in a 72-year-old woman who had been suffering from bilateral breast cancers. Histopathologically, the keloids showed unique distribution of α-SMA+, CD34- myofibroblasts and α-SMA-, CD34+ fibroblasts depending on the region. High serum levels of tumor growth factor-β were detected at 6 months after the development of the breast keloids, but not at 10 months. CD163-positive cells were abundantly detected in the skin of the elevated portion of the keloids. In contrast, these cells were considerably less numerous in the skin of the central healing portion compared with the skin of the elevated expanding portion. One interesting idea based on these results is that high levels of tumor growth factor-β released from CD163-positive cells played a crucial role in the formation of breast keloids through active induction of fibroblast differentiation into myofibroblasts. The present case strongly supports the previously proposed idea that keloids can form as a paraneoplastic phenomenon in breast cancer patients with keloid constitution.

Co-inhibitory molecules have become the key targets in cancer immunotherapy with the strategy of blocking immune checkpoints to reverse the pathogenic regulation of T cells. However, their expression regulations in NK cells, the most important innate immune cells against tumor, remain largely undefined. In this study, we showed that the expressions of co-inhibitors on NK cells, including LAG-3, PD-1, and TIGIT, are differently regulated by cytokines IL-10, IL-12, IL-15, IFN-α, and TGF-β. Among the tested cytokines, IL-12 is the most powerful inducer of LAG-3, and TGF-β is the strongest suppresser of PD-1. Notably, the expression of these co-inhibitors responds to the time course of stimulus progressively. Together, these findings illustrated that the co-inhibitors on NK cells express differently in response to cytokine stimulations of IL-10, IL-12, IL-15, IFN-α, and TGF-β, providing an initial information on the expression regulation of co-inhibitors in human NK cells.