Incidence and Direct Medical Cost of Adjustment Disorder and in Korea Using National Health Insurance Service Claims Data From 2011 to 2017.

OBJECTIVE: We aimed to investigate the annual incidence and direct medical cost of adjustment disorder in general population using the National Health Insurance Service Database (NHID) in Korea. METHODS: To examine the incidence, we selected patients who had at least one medical claim for adjustment disorder and had not been diagnosed in the previous 365 days, from 2010 to 2017. RESULTS: The number of newly diagnosed cases of adjustment disorder from 2011 to 2017 were total 101,922. Annual incidence of adjustment disorder was ranged from 22.0 to 36.8 per 100,000 persons. The incidence of adjustment disorder was found more in female and highest among 70-79 years of age group and medical aid beneficiaries group. Annual prevalence of adjustment disorder was in the range from 95.4 to 116.4 per 100,000 persons. Estimated annual medical cost per person of adjustment disorder was ranged from 162 to 231.4 US dollars. CONCLUSION: From 2011 to 2017, the annual incidence and direct medical cost of adjustment disorder in Korea were increased. Proper information on adjustment disorder will not only allows us to accumulate more knowledge but also lead to more appropriate therapeutic interventions.

Celecoxib induces apoptosis through Akt inhibition in 5-fluorouracil-resistant gastric cancer cells.

Gastric cancer is the fifth leading cause of cancer and a global public health problem. 5-Fluorouracil (5-FU) is the primary drug chosen for the treatment of advanced gastric cancer, but acquired cancer drug resistance limits its effectiveness and clinical use. Proliferation assays showed that a gastric carcinoma cell line, AGS and 5-FU-resistant AGS cells (AGS FR) treated with 3-100 µM 5-FU for 48 h or 72 h showed different sensitivities to 5-FU. Immunoblot assay demonstrated that AGS FR cells expressed more COX-2 and PGE2-cognated receptor EP2 than AGS cells. AGS FR cells considerably produced PGE2 than AGS upon stimulation with 5-FU. These results suggest that COX-2 expression is associated with 5-FU resistance. Unlike AGS FR cells, AGS cells showed increased levels of both cleaved caspase-3 and Bax following 5-FU treatment. Treatment of cells with the COX-2 selective inhibitor celecoxib induced cell death of AGS FR cells in a time- and concentration-dependent manner. FACS analysis showed that celecoxib at high doses caused apoptotic cell death, demonstrating a concentration-dependent increase in the cell populations undergoing early apoptosis and late apoptosis. This apoptotic induction was strongly supported by the expression profiles of apoptosis- and survival-associated proteins in response to celecoxib; pro-apoptotic cellular proteins increased while expressions of COX-2 and p-Akt were downregulated in a concentration-dependent manner. An increase in PTEN expression was accompanied with downregulation of p-Akt. Based on the data that downregulation of COX-2 was correlated with the concentrations of celecoxib, COX-2 may play a key role in celecoxib-induced cell death of AGS FR cells. Butaprost, the EP2 agonist, promoted proliferative activity of AGS FR cells in a concentration-dependent manner compared with AGS cells. In cells exposed to butaprost, expressions of COX-2 and p-Akt were increased in a concentration-dependent manner with concomitantly reduced PTEN levels. Taken together, 5-FU-resistance in gastric cancer is correlated with COX-2 expression, and therefore the selective inhibition of COX-2 leads to suppression of cell proliferation of AGS FR cells. Modulation of COX-2 expression and its catalytic activity may be a potential therapeutic strategy to overcome 5-FU-resistant gastric cancer.

Thymoquinone induces apoptosis of human epidermoid carcinoma A431 cells through ROS-mediated suppression of STAT3.

Black seed (Nigella sativa) oil has been used in various dermatological applications, and its major constituent, thymoquinone (TQ) has been shown to exhibit antiproliferative activity against various cancer cells. In this study, we tried to provide a mechanistic basis of apoptosis induced by TQ. Skin squamous carcinoma A431 cells were treated with TQ to monitor the apoptosis induced by TQ. Western blot analysis was performed to detect expression of apoptotic or anti-apoptotic proteins. Cell viability and apoptosis were measured by using the MTT test and FACS analysis, respectively. The induction of intracellular reactive oxygen species (ROS) by TQ was evaluated by 2',7'-dichlorofluorescein diacetate staining. In vivo xenograft study was followed to confirm the antiproliferative effect of TQ. Treatment of A431 cells with TQ-induced apoptosis, which was associated with the induction of p53 and Bax, inhibition of Mdm2, Bcl-2, and Bcl-xl expression, and activation of caspase-9, -7, and -3. TQ inhibited the constitutive phosphorylation and DNA binding activity of signal transducer and activator of transcription-3 (STAT3) in A431 cells by blocking the phosphorylation of the upstream kinase, Src. Moreover, the expression of STAT3 target gene products, cyclin D1 and survivin, was attenuated by TQ treatment. The generation of ROS was increased during TQ-induced apoptosis, and the pretreatment of N-acetyl cysteine, a ROS scavenger, reversed the apoptotic effect of TQ. In vivo study with NOD scid gamma (NSG) mice confirmed the inhibitory effect of TQ on the growth of A431 cells. Our results provide the first demonstration that TQ induces the apoptosis of A431 cells through generation of ROS and inhibition of STAT3 signaling.

Bioactive fish collagen/polycaprolactone composite nanofibrous scaffolds fabricated by electrospinning for 3D cell culture.

One of the most challenging objectives of 3D cell culture is the development of scaffolding materials with outstanding biocompatibility and favorable mechanical strength. In this study, we fabricated a novel nanofibrous scaffold composed of fish collagen (FC) and polycaprolactone (PCL) blends by using the electrospinning method. Nanofibrous scaffolds were characterized using a scanning electron microscope (SEM), and it was revealed that the diameter of nanofibers decreased as FC content was increased in the FC/PCL composite nanofibers. The cytocompatibility of the FC/PCL scaffolds was evaluated by SEM, WST-1 assay, confocal microscopy, western blot, and RT-PCR. It was found that the scaffolds not only facilitated the adhesion, spreading, protrusions, and proliferation of thymic epithelial cells (TECs), but also stimulated the expression of genes and proteins involved in cell adhesion and T-cell development. Thus, these results suggest that the FC/PCL composite nanofibrous scaffolds will be a useful model of 3D cell culture for TECs and may have wide applicability in the future for engineering tissues or organs.