Diosgenin Induces Apoptosis in HepG2 Cells through Generation of Reactive Oxygen Species and Mitochondrial Pathway

Diosgenin, a naturally occurring steroid saponin found abundantly in legumes and yams, is a precursor of various synthetic steroidal drugs. Diosgenin is studied for the mechanism of its action in apoptotic pathway in human hepatocellular carcinoma cells. Based on DAPI staining, diosgenin-treated cells manifested nuclear shrinkage, condensation, and fragmentation. Treatment of HepG2 cells with 40 μM diosgenin resulted in activation of the caspase-3, -8, -9 and cleavage of poly-ADP-ribose polymerase (PARP) and the release of cytochrome c. In the upstream, diosgenin increased the expression of Bax, decreased the expression of Bid and Bcl-2, and augmented the Bax/Bcl-2 ratio. Diosgenin-induced, dose-dependent induction of apoptosis was accompanied by sustained phosphorylation of JNK, p38 MAPK and apoptosis signal-regulating kinase (ASK)-1, as well as generation of the ROS. NAC administration, a scavenger of ROS, reversed diosgene-induced cell death. These results suggest that diosgenin-induced apoptosis in HepG2 cells through Bcl-2 protein family-mediated mitochndria/caspase-3-dependent pathway. Also, diosgenin strongly generated ROS and this oxidative stress might induce apoptosis through activation of ASK1, which are critical upstream signals for JNK/p38 MAPK activation in HepG2 cancer cells

Overhydration measured by bioimpedance analysis and the survival of patients on maintenance hemodialysis: a single-center study

AbstractBackgroundBioimpedance analysis (BIA) helps measuring the constituents of the body noninvasively. Prior studies suggest that BIA-guided fluid assessment helps to predict survival in dialysis patients. We aimed to evaluate the clinical usefulness of BIA for predicting the survival rate of hemodialysis patients in Korea.MethodsWe conducted a single-center retrospective study. All patients were diagnosed with end-stage renal disorder and started maintenance hemodialysis between June 2009 and April 2014. BIA was performed within the 1st week from the start of hemodialysis. The patients were classified into 2 groups based on volume status measured by the body composition monitor (BCM; Fresenius): an overhydrated group [OG; overhydration/extracellular water (OH/ECW) >15%] and a nonoverhydrated group (NOG; OH/ECW ≤15%).ResultsA total of 344 patients met the inclusion criteria. Of these, 252 patients (73.3%) were categorized into the OG and 92 patients (26.7%) into the NOG. Age- and sex-matching patients were selected with a rate of 2:1. Finally, 160 overhydrated patients and 80 nonoverhydrated patients were analyzed. Initial levels of hemoglobin and serum albumin were significantly lower in the OG. During follow-up, 43 patients from the OG and 7 patients from the NOG died (median follow-up duration, 24.0 months). The multivariate-adjusted all-cause mortality was significantly increased in the OG (odds ratio, 2.569; P = 0.033) and older patients (odds ratio, 1.072/y; P < 0.001). No significant difference of all-cause or disease-specific admission rate was observed between the 2 groups.ConclusionThe ratio of OH/ECW volume measured with body composition monitor is related to the overall survival of end-stage renal disorder patients who started maintenance hemodialysis

Initial serum sodium concentration determines the decrease in sodium level after terlipressin administration in patients with liver cirrhosis

BACKGROUND: Terlipressin, as a prodrug of vasopressin, has agonistic effects on the V1 receptor and partial agonistic effects on renal vasopressin V2 receptors. However, its effects on serum sodium concentration are controversial. METHODS: This study retrospectively investigated 127 patients with liver cirrhosis to examine the incidence and risk factors for the decrease in serum sodium level following terlipressin administration. RESULTS: Terlipressin was prescribed for bleeding control (99) and management of hepatorenal syndrome (28). Serum sodium level decreased from 134.0 ± 6.5 mmol/L to 130.4 ± 6.2 mmol/L during or after terlipressin treatment (P < 0.001) in all patients. In 45 patients (35.4%), the serum sodium concentration decreased by > 5 mmol/L, in 29 patients (22.8%); by 5–10 mmol/L; and in 16 patients (12.6%), by > 10 mmol/L. Five patients in the latter group showed neurological manifestations. In the univariate analysis, several factors including age, purpose of use, serum creatinine, and Model for End-Stage Liver Disease score, representing liver function, were significantly associated with the decrease in serum sodium after terlipressin administration. However, a multivariate analysis revealed that only initial sodium level was the most powerful predictor of terlipressin-induced reduction in serum sodium. CONCLUSION: An acute reduction in serum sodium concentration was not uncommon during terlipressin treatment, and the baseline serum sodium level was closely related to the reduction in serum sodium concentration

The C-terminal region of Bfl-1 sensitizes non-small cell lung cancer to gemcitabine-induced apoptosis by suppressing NF-κB activity and down-regulating Bfl-1

Gemcitabine is used to treat several cancers including lung cancer. However, tumor cells often escape gemcitabine-induced cell death via various mechanisms, which include modulating bcl-2 family members and NF-κB activation. We previously reported that the C-terminal region of Bfl-1 fused with GFP (BC) is sufficient to induce apoptosis in 293T cells. In the present study, we investigated the anti-tumor effect of combined BC gene therapy and gemcitabine chemotherapy in vitro and in vivo using non-small cell lung cancer cell lines and a xenograft model. Cell lines were resistant to low dose gemcitabine (4-40 ng/ml), which induced NF-κB activation and concomitant up-regulation of Bfl-1 (an NF-κB-regulated anti-apoptotic protein). BC induced the apoptosis of A549 and H157 cells with caspase-3 activation. Furthermore, co-treatment with BC and low dose gemcitabine synergistically and efficiently induced mitochondria-mediated apoptosis in these cells. When administered alone or with low dose gemcitabine, BC suppressed NF-κB activity, inhibited the nuclear translocation of p65/relA, and down-regulated Bfl-1 expression. Furthermore, direct suppression of Bfl-1 by RNA interference sensitized cells to gemcitabine-induced cell death, suggesting that Bfl-1 importantly regulates lung cancer cell sensitivity to gemcitabine. BC and gemcitabine co-treatment also showed a strong anti-tumor effect in a nude mouse/A549 xenograft model. These results suggest that lung cancer cells become resistant to gemcitabine via NF-κB activation and the subsequent overexpression of Bfl-1, and that BC, which has both pro-apoptotic and NF-κB inhibitory effects, could be harnessed as a gene therapy to complement gemcitabine chemotherapy in non-small cell lung cancer

Inappropriate antidiuretic hormone syndrome presenting as ectopic antidiuretic hormone-secreting gastric adenocarcinoma: a case report

INTRODUCTION: Although the syndrome of inappropriate antidiuretic hormone has connection with various malignant tumors, there are few reports associated with advanced gastric cancer. CASE PRESENTATION: We describe the case of a 63-year-old Korean male with inappropriate antidiuretic hormone syndrome due to an ectopic antidiuretic hormone-producing advanced gastric adenocarcinoma manifested with overt serum hypo-osmolar hyponatremia and high urinary sodium concentrations. His adrenal, thyroidal, and renal functioning were normal, and the hyponatremia improved following removal of the tumor. The cancer cells were immunostained and found to be positive for the antidiuretic hormone. To our knowledge, this is the first report of an antidiuretic hormone-secreting advanced gastric adenocarcinoma associated with the syndrome of inappropriate antidiuretic hormone, showing cancer cells immunostained for the antidiuretic hormone. CONCLUSIONS: Although a strong relationship between gastric cancer and the syndrome of inappropriate antidiuretic hormone remains to be established, we suggest that gastric cancer could be included as a differential diagnosis of cancer that is associated with the syndrome of antidiuretic hormone

Evaluation of the Biodegradation Efficiency of Four Various Types of Plastics by Pseudomonas aeruginosa Isolated from the Gut Extract of Superworms

Plastic waste worldwide is becoming a serious pollution problem for the planet. Various physical and chemical methods have been tested in attempts to remove plastic dumps. However, these have usually resulted in secondary pollution issues. Recently, the biodegradation of plastic by fungal and bacterial strains has been spotlighted as a promising solution to remove plastic wastes without generating secondary pollution. We have previously reported that a Pseudomonas aeruginosa strain isolated from the gut of a superworm is capable of biodegrading polystyrene (PS) and polyphenylene sulfide (PPS). Herein, we demonstrate the extraordinary biodegradative power of P. aeruginosa in efficiently depolymerizing four different types of plastics: PS, PPS, polyethylene (PE) and polypropylene (PP). We further compared biodegradation rates for these four plastic types and found that PE was biodegraded fastest, whereas the biodegradation of PP was the slowest. Moreover, the growth rates of P. aeruginosa were not always proportional to biodegradation rates, suggesting that the rate of bacterial growth could be influenced by the composition and properties of intermediate molecules produced during plastic biodegradation, and these may supply useful cellular precursors and energy. In conclusion, an initial screening system to select the most suitable bacterial strain to biodegrade certain types of plastic is particularly important and may be necessary to solve plastic waste problems both presently and in the future. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.1

real world efficacy and safety of nebivolol in korean patients with hypertension from the benefit korea study

Objective:The efficacy and safety of nebivolol in patients with hypertension is well established, but its effect in Asian patients with essential hypertension in the real world has not been studied.Methods:Adult South Korean patients with essential hypertension, with or without comorbidities, were

Sensitization rates of airborne pollen and mold in children

PurposeAeroallergens are important causative factors of allergic diseases. Previous studies on aeroallergen sensitization rates investigated patients groups that had visited pediatric allergy clinics. In contrast, we investigated sensitization rates in a general population group of elementary school to teenage students in Incheon, Jeju, and Ulsan.MethodsAfter obtaining parental consent, skin-prick tests were performed on 5,094 students between March and June 2010. Elementary school students were tested for 18 common aeroallergens, whereas middle and high school students were tested for 25 allergens. The 25 allergens included Dermatophagoides pteronyssinus, Dermatophagoides farinae, pollen (birch, alder, oak, Japanese cedar, pine, willow, elm, maple, Bermuda grass, timothy grass, rye grass, orchard grass, meadow grass, vernal grass, mugwort, Japanese hop, fat hen, ragweed, and plantain), and mold (Penicillatum, Aspergillus, Cladosporium, and Alternaria).ResultsThe sensitization rates in descending order were 25.79% (D. pteronyssinus), 18.66% (D. farinae), 6.20% (mugwort), and 4.07% (willow) in Incheon; 33.35% (D. pteronyssinus), 24.78% (D. farinae), 15.36% (Japanese cedar), and 7.33% (Alternaria) in Jeju; and 32.79% (D. pteronyssinus), 30.27% (D. farinae), 10.13% (alder), and 8.68% (birch) in Ulsan. The dust mite allergen showed the highest sensitization rate among the 3 regions. The sensitization rate of tree pollen was the highest in Ulsan, whereas that of Alternaria was the highest in Jeju. The ragweed sensitization rates were 0.99% in Incheon, 1.07% in Jeju, and 0.81% in Ulsan.ConclusionThe differences in sensitization rates were because of different regional environmental conditions and distinct surrounding biological species. Hence, subsequent nationwide studies are required