The anion fac-[Fe(CO)3I3]− undergoes rapid decomposition to release CO and involve iodine radical. The CO-release can be tuned by its cations. The radical causes severe cytotoxicity which may endow the anion a great potential as an anticancer drug.

Four iron(II) carbonyl complexes, fac-[Fe (CO) 3 X 2 (py)] (X = I − , 1 and Br − , 3), fac-[{Fe (CO) 3 X 2 } 2 (bipy)] (X = I − , 2 and Br − , 4), were facilely synthesized by reacting cis-[Fe (CO) 4 X 2 ] (X = I − , Br −) with pyridine (py) and 4,4 0-dipyridine (bipy) ligands, respectively, in good yields (70%85%). These complexes were fully characterized, and the structures of Complexes 2 and 3 were crystallographically analyzed. In dimethyl sulfoxide, they decomposed rapidly to release carbon monoxide (CO), and in methanol, they showed better stability which allowed kinetically analyzing their decomposing behaviors. The selfdecomposing in methanol fitted first-order kinetics with a half-time ranging from several minutes to 1 h. Our results suggested that the ligand with great conjugation (bipy) and strong electron-donating capability (iodide) could stabilize the iron(II) carbonyl complexes. The decomposition of the iodo complexes (1 and 2) involved the production of iodine radicals. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assessments revealed that the efficacy against human bladder carcinoma cell line (RT112) is in the following trend: 1 > 2 > 3 > 4. The relatively strong efficacy of Complexes 1 and 2 is mainly contributed to the in situ generated iodine radicals. The combination of the cytotoxicity of the in situ generated radicals with the anticancer activity of CO as reported in literatures may lead to developing novel anticancer drugs with enhanced efficacy. K E Y W O R D S anticancer activity, carbon monoxide release and kinetics, iodine radical, iron carbonyl compounds, solvolysis Zhuming Guo and Jing Jin contributed equally to this work.

Non-typhoidal Salmonella (NTS) typically causes self-limiting diarrheal disease but may occasionally lead to invasive infection. This study investigated the epidemiology and antimicrobial resistance of children with NTS infection between 2012 and 2019. We retrospectively analyzed pediatric patients with NTS infections, confirmed by positive cultures, in a tertiary medical center in Taiwan in 2012 and 2019. Clinical features and laboratory data of the patients were collected. Changes in the serogroup category and antimicrobial resistance were also analyzed. Of the total 797 isolates collected, 55 had NTS bacteremia. Compared with the resistance rates in 2012, the rates of resistances to third-generation cephalosporin and ciprofloxacin were significantly higher in 2019 (4.1% vs 14.3%, P < 0.001; 1.9% vs 28.6%, P < 0.001), especially in groups B, D, and E. Moreover, we observed significantly higher antimicrobial resistance (25.3%) to third-generation cephalosporin, and approximately half the NTS isolates in the infant group were multidrug resistant – a higher rate than those of other age groups in 2019. Invasive NTS often presented with a longer fever duration, lower hemoglobin level and with no elevated C-reactive protein (P < 0.05). Non-invasive NTS isolates in 2019 were significantly more resistant to ceftriaxone (P < 0.001) and ciprofloxacin (P < 0.001) than those in 2012. The antimicrobial resistance of NTS in children has increased progressively in the past decade, and different serogroups exhibited different resistance patterns. During this period, infants showed the highest risk to get a third-generation cephalosporin-resistant NTS infection. The high rates of antimicrobial resistance among children with NTS in Taiwan merit continual surveillance.

No abstract

Mitogen activated protein kinase phosphatase-1 (MKP-1) has been revealed to be overexpressed in bladder cancer, particularly in non-muscle invasive bladder cancer. MKP-1 may also be associated with chemotherapy resistance. However, the underlying mechanism is yet to be elucidated. The current study investigated the expression of MKP-1 by performing immunohistochemistry in surgically resected specimens obtained from primary and recurrent patients with bladder cancer. The results revealed that MKP-1 expression increased in recurrent patients. Additionally, a 3D model of the human bladder cancer cell line, RT112, was established to determine the role of MKP-1 in drug resistance. The results demonstrated that MKP-1 overexpression protected bladder cancer cells against cell death. Contrarily, MKP-1 knockdown was revealed to sensitize cells to death. In addition, the application of MAPK inhibitors effectively increased RT112 cell sensitivity to pirarubicin. In conclusion, the results of the current study indicated that MKP-1 treatment resulted in bladder cancer cell chemoresistance via JNK, ERK and p38 pathways. MKP-1 may also serve as a potential therapeutic target for chemoresistance in patients with bladder cancer.

Melanoma is a common type of cutaneous tumor, but current drug treatments do not satisfy clinical practice requirements. At present, mitochondrial uncoupling is an effective antitumor treatment. Triclosan, a common antimicrobial, also acts as a mitochondrial uncoupler. The aims of the present study were to investigate the effects of triclosan on melanoma cells and the underlying mechanisms. Mitochondrial membrane potential (MMP), mitochondrial morphology, mitochondrial reactive oxygen species (mito-ROS), intracellular superoxide anion and [Ca 2+ ] i were measured using confocal microscopy. It was found that triclosan application was associated with decreased A375 cell viability in a dose-and time-dependent manner and these effects may have cell specificity. Furthermore, triclosan induced MMP depolarization, ATP content decrease, mito-ROS and [Ca 2+ ] i level increases, excessive mitochondrial fission, AMP-activated protein kinase (AMPK) activation and STAT3 inhibition. Moreover, these aforementioned effects were reversed by acetylcysteine treatment. Triclosan acute treatment also induced mitochondrial swelling, which was reversed after AMPK-knockdown associated with [Ca 2+ ] i overload. Cell death was caused by STAT3 inhibition but not AMPK activation. Moreover, triclosan induced autophagy via the ROS/AMPK/p62/microtubule-associated protein 1A/1B-light chain 3 (LC3) signaling pathway, which may serve a role in feedback protection. Collectively, the present results suggested that triclosan increased mito-ROS production in melanoma cells, following induced cell death via the STAT3/Bcl-2 pathway and autophagy via the AMPK/p62/LC3 pathway.

Rosin derivatives such as dehydroabietic acid and dehydroabietic amine belonging to diterpenoids have similar structure with androgen that inhibited the occurrence and development of prostate cancer. In this study, the effects and possible mechanism of the rosin derivative IDOAMP on prostate cancer were investigated. Our results showed that IDOAMP effectively inhibited cell viabilities of LNCaP, PC3, and DU145 prostate cells. After the treatment with IDOAMP, the levels of cleaved-PARP, LC3BII/I, and HMGB1 were increased, whereas the expression of GPX4 was decreased. Interestingly, cell viability was reversed by the supplements of necrostatin-1 and necrosulfonamide. Meanwhile, the IDOAMP downregulated the expression of human Aurora kinase A that was overexpressed in prostate cancer. In addition, co-IP results showed that IDOAMP inhibited the binding of Aurora kinase A to the receptor-interacting serine/threonine kinase 1 (RIPK1) and RIPK3. However, the binding of RIPK1 to FADD, RIPK3, or MLKL was significantly promoted. Further studies showed that the phosphorylation levels of RIPK1, RIPK, and MLKL were increased in a concentration-dependent manner. In in vivo model, IDOAMP reduced the tumor volumes and weights. In conclusion, IDOAMP directly inhibited Aurora kinase A and promoted the RIPK1/RIPK3/MLKL necrosome activation to inhibit the prostate cancer.

No abstract