Lysosome-targeted ruthenium(II) complexes induce both apoptosis and autophagy in HeLa cells.

Ruthenium complexes with good biological properties have attracted increasing attention in recent decades. In this work, three ruthenium polypyridine complexes containing 5-fluorouracil derivatives as ligands, [Ru(bpy)2(L)]2+ (Ru1), [Ru(phen)2(L)]2+ (Ru2), [Ru(dip)2(L)]2+ (Ru3) (L = 1-((1,10-phenanthroline-5-amino) pentyl)-5-fluorouracil; bpy = 2,2'-bipyridine; phen =1,10-phenanthroline; dip = 4,7-diphenyl-1,10-phenanthroline), were synthesized and characterized. Based on in vitro cytotoxicity tests, Ru3 (IC50 = 7.35 ± 0.39 µM) showed the best anticancer activity among three compounds in the selected cell lines. It is worth noting that Ru3 also exerts less cytotoxicity on LO2 cell lines, with an IC50 value 5 times higher than that on HeLa cells, indicating its selective activity. Mechanism studies revealed that Ru3 can specifically target lysosomes and induce cell apoptosis in a caspase-dependent manner. Specifically, Ru3 can arrest cell cycle at the G0/G1 phase, increase the intracellular reactive oxygen species (ROS) level, and then damage DNA. In short, Ru3 can eventually cause cell death through the synergy of inducing apoptosis and autophagy, which was further proven by western blot assay results.

Visible-Light-Mediated Oxidative Cyclization of 2-Aminobenzyl Alcohols and Secondary Alcohols Enabled by an Organic Photocatalyst.

This paper describes a visible-light-mediated oxidative cyclization of 2-aminobenzyl alcohols and secondary alcohols to produce quinolines at room temperature. This photocatalytic method employed anthraquinone as an organic small-molecule catalyst and DMSO as an oxidant. According to this present procedure, a series of quinolines were prepared in satisfactory yields.

Cyclometalated iridium(III) complexes as mitochondria-targeted anticancer and antibacterial agents to induce both autophagy and apoptosis.

Mitochondrial damage will hinder the energy production of cells and produce excessive ROS (reactive oxygen species), resulting in cell death through autophagy or apoptosis. In this paper, four cyclometalated iridium(III) complexes (Ir1: [Ir(piq)2L]PF6; Ir2: [Ir(bzq)2L]PF6; Ir3: [Ir(dfppy)2L]PF6; Ir4: [Ir(thpy)2L]PF6; piq = 1-phenylisoquinoline; bzq = benzo[h]quinoline; dfppy = 2-(2,4-difluorophenyl)pyridine;thpy = 2-(2-thienyl)pyridine; L = 1,10-phenanthroline-5-amine) were synthesized and characterized. Cytotoxicity tests show that these complexes have excellent cytotoxicity to cancer cells, and mechanism studies indicatethat these complexes can specifically target mitochondria. Complexes Ir1 and Ir2 can damage the function of mitochondria, subsequently increasing intracellular levels of ROS, decreasing MMP (mitochondrial membrane potential), and interfering with ATP energy production, which leads to autophagy and apoptosis. Furthermore, autophagy induced by Ir1 and Ir2 can promote cell death in coordination with apoptosis. Surprisingly, these four complexes also showed moderate antibacterial activity to S. aureusand P. aeruginosa.

Mitochondria-targeted Re(I) complexes bearing guanidinium as ligands and their anticancer activity.

As the "powerhouse" of a cell, mitochondria maintain energy homeostasis, synthesize ATP via oxidative phosphorylation, generate ROS signaling molecules, and modulate cell apoptosis. Herein, three Re(I) complexes bearing guanidinium derivatives have been synthesized and characterized. All of these complexes exhibit moderate anticancer activity in HepG2, HeLa, MCF-7, and A549 cancer cells. Mechanism studies indicate that complex 3, [Re(CO)3(L)(Im)](PF6)2, can selectively localize in the mitochondria and induce cancer cell death through mitochondria-associated pathways. In addition, complex 3 can effectively depress the ability of cell migration, cell invasion, and colony formation.

Guanidine-modified cyclometalated iridium(III) complexes for mitochondria-targeted imaging and photodynamic therapy.

PDT is a well-established therapeutic modality for many types of cancer. Photoluminescent cyclometalated iridium(III) complexes are one of the most commonly used classes of organometallic compounds with potential beneficial applications in bioimaging and as promising anticancer agents. In the present study, three new cyclometalated iridium(III) complexes (Ir1-Ir3) containing guanidinium ligands were found to exert excellent cytotoxic effects on different types of cancer cells upon light irradiation at 425 nm. Notably, Ir1 conferred almost no dark toxicity (IC50 > 100 µM) to HepG2 cells, but the value decreased by 387-fold to 0.36 µM following 10 min of light irradiation (425 nm). Further mechanistic investigation revealed that complex Ir1 could induce apoptosis via the activation of reactive oxygen species (ROS)-mediated mitochondrial signaling pathways in the presence or absence of light irradiation. In vivo studies demonstrated that Ir1 significantly inhibited tumor growth in HepG2 xenograft-bearing mice under light irradiation at 425 nm. Taken together, these findings indicate that designing PDT-based Ir(III) complexes may hold a great deal of promise for anticancer drug development.

Comparison and reflections on the training of rehabilitation physicians in Taiwan and Mainland China / 中华医学教育探索杂志

Rehabilitation physician training is an important part of the development of rehabilitation medicine.Rehabilitation physician education in Taiwan has a complete and standardized training system,and rehabilitation physician training in mainland China is mainly achieved through standardized residency training.This article compares the differences in training processes for rehabilitation physicians in education in medical colleges and universities,residency training,and specialist training between Taiwan and mainland China.The results show that rehabilitation physician training in Taiwan is rigorous and orderly,with reasonable contents,clear objectives,strong specialty,and standardized assessment,while in mainland China,rehabilitation physicians in mainland China have insufficient training time,and there is a lack of detailed training plan and unified assessment standards.Rehabilitation physician training in mainland China needs to learn from advanced experience,further reform the training process,improve the operability of the overall education program,and perfect the training system of rehabilitation physicians.

Acute Reversible Charles Bonnet Syndrome Following Eye Patch Placement.

Charles Bonnet syndrome (CBS) is characterised by recurrent vivid visual hallucinations in the presence of normal cognition. We present a case of CBS secondary to eye patching following Pars Plana Vitrectomy with an unusually acute onset in a 48-year-old woman. She presented with formed visual hallucinations that started less than 30 min after patching of her left eye. The patch was removed after 2 d, and these hallucinations persisted 2 d following eye patch removal. It is important that the ophthalmic surgeon be aware of the potential for development of CBS and offer appropriate referral and reassurance should it occur.

Cognitive functioning in schizophrenia with or without diabetes / 中南大学学报(医学版)

Objective To determine the influence of schizophrenia patients with diabetes on cognitive function.Methods Altogether 78 schizophrenia patients with diabetes and 118 patients with schizophrenia were enrolled and Negative and Positive Syndrome Scale,Wechsler Memory Scale-Revised Visual Reproduction Test,Wechsler Adult Intelligence Scale-Revised Digit Symbol Test,Computerized Wisconsin Card Sorting Test,Trail Making Tests,Part A and B,and Wechsler Adult Intelligence Scale-Revised Digit Span Test were used to assess the clinical syndrome and to test the cognitive function.ResultsImpairment of Processing Speed,Attention/Working Memory,Executive Functioning and Visual Memory in schizophrenia patients with diabetes was significantly poorer than that of the schizophrenia patients ( all P ＜ 0.05 ).WAIS-R Digit Symbol Test score and Trail Making Test A and B scores were associated with diabetes duration and age at diabetes onset (P ＜0.01 ).Conclusion The impairment of cognitive function in schizophrenia patients with diabetes is severer than schizophrenia patients,suggesting that the prevention and management of diabetes may improve cognitive outcome in schizophrenia patients.

Improvement of dermal needle and body acupuncture on pain due to lumbar strain and hyperplastic spondylitis / 中国组织工程研究

BACKGROUND:Pain is the extremely common disease in clinic. At present, acupuncture provides good therapeutic effect on it. But, there are many methods in acupuncture with various advantages individually.To understand the differences in therapeutic effects on pain with various needling techniques is significant in clinic. In 1999, the relevant observation was carried on in the demand of Ecuadorian Medical Pain Association.OBJECTIVE: To observe the differences in therapeutic effects on pain with various needling techniques.DESIGN: Randomized controlled observation was designed.SETTING: Department of Pain, Hospital General de las FF. AA. Quito, Ecuador, Department of Traditional Chinese Medicine and 1st Department of Surgery, General Hospital of Chengdu MilitaryArea Command of Chinese PLA.PARTICIPANTS: Totally 360 cases of lumber strain and hyperplastic spondylitis were selected in Department of Pain, Clinic of Ecuadorian 3rd Military General Hospital from May 1999 to November 2000, in which,179 cases were lumber strain and 181 cases were hyperplastic spondylitis.The groups were randomized in two kinds of diseases, named for lumber strain, dermal-needling group (88 cases) and body-acupuncture group (91cases); for hyperplastic spondylitis, dermal-needling group (92 cases) and body-acupuncture group (89 cases).METHODS: Dermal needling and body acupuncture were used to treat the diseases respectively and the symptom changes were observed before and after treatment simultaneously. The treatment was given once every two days. 5 treatments made one basic course for lumber strain and 7 treatments for hyperplastic spondylitis. The treating results were evaluated according to Budzynski grading criteria on pain. MEPS statistical software was used for statistical management of data.MAIN OUTCOME MEASURES: Pain relieving before and after treatment with dermal needling and body acupuncture for lumber strain and hyperplastic spondylitis was evaluated. Correlative analysis on therapeutic effects and course of treatment for different diseases with same therapy and on same disease with different therapies were carried on.RFSULTS: Altogether 366 cases were observed and 6 of them were excluded. Totally, 360 cases finished the experiment. ① The severity was alleviated in pain grading after treatment with dermal needling and body acupuncture compared with that before the treatment (P ＜ 0.01). ② In treatment of lumber strain and hyperplastic spondylitis with dermal needling, the therapeutic effects on lumber strain were more remarkable (P ＜ 0.01). The therapeutic effects of dermal needling on lumber strain were superior to that of body acupuncture (P ＞ 0.05). ③ The therapeutic effects of body acupuncture group on pain of Ⅰ grade in hyperplastic spondylitis were remarkably better than that of dermal needling group,but the significant difference in the total therapeutic effects of two techniques did not present (P ＞ 0.05). ④ When pain grading was reduced by 1 level in two groups, the average times of treatment in dermal needling group were less than that in body-acupuncture group (P ＜ 0.05).CONCLUSION: Good therapeutic effects of dermal needling and body acupuncture are achieved for both hyperplastic spondylitis and lumber strain,in which, the therapeutic effects of dermal needling are remarkable on injury of soft tissue and achieved swiftly; body acupuncture improves pain in hyperplastic spondylitis more radically compared with dermal needling.