Rhodium(III)-Picolinamide Complexes Act as Anticancer and Antimetastasis Agents via Inducing Apoptosis and Autophagy.

As a continuation of our endeavors in discovering metal-based drugs with cytotoxic and antimetastatic activities, herein, we reported the syntheses of 11 new rhodium(III)-picolinamide complexes and the exploration of their potential anticancer activities. These Rh(III) complexes showed high antiproliferative activity against the tested cancer cell lines in vitro. The mechanism study indicated that Rh1 ([Rh(3a)(CH3CN)Cl2]) and Rh2 ([Rh(3b)(CH3CN)Cl2]) inhibited cell proliferation by multiple modes of action via cell cycle arrest, apoptosis, and autophagy and inhibited cell metastasis via FAK-regulated integrin ß1-mediated suppression of EGFR expression. Furthermore, Rh1 and Rh2 significantly inhibited bladder cancer growth and breast cancer metastasis in a xenograft model. These rhodium(III) complexes could be developed as potential anticancer agents with antitumor growth and antimetastasis activity.

Potent Zinc(II)-Based Immunogenic Cell Death Inducer Triggered by ROS-Mediated ERS and Mitochondrial Ca2+ Overload.

Zn1 and Zn2 are Zn-based complexes that activate the immunogenic cell death (ICD) effect by Ca2+-mediated endoplasmic reticulum stress (ERS) and mitochondrial dysfunction. Compared with Zn1, Zn2 effectively caused reactive oxidative species (ROS) overproduction in the early phase, leading to ERS response. Severe ERS caused the release of Ca2+ from ER to cytoplasm and further to mitochondria. Excessive Ca2+ in mitochondria triggered mitochondrial dysfunction. The damage-associated molecular patterns (DAMPs) of CRT, HMGB1, and ATP occurred in T-24 cells exposed to Zn1 and Zn2. The vaccination assay demonstrated that Zn1 and Zn2 efficiently suppressed the growth of distant tumors. The elevated CD8+ cytotoxic T cells and decreased Foxp3+ cells in vaccinated mice supported our conclusion. Moreover, Zn1 and Zn2 improved the survival rate of mice compared with oxaliplatin. Collectively, our findings provided a new design strategy for a zinc-based ICD inducer via ROS-induced ERS and mitochondrial Ca2+ overload.

Copper(II) complex enhanced chemodynamic therapy through GSH depletion and autophagy flow blockade.

Three copper(II) complexes C1-C3 were synthesized and fully characterized as chemodynamic therapy (CDT) anticancer agents. C1-C3 showed greater cytotoxicity than their ligands toward SK-OV-3 and T24 cells. Particularly, C2 showed high cytotoxicity toward T24 cells and low cytotoxicity toward normal human HL-7702 and WI-38 cells. Mechanistic studies demonstrated that C2 oxidized GSH to GSSG and produced ˙OH, which induced mitochondrial dysfunction and ER stress, finally leading to apoptosis of T24 cells. In addition, C2 inhibited autophagy by blocking autophagy flow, thereby closing the self-protection pathway of oxidative stress to enhance CDT. Importantly, C2 significantly inhibited T24 tumor growth with 57.1% inhibition in a mouse xenograft model. C2 is a promising lead as a potential CDT anticancer agent.

An empirical study on the effect of tennis sports on visual health of primary school students / 中国学校卫生

Objective@#To explore the impact of tennis on the visual health of primary school students, so as to provide a basis for myopia prevention.@*Methods@#In September 2021, a total of 202 third grade students from Fengtai Affiliated School of Renmin University of China in Beijing were recruited, with 75 students in the intervention group and 127 students in the control group. In addition to attending the same cultural and physical education courses, the intervention group added a tennis course twice a week and tested their vision before the intervention (September 2021), middle (January 2022) and later (June 2022). Data collected at different time points in the two groups were analyzed by using independent sample t-test for comparison between blocks, and single factor repeated measurement ANOVA for analysis of time point factors.@*Results@#After intervention, among male subjects, the average visual acuity of the left and right eyes in the intervention group were higher than that in the control group at the third visual acuity test (left eye:5.00±0.13,4.88±0.29, right eye:5.00±0.12,4.88±0.30, t =2.33, 2.36, P <0.05). Among female subjects, the second visual acuity test (left eye:5.03±0.17, 4.86±0.21, right eye:5.03±0.15, 4.85±0.23) and the third visual acuity test (left eye:4.97±0.13, 4.81±0.23, right eye:4.97±0.14, 4.82±0.24) showed that the average visual acuity of the left and right eyes in the intervention group were higher than that in the control group among females (second: t =3.84, 3.87, third: t =3.70, 3.46, P < 0.01 ). After intervention, the detection rate of visual impairment in both males and females control groups increased at three tests, with statistically significant differences ( χ 2=17.86, 34.77, P <0.01). In the first visual acuity test, there was no statistically significant difference in the detection rate of visual impairment between the control group and the intervention group for both males and females ( χ 2=0.01, 0.10, P >0.05). The third visual impairment detection rate of males in the intervention group was lower than that of the control group (20.00% vs 45.45%), while the second and third visual impairment detection rates of female students in the intervention group were lower than those of the control group (22.86% vs 54.00%; 28.57% vs 70.00%) ( χ 2=7.34, 8.24, 14.18, P < 0.01).@*Conclusions@#Tennis can alleviate and prevent the occurrence of myopia in primary school students to a certain extent. Sports such as tennis should be actively promoted to protect the visual health of primary school students.

Copper(II) Complexes of Halogenated Quinoline Schiff Base Derivatives Enabled Cancer Therapy through Glutathione-Assisted Chemodynamic Therapy and Inhibition of Autophagy Flux.

Twelve new complexes Cu(L1)2-Cu(L12)2 were designed and synthesized to improve their chemotherapeutic properties. They showed considerable antiproliferative activity against T24 cancer cells but lower cytotoxicity to human normal cells HL-7702 and WI-38. A mechanism study indicated that Cu(L4)2 and Cu(L10)2 were reduced to Fenton-like Cu+ by glutathione depletion, and the resulting Cu+ catalyzed the generation of highly toxic hydroxyl radicals from excess H2O2. Simultaneously, Cu(L4)2 and Cu(L10)2 could decrease the catalase activity to restrain H2O2 transfer to H2O for enhanced chemodynamic therapy (CDT). These induced mitochondrial dysfunctions and endoplasmic reticulum stress to induce T24 cell apoptosis. In addition, Cu(L4)2 and Cu(L10)2 inhibited autophagy flux to promote cell apoptosis. Cu(L4)2 and Cu(L10)2 demonstrated strong tumor inhibition ability in the T24 xenograft model. Moreover, Cu(L10)2 showed higher antitumor activity and a better safety profile than the CDT agent Cu1. Cu(L10)2 exhibited excellent pharmacokinetic properties. Collectively, Cu(L4)2 and Cu(L10)2 could be developed as potential CDT candidates for cancer treatment.