Synthesis, in vitro antitumor evaluation and structure activity relationship of heptacoordinated amino-bis(Phenolato) Ti(IV) complexes stabilized by 2,6-dipicolinic acid.

Eighteen novel Ti(IV) complexes stabilized by different chelating amino-bis(phenolato) (ONNO, ONON, ONOO) ligands and 2,6-dipicolinic acid as a second chelator were synthesized with isolated yields ranging from 79 to 93%. Complexes were characterized by 1H and 13C-NMR spectroscopy, as well as by HRMS and X-Ray diffraction analysis. The good to excellent aqueous stability of these Ti(IV) complexes can be modulated by the substitutions on the 2-position of the phenolato ligands. Most of the synthesized Ti(IV) complexes demonstrated potent inhibitory activity against Hela S3 and Hep G2 tumor cells. Among them, the naphthalenyl based Salan type 2j, 2-picolylamine based [ONON] type 2n and N-(2-hydroxyethyl) based [ONOO] type 2p demonstrated up to 40 folds enhanced cytotoxicity compared to cisplatin together with a significantly reduced activity against healthy AML12 cells. The three Ti(IV) complexes exhibited fast cellular uptake by Hela S3 cells and induced almost exclusively apoptosis. 2j could trigger higher level of ROS generation than 2p and 2n.

Hyaluronic acid/dextran-based polymeric micelles co-delivering ursolic acid and doxorubicin to mitochondria for potentiating chemotherapy in MDR cancer.

Cancer multidrug resistance (MDR) dramatically hindered the efficiency of standard chemotherapy. Mitochondria are highly involved in the occurrence and development of MDR; thus, inducing its malfunction will be an appealing strategy to treat MDR tumors. In this paper, a natural polysaccharides-based nanoplatform (TDTD@UA/HA micelles) with cell and mitochondria dual-targeting ability was facilely fabricated to co-deliver ursolic acid (UA) and doxorubicin (DOX) for combinatorial MDR therapy. TDTD@UA/HA micelles featured a spherical morphology, narrow size distribution (∼140 nm), as well as favorable drug co-loading capacity (DOX: 8.41 %, UA: 9.06 %). After hyaluronic acid (HA)-mediated endocytosis, the lysosomal hyaluronidase promoted the degradation of HA layer and then the positive triphenylphosphine groups were exposed, which significantly enhanced the mitochondria-accumulation of nano micelles. Subsequently, DOX and UA were specifically released into mitochondria under the trigger of endogenous reactive oxygen species (ROS), followed by severe mitochondrial destruction through generating ROS, exhausting mitochondrial membrane potential, and blocking energy supply, etc.; ultimately contributing to the susceptibility restoration of MCF-7/ADR cells to chemotherapeutic agents. Importantly, TDTD@UA/HA micelles performed potent anticancer efficacy without distinct toxicity on the MDR tumor-bearing nude mice model. Overall, the versatile nanomedicine represented a new therapeutic paradigm and held great promise in overcoming MDR-related cancer.

Long-term trends in incidence, mortality and burden of liver cancer due to specific etiologies in Hubei Province.

Liver cancer, a chronic non-communicable disease, represents a serious public health problem. Long-term trends in the burden of liver cancer disease are heterogeneous across regions. Incidence and mortality of liver cancer, based on the Global Burden of Disease, were collected from the Chinese Centre for Disease Control and Prevention. Age-period-cohort model was utilized to reveal the secular trends and estimate the age, period and cohort effects on primary liver cancer due to specific etiologies. Both the age-standardized incidence and mortality rate of liver cancer in Hubei province were on the rise, although there were discrepancies between gender groups. From age-period-cohort analysis, both incidence and mortality of liver cancer due to Hepatitis B virus were the highest in all age groups. The incidence of all liver cancer groups increased with time period in males, while this upward trend was observed in females only in liver cancer due to alcohol use group. Cohort effects indicated the disease burden of liver cancer decreased with birth cohorts. Local drifts showed that the incidence of liver cancer due to specific etiologies was increasing in the age group of males between 40 and 75 years old. The impact of an aging population will continue in Hubei Province. the disease burden of liver cancer will continue to increase, and personalized prevention policies must be adopted to address these changes.

Anti-tumoral Titanium(IV) Complexes Stabilized with Phenolato Ligands and Structure-Activity Relationship.

Titanocene dichloride and budotitane have opened a new chapter in medicinal chemistry of titanium(IV) complexes being novel non-platinum antitumor metallic agents. Numerous efforts have led to the discovery of the diamino bis-phenolato titanium(IV) complexes. Among which, the [ONNO] and [ONON] type ligands namely Salan, Salen and Salalen coordinated titanium(IV) alkoxyl complexes have demonstrated significantly enhanced aqueous stability, their in vitro and in vivo antitumor efficacy, mechanism of action, structure-activity relationships and combined tumor therapy have been intensively investigated. Replacement of the labile alkoxyls with a second chelator resulted in structural rigid titanium(IV) complexes, which showed exceedingly good aqueous stability and potent antitumor activity both in vitro and in vivo. The unique ligand system successfully allowed the access of isotopic [45Ti]Titanium(IV) complexes, post-synthetic modification, facile synthetic protocols and antitumor congeneric zirconium(IV) and hafnium(IV) complexes. This review presents recent research progress in the field of antitumor group 4 metal complexes stabilized with phenolato ligands; especially their structure-activity relationships are summarized.

Ambient particulate matter, a novel factor hindering life spans of HIV/AIDS patients: Evidence from a ten-year cohort study in Hubei, China.

BACKGROUND: The life spans of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients have been extended in the era of antiretroviral therapy. However, few studies have considered the influence of the environment on the life expectancy of people living with HIV/AIDS. Several studies have investigated mortality and air pollution associations, but the evidence for associations between long-term exposure to particulate matter (PM) and mortality among HIV/AIDS patients remains extremely sparse. METHODS: We conceived a dynamic cohort study by enrolling people with HIV/AIDS from 103 counties in Hubei province, China from 2010 to 2019, with 23,809 persons and 78,457.2 person-years of follow-up. The county-level annual concentrations of PM2.5 and PM10 were extracted from the ChinaHighAirPollutants dataset. Cox proportional hazards models with time-varying exposures were conducted to assess the associations between PM and mortality. RESULTS: Per 1 µg/m3 increased in PM2.5 and PM10 would elevate 0.69 % (95 % CIs: 0.39, 1.00) and 0.39 % (95 % CIs: 0.18, 0.59) risk of all-cause deaths (ACD) and 1.65 % (95 % CIs: 1.14, 2.17) and 0.90 % (95 % CIs: 0.56, 1.24) of AIDS-related deaths (ARD), respectively. Significantly stronger associations of PM-ARD were found in patients aged over 60 years old, with corresponding excess risk of 2.66 % (95 % CIs: 1.76, 3.58) for PM2.5 and 1.62 (95 % CIs: 1.01, 2.23) for PM10. CONCLUSIONS: This study added to the existing evidence that long-term exposure to ambient PM adversely affects the life spans of HIV/AIDS patients. Hence, public health departments should take proactive measures to prevent further life loss and promote survival among those living with HIV/AIDS.

Trends in the global burden of oral cancer joint with attributable risk factors: Results from the global burden of disease study 2019.

OBJECTIVES: To investigate the characteristics of risk factors for oral cancer and the disease burden they caused. MATERIALS AND METHODS: Data from GBD2019, where the EAPC was calculated to understand mortality trends and the APC model was used for the analysis of age characteristics. RESULTS: Overall oral cancer mortality showed a promising downward trend [EAPC = -0.05 (-0.08 to -0.02)]. Oral cancer mortality attributable to tobacco chewing alone showed a significant upward trend [EAPC = 0.44 (0.36-0.52)]. Males are the majority of oral cancer deaths, while the disease burden of oral cancer in females could be largely attributable to chewing tobacco. The age of death attributable to each risk factor for oral cancer is concentrated between 45 and 74 years. Mortality for oral cancer caused by alcohol and smokeless tobacco was increasing in younger age groups (age < 45), and this trend was more pronounced in middle and middle-high SDI areas. The disease burden of oral cancer in high SDI regions was mainly attributed to alcohol consumption, while in middle and lower SDI regions it was mainly attributed to tobacco. CONCLUSION: Smokeless tobacco proved a critical factor in the significant regional distribution of oral cancer. Oral cancer is on the increase in younger age groups. According to the characteristics of the distribution of risk factors, in traditionally high-incidence regions, such as India and Pakistan, oral cancer kept the highest ASDR, but was not experiencing the fastest growth rate. Additionally, it was oral cancer in middle SDI regions that needs more attention.

Long-term exposure to air pollution might decrease bone mineral density T-score and increase the prevalence of osteoporosis in Hubei province: evidence from China Osteoporosis Prevalence Study.

We hypothesized that air pollution could cause oxidative damage and inflammation in the human body, which was linked to bone loss. Our result showed that long-term exposure to air pollution might decrease bone mineral density (BMD) T-score and increase the prevalence of osteoporosis in Hubei province. INTRODUCTION: Osteoporosis is becoming an increasingly serious public health problem with the advent of global aging. Long-term exposure to air pollution has been linked to multitudinous adverse health outcomes, but evidence is still relatively limited and inconsistent for BMD T-score and osteoporosis. This study aimed at exploring the associations between long-term exposure to air pollution and BMD T-score and osteoporosis. METHODS: The Hubei part of the China Osteoporosis Prevalence Study was extracted. Data on air pollutants were collected by the national air quality real-time release platform of China Environmental Monitoring Station. Linear mixed models and multilevel logistic regression analyses were performed to assess the associations between air pollution and BMD T-score and osteoporosis, respectively. Subgroup analyses were conducted to identify vulnerable populations. RESULTS: A total of 1845 participants were included in this cross-section study. Per 10 ug/m3 increase in PM2.5 and SO2 were associated with 0.20 (95% CI: 0.04, 0.36) and 0.31 (95% CI: 0.11, 0.51) decrease in BMD T-score of the neck of femur, respectively. Per 10 ug/m3 increase in CO was linked with 0.03 (95% CI: 0.02, 0.05) decrease in BMD T-score of the total hip. Per 1 ug/m3 increase in PM2.5 was associated with 5% increase in the prevalence of osteoporosis in all participants. In general, the higher concentrations of PM2.5 with the more adverse effect on osteoporosis (P for trend = 0.01). The impact of PM2.5 on osteoporosis in males was higher than that in females [1.29, 95% CI (1.11, 1.50) vs 1.01, 95% CI (0.95, 1.07)]. Per 1 ug/m3 increase in PM10 corresponded with 4% elevation in the risks of osteoporosis in rural population. The ORs (95% CI) for the association of osteoporosis and NO2 in ever/current smoking and drinking population were 1.07 (1.01, 1.13) and 1.05 (1.00, 1.09), respectively. SO2 had a statistically significant positive effect on people with comorbidity [OR = 1.10, (95% CI: 1.00 to 1.21)], while none in people without comorbidity [OR = 0.96, (95% CI: 0.88 to 1.05)]. CONCLUSION: Our study provided evidence that long-term exposure to PM2.5 was linked with the decreased BMD T-score and increased risk of osteoporosis among all participants. The adverse impacts of PM2.5, PM10, and NO2 were larger in males than in females. People having comorbidity, living in rural areas, and current/ever smoking or drinking were more vulnerable to air pollution. Public health departments should consider air pollution to formulate better preventive measures for osteoporosis.

Effect of Vacuum Heat Treatment on the Element Diffusion Behavior and Corrosion Resistance of Al2O3-3wt.%TiO2 Coating of Q235 Steel.

In this study, we address the effect of vacuum heat treatment on the morphology of Al2O3-3wt.%TiO2 coating, element diffusion behavior, coating hardness, and corrosion resistance. The pores, cracks, and non-liquefied particles on the as-heat treated coating surface of the vacuum-heat-treated coating were observed and compared with the as-sprayed coating using a scanning electron microscope. The diffusion behavior of the elements in the coating was demonstrated by using a line scanning of a cross-section of the coating. Hardness and corrosion-resistance test results were used to judge the effect of a vacuum heat treatment on the coating. The research results show that compared with atmospheric heat treatment, the vacuum heat treatment had less effect on the pores, cracks, and non-liquefied particles on the surface of the coating. However, in the absence of new oxide formation, the pores and cracks in the cross-section of the coating were significantly improved by the vacuum heat treatment. The surface hardness and corrosion resistance of the coating were significantly improved. The crack defects were eliminated, and the uniformity of TiO2 distribution was improved, which are the main factors that improved the coating performance after vacuum heat treatment. The combination of the coating and the substrate is strengthened, and an Al2O3 and TiO2 interdiffusion zone is formed when the coating undergoes vacuum heat treatment, which is the main mechanism improving the performance of the AT3 coating.