Global Burden and Inequality of Dental Caries, 1990 to 2019.

Previous studies on the global burden of caries primarily focused on simple descriptive statistics. We aimed to characterize the burden, trends, and inequalities of untreated caries of permanent and deciduous teeth from 1990 to 2019 at the global, regional, and national levels through an array of analytic approaches. Estimates of caries burden were extracted from the Global Burden of Disease Study 2019. Decomposition analysis was performed to examine the contribution of demographic and epidemiologic factors to the evolving number of prevalent caries cases. In portfolio analysis, the caries epidemiologic profile of each country was categorized by terciles of age-standardized prevalence in 2019 and average annual percentage change from 1990 to 2019. Sociodemographic attribution analysis was performed to reveal the scale of inequality in burden of caries. Age-standardized prevalence of caries in permanent and deciduous teeth decreased 3.6% (95% uncertainty interval, 2.6% to 4.5%) and 3.0% (1.3% to 4.9%), respectively. Population growth was the key driver of the changes in the number of caries cases, especially in sub-Saharan Africa (percentage contribution: 126.6%, permanent teeth; 103.0%, deciduous teeth). Caries prevalence in the permanent dentition was lower in more developed countries, whereas a reverse trend was noted in the deciduous dentition, except for the highest sociodemographic quintile where caries prevalence was the lowest. Globally, 64.6 million (95% CI, 64.4 to 64.9 million) and 62.9 million (62.8 to 63.1 million) prevalent cases of caries in permanent and deciduous teeth were attributable to sociodemographic inequality in 2019. This amounted to 3.2% (3.2% to 3.2%) and 12.1% (12.1% to 12.1%) of the global number of prevalent cases of caries in permanent and deciduous teeth. Burden of dental caries remains a global public health challenge. A systemwide reform of the global oral health care system is needed to tackle the causes of the burden and inequality of dental caries.

20-Hydroxyecdysone-upregulated proteases involved in Bombyx larval fat body destruction.

During insect larval-pupal metamorphosis, the obsolete larval organs and tissues undergo histolysis and programmed cell death to recycle cellular materials. It has been demonstrated that some cathepsins are essential for histolysis in larval tissues, but the process of tissue destruction is not well documented. Fat body, the homologous organ to mammalian liver and adipose tissue, goes through a distinct destruction process during larval-pupal transition. Herein, we found that most of the Bombyx proteases - including Bombyx cathepsin B (BmCatB) (BmCatLL-2), Bombyx cathepsin D (BmCatD), Bombyx cathepsin L like-1 (BmCatLL-1) and -2(BmCatLL-2), Bombyx fibroinase (BmBcp), Bombyx matrix metalloprotease (BmMmp), Bombyx A disintegrin and metalloproteinase with thrombospondin motifs 1 (BmAdamTS-1), Bombyx A disintegrin and metalloproteinase with thrombospondin motifs like (BmAdamTS L) and Bombyx cysteine protease inhibitor (Bmbcpi)- were expressed highly in fat body during feeding and metamorphosis, with a peak occurring during the nonfeeding moulting or prepupal stage, as well as being responsive to 20-hydroxyecdysone (20E). The aforementioned protease genes expression was upregulated by injection of 20E into the feeding larvae, while blocking 20E signalling transduction led to downregulation. Western blotting and immunofluorescent staining of BmCatB and BmBcp confirmed the coincident variation of their messenger RNA (mRNA) and protein level during the development and after the treatments. Moreover, BmCatB, BmBcp, BmMmp and BmAdamTS-1 RNA interference all led to blockage of larval fat body destruction. Taken together, we conclude that 20E regulates larval fat body destruction by upregulating related protease gene expression and protein levels during larval-pupal transition.

All-trans retinoic acid prevents the development of type 1 diabetes by affecting the levels of interferon gamma and interleukin 4 in streptozotocin-induced murine diabetes model.

The aim of this study was to explore the molecular mechanism by which all-trans retinoic acid (ATRA) prevents type 1 diabetes mellitus (T1DM). Fifty ICR mice were randomly assigned to three groups: prevention group [N = 20; mice received 10 mg/kg ATRA daily for 5 days and then 60 mg/kg streptozotocin (STZ) for 5 days]; diabetic group (N = 20, mice received 95% sterile peanut oil and 5% dimethyl sulfoxide for 5 days and then 60 mg/kg STZ for 5 days); and control group (N = 10, mice received 95% sterile peanut oil and 5% dimethyl sulfoxide for 5 days and then citrate buffer for 5 days). Blood glucose was measured using blood glucose test strips and serum insulin was measured by radioimmunoassay. Islets cell morphology was assessed by microscopy and ELISA was used to measure the serum levels of interferon gamma (IFN-γ) and interleukin 4 (IL- 4). In the prevention group, blood sugar levels were found to be reduced and serum insulin levels increased compared with the levels in the diabetic group (P < 0.05), indicating that ATRA prevented the STZ-induced damage to islet cells. Meanwhile, ATRA was shown to decrease the levels of IFN-γ and increase the levels of IL-4 as well as the IFN-γ/IL-4 ratio in STZ-treated animals (P < 0.05). These findings suggest that ATRA prevents the recurrence of autoimmune insulitis. This study demonstrated that ATRA effectively prevents the progression of T1DM in a murine model of the disease by reducing IFN-γ levels and increasing IL-4 levels.

Synthesis and pharmacokinetic evaluation of novel N-acyl-cordycepin derivatives with a normal alkyl chain.

For slowing down the too fast metabolic velocity and increasing the bioavailability of cordycepin, four N-acyl-(propionyl-, octanoyl-, lauroyl- and stearoyl-) cordycepin derivatives were synthesized chemically and their pharmacokinetic profiles were investigated in this study. The results show that time of maximum concentration (T(max)) and half-life (t(1/2)) would be elongated with the increase of the alkyl chain length, but maximum concentration (C(max)) and area under concentration-time curve (AUC) increased initially, then decreased when the number of alkyl carbon exceeded eight. The T(max), C(max) and AUC of N-octanoyl-cordycepin were nearly 4, 30 and 68 times, respectively, higher than that of cordycepin. All derivatives could be transformed into cordycepin in vivo and the concentration of transformed cordycepin was proportional to that of derivatives. It indicated that N-octanoyl modification could decrease the metabolic velocity and increase the bioavailability of cordycepin to the maximum, thus it might be a promising prodrug of cordycepin.