Drying Process of HPMC-Based Hard Capsules: Visual Experiment and Mathematical Modeling.

Using plant-based polysaccharide gels to produce hard capsules is a novel application of this technology in the medicinal field, which has garnered significant attention. However, the current manufacturing technology, particularly the drying process, limits its industrialization. The work herein employed an advanced measuring technique and a modified mathematical model to get more insight into the drying process of the capsule. Low field magnetic resonance imaging (LF-MRI) technique is adopted to reveal the distribution of moisture content in the capsule during drying. Furthermore, a modified mathematical model is developed by considering the dynamic variation of the effective moisture diffusivity (Deff) according to Fick's second law, which enables accurate prediction of the moisture content of the capsule with a prediction accuracy of ±15%. The predicted Deff ranges from 3 × 10-10 to 7 × 10-10 m2·s-1, which has an irregular variation with a time extension. Moreover, as temperature increases or relative humidity decreases, there is an increased acceleration of moisture diffusion. The work provides a fundamental understanding of the drying process of the plant-based polysaccharide gel, which is crucial for enhancing the industrial preparation of the HPMC-based hard capsules.

Effects of low dose radiation on behavior rhythm of zebrafish (Danio rerio).

Biological rhythm refers to the internal regulation of various life activities of an organism, which are determined by the specific time structure sequences of each individual. Behavior rhythm is the most intuitive embodiment of biological rhythm. To study the effect of low dose radiation on behavioral rhythm, zebrafish (Danio rerio) was used as a model organism in this study. The early embryos of zebrafish were irradiated at doses of 0.01, 0.1, and 1 Gy to observe the changes in zebrafish development, circadian rhythm, key clock genes, related RNA and protein expression, and melatonin. The results revealed that 0.1 and 1 Gy radiation could lead to different degrees of telencephalic nerve cell apoptosis and the formation of vacuolar structures. 0.1 and 1 Gy radiation could reduce the hatching rate of zebrafish embryos at 72 hpf and delay embryo hatching. The analysis of circadian behavior at 120 hpf demonstrated that 1 Gy dose of radiation altered the circadian rhythm of zebrafish, as well as decreased the distance, amplitude, and phase of movement. RT-PCR analysis of the key clock genes (bmal1b, clock1a, per1b, per2, cry2, and nr1d1) involved in regulating circadian rhythm was performed. The results showed that 1 Gy radiation could interfere with the expression of clock genes in zebrafish embryos and upregulate bmal1b, clock1a, and per1b. Western blot experiments further verified the protein expression of key clock genes, bmal1b and clock. Detection of melatonin secretion at different time points over 24 h showed that radiation doses of 0.1 and 1 Gy could increase melatonin secretion. Based on these findings, it is speculated that a certain dose of radiation may affect melatonin secretion, which impacts the telencephalon structure and ontogeny of zebrafish, delays hatching, and changes the circadian rhythm. This effect is thought to be achieved through upregulating the expression of circadian rhythm genes, clock1a and per1b and related proteins, which may be responsible for the abnormal circadian rhythm caused by radiation.

Circadian clock and cell cycle: Cancer and chronotherapy.

The circadian clock is an endogenous timing system that ensures that various physiological processes have nearly 24 h circadian rhythms, including cell metabolism, division, apoptosis, and tumor production. In addition, results from animal models and molecular studies underscore emerging links between the cell cycle and the circadian clock. Mutations in the core genes of the circadian clock' can disrupt the cell cycle, which in turn increases the possibility of tumors. At present, tumor chronotherapy, which relies on a circadian clock mechanism, is developing rapidly for optimizing the time of drug administration in tumor treatment to improve drug efficacy and safety. However, the relationship between the circadian clock and the cell cycle is extremely complicated. This review summarizes the possible connection between the circadian clock and the cell cycle. In addition, the review provides evidence of the influence of the circadian clock on senescence and cancer.

The Threshold Effects of Low-Dose-Rate Radiation on miRNA-Mediated Neurodevelopment of Zebrafish.

The biological effects and regulatory mechanisms of low-dose and low-dose-rate radiation are still rather controversial. Therefore, in this study we investigated the effects of low-dose-rate radiation on zebrafish neurodevelopment and the role of miRNAs in radiation-induced neurodevelopment. Zebrafish embryos received prolonged gamma-ray irradiation (0 mGy/h, 0.1 mGy/h, 0.2 mGy/h, 0.4 mGy/h) during development. Neurodevelopmental indicators included mortality, malformation rate, swimming speed, as well as the morphology changes of the lateral line system and brain tissue. Additionally, spatiotemporal expression of development-related miRNAs (dre-miR-196a-5p, dre-miR-210-3p, dre-miR-338) and miRNA processing enzymes genes (Dicer and Drosha) were assessed by qRT-PCR and whole mount in situ hybridization (WISH). The results revealed a decline in mortality, malformation and swimming speed, with normal histological and morphological appearance, in zebrafish that received 0.1 mGy/h; however, increased mortality, malformation and swimming speed were observed, with pathological changes, in zebrafish that received 0.2 mGy/h and 0.4 mGy/h. The expression of miRNA processing enzyme genes was altered after irradiation, and miRNAs expression was downregulated in the 0.1 mGy/h group, and upregulated in the 0.2 mGy/h and 0.4 mGy/h groups. Furthermore, ectopic expression of dre-miR-210-3p, Dicer and Drosha was also observed in the 0.4 mGy/h group. In conclusion, the effect of low-dose and low-dose-rate radiation on neurodevelopment follows the threshold model, under the regulation of miRNAs, excitatory effects occurred at a dose rate of 0.1 mGy/h and toxic effects occurred at a dose rate of 0.2 mGy/h and 0.4 mGy/h.

Drying Behavior and Kinetics of Drying Process of Plant-Based Enteric Hard Capsules.

The drying process is a significant step in the manufacturing process of enteric hard capsules, which affects the physical and chemical properties of the capsules. Thus, the drying characteristics of plant-based enteric hard capsules were investigated at a constant air velocity of 2 m/s in a bench scale hot-air dryer under a temperature range of 25 to 45 °C and relative humidity of 40 to 80%. Results indicate that the drying process of the capsules mainly occur in a falling-rate period, implying that moisture transfer in the capsules is governed by internal moisture diffusion rate. High temperature and low relative humidity reduce drying time but increase the drying rate of the capsules. Investigation results of the mechanical properties and storage stability of the capsules, however, reveal that a fast drying rate leads to plant-based enteric hard capsules of low quality. Scanning electron microscopy further demonstrates that more layered cracks appear in capsules produced under a faster drying rate. The Page model yielded the best fit for describing thin-layer drying of the capsules based on the coefficient of determination and reduced chi-square. Moreover, it was established that the effective moisture diffusivity of the capsules increases with an increase in drying temperature or reduction in relative humidity.

The role of protein kinase C alpha in tri-ortho-cresyl phosphate-induced autophagy in human neuroblastoma SK-N-SH cells.

As an organophosphorus ester, tri-ortho-cresyl phosphate (TOCP) has been widely used in agriculture and industry. It is reported that TOCP can induce organophosphate-induced delayed neuropathy (OPIDN) in sensitive animal and human species. However, the exact molecular mechanisms underlying TOCP-induced neurotoxicity are still unknown. In this study, we found that TOCP could induce autophagy by activating protein kinase C alpha (PKCα) signaling in neuroblastoma SK-N-SH cells. PKCα activators could positively regulate TOCP-induced autophagy by increasing the expression levels of neighbor BRCA1 gene protein 1 (NBR1), LC3 and P62 autophagic receptor protein. Furthermore, PKCα activation impaired the ubiquitin-proteasome system (UPS), resulting in inhibition of proteasome activity and accumulation of ubiquitinated proteins. UPS dysfunction could stimulate autophagy to serve as a compensatory pathway, which contributed to the accumulation of the abnormally hyperphosphorylated tau proteins and degradation of impaired proteins of the MAP 2 and NF-H families in neurodegenerative disorders.