Potential metal-related strategies for prevention and treatment of COVID-19.

Abstract: The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed severe threats to human health, public safety, and the global economy. Metal nutrient elements can directly or indirectly take part in human immune responses, and metal-related drugs have served as antiviral drugs and/or enzyme inhibitors for many years, providing potential solutions to the prevention and treatment of COVID-19. Metal-based drugs are currently under a variety of chemical structures and exhibit wide-range bioactivities, demonstrating irreplaceable advantages in pharmacology. This review is an intention to summarize recent progress in the prevention and treatment strategies against COVID-19 from the perspective of metal pharmacology. The current and potential utilization of metal-based drugs is briefly introduced. Specifically, metallohydrogels that have been shown to present superior antiviral activities are stressed in the paper as potential drugs for the treatment of COVID-19.

[Clinical epidemiological analysis of 3602 cases of primary liver cancer in Xinjiang].

OBJECTIVE: To investigate the clinical epidemiological characteristics and the major causes of primary liver cancer (PLC) in Xinjiang region. METHODS: The clinical epidemiological information on the first page of case history of 3602 PLC patients, which were diagnosed in our hospital from January 2002 to December 2010, were retrospectively reviewed and analyzed. RESULTS: Among the 3602 cases, the men/women gender ratio was 3.72:1; The proportion of Han, Uighur, Kazakh, and other nationality (Hui, Mongolian, Manchu, Xibo nationality) was 81.95%, 9.30%, 4.14%, 2.89%, and 1.72%, respectively. The comparative difference between Uighur and Han nationalities was significant (P < 0.05). The hepatitis virus detection results showed that HBs-Ag was positive in 1680 cases (59.57%), HCV-Ab was positive in 229 cases (9.41%). Virus detection was negative in 888 patients (24.65%). The hepatitis B virus positive rate in Uygur patients was 36.13% and in Kazakh patients was 40.37%, both significantly lower than that in patients of Han nationality (63.18%, P < 0.05). CONCLUSIONS: In Xinjiang region, the infection rate of hepatitis B virus in Uygur and Kazak people is significantly lower than that in Han people. The distribution of gender and age does not differ significantly among different nationalities, compared with those in other regions. The prevalence of primary liver cancer in Xinjiang region has certain regional characteristics and features.

[Effect of 6 MeV radiotherapy on secondary Echinococcus multilocularis infection in rats].

OBJECTIVE: To explore the effect of 6-MeV X-ray radiotherapy on secondary Echinococcus multilocularis infection in rats. METHODS: Female SD rats were used to develop a secondary infection model, and then randomly divided into experimental group and control group (5/group). Rats in experimental group received two irradiations at 7-day intervals with the same dose (20 Gy) which applied with 6-MeV ray. The rats in control group did not receive any treatment. At one month after the second irradiation, the pathomorphological changes of E. multilocularis cysts were observed. RESULTS: Cysts in experimental group showed different degrees of damage, including that the laminated layer and germinal layer became swollen and separated from each other, brood capsules and protoscoleces were rare. The structure of cysts was normal in control group, laminated layer and germinal layer were clear, and there were many protoscoleces in the brood capsule. CONCLUSION: 6 MeV radiotherapy can inhibit the growth of E. multilocularis.

[X-ray irradiation against Echinococcus multilocularis protoscoleces in vitro].

OBJECTIVE: To explore the effect of X-ray irradiation on Echinococcus multilocularis protoscoleces in vitro. METHODS: Echinococcus multilocularis protoscoleces were collected from cysts of infected Meriones meridianus and then cultured in RPMI 1640 medium. Protoscoleces were subpackaged into culture flasks at a density of about 10(4) per flask after culture for 3 days. Each group has 10 culture flasks. There were seven groups named as blank control group, low dose group (15 Gy and 30 Gy), medium dose group (45 Gy and 60 Gy), high dose group (75 Gy and 90 Gy), albendazole group (2 500 ng/ml), 45 Gy X-ray + 2 500 ng/ml albendazole group, and 75 Gy X-ray + 2 500 ng/ml albendazole group. Protoscoleces received three radiations on every other day with a source-skin distance of 100 cm and at a dose rate of 200 cGy/min after 3 days in culture. At each day after irradiation, protoscoleces were counted by light microscope with 0.1% eosin staining, and calculated mortality rate (per 100 protoscoleces) until all the parasites in experimental groups died. At the same time, the morphological changes of protoscoleces were observed. RESULTS: There were significant differences in protoscolex mortality between X-ray groups and blank control group (P < 0.05), between X-ray + albendazole groups and albendazole group (P < 0.05). Protoscolex mortality in albendazole group were higher than that of blank control group (P < 0.05). Significant difference were also found in protoscolex mortality between albendazole combined with radiation and radiation only (P < 0.05). Before radiation, protoscoleces was normal with complete structure. After radiation, the parasites were mostly valgus type protoscoleces with disordered rostellar hooks and deformed acetabulum, and finally died. CONCLUSION: X-ray can kill Echinococcus multilocularis protoscoleces in vitro.

Curative effect of radiotherapy at various doses on subcutaneous alveolar echinococcosis in rats.

BACKGROUND: Alveolar echinococcosis (AE) is a disease in human and animals, and the cure rate is unsatisfactory. This study aimed to investigate the curative efficacy of different doses of locally applied radiotherapy on alveolar echinococcosis in rats. METHODS: Rats infected with Echinococcus multilocularis were randomly divided into 4 groups of 15 rats each: low-, middle-, and high-irradiation groups and a control group. Rats in the control group underwent no treatment, while rats in the irradiation groups received 6-MeV radiotherapy at 20 Gy/8 f, 40 Gy/8 f, and 60 Gy/8 f respectively, once every 3 days for a total of 8 times. One month after radiotherapy, wet weight and AE vesicle inhibitory rate were detected in rats of each group. Histopathologic and ultrastructural observations of tissues with AE lesions were performed. RESULTS: In the treatment groups, an obvious inhibitory effect was found in AE rats; the inhibitory rates were 50%, 72%, and 82%, respectively. There were also statistical differences in pathological changes and average wet weight of the lesions compared with the control group (P < 0.05). In the treatment groups, injuries of various degrees were found in the ultrastructure of the laminated and germinal layers in the capsular wall of AE, and injury was most severe in the high-dose group. CONCLUSION: Radiotherapy has a dose-dependent inhibitory effect on the growth of AE.