Simulated weightlessness led to the transformation of glycolipid metabolism in the livers of mice / La antigravedad simulada provocó la transformación del metabolismo de los glicolípidos en el hígado de ratones / Antigravidade simulada levou à transformação do metabolismo de glicolipídios no fígado de camundongos

ABSTRACT Objectives: The effects of weightlessness on the liver were studied using a tail suspension (TS) male mouse model. Methods: The effects of 0-, 2- and 4-week TS (CON, TS2 and TS4 groups) on glycogen and lipid content, as well as on the molecular processes of the synthesis and degradation pathways, were examined. Results: (1) The number of glycogenosomes under ultrastructure and the glycogen content were considerably larger in the TS4 group than in the other two groups. (2) In the TS4 group, glycogen synthase activity remained constant while glycogen phosphorylase activity dropped, indicating that glycogen breakdown was reduced. (3) The livers of the TS2 group had the highest lipid and triglyceride content, indicating lipid buildup in the liver at this time. (4) In the TS2 group, the activities of the fatty acid synthesis-related factors acetyl-CoA carboxylase and fatty acid synthase increased, while hepatic lipase decreased, indicating that lipid synthesis increased, while decomposition decreased. (5) In the TS2 group, the protein expression of glucose transporters 1 and 2 increased. Conclusions: From TS2 weeks to TS4 weeks, the main energy consumption mode in the livers of mice transitioned from glucose metabolism to lipid metabolism as glucose use decreased. Level of evidence II; Comparative prospective study.

RESUMEN Objetivos: Se estudiaron los efectos de la antigravedad en el hígado utilizando un modelo de ratón macho en prueba de suspensión de la cola (TS, tail suspension). Métodos: Se examinaron los efectos de la TS a las 0, 2 y 4 semanas (grupos CON, TS2 y TS4) sobre el contenido de glucógeno y lípidos, así como sobre los procesos moleculares de las vías de síntesis y degradación. Resultados: (1) El número de glucogenosomas ultraestructurales y el contenido de glucógeno fueron expresivamente más altos en el grupo TS4 que en los otros dos grupos. (2) En el grupo TS4, la actividad de la glucógeno sintasa se mantuvo constante, mientras que la actividad de la glucógeno fosforilasa disminuyó, lo que indica que la degradación del glucógeno se redujo. (3) Los hígados del grupo TS2 presentaron el mayor contenido de lípidos y triglicéridos, lo que indica la acumulación de lípidos en el hígado en ese momento. (4) En el grupo TS2, la actividad de los factores relacionados con la síntesis de ácidos grasos acetil-CoA carboxilasa y ácido graso sintasa aumentó, mientras que la lipasa hepática disminuyó, indicando que la síntesis de lípidos aumentó mientras que la descomposición disminuyó. (5) En el grupo TS2, la expresión proteica de los transportadores de glucosa 1 y 2 aumentó. Conclusiones: Desde la semana TS2 hasta la semana TS4, el principal modo de consumo de energía en el hígado de los ratones pasó del metabolismo de la glucosa al metabolismo de los lípidos a medida que disminuía el uso de la glucosa. Nivel de Evidencia II, Estudio retrospectivo comparativo.

RESUMO Objetivos: Os efeitos da antigravidade no fígado foram estudados usando um modelo de camundongo macho com a suspensão pela cauda (TS, tail suspension). Métodos: Foram examinados os efeitos da TS em 0, 2 e 4 semanas (grupos CON, TS2 e TS4) sobre o conteúdo de glicogênio e lipídios, bem como nos processos moleculares das vias de síntese e degradação. Resultados: (1) O número de glicogenossomos ultraestruturais e o teor de glicogênio foram expressivamente maiores no grupo TS4 do que nos outros dois grupos. (2) No grupo TS4, a atividade de glicogênio sintase permaneceu constante, enquanto a atividade de glicogênio fosforilase caiu, indicando que a degradação do glicogênio foi reduzida. (3) Os fígados do grupo TS2 tiveram o maior teor lipídico e de triglicérides, indicando acúmulo de lipídios no fígado no momento. (4) No grupo TS2, a atividade dos fatores relacionados com a síntese de ácidos graxos acetil-CoA carboxilase e ácido graxo sintase aumentaram, enquanto a lipase hepática diminuiu, indicando que a síntese de lipídios aumentou, enquanto a decomposição diminuiu. (5) No grupo TS2, a expressão proteica dos transportadores de glicose 1 e 2 aumentou. Conclusões: De TS2 semanas para TS4 semanas, o principal modo de consumo de energia no fígado de camundongos passou do metabolismo da glicose para o metabolismo lipídico, à medida que o uso de glicose diminuiu. Nível de evidência II, Estudo retrospectivo comparativo.

In Silico Screening of Potential Spike Glycoprotein Inhibitors of SARS-CoV-2 with Drug Repurposing Strategy / 中国结合医学杂志

OBJECTIVE@#To select potential molecules that can target viral spike proteins, which may potentially interrupt the interaction between the human angiotension-converting enzyme 2 (ACE2) receptor and viral spike protein by virtual screening.@*METHODS@#The three-dimensional (3D)-coordinate file of the receptor-binding domain (RBD)-ACE2 complex for searching a suitable docking pocket was firstly downloaded and prepared. Secondly, approximately 15,000 molecular candidates were prepared, including US Food and Drug Administration (FDA)-approved drugs from DrugBank and natural compounds from Traditional Chinese Medicine Systems Pharmacology (TCMSP), for the docking process. Then, virtual screening was performed and the binding energy in Autodock Vina was calculated. Finally, the top 20 molecules with high binding energy and their Chinese medicine (CM) herb sources were listed in this paper.@*RESULTS@#It was found that digitoxin, a cardiac glycoside in DrugBank and bisindigotin in TCMSP had the highest docking scores. Interestingly, two of the CM herbs containing the natural compounds that had relatively high binding scores, Forsythiae fructus and Isatidis radix, are components of Lianhua Qingwen (), a CM formula reportedly exerting activity against severe acute respiratory syndrome (SARS)-Cov-2. Moreover, raltegravir, an HIV integrase inhibitor, was found to have a relatively high binding score.@*CONCLUSIONS@#A class of compounds, which are from FDA-approved drugs and CM natural compounds, that had high binding energy with RBD of the viral spike protein. Our work provides potential candidates for other researchers to identify inhibitors to prevent SARS-CoV-2 infection, and highlights the importance of CM and integrative application of CM and Western medicine on treating COVID-19.

In Silico Screening of Potential Spike Glycoprotein Inhibitors of SARS-CoV-2 with Drug Repurposing Strategy / 中国结合医学杂志

OBJECTIVE@#To select potential molecules that can target viral spike proteins, which may potentially interrupt the interaction between the human angiotension-converting enzyme 2 (ACE2) receptor and viral spike protein by virtual screening.@*METHODS@#The three-dimensional (3D)-coordinate file of the receptor-binding domain (RBD)-ACE2 complex for searching a suitable docking pocket was firstly downloaded and prepared. Secondly, approximately 15,000 molecular candidates were prepared, including US Food and Drug Administration (FDA)-approved drugs from DrugBank and natural compounds from Traditional Chinese Medicine Systems Pharmacology (TCMSP), for the docking process. Then, virtual screening was performed and the binding energy in Autodock Vina was calculated. Finally, the top 20 molecules with high binding energy and their Chinese medicine (CM) herb sources were listed in this paper.@*RESULTS@#It was found that digitoxin, a cardiac glycoside in DrugBank and bisindigotin in TCMSP had the highest docking scores. Interestingly, two of the CM herbs containing the natural compounds that had relatively high binding scores, Forsythiae fructus and Isatidis radix, are components of Lianhua Qingwen (), a CM formula reportedly exerting activity against severe acute respiratory syndrome (SARS)-Cov-2. Moreover, raltegravir, an HIV integrase inhibitor, was found to have a relatively high binding score.@*CONCLUSIONS@#A class of compounds, which are from FDA-approved drugs and CM natural compounds, that had high binding energy with RBD of the viral spike protein. Our work provides potential candidates for other researchers to identify inhibitors to prevent SARS-CoV-2 infection, and highlights the importance of CM and integrative application of CM and Western medicine on treating COVID-19.