Objective: Sarcopenia causes loss of skeletal muscle and function, thus seriously affecting the physical function and quality of life in the elderly. This article discusses the specific molecular mechanism and ameliorating effects of Tudangshen (TDS) on sarcopenia in elderly rats with type 2 diabetes mellitus (T2DM).Methods: Elderly Sprague-Dawley (SD) rats were randomly selected and fed with a high-fat diet combined with an intraperitoneal injection of streptozotocin to establish T2DM model. The model rats were stratified and randomly divided into the model group, metformin group, TDS high-dose group, TDS medium-dose group, and TDS low-dose group according to blood glucose combined with body weight, and the same batch of old SD rats was set as the normal control group. The effects of TDS in an elderly T2DM sarcopenia rat model were evaluated by observing the body positions of the rats, analyzing blood biochemistry, testing exercise capacity, and pathologically staining sectioned gastrocnemius muscle tissues. The molecular mechanisms of the effects were analyzed using quantitative real-time polymerase chain reaction and western blotting.Results: TDS has no statistically significant effect on blood glucose, insulin and glycosylated serum protein in aged rats with T2DM, but it can reduce levels of glycosylated serum protein, total cholesterol, triglycerides, and low-density lipoprotein; it improves pathological changes in rat gastrocnemius muscle tissues, and increases muscle cell activity in elderly rats with T2DM and sarcopenia. TDS also promoted the upregulation of the expression of mammalian target of rapamycin (mTOR)/protein kinase B (PKB/AKT)/phosphatidylinositol 3-kinase (PI3K)/ribosomal protein S6 kinase/eukaryotic initiation factor 4E binding rotein1 mRNA in rats and triggered an increase in corresponding protein levels.Conclusions: TDS alleviated muscle decline in elderly rats with T2DM by activating the PI3K/AKT/mTOR signaling pathway and regulating the synthesis of corresponding proteins.

Dear Editor, COVID-19 associated with SARS-CoV-2 virus is an ongoing global pandemic. 1 Although great efforts have been made, the COVID-19 situation is still very serious due to the rapid mutation rate of SARS-COV-2 and the increase of drug resistance. 2 Patients with lung cancer are more susceptible to COVID-19 because of their immunosuppressed state and fragile lung tissue. 3,4 angiotensin converting enzyme 2 (ACE2) has been confirmed to be the key entry site for the SARS-CoV-2 virus 5 ; however, the roles of ACE and TMEM27, the other two genes in ACEs gene family (ACEs) with high homology to ACE2, in lung cancer and COVID-19 have not been entirely clarified.As shown in Figure 1, data related to ACEs, SARS-CoV-2 and lung cancer were obtained from several databases. The relationship among the three was analyzed to provide ideas for prevention and control of SARS-CoV-2 infection of lung cancer patients. The transcriptional levels of ACEs in 20 cancers were compared to transcription profiles in normal tissues. The dates showed that the transcriptional level of ACE was downregulated in four studies, whereas transcriptional levels of ACE2 and TMEM27 were only one study elevated in patients with lung cancer (Figure S1, Table S1). And we further revalidated the transcription level of ACEs in lung cancer patients in UALCAN database. It was found that ACE was dramatically downregulated in lung tumor tissues (Figure S2A,B), whereas ACE2 was at a high transcriptional level in lung tumor tissues (Figure S2C,D). TMEM27 was overexpressed in lung adenocarcinoma (LUAD), while it was downregulated in lung squamous carcinoma (LUSC) (Figure S2E,F). We further checked the protein expression levels of ACEs in lung cancer (Figure S3A-C).Then, the relationship between transcriptional levels of ACEs and the clinicopathological parameters of lungThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

BackgroundIron is an essential nutrient element, and iron metabolism is related to many diseases. Ferroptosis is an iron-dependent form of regulated cell death associated with ischemic stroke (IS). Hence, this study intended to discover and validate the possible ferroptosis-related genes involved in IS.Materials and methodsGSE16561, GSE37587, and GSE58294 were retrieved from the GEO database. Using R software, we identified ferroptosis-related differentially expressed genes (DEGs) in IS. Protein-protein interactions (PPIs) and enrichment analyses were conducted. The ROC curve was plotted to explore the diagnostic significance of those identified genes. The consistent clustering method was used to classify the IS samples. The level of immune cell infiltration of different subtypes was evaluated by ssGSEA and CIBERSORT algorithm. Validation was conducted in the test sets GSE37587 and GSE58294.ResultsTwenty-one ferroptosis-related DEGs were detected in IS vs. the normal controls. Enrichment analysis shows that the 21 DEGs are involved in monocarboxylic acid metabolism, iron ion response, and ferroptosis. Moreover, their expression levels were pertinent to the age and gender of IS patients. The ROC analysis demonstrated remarkable diagnostic values of LAMP2, TSC22D3, SLC38A1, and RPL8 for IS. Transcription factors and targeting miRNAs of the 21 DEGs were determined. Vandetanib, FERRIC CITRATE, etc., were confirmed as potential therapeutic drugs for IS. Using 11 hub genes, IS patients were categorized into C1 and C2 subtypes. The two subtypes significantly differed between immune cell infiltration, checkpoints, and HLA genes. The 272 DEGs were identified from two subtypes and their biological functions were explored. Verification was performed in the GSE37587 and GSE58294 datasets.ConclusionOur findings indicate that ferroptosis plays a critical role in the diversity and complexity of the IS immune microenvironment.

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