MedComm - Future medicine最新文献

At the end of 2019, the new coronavirus began to spread around the world. World Health Organization named this virus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which caused coronavirus disease (COVID-19). In most people without underlying medical conditions, symptoms of SARS-CoV-2 infection are often mild and nonlethal. However, patients with cancer have significantly higher rates of severe SARS-CoV-2 infection and disease-related mortality than normal individuals.¹ Numerous studies have shown that progressive malignancy is an independent risk factor for severe SARS-CoV-2 infection and related death. The incidence of long-term sequelae of SARS-CoV-2 infection in cancer patients is estimated at 15%–30%.² Although the use of vaccines has reduced the chance of severe SARS-CoV-2 infection incidence, large-scale trials often exclude cancer patients. It remains to be seen how effective and safe the vaccine is in cancer patients and how long it is durable. Multiorgan single-cell sequencing analysis confirmed that key receptors for SARS-CoV-2 infection in humans include ACE2 (angiotensin-converting enzyme 2), TMPRSS2 (transmembrane serine protease 2), NRP1 (neuropilin-1), AXL (AXL receptor tyrosine kinase), FURIN, and CTSL1 (cathepsin L1).³ SARS-CoV-2 infection may directly or indirectly lead to acute kidney injury, which may be related to the cytophilic effects of the virus and cytokine-induced systemic inflammatory responses. These receptors may play a key role in SARS-CoV-2 infection-induced acute kidney injury and even death. These key receptors provide crucial evidence for the development of antiviral drugs for SARS-CoV-2. However, further research on these receptors in cancer patients is warranted.

First, the expression profiling of prognosis prediction was investigated in multicancers. We found that except TMPRSS2, the remaining five receptors (ACE2, NRP1, AXL, FURIN, and CTSL1) were upregulated in various cancers, especially in kidney renal clear cell carcinoma (KIRC) (Figure 1A). The relationship between these receptors and the prognosis of cancer patients was analyzed. The results suggested that these four receptors, ACE2, NRP1, FURIN, and CTSL1, were prognostic risk factors in various cancers such as glioma, while in KIRC, they are protective factors for overall survival (Figure 1B). Similarly, ACE2, NRP1, and CTSL1 receptors were prognostic risk factors in gliomas and other tumors, and protective factors for disease progression-free survival in KIRC (Figure 1B). The protective induction of these three receptors on KIRC was also confirmed in the GSE29609 data set and the Japan-KIRC database (Figure 1C). The expression pattern of SARS-CoV-2 infection-related receptors in KIRC is different from other malignancies. ACE2, NRP1, and CTSL1 were highly expressed in KIRC tissues, but they were prognostic protective factors for patients. This may be rela

RNA methylation plays a key role across biological processes, which could be utilized as new weapons for cancer management. However, the implication of RNA methylation regulators in cancers, especially in clear cell renal cell cancer (ccRCC), remains largely unknown. We investigated the multiomics profile of RNA methylation regulators at the pan-cancer level. We found most RNA methylation regulators were dysregulated in cancers, which might be explained by genomic mutation and copy number variation. A novel subtype of ccRCC, RNA modification cancer subtype 2 (RMCS2), was identified and verified among different ccRCC cohorts. RMCS2 led to a shortened overall survival and had an activated state of PI3K-AKT-mTOR, KRAS, and retinoic acid metabolism signals, which resulted in an immune exhausted phenotype. In summary, our findings demonstrated that the aberrance of RNA methylation regulators was a common biological phenomenon pan-cancer. Dysregulated RNA methylation patterns could reshape tumor immunity thus impacting patients' prognosis and therapeutic response, and could function as a promising tool for ccRCC patients.

Regeneration of bone lost by trauma, diseases and aging, and restoration of its load-bearing function are major clinical challenges. Hydroxyapatite (HA) is a clinically proven scaffold material for bone grafting, but the random-pore structure limits the homing of the cells inside the graft and the bone regeneration progresses with the resorption of the graft material. This work is based on the hypothesis that aligned through pores in the graft will lead to a faster healing by homing the local cells inside and provide a better environment for new bone formation through the graft structure. The investigation was done using aligned porous HA scaffolds seeded with human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) and cultured in a multiwell format bioreactor setup. The cell adhesion was studied by microscopy, cell proliferation was evaluated by Alamar blue assay and osteogenic differentiation was confirmed by biochemical and molecular assays. The results indicate that the hWJ-MSCs infiltrated through the aligned porous network of the scaffold, proliferated well when cultured in the expansion medium, and differentiated into osteogenic lineage when cultured in the differentiation medium.