Targeting deubiquitinase OTUB1 protects vascular smooth muscle cells in atherosclerosis by modulating PDGFR β
In this study, RNAi screening in human aortic smooth muscle cells was performed to explore the effects of OTU family deubiquitinases, which revealed that silencingOTUB1 inhibited PDGF-BB-stimulated VSMC phenotype switch. Furtherin vivo studies usingApoe−/− mice revealed that knockdown ofOTUB1 in VSMCs alleviated atherosclerosis plaque burden in the advanced stage and led to a stable plaque phenotype. Moreover, VSMC proliferation and migration upon PDGF-BB stimulation could be inhibited by silencingOTUB1 in vitro. Unbiased RNA-sequencing data indicated that knocking downOTUB1 influenced VSMC differentiation, adhesion, a...
Source: Frontiers of Medicine - April 22, 2024 Category: General Medicine Source Type: research

Pathological progression of osteoarthritis: a perspective on subchondral bone
AbstractOsteoarthritis (OA) is a degenerative bone disease associated with aging. The rising global aging population has led to a surge in OA cases, thereby imposing a significant socioeconomic burden. Researchers have been keenly investigating the mechanisms underlying OA. Previous studies have suggested that the disease starts with synovial inflammation and hyperplasia, advancing toward cartilage degradation. Ultimately, subchondral-bone collapse, sclerosis, and osteophyte formation occur. This progression is deemed as “top to bottom.” However, recent research is challenging this perspective by indicating that initia...
Source: Frontiers of Medicine - April 15, 2024 Category: General Medicine Source Type: research

Cancer stem cell-immune cell crosstalk in the tumor microenvironment for liver cancer progression
AbstractCrosstalk between cancer cells and the immune microenvironment is determinant for liver cancer progression. A tumor subpopulation called liver cancer stem cells (CSCs) significantly accounts for the initiation, metastasis, therapeutic resistance, and recurrence of liver cancer. Emerging evidence demonstrates that the interaction between liver CSCs and immune cells plays a crucial role in shaping an immunosuppressive microenvironment and determining immunotherapy responses. This review sheds light on the bidirectional crosstalk between liver CSCs and immune cells for liver cancer progression, as well as the underlyi...
Source: Frontiers of Medicine - April 11, 2024 Category: General Medicine Source Type: research

Trajectory of COVID-19 response and management strategy in China: scientific rationale driven strategy adjustments
This article gives a systematic review of the trajectory of COVID-19 development in China, summarizes the critical policy arrangements and provides evidence for the adj ustment during policy making process, so as to share experiences with international community and contribute to the global health for all humanity. (Source: Frontiers of Medicine)
Source: Frontiers of Medicine - April 2, 2024 Category: General Medicine Source Type: research

Emergence of SARS and COVID-19 and preparedness for the next emerging disease X
AbstractSevere acute respiratory syndrome (SARS) and Coronavirus disease 2019 (COVID-19) are two human Coronavirus diseases emerging in this century, posing tremendous threats to public health and causing great loss to lives and economy. In this review, we retrospect the studies tracing the molecular evolution of SARS-CoV, and we sort out current research findings about the potential ancestor of SARS-CoV-2. Updated knowledge about SARS-CoV-2-like viruses found in wildlife, the animal susceptibility to SARS-CoV-2, as well as the interspecies transmission risk of SARS-related coronaviruses (SARSr-CoVs) are gathered here. Fin...
Source: Frontiers of Medicine - April 2, 2024 Category: General Medicine Source Type: research

A distinct “repair” role of regulatory T cells in fracture healing
AbstractRegulatory T cells (Tregs) suppress immune responses and inflammation. Here, we described the distinct nonimmunological role of Tregs in fracture healing. The recruitment from the circulation pool, peripheral induction, and local expansion rapidly enriched Tregs in the injured bone. The Tregs in the injured bone displayed superiority in direct osteogenesis over Tregs from lymphoid organs. Punctual depletion of Tregs compromised the fracture healing process, which leads to increased bone nonunion. In addition, bone callus Tregs showed unique T-cell receptor repertoires. Amphiregulin was the most overexpressed protei...
Source: Frontiers of Medicine - March 16, 2024 Category: General Medicine Source Type: research

Dysregulated N6-methyladenosine modification in peripheral immune cells contributes to the pathogenesis of amyotrophic lateral sclerosis
AbstractAmyotrophic lateral sclerosis (ALS) is a progressive neurogenerative disorder with uncertain origins. Emerging evidence implicates N6-methyladenosine (m6A) modification in ALS pathogenesis. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and liquid chromatography –mass spectrometry were utilized for m6A profiling in peripheral immune cells and serum proteome analysis, respectively, in patients with ALS (n = 16) and controls (n = 6). The single-cell transcriptomic dataset (GSE174332) of primary motor cortex was further analyzed to illuminate the biological implications of differentially methylated genes ...
Source: Frontiers of Medicine - March 16, 2024 Category: General Medicine Source Type: research

Arginine methylation of ALKBH5 by PRMT6 promotes breast tumorigenesis via LDHA-mediated glycolysis
AbstractALKBH5 is a master regulator of N6-methyladenosine (m6A) modification, which plays a crucial role in many biological processes. Here, we show that ALKBH5 is required for breast tumor growth. Interestingly, PRMT6 directly methylates ALKBH5 at R283, which subsequently promotes breast tumor growth. Furthermore, arginine methylation of ALKBH5 by PRMT6 increases LDHA RNA stability via m6A demethylation, leading to increased aerobic glycolysis. Moreover, PRMT6-mediated ALKBH5 arginine methylation is confirmed in PRMT6-knockout mice. Collectively, these findings identify a PRMT6-ALKBH5-LDHA signaling axis as a novel targe...
Source: Frontiers of Medicine - March 11, 2024 Category: General Medicine Source Type: research

Immune landscape and response to oncolytic virus-based immunotherapy
In conclusion, this review offers a concise and comprehensive synopsis of the current status and future prospects of OV-based immunotherapy, underscoring its remarkable potential as an effective immunotherapeutic agent for cancer treatment. (Source: Frontiers of Medicine)
Source: Frontiers of Medicine - March 8, 2024 Category: General Medicine Source Type: research

Gut microbiota-dependent phenylacetylglutamine in cardiovascular disease: current knowledge and new insights
AbstractPhenylacetylglutamine (PAGln) is an amino acid derivate that comes from the amino acid phenylalanine. There are increasing studies showing that the level of PAGln is associated with the risk of different cardiovascular diseases. In this review, we discussed the metabolic pathway of PAGln production and the quantitative measurement methods of PAGln. We summarized the epidemiological evidence to show the role of PAGln in diagnostic and prognostic value in several cardiovascular diseases, such as heart failure, coronary heart disease/atherosclerosis, and cardiac arrhythmia. The underlying mechanism of PAGln is now con...
Source: Frontiers of Medicine - March 1, 2024 Category: General Medicine Source Type: research

EBV-associated lymphoproliferative disease post-CAR-T cell therapy
AbstractEpstein –Barr virus (EBV)-associated lymphoproliferative diseases (EBV-LPDs) are common complications that occur after solid organ transplantation or allogeneic hematopoietic stem-cell transplantation (HSCT). However, their occurrence and treatment post-chimeric antigen receptor-modified T (CAR-T) cell th erapy has not been reported. Two patients had been diagnosed with EBV-positive aggressive B-cell lymphoma and experienced relapses after multiple lines of treatment. After receiving CAR-T cell therapy in tandem with autologous HSCT, the patients achieved complete remission. However, with a median ti me of 38.5 m...
Source: Frontiers of Medicine - February 8, 2024 Category: General Medicine Source Type: research

Revisiting China ’s response to coronavirus disease 2019
(Source: Frontiers of Medicine)
Source: Frontiers of Medicine - February 1, 2024 Category: General Medicine Source Type: research

Insights into optimizing exosome therapies for acute skin wound healing and other tissue repair
AbstractExosome therapy holds great promise as a novel approach to improve acute skin wound healing. This review provides a comprehensive overview of the current understanding of exosome biology and its potential applications in acute skin wound healing and beyond. Exosomes, small extracellular vesicles secreted by various stem cells, have emerged as potent mediators of intercellular communication and tissue repair. One advantage of exosome therapy is its ability to avoid potential risks associated with stem cell therapy, such as immune rejection or stem cells differentiating into unwanted cell types. However, further rese...
Source: Frontiers of Medicine - January 13, 2024 Category: General Medicine Source Type: research

Unraveling the complex roles of macrophages in obese adipose tissue: an overview
AbstractMacrophages, a heterogeneous population of innate immune cells, exhibit remarkable plasticity and play pivotal roles in coordinating immune responses and maintaining tissue homeostasis within the context of metabolic diseases. The activation of inflammatory macrophages in obese adipose tissue leads to detrimental effects, inducing insulin resistance through increased inflammation, impaired thermogenesis, and adipose tissue fibrosis. Meanwhile, adipose tissue macrophages also play a beneficial role in maintaining adipose tissue homeostasis by regulating angiogenesis, facilitating the clearance of dead adipocytes, an...
Source: Frontiers of Medicine - January 2, 2024 Category: General Medicine Source Type: research

Small-molecule anti-COVID-19 drugs and a focus on China ’s homegrown mindeudesivir (VV116)
AbstractThe coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir –ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir–ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19. However, the existing treatment options have li mitations, and effective treatment strategies that ...
Source: Frontiers of Medicine - January 2, 2024 Category: General Medicine Source Type: research