MedComm - Future medicine最新文献

This study aimed to investigate the awareness of high and pathological myopia among patients with high myopia. A cross-sectional multicenter survey involving both physicians and patients was conducted between February and April 2021. The outpatient education status, doctors' expectations toward patient education, patients' awareness of high/pathological myopia, and their access to relevant knowledge were inquired, and the proportions of patients with myopia, including high and pathological myopia, were assessed. In total, the survey involved 6975 physicians and patients with myopia from 161 medical institutions in China. The prevalence of high myopia among patients was 11.3%, with 22.59% having pathological myopia. Among those with pathological myopia, 22.45% experienced high myopia complications. Approximately 48.7% of the physicians believed that patients had only a vague idea about high/pathological myopia, with certain misconceptions. Additionally, most outpatients (61.4%) had no access to specialized staff for patient education. Patients' preferences and requirements for online ophthalmology information varied based on family background, medical history, and cognition toward myopia. This study demonstrated that the awareness level among patients with myopia regarding high and pathological myopia is currently insufficient. Therefore, it is important to enhance education efforts to reduce the incidence of adverse outcomes.

Inflammatory bowel disease (IBD), which encompasses ulcerative colitis (UC) and Crohn's disease (CD), refers to a chronic and recurrent nonspecific inflammatory condition affecting the mucosal and submucosal layers of the intestines. A positive family history has been identified as a risk factor for the onset of IBD, likely influenced by genetic and environmental factors. In addition to intestinal damage, patients may have extraintestinal manifestations such as inflammation of the skin, eyes, and joints, inflammation of the liver or bile ducts, kidney stones, iron-deficiency anemia, and growth retardation in children, which may complicate diagnosis and treatment. Therefore, investigating the mechanisms of IBD and finding precise therapeutic targets provides enormous benefits to patients with IBD. Multiple studies have consistently demonstrated the influential role of dietary metabolism and aging in the development of IBD. Moreover, emerging evidence suggests that aging often coincides with alterations in epigenetic modifications, while diet metabolism mediates these epigenetic changes. Epigenetics has emerged as a prospective field for identifying novel biomarkers to facilitate the diagnosis, prognosis, and treatment of diseases. Therefore, in this perspective, we summarize the cross-talk between epigenetic modifications, diet metabolism, and aging in the pathogenesis of IBD and attempt to identify new potential therapeutic targets and strategies.

Although immunoassays are an indispensable tool for scientific research, antibody specificity has been recognized as a major challenge to the rigor and reproducibility of research findings. A 2016 proposal published by the International Working Group for Antibody Validation identified five pillars of antibody validation.¹ Among these is genetic validation, in which “The expression of the target protein is eliminated or significantly reduced by genome editing or RNA interference.”

Y chromosome-encoded genes present unique opportunities and challenges to validate antibodies on this genetic principle. Fortunately, readily available female-derived cells and tissues can serve as a target-negative source material, which is far more convenient than typical sources of genetic validation, which require knockout or knockdown approaches to a target gene. However, an additional challenge for the specificity of these antibodies is that many Y chromosome proteins have “gametologs,” or highly homologous genes encoded on the X chromosome. As gametologs can share over 90% amino acid identity, these protein targets present unique specificity challenges. However, this obstacle has not impeded commercial antibody suppliers who market hundreds of antibodies with purported specificity for Y chromosome-encoded genes.

We performed an analysis of the extent to which Y chromosome gene-targeted commercial antibodies recognize female-derived materials using data provided in their marketing materials (a detailed methodology is provided in the Supporting Information). Table 1 lists 65 antibodies purporting to target a Y chromosome-encoded gene with company-supplied marketing demonstrating immunoreactivity in female-derived tissues. Product page URLs are provided in Supporting Information: Table S1. For one example, an antibody targeting sex-determining region chromosome Y marketed by MyBioSource (catalog # MBS8513980) presents validation data in HeLa cells, which is a cervical cancer cell line with no Y chromosomes.²

Among these antibodies, frequently used female-derived cell lines were HeLa, 30/65 (46%), HEK293T, female human embryonic kidney cells used in 14 (22%), and MCF-7 breast cancer cells used in 7 (11%). One antibody, a rabbit polyclonal raised against the “N terminus” of DEAD-box helicase 3 Y-linked (DDX3Y) (LS Biosciences, catalog # LS-C355991) presented positive immunohistochemistry in human breast cancer tissue. While not definitively a Y-chromosome absent tissue, we included this as a likely female-positive tissue, based on the prevalence of breast cancer in females compared to males being roughly 99-to-1 in the United States.³ Among 65 antibodies, we noted just two that had disclaimers warning that the antibody may cross-react with homologous X chromosome-encoded proteins.

This survey provides evidence of widespread off-target antigen recognition in commercial ant

Metabolic dysregulation is a hallmark of cancer, underpinning diverse aggressive behaviors such as uncontrolled proliferation, immune evasion, and metastasis. Despite the potential of tumor metabolites as biomarkers, their utility has been hampered by metabolic heterogeneity. Exploring cancer metabolism aims to discern shared metabolic pathways and have a better understanding the metabolic heterogeneity of tumors. This approach offers a holistic view of cancer metabolism, facilitating the identification of multicancer-relevant metabolic targets and the development of more broadly effective therapeutics. In this review, we present a comprehensive overview of the current landscape of cancer metabolism and its prospective applications in cancer diagnosis and prognosis. We delineate common metabolic aberrations observed across a spectrum of cancer types and elucidate the unique metabolic signatures characterizing the six leading causes of cancer-related mortality. Furthermore, we survey the utilization of untargeted metabolomics and single-cell technologies in cancer screening, diagnosis, and prognosis, while also spotlighting available data resources for pan-cancer metabolomics analyses. Throughout this discussion, we tackle prevailing research challenges and propose strategies aimed at enhancing cancer management. Our objective is to furnish valuable insights that can inform and guide future research endeavors in the dynamic realm of cancer metabolism.

Given the numerous crucial roles of RNA molecules in disease initiation and progression, RNAs have emerged as promising therapeutic targets for many diseases. Tong et al. report their discovery¹ of small-molecule bioactive degraders that selectively bind to disease-associated RNAs and recruit ribonuclease (RNase) enzymes to facilitate the degradation of RNAs. They have demonstrated the therapeutic potential of RNA degraders in the animal models of different cancers. The findings pave the way to target the development of novel RNA-targeted small-molecule drugs.

Despite considerable advances in drug discovery, there are only hundreds of proteins that have been targeted by approved drugs, compared to the estimated 20,000 human genes. To widen the scope of druggable targets, sustained research efforts have been devoted to modulating the challenging “undruggable” targets in novel ways. Targeting cellular RNA represents one such emerging strategy with the potential to expand the scope that can be drugged. There are multiple different classes of RNA molecules, contributing to various and essential biological functions. Messenger RNA (mRNA) and ribosomal RNA are involved in gene expression and protein synthesis. Noncoding RNAs are critical for the regulation of transcription and translation, such as long noncoding RNA, microRNA (miRNA), and antisense RNAs. Recent evidence has illustrated the important roles of RNA in various diseases, including neurodegenerative diseases, cancer, genetic disorders, and viral infections.²

A range of natural RNA-processing mechanisms have been leveraged to develop RNA-based therapeutics. They provide potential ways to specifically inhibit the expression of disease-related genes and prevent the translation of corresponding proteins. The most well-known RNA-based therapeutics include small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs).³ The siRNAs are double-stranded RNA molecules with 20–25 nucleotides. The ASOs are short synthetic single-stranded DNA or RNA. Both siRNAs and ASOs are gene silencers designed to target RNA molecules in a sequence-specific manner. However, one of the challenges that hindered their clinical application is their limited in vivo stability and cellular permeability due to their large molecular weight. Drug delivery systems are required to deliver the therapeutics intracellularly and systemically.⁴

Small molecules usually follow Lipinski's rule of five and face no such impediments. Compared to oligonucleotides, small-molecule drugs targeting RNAs have the advantage of nonimmunogenic and lower molecular weight. This makes them more effective in cell penetration and overcomes the delivery challenges of RNA-based therapeutics. Orally delivered small molecules also significantly increase patient comfort and compliance. Traditionally, small molecules have been primarily

Inflammation is characterized by activation of the immune and nonimmune cells that act by removing the stress stimuli such as pathogens, toxins and so on. It can be categorized in two types namely, acute and chronic inflammation that depends on the extent of the injury caused due to inflammation. Basically, acute inflammatory responses regulate various cellular and molecular events and the interaction of different types of immune cells, that helps to minimize the injury. These events may lead to recovery of tissue homeostasis during acute inflammation. However, during chronic inflammation as in neurodegenerative diseases, a variety of key players orchestrate the process to amplify the magnitude of inflammation.¹

Mitogen-activated protein kinases (MAPKs) are one of the widely studied kinase family that composed of three well known subfamily: p38 MAPKs, extracellular signal-regulated protein kinases (ERKs) and c-Jun N-terminal kinases (JNKs). The p38MAPKs are encoded by p38α, p38β, p38γ, and p38δ genes. It has been shown that the p38MAPK pathway is critically involved in the regulation of inflammation via activation of TLR4 receptor. MAPK-activated protein kinase 2 (MK2) is one of the key substrates downstream to p38α/p38β, which on phosphorylation regulate the production and signaling of pro-inflammatory cytokines.^{2, 3}

The inhibition of MK2 by tool compound, PF-3644022 has shown reduction of inflammatory biomarkers in various in vitro and in vivo models.⁴ So, the present study is designed to investigate and compare the anti-inflammatory effects of quercetin⁵ with MK2 inhibitor, PF-3644022 in LPS induced SH-SY5Y cell line in vitro and rat whole blood ex vivo.

The computational docking study (binding affinity) data was obtained through the Auto Dock Vina software and the interaction among the protein-ligand inhibition was studied through Biovia (discovery studio) and Ligplot+ software (Figure 1A-D). The structure-based binding site identification study method was performed to compare the binding affinities among PF-3644022 and quercetin against MK2 protein. The binding affinity of PF-3644022 with MK2 was found to be −8.4 Kcal/mol. The interaction between PF-3644022 and MK2 is divided into two types. At first, it formed one hydrophilic bond having bond length 3.17 Å against Arg 149 (A chain) of MK2 protein. Second, the hydrophobic bonds were formed with Glu 165, Ser 169, Asn 200, Lys 168, Ile 202, Tyr 194, Ile 166, and pro 199 in MK2 protein. The binding affinity of quercetin was found to be −8.1 Kcal/mol. The interaction between quercetin and MK2 showed that there were four hydrophilic bonds with showing different bond length against MK2 protein amino acid sequence like Asp 207 (2.70 Å), Glu 139(2.70 Å), Leu 141(2.80 Å), and Glu 145(2.91 Å). This binding also showed hydrophobic interaction against MK2 protein amino acid such as Gly 73