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β-Thalassaemia is one of the most common monogenic diseases with no effective cure in the majority of patients. Unbalanced production of α-globin in the presence of defective synthesis of β-globin is the primary mechanism for anaemia in β-thalassaemia. Clinical genetic data accumulated over three decades have clearly demonstrated that direct suppression of α-globin and induction of γ-globin are effective in reducing the globin chain imbalance in erythroid cells hence improving the clinical outcome of patients with β-thalassaemia. Here, we show that the histone deacetylase inhibitor drug, vorin
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Epigenetic regulation of gene transcription by small molecule inhibitors of histone deacetylases (HDAC) is a novel cancer therapy. Vorinostat (Zolinza()) is the first FDA approved HDAC-inhibitor for treatment of patients with cutaneous T cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies. Vorinostat was active against solid tumors and hematologic malignancies as intravenous and oral preparations in Phase I development. In two Phase II trials, vorinostat was safe and effective at an oral dose of 400 mg/day with an overall response r
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BackgroundRheumatoid arthritis (RA) and idiopathic pulmonary fibrosis (IPF) share a common pathogenic mechanism, but the underlying mechanisms remain ambiguous. Our study aims at exploring the genetic-level pathogenic mechanism of these two diseases.MethodsWe carried out bioinformatics analysis on the GSE55235 and GSE213001 datasets. Machine learning was employed to identify candidate genes, which were further verified using the GSE92592 and GSE89408 datasets, as well as quantitative real-time PCR (qRT-PCR). The expression levels of TOP2A in RA and IPF in vitro models were confirmed using West
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Cancer remains a heavy health burden resulting in a high rate of mortality around the world. The presently used anticancer drugs suffer from several shortcomings, such as drug toxicity, poor biodegradability and bioavailability, and poor water solubility and drug resistance. Cancer is treated effectively by combination therapy whereby two or more anticancer drugs are employed. Most of the combination chemotherapies result in a synergistic effect and overcome drug resistance. Furthermore, the design of polymer-based nanocarriers for combination therapy has been reported by several researchers t
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Cells must maintain their proteome homeostasis by balancing protein synthesis and degradation. This is facilitated by evolutionarily-conserved processes, including the unfolded protein response and the proteasome-based system of protein clearance, autophagy, and chaperone-mediated autophagy. In some hematological malignancies, including acute myeloid leukemia, misfolding or aggregation of the wild-type p53 tumor-suppressor renders cells unable to undergo apoptosis, even with an intact p53 DNA sequence. Moreover, blocking the proteasome pathway triggers lymphoma cell apoptosis. Extensive studie
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BackgroundPsilocybin, a naturally occurring psychedelic compound found in certain species of mushrooms, is known for its effects on anxiety and depression. It has recently gained increasing interest for its potential therapeutic effects, particularly in patients with advanced cancer. This systematic review and meta-analysis aim to evaluate the effects of psilocybin on adult patients with advanced cancer.AimTo investigate the therapeutic effect of psilocybin in patients with advanced cancer.MethodsA comprehensive search of electronic databases was conducted in PubMed, Cochrane Central Register
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Exosomes, which are nano-sized transport bio-vehicles, play a pivotal role in maintaining homeostasis by exchanging genetic or metabolic information between different cells. Exosomes can also play a vital role in transferring virulent factors between the host and parasite, thereby regulating host gene expression and the immune interphase. The association of inflammation with disease development and the potential of exosomes to enhance or mitigate inflammatory pathways support the notion that exosomes have the potential to alter the course of a disease. Clinical trials exploring the role of exo
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Background and Objective: This study aims to find the key immune genes and mechanisms of low bone mineral density (LBMD) in ankylosing spondylitis (AS) patients. Methods: AS and LBMD datasets were downloaded from the GEO database, and differential expression gene analysis was performed to obtain DEGs. Immune-related genes (IRGs) were obtained from ImmPort. Overlapping DEGs and IRGs got I-DEGs. Pearson coefficients were used to calculate DEGs and IRGs correlations in the AS and LBMD datasets. Louvain community discovery was used to cluster the co-expression network to get gene modules. The modu
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The transition of immunotherapy administration from intravenous infusion to subcutaneous (SC) administration of monoclonal antibody formulations for oncology patients has garnered significant interest. SC administration offers multiple benefits, including potential for at-home administration, enhanced patient compliance, reduced hospital congestion, lowered health care costs, and improved sustainability by reducing drug wastage and minimizing environmental impact. However, for many biologics, the shift to SC administration requires the development of high-concentration monoclonal antibody prod
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According to the latest consensus, many traditional diseases are considered metabolic diseases, such as cancer, type 2 diabetes, obesity, and cardiovascular disease. Currently, metabolic diseases are increasingly prevalent because of the ever-improving living standards and have become the leading threat to human health. Multiple therapy methods have been applied to treat these diseases, which improves the quality of life of many patients, but the overall effect is still unsatisfactory. Therefore, intensive research on the metabolic process and the pathogenesis of metabolic diseases is imperati
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Psoriasis is an incurable skin disease that develops in about two-thirds of patients before the age of 40 and requires lifelong treatment; its pathological mechanisms have not been fully elucidated. The core pathological process of psoriasis is epidermal thickening caused by the excessive proliferation of epidermal keratinocytes, which is similar to the key feature of cancer; the malignant proliferation of cancer cells causes tumor enlargement, suggesting that there is a certain degree of commonality between psoriasis and cancer. This article reviews the pathological mechanisms that are common
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BackgroundMalignancy is a significant, life-limiting complication after lung transplantation (LuTx) and the second common long-term cause of death. We aimed to investigate its incidence and effect on the outcome.MethodsThis is a retrospective observational study. Between 1996 and 2022, n = 627 lung transplantations (LuTx) were performed in our department. We used our institutional database to identify recipients with malignancies after LuTx and examined the malignancies' incidence and mortality.ResultsN = 59 malignancies occurred in n = 55 (8.8%) LuTx recipients. The post-LTx malignancies inci
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Despite impressive efforts invested in epigenetic research in the last 50 years, clinical applications are still lacking. Only a few university hospital centers currently use epigenetic biomarkers at the bedside. Moreover, the overall concept of precision medicine is not widely recognized in routine medical practice and the reductionist approach remains predominant in treating patients affected by major diseases such as cancer and cardiovascular diseases. By its' very nature, epigenetics is integrative of genetic networks. The study of epigenetic biomarkers has led to the identification of num
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Amyloid light chain (AL) amyloidosis is a rare, debilitating, often fatal disease. Symptoms of cardiomyopathy are common presenting features, and patients often are referred to cardiologists. Cardiac amyloid infiltration is the leading predictor of death. However, the variable presentation and perceived rarity of the disease frequently lead to delay in suspecting amyloidosis as a cause of heart failure, leading to misdiagnoses and a marked delay in diagnosis, with devastating consequences for the patient. A median time from symptom onset to correct diagnosis of about 2 years is often too long
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Research on the neurobiology of cancer, which lies at the border of neuroscience and oncology, has elucidated the mechanisms and pathways that enable the nervous system to modulate processes associated with cancer initiation and progression. This research has also shown that several drugs which modulate interactions between the nervous system and the tumor micro- and macroenvironments significantly reduced the progression of cancer in animal models. Encouraging results were also provided by prospective clinical trials investigating the effect of drugs that reduce adrenergic signaling on the co
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Bone and joint-related diseases, including osteoarthritis (OA), rheumatoid arthritis (RA), and bone tumors, pose significant health challenges due to their debilitating effects on the musculoskeletal system. 14-3-3 proteins, a family of conserved regulatory molecules, play a critical role in the pathology of these diseases. This review discusses the intricate structure and multifunctionality of 14-3-3 proteins, their regulation of signaling pathways, and their interactions with other proteins. We underscore the significance of 14-3-3 proteins in the regulation of osteoblasts, osteoclasts, chon
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The prevalence of secondary hyperparathyroidism (SHPT) in advanced chronic kidney disease (CKD) exceeds 80 %. Our previous study indicated that photodynamic therapy (PDT) has potential for treating SHPT. Long noncoding RNA (lncRNA) is involved in various oxidative stress and apoptotic processes, but the molecular mechanism remains unreported. In this study, we found that PDT induced apoptosis in SHPT through reactive oxygen species (ROS) accumulation. The expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and heme oxygenase 1 (HO-1) within SHPT was upregulated after
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Cancer development and progression are increasingly understood to arise from dynamic interactions between genetic alterations and environmentally driven epigenetic regulation, with dietary exposures representing one of the most biologically influential and modifiable factors. Given the expanding evidence linking nutrition to epigenomic remodeling, a comprehensive synthesis of how specific dietary components influence cancer-relevant epigenetic mechanisms is needed to clarify their preventive and therapeutic relevance. This review brings together mechanistic, epidemiologic, and translational fi
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The term 'autophagy' literally translates to 'self-eating' and alterations to autophagy have been identified as one of the several molecular changes that occur with aging in a variety of species. Autophagy and aging, have a complicated and multifaceted relationship that has recently come to light thanks to breakthroughs in our understanding of the various substrates of autophagy on tissue homoeostasis. Several studies have been conducted to reveal the relationship between autophagy and age-related diseases. The present review looks at a few new aspects of autophagy and speculates on how they m
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