Signaling pathways AND Review

Chromatin remodeling is a critical step in the DNA damage response, and the ATP-dependent chromatin remodelers are a group of epigenetic regulators that alter nucleosome assembly and regulate transcription factor accessibility to DNA, preventing genomic instability and tumorigenesis caused by DNA damage. The SWI/SNF chromatin remodeling complex is one of them, and mutations in the gene encoding the SWI/SNF subunit are frequently found in digestive tumors. We review the most recent literature on the role of SWI/SNF complexes in digestive tumorigenesis, with different SWI/SNF subunits playing different roles...

The introduction of novel immunotherapies has significantly transformed the treatment landscape of genitourinary (GU) cancers, even becoming the standard of care in some settings. One such type of immunotherapy, immune checkpoint inhibitors (ICIs) like nivolumab, ipilimumab, pembrolizumab, and atezolizumab play a pivotal role by disturbing signaling pathways that limit the immune system's ability to fight tumor cells. Despite the profound impact of these treatments, not all tumors are responsive. Recent research efforts have been focused on understanding how cancer cells manage to evade the immune response and identifying the possible mechanisms behind resistance to immunotherapy...

BACKGROUND: Diosmetin is an O-methylated flavone and the aglycone part of the flavonoid glycosides diosmin that occurs naturally in citrus fruits. Pharmacologically, diosmetin is reported to exhibit anticancer, antimicrobial, antioxidant, oestrogenic, and anti-inflammatory activities. OBJECTIVE: This comprehensive review was aimed to critically explore diverse pharmacological activities exhibited by diosmetin. Along with that, this review can also identify potential research areas with an elucidation of the multifactorial underlying signaling mechanism of action of diosmetin in different diseases...

Diabetes Mellitus develops when the body becomes unable to fuel its cells with glucose, which results in the accumulation of sugar excess in the bloodstream. Because it has diverse pathophysiological impacts on the body, diabetes mellitus represents a significant issue of concern in an attempt to find suitable treatment modalities and medications for afflicted diabetic patients. Glucagon-like peptide 1 (GLP-1) plays a pivotal role in the incretin effect, emerging as a prospective treatment for diabetes mellitus and a promising means of regenerating pancreatic cells, whether directly or through its receptor agonists...

Osteoporosis is a systemic metabolic disease characterized by disrupted bone formation/resorption and homeostasis. Flavonoids extracted from traditional Chinese medicinal plants regulate bone homeostasis by intervening in differentiating bone marrow mesenchymal stem cells, balancing the bone immune system, inhibiting oxidative stress response, and reversing iron overload. The target molecules and signaling pathways, such as Wnt/β-catenin and OPG/RANKL/RANK, directly affect osteoblast/osteoclast activity, exhibiting significant potential in the treatment of OP...

Abrocitinib is a highly selective Janus kinase 1 (JAK1) inhibitor that can block a multitude of inflammatory signaling pathways that underlie atopic dermatitis (AD). In addition, abrocitinib inhibits JAK1 signaling in sensory neurons to alleviate acute and chronic pruritus during AD. However, substantial variations in efficacy and safety risks remain due to variations in doses applied in clinical use. Therefore for the present study, differences in the efficacy and tolerability of 100 and 200 mg abrocitinib for treating pruritus and eczema symptoms in patients with moderate-to-severe AD were evaluated compared with placebo...

The diagnostics of colorectal cancer (CRC) and precancerous lesions in the colon is one of the most urgent matters to be considered for the modern protocols of complex examination, recommended for use from the age of 45 years, and including both instrumental and laboratory methods of research: Colonoscopy, CT colonography, flexible sigmoidoscopy, fecal occult blood test, fecal immunohistochemistry test and stool DNA test Nevertheless, the removal of those precancerous lesions does not solve the issue, and, apart from the regular endoscopic monitoring of patients who are at a high risk of developing CRC, the pharmacological treatment of certain key pathogenic mechanisms leading to the development of CRC is required...

OBJECTIVE: This article addresses the persistent challenge of Delayed Hospital Discharge (DHD) and aims to provide a comprehensive overview, synthesis, and actionable, sustainable plan based on the synthesis of the systematic review articles spanning the past 24 years. Our research aims to comprehensively examine DHD, identifying its primary causes and emphasizing the significance of effective communication and management in healthcare settings. METHODS: We conducted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) method for synthesizing findings from 23 review papers published over the last two decades, encompassing over 700 studies...

The activity of HIV-1 and its viral proteins within the central nervous system (CNS) is responsible for a wide array of neuropathological effects, resulting in a spectrum of neurocognitive deficits defined as HIV-associated neurocognitive disorders (HAND). Amongst the various viral proteins, the transactivator of transcription (Tat) remains detectable even with effective antiretroviral therapy (ART) and suppressed viremia, highlighting the significance of this protein in the modern ART era. Tat has been extensively researched in both fundamental and clinical settings due to its role in neuroinflammation, neuronal damage, and neurocognitive impairment amongst people living with HIV (PLHIV)...

Obesity is a significant risk factor for health issues like type 2 diabetes and cardiovascular disease. It often proves resistant to traditional lifestyle interventions, prompting a need for more precise therapeutic strategies. This has led to a focus on signaling pathways and neuroendocrine mechanisms to develop targeted obesity treatments. Recent developments in obesity management have been revolutionized by introducing novel glucagon-like peptide-1 (GLP-1) based drugs, such as semaglutide and tirzepatide...

Ferroptosis, a novel form of cell death regulation, was identified in 2012. It is characterized by unique features that differentiate it from other types of cell death, including necrosis, apoptosis, autophagy, and pyroptosis. Ferroptosis is defined by an abundance of iron ions and lipid peroxidation, resulting in alterations in subcellular structures, an elevation in reactive oxygen species (ROS), a reduction in glutathione (GSH) levels, and an augmentation in Fe (II) cytokines. Ferroptosis, a regulated process, is controlled by an intricate network of signaling pathways, where multiple stimuli can either enhance or hinder the process...

Macropinocytosis (MP), the actin-dependent bulk uptake of extracellular fluids, plays a central role in nutrient scavenging, allowing cancer cells to sustain their growth in the hypoxic and nutrient-deprived microenvironment often found in solid tumours. The lack of soluble nutrients and several oncogenic signalling pathways, with RAS being the most studied, push MP-dependent internalisation of extracellular proteins, which are then digested in the lysosomes, replenishing the intracellular nutrient pools. This review will highlight recent advances in understanding how MP is regulated in hypoxic cancers, how it impinges on chemoresistance, and how different MP cargos facilitate tumour growth...

The signaling lymphocytic activation molecule (SLAM) family participates in the modulation of various innate and adaptive immune responses. SLAM family (SLAMF) receptors include nine transmembrane glycoproteins, of which SLAMF3 (also known as CD229 or Ly9) has important roles in the modulation of immune responses, from the fundamental activation and suppression of immune cells to the regulation of intricate immune networks. SLAMF3 is mainly expressed in immune cells, such as T, B, and natural killer cells. It has a unique molecular structure, including four immunoglobulin-like domains in the extracellular domain and two immunoreceptor tyrosine-based signaling motifs in the intracellular structural domains...

Liver cancer currently represents the leading cause of cancer-related death worldwide. The majority of liver cancer arises in the context of chronic inflammation and cirrhosis. Surgery, radiation therapy, and chemotherapy have been the guideline-recommended treatment options for decades. Despite enormous advances in the field of liver cancer therapy, an effective cure is yet to be found. Plant-derived polyphenols constitute a large family of phytochemicals, with pleiotropic effects and little toxicity. They can drive cellular events and modify multiple signaling pathways which involves initiation, progression and metastasis of liver cancer and play an important role in contributing to anti-liver cancer drug development...

Among the most common molecular alterations detected in non-small-cell lung cancer (NSCLC) are mutations in Kristen Rat Sarcoma viral oncogene homolog (KRAS). KRAS mutant NSCLC is a heterogenous group of diseases, different from other oncogene-driven tumors in terms of biology and response to therapies. Despite efforts to develop drugs aimed at inhibiting KRAS or its signaling pathways, KRAS had remained undruggable for decades. The discovery of a small pocket in the binding switch II region of KRASG12C has revolutionized the treatment of KRASG12C -mutated NSCLC patients...

Mechanosensitive ion channels are widely distributed in the heart, lung, bladder and other tissues, and plays an important role in exercise-induced cardiovascular function promotion. By reviewing the PubMed databases, the results were summarized using the terms "Exercise/Sport", "Piezo1", "Transient receptor potential (TRP)" and "Cardiovascular" as the keywords, 124-related papers screened were sorted and reviewed. The results showed that: (1) Piezo1 and TRP channels play an important role in regulating blood pressure and the development of cardiovascular diseases such as atherosclerosis, myocardial infarction, and cardiac fibrosis; (2) Exercise promotes cardiac health, inhibits the development of pathological heart to heart failure, regulating the changes in the characterization of Piezo1 and TRP channels; (3) Piezo1 activates downstream signaling pathways with very broad pathways, such as AKT/eNOS, NF-κB, p38MAPK and HIPPO-YAP signaling pathways...

Acute myeloid leukaemia (AML) is a complex haematological malignancy characterised by diverse genetic alterations leading to abnormal proliferation of myeloid precursor cells. One of the most significant genetic alterations in AML involves mutations in the FLT3 gene, which plays a critical role in haematopoiesis and haematopoietic homeostasis. This review explores the current understanding of FLT3 gene mutations and isoforms and the importance of the FLT3 protein in AML. FLT3 mutations, including internal tandem duplications (FLT3-ITD) and point mutations in the tyrosine kinase domain (FLT3-TKD), occur in 25-30% in AML and are associated with poor prognosis...

The Hedgehog (Hh) signaling pathway orchestrates its influence through a dynamic interplay of Hh proteins, the cell surface receptor Ptch1, Smo, and Gli transcription factors, contributing to a myriad of developmental events. Indian Hedgehog (Ihh) and Gli zinc finger transcription factor 1 (Gli1) play crucial roles in developmental regulation within the Hh signaling pathway. Ihh regulates chondrocyte proliferation, differentiation, and bone formation, impacting the development of cranial bones, cartilage, and the temporomandibular joint (TMJ)...

Atopic dermatitis (AD) is a relapsing inflammatory skin condition that has become a global health issue with complex etiology and mounting prevalence. The association of AD with skin and gut microbiota has been revealed by virtue of the continuous development of sequencing technology and genomics analysis. Also, the gut-brain-skin axis and its mutual crosstalk mechanisms have been gradually verified. Accordingly, the microbiota-skin-gut axis also plays an important role in allergic skin inflammation. Herein, we reviewed the relationship between the microbiota-skin-gut axis and AD, explored the underlying signaling molecules and potential pathways, and focused on the potential mechanisms of probiotics, antimicrobial peptides (AMPs), coagulase-negative staphylococci transplantation, fecal microbiota transplantation, AMPs, and addition of essential fatty acids in alleviating AD, with the aim to provide a new perspective for targeting microbiota in the treatment of allergic skin inflammation...

Pregnancy-associated breast cancer (PABC) presents unique challenges due to its occurrence during or shortly after pregnancy. Pregnancy-associated plasma protein A (PAPP-A) has emerged as a potential biomarker and regulator in PABC. This comprehensive review examines the role of PAPP-A in PABC, highlighting its involvement in tissue remodeling and cancer progression. Molecular mechanisms linking PAPP-A to breast cancer, including signaling pathways and interactions with other molecules, are explored. The review also discusses the diagnostic and therapeutic implications of PAPP-A dysregulation in PABC, emphasizing the need for further research to elucidate underlying mechanisms and develop targeted therapies...