Current state of signaling pathways associated with the pathogenesis of idiopathic pulmonary fibrosis.

Idiopathic Pulmonary Fibrosis (IPF) represents a chronic and progressive pulmonary disorder distinguished by a notable mortality rate. Despite the elusive nature of the pathogenic mechanisms, several signaling pathways have been elucidated for their pivotal roles in the progression of this ailment. This manuscript aims to comprehensively review the existing literature on the signaling pathways linked to the pathogenesis of IPF, both within national and international contexts. The objective is to enhance the comprehension of the pathogenic mechanisms underlying IPF and offer a scholarly foundation for the advancement of more efficacious therapeutic strategies, thereby fostering research and clinical practices within this domain.

Role of growth differentiation factor 15 in cancer cachexia (Review).

Growth differentiation factor 15 (GDF15), a member of the transforming growth factor-ß family, is a stress-induced cytokine. Under normal circumstances, the expression of GDF15 is low in most tissues. It is highly expressed during tissue injury, inflammation, oxidative stress and cancer. GDF15 has been established as a biomarker in patients with cancer, and is associated with cancer cachexia (CC) and poor survival. CC is a multifactorial metabolic disorder characterized by severe muscle and adipose tissue atrophy, loss of appetite, anemia and bone loss. Cachexia leads to reductions in quality of life and tolerance to anticancer therapy, and results in a poor prognosis in cancer patients. Dysregulated GDF15 levels have been discovered in patients with CC and animal models, where they have been found to be involved in anorexia and weight loss. Although studies have suggested that GDF15 mediates anorexia and weight loss in CC through its neuroreceptor, glial cell-lineage neurotrophic factor family receptor α-like, the effects of GDF15 on CC and the potential regulatory mechanisms require further elucidation. In the present review, the characteristics of GDF15 and its roles and molecular mechanisms in CC are elaborated. The targeting of GDF15 as a potential therapeutic strategy for CC is also discussed.

The roles of P-selectin in cancer cachexia.

P-selectin, a cell adhesion molecule of the selectin family, is expressed on the surface of activated endothelial cells (ECs) and platelets. Binding of P-selectin to P-selectin glycoprotein ligand-1 (PSGL-1) supports the leukocytes capture and rolling on stimulated ECs and increases the aggregation of leukocytes and activated platelets. Cancer cachexia is a systemic inflammation disorder characterized by metabolic disturbances, reduced body weight, loss of appetite, fat depletion, and progressive muscle atrophy. Cachexia status is associated with increased pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), which activates ECs to release P-selectin. Single-nucleotide polymorphisms (SNPs) loci of P-selectin encoding gene SELP are associated with higher level of plasma P-selectin and increase the susceptibility to cachexia in cancer patients. Elevated P-selectin expression has been observed in the hypothalamus, liver, and gastrocnemius muscle in animal models with cancer cachexia. Increased P-selectin may cause excessive inflammatory processes, muscle atrophy, and blood hypercoagulation, thus facilitating the development of cancer cachexia. In this review, physiological functions of P-selectin and its potential roles in cancer cachexia have been summarized. We also discuss the therapeutic potential of P-selectin inhibitors for the treatment of cancer cachexia.

Migraine-like Visual Aura Rriggered by a Large Aneurysm in the Left Extracranial Internal Carotid Artery with Successful Prevention of Recurrence by the new Anticoagulant Dabigatran: First Case Report.

PURPOSE: We present a rare case of late-onset migraine-like visual aura triggered by a large aneurysm in the left extracranial internal carotid artery. To the best of our knowledge, this is the first case of migraine-like visual aura triggered by an extracranial internal carotid artery (ICA) aneurysm. This is also the first case of migraine-like visual aura with probable thromboembolic trigger being successfully treated with a new anticoagulant, dabigatran. CASE REPORT: A 61-year-old woman complained about stereotypical episodes of a short-lasting flickering light in the right visual field for about half a year. Magnetic resonance imaging (MRI) of the head revealed a large aneurysm arising from the mid-cervical portion of the left internal carotid artery (ICA). After anticoagulant therapy with 110 mg of dabigatran twice a day, she became free from the visual symptom. CONCLUSION: Late-onset migraine with aura, especially typical aura without headache should be diagnosed carefully since it can be a challenge to distinguish it from signaling something serious. Micro-thromboembolism, commonly cardiogenic, but rarely arising from a carotid aneurysm, can trigger cerebral ischemic injury, causing transient neuronal hyperexcitability and cortical spreading depression (CSD)-like ''spontaneous'' waves propagating through the penumbra of the injured region into normally perfused tissue. The resultant symptoms may semiologically mimic visual aura. Migraine-like visual aura in this patient was successfully treated with dabigatran. It may not only imply that the patient's migraine-like visual aura was a thromboembolic event, but may also suggest the potential efficacy of the new anticoagulant, dabigatran, as the optimal alternative of warfarin in treating a thromboembolic event arising from a carotid aneurysm.