Rejected

The histone demethylase KDM4A is reported to be overexpressed and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of H3K9 or H3K36 methylation marks. However, the biological role and mechanism of KDM4A in prostate cancer remain unclear. Herein, we reported KDM4A expression was upregulation in PTEN knockout mouse prostate tissue. Depletion of KDM4A in prostate cancer cells inhibited their proliferation and survival in vivo and vitro. Further studies reveal that USP1 is a deubiquitinase that regulates KDM4A K48-linked deubiquitin and stability. Interestingly, we found c-Myc was a key downstream effector of USP1-KDM4A/AR axis in driving prostate cancer cell proliferation. Notably, upregulation of KDM4A expression with high USP1 expression were observed in most prostate tumors and inhibition of USP1 promotes prostate cancer cells response to therapeutic agent_enzalutamide. Our studies propose USP1 may be an anti-cancer therapeutic target in prostate cancer.

Small fiber neuropathy is rare in children. It has been associated with several autoimmune disorders, but there are no reports of an autoinflammatory etiology. Methods The data of four children presenting with erythromelalgia and neuropathic pain in 2014-2019 were collected retrospectively from the electronic database of a pediatric medical center.

Immune system alteration has been implicated in the pathogenesis of chronic pain conditions, epilepsy and generalized anxiety disorder. Targeting cytokines has recently been proposed for the management of such conditions. Pregabalin (PGB) is an antiepileptic agent used for the management of these conditions. However, little is known about its immunomodulatory effects on cytokine secretion in vivo and in vitro. Hence, a mitogen (Lipopolysaccharide [LPS] or Concanavalin A [ConA])-induced murine model of inflammation was used to investigate the effect of PGB on in vivo and in vitro IL-1β, IL-6, TNF-α and IL-2 cytokine secretion using ELISA. In addition, PGB effect on spleen histology, as a lymphoid organ, was examined. Our results revealed that PGB significantly inhibited the secretion of ConA-induced IL-6 secretion, basal and ConA-induced TNF-α and IL-2 secretion in splenocytes in vitro. In vivo, PGB inhibited basal and LPS/ConA-induced IL-6 and TNF-α secretion in addition to LPS-induced IL-1β and ConA-induced IL-2 secretion. Moreover, PGB attenuated mitogen-induced inflammatory changes in the spleen. These findings provide an evidence of the anti-inflammatory properties of PGB on cytokine secretion and lymphoid organ inflammation. This might give insights into the role of PGB in the management of the inflammatory state in PGB-indicated conditions.

Nociceptive stimuli to the orofacial region are typically received by the peripheral terminal of trigeminal ganglion (TG) neurons, and noxious orofacial information is subsequently conveyed to the trigeminal spinal subnucleus caudalis and the upper cervical spinal cord (C1-C2). This information is further transmitted to the cortical somatosensory regions and limbic system via the thalamus, which then leads to the perception of pain. It is a well-established fact that the presence of abnormal pain in the orofacial region is etiologically associated with neuroplastic changes that may occur at any point in the pain transmission pathway from the peripheral to the central nervous system (CNS). Recently, several studies have reported that functional plastic changes in a large number of cells, including TG neurons, glial cells (satellite cells, microglia, and astrocytes), and immune cells (macrophages and neutrophils), contribute to the sensitization and disinhibition of neurons in the peripheral and CNS, which results in orofacial pain hypersensitivity.

Physiological pain protects the body and its systems from damage, but pathological pain has no obvious biological role. Complementary alternative medicine (CAM) agents are being increasingly studied in the treatment of clinical pain, and some dietary constituents (polyphenol, carotenoids, and fatty acids) and supplements may modify pain pathways. Because these substances modulate neuronal excitability-including the trigeminal pain pathway via various voltage-gated ionic channels and transient receptor potential and ligand-gated channels, dietary constituents could contribute to CAM as therapeutic agents for attenuating orofacial noxious sensory information. This review summarizes the current understanding of the mechanisms by which dietary constituents might attenuate excitability of trigeminal nociceptive neurons implicated in blocking pain, particularly in relation to the authors' recent experimental data, and discusses the development of functional foods and the contribution of dietary constituents in the relief of clinical dental pain without the side effects of nonsteroidal anti-inflammatory drugs.

Acute respiratory distress syndrome (ARDS) is caused by rapid-onset (within hours) acute inflammatory processes in lung tissue, and it is a life-threatening condition with high mortality. The treatment of ARDS to date is focused on the prevention of further iatrogenic damage of the lung rather than the treatment of the initial inflammatory process. Several preclinical studies have revealed a beneficial effect of iloprost on the control of pulmonary inflammation, and in a small number of patients with ARDS, iloprost treatment resulted in improved oxygenation. Therefore, we plan to conduct a large multicenter trial to evaluate the effect of iloprost on ARDS.

To assess the antipsychotic efficacy and safety of a combination of olanzapine and samidorphan (OLZ/SAM).

A retrospective study using a national insurance claims database.

Pediatric spinal vascular malformations are rare entities that typically present with symptoms from their effect on surrounding structures. Here we report a unique case of lumbar spinal dural/perimedullary arteriovenous fistula (AVF) that presented with intraventricular hemorrhage and hydrocephalus. The previously healthy child presented with lethargy and headache, and initial imaging revealed only ventriculomegaly with trace intraventricular blood. His mental status improved with CSF diversion via an external ventricular drain. Further workup revealed a spinal AVF that was treated via endovascular embolization. His course was complicated by vasospasm requiring endovascular treatment and he eventually required ventriculoperitoneal shunt placement. He made a full recovery and has returned to his normal activities. This is a unique case of spinal AVF presentation and highlights the importance of considering imaging of the entire neuroaxis during workup for hydrocephalus.