Ionizing Radiation-Induced Brain Cell Aging and the Potential Underlying Molecular Mechanisms.

Population aging is occurring rapidly worldwide, challenging the global economy and healthcare services. Brain aging is a significant contributor to various age-related neurological and neuropsychological disorders, including Alzheimer's disease and Parkinson's disease. Several extrinsic factors, such as exposure to ionizing radiation, can accelerate senescence. Multiple human and animal studies have reported that exposure to ionizing radiation can have varied effects on organ aging and lead to the prolongation or shortening of life span depending on the radiation dose or dose rate. This paper reviews the effects of radiation on the aging of different types of brain cells, including neurons, microglia, astrocytes, and cerebral endothelial cells. Further, the relevant molecular mechanisms are discussed. Overall, this review highlights how radiation-induced senescence in different cell types may lead to brain aging, which could result in the development of various neurological and neuropsychological disorders. Therefore, treatment targeting radiation-induced oxidative stress and neuroinflammation may prevent radiation-induced brain aging and the neurological and neuropsychological disorders it may cause.

Role of circular RNAs in gastrointestinal tumors and drug resistance.

The incidence of gastrointestinal cancers has increased significantly over the past decade and gastrointestinal malignancies now rank among the leading causes of mortality globally. Although newer therapeutic strategies such as targeted therapies have greatly improved patient outcomes, their clinical success is limited by drug resistance, treatment failure and recurrence of metastatic disease. Therefore, there is an urgent need for further research identifying accurate and reliable biomarkers for precise treatment strategies. Circular RNAs (circRNAs) exhibit a covalently closed structure, high stability and biological conservation, and their expression is associated with the occurrence and development of gastrointestinal tumors. Moreover, circRNAs may significantly influence drug resistance of gastrointestinal cancers. In this article, we review the role of circRNAs in the occurrence and development of gastrointestinal cancer, their association with drug resistance, and potential application for early diagnosis, treatment and prognosis in gastrointestinal malignancies. Furthermore, we summarize characteristics of circRNA, including mechanism of formation and biological effects via mRNA sponging, chromatin replication, gene regulation, translational modification, signal transduction, and damage repair. Finally, we discuss whether circRNA-related noninvasive testing may be clinically provided in the future. This review provides new insights for the future development of diagnostics and therapeutics based on circRNAs in gastrointestinal tumors.

Diagnosis of mast cell activation syndrome: a global "consensus-2".

The concept that disease rooted principally in chronic aberrant constitutive and reactive activation of mast cells (MCs), without the gross MC neoplasia in mastocytosis, first emerged in the 1980s, but only in the last decade has recognition of "mast cell activation syndrome" (MCAS) grown significantly. Two principal proposals for diagnostic criteria have emerged. One, originally published in 2012, is labeled by its authors as a "consensus" (re-termed here as "consensus-1"). Another sizable contingent of investigators and practitioners favor a different approach (originally published in 2011, newly termed here as "consensus-2"), resembling "consensus-1" in some respects but differing in others, leading to substantial differences between these proposals in the numbers of patients qualifying for diagnosis (and thus treatment). Overdiagnosis by "consensus-2" criteria has potential to be problematic, but underdiagnosis by "consensus-1" criteria seems the far larger problem given (1) increasing appreciation that MCAS is prevalent (up to 17% of the general population), and (2) most MCAS patients, regardless of illness duration prior to diagnosis, can eventually identify treatment yielding sustained improvement. We analyze these proposals (and others) and suggest that, until careful research provides more definitive answers, diagnosis by either proposal is valid, reasonable, and helpful.

Radioprotective Effect of Flavonoids on Ionizing Radiation-Induced Brain Damage.

Patients receiving brain radiotherapy may suffer acute or chronic side effects. Ionizing radiation induces the production of intracellular reactive oxygen species and pro-inflammatory cytokines in the central nervous system, leading to brain damage. Complementary Chinese herbal medicine therapy may reduce radiotherapy-induced side effects. Flavonoids are a class of natural products which can be extracted from Chinese herbal medicine and have been shown to have neuroprotective and radioprotective properties. Flavonoids are effective antioxidants and can also inhibit regulatory enzymes or transcription factors important for controlling inflammatory mediators, affect oxidative stress through interaction with DNA and enhance genomic stability. In this paper, radiation-induced brain damage and the relevant molecular mechanism were summarized. The radio-neuro-protective effect of flavonoids, i.e., antioxidant, anti-inflammatory and maintaining genomic stability, were then reviewed. We concluded that flavonoids treatment may be a promising complementary therapy to prevent radiotherapy-induced brain pathophysiological changes and cognitive impairment.

Patient characteristics of suspected mast-cell activation syndrome with sinonasal obstruction: a single institution experience.

BACKGROUND: Mast-cell activation syndrome (MCAS) is increasingly recognized. Sinonasal obstruction is common among these patients. There is a paucity of literature describing the characteristics of MCAS and treatment outcomes. METHODS: Retrospective review of 192 patients with nasal congestion July 2017 to May 2019 among 3 providers (1 allergist, 2 rhinologists) was conducted. Suspected MCAS criteria were as follows: (1) at least 2 recurrent severe symptoms in addition to nasal congestion: flushing, pruritus, urticaria, angioedema, wheezing, throat swelling, headache, hypotension, diarrhea; (2) clinical response to medications that target mast cell mediators. Quality of life (QOL) outcomes were quantified using the 22-item Sino-Nasal Outcome Test (SNOT-22). RESULTS: Thirty-two patients with nasal congestion were suspected of MCAS. The median age was 47 years; 24 of 32 were female; 13 of 32 had prior history of sinonasal surgery and 11 of 32 allergen immunotherapy. Out of 32, 19 had history of asthma, 10 drug allergy, 11 food allergy, and 10 anaphylaxis. The median number of medications targeting mast cell activation was 4 (range, 2-7). Eleven patients were offered surgery by a rhinologist after adequate medical management. Three of 32 patients showed elevation of serum tryptase. Fourteen completed pretreatment and posttreatment SNOT-22 (4/14 surgery, 10/14 medical management). Pretreatment score was 59.8 ± 6.2 (mean ± standard error [SEM]) and posttreatment score was 42.8 ± 6.7; the difference was statistically and clinically significant (p = 0.0015). Both groups showed a mean 17-point reduction. CONCLUSION: A multidisciplinary approach to the treatment of sinonasal symptoms using both escalation of medical therapy and surgical approaches may improve QOL of patients with suspected MCAS. Consensus criteria for MCAS, which includes elevation in tryptase over baseline during an episode, may exclude the full spectrum of individuals with MCAS from potentially beneficial treatment.