Recently, increasing evidence has suggested the association between gut dysbiosis and Alzheimer's disease (AD) progression, yet the role of gut microbiota in AD pathogenesis remains obscure. Herein, we provide a potential mechanistic link between gut microbiota dysbiosis and neuroinflammation in AD progression. Using AD mouse models, we discovered that, during AD progression, the alteration of gut microbiota composition leads to the peripheral accumulation of phenylalanine and isoleucine, which stimulates the differentiation and proliferation of pro-inflammatory T helper 1 (Th1) cells. The brain-infiltrated peripheral Th1 immune cells are associated with the M1 microglia activation, contributing to AD-associated neuroinflammation. Importantly, the elevation of phenylalanine and isoleucine concentrations and the increase of Th1 cell frequency in the blood were also observed in two small independent cohorts of patients with mild cognitive impairment (MCI) due to AD. Furthermore, GV-971, a sodium oligomannate that has demonstrated solid and consistent cognition improvement in a phase 3 clinical trial in China, suppresses gut dysbiosis and the associated phenylalanine/isoleucine accumulation, harnesses neuroinflammation and reverses the cognition impairment. Together, our findings highlight the role of gut dysbiosis-promoted neuroinflammation in AD progression and suggest a novel strategy for AD therapy by remodelling the gut microbiota.

Oxidative stress, in which production of highly reactive oxygen species (ROS) and reactive nitrogen species (RNS) overwhelms antioxidant defenses, is a feature of many neurological diseases and neurodegeneration. ROS and RNS generated extracellularly and intracellularly by various processes initiate and promote neurodegeneration in CNS. ROS and RNS can directly oxidize and damage macromolecules such as DNA, proteins, and lipids, culminating in neurodegeneration in the CNS. Neurons are most susceptible to direct oxidative injury by ROS and RNS. ROS and RNS can also indirectly contribute to tissue damage by activating a number of cellular pathways resulting in the expression of stress-sensitive genes and proteins to cause oxidative injury. Moreover, oxidative stress also activates mechanisms that result in a glia-mediated inflammation that also causes secondary neuronal damage. Associated with neuronal injuries caused by many CNS insults is an activation of glial cells (particularly astrocytes and microglia) at the sites of injury. Activated glial cells are thus histopathological hallmarks of neurodegenerative diseases. Even though direct contact of activated glia with neurons per se may not necessarily be toxic, the immune mediators (e.g. nitric oxide and reactive oxygen species, pro-inflammatory cytokines and chemokines) released by activated glial cells are currently considered to be candidate neurotoxins. Therefore, study of the protective role of antioxidant compounds on inhibition of the inflammatory response and correcting the fundamental oxidant/antioxidant imbalance in patients suffering from neurodegenerative diseases are important vistas for further research. The purpose of this review is to summarize the current evidence in support of this critical role played by oxidative stress of neuronal and glial origin in neurodegenerative diseases. The mechanistic basis of the neuroprotective activity of antioxidants does not only rely on the general free radical trapping or antioxidant activity per se in neurons, but also the suppression of genes induced by pro-inflammatory cytokines and other mediators released by glial cells. We propose that combinations of agents which act at sequential steps in the neurodegenerative process can produce additive neuroprotective effects. A cocktail of multiple antioxidants with anti-inflammatory agents may be more beneficial in the prevention of neurodegenerative disease. A clearer appreciation of the potential therapeutic utility of antioxidants would emerge only when the complexity of their effects on mechanisms that interact to determine the extent of oxidative damage in vivo are more fully defined and understood.

Higher serum concentrations of PFOA and PFHxS are associated with total T3, total T4, and free T4 in the U.S. general population. More studies are warranted to clarify the causal relationship between PFCs and thyroid function.

These data not only demonstrated SAA was useful in predicting survival of patients with gastric cancer, but they also showed that SAA was a valuable tool for postoperative follow-up.

Intracranial aneurysm is a common life-threatening disease. Computed tomography angiography is recommended as the standard diagnosis tool; yet, interpretation can be time-consuming and challenging. We present a specific deep-learning-based model trained on 1,177 digital subtraction angiography verified bone-removal computed tomography angiography cases. The model has good tolerance to image quality and is tested with different manufacturers. Simulated real-world studies are conducted in consecutive internal and external cohorts, in which it achieves an improved patient-level sensitivity and lesion-level sensitivity compared to that of radiologists and expert neurosurgeons. A specific cohort of suspected acute ischemic stroke is employed and it is found that 99.0% predicted-negative cases can be trusted with high confidence, leading to a potential reduction in human workload. A prospective study is warranted to determine whether the algorithm could improve patients’ care in comparison to clinicians’ assessment.