Chronic Diseases and Translational Medicine最新文献

The lung immune response consists of various cells involved in both innate and adaptive immune processes. Innate immunity participates in immune resistance in a nonspecific manner, whereas adaptive immunity effectively eliminates pathogens through specific recognition. It was previously believed that adaptive immune memory plays a leading role during secondary infections; however, innate immunity is also involved in immune memory. Trained immunity refers to the long-term functional reprogramming of innate immune cells caused by the first infection, which alters the immune response during the second challenge. Tissue resilience limits the tissue damage caused by infection by controlling excessive inflammation and promoting tissue repair. In this review, we summarize the impact of host immunity on the pathophysiological processes of pulmonary infections and discuss the latest progress in this regard. In addition to the factors influencing pathogenic microorganisms, we emphasize the importance of the host response.

Sagittal computed tomography of lumbal spine showing dural ectasia and Tarlow Cyst (red arrows) (A). Magnetic resonance imaging (MRI) axial slice, susceptibility-weighted imaging (SWI) sequences showing siderosis in cerebellar sulci (red arrows) and in the inset uncharacteristic iron deposition in dental nuclei, more pronounced on the left side (red arrows) (B, inset). MRI, SWI, axial slice, showing numerous foci of superficial siderosis (C).

In recent years, emphasis has shifted from preventing and treating chronic obstructive pulmonary disease (COPD) to early prevention, early treatment, and disease stabilization, with the main goal of improving patients’ quality of life and reducing the frequency of acute exacerbations. This review summarizes pharmacological therapies for stable COPD.

Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease and the third leading cause of death worldwide. Developments in next-generation sequencing technology have improved microbiome analysis, which is increasingly recognized as an important component of disease management. Similar to the gut, the lung is a biosphere containing billions of microbial communities. The lung microbiome plays an important role in regulating and maintaining the host immune system. The microbiome composition, metabolites of microorganisms, and the interactions between the lung microbiome and the host immunity profoundly affect the occurrence, development, treatment, and prognosis of COPD. In this review, we drew comparisons between the lung microbiome of healthy individuals and that of patients with COPD. Furthermore, we summarize the intrinsic interactions between the host and the overall lung microbiome, focusing on the underlying mechanisms linking the microbiome to the host innate and adaptive immune response pathways. Finally, we discuss the possibility of using the microbiome as a biomarker to determine the stage and prognosis of COPD and the feasibility of developing a novel, safe, and effective therapeutic target.

The amyloid hypothesis states that the buildup of ß-amyloid in the brain is the main factor for Alzheimer's disease (AD) pathogenesis. An imbalance between ß-amyloid production and ß-amyloid clearance causes the advanced stages of the disease, including the development of neurofibrillary tangles containing tau protein.¹

Many medications that aim to reduce ß-amyloid in AD are not clinically effective. FDA has approved aducanumab, one of four anti-ß-amyloid antibodies that have been demonstrated to mediate the removal of amyloid plaque from the brains of AD patients. FDA accepted the decrease of amyloid plaque as a surrogate endpoint for aducanumab. But there is intense disagreement over the justification for approval and the scope of the clinical benefit provided by antiamyloid antibodies.²

One side effect of the antibodies is brain edema, effusion, and hemorrhages, so called amyloid-related imaging abnormalities (ARIA). ARIA occurs in aged squirrel monkeys as well as in humans.³

Lecanemab, an antiamyloid monoclonal antibody, was associated with edema or effusions in 12.4% of subjects, including three fatal brain hemorrhages; the placebo group had 1.7% brain edema.^4-9 In the case of donanemab, another anti-amyloid monoclonal antibody, if edema or effusion occurred with the first three doses of the drug, the dosage was not increased.¹⁰

A serious clinical condition, brain edema is defined by a pathological swelling of the brain tissue brought on by an increase in the water content of the brain. In humans¹¹ and in a mouse model, APOE isoform affects neurological prognosis following intracerebral hemorrhage. Poor functional outcome and more cerebral edema are linked to APOE4.¹² Three SNPs of the ABCC8 gene, rs2283261, rs3819521, and rs2283258, are significantly associated with brain edema, measured by increased intracranial pressure and CT imaging. Haptoglobin type, Hp2 versus Hp1, may also influence brain edema.¹³

Aquaporins, a family of water channel proteins that have been found in animals, may provide an explanation for AD brain edema. Aquaporin-4 (AQP4), the most significant form of aquaporin in the central nervous system, mediates water homeostasis in healthy and pathological settings, such as severe brain injury.^{13, 14}

Because brain edema has occurred during clinical trials of most anti-amyloid antibodies, we hypothesize that ß-amyloid might be an important element in brain water homeostasis. Removing ß-amyloid could cause brain edema and bleeding in some AD patients. To investigate this idea, we analyzed structures of aquaporin-4 and ß-amyloid from the RCSB protein data bank.

To help identify the brain regions where anti-amyloid antibodies may act, we used the Allen Brain Atlas and the H

Environmental factors, including chemical/physical pollutants, as well as lifestyle and psychological factors, contribute greatly to the pathways leading to cardiometabolic diseases with a heavy disease burden and economic loss. The concept of exposomes provides a novel paradigm for combining all exposure characteristics to evaluate disease risk. A solution-like exposome requires technological support to provide continuous data to monitor vital signs and detect abnormal fluctuations. Wearable devices allow people to conveniently monitor signals during their daily routines. These new technologies empower users to more actively prevent and manage cardiometabolic disease by reviewing risk factors of the disease, especially lifestyle factors, such as sleeping time, screen time, and mental health condition. Devices with multiple sensors can monitor electrocardiography data, oxygen saturation, intraocular pressure, respiratory rate, and heart rate to enhance the exposome study and provide precise suggestions for disease prevention and management.

Childhood obesity is one of the biggest public health challenges globally. It is associated with various adverse health consequences throughout life. Prevention and early intervention represent the most reasonable and cost-effective approaches. Considerable progress has been achieved in the management of obesity in children and adolescents; yet, implementation in the real world remains a challenge. This article aimed to present an overview of the diagnosis and management of obesity in children and adolescents.