Chronic Diseases and Translational Medicine最新文献

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.

Obesity and diabetes mellitus are common metabolic diseases prevalent worldwide. Mice are commonly used to study the pathogenesis of these two conditions. Obesity and diabetes mellitus are induced by administering a high-fat diet in many studies although other diet-induced models are also used. Several factors may influence the outcome of the studies done to study diet-induced obesity in mice. The immune system plays a crucial role in the susceptibility of mice to develop obesity and metabolic disease. In this article, the reasons for differences in susceptibility to develop obesity and diabetes mellitus in mice in response to high-fat-diet feeding and the influence of immunological bias of the mice strain used in studies are evaluated. Mice strains that induce proinflammatory and Th1-type immune responses are found to be susceptible to high-fat-diet-induced obesity. A few studies which directly compared the effect of a high-fat diet on obesity and diabetic phenotype in Th1- and Th2-biased mice strains were briefly analyzed. Based on the observations, it is proposed that the liver and adipose tissue may respond differently to high-fat-diet feeding regimens in Th1- and Th2-biased mice strains. For instance, in Th1-biased mice, adipose tissue fat content was high both in the baseline as well as in response to a high-fat diet whereas in the liver, it was found to be less. It can be inferred that the immune responses to diet-induced models may provide insights into the pathogenesis of obesity and diabetes mellitus.