Chinese medical journal
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Chinese medical journal · May 2022
ReviewBile acids and sphingolipids in non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) is one of the fastest-growing diseases, and its global prevalence is estimated to increase >50% by 2030. NAFLD is comorbid with metabolic syndrome, obesity, type 2 diabetes, and insulin resistance. Despite extensive research efforts, there are no pharmacologic or biological therapeutics for the treatment of NAFLD. ⋯ Moreover, the identification of bile acids as activators of sphingolipid-mediated signaling pathways established a novel theory for bile acid and sphingolipid biology. In this review, we summarize the recent advances in the understanding of bile acid and sphingolipid-mediated signaling pathways as potential contributors to NAFLD. A better understanding of the pathologic effects mediated by bile acids and sphingolipids will facilitate the development of new diagnostic and therapeutic strategies for NAFLD.
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Chinese medical journal · May 2022
ReviewCharacteristics, phenotypes, mechanisms and management of severe asthma.
Severe asthma is "asthma which requires treatment with high dose inhaled corticosteroids (ICS) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming 'uncontrolled' or which remains 'uncontrolled' despite this therapy." The state of control was defined by symptoms, exacerbations and the degree of airflow obstruction. Therefore, for the diagnosis of severe asthma, it is important to have evidence for a diagnosis of asthma with an assessment of its severity, followed by a review of comorbidities, risk factors, triggers and an assessment of whether treatment is commensurate with severity, whether the prescribed treatments have been adhered to and whether inhaled therapy has been properly administered. Phenotyping of severe asthma has been introduced with the definition of a severe eosinophilic asthma phenotype characterized by recurrent exacerbations despite being on high dose ICS and sometimes oral corticosteroids, with a high blood eosinophil count and a raised level of nitric oxide in exhaled breath. ⋯ No targeted treatments are currently available for non-T2 inflammatory phenotypes. Long-term azithromycin and bronchial thermoplasty may be considered. The future lies with molecular phenotyping of the airway inflammatory process to refine asthma endotypes for precision medicine.
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Chinese medical journal · May 2022
ReviewUpdate on lymphocyte-activation gene 3 (LAG-3) in cancers: from biological properties to clinical applications.
Immunotherapy that targets checkpoints, especially programmed cell death protein 1 and programmed cell death ligand 1, has revolutionized cancer therapy regimens. The overall response rate to mono-immunotherapy, however, is limited, emphasizing the need to potentiate the efficacy of these regimens. ⋯ Increasing evidence, particularly in the last 5 years, has shown the potential of LAG-3 blockade in anti-tumor immunity. This review provides an update on the biological properties and clinical applications of LAG-3 in cancers.
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Chinese medical journal · May 2022
ReviewHepatocyte nuclear factor 4α in the pathogenesis of non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver disease worldwide. It refers to a range of liver conditions affecting people who drink little or no alcohol. NAFLD comprises non-alcoholic fatty liver and non-alcoholic steatohepatitis (NASH), the more aggressive form of NAFLD. ⋯ In this review, we summarize the recent advances in the understanding of the pathogenesis of NAFLD with a focus on the regulation of HNF4α and the role of hepatic HNF4α in NAFLD. Several lines of evidence have shown that hepatic HNF4α plays a key role in the initiation and progression of NAFLD. Recent data suggest that hepatic HNF4α may be a promising target for treatment of NAFLD.
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Chinese medical journal · May 2022
ReviewTargeting the elabela/apelin-apelin receptor axis as a novel therapeutic approach for hypertension.
Hypertension is the leading risk factor for global mortality and morbidity and those with hypertension are more likely to develop severe symptoms in cardiovascular and cerebrovascular system, which is closely related to abnormal renin-angiotensin system and elabela/apelin-apelin receptor (APJ) axis. The elabela/apelin-APJ axis exerts essential roles in regulating blood pressure levels, vascular tone, and cardiovascular dysfunction in hypertension by counterbalancing the action of the angiotensin II/angiotensin II type 1 receptor axis and enhancing the endothelial nitric oxide (NO) synthase/NO signaling. Furthermore, the elabela/apelin-APJ axis demonstrates beneficial effects in cardiovascular physiology and pathophysiology, including angiogenesis, cellular proliferation, fibrosis, apoptosis, oxidative stress, and cardiovascular remodeling and dysfunction during hypertension. ⋯ Finally, both loss-of-function and gain-of-function approaches have defined critical roles of the elabela/apelin-APJ axis in reducing the development and severity of hypertensive diseases. Thus, targeting the elabela/apelin-APJ axis has emerged as a pre-warning biomarker and a novel therapeutic approach against progression of hypertension, and an increased understanding of cardiovascular actions of the elabela/apelin-APJ axis will help to develop effective interventions for hypertension. In this review, we focus on the physiology and biochemistry, diverse actions, and underlying mechanisms of the elabela/apelin-APJ axis, highlighting its role in hypertension and hypertensive cardiovascular injury and dysfunction, with a view to provide a prospective strategy for hypertensive disease therapy.