Explore the vast range of titles available.

Mitochondrial dysfunction is increasingly recognized as a central contributor to the pathogenesis of cardiovascular diseases (CVDs), including heart failure, ischemic heart disease, hypertension, and cardiomyopathy. Mitochondria, known as the powerhouses of the cell, play a vital role in maintaining cardiac energy homeostasis, regulating reactive oxygen species (ROS) production and controlling cell death pathways. Dysregulated mitochondrial function results in impaired adenosine triphosphate (ATP) production, excessive ROS generation, and activation of apoptotic and necrotic pathways, collectively driving the progression of CVDs. This review provides a detailed examination of the molecular mechanisms underlying mitochondrial dysfunction in CVDs, including mutations in mitochondrial DNA (mtDNA), defects in oxidative phosphorylation (OXPHOS), and alterations in mitochondrial dynamics (fusion, fission, and mitophagy). Additionally, the role of mitochondrial dysfunction in specific cardiovascular conditions is explored, highlighting its impact on endothelial dysfunction, myocardial remodeling, and arrhythmias. Emerging therapeutic strategies targeting mitochondrial dysfunction, such as mitochondrial antioxidants, metabolic modulators, and gene therapy, are also discussed. By synthesizing recent advances in mitochondrial biology and cardiovascular research, this review aims to enhance understanding of the role of mitochondria in CVDs and identify potential therapeutic targets to improve cardiovascular outcomes.

Alzheimer’s disease (AD) impacts more than half a million people worldwide, with no cure available. The regulatory approval of three anti-amyloid monoclonal antibodies (mAbs), including aducanumab, lecanemab, and donanemab, has established immunotherapy as a therapeutic approach to modify disease progression. Its multifactorial pathology, which involves amyloid-β (Aβ) plaques, tau neurofibrillary tangles, neuroinflammation, and cerebrovascular dysfunction, limits the efficacy of single-target therapies. The restricted blood–brain barrier (BBB) penetration and amyloid-related imaging abnormalities (ARIA), together with small treatment effects, demonstrate the necessity for advanced biologic therapies. Protein engineering advancements have created bispecific antibodies that bind to pathological proteins (e.g., Aβ, tau) and BBB shuttle receptors to boost brain delivery and dual therapeutic effects. This review combines existing information about antibody-based therapy in AD by focusing on bispecific antibody formats and their preclinical and clinical development, as well as biomarker-based patient selection and upcoming combination strategies. The combination of rationally designed bispecific antibodies with fluid and imaging biomarkers could show potential for overcoming existing therapeutic challenges and delivering significant clinical advantages.

Coronavirus-19 (COVID-19) caused by SARS-CoV-2 has become a global pandemic. Risk of transmission may occur during endoscopy and the goal is to prevent infection among healthcare professionals while providing essential services to patients. Asia was the first continent to have a COVID-19 outbreak, and this position statement of the Asian Pacific Society for Digestive Endoscopy shares our successful experience in maintaining safe and high-quality endoscopy practice at a time when resources are limited. Sixteen experts from key societies of digestive endoscopy in Asia were invited to develop position statements, including patient triage and risk assessment before endoscopy, resource prioritisation and allocation, regular monitoring of personal protective equipment, infection control measures, protective device training and implementation of a strategy for stepwise resumption of endoscopy services after control of the COVID-19 outbreak.

Mitochondrial dysfunction represents a pivotal characteristic of numerous neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. These conditions, distinguished by unique clinical and pathological features, exhibit shared pathways leading to neuronal damage, all of which are closely associated with mitochondrial dysfunction. The high metabolic requirements of neurons make even minor mitochondrial deficiencies highly impactful, driving oxidative stress, energy deficits, and aberrant protein processing. Growing evidence from genetic, biochemical, and cellular investigations associates impaired electron transport chain activity and disrupted quality-control mechanisms, such as mitophagy, with the initial phases of disease progression. Furthermore, the overproduction of reactive oxygen species and persistent neuroinflammation can establish feedforward cycles that exacerbate neuronal deterioration. Recent clinical research has increasingly focused on interventions aimed at enhancing mitochondrial resilience—through antioxidants, small molecules that modulate the balance of mitochondrial fusion and fission, or gene-based therapeutic strategies. Concurrently, initiatives to identify dependable mitochondrial biomarkers seek to detect pathological changes prior to the manifestation of overt symptoms. By integrating the current body of knowledge, this review emphasizes the critical role of preserving mitochondrial homeostasis as a viable therapeutic approach. It also addresses the complexities of translating these findings into clinical practice and underscores the potential of innovative strategies designed to delay or potentially halt neurodegenerative processes.

The incidence of young-onset colorectal cancer (CRC) is reported to be increasing in the Western world. There are no population-based studies assessing the trend across Asia. We performed a multinational cohort study involving four Asian countries/regions, namely Taiwan, Korea, Japan, and Hong Kong. The magnitude and direction of trend in the incidence of young-onset CRC (age < 50) were quantified using Joinpoint Regression Program to estimate average annual percentage change (AAPC). In Taiwan (1995-2014), incidence of young-onset CRC significantly increased in both men (colon cancer: 4.9-9.7 per 100,000; rectal cancer: 4.0-8.3 per 100,000) and women (colon cancer: 5.1-9.7 per 100,000; rectal cancer: 3.8-6.4 per 100,000). In Korea (1999-2014), incidence of young-onset CRC significantly increased in both men (colon cancer: 5.0-10.4 per 100,000; rectal cancer: 4.9-14.0 per 100,000) and women (colon cancer: 4.1-9.6 per 100,000; rectal cancer: 4.1-9.1 per 100,000). The most pronounced change was observed with male rectal cancer, increasing by 3.9% per year in Taiwan (AAPC + 3.9, 95% confidence interval + 3.3 to +4.5, P < 0.05) and 6.0% per year in Korea (AAPC +6.0, 95% confidence interval + 4.5 to +7.6, P < 0.05). Only a significant increase in rectal cancer was noted in Japan (male rectal cancer: 7.2-10.1 per 100,000, female rectal cancer 4.7-6.7 per 100,000) and Hong Kong (male rectal cancer: 4.4-7.0 per 100,000). Increasing trend in young-onset CRC is not limited to the Western world. This finding may have implications on screening program for CRC in these countries/regions.

A potent P2Y12 inhibitor-based dual antiplatelet therapy is recommended for up to 1 year in patients with acute coronary syndrome receiving percutaneous coronary intervention (PCI). The greatest benefit of the potent agent is during the early phase, whereas the risk of excess bleeding continues in the chronic maintenance phase. Therefore, de-escalation of antiplatelet therapy might achieve an optimal balance between ischaemia and bleeding. We aimed to investigate the safety and efficacy of a prasugrel-based dose de-escalation therapy. HOST-REDUCE-POLYTECH-ACS is a randomised, open-label, multicentre, non-inferiority trial done at 35 hospitals in South Korea. We enrolled patients with acute coronary syndrome receiving PCI. Patients meeting the core indication for prasugrel were randomly assigned (1:1) to the de-escalation group or conventional group using a web-based randomisation system. The assessors were masked to the treatment allocation. After 1 month of treatment with 10 mg prasugrel plus 100 mg aspirin daily, the de-escalation group received 5 mg prasugrel, while the conventional group continued to receive 10 mg. The primary endpoint was net adverse clinical events (all-cause death, non-fatal myocardial infarction, stent thrombosis, repeat revascularisation, stroke, and bleeding events of grade 2 or higher according to Bleeding Academic Research Consortium [BARC] criteria) at 1 year. The absolute non-inferiority margin for the primary endpoint was 2·5%. The key secondary endpoints were efficacy outcomes (cardiovascular death, myocardial infarction, stent thrombosis, and ischaemic stroke) and safety outcomes (bleeding events of BARC grade ≥2). The primary analysis was in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02193971. From Sept 30, 2014, to Dec 18, 2018, 3429 patients were screened, of whom 1075 patients did not meet the core indication for prasugrel and 16 were excluded due to randomisation error. 2338 patients were randomly assigned to the de-escalation group (n=1170) or the conventional group (n=1168). The primary endpoint occurred in 82 patients (Kaplan-Meier estimate 7·2%) in the de-escalation group and 116 patients (10·1%) in the conventional group (absolute risk difference −2·9%, pnon-inferiority<0·0001; hazard ratio 0·70 [95% CI 0·52–0·92], pequivalence=0·012). There was no increase in ischaemic risk in the de-escalation group compared with the conventional group (0·76 [0·40–1·45]; p=0·40), and the risk of bleeding events was significantly decreased (0·48 [0·32–0·73]; p=0·0007). In east Asian patients with acute coronary syndrome patients receiving PCI, a prasugrel-based dose de-escalation strategy from 1 month after PCI reduced the risk of net clinical outcomes up to 1 year, mainly driven by a reduction in bleeding without an increase in ischaemia. Daiichi Sankyo, Boston Scientific, Terumo, Biotronik, Qualitech Korea, and Dio.

Nanoparticles-based glues have recently been shown with substantial potential for hydrogel adhesion. Nevertheless, the transformative advance in hydrogel-based application places great challenges on the rapidity, robustness, and universality of achieving hydrogel adhesion, which are rarely accommodated by existing nanoparticles-based glues. Herein, we design a type of nanohesives based on the modulation of hydrogel mechanics and the surface chemical activation of nanoparticles. The nanohesives can form robust hydrogel adhesion in seconds, to the surface of arbitrary engineering solids and biological tissues without any surface pre-treatments. A representative application of hydrogel machine demonstrates the tough and compliant adhesion between dynamic tissues and sensors via nanohesives, guaranteeing accurate and stable blood flow monitoring in vivo. Combined with their biocompatibility and inherent antimicrobial properties, the nanohesives provide a promising strategy in the field of hydrogel based engineering. Achieving rapid, robust, and universal hydrogel adhesion poses challenges for nanoparticle-based glues. Here, the authors present nanohesives that can adhere to diverse surfaces without pre-treatment based on hydrogel mechanics design and interface chemistry modification.

The Asia-Pacific region has the largest number of cases of colorectal cancer (CRC) and one of the highest levels of mortality due to this condition in the world. Since the publishing of two consensus recommendations in 2008 and 2015, significant advancements have been made in our knowledge of epidemiology, pathology and the natural history of the adenoma-carcinoma progression. Based on the most updated epidemiological and clinical studies in this region, considering literature from international studies, and adopting the modified Delphi process, the Asia-Pacific Working Group on Colorectal Cancer Screening has updated and revised their recommendations on (1) screening methods and preferred strategies; (2) age for starting and terminating screening for CRC; (3) screening for individuals with a family history of CRC or advanced adenoma; (4) surveillance for those with adenomas; (5) screening and surveillance for sessile serrated lesions and (6) quality assurance of screening programmes. Thirteen countries/regions in the Asia-Pacific region were represented in this exercise. International advisors from North America and Europe were invited to participate.

ObjectiveAlthough mass eradication of Helicobacter pylori has been proposed as a means to eliminate gastric cancer, its long-term effects remain unclear.DesignMass eradication of H. pylori infection was launched in 2004 and continued until 2018 for a high-risk Taiwanese population aged 30 years or older dwelling on Matsu Islands with prevalent H. pylori infection. Test positives for the 13C-urea breath test underwent eradication therapy. We evaluated the effectiveness of the mass eradication in reducing two main outcomes, incidence and mortality rates of gastric cancer, until the end of 2016 and 2018, respectively.ResultsAfter six rounds of mass screening and eradication, the coverage rate reached 85.5% (6512/7616). The referral rate for treatment was 93.5% (4286/4584). The prevalence rates of H. pylori fell from 64.2% to 15.0% with reinfection rates of less than 1% per person-year. The presence and severity of atrophic gastritis and intestinal metaplasia also decreased with time. Compared with the historical control period from 1995 to 2003, the effectiveness in reducing gastric cancer incidence and mortality during the chemoprevention period was 53% (95% CI 30% to 69%, p<0.001) and 25% (95% CI −14% to 51%, p=0.18), respectively. No significant changes were noted in the incidence rates of other digestive tract cancers or the antibiotic resistance rate of H. pylori.ConclusionPopulation-based eradication of H. pylori has significantly reduced gastric cancer incidence with no increase in the likelihood of adverse consequences. A significant reduction in mortality is likely to be achieved with a longer follow-up period.Trial registration number NCT00155389