It is a complex disease with multiple pathogenesis that causes pulmonary hypertension (PH). In addition to the commonly used drugs for treating PH, pharmacogenomic therapies are facilitating the innovation of personalized medicine to treat PH. Meanwhile, gene therapy has been extensively studied but is a quite challenging task. Furthermore, the gradual widespread application of omics analyses, big data and machine learning is a trend to improve the efficacy of drugs and gene therapy of PH. They are widely used in the screening of drug therapeutic targets and predicting drugs therapeutic effect. The emergence of innovative diagnosis and treatment approaches for PH opens pathways for combining personalized medicine with established pharmacological and gene therapies to achieve effective treatment strategies and further decrease the mortality rate associated with this disease.
Computer vision has facilitated the execution of various computer-aided diagnostic tasks. From a methodological perspective, these tasks are primarily implemented using two dominant strategies: end-to-end Deep learning (DL)-based methods and traditional feature engineering-based methods. DL methods are capable of automatically extracting, analyzing, and filtering features, leading to final decision-making from whole slide images. However, these methods are often criticized for the “black box” issue, a significant limitation of DL. In contrast, traditional feature engineering-based methods involve well-defined quantitative input features. But it was considered as less potent than DL methods. Advances in segmentation technology and the development of quantitative histomorphometric (QH) feature representation have propelled the evolution of feature engineering-based methods. This review contrasts the performance differences between the two methods and traces the development of QH feature representation. The conclusion is that, with the ongoing progress in QH feature representation and segmentation technology, methods based on QH features will leverage their advantages— such as explainability, reduced reliance on large training datasets, and lower computational resource requirements—to play a more significant role in some clinical tasks. They may even replace DL methods somewhat or be used in conjunction with them to achieve accurate and understandable results.
Psychobiotics are a distinct category of probiotics known for their beneficial effects on human health, particularly in influencing mental well-being. Typical psychobiotics include genera such as Lactobacillus, Streptococcus, and Bifidobacterium. The gut microbiota influences bidirectional communication between the brain and the gastrointestinal (GI) system. Neurons in the enteric nervous system directly interact with neurotransmitters, short-chain fatty acids (SCFAs), gut hormones, and anti-inflammatory cytokines produced by the gut microbiota, thereby affecting signal transmission in the central nervous system. Unlike traditional probiotics, psychobiotics have the capacity to generate or stimulate the host to produce neurotransmitters, SCFAs, gut hormones, and anti-inflammatory cytokines. It is precisely this potential that has led to the widespread use of psychobiotics over the past decade to improve and treat mental disorders. This article briefly reviews the clinical applications of psychobiotics in improving and treating conditions such as neurodevelopmental disorders, neurodegenerative diseases, depression and anxiety. It is proposed that the novel therapeutic approach of using Bacillus licheniformis as an adjuvant treatment for patients with depression shows a certain degree of feasibility. Finally, this review suggests that the current evidence regarding the improvement and treatment of mental and neurological disorders with psychobiotics is still limited. Further in-depth research is needed to clarify their effectiveness and mechanisms of action in the clinical management of various mental disorders.
Cervical cancer is one of the most common malignant tumors that seriously threaten women’s health. Persistent infection with high risk human papillomavirus (HPV) is closely related to the progression of cervical cancer. Cervical cancer screening is an effective measure to reduce the incidence and mortality of cervical cancer. The two most common screening strategies are cytology and HPV testing, but they easily lead to missed diagnosis or overdiagnosis. To overcome such limitations, a new triage method needs to be explored. The World Health Organization second edition guideline includes DNA methylation testing as a new method to be evaluated. DNA methylation is a common epigenetic modification and is considered to be closely related to the occurrence and development of tumors. In recent years, many methylated genes have been found to be biomarkers for cervical cancer and precancerous lesions diagnosis. In this paper, we focus on the role and application of host DNA methylation, HPV DNA methylation, as well as combined host and HPV DNA methylation in the screening of cervical cancer and precancerous lesions.
Precise resection of orbital tumors is a critically important but elusive issue. Fluorescence imaging in the near-infrared II window (NIR-II) holds the potential to provide the surgeons with real-time identification for orbital tumors. Here, for the first time, we evaluated the feasibility and clinical value of NIR-II fluorescence imaging in orbital tumor surgery. To establish the method of NIR-II fluorescence imaging for orbital tumors, we developed a NIR-II fluorescence imaging system and indocyanine green (ICG) served as the fluorescent contrast agent. Twenty-two patients diagnosed with orbital tumors and scheduled for standard-of-care surgery were enrolled in this study. Timecourse NIR-II fluorescence imaging of two patients with superficial orbital tumors showed the optimum imaging time was 2 h post injection of ICG. Fifteen patients were allocated for diagnostic test, which showed that both the in situ and ex vivo NIR-II fluorescence imaging showed better sensitivity and specificity than the surgeon judgment. In the feasibility trial of the remaining five patients, the surgeon encountered 34 suspicious regions and surgical decisions were changed nine times due to NIR-II fluorescence imaging. The resultant seven additional resections were justified by histopathology and the two conservative treatments did not result in recurrence. Based on these findings, we suggested that ICG-based NIR-II fluorescence imaging was feasible to guide precise resection of orbital tumors. A future randomized controlled trial with a larger cohort is encouraged to further verify the clinical value.
The field of extracellular vesicle (EV) research has rapidly evolved, revealing their significant roles in various biological processes and clinical applications. Allergic diseases are prevalent immunological disorders characterized by exaggerated hypersensitivity reactions to allergens, leading to diverse clinical manifestations that can severely impact quality of life. Recently, studies have underscored the pivotal role of EVs in allergic conditions, including asthma, allergic rhinitis, and atopic dermatitis. In this review, we provide a comprehensive overview of recent advances in the separation and characterization of EVs, their roles in allergic diseases, and their diagnostic value as biomarkers. Additionally, we explore the therapeutic potential of EVs for the treatment and prevention of allergic conditions. Overall, the emerging insights into EVs present promising opportunities for enhancing the diagnosis, treatment, and management of allergic diseases.
Abnormal gut microbiota is associated with the occurrence of depression, but the specific pathophysiological role of gut microbiota in the pathogenesis of depression is still unknown. We found that the levels of serum steroid hormone testosterone in male patients with depression were lower than in healthy controls. Using testosterone as the only carbon source, the testosteronedegrading bacteria Arthrobacter koreensis was isolated from fecal of low testosterone male patients with depression. We found that A. koreensis administration in mice led to reduced serum testosterone levels and depression-like behaviors, which were improved by antibiotic treatment. Using whole genome sequencing, the gene mediating testosterone degradation in A. koreensis was identified and annotated as 3α-hydroxysteroid dehydrogenase (3α-HSD). Escherichia coli heterologously expressing 3α-HSD obtained the capacity to degrade testosterone, causing depression-like behaviors after gavage to mice. Testosterone supplementation improves depression-like behavior in mice induced by gavage of Escherichia coli heterologously expressing 3α-HSD. Finally, the universality of 3α-HSD in gut of male patients with depression was higher than that of healthy controls. Overall, our results revealed a new pathway that potentially links testosterone degradation by gut microbes harboring 3α-HSD enzymes to the pathogenesis of depression. Gut microbial 3α-HSD can induce depression in mice via testosterone degradation. This means that 3α-HSD expressed by gut bacteria may be a potential target for depression in men.
The emergence of antibiotic-resistant bacteria poses a significant challenge to the prompt and appropriate treatment of pathogenic bacteria infections, such as acute bacterial skin and skin-structure infections (ABSSSI), especially in the presence of biofilms. Bacterial biofilms are naturally resistant to antibiotics and the human immune system, making biofilm-based infections extremely difficult to treat. Therefore, developing new antibacterial therapies targeting biofilms is crucial. Aggregation-induced emission luminogens with fluorescence in the second near-infrared window (NIR-II AIEgens), which can be activated by a near-infrared laser to generate heat, offer an effective and precise photothermal therapy (PTT) approach for treating deep-tissue bacterial infections. However, the presence of biofilms impedes the entry of photosensitizers into the infected area, requiring higher drug doses and increasing the risk of PTT. Herein, we developed a biocompatible AIEgen-based biohybrid nano formulation that incorporates the BPBBT (NIR-II AIEgen) and antibiofilm α-amylase into a red blood cell (RBC) membrane-derived nanovesicle carrier for a PTT/biofilm degradation combination therapy. The synergistic effect of this new formulation enhances both the photothermal capability of BPBBT and the biofilm degradation compared to traditional individual treatments. The new combination therapy demonstrated significant improvement in treating severe Staphylococcus aureus infections caused by biofilms in vitro and in vivo, presenting a promising alternative to traditional antibiotic therapy.
Increasing studies have demonstrated that PIWI-interacting RNAs (piRNAs) in circulating exosomes can serve as novel molecular biomarkers for tumor liquid biopsy. However, methods for in situ detection of piRNAs encased in exosomes are limited. In this study, we designed a spherical nucleic acid probe named piR-651, which can enter exosomes simply by incubating with them for 2 h and in situ detect piR-651 with a detection limit of 5 × 107 particles/µL. Based on this probe, we established a liquid biopsy method for the in situ detection of piR-651 in plasma exosomes. The assay could distinguish the expression levels of piR-651 between 21 breast cancer patients and 22 healthy individuals. The receiver operating characteristic curve shows an area under the curve as 0.9931 and the diagnostic sensitivity and specificity at the best cutoff are 85.7% and 100%, respectively. The probe can also easily perform in situ imaging of piR-651 in living cells. To avoid low sensitivity and kinetics in detecting large-sized PIWI-interacting RNA complexes, we rationally designed the structure and detection scheme of piR-651 probe, which was synthesized by modifying 13-nm gold particles with high-density Anchor-Report DNA duplexes through the butanol dehydration method. The new design of the gold nanoparticle nucleic acid probe can be applied to the fabrication of nucleic acid probes targeting other large-volume nucleic acids for developing more molecular biomarker-based liquid biopsy for cancer diagnosis.
Nonalcoholic fatty liver disease (NAFLD) encompasses a broad range of conditions, commencing with simple steatosis and progressing to nonalcoholic steatohepatitis, with the possibility of further deterioration into fibrosis, cirrhosis, and ultimately, hepatocellular carcinoma. Unfortunately, there is currently no approved medication for treating NAFLD-associated liver steatosis. This underscores the need for improved therapeutic approaches that can modulate lipid metabolism and halt the transition from liver steatosis to chronic liver disease. Our previous studies have demonstrated that apoptotic vesicles (apoVs), which are produced during apoptosis, show great potential in regulating liver homeostasis. However, whether they can ameliorate NAFLD is unknown. In our research, apoVs derived from platelets (PLT-apoVs) as well as apoVs derived from mesenchymal stem cells (MSC-apoVs) were used to treat NAFLD. The results showed that PLT-apoVs exhibited superior effects in diminishing lipid accumulation in liver induced by high-fat diet than MSCapoVs. Through proteomic analysis, we defined and validated apolipoprotein A-II (APOA2) as a regulator for apoV-mediated MSC adipogenesis, which could be used as a target to enhance apoV therapeutic potential in the lipid metabolism biomedical field. Owing to the higher expression of APOA2, PLTapoVs showed better therapeutic effects than MSC-apoVs. Our results pave the way to apoV-based therapy for NAFLD.
Artificial intelligence (AI) is rapidly advancing, yet its applications in radiology remain relatively nascent. From a spatiotemporal perspective, this review examines the forces driving AI development and its integration with medicine and radiology, with a particular focus on advancements addressing major diseases that significantly threaten human health. Temporally, the advent of foundational model architectures, combined with the underlying drivers of AI development, is accelerating the progress of AI interventions and their practical applications. Spatially, the discussion explores the potential of evolving AI methodologies to strengthen interdisciplinary applications within medicine, emphasizing the integration of AI with the four critical points of the imaging process, as well as its application in disease management, including the emergence of commercial AI products. Additionally, the current utilization of deep learning is reviewed, and future advancements through multimodal foundation models and Generative Pre-trained Transformer are anticipated.
Wearable therapy represents a research frontier where material science, electrical engineering, and medical disciplines intersect, offering significant potential for remote and portable healthcare. Unlike conventional approaches that rely on rigid materials, the ability to stretch is crucial for therapeutic devices to achieve enhanced mechanical adaptability. Moreover, the conformable integration of these devices into the body is pivotal in establishing reliable interfaces for long-term treatment. These emerging devices provide an attractive platform for developing new therapeutic protocols that do not disrupt daily activities. This review comprehensively overviews recent progress in stretchable and body-conformable electronics for wearable therapeutic applications. The discussion begins with the design and fabrication of these devices through structural designs and material innovation. The therapeutic mechanisms adopted by these devices are then systematically explored. Furthermore, the article delineates the crucial characteristics of wearable therapeutic devices, such as biocompatibility, secure skin attachment, and effective moisture management. This review article is poised to inspire innovative device designs and treatment protocols for future medical technology.
