MedComm - Future medicine最新文献

Recently a research article titled “Nuclear export of circular RNA” was published online in Nature¹ as a collaboration between Ngo et al. This study revealed a distinct circular RNA (circRNA) transport mechanism compared to that of linear RNA and identified unique molecular pathways involved in circRNA transport, including key proteins such as Ran-GTP, IGF2BP1, and exportin-2.

CircRNA is a closed-loop structured noncoding RNA formed via pre-messenger RNA (mRNA) back-splicing. It regulates gene expression and participates in translation. CircRNA is associated with varieties of diseases, including those of the autoimmune, heart, liver, Alzheimer's, and cancer. It is important in cellular biology and disease research, and primarily exist in the cytoplasm; however, its translocation mechanism from the nucleus to cytoplasm remains unknown. In view of this, the research team conducted scientific research experiments.

In this study, the research team confirmed that most circRNAs were primarily located in the cytoplasm. They then depleted candidate proteins known to be involved in the transport of various linear RNA subtypes to examine whether the depletion would lead to circRNAs accumulation in the nucleus. The results showed that depletion of ALY, GANP, NXF1, UAP56, URH49, and exportin-5 did not affect circRNA transport. This indicated that bulk transport of circRNAs did not require a conventional mRNA export pathway. In contrast, they found that depleting the receptor CRM1 for ribosomal RNA and small nuclear RNA transport decreased nuclear circRNA content.² This unusual phenomenon attracted the attention of the research team. To further confirm this phenomenon, the cells were treated with the CRM1 inhibitor Selinexor, which also decreased the nuclear circRNA content and increased the cytoplasmic content.

The research team speculated that the CRM1 depletion could have been due to Ran-GTP consumption during nuclear transport complex assembly.³ Therefore, CRM1 depletion could inhibit the assembly of the nuclear transport complex, thereby enhancing circRNA transport. Thus, they designed two experimental methods: measuring the nuclear and total cellular Ran content after CRM1 depletion using immunofluorescence and treating cells with sorbitol, a Ran-GTP inhibitor. These results confirmed that circRNA export depended on Ran-GTP.

The research team hypothesized that circRNA was transported via a transport protein under Ran-GTP-dependent conditions. Biotinylated SMARCA5 circRNA and linear RNA were used. The Ran content was controlled to identify protein exportin-2 using SMARCA5. Exportin-2 was then depleted in the cells, which increased nuclear circRNA content, but did not affect linear RNA. To ensure that the effect on circRNA export was not the result of the small interfering RNA (siRNA's) off-target effects, the depletion experiment was repeated with a

The rising psychological issues among cancer patients call for timely treatment. Psychological issues such as anxiety, depression, and distress are particularly common among cancer patients and have a significant impact on their treatment and prognostic outcomes. Distraction has been proven to mitigate mental disorders as a strategy of intervention. Digital tools like social short video platforms offer cost-effective mental healthcare potential, but there is a lack of longitudinal studies demonstrating their intervention effectiveness. This study aimed to assess the impact of social short video platforms on the psychological well-being of cancer patients, focusing on anxiety, depression, and distress. We studied 455 digestive system cancer patients using mixed methods. The effect on psychological symptoms was evaluated via cross-sectional analysis of 392 patients and pre-post intervention analysis of 63 patients, employing the Hospital Anxiety and Depression Scale and Distress Thermometer. The findings showed lower anxiety, depression, and distress scores among regular users of social short video platforms. The intervention led to reduced anxiety and depression scores. As a prevalent app of social short video platforms, these platforms might be a safe and convenient nonpharmacological assisted tool for enhancing mental health care during cancer treatment.

Severe trauma is a critical aspect of medical practice, profoundly impacting patient care and outcomes. Over the past 20 years, advancements in trauma care concepts and the utilization of advanced technologies have led to substantial growth in severe trauma research, evidenced by a notable increase in research activity and subsequent publications. To understand the publication landscape in severe trauma, identify prevailing research trends, and highlight areas requiring further development for future insights, we conducted a bibliometric analysis. Our analysis indicates that there are 16,939 severe trauma-related publications from the past 20 years, with a continuous increase in publication volume, particularly showing a rapid growth trend from 2018 to 2021. The United States leads in both volume and citation frequency. Moreover, we synthesized data on productive countries/regions and research institutions, showcasing extensive collaboration across diverse geographic locations and institutional affiliations. Substantial progress has been achieved in severe trauma research, particularly in clinical diagnosis, treatment, epidemiology, prevention, and pathogenesis. However, there is still a gap in adopting cutting-edge interdisciplinary methodologies. This study provides a comprehensive overview of the current state of severe trauma research and suggests pathways for future advancement.

In a recent article published in Nature, Xia et al. found that the insertion of a specific AluY element in the sixth intron of the primate TBXT gene may lead to the evolution of tail loss.¹ The significance of this study emphasizes that uncovering the genetic mechanism in facilitating tail-loss evolution in hominoids can contribute to understanding evolutionary pressure that boosts the formation of human traits and evolutionary diseases.

From a Darwinian evolutionary perspective, the lack of a tail is one of the key features in the evolution from hominids, signifying the anatomical shift from primitive ancestors to modern humans, especially the disappearance of the external tail.² This unique transformation not only illustrates a remarkable chapter in our biological history, but also underscores the intricate interplay of heredity and evolution. The story of the tail, or more precisely, its absence opens a window into how minor genetic alterations can orchestrate remarkable developmental changes. Alu elements are a type of short interspersed nuclear element (SINE) found abundantly in the human genome. Alu elements, as a class of transposable elements unique to the primate genome, exert a profound influence on genome evolution. These elements increase genomic instability by providing the most common homologous sequences for non-allelic homologous recombination events, which can lead to disease. Through delving deeper into the TBXT gene, Xia et al. revealed a human-specific insertion of an Alu element that is oriented in the opposite direction to the neighboring Alu element, forming a pair that may have led to human-specific gene splicing that affects gene expression. Validated by a mouse model, this splicing was found to alter TBXT gene expression, resulting in missing or shortened tails in mice,¹ providing strong support for the theory that exon skipping leads to tail deletion (Figure 1).

To investigate the genetic mechanism of ancient human-specific selective splicing events, Xia et al. used CRISPR-Cas9 to knock out the AluY element and its interaction with the AluSx1 element in human embryonic stem cells. By modeling the developmental expression pattern of the TBXT gene, Xia et al. revealed that the deletion of the AluY element almost completely blocked the TBXT^Δexon6 heterodimeric transcripts production.³ These findings highlight the complex role of transposable factor interactions in gene regulation and the importance of TBXT isoform expression in tail development.

The loss of the tail is a complex and widely debated topic in biological evolution, involving a delicate balance between evolution and degeneration. From an evolutionary perspective, the loss of the tail in humans and other upright walking organisms is considered to be an adaptive evolution to a new environment and way of life, in whic

In the realm of malignant tumor treatment, particularly regarding hematologic malignancies, chimeric antigen receptor T-cell (CAR-T) immunotherapy has witnessed remarkable advancements in recent years. This approach involves genetically modifying and engineering a patient's T-cells ex vivo to express a specific CAR, known as CAR-T cells. When these modified cells are reintroduced into the patient, they can specifically recognize target antigens and exhibit highly efficient cytotoxicity against cells expressing these antigens, making them suitable for the treatment of malignant tumors. CD19, which is expressed on the surface of B lymphocytes at different stages of differentiation, has been identified as a suitable target for the treatment of most B-cell lymphomas. CAR-T cells targeting CD19 have demonstrated excellent specificity, cytotoxicity, and persistence in both in vitro and clinical trials, showing tremendous potential for application. However, identifying appropriate targets for CAR-T therapy in solid tumors remains a challenge, leading to limited advancements in this area. This review discusses the mechanisms, applications, limitations, and prospects of CAR-T therapy in hematologic malignancies and solid tumors, aiming to provide directions for future research in this field.

A recent study by Wong et al. was published in the journal “Cell” and illuminates a potential role for serotonin reduction in mediating cognitive impairment following postacute sequelae of COVID (PASC) or Long COVID.¹ This research highlight explores the mechanisms underlying viral infection-mediated serotonin reduction, and unveils therapeutic targets which could alter the way we approach Long COVID in clinical practice.

In the aftermath of the COVID-19 pandemic, patients are increasingly presenting with debilitating symptoms persisting for months after acute SARS-CoV-2 infection.² The constellation of symptoms, collectively termed Long COVID, are heterogeneous and involves multiple body systems. Despite the significant impact of Long COVID on healthcare resources and patients' quality of life, the mechanisms underlying these symptoms remain largely enigmatic. However, in a groundbreaking study, Wong et al. illuminate a potential link between viral-induced inflammation, serotonin reduction, and cognitive deficits in individuals suffering from Long COVID.¹

Wong et al. analysed a range of metabolites in the serum of patients exhibiting symptoms of both acute and post-acute COVID-19 infection, and found amino acid metabolites, such as serotonin were depleted throughout the acute and chronic phases of infection. Interestingly, patients with Long COVID had lower serotonin levels compared to those who fully recovered from their initial infection. Indeed, serotonin levels in the bloodstream were predictive of long-term symptom burden after initial COVID infection, and strongly suggests a potential role for serotonin in the pathophysiology of Long COVID. Similar reductions in serotonin levels were found in other infections such as varicella-zoster virus and lymphocytic choriomeningitis virus, suggesting that reduced serotonin may be a shared characteristic of systemic viral infections.

The study then turned to mouse models of viral infection to characterise the mechanisms underpinning serotonin reduction, and found increased type 1 interferon (IFN) signalling. Importantly, IFN signalling was persistently upregulated in long COVID, and inhibition of the IFN alpha receptor prevented viral infection-induced serotonin depletion. This effect was abolished in mice with impaired IFN signalling.

Serotonin is predominantly synthesized in the gastrointestinal tract, where it is produced from an essential dietary amino acid called tryptophan.³ This study also found that individuals with acute and persistent COVID-19 infection had reduced plasma tryptophan levels, hinting at a potential limitation in serotonin production during viral infections. This suggests individuals with congenital or acquired tryptophan deficiency may be more susceptible to developing long COVID. RNA sequencing of small intestinal epithelium found that genes involved in a

In a recent article published in Science, Choi et al. introduce an innovative approach to cardiac rhythm control through a newly developed, temporary, wireless, bioresorbable pacemaker.¹ This pacemaker operates in a closed-loop fashion, dynamically adjusting pacing parameters to match metabolic demands of the heart while ensuring mechanical robustness and compatibility with magnetic resonance imaging.

The system comprises three implantable, bioresorbable components, a pacemaker, an anti-inflammatory drug-eluting patch, and a power harvesting unit. Additionally, it includes three skin-interfaced components, a set of physiological sensors, a wireless power transfer module, and a haptic actuator. An external, handheld device with a software application is used for data-management and control (Figure 1).¹ After patient recovery, the skin-interfaced devices, including sensors are easily removed.

The motivation behind the use of biodegradable implantable sensors stems from the necessity to monitor and treat postoperative complications effectively. Such implants mitigate risks associated with nonbiodegradable alternatives, including bacterial colonization and infection, as well as the challenges associated with their removal, particularly in sensitive areas. Clinical trials will determine the accuracy of pacing and electrocardiogram (ECG) recordings with skin-interfaced sensors. It also remains to be found whether combinatorial sensor-actuator transient implants with biodegradable sensors will be more accurate since implantable sensors may provide more accurate data compared to skin-interfaced sensors.

Biodegradable sensors also offer opportunities for minimally invasive and temporary monitoring and therapeutic interventions, enabling real-time tracking of physiological parameters and targeted delivery of therapeutic agents or electrical stimulation to specific areas of the body.² Unlike skin-interfaced sensors, implantable biodegradable sensors do not need to withstand the movements of the body, and they minimally infringe on them. They are also less cumbersome, and they are comfortable for patients.

Although it is advantageous to have implants that can degrade and disappear, their degradation can lead to a inflammatory reaction. Uncontrolled, it becomes chronic and leads to fibrous tissue encapsulation of the implant and sensor and hindrance of their function. Therefore, the fibro-inflammatory reaction needs to be properly kept under control. Choi et al.¹ used an anti-inflammatory steroid (dexamethasone acetate)-eluting patch. Alternative strategies that may be considered in the future are using anti-inflammatory drug release, implant coating, micro- and nanopatterning, and surface functionalization, which may simplify the implant design. Because the use of stiff materials leads to the activation of integrin and the release

Postoperative acute kidney injury requiring dialysis (PO-AKID) is a serious adverse event that not only affects acute morbidity and mortality, but also long-term prognosis. Here, we developed a practical and explainable web-based calculator (PO-AKID-teller) to detect patients who might experience PO-AKID after acute type A aortic dissection (ATAAD) surgery. This retrospective study reviewed 549 patients undergoing ATAAD surgery from October 2016 to June 2021. PO-AKID frequency was 19.7% (108 of 549 patients). The initial dataset was split into an 80% training cohort (n = 439) and a 20% test cohort (n = 110). There were seven predictors that could indicate PO-AKID, including prior cardiovascular surgery, platelet, serum creatinine, the terminal site of dissection involvement, right coronary artery involvement, estimated blood loss, and urine output. Among six machine learning classifiers, the random forest model exhibited the best predictive performance, with an area under the curve of 0.863 in the training cohort and 0.763 in the test cohort. This model was translated into a web-based risk calculator PO-AKID-teller to estimate an individual's probability of PO-AKID. The PO-AKID-teller can accurately estimate an individual's risk for PO-AKID in an interpretable manner, which may aid in informed decision-making, patient counseling, perioperative optimization, and longer-term care provision.

The eye serves as a unique window into systemic health, offering clinicians a valuable opportunity for early detection and targeted treatment. Against this backdrop, advancements in artificial intelligence (AI) and ophthalmic imaging are converging to pave the way for more precise and predictive diagnostics. This review aims to elucidate the transformative role of AI in utilizing ophthalmic imaging for the detection and prediction of systemic diseases. We begin by introducing the advantages of the eye as a valuable tool for detecting systemic diseases. We also provide an overview of various ophthalmic imaging techniques that have proven useful in predicting systemic ailments. Then, we summarize two research patterns for analyzing ocular data, followed by the introduction of current AI applications using ophthalmic images that significantly increase diagnostic precision. Despite the promise, challenges such as data heterogeneity and model interpretability persist, which are also covered in this review. We conclude by discussing future directions and the immense potential these AI-enabled approaches hold for revolutionizing healthcare. As AI technologies advance, their potential integration with ophthalmic imaging offers promising avenues for improving the diagnosis, prediction, and management of various systemic diseases, thereby contributing to the evolving landscape of integrated healthcare.

Diabetic nephropathy (DN) represents a prevalent chronic microvascular complication of diabetes mellitus (DM) and is a major cause of end-stage renal disease. The anfractuous surrounding of DN pathogenesis and the intricate nature of this metabolic disorder often pose challenges in both the diagnosis and treatment of DN compared to other kidney diseases. Hyperglycaemia in DM predispose vulnerable renal cells into microenvironmental disequilibrium and thereby results in innate immunocytes infiltration including neutrophils, macrophages, myeloid-derived suppressor cells, dendritic cells, and so forth. These immune cells play dual roles in kidney injury and closely correlated with the degree of proteinuria in DN patients. Additionally, innate immune signaling cascades, initiated by altered metabolic and hemodynamic in diabetic context, are crucial in instigating and perpetuating renal inflammation, which detrimentally contribute to DN pathogenesis. As such, anti-inflammatory therapies, particularly those targeting innate immunity, hold renoprotective promise in DN. In this article, we reviewed the origin and feature of the above four prominent kidney innate immune cells, analyze their pathogenic role in DN, and discuss potential targeted-therapeutic strategies, aiming to enhance the current understanding of renal innate immunity and hence help to discover promising therapeutic approaches for DN.