Bioscience trends最新文献

On May 5, 2023, the WHO declared that the COVID-19 pandemic no longer constitutes a public health emergency of international concern (PHEIC), but SARS-CoV-2 continues to spread and evolve on a global scale. The WHO reported that COVID-19 still poses a threat to humanity, and especially in some areas with large numbers of infected people. For some high-risk COVID-19 patients, such as those with underlying conditions, elderly patients, patients who need long-term immunosuppressive therapy after organ transplantation, patients with immunosuppressive diseases, patients who tend not to test negative for SARS-CoV-2 despite standard antiviral therapy, and cancer patients, special attention is still required after infection with SARS-CoV-2. How to clear SARS-CoV-2 in a timely manner is the key to treating such patients. Based on the demands of clinical practice and medical evidence, the National Center for Infectious Diseases of China assembled experts from relevant disciplines to reach the Chinese expert consensus on the combined use of antivirals to treat COVID-19, providing timely suggestions to resolve the medication issues that have been plaguing clinical practice. The consensus suggests that for special patients, combined medication can promptly eliminate the virus without increasing the risk to patient safety.

Treatments for solid tumors, the most common malignant neoplasms, are often confounded by tumor microenvironments that impede the achievement of uniform anti-tumor effects throughout the entire malignant mass, which contributes to recurrence and progression, negatively impacting clinical outcomes. Improved treatment methods for solid malignancies are therefore needed. Mesenchymal stromal cells (MSCs) have been investigated for treatments for various types of solid tumor cancers due to their ability to target tumor cells with similar cell surface protein profiles. MSC-derived exosomes (MSC-Exos) elicit many of the tumor cell responses produced by MSC with no potential for differentiation and reduced risks of adverse effects. We surveyed the literature and clinical trials registries to identify studies investigating MSC-Exo-based anti-cancer therapies for gastric cancer, colorectal cancer, breast cancer, lung cancer, brain cancer, pancreatic cancer, and urological malignancies, and summarize the results of relevant studies herein to provide a comprehensive description of the therapeutic effects and potential clinical applications of MSC-Exos for the treatment of solid tumor malignancies. We include a summary of relevant clinical trials performed to date in an attempt to assess the data available regarding MSC-Exo safety, and propose future efforts regarding the requirements for transitioning forward from phase-1, 2 trials.

Premature ovarian failure (POF), also referred to as premature ovarian insufficiency (POI), is a multifactorial reproductive endocrine disorder characterized by amenorrhea, infertility, hypoestrogenism, and elevated gonadotropin levels before the age of 40. Emerging evidence links its pathogenesis to oxidative stress and dysregulation of the autophagy-apoptosis balance in ovarian cells. Excessive accumulation of reactive oxygen species (ROS) impairs mitochondrial function in oocytes, while aberrant autophagy and granulosa cell apoptosis accelerate the depletion of primordial follicles. The AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway serves as a critical nexus between energy metabolism, oxidative stress, and cell survival. Traditional Chinese medicine (TCM), with its multi-component and multi-target characteristics, has demonstrated unique advantages in modulating the AMPK/mTOR pathway to restore ovarian function. This review synthesizes recent findings on single herbs, classical formulas, and non-pharmacological therapies (acupuncture and moxibustion). Mechanistic studies have revealed that these interventions can activate AMPK, inhibit mTOR overactivation, enhance Nrf2-mediated antioxidant defenses, reduce ROS production, and rebalance autophagy and apoptosis via pathways such as PI3K/Akt and SIRT1/p53. By aligning stage-specific regulation of AMPK/mTOR signaling with the TCM principle of syndrome differentiation, this integrative approach provides theoretical guidance for precise, personalized treatment to optimize multi-target strategies for POF management.

Effective antiretroviral therapy (ART) depends on adequate drug exposure. Plasma ART concentrations provide a short-term assessment of drug exposure, and hair promises to be an alternative matrix for measuring long-term exposure. We aimed to determine the association between plasma and hair ART concentrations and explore the therapeutic concentrations in hair. A cohort study in which HIV-infected adults receiving tenofovir disoproxil fumarate (TDF) + lamivudine (3TC) + efavirenz (EFV) regimen for at 6 months were recruited and paired hair and plasma samples collected at about 6±1 months of ART. Previously validated liquid chromatography and tandem mass spectrometry methods were used to measure ART concentrations in plasma and hair. Among 74 participants enrolled, 47 used a 400 mg dose of EFV daily and 27 used 600 mg EFV daily. Hair and plasma EFV concentrations were strongly correlated, with particularly strong association observed in the 600 mg EFV group. The hair EFV concentration of female participants was significantly higher than in male participants, which might be the inter-individual variations in the drug metabolism and dissolution and life habits. The concentrations of TDF and 3TC in hair are too low to determine effective threshold and relationship with plasma drugs concentrations. The accumulation and correlation of hair and plasma EFV concentrations promise to determine a therapeutic range in hair. The therapeutic range for EFV in hair needs to be calculated in order to give quantitative results more value within the field of drug exposure assessment.

Influenza is an acute respiratory infectious disease caused by influenza viruses, and it poses a serious threat to global public health. High-risk groups include the elderly, infants and young children, pregnant women, and patients with chronic underlying diseases. These groups are prone to developing severe illness after infection, which can lead to serious complications and even death. Early antiviral treatment is key to reducing the rate of severe illness and death. Currently, authoritative guidelines at home and abroad recommend early, single-agent antiviral therapy as the standard regimen. However, anti-influenza virus monotherapy has problems such as drug resistance and poor therapeutic effect. To address these problems, this consensus was developed by organizing experts from the departments of Infectious Diseases, Respiratory Medicine, Critical Care Medicine, and Pharmacy. These experts systematically sorted out domestic and international evidence on combined antiviral therapy for influenza and formulated expert recommendations on combined antiviral therapy for influenza in specific populations.

Aging constitutes a major risk factor for pan-cancer development, with epidemiological studies indicating that 60% of new malignancies occur in adults age 65 and older. This review synthesizes cutting-edge insights from single-cell sequencing databases (e.g., TCGA and GEO) that decipher how aging reprograms the tumor microenvironment (TME) to fuel carcinogenesis. Single-cell RNA sequencing (scRNA-seq) has revealed that senescent cell subpopulations (e.g., CDKN2A⁺/LMNB1^- cells) accumulate in aged tissues at frequencies up to 15%, driving genomic instability and secrete pro-tumorigenic senescence-associated secretory phenotype (SASP) factors (IL-6 and TGF-β). These factors remodel the TME by inducing fibroblast activation and extracellular matrix degradation, accelerating metastasis by 40-70% in murine models. Crucially, immunosenescence diminishes anti-tumor immunity, with scRNA-seq profiling showing 40-60% increases in exhausted PD-1⁺ T cells and immunosuppressive myeloid cells in aged TMEs. Pan-cancer analyses have identified conserved aging gene signatures (e.g., p16INK4a upregulation in 12+ cancer types) that correlate with 30-50% poorer survival. While technical challenges persist - including batch effects in scRNA-seq data and low senescent cell abundance (< 5%) - emerging solutions like deep learning can enhance detection sensitivity. Therapeutically, senolytic strategies deplete senescent cells, improving drug response by 3.5-fold in preclinical trials. Future research must integrate multi-omics and AI to examine aging-related targets, advancing personalized interventions for aging-associated malignancies.

The medical metaverse, with its potential for efficient care delivery, improved patient outcomes, and reduced healthcare costs, is profoundly impacting global healthcare systems. Scholars researching this topic primarily focus on exploring specific scenarios for its use. This article aims to analyze the development trajectory, potential applications, and directions for management optimization within the medical metaverse. Through a case study of China, we review the current status of use of the medical metaverse and systematically examine its future prospects and challenges. We contend that the medical metaverse offers significant value in enabling equitable distribution of healthcare resources, enhancing medical care efficiency, promoting the integration of medical education, research, and clinical practice, and assisting in public health management. To ensure sustainable development, however, the imperative task is to proactively devise technical standards and legal regulatory frameworks and to dynamically monitor the effectiveness of medical metaverse technologies, with the ultimate aim of maximizing the value of the medical metaverse.

Early-stage diagnosis offers the greatest survival advantage in oncology, and yet conventional liquid-biopsy markers - circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) - depend on cell death or mechanical shedding and therefore appear late in disease progression. Exosomes, 40-160 nm lipid-bilayer vesicles secreted by viable cells, emerge earlier, outnumber CTCs by several orders of magnitude, and preserve multi-omic cargo that mirrors intratumor heterogeneity. Rapid advances in enabling technologies are driving continual breakthroughs in exosome-based liquid biopsy, laying a solid foundation for its accelerated translation into clinical practice. Key hurdles remain: standardizing exosome isolation, defining quantitative cut-offs that separate malignant from inflammatory EV surges, and building probabilistic multi-omic models to pinpoint tissue origin. Eliminating these obstacles could advance detection by months and shift care from late salvage to true early interception.

Neurotropin, a non-protein extract widely used for the treatment of neuropathic pain, has recently been reported to protect against ischemic brain injury, enhance remyelination in demyelinating diseases, and ameliorate neuroinflammation and memory deficits. However, its role in microglial polarization and mitochondrial dysfunction in Alzheimer's disease (AD) remains poorly understood. In this study, we investigated the therapeutic potential of Neurotropin in the 5xFAD mouse model of AD. Neurotropin administration alleviated cognitive decline, reduced amyloid-β (Aβ) deposition, suppressed neuroinflammation, and preserved neuronal density. Mechanistically, Neurotropin improved mitochondrial morphology, restored ATP production, increased mitochondrial DNA copy number, and reduced oxidative stress while promoting a shift in microglial polarization from the pro-inflammatory M1 phenotype toward the anti-inflammatory M2 phenotype. Transcriptomic and molecular analyses revealed that calcium homeostasis modulator family member 2 (Calhm2) was markedly upregulated in 5xFAD mice, colocalized with microglia, and transcriptionally regulated by fused in sarcoma (FUS), while Calhm2 interacted with EF-hand domain containing protein D2 (EFhd2). Neurotropin suppressed FUS-mediated Calhm2 transcription and attenuated Calhm2-EFhd2 interaction. Importantly, overexpression of Calhm2 in both microglial cells and 5xFAD mice abolished the beneficial effects of Neurotropin, leading to exacerbated mitochondrial dysfunction, oxidative stress, and inflammatory cytokine release. Together, these findings identify Calhm2 as a critical mediator of Neurotropin's neuroprotective effects and demonstrate that Neurotropin alleviates AD pathology by suppressing FUS-dependent Calhm2 transcription and blocking the Calhm2/EFhd2 interaction. This study provides new insights into the mechanism of Neurotropin action and highlights its therapeutic potential for AD.

The persistent mutation of the novel coronavirus (SARS-CoV-2) not only remains a threat to human health but also continues to challenge existing antiviral therapeutic strategies. In current clinical practice, the resistance of novel coronavirus to antivirals, the rebound of viral load after treatment with drugs such as nirmatrelvir/ritonavir (NTV/r), and the urgent need for rapid clearance of the virus in the management of critically and emergently ill patients suggest that the existing single-drug regimens may have limitations and that the intensity of suppression may be insufficient in some cases. In clinical practice, we have observed that a combination of antivirals with different mechanisms of action can result in better efficacy and not significantly increase adverse drug reactions (ADRs). For some immunosuppressed, post-transplantation, or other special patients in particular, such as those in whom COVID-19 nucleic acids tended not to be negative after conventional treatment, when virus clearance is still the main goal, the combination of small-molecule antivirals can help to clear the virus as early as possible and attempt to improve the success rate of salvage. Based on evidence-based medicine and in light of the current situation of China, we assembled experts from disciplines such as infectious diseases, respiratory medicine, critical care medicine, and clinical pharmacy into a group to carry out a systematic literature search and identify key issues and to put forward relevant recommendations to reach an Expert Consensus on Combined Use of Oral Small-molecule Antivirals to Treat COVID-19, which is intended to serve as a reference for clinical practice.