Hu Wang

Background: Mesenchymal stem cell (MSC)‐based therapies have emerged as a promising approach for Alzheimer's disease (AD), owing to their neuroprotective, anti‐inflammatory, and immunomodulatory properties. However, the optimal delivery route for maximizing therapeutic efficacy within the central nervous system remains unclear. This study aimed to directly compare the therapeutic effects of intravenous versus intrathecal transplantation of human umbilical cord‐derived mesenchymal stem cells (HUCMSCs) in a transgenic AD mouse model (5xFAD). Methods: HUCMSCs were isolated, characterized, and administered to 5xFAD mice via intravenous or intrathecal routes. Cognitive function was assessed using the Morris water maze. Amyloid plaque burden, microglial activation, microglial barrier integrity, and axonal dystrophy were evaluated through immunofluorescence and confocal microscopy. The expression of TREM2, DAP12, and Syk was analyzed to elucidate underlying molecular mechanisms. Results: Intrathecal transplantation of HUCMSCs significantly improved spatial learning and memory in 5xFAD mice compared to intravenous delivery. HUCMSC treatment substantially reduced amyloid plaque burden and axonal dystrophy, while promoting microglial activation and enhancing the protective function of the microglial barrier. Additionally, HUCMSC administration upregulated TREM2, DAP12, and Syk expression, with intrathecal delivery inducing more robust activation of these microglial signaling pathways than intravenous infusion. Conclusions: HUCMSC transplantation alleviates cognitive deficits and modulates key pathological and molecular features of AD in the 5xFAD mouse model, with intrathecal administration demonstrating superior therapeutic efficacy compared to intravenous delivery. These findings underscore the critical importance of optimizing cell delivery routes to enhance the clinical potential of stem cell‐based interventions for AD.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment and neuronal loss, with pathological hallmarks including Aβ plaque deposition and tau tangles. At present, the early diagnosis and treatment of AD still face great challenges, such as limited diagnostic methods, difficulty in blood-brain barrier (BBB) penetration, complex disease mechanisms, and lack of highly effective targeted therapies. Antibody drugs have shown broad prospects in the field of AD due to their high specificity, engineering and multifunctional therapeutic potential, include targeted Aβ clearance, tau pathological regulation, imaging probes, and blood biomarkers. In the future, with the development of antibody engineering technologies (such as PROTAC-antibody conjugates and antibody-based gene therapies), the precision diagnosis and treatment of AD is expected to usher in new breakthroughs. This article systematically reviews the latest advances in the treatment and diagnosis of AD and discusses their potential for clinical translation.

Paget's disease of bone (PDB) is a chronic skeletal disorder characterized by abnormal bone remodeling and structural deformities, yet its underlying molecular mechanisms remain poorly understood. Genetic mutations in regulatory genes have been implicated in the PDB, potentially disrupting osteoclast activity and leading to excessive bone resorption and abnormal bone formation. Current research has largely focused on clinical phenotypes and downstream pathways, relying on molecular biology approaches and omics analyses to elucidate mechanisms. However, the impact of genetic mutations on the biophysical properties and functional dynamics of biomacromolecules remain unclear. Phase separation (PS), a process essential for biomolecular condensate organization and cellular function, has been implicated in various diseases but is unexplored in the PDB. This study investigates the PS properties of ZNF687, a zinc finger protein associated with PDB. Structural predictions and sequence analyses identified intrinsically disordered regions (IDRs) within ZNF687 that may drive PS, while protein interaction predictions suggest its involvement in bone remodeling pathways. These findings provide a novel perspective linking PS to PDB pathogenesis and highlight ZNF687 as a potential target for further investigation.

Mesenchymal stem cells (MSCs) hold significant promise for regenerative medicine and tissue engineering due to their unique multipotent differentiation ability and immunomodulatory properties. MSC therapy is widely discussed and utilized in clinical treatment. However, during both in vitro expansion and in vivo transplantation, MSCs are prone to senescence, an irreversible growth arrest characterized by morphological, gene expression, and functional changes in genomic regulation. The microenvironment surrounding MSCs plays a crucial role in modulating their senescence phenotype, influenced by factors such as hypoxia, inflammation, and aging status. Numerous strategies targeting MSC senescence have been developed, including senolytics and senomorphic agents, antioxidant and exosome therapies, mitochondrial transfer, and niche modulation. Novel approaches addressing replicative senescence have also emerged. This paper comprehensively reviews the current molecular manifestations of MSC senescence, addresses the environmental impact on senescence, and highlights potential therapeutic strategies to mitigate senescence in MSC-based therapies. These insights aim to enhance the efficacy and understanding of MSC therapies.

Although groundbreaking biotechnological techniques such as gene editing have significantly progressed, the effective and targeted transport of therapeutic agents into host cells remains a major obstacle to the development of biotherapeutics. Confronting the unique challenge posed by large macromolecules such as proteins, peptides, and nucleic acids adds complexity to this issue. Recent findings reveal that the supercharging of proteins and peptides not only enables control over critical properties, such as temperature resistance and catalytic activity, but also holds promise as a viable strategy for their use in drug delivery. This review provides a concise summary of the attributes of supercharged proteins and peptides, encompassing both their natural occurrence and engineered variants. Furthermore, it sheds light on the present status and future possibilities of supercharged proteins and peptides as carriers for significant biomolecules in the realms of medical research and therapeutic applications.

Osteogenesis imperfecta (OI) is an uncommon genetic disorder characterized by shortness of stature, hearing loss, poor bone mass, recurrent fractures, and skeletal abnormalities. Pathogenic variations have been found in over 20 distinct genes that are involved in the pathophysiology of OI, contributing to the disorder's clinical and genetic variability. Although medications, surgical procedures, and other interventions can partially alleviate certain symptoms, there is still no known cure for OI. In this Review, we provide a comprehensive overview of genetic pathogenesis, existing treatment modalities, and new developments in biotechnologies such as gene editing, stem cell reprogramming, functional differentiation, and transplantation for potential future OI therapy.

Introduction: Intramuscular hemangioma (IMH) is a rare type of benign tumor that represents less than 1% of all hemangiomas. Chronic pain and a palpable mass are the most common symptoms. Due to the atypical clinical characteristics of the disease, accurate diagnosis is difficult. Misdiagnosis of IMH as malignancy can occur due to similarities in imaging features between IMH and malignancy. To diagnose IMH accurately, multiple imaging modalities, including X-ray, MRI, CT, and ¹⁸F-FDG PET/CT, can be used. However, the final diagnosis of IMH is confirmed through histopathological examination. Case: This case reports a 16-year-old girl diagnosed with IMH in the triceps brachii muscle. Seek medical attention due to pain and discomfort in the left shoulder. Initial imaging with contrast-enhanced MRI and CT suggested synovial sarcomata. The moderate uptake of FDG on positron emission tomography/computed tomography (PET/CT) also raised suspicions of malignancy. The pathological findings revealed an intramuscular hemangioma with thrombosis and thrombus organization. Conclusion: The accurate diagnosis of IMH can be challenging due to the absence of distinct clinical symptoms and imaging findings. When evaluating periarticular intramuscular lesions, IMH should be considered if the MRI shows mixed signals with heterogeneous enhancement. Despite the moderate uptake of FDG seen in some IMH cases, it should not automatically rule out the possibility of IMH. Hence, a combination of imaging modalities and histopathological examination is crucial in ensuring a correct diagnosis of IMH.

COVID-19 (Coronavirus Disease 2019) is an infectious disease caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and has globally infected 768 million people and caused over 6 million deaths. COVID-19 primarily affects the respiratory system but increasing reports of neurologic symptoms associated with COVID-19 have been reported in the literature. The exact mechanism behind COVID-19 neurologic pathophysiology remains poorly understood due to difficulty quantifying clinical neurologic symptoms in humans and correlating them to findings in human post-mortem samples and animal models. Thus, robust preclinical experimental models for COVID-19 neurologic manifestations are urgently needed. Here, we review recent advances in in vitro, in vivo, and other models and technologies for studying COVID-19 including primary cell cultures, pluripotent stem cell-derived neurons and organoids, rodents, nonhuman primates, 3D bioprinting, artificial intelligence, and multiomics. We specifically focus our discussion on the contribution, recent advancements, and limitations these preclinical models have on furthering our understanding of COVID-19's neuropathic physiology. We also discuss these models' roles in the screening and development of therapeutics, vaccines, antiviral drugs, and herbal medicine, and on future opportunities for COVID-19 neurologic research and clinical management.