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Redox Biology May 2024During cerebral ischemia-reperfusion conditions, the excessive reactive oxygen species in the ischemic penumbra region, resulting in neuronal oxidative stress,... (Review)
Review
During cerebral ischemia-reperfusion conditions, the excessive reactive oxygen species in the ischemic penumbra region, resulting in neuronal oxidative stress, constitute the main pathological mechanism behind ischemia-reperfusion damage. Swiftly reinstating blood perfusion in the ischemic penumbra zone and suppressing neuronal oxidative injury are key to effective treatment. Presently, antioxidants in clinical use suffer from low bioavailability, a singular mechanism of action, and substantial side effects, severely restricting their therapeutic impact and widespread clinical usage. Recently, nanomedicines, owing to their controllable size and shape and surface modifiability, have demonstrated good application potential in biomedicine, potentially breaking through the bottleneck in developing neuroprotective drugs for ischemic strokes. This manuscript intends to clarify the mechanisms of cerebral ischemia-reperfusion injury and provides a comprehensive review of the design and synthesis of antioxidant nanomedicines, their action mechanisms and applications in reversing neuronal oxidative damage, thus presenting novel approaches for ischemic stroke prevention and treatment.
PubMed: 38759419
DOI: 10.1016/j.redox.2024.103185 -
Medicine May 2024This bibliometric analysis explored the knowledge structure of and research trends in the relationship between light and myopia.
BACKGROUND
This bibliometric analysis explored the knowledge structure of and research trends in the relationship between light and myopia.
METHODS
Relevant literature published from 1981 to 2024 was collected from the Web of Science Core Collection database. Visual maps were generated using CiteSpace and VOSviewer. We analyzed the included studies in terms of the annual publication count, countries, institutional affiliations, prolific authors, source journals, top 10 most cited articles, keyword co-occurrence, and cocitations.
RESULTS
A total of 525 papers examining the relationship between light and myopia published between 1981 and 2024 were collected. The United States ranked first in terms of the number of publications and actively engaged in international cooperation with other countries. The New England College of Optometry, which is located in the United States, was the most active institution and ranked first in terms of the number of publications. Schaeffel Frank was the most prolific author. The most active journal in the field was Investigative Ophthalmology & Visual Science. The most frequently cited paper in the included studies was written by Saw, SM and was published in 2002. The most common keywords in basic research included "refractive error," "longitudinal chromatic aberration," and "compensation." The most common keywords in clinical research mainly included "light exposure," "school," and "outdoor activity." The current research hotspots in this field are "progression," "refractive development," and "light exposure." The cocitation analysis generated 17 clusters.
CONCLUSION
This study is the first to use bibliometric methods to analyze existing research on the relationship between light and myopia. In recent years, the intensity and wavelength of light have become research hotspots in the field. Further research on light of different intensities and wavelengths may provide new perspectives in the future for designing more effective treatments and interventions to reduce the incidence of myopia.
Topics: Bibliometrics; Myopia; Humans; Light; Biomedical Research
PubMed: 38758893
DOI: 10.1097/MD.0000000000038157 -
Medicine May 2024Cancer stem cells (CSCs) are a subset of cells with self-renewal ability and tumor generating potential. Accumulated evidence has revealed that CSCs were shown to...
Cancer stem cells (CSCs) are a subset of cells with self-renewal ability and tumor generating potential. Accumulated evidence has revealed that CSCs were shown to contribute to tumorigenesis, metastasis, recurrence and resistance to chemoradiotherapy. Therefore, CSCs were regarded as promising therapeutic targets in cancer. This study is the first to reveal the development process, research hotspots, and trends of entire CSCs research field through bibliometric methods. All relevant publications on CSCs with more than 100 citations (notable papers) and the 100 most cited papers (top papers) during 1997 to 2023 were extracted and analyzed. Cancer research published the largest number of papers (184 papers). The USA accounted for the most publications (1326 papers). Rich, JN was the author with the most publications (56 papers) and the highest M-index (3.111). The most contributive institution was the University of Texas System (164 papers). Before 2007, research mainly focused on the definition and recognition of CSCs. Between 2007 and 2016, with the emergence of the terms such as "sonic hedgehog," "metabolism," "oxidative phosphorylation," and "epithelial mesenchymal transition," research began to shift toward exploring the mechanisms of CSCs. In 2016, the focus transitioned to the tumor microenvironment and the ecological niches. The analysis of papers published in major journals since 2021 showed that "transcription," "inhibition," and "chemoresistance" emerged as new focused issues. In general, the research focus has gradually shifted from basic biology to clinical transformation. "Tumor microenvironment" and "chemo-resistance" should be given more attention in the future.
Topics: Neoplastic Stem Cells; Bibliometrics; Humans; Biomedical Research; Neoplasms; Tumor Microenvironment
PubMed: 38758889
DOI: 10.1097/MD.0000000000038125 -
Medicine May 2024Radiology has become a fundamental constituent of the modern medicine. However, it has been observed that medical students in Pakistan often lack sufficient guidance and...
Radiology has become a fundamental constituent of the modern medicine. However, it has been observed that medical students in Pakistan often lack sufficient guidance and education in this field. This study aims to establish whether Pakistani medical students possess the requisite basic knowledge required in radiology and their attitude and perception toward radiology as a potential career path. This cross-sectional study conducted a survey among 530 medical students of Pakistan via a self-reported online questionnaire from August 01, 2021 to September 01, 2021. The data collected were analyzed using the SPSS software, along with logistic regression analyses to identify factors associated with interest in pursuing radiology as a career and possessing a comprehensive understanding of radiology among medical students. Of the 530 participants, 44.2% rated their understanding of radiology as "poor" with only 17% indicating interest to pursue a career in radiology. Logistic regression model showed significantly higher odds of radiology as a career among males (Crude odds ratio [COR] = 1.78, 95% confidence interval [CI] = 1.17-2.72, P = .007), medical students of Punjab (COR = 1.55, 95% CI = 1.01-2.40, P = .048), and those, who self-reported their knowledge of radiology as excellent (COR = 14.35, 95% CI = 5.13-40.12, P < .001). In contrast, medical students from Punjab (COR = 0.504, 95% CI = 0.344-0.737, P < .001) and second-year medical students (COR = 0.046, 95% CI = 0.019-0.107, P < .001) had lower odds of good knowledge. Our study suggests that the medical student's knowledge of radiology is deficient. Thus, it is advised that radiological societies work with medical school boards to integrate thorough and early radiology exposure into the undergraduate curriculum.
Topics: Humans; Students, Medical; Cross-Sectional Studies; Pakistan; Male; Female; Career Choice; Radiology; Surveys and Questionnaires; Young Adult; Adult
PubMed: 38758871
DOI: 10.1097/MD.0000000000038156 -
Medicine May 2024To investigate the regulatory patterns of Chinese patent medicine (CPM) interventions on lipid metabolism disorders in patients with type 2 diabetes mellitus (T2DM)... (Meta-Analysis)
Meta-Analysis
Regulatory patterns of Chinese patent medicine for lipid metabolism disorders in patients with type 2 diabetes mellitus complicated by ischemic stroke: A systematic review and network meta-analysis.
BACKGROUND
To investigate the regulatory patterns of Chinese patent medicine (CPM) interventions on lipid metabolism disorders in patients with type 2 diabetes mellitus (T2DM) complicated by ischemic stroke.
METHODS
Two researchers independently searched 8 major databases and created a comprehensive database containing all randomized controlled trials (RCTs) that investigated the application of "blood-activating and stasis-removing" CPM in the treatment of stroke combined with T2DM until October 1, 2022. The collected data were compiled and organized in Excel. Quality assessment was performed using the Cochrane 5.3 bias risk assessment tool, and the network meta-analysis was conducted using R software.
RESULTS
A total of 12 articles were included in the final analysis, covering 4 types of CPM: Naoxintong Capsules (NXT), Tongmai Jiangtang Capsules, Tongxinluo Capsules (TXL), and Yindan Xinnaotong Soft Capsules. Among these, CPM formulations containing herbs with blood-activating and stasis-removing properties were the most commonly used. The results of the network meta-analysis are as follows: (1) the combination of 3 CPM formulations showed superior efficacy in improving total cholesterol levels compared to conventional Western medicine treatment (CT). In particular, Yindan Xinnaotong Soft Capsules + CT (surface under the cumulative ranking curve [SUCRA] = 97.24%) demonstrated the highest efficacy, followed by NXT + CT (SUCRA = 66.23%), and then TXL + CT (SUCRA = 55.16%). (2) TXL + CT treatment exhibited the most promising efficacy in improving triglyceride levels (P < .05), while the effects of the other 3 CPM formulations were not statistically significant. (3) In terms of improving low-density lipoprotein levels, NXT + CT (SUCRA = 82.27%) showed better efficacy than TXL + CT (SUCRA = 73.99%), while the effects of the other 2 CPM formulations were not statistically significant. (4) The combination of CPM formulations and CT resulted in a lower incidence of adverse reactions compared to CT (P < .05).
CONCLUSION
The treatment of patients with T2DM complicated by ischemic stroke commonly involved the use of "blood-activating and stasis-removing" herbal medicines. These herbal medicines have shown effectiveness in regulating patients' blood lipid levels. However, it is crucial to acknowledge that the analysis was influenced by variations in the number and quality of RCTs involving different CPM formulations. Therefore, additional validation through large-scale, high-quality RCT studies is required.
Topics: Diabetes Mellitus, Type 2; Humans; Drugs, Chinese Herbal; Ischemic Stroke; Network Meta-Analysis; Lipid Metabolism Disorders; Randomized Controlled Trials as Topic; Medicine, Chinese Traditional
PubMed: 38758863
DOI: 10.1097/MD.0000000000035050 -
Medicine May 2024Studies have suggested that Vitamin D deficiency is associated with the occurrence of both type 1 and type 2 diabetes, and that vitamin D-binding proteins (VDBP) are...
Studies have suggested that Vitamin D deficiency is associated with the occurrence of both type 1 and type 2 diabetes, and that vitamin D-binding proteins (VDBP) are necessary for metabolic stress in pancreatic α-cells. However, the causal relationship between serum 25-hydroxyvitamin D [25(OH)D] levels, VDBP, and the risk of diabetes mellitus (DM) remains unclear. Mendelian randomization (MR) was used to investigate the causal relationship between 25(OH)D, VDBP, and DM. Relevant recent data were downloaded from the NHGRI-EBI Catalog of published genome-wide association studies (GWAS) and filtered for single nucleotide polymorphisms (SNPs). We used multiple MR methods, including inverse variance weighting (IVW), and performed sensitivity analyses to detect whether pleiotropy or heterogeneity biased the results. There was a causal relationship between genetically predicted VDBP levels and serum 25(OH)D levels, and serum 25(OH)D levels increased with increasing VDBP levels (IVW: β = 0.111, OR = 1.117, 95% CI:1.076-1.162, P = 1.41 × 10-8). There was no causal relationship between the genetically predicted VDBP levels, serum 25(OH)D levels, and DM (VDBP: IVW β:0.001, OR:1.001, 95% CI:0.998-1.003, P > .05; 25(OH)D: IVW β: -0.009, OR:0.991, 95% CI:0.982-1.001, P = .068). Sensitivity analysis indicated that horizontal pleiotropy was unlikely to bias causality in this study. MR analysis results demonstrated a positive causal relationship between VDBP levels and serum 25(OH)D levels in the European population. The 25(OH)D and VDBP levels were not causally related to an increased risk of diabetes.
Topics: Humans; Mendelian Randomization Analysis; Vitamin D-Binding Protein; Vitamin D; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Diabetes Mellitus, Type 2; Vitamin D Deficiency
PubMed: 38758851
DOI: 10.1097/MD.0000000000038219 -
PloS One 2024Mpox (formerly known as monkeypox) virus and some related poxviruses including smallpox virus pose a significant threat to public health, and effective prevention and...
Mpox (formerly known as monkeypox) virus and some related poxviruses including smallpox virus pose a significant threat to public health, and effective prevention and treatment strategies are needed. This study utilized a reverse vaccinology approach to retrieve conserved epitopes for monkeypox virus and construct a vaccine that could provide cross-protection against related viruses with similar antigenic properties. The selected virulent proteins of monkeypox virus, MPXVgp165, and Virion core protein P4a, were subjected to epitope mapping for vaccine construction. Two vaccines were constructed using selected T cell epitopes and B cell epitopes with PADRE and human beta-defensins adjuvants conjugated in the vaccine sequence. Both constructs were found to be highly antigenic, non-allergenic, nontoxic, and soluble, suggesting their potential to generate an adequate immune response and be safe for humans. Vaccine construct 1 was selected for molecular dynamic simulation studies. The simulation studies revealed that the TLR8-vaccine complex was more stable than the TLR3-vaccine complex. The lower RMSD and RMSF values of the TLR8 bound vaccine compared to the TLR3 bound vaccine suggested better stability and consistency of hydrogen bonds. The Rg values of the vaccine chain bound to TLR8 indicated overall stability, whereas the vaccine chain bound to TLR3 showed deviations throughout the simulation. These results suggest that the constructed vaccine could be a potential preventive measure against monkeypox and related viruses however, further experimental validation is required to confirm these findings.
Topics: Humans; Monkeypox virus; Molecular Dynamics Simulation; Epitopes, T-Lymphocyte; Epitopes, B-Lymphocyte; Computer Simulation; Poxviridae; Viral Vaccines; Epitope Mapping; Mpox (monkeypox); Animals; Toll-Like Receptor 8
PubMed: 38758816
DOI: 10.1371/journal.pone.0300778 -
Science Advances May 2024At the synapse, presynaptic neurotransmitter release is tightly controlled by release machinery, involving the soluble -ethylmaleimide-sensitive factor attachment...
At the synapse, presynaptic neurotransmitter release is tightly controlled by release machinery, involving the soluble -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins and Munc13. The Ca sensor Doc2 cooperates with Munc13 to regulate neurotransmitter release, but the underlying mechanisms remain unclear. In our study, we have characterized the binding mode between Doc2 and Munc13 and found that Doc2 originally occludes Munc13 to inhibit SNARE complex assembly. Moreover, our investigation unveiled that EphB2, a presynaptic adhesion molecule (SAM) with inherent tyrosine kinase functionality, exhibits the capacity to phosphorylate Doc2. This phosphorylation attenuates Doc2 block on Munc13 to promote SNARE complex assembly, which functionally induces spontaneous release and synaptic augmentation. Consistently, application of a Doc2 peptide that interrupts Doc2-Munc13 interplay impairs excitatory synaptic transmission and leads to dysfunction in spatial learning and memory. These data provide evidence that SAMs modulate neurotransmitter release by controlling SNARE complex assembly.
Topics: SNARE Proteins; Animals; Neurotransmitter Agents; Nerve Tissue Proteins; Phosphorylation; Receptor, EphB2; Calcium-Binding Proteins; Synaptic Transmission; Protein Binding; Humans; Mice; Rats
PubMed: 38758791
DOI: 10.1126/sciadv.adi7024 -
Cell Reports May 2024Signal-regulatory protein alpha (SIRPα) has recently been found to be highly expressed in podocytes and is essential for maintaining podocyte function. However, its...
Signal-regulatory protein alpha (SIRPα) has recently been found to be highly expressed in podocytes and is essential for maintaining podocyte function. However, its immunoregulatory function in podocytes remains elusive. Here, we report that SIRPα controls podocyte antigen presentation in specific T cell activation via inhibiting spleen tyrosine kinase (Syk) phosphorylation. First, podocyte SIRPα under lupus nephritis (LN) conditions is strongly downregulated. Second, podocyte-specific deletion of SIRPα exacerbates renal disease progression in lupus-prone mice, as evidenced by an increase in T cell infiltration. Third, SIRPα deletion or knockdown enhances podocyte antigen presentation, which activates specific T cells, via enhancing Syk phosphorylation. Supporting this, Syk inhibitor GS-9973 prevents podocyte antigen presentation, resulting in a decrease of T cell activation and mitigation of renal disease caused by SIRPα knockdown or deletion. Our findings reveal an immunoregulatory role of SIRPα loss in promoting podocyte antigen presentation to activate specific T cell immune responses in LN.
PubMed: 38758648
DOI: 10.1016/j.celrep.2024.114249 -
Journal of Cellular and Molecular... May 2024Ferroptosis is a distinct mode of cell death, distinguishing itself from typical apoptosis by its reliance on the accumulation of iron ions and lipid peroxides. Cells... (Review)
Review
Ferroptosis is a distinct mode of cell death, distinguishing itself from typical apoptosis by its reliance on the accumulation of iron ions and lipid peroxides. Cells manifest an imbalance between oxidative stress and antioxidant equilibrium during certain pathological contexts, such as tumours, resulting in oxidative stress. Notably, recent investigations propose that heightened intracellular reactive oxygen species (ROS) due to oxidative stress can heighten cellular susceptibility to ferroptosis inducers or expedite the onset of ferroptosis. Consequently, comprehending role of ROS in the initiation of ferroptosis has significance in elucidating disorders related to oxidative stress. Moreover, an exhaustive exploration into the mechanism and control of ferroptosis might offer novel targets for addressing specific tumour types. Within this context, our review delves into recent fundamental pathways and the molecular foundation of ferroptosis. Four classical ferroptotic molecular pathways are well characterized, namely, glutathione peroxidase 4-centred molecular pathway, nuclear factor erythroid 2-related factor 2 molecular pathway, mitochondrial molecular pathway, and mTOR-dependent autophagy pathway. Furthermore, we seek to elucidate the regulatory contributions enacted by ROS. Additionally, we provide an overview of targeted medications targeting four molecular pathways implicated in ferroptosis and their potential clinical applications. Here, we review the role of ROS and oxidative stress in ferroptosis, and we discuss opportunities to use ferroptosis as a new strategy for cancer therapy and point out the current challenges persisting within the domain of ROS-regulated anticancer drug research and development.
Topics: Ferroptosis; Humans; Oxidative Stress; Neoplasms; Reactive Oxygen Species; Animals; Signal Transduction; Autophagy; Antineoplastic Agents; Mitochondria
PubMed: 38757920
DOI: 10.1111/jcmm.18399