Decoding trends in mRNA vaccine research: A comprehensive bibliometric study.

BACKGROUND: In recent years, infectious diseases like COVID-19 have had profound global socio-economic impacts. mRNA vaccines have gained prominence due to their rapid development, industrial adaptability, simplicity, and responsiveness to new variants. Notably, the 2023 Nobel Prize in Physiology or Medicine recognized significant contributions to mRNA vaccine research. METHODS: Our study employed a comprehensive bibliometric analysis using the Web of Science Core Collection (WoSCC) database, encompassing 5,512 papers on mRNA vaccines from 2003 to 2023. We generated cooperation maps, co-citation analyses, and keyword clustering to evaluate the field's developmental history and achievements. RESULTS: The analysis yielded knowledge maps highlighting countries/institutions, influential authors, frequently published and highly cited journals, and seminal references. Ongoing research hotspots encompass immune responses, stability enhancement, applications in cancer prevention and treatment, and combating infectious diseases using mRNA technology. CONCLUSIONS: mRNA vaccines represent a transformative development in infectious disease prevention. This study provides insights into the field's growth and identifies key research priorities, facilitating advancements in vaccine technology and addressing future challenges.

HIF-1-dependent heme synthesis promotes gemcitabine resistance in human non-small cell lung cancers via enhanced ABCB6 expression.

Gemcitabine is commonly used to treat various cancer types, including human non-small cell lung cancer (NSCLC). However, even cases that initially respond rapidly commonly develop acquired resistance, limiting our ability to effectively treat advanced NSCLC. To gain insight for developing a strategy to overcome gemcitabine resistance, the present study investigated the mechanism of gemcitabine resistance in NSCLC according to the involvement of ATP-binding cassette subfamily B member 6 (ABCB6) and heme biosynthesis. First, an analysis of ABCB6 expression in human NSCLCs was found to be associated with poor prognosis and gemcitabine resistance in a hypoxia-inducible factor (HIF)-1-dependent manner. Further experiments showed that activation of HIF-1α/ABCB6 signaling led to intracellular heme metabolic reprogramming and a corresponding increase in heme biosynthesis to enhance the activation and accumulation of catalase. Increased catalase levels diminished the effective levels of reactive oxygen species, thereby promoting gemcitabine-based resistance. In a mouse NSCLC model, inhibition of HIF-1α or ABCB6, in combination with gemcitabine, strongly restrained tumor proliferation, increased tumor cell apoptosis, and prolonged animal survival. These results suggest that, in combination with gemcitabine-based chemotherapy, targeting HIF-1α/ABCB6 signaling could result in enhanced tumor chemosensitivity and, thus, may improve outcomes in NSCLC patients.

In vitro and in vivo evaluation of DC-targeting PLGA nanoparticles encapsulating heparanase CD4+ and CD8+ T-cell epitopes for cancer immunotherapy.

Heparanase has been identified as a universal tumor-associated antigen, but heparanase epitope peptides are difficult to recognize. Therefore, it is necessary to explore novel strategies to ensure efficient delivery to antigen-presenting cells. Here, we established a novel immunotherapy model targeting antigens to dendritic cell (DC) receptors using a combination of heparanase CD4+ and CD8+ T-cell epitope peptides to achieve an efficient cytotoxic T-cell response, which was associated with strong activation of DCs. First, pegylated poly(lactic-coglycolic acid) (PLGA) nanoparticles (NPs) were used to encapsulate a combined heparanase CD4+ and CD8+ T-cell epitope alone or in combination with Toll-like receptor 3 and 7 ligands as a model antigen to enhance immunogenicity. The ligands were then targeted to DC cell-surface molecules using a DEC-205 antibody. The binding and internalization of these PLGA NPs and the activation of DCs, the T-cell response and the tumor-killing effect were assessed. The results showed that PLGA NPs encapsulating epitope peptides (mHpa399 + mHpa519) could be targeted to and internalized by DCs more efficiently, stimulating higher levels of IL-12 production, T-cell proliferation and IFN-γ production by T cells in vitro. Moreover, vaccination with DEC-205-targeted PLGA NPs encapsulating combined epitope peptides exhibited higher tumor-killing efficacy both in vitro and in vivo. In conclusion, delivery of PLGA NP vaccines targeting DEC-205 based on heparanase CD4+ and CD8+ T-cell epitopes are suitable immunogens for antitumor immunotherapy and have promising potential for clinical applications.

Effect of Gender on Iron-induced Brain Injury in Low Aerobic Capacity Rats.

Brain iron overload has a key role in brain injury after intracerebral hemorrhage (ICH). Low aerobic capacity is a risk factor for cardiovascular disease and our previous study demonstrated that ICH-induced brain injury is enhanced in rats with low aerobic capacity (low capacity runners; LCRs). We have found that ICH-induced injury is less in female rats compared with that in males. In the present study, we examined the effects of gender on iron-induced brain injury in rats with low aerobic capacity. Adult male and female LCR rats had an intracaudate injection of FeCl2 (50 µl 0.5 mM). T2 Magnetic resonance imaging was carried out at 24 h to determine brain swelling and T2 brain lesion volume. Albumin leakage, an indicator of blood-brain barrier (BBB) disruption, and heme oxygenase-1 (HO-1, a stress marker) levels were determined. Male LCR rats had more severe hemisphere swelling (difference of ipsilateral to contralateral hemisphere volume: 16.6 ± 4.1 vs 11.1 ± 2.6 % in females, p < 0.05) and larger T2 lesion volumes (120 ± 28 vs 87 ± 27 mm(3) in females, p < 0.05) after iron injection. Iron also resulted in more severe BBB disruption in the ipsilateral hemisphere of males (albumin levels: 7,717 ± 1,502 pixels in males vs 5,287 ± 1,342 pixels in females; p < 0.05). The immunoreactivity of HO-1 was also significantly higher in males than females (HO-1/ß-actin: 1.31 ± 0.44 vs 1.03 ± 0.05, p < 0.05). Female LCR rats had less iron-induced brain swelling, smaller lesion volumes, and reduced BBB disruption and HO-1 upregulation compared with male LCR rats. This may contribute to the reduced ICH-induced brain injury found in females.

Iron-induced necrotic brain cell death in rats with different aerobic capacity.

Brain iron overload has a key role in brain injury after intracerebral hemorrhage (ICH). Our recent study demonstrated that ICH-induced brain injury was greater in low capacity runner (LCR) than in high capacity runner (HCR) rats. The present study examines whether iron-induced brain injury differs between LCRs and HCRs. Adult male LCR and HCR rats had an intracaudate injection of iron or saline. Rats were euthanized at 2 and at 24 h after T2 magnetic resonance imaging, and the brains were used for immunostaining and Western blotting. LCRs had more hemispheric swelling, T2 lesion volumes, blood-brain barrier disruption, and neuronal death at 24 h after iron injection (p < 0.05). Many propidium iodide (PI)-positive cells, indicative of necrotic cell death, were observed in the ipsilateral basal ganglia of both HCRs and LCRs at 2 h after iron injection. PI fluorescence intensity was higher in LCRs than in HCRs. In addition, membrane attack complex (MAC) expression was increased at 2 h after iron injection and was higher in LCRs than in HCRs. The PI-positive cells co-localized with MAC-positive cells in the ipsilateral basal ganglia. Iron induces more severe necrotic brain cell death, brain swelling, and blood-brain barrier disruption in LCR rats, which may be related with complement activation and MAC formation.

Role of red blood cell lysis and iron in hydrocephalus after intraventricular hemorrhage.

Thrombin and iron are two major players in intracerebral hemorrhage-induced brain injury and our recent study found that thrombin contributes to hydrocephalus development in a rat model of intraventricular hemorrhage (IVH). This study investigated the role of red blood cell (RBC) lysis and iron in hydrocephalus after IVH. There were three parts to this study. First, male Sprague-Dawley rats received an injection of saline, packed, or lysed RBCs into the right lateral ventricle. Second, rats had an intraventricular injection of iron or saline. Third, the rats received intraventricular injection of lysed RBCs mixed with deferoxamine (0.5 mg in 5 µL saline) or saline. All rats underwent magnetic resonance imaging at 24 hours and were then euthanized for brain edema measurement, western blot analysis, or brain histology. We found that intraventricular injection of lysed RBCs, but not packed RBCs, resulted in ventricular enlargement and marked increases in brain heme oxygenase-1 and ferritin at 24 hours. Intraventricular injection of iron also resulted in ventricular enlargement and ventricular wall damage 24 hours later. Coinjection of deferoxamine reduced lysed RBC-induced ventricular enlargement (P<0.01). These results suggest that iron, a degradation product of hemoglobin, has an important role in hydrocephalus development after IVH.

Impaired white-matter integrity in photosensitive epilepsy: a DTI study using tract-based spatial statistics.

BACKGROUND AND PURPOSE: The present study was designed to map alterations in brain white-matter in photosensitive epilepsy (PSE) by applying tract-based spatial statistics (TBSS) analysis. METHODS: Diffusion tensor-imaging (DTI) data from MRI brain scans were collected from eight PSE patients and 16 gender- and age-matched non-epileptic controls using a SIEMENS Trio 3.0-Tesla scanner. For the white-matter analysis, DTI scans were processed using FSL software (http://www.fmrib.ox.ac.uk/fsl/index.html). Fractional anisotropy (FA) values in the PSE and control groups were compared using TBSS analysis corrected for multiple comparisons using threshold-free cluster enhancement. RESULTS: Compared with the control subjects, the corpus callosum of PSE patients had significantly lower FA values. CONCLUSION: Our DTI study indicates that white-matter in the corpus callosum was abnormal in PSE patients, and that DTI methods can serve as useful non-invasive tools to evaluate white-matter changes in PSE patients.

Reduced white matter integrity in primary open-angle glaucoma: a DTI study using tract-based spatial statistics.

BACKGROUND AND PURPOSE: The present study was designed to map the alteration of white matter in primary open-angle glaucoma (POAG) by applying tract-based spatial statistics (TBSS) analysis. METHODS: Diffusion tensor imaging (DTI) data from MRI brain scans were collected from 15 POAG patients and 15 gender- and age-matched non-glaucoma controls using a SIEMENS Trio 3.0-Tesla scanner. For the white-matter analysis, DTI images were processed using FSL software (http://www.fmrib.ox.ac.uk/fsl/index.html). Fractional anisotropy (FA) between the POAG and control groups was compared by TBSS analysis corrected for multiple comparisons using threshold-free cluster enhancement (TFCE). RESULTS: Compared with non-glaucoma subjects, the occipital white matter in POAG patients had significantly lower FA values (p<0.05, corrected). CONCLUSION: The change in white-matter FA may indicate atrophy of the visual cortex that may be important in the diagnosis and treatment of POAG patients.

Voxel-based morphometry of the visual-related cortex in primary open angle glaucoma.

PURPOSE: To study changes in the morphometric characteristics of the whole brain visual-related cortex in various stages of primary open angle glaucoma (POAG) in vivo. MATERIALS AND METHODS: Thirty POAG patients (nine early stage cases and 21 advanced-late stage cases) and 30 gender-, education-, and age-matched healthy controls were enrolled in the study. Image data were obtained with a T1 weighted three-dimensional magnetization prepared rapid acquisition gradient echo sequence (T1WI 3D MP RAGE). Voxel-based morphometry (VBM) analysis was used to assess regional differences in gray matter (GM) densities on T1WI 3D MP RAGE scans of patients versus controls. RESULTS: Compared with controls, brain regions with GM density changes were not found in the early stage of POAG patients but were found in the advanced-late stage of POAG patients. These changes with GM density reduction were mainly located in the bilateral primary visual cortex (BA17 and BA18), bilateral paracentral lobule (BA5), right precentral gyrus (BA6), right middle frontal gyrus (BA9), right inferior temporal gyrus (BA20), right angular gyrus (BA39), left praecuneus (BA7), left middle temporal gyrus (BA21), and superior temporal gyrus (BA22). Conversely, patients showed increased GM density in BA39 near the most damaged regions. In addition, in the advanced-late stage of POAG, some reduced GM density areas were related to binocular mean defect (MD) and disease duration (ranging from r = -0.761 to r = -0.458). CONCLUSIONS: Our results suggest that there are different types of pathogenesis at different stages of POAG. Atrophy and degeneration of the visual-related cortex existed in the dorsal and ventral visual pathways in the advanced-late stage of POAG but were not found in the early stage of POAG using VBM. Such GM density changes are likely associated with the pathogenesis of POAG.

A voxel-based morphometric analysis of cerebral gray matter in subcortical ischemic vascular dementia patients and normal aged controls.

BACKGROUND AND PURPOSE: The present study was designed to detect the abnormalities of the cerebral grey-matter density in subcortical ischemic vascular dementia patients by FSL-VBM method to promote the early diagnosis of it. METHODS: Nine subcortical ischemic vascular dementia patients and nine age-matched normal controls underwent MRI brain structure scanning that was performed on a SIEMENS AVANTO 1.5 Tesla scanner and standard T1-weighted high-resolution anatomic scans of MPRAGE sequence were obtained. The 3-demensional MPRAGE images were processed with FSL-VBM package and the cerebral gray matter density was compared between the subcortical ischemic vascular dementia patients and normal controls. RESULTS: Compared with the normal control group, the cerebral gray matter density of subcortical ischemic vascular dementia patients was found significantly decreasing, including brain regions of thalamus, parietal lobe, frontal lobe and temporal lobe (P<0.05). CONCLUSIONS: The cerebral gray matter density alterations have closed correlation with cognitive dysfunction in subcortical ischemic vascular dementia patient and can be detected by MRI. MRI has some potential value in the diagnosis of them.

Alterations of whole-brain cortical area and thickness in mild cognitive impairment and Alzheimer's disease.

Gray matter volume and density of several brain regions, determined by magnetic resonance imaging (MRI), are decreased in Alzheimer's disease (AD). Animal studies have indicated that changes in cortical area size is relevant to thinking and behavior, but alterations of cortical area and thickness in the brains of individuals with AD or its likely precursor, mild cognitive impairment (MCI), have not been reported. In this study, 25 MCI subjects, 30 AD subjects, and 30 age-matched normal controls were recruited for brain MRI scans and Functional Activities Questionnaire (FAQ) assessments. Based on the model using FreeSurfer software, two brain lobes were divided into various regions according to the Desikan-Killiany atlas and the cortical area and thickness of every region was compared and analyzed. We found a significant increase in cortical area of several regions in the frontal and temporal cortices, which correlated negatively with MMSE scores, and a significant decrease in cortical area of several regions in the parietal cortex and the cingulate gyrus in AD subjects. Increased cortical area was also seen in some regions of the frontal and temporal cortices in MCI subjects, whereas the cortical thickness of the same regions was decreased. Our observations suggest characteristic differences of the cortical area and thickness in MCI, AD, and normal control subjects, and these changes may help diagnose both MCI and AD.

Impaired resting-state functional integrations within default mode network of generalized tonic-clonic seizures epilepsy.

Generalized tonic-clonic seizures (GTCS) are characterized by unresponsiveness and convulsions, which cause complete loss of consciousness. Many recent studies have found that the ictal alterations in brain activity of the GTCS epilepsy patients are focally involved in some brain regions, including thalamus, upper brainstem, medial prefrontal cortex, posterior midbrain regions, and lateral parietal cortex. Notably, many of these affected brain regions are the same and overlap considerably with the components of the so-called default mode network (DMN). Here, we hypothesize that the brain activity of the DMN of the GTCS epilepsy patients are different from normal controls, even in the resting state. To test this hypothesis, we compared the DMN of the GTCS epilepsy patients and the controls using the resting state functional magnetic resonance imaging. Thirteen brain areas in the DMN were extracted, and a complete undirected weighted graph was used to model the DMN for each participant. When directly comparing the edges of the graph, we found significant decreased functional connectivities within the DMN of the GTCS epilepsy patients comparing to the controls. As for the nodes of the graph, we found that the degree of some brain areas within the DMN was significantly reduced in the GTCS epilepsy patients, including the anterior medial prefrontal cortex, the bilateral superior frontal cortex, and the posterior cingulate cortex. Then we investigated into possible mechanisms of how GTCS epilepsy could cause the reduction of the functional integrations of DMN. We suggested the damaged functional integrations of the DMN in the GTCS epilepsy patients even during the resting state, which could help to understand the neural correlations of the impaired consciousness of GTCS epilepsy patients.

Regional atrophy of the basal ganglia and thalamus in idiopathic generalized epilepsy.

PURPOSE: To determine the regional changes in the shapes of subcortical structures in idiopathic generalized epilepsy using a vertex-based analysis method. Earlier studies found that gray matter volume in the frontal, parietal, and temporal lobes is significantly altered in idiopathic generalized epilepsy (IGE). Research has indicated that a relationship exists between the brain's subcortical structures and epilepsy. However, little is known about possible changes in the subcortical structures in IGE. MATERIALS AND METHODS: This study aims to determine the changes in the shape of subcortical structures in IGE using vertex analysis. Fourteen male patients with IGE and 28 age- and sex-matched healthy controls were included in this study, which used high-resolution magnetic resonance imaging. We performed a vertex-based shape analysis, in which we compared patients with IGE with the controls, on the subcortical structures that we had obtained from the MRI data. RESULTS: Statistical analysis showed significant regional atrophy in the left thalamus, left putamen and bilateral globus pallidus in patients with IGE. CONCLUSION: These results indicate that regional atrophy of the basal ganglia and the thalamus may be related to seizure disorder. In the future, these findings may prove useful for choosing new therapeutic regimens.

Cerebellum abnormalities in idiopathic generalized epilepsy with generalized tonic-clonic seizures revealed by diffusion tensor imaging.

Although there is increasing evidence suggesting that there may be subtle abnormalities in idiopathic generalized epilepsy (IGE) patients using modern neuroimaging techniques, most of these previous studies focused on the brain grey matter, leaving the underlying white matter abnormalities in IGE largely unknown, which baffles the treatment as well as the understanding of IGE. In this work, we adopted multiple methods from different levels based on diffusion tensor imaging (DTI) to analyze the white matter abnormalities in 14 young male IGE patients with generalized tonic-clonic seizures (GTCS) only, comparing with 29 age-matched male healthy controls. First, we performed a voxel-based analysis (VBA) of the fractional anisotropy (FA) images derived from DTI. Second, we used a tract-based spatial statistics (TBSS) method to explore the alterations within the white matter skeleton of the patients. Third, we adopted region-of-interest (ROI) analyses based on the findings of VBA and TBSS to further confirm abnormal brain regions in the patients. At last, considering the convergent evidences we found by VBA, TBSS and ROI analyses, a subsequent probabilistic fiber tractography study was performed to investigate the abnormal white matter connectivity in the patients. Significantly decreased FA values were consistently observed in the cerebellum of patients, providing fresh evidence and new clues for the important role of cerebellum in IGE with GTCS.

Occipital lobe's cortical thinning in ametropic amblyopia.

BACKGROUND AND PURPOSE: The present study was designed to detect the abnormalities of the cortical thickness in children with ametropic amblyopia by a computer-aided MRI technique. METHODS: Nine children with ametropic amblyopia and eight age-matched normal controls underwent MRI brain scanning that was performed on a Siemens Avanto 1.5-T scanner, and standard T(1)-weighted high-resolution anatomic scans of magnetization-prepared rapid gradient echo (MPRAGE) sequence were obtained. For the cortical thickness analysis, 3D MPRAGE images were processed with FreeSurfer software package (http://www.nmr.mgh.harvard.edu/freesurfer/), and the cortical thicknesses were compared between the patient group and the normal control group. RESULTS: The cortical thicknesses of the lingual and pericalcarine areas in the left hemisphere and of the cuneus, lateraloccipital and lingual areas in the right hemisphere in the amblyopic group were significantly thinner than those of the control group (P<.05). CONCLUSION: The changes in cortical thickness of several occipital regions in amblyopic patients may be important in the diagnosis and treatment of this disease.