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Annals of Indian Academy of Neurology Apr 2024
PubMed: 38819412
DOI: 10.4103/aian.aian_1104_23 -
Neural Regeneration Research Feb 2025JOURNAL/nrgr/04.03/01300535-202502000-00030/figure1/v/2024-05-28T214302Z/r/image-tiff In patients with Alzheimer's disease, gamma-glutamyl transferase 5 (GGT5)...
JOURNAL/nrgr/04.03/01300535-202502000-00030/figure1/v/2024-05-28T214302Z/r/image-tiff In patients with Alzheimer's disease, gamma-glutamyl transferase 5 (GGT5) expression has been observed to be downregulated in cerebrovascular endothelial cells. However, the functional role of GGT5 in the development of Alzheimer's disease remains unclear. This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer's disease, as well as the underlying mechanism. We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer's disease (Aβ1-42-treated hCMEC/D3 and bEnd.3 cells), as well as in the APP/PS1 mouse model. Additionally, injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits. Interestingly, increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-β in the brains of APP/PS1 mice. This effect may be attributable to inhibition of the expression of β-site APP cleaving enzyme 1, which is mediated by nuclear factor-kappa B. Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer's disease pathogenesis, and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice. These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer's disease.
PubMed: 38819065
DOI: 10.4103/NRR.NRR-D-23-01525 -
Neural Regeneration Research Feb 2025
PubMed: 38819059
DOI: 10.4103/NRR.NRR-D-24-00207 -
World Journal of Hepatology May 2024In recent years, approximately half of the newly diagnosed cases and mortalities attributed to hepatocellular carcinoma (HCC) have been reported in China. Despite the...
BACKGROUND
In recent years, approximately half of the newly diagnosed cases and mortalities attributed to hepatocellular carcinoma (HCC) have been reported in China. Despite the high incidence of HCC, there remains a paucity of data regarding the natural growth pattern and the determination of optimal surveillance intervals specific to the Chinese population.
AIM
To quantify the natural tumor growth pattern of HCC in regional China.
METHODS
A retrospective analysis was performed on patients from a single institution in Southwest China who had undergone two or more serial dynamic computed tomography or magnetic resonance imaging scans between 2014 and 2020, without having received any anti-cancer therapy. Tumor growth was assessed using tumor volume doubling time (TVDT) and tumor growth rate (TGR), with volumes measured manually by experienced radiologists. Simple univariate linear regression and descriptive analysis were applied to explore associations between growth rates and clinical factors.
RESULTS
This study identifies the median TVDT for HCC as 163.4 d, interquartile range (IQR) 72.1 to 302.3 d, with a daily TGR of 0.42% (IQR 0.206%-0.97%). HCC growth patterns reveal that about one-third of tumors grow indolently with TVDT exceeding 270 d, another one-third of tumors exhibit rapid growth with TVDT under 90 d, and the remaining tumors show intermediate growth rates, with TVDT ranging between 3 to 9 months.
CONCLUSION
The identified TGRs support biannual surveillance and follow-up for HCC patients in certain regions of China. Given the observed heterogeneity in HCC growth, further investigation is warranted.
PubMed: 38818290
DOI: 10.4254/wjh.v16.i5.800 -
Journal of Cancer 2024CD52 is an important functional regulator involved in the development of human cancer. In this study, the clinical significance and biological function of CD52 in the...
CD52 is an important functional regulator involved in the development of human cancer. In this study, the clinical significance and biological function of CD52 in the malignant behavior of non-small cell lung cancer (NSCLC) were explored. In this study, immunohistochemical (IHC) staining was performed to determine the expression pattern of CD52 in NSCLC. Loss of function assays were used to evaluate the biological functions of CD52 in NSCLC cells and . Our data indicated that the expression of CD52 was significantly elevated in NSCLC and correlated with the patient prognosis. Functionally, downregulation of CD52 expression significantly suppressed the proliferation, migration, aerobic glycolysis and tumorigenesis of NSCLC cells. Moreover, CD52 regulated aerobic glycolysis of NSCLC cells through the AKT pathway. Furthermore, aerobic glycolysis induced by 2-DG inhibited the proliferation of NSCLC cells. In conclusion, CD52 knockdown inhibited aerobic glycolysis and malignant behavior of NSCLC cells through AKT signaling pathway, which may be employed in an alternative therapeutic target for NSCLC.
PubMed: 38817869
DOI: 10.7150/jca.86511 -
Journal of Cancer 2024Pulmonary diseases and esophageal cancer are highly prevalent conditions with rising incidence worldwide. Prior evidence supports shared environmental and behavioral...
Pulmonary diseases and esophageal cancer are highly prevalent conditions with rising incidence worldwide. Prior evidence supports shared environmental and behavioral factors, but less is known regarding potential genetic links underlying this comorbidity. This study aimed to elucidate the complex genetic relationship between chronic lung diseases and esophageal cancer risk. Linkage disequilibrium score regression assessed the genetic correlation between esophageal cancer and asthma, COPD, and idiopathic pulmonary fibrosis leveraging extensive GWAS datasets. Pleiotropic analysis, gene-set enrichment, eQTL mapping, and mendelian randomization causality analyses were then conducted to identify specific shared genetic variants, enriched pathways, causal relationships and gene regulatory mechanisms connecting lung disease and cancer susceptibility. Significant genetic correlations were observed between esophageal cancer and both COPD and asthma, but not idiopathic pulmonary fibrosis. Further analyses identified 13 pleiotropic loci and 6 shared genes including CHRNA4, ERBB3, and SMAD3, as well as pathways related to immune function. eQTL integration highlighted 53 genes like SOCS1, FGF2, and CHRNA5 with tissue-specific regulatory effects on disease risk. Bidirectional relationships were noted, whereby genetic predisposition to asthma and COPD increased esophageal cancer risk, while cancer liability reciprocally raised pulmonary fibrosis risk. These genomic analyses provide initial evidence that shared genetic factors may underpin the comorbidity between lung conditions and esophageal malignancy. The genes and pathways identified offer insights into biological mechanisms linking both diseases, aiding future screening, prevention and therapeutic efforts to mitigate this growing comorbidity burden.
PubMed: 38817868
DOI: 10.7150/jca.95437 -
Journal of Cancer 2024The infection by Kaposi's sarcoma-associated herpesvirus (KSHV) is one of the most common causes of death in AIDS patients. Our studies have found that KSHV can infect...
The infection by Kaposi's sarcoma-associated herpesvirus (KSHV) is one of the most common causes of death in AIDS patients. Our studies have found that KSHV can infect SH-SY5Y cells (named SK-RG) and mTOR was up-regulated, which results in remarkable enhancement of cell proliferation, migration. But the regulatory role of mTOR in KSHV infected neurons has not yet been fully elucidated. Here, we find that miR-769-3p is decreased in SK-RG cells, which can exert anti-KSHV effect through negatively regulating the expression of mTOR. The knockdown of mTOR or overexpress of miR-769-3p decreased the proliferation, migration ability and cell cycle related protein of SK-RG cells, and the expression of KSHV related genes. In contrast, activating mTOR function by 3BDO treatment weakened the cellular behaviors of miR-769-3p overexpressing cells. Meanwhile, overexpressed miR-769-3p and rapamycin showed a shared inhibition trend in the effects on cell proliferation and motility. Our data indicated that miR-769-3p can inhibit cell proliferation and migration by down regulating mTOR in KSHV infected SH-SY5Y cells, and can be a candidate molecule for anti-KSHV therapy.
PubMed: 38817860
DOI: 10.7150/jca.93595 -
Journal of Cancer 2024: Cancer development involves alterations in key cellular pathways, with aspartate β-hydroxylase (ASPH) emerging as an important player in tumorigenesis. ASPH is...
: Cancer development involves alterations in key cellular pathways, with aspartate β-hydroxylase (ASPH) emerging as an important player in tumorigenesis. ASPH is upregulated in various cancer types, where it promotes cancer progression mainly by regulating the Notch1 and SRC pathways. : This study explored the responses of various human cervical, pharyngeal, and breast tumor cell lines to second- and third-generation ASPH inhibitors (MO-I-1151 and MO-I-1182) using proliferation, migration, and invasion assays; western blotting; and cell cycle analysis. : ASPH inhibition significantly reduced cell proliferation, migration, and invasion and disrupted both the canonical and noncanonical Notch1 pathways. The noncanonical pathway was particularly mediated by AKT signaling. Cell cycle analysis revealed a marked reduction in cyclin D1 expression, further confirming the inhibitory effect of ASPH inhibitors on cell proliferation. Additional analysis revealed G0/G1 arrest and restricted progression into S phase, highlighting the regulatory impact of ASPH inhibitors on the cell cycle. Furthermore, ASPH inhibition induced distinctive alterations in nuclear morphology. The high heterogeneity in the responses of individual tumor cell lines to ASPH inhibitors, both quantitatively and qualitatively, underscores the complex network of mechanisms that are regulated by ASPH and influence the efficacy of ASPH inhibition. The effects of ASPH inhibitors on Notch1 pathway activity, cyclin D1 expression, and nuclear morphology contribute to the understanding of the multifaceted effects of these inhibitors on cancer cell behavior. : This study not only suggests that ASPH inhibitors are effective against tumor cell progression, in part through the induction of cell cycle arrest, but also highlights the diverse and heterogeneous effects of these inhibitors on the behavior of tumor cells of different origins.
PubMed: 38817852
DOI: 10.7150/jca.94452 -
World Journal of Cardiology May 2024Mitral valvuloplasty using artificial chordae tendineae represents an effective surgical approach for treating mitral regurgitation. Achieving precise measurements of...
BACKGROUND
Mitral valvuloplasty using artificial chordae tendineae represents an effective surgical approach for treating mitral regurgitation. Achieving precise measurements of artificial chordae tendineae length (CL) is an important factor in the procedure; however, no objective index currently exists to facilitate this measurement. Therefore, preoperative assessment of CL is critical for surgical planning and support. Four-dimensional x-ray micro-computed tomography (4D-CT) may be useful for accurate CL measurement considering that it allows for dynamic three-dimensional (3D) evaluation compared to that with transthoracic echocardiography, a conventional inspection method.
AIM
To investigate the behavior and length of mitral chordae tendineae during systole using 4D-CT.
METHODS
Eleven adults aged > 70 years without mitral valve disease were evaluated. A 64-slice CT scanner was used to capture 20 phases in the cardiac cycle in electrocardiographic synchronization. The length of the primary chordae tendineae was measured from early systole to early diastole using the 3D image. The primary chordae tendineae originating from the anterior papillary muscle and attached to the A1-2 region and those from the posterior papillary muscle and attached to the A2-3 region were designated as cA and cP, respectively. The behavior and maximum lengths [cA (ma), cP (max)] were compared, and the correlation with body surface area (BSA) was evaluated.
RESULTS
In all cases, the mitral anterior leaflet chordae tendineae could be measured. In most cases, the cA and cP chordae tendineae could be measured visually. The mean cA (max) and cP (max) were 20.2 mm ± 1.95 mm and 23.5 mm ± 4.06 mm, respectively. cP (max) was significantly longer. The correlation coefficients (r) with BSA were 0.60 and 0.78 for cA (max) and cP (max), respectively. Both cA and cP exhibited constant variation in CL during systole, with a maximum 1.16-fold increase in cA and a 1.23-fold increase in cP from early to mid-systole. For cP, CL reached a plateau at 15% and remained elongated until end-systole, whereas for cA, after peaking at 15%, CL shortened slightly and then moved toward its peak again as end-systole approached.
CONCLUSION
The study suggests that 4D-CT is a valuable tool for accurate measurement of both the length and behavior of chordae tendineae within the anterior leaflet of the mitral valve.
PubMed: 38817650
DOI: 10.4330/wjc.v16.i5.274 -
World Journal of Stem Cells May 2024Thrombocytopenia 2, an autosomal dominant inherited disease characterized by moderate thrombocytopenia, predisposition to myeloid malignancies and normal platelet size...
BACKGROUND
Thrombocytopenia 2, an autosomal dominant inherited disease characterized by moderate thrombocytopenia, predisposition to myeloid malignancies and normal platelet size and function, can be caused by 5'-untranslated region (UTR) point mutations in ankyrin repeat domain containing 26 (ANKRD26). Runt related transcription factor 1 (RUNX1) and friend leukemia integration 1 (FLI1) have been identified as negative regulators of . However, the positive regulators of are still unknown.
AIM
To prove the positive regulatory effect of GATA binding protein 2 (GATA2) on transcription.
METHODS
Human induced pluripotent stem cells derived from bone marrow (hiPSC-BM) and urothelium (hiPSC-U) were used to examine the expression pattern in the early stage of differentiation. Then, transcriptome sequencing of these iPSCs and three public transcription factor (TF) databases (Cistrome DB, animal TFDB and ENCODE) were used to identify potential TF candidates for . Furthermore, overexpression and dual-luciferase reporter experiments were used to verify the regulatory effect of the candidate TFs on . Moreover, using the GENT2 platform, we analyzed the relationship between expression and overall survival in cancer patients.
RESULTS
In hiPSC-BMs and hiPSC-Us, we found that the transcription levels of varied in the absence of RUNX1 and FLI1. We sequenced hiPSC-BM and hiPSC-U and identified 68 candidate TFs for . Together with three public TF databases, we found that GATA2 was the only candidate gene that could positively regulate . Using dual-luciferase reporter experiments, we showed that GATA2 directly binds to the 5'-UTR of and promotes its transcription. There are two identified binding sites of GATA2 that are located 2 kb upstream of the TSS of . In addition, we discovered that high expression is always related to a more favorable prognosis in breast and lung cancer patients.
CONCLUSION
We first discovered that the transcription factor GATA2 plays a positive role in transcription and identified its precise binding sites at the promoter region, and we revealed the importance of ANKRD26 in many tissue-derived cancers.
PubMed: 38817334
DOI: 10.4252/wjsc.v16.i5.538