Bibliometric analysis of PTEN in neurodevelopment and neurodegeneration.

Phosphatase and tensin homologue deleted on chromosome ten (PTEN) was initially recognized as a significant regulator of cancer suppression and could impede cancer cell survival, proliferation, and energy metabolism. PTEN is highly expressed in neurons and performs crucial functions in neurogenesis, synaptogenesis, and neuronal survival. Disruption of PTEN activity may also result in abnormal neuronal function and is associated with various neurological disorders, including stroke, seizures, and autism. Although several studies have shown that PTEN is involved in the development and degenerative processes of the nervous system, there is still a lack of in-depth studies that summarize and analyse patterns of cooperation between authors, institutions, countries, and journals, as well as research hotspots and trends in this important field. To identify and further visualize the cooperation and comprehend the development and trends of PTEN in the nervous system, especially in neural development and neurological diseases, we used a bibliometric analysis to identify relevant publications on this topic. We first found that the number of publications displayed a growing trend with time, but this was not stable. Universities, institutions, and authors from the United States are leading in this area of research. In addition, many cutting-edge research results have been discovered, such as key regulatory molecules and cellular mechanisms of PTEN in the nervous system, which may provide novel intervention targets and precise therapeutic strategies for related pathological injuries and diseases. Finally, the literature published within the last 5 years is discussed to identify future research trends regarding PTEN in the nervous system. Taken together, our findings, analysed using bibliometrics, may reflect research hotspots and trends, providing a reference for studying PTEN in the nervous system, especially in neural development and neurological diseases. These findings can assist new researchers in developing their research interests and gaining basic information. Moreover, our findings also may provide precise clinical guidelines and strategies for treating nervous system injuries and diseases caused by PTEN dysfunction.

A bibliometric analysis of hotpots and trends for the relationship between skin inflammation and regeneration.

Background: Skin regeneration is a challenging issue worldwide. Increasing research has highlighted the role of immune cells in healing and the underlying regulatory mechanism. The purpose of this study was to identify the hotspots and trends in skin regeneration and inflammation research through bibliometrics and to provide insights into the future development of fundamental research and disease treatment. Methods: Publications were collected from the Web of Science Core Collection on March 1, 2022. Articles and reviews published in English from January 1, 1999, to December 31, 2022, were selected, and statistical analyses of countries, institutions, authors, references, and keywords were performed using VOSviewer 1.6.18 and CiteSpace 5.8. Results: A total of 3,894 articles and reviews were selected. The number of publications on skin inflammation and regeneration showed an increasing trend over time. Additionally, authors and institutions in the United States, United Kingdom, Canada, and China appeared to be at the forefront of research in the field of skin inflammation and regeneration. Werner Sabine published some of the most cited papers. Wound Repair and Regeneration was the most productive journal, while Journal of Investigative Dermatology was the most cited journal. Angiogenesis, diamonds, collagen, cytokine, and keratinocytes were the five most commonly used keywords. Conclusion: The number of publications on skin inflammation and regeneration show an increasing trend. Moreover, a series of advanced technologies and treatments for skin regeneration, such as exosomes, hydrogels, and wound dressings, are emerging, which will provide precise information for the treatment of skin wounds. This study can enhance our understanding of current hotspots and future trends in skin inflammation and regeneration research, as well as provide guidelines for fundamental research and clinical treatment.

A bibliometric analysis of PIN1 and cell death.

Background: Regulation of cell death plays a key role in numerous diseases. As a proline isomerase, prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) is important for the regulation of signaling pathways. An in-depth understanding of how Pin1 participates in the process of cell death, which affects the occurrence and development of diseases, will aid in the discovery of new disease mechanisms and therapeutic methods. Thus, the purpose of our study was to discover the research trends and hotspots of Pin1 and cell death through bibliometric analyses and to provide insights for understanding the future development of basic research and treatment of diseases. Methods: Documents were extracted from the Web of Science Core Collection on 7 May 2022. We selected articles and reviews published in English from 2000 to 2021, and visual and statistical analyses of countries, institutions, authors, references and keywords were performed using VOSviewer 1.6.18 and CiteSpace 5.8. Results: A total of 395 articles and reviews were selected. Since 2001, the number of articles on Pin1 and cell death has increased annually. Publications come from 43 countries, with the US having the most publications and citations. We identified 510 authors, with Giannino Del Sal having the most articles and Paola Zacchi having the most co-citations. The Journal of Biological Chemistry is the most researched journal, and Nature and its subjournals are the most cited journals. Apoptosis, phosphorylation, and breast cancer were the three most common keywords. Conclusion: The number of documents showed an increasing trend from 2001 to 2014. Stagnant growth after 2014 may be related to the absence of new research hotspots. Cooperative links between core institutions need to be strengthened, and the institution with the highest citation count in recent years is Fujian Medical University in China. The role of Pin1 in cell death requires further research to discover new research hotspots. Before breakthroughs in molecular mechanism or signaling pathway research, future research will focus more on the treatment of diseases represented by Pin1 inhibitors.

A predictive nomogram for two-year growth of CT-indeterminate small pulmonary nodules.

OBJECTIVES: Lung cancer is the most common cancer and the leading cause of cancer-related death worldwide. The optimal management of computed tomography (CT)-indeterminate pulmonary nodules is important. To optimize individualized follow-up strategies, we developed a radiomics nomogram for predicting 2-year growth in case of indeterminate small pulmonary nodules. METHODS: A total of 215 histopathology-confirmed small pulmonary nodules (21 benign and 194 malignant) in 205 patients with ultra-high-resolution CT (U-HRCT) were divided into growth and nongrowth nodules and were randomly allocated to the primary (n = 151) or validation (n = 64) group. The least absolute shrinkage and selection operator (LASSO) method was used for radiomics feature selection and radiomics signature determination. Multivariable logistic regression analysis was used to develop a radiomics nomogram that integrated the radiomics signature with significant clinical parameters (sex and nodule type). The area under the curve (AUC) was applied to assess the predictive performance of the radiomics nomogram. The net benefit of the radiomics nomogram was assessed using a clinical decision curve. RESULTS: The radiomics signature and nomogram yielded AUCs of 0.892 (95% confidence interval [CI]: 0.843-0.940) and 0.911 (95% CI: 0.867-0.955), respectively, in the primary group and 0.826 (95% CI: 0.727-0.926) and 0.843 (95% CI: 0.749-0.937), respectively, in the validation group. The clinical usefulness of the nomogram was demonstrated by decision curve analysis. CONCLUSIONS: A radiomics nomogram was developed by integrating the radiomics signature with clinical parameters and was easily used for the individualized prediction of two-year growth in case of CT-indeterminate small pulmonary nodules. KEY POINTS: • A radiomics nomogram was developed for predicting the two-year growth of CT-indeterminate small pulmonary nodules. • The nomogram integrated a CT-based radiomics signature with clinical parameters and was valuable in developing an individualized follow-up strategy for patients with indeterminate small pulmonary nodules.

Effects and mechanisms of FBXO31 on Taxol chemoresistance in esophageal squamous cell carcinoma.

Taxol is commonly used chemotherapy regimen for esophageal squamous cell carcinoma (ESCC). Study of the underlying mechanisms of Taxol chemoresistance provides better understanding of esophageal cancer treatment and may provide a rational molecular target for diagnosis and intervention. Here we showed FBXO31, which was reported to be highly expressed in ESCC and significantly associated with poor prognosis, could regulate ESCC chemosensitivity to Taxol. Silencing of FBXO31 in ESCC cells sensitized cells to Taxol treatment, evidenced by FACS analysis and TUNEL assay, showing as an increased apoptotic population in FBXO31-knockdown cells compared to the control cells. The mass spectrometry data and coimmunoprecipitation results showed FBXO31 could bind with cofilin-1. Cofilin-1 knockdown in FBXO31-overexpression cells reversed FBXO31-induced suppression of cell apoptosis, suggesting FBXO31-mediated Taxol chemoresistance is associated with cofilin-1. Furthermore, in vivo experiments confirmed that knockdown of FBXO31 sensitized ESCC to Taxol treatment. This finding substantiated a pivotal role of FBOX31 in ESCC chemoresistance, indicating that FBXO31 may be a potential indicator or target for drug resistance in ESCC.

Contrast-enhanced CT longitudinal tail sign as a marker of positive resection margins in adenoid cystic carcinoma of the central airway.

BACKGROUND: Due to submucosal infiltration's biological nature along the airway, adenoid cystic carcinoma (ACC) frequently leaves positive surgical margins. This study evaluated the clinicopathologic, and computed tomography (CT) features for predicting surgical margin status in central airway ACC. METHODS: We retrospectively analyzed the files of 71 patients with ACC of the central airway proven by histopathology and surgery who had presented between January 2010 and December 2018. All patients were classified into positive and negative surgical margin groups according to margin status. Univariate analysis and multivariable logistic regression models were then performed to compare demography, histopathology, and CT characteristics between ACC patients with positive and negative margins. RESULTS: After surgical resection, 59 (83.1%) patients had positive margins, and 12 (16.9%) had negative margins. The contrast-enhanced CT (CECT) longitudinal tail sign (LTS) was identified in 55 of 59 (93.2%) patients with positive margins and was the only feature that had a significant association with positive margins (odds ratio 41.250, 95% CI: 7.886-215.767; P<0.001). Moreover, positive margins in upper or/and lower directions were associated with the LTS in corresponding directions (P<0.001). CONCLUSIONS: Most central airway ACC patients exhibited positive margins following surgery. The appearance of the LTS on CECT was significantly associated with positive margins and could help preoperatively predict the submucosal invasion of ACC.

CT diagnosis and prognosis prediction of tracheal adenoid cystic carcinoma.

PURPOSE: To evaluate computed tomography (CT) features and establish a predictive model for the clinical diagnosis and prognosis of tracheal adenoid cystic carcinoma (ACC). METHOD: From January 2010 to December 2018, 82 patients with tracheal tumors, including 46 patients with ACC confirmed by surgery and histopathology, were enrolled in this study. These patients' clinicopathologic information, CT features and survival outcomes were recorded and analyzed. Independent predictors of diagnosis and prognosis of tracheal ACC were determined by both univariate and multivariate analyses. RESULTS: Compared with tracheal non-ACC patients, univariate analysis showed that ACC patients were more likely to have extensive longitudinal length (p < 0.001) and to appear as annular wall thickening (p = 0.001), transmural growth (p = 0.036), poorly defined border (p = 0.003) and mild enhancement (p = 0.001). Multivariate logistic analysis showed that longitudinal length and enhancement degree were independent predictors of tracheal ACC. The 3-year and 5-year disease-free survival (DFS) were 75.7 % and 64.5 %, respectively. Longitudinal length (≥ 34 mm), transverse length (≥ 20 mm) and transmural growth were associated with poor DFS in univariate analysis. After multivariate adjustment, only transverse length (≥ 20 mm) was an adverse prognostic factor for DFS (hazard ratio = 4.594, 95 % confidence interval = 1.240-17.017; p = 0.022). CONCLUSIONS: CT longitudinal length and enhancement degree of tumors showed satisfactory discrimination for tracheal ACC. Excessive CT transverse length might be an unfavorable indicator for ACC recurrence and could be helpful for predicting the survival outcomes of ACC at the initial diagnosis.

Regulatory role of calpain in neuronal death.

Calpains are a group of calcium-dependent proteases that are over activated by increased intracellular calcium levels under pathological conditions. A wide range of substrates that regulate necrotic, apoptotic and autophagic pathways are affected by calpain. Calpain plays a very important role in neuronal death and various neurological disorders. This review introduces recent research progress related to the regulatory mechanisms of calpain in neuronal death. Various neuronal programmed death pathways including apoptosis, autophagy and regulated necrosis can be divided into receptor interacting protein-dependent necroptosis, mitochondrial permeability transition-dependent necrosis, pyroptosis and poly (ADP-ribose) polymerase 1-mediated parthanatos. Calpains cleave series of key substrates that may lead to cell death or participate in cell death. Regarding the investigation of calpain-mediated programed cell death, it is necessary to identify specific inhibitors that inhibit calpain mediated neuronal death and nervous system diseases.

Using drugs to target necroptosis: dual roles in disease therapy.

Necroptosis is programmed necrosis, a process which has been studied for over a decade. The most common accepted mechanism is through the RIP1-RIP3-MLKL axis to regulate necroptotic cell death. As a result of previous studies on necroptosis, positive regulation for promoting necroptosis such as HSP90 stabilization and hyperactivation of TAK1 on RIP1 is clear. Similarly, the negative regulation of necroptosis, such as through caspase 8, c-FLIP, CHIP, MK2, PELI1, ABIN-1, is also clear. Therefore, the promise of corresponding applications in treating diseases becomes hopeful. Studies have shown that necroptosis is involved in the development of many diseases, such as ischemic injury diseases in various organs, neurodegenerative diseases, infectious diseases, and cancer. Given these results, drugs that inhibit or trigger necroptosis can be discovered to treat diseases. In this review, we briefly introduce up to date concepts concerning the mechanism of necroptosis, the diseases that involve necroptosis, and the drugs that can be applied to treat such diseases.

Inhibition of HSP90α protects cultured neurons from oxygen-glucose deprivation induced necroptosis by decreasing RIP3 expression.

Heat shock protein 90α (HSP90α) maintains cell stabilization and regulates cell death, respectively. Recent studies have shown that HSP90α is involved in receptor interacting protein 3 (RIP3)-mediated necroptosis in HT29 cells. It is known that oxygen and glucose deprivation (OGD) can induce necroptosis, which is regulated by RIP3 in neurons. However, it is still unclear whether HSP90α participates in the process of OGD-induced necroptosis in cultured neurons via the regulation of RIP3. Our study found that necroptosis occurs in primary cultured cortical neurons and PC-12 cells following exposure to OGD insult. Additionally, the expression of RIP3/p-RIP3, MLKL/p-MLKL, and the RIP1/RIP3 complex (necrosome) significantly increased following OGD, as measured through immunofluorescence (IF) staining, Western blotting (WB), and immunoprecipitation (IP) assay. Additionally, data from computer simulations and IP assays showed that HSP90α interacts with RIP3. In addition, HSP90α was overexpressed following OGD in cultured neurons, as measured through WB and IF staining. Inhibition of HSP90α in cultured neurons, using the specific inhibitor, geldanamycin (GA), and siRNA/shRNA of HSP90α, protected cultured neurons from necrosis. Our study showed that the inhibitor of HSP90α, GA, rescued cultured neurons not only by decreasing the expression of total RIP3/MLKL, but also by decreasing the expression of p-RIP3/p-MLKL and the RIP1/RIP3 necrosome. In this study, we reveal that inhibition of HSP90α protects primary cultured cortical neurons and PC-12 cells from OGD-induced necroptosis through the modulation of RIP3 expression.

The Toxic Effect of ALLN on Primary Rat Retinal Neurons.

N-acetyl-leucyl-leucyl-norleucinal (ALLN), an inhibitor of proteasomes and calpain, is widely used to reduce proteasomes or calpain-mediated cell death in rodents. However, ALLN is toxic to retinal neurons to some extent. At the concentration of 10 µM, ALLN is non-toxic to cortical neurons, but induces cell death of retinal neurons in vitro. The tolerance concentration of ALLN for retinal neurons is unclear, and the precise mechanism of cell death induced by ALLN remains elusive. In this study, we investigated the toxic effect of ALLN on primary retinal neurons. The 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed no significant changes of cell viability at 1 µM but decreased cell viability after treatment of ALLN at 2.5, 5, and 7.5 µM. Lactate dehydrogenase (LDH) release was highly elevated and propidium iodide (PI)-positive cells were significantly increased at 2.5, 5, and 7.5 µM after all treatment times. Moreover, the protein levels of caspase-3 were up-regulated at 5 and 7.5 µM after 12 and 24 h of ALLN treatment. The ratio of Bax/Bcl-2 was raised and Annexin V-positive cells were increased at 5 and 7.5 µM after 12 and 24 h of ALLN treatment. However, there were no significant changes in either the ratio of microtubule-associated protein 1 light chain 3 (LC3) II/LC3 I or monodansylcadaverine (MDC) staining. Our data clearly show that at the concentrations equal to and higher than 2.5 µM, ALLN may induce cell death of primary retinal neurons by necrosis and apoptosis, but not autophagy. These suggest that primary retinal neurons are more susceptible to ALLN treatment and provide a possible mechanism for the cell death of ALLN-sensitive cells in ALLN injury.