bluuebunny/crossref_metadata_2025 huggingface dataset:
Acupuncture decreases amygdala functional connectivity in subjective tinnitus
Authors: Zhang Yating , Zha Bixiang , Shi Haiping , Cheng Ling , Fan Yinqiu , Zhang Wanlin , Rong Zhihao , Jin Zhaoxing , Gao Nan , Yang Jun , Zhang Qingping
Published: December 2022

Introduction

Subjective tinnitus is a common and intractable ear disease. The effectiveness of acupuncture in the treatment of subjective tinnitus has been confirmed, but its mechanism of action is not clear. The structures of the amygdala (AMYG) are mainly closely related to emotion in the human brain. This study aimed to investigate the changes in functional connectivity (FC) of AMYG in subjective tinnitus to elucidate the neural mechanism of acupuncture.

Methods

Correlation scale scores of 26 patients with subjective tinnitus were collected, including Tinnitus Evaluation Questionnaire (TEQ), Tinnitus Handicap Inventory (THI) and Visual Analog Scale (VAS). Meanwhile, rs-fMRI data were collected before and after acupuncture treatment in the patients, and in healthy controls (HC) matching the patient's gender and age. Then, AMYG was selected as region of interest to perform FC analysis. Finally, FC patterns of AMYG were first compared between patients with subjective tinnitus and HC, and then within subjects pre-acupuncture and post-acupuncture. Simple linear regression models between correlation scale scores and FC-values were established as well.

Results

Acupuncture treatment relieved the severity of tinnitus. With the acupuncture treatment, the total THI score, TEQ score, and VSA score of patients were significantly lower than before (p < 0.05). Compared with HC, FC of tinnitus patients between AMYG and right inferior temporal gyrus and right precuneus significantly decreased before acupuncture (voxel p < 0.001, cluster p < 0.05, corrected with GRF), while FC of tinnitus patients between AMYG and left superior frontal gyrus and right superior temporal gyrus significantly decreased after acupuncture treatment (voxel p < 0.001, cluster p < 0.05, corrected with GRF). FC of tinnitus patients between the AMYG and right superior frontal gyrus and left paracingulate gyrus showed significant decrease after acupuncture treatment (voxel p < 0.001, cluster p < 0.05, corrected with GRF). Besides, the linear regression models of the effect of THI on FC and VAS on FC performed were statistically significant (p < 0.05).

Discussion

The findings demonstrate that acupuncture can decrease FC of AMYG, which could be positively correlated with the relief of tinnitus symptoms. This result suggests that acupuncture stimulation can effectively relieve the severity of tinnitus by decreasing FC of AMYG in subjective tinnitus patients.
Sound out the impaired perfusion: Photoacoustic imaging in preclinical ischemic stroke
Authors: Menozzi Luca , Yang Wei , Feng Wuwei , Yao Junjie
Published: December 2022

Acoustically detecting the optical absorption contrast, photoacoustic imaging (PAI) is a highly versatile imaging modality that can provide anatomical, functional, molecular, and metabolic information of biological tissues. PAI is highly scalable and can probe the same biological process at various length scales ranging from single cells (microscopic) to the whole organ (macroscopic). Using hemoglobin as the endogenous contrast, PAI is capable of label-free imaging of blood vessels in the brain and mapping hemodynamic functions such as blood oxygenation and blood flow. These imaging merits make PAI a great tool for studying ischemic stroke, particularly for probing into hemodynamic changes and impaired cerebral blood perfusion as a consequence of stroke. In this narrative review, we aim to summarize the scientific progresses in the past decade by using PAI to monitor cerebral blood vessel impairment and restoration after ischemic stroke, mostly in the preclinical setting. We also outline and discuss the major technological barriers and challenges that need to be overcome so that PAI can play a more significant role in preclinical stroke research, and more importantly, accelerate its translation to be a useful clinical diagnosis and management tool for human strokes.
Mu-opioid receptor and receptor tyrosine kinase crosstalk: Implications in mechanisms of opioid tolerance, reduced analgesia to neuropathic pain, dependence, and reward
Authors: Gamble Mackenzie C. , Williams Benjamin R. , Singh Navsharan , Posa Luca , Freyberg Zachary , Logan Ryan W. , Puig Stephanie
Published: December 2022

Despite the prevalence of opioid misuse, opioids remain the frontline treatment regimen for severe pain. However, opioid safety is hampered by side-effects such as analgesic tolerance, reduced analgesia to neuropathic pain, physical dependence, or reward. These side effects promote development of opioid use disorders and ultimately cause overdose deaths due to opioid-induced respiratory depression. The intertwined nature of signaling via μ-opioid receptors (MOR), the primary target of prescription opioids, with signaling pathways responsible for opioid side-effects presents important challenges. Therefore, a critical objective is to uncouple cellular and molecular mechanisms that selectively modulate analgesia from those that mediate side-effects. One such mechanism could be the transactivation of receptor tyrosine kinases (RTKs) via MOR. Notably, MOR-mediated side-effects can be uncoupled from analgesia signaling via targeting RTK family receptors, highlighting physiological relevance of MOR-RTKs crosstalk. This review focuses on the current state of knowledge surrounding the basic pharmacology of RTKs and bidirectional regulation of MOR signaling, as well as how MOR-RTK signaling may modulate undesirable effects of chronic opioid use, including opioid analgesic tolerance, reduced analgesia to neuropathic pain, physical dependence, and reward. Further research is needed to better understand RTK-MOR transactivation signaling pathways, and to determine if RTKs are a plausible therapeutic target for mitigating opioid side effects.
High-pressure treatment enhanced aromatic compound concentrations of melon juice and its mechanism
Authors: Liu Xiao , Wang Ruiqi , Liu He , Wang Yubin , Shi Yue , Zhang Chao
Published: December 2022

Introduction

The flavor deterioration blocks the development of melon juice.

Methods

The effects of ultra-high temperature (UHT) and high pressure (HP) treatments on the aromatic compound concentrations of melon juice and their mechanisms were explored with fresh juice as the control.

Results

A total of 57 volatile compounds were identified by gas chromatography-tandem mass spectrometry analysis. β-ionone was shown to be the major aromatic component of melon juice for the first time. The HP at 200 MPa for 20 min increased the total volatile concentration of melon juice by 1.54 and 3.77 times the control and UHT, respectively. Moreover, the sum concentration of a major aromatic component in the HP treatment was 1.49 and 5.94 times higher than that of the control and UHT, respectively.

Discussion

The HP treatment raised the concentration of volatile and aromatic components of melon juice by reducing their surface tension.
IL-1β enhances cell viability and decreases 5-FU sensitivity in novel colon cancer cell lines derived from African American patients
Authors: Spagnardi Marzia , Paredes Jenny , Zabaleta Jovanny , Garai Jone , Reyes Tiana , Martello Laura A. , Williams Jennie L.
Published: December 2022

Background

In the U.S., African Americans (AAs) present with the highest incidence and mortality rates for Colorectal Cancer (CRC). When compared to Caucasian American (CA) patients, AAs also have reduced response to the first line standard of care chemotherapeutic agent 5-Fluorouracil (5-FU). Previously, we observed differential gene expression between the two populations, suggesting that colon tumors from AA patients display a decreased antitumor immune response and an increased expression of genes encoding proteins involved in inflammatory processes, such as Interleukin-1β (IL-1β). Here, we investigate the role of IL-1β in modifying chemotherapeutic response and altering expression of proteins in novel AA and well-established CA colon cancer cell lines.

Methods

RNA sequencing analysis was performed to detect expression of genes involved in inflammation in AA and CA colon cancer cells. The effects of IL-1β on 5-FU response was evaluated by assessing cell viability (MTS assay) and apoptosis (flow cytometry analysis) following treatment with 5-FU alone or in combination with the cytokine. Further, we used an IL-1 receptor antagonist (IL-1Ra) to inhibit IL-1β-induced effects on 5-FU sensitivity and NF-kB pathway activation.

Results

AA colon cancer cell lines present significant increase in expression of genes IL1R2 (373-fold change (FC), IRAK1 (3.24 FC), IKBKB, (5.33 FC) NF-KB IA (5.95 FC), MYD88, (3.72 FC), IRAK3 (161 FC), TRAF5 (4.1 FC). A significant decrease in the response to 5-FU treatment, as well as a significant increase in phosphorylation of IκBα and secretion of IL-8, was seen following IL-1β treatment, in both AA and CA cell lines. Finally, treatment with IL-1Ra was able to reverse the effects induced by IL-1β, by increasing the cells sensitivity to 5-FU. IL-1Ra also inhibited phosphorylation of IκBα and IL-8 secretion.

Conclusions

Our results suggest a differential expression of inflammatory genes and proteins that might regulate the different response to IL-1β between AA and CA colon cancer cell lines. Our data also demonstrates that IL-1β is involved in modulating 5-FU response in both AA and CA colon cancer cell lines. Further investigation of these mechanisms might help elucidate the differences seen in incidence, mortality and response to therapy in AA colon cancer patients.
An autophagy-related four-lncRNA signature helps to predict progression-free survival of neuroblastoma patients
Authors: Wang Jing , Meng Xinyao , Chen Ke , Feng Jiexiong
Published: December 2022

Background

This study aimed to identify autophagy-related long non-coding RNAs (lncRNAs) associated with progression of neuroblastoma (NB), and to build an autophagy-related lncRNA signature that helps to predict progression-free survival (PFS) of NB.

Methods

Three independent gene expression datasets were utilized in this study. Autophagy-related genes (ARG) associated with PFS of NB patients were firstly identified by univariate Cox survival analysis. lncRNAs correlated with those PFS-related ARGs were then identified. The least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analyses were performed to select out those lncRNAs with the best prognostic value for PFS. The Receiver Operating Characteristic (ROC) and Area Under Curve (AUC) analyses were performed to assess the prediction accuracy.

Results

Four autophagy-related lncRNAs (AL356599.1, AC022075.1, AC020928.1 and LINC02076) were found to be with the best prognostic value and integrated into a four-lncRNA risk signature for predicting PFS of NB patients. The four-lncRNA signature significantly stratify NB patients into two risk groups, with high-risk group has significantly poorer PFS than the low-risk group. The prognostic role of the lncRNA signature was independent with other clinical risk factors. The ROC curves revealed that the lncRNA signature has a good performance in predicting PFS (AUC > 0.70). A nomogram based on COG (Children’s Oncology Group) risk and the lncRNA risk score was constructed, showing good prediction accuracy (C-index = 0.700). The prognostic ability of the nomogram was better than that of COG risk alone (AUC = 0.790 versus AUC = 0.748). GSEA analyses revealed that multiple autophagy-related gene sets are significantly enriched in the low-risk group.

Conclusions

We identified an autophagy-related four-lncRNA signature that could help to predict the PFS of NB patients. Autophagy-related gene sets are significantly enriched in low-risk group, suggesting tumor suppressive roles of autophagy in NB.
Weighted gene co-expression network reveals driver genes contributing to phenotypes of anaplastic thyroid carcinoma and immune checkpoint identification for therapeutic targets
Authors: Dong Xingxing , Yang Yalong , Hou Jinxuan , Chen Weizhen , Yuan Qianqian , Xu Gaoran , Liu Jiuyang , Li Chengxin , Wu Gaosong
Published: December 2022

Background

Anaplastic thyroid carcinoma (ATC) is a rare but extremely malignant tumor, with a rapid growth rate and early metastasis thus leading to poor survival of patients. The molecular mechanisms underlying these aggressive traits of ATC remain unknown, which impedes the substantial progress in treatment to prolong ATC patient survival.

Methods

We applied weighted gene co-expression network analysis (WGCNA) to identify ATC-specific modules. The Metascape web and R package clusterProfiler were employed to perform enrichment analysis. Combined with differentially expressed gene analysis, we screened out the most potential driver genes and validated them using receiver operator characteristic (ROC) analysis, quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting, immunohistochemistry (IHC), and triple immunofluorescence staining.

Results

A gene expression matrix covering 75 normal samples, 83 papillary thyroid carcinoma (PTC), 26 follicular thyroid carcinoma (FTC), 19 poor-differentiated thyroid carcinoma (PDTC), and 41 ATC tissue samples were integrated, based on which we detected three most potential ATC-specific modules and found that hub genes of these modules were enriched in distinct biological signals. Hub genes in the turquoise module were mainly enriched in mitotic cell cycle, tube morphogenesis, and cell differentiation, hub genes in the magenta module were mainly clustered in the extracellular matrix organization, positive regulation of cell motility, and regulation of Wnt signaling pathway, while hub genes in the blue module primarily participated in the inflammatory response, innate immune response, and adaptive immune response. We showed that 9 top genes, 8 transcription factors (TFs), and 4 immune checkpoint genes (ICGs) were differentially expressed in ATC compared to other thyroid samples and had high diagnostic values for ATC, among which, 9 novel ATC-specific genes (ADAM12, RNASE2, CASP5, KIAA1524, E2F7, MYBL1, SRPX2, HAVCR2, and TDO2) were validated with our clinical samples. Furthermore, we illustrated that ADAM12, RNASE2, and HAVCR2 were predominantly present in the cytoplasm.

Conclusion

Our study identified a set of novel ATC-specific genes that were mainly related to cell proliferation, invasion, metastasis, and immunosuppression, which might throw light on molecular mechanisms underlying aggressive phenotypes of ATC and provide promisingly diagnostic biomarkers and therapeutic targets.
Safety profile of robotic-assisted transperineal MRI-US-fusion guided biopsy of the prostate
Authors: Walter Manuel , Trotsenko Pawel , Breit Hanns-Christian , Keller Nicola , Meyer Anja , Winkel David Jean , Seifert Hans Helge , Wetterauer Christian
Published: December 2022

Introduction

Robotic-assisted transperineal MRI-US-fusion guided biopsy of the prostate is a novel and highly accurate procedure. The aim of this study was to evaluate the MonaLisa prostate biopsy system in terms of safety, tolerability, and patient-related outcomes.

Methods

This prospective study included 228 patients, who had undergone Robotic-assisted transperineal MRI-US-fusion guided biopsy of the prostate at the University Hospital Basel between January 2020 and June 2022. Peri-operative side effects, functional outcomes and patient satisfaction were assessed.

Results

Mean pain score on the day of biopsy was 1.3 points on VAS, which remained constant on the day after biopsy. Overall, 32 of 228 patients (14%) developed grade I complications according to Clavien-Dindo classification. No higher-grade complications occurred. Gross haematuria, hematospermia and acute urinary retention occurred in 145/228 (63.6%), 98/228 (43%) and 32/228 (14%) patients, respectively. One patient (0.4%) developed urinary tract infection.

Conclusions

Robotic-assisted transperineal MRI-US-fusion guided biopsy of the prostate performed under general anesthesia is a safe and well tolerated procedure. This technique allows to omit perioperative prophylaxis and at the same time minimizes the risk of infectious complications. We attribute the favorable risk profile and tolerability to the minimal invasive approach via two entry points.
Advances in highly active one-carbon metabolism in cancer diagnosis, treatment and drug resistance: A systematic review
Authors: Liu Shuang , Wang Zheng-Miao , Lv Dong-Mei , Zhao Yi-Xuan
Published: December 2022

Study background objectives

Cancer poses a significant health concern as it is incurable. Every year, research on how to treat and eradicate this chronic condition is done. This systematic review will unmask the recent developments concerning highly active 1C metabolism with regard to cancer diagnosis, treatment, and drug resistance. The significance of this study is rolling out evidence-based evidence on the importance of one-carbon metabolism in cancer diagnosis and treatment.

Methods

Eight randomized controlled trials (RCTs) were reviewed from five electronic databases – EMBASE, Scopus Review, Google Scholar, Web of Science, and PubMed. Outcomes from the eight studies were analyzed to paint a picture of the topic in question. While the Preferred Reporting Items for Systematic Reviews and Meta-Analysis’ (PRISMA) protocol guided the initial literature search, The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach informed quality assessments of the eligible studies.

Conclusion

Since its emergence in the 1980s, 1C metabolism has been investigated and broadened to capture essential aspects of cancer treatment, diagnosis, and drug resistance. The review found that metabolites like folic acid could be used to detect different types of cancer. The metabolic pathways could induce tumorigenesis and DNA methylation, hence drug resistance.

Systematic review registration

https://inplasy.com/projects/, identifier INPLASY2022110099.
Emerging role of Protein Kinase CK2 in Tumor immunity
Authors: Chen Leichong , Zhang Sijia , Li Qianwen , Li Junyu , Deng Huilin , Zhang Sheng , Meng Rui
Published: December 2022

Protein kinase CK2, a conserved serine/threonine-protein kinase, is ubiquitous in cells and regulates various intracellular processes, especially in tumor cells. As one of the earliest discovered protein kinases in humans, CK2 plays a crucial role in phosphorylating or associating with hundreds of substrates to modulate several signaling pathways. Excellent reviews have reported that the overexpression of CK2 could be observed in many cancers and was closely associated with tumor occurrence and development. The elevation of CK2 is also an indicator of a poor prognosis. Recently, increasing attention has been paid to the relationship between CK2 and tumor immunity. However, there is no comprehensive description of how CK2 regulates the immune cells in the tumor microenvironment (TME). Also, the underlying mechanisms are still not very clear. In this review, we systematically summarized the correlation between CK2 and tumor immunity, primarily the effects on various immune cells, both in innate and adaptive immunity in the TME. With the comprehensive development of immunotherapy and the mounting transformation research of CK2 inhibitors from the bench to the clinic, this review will provide vital information to find new treatment options for enhancing the efficacy of immunotherapy.
A novel panel of clinically relevant miRNAs signature accurately differentiates oral cancer from normal mucosa
Authors: Mehterov Nikolay , Sacconi Andrea , Pulito Claudio , Vladimirov Boyan , Haralanov Georgi , Pazardjikliev Dimitar , Nonchev Boyan , Berindan-Neagoe Ioana , Blandino Giovanni , Sarafian Victoria
Published: December 2022

Introduction

Although a considerable body of knowledge has been accumulated regarding the early diagnosis and treatment of oral squamous cell carcinoma (OSCC), its survival rates have not improved over the last decades. Thus, deciphering the molecular mechanisms governing oral cancer will support the development of even better diagnostic and therapeutic strategies. Previous studies have linked aberrantly expressed microRNAs (miRNAs) with the development of OSCC.

Methods

We combined bioinformatical and molecular methods to identify miRNAs with possible clinical significance as biomarkers in OSCC. A set of 10 miRNAs were selected via an in silico approach by analysing the 3’untranslated regions (3’UTRs) of cancer-related mRNAs such as FLRT2, NTRK3, and SLC8A1, TFCP2L1 and etc. RT-qPCR was used to compare the expression of in silico identified miRNAs in OSCC and normal tissues (n=32).

Results

Among the screened miRNAs, miR-21-5p (p < 0.0001), miR-93-5p (p < 0.0197), miR-146b-5p (p <0.0012), miR-155-5p (p < 0.0001), miR-182-5p (p < 0.0001) were significantly overexpressed, whereas miR-133b (p < 0.05) was significantly downregulated in OSCC tissues, a scenario confirmed in two additional OSCC validation cohorts: Regina Elena National Cancer Institute (IRE cohort, N=74) and The Cancer Genome Atlas Data Portal (TCGA cohort, N=354). Initial stage tumors (T1, T2) expressed significantly higher levels of miR-133b (p < 0.0004) compared to more advanced ones (T3, T4). Also, we identified miR-93-5p (p < 0.0003), miR-133b (p < 0.0017) and miR-155-5p (p < 0.0004) as correlated with HPV-induced OSCC. The high expression of these 6 miRNAs as a signature predicted shorter disease-free survival (DFS) and could efficiently distinguish OSCC cases from healthy controls with areas under the curve (AUC) of 0.91 with sensitivity and specificity of 0.98 and 0.6, respectively. Further target identification analysis revealed enrichment of genes involved in FOXO, longevity, glycan biosynthesis and p53 cancer-related signaling pathways. Also, the selected targets were underexpressed in OSCC tissues and showed clinical significance related to overall survival (OS) and DFS.

Discussion

Our results demonstrate that a novel panel consisting of miR-21-5p, miR-93-5p, miR-133b, miR-146b-5p, miR-155-5p and miR-182-5p could be used as OSCC-specific molecular signature with diagnostic and prognostic significance related to OS and DFS.
Case report: Paratesticular dedifferentiated liposarcoma with poor prognosis
Authors: Suto Hirotaka , Inui Yumiko , Okamura Atsuo
Published: December 2022

Background/Aim

Most paratesticular liposarcomas (PLPSs) are well-differentiated liposarcomas (WDLPSs) with favourable prognoses. As such, the rare occurrence of PLPS often leads to its misdiagnosis as a hernia or hydrocele on physical examination. Curative resection of the tumour may not be possible in cases where PLPSs have transformed into dedifferentiated liposarcomas (DDLPSs) owing to a delay in diagnosis. Herein, we describe a case of unresectable paratesticular dedifferentiated liposarcoma (PDDLPS) with poor prognosis due to delayed diagnosis.

Case Report

A 57-year-old man visited our hospital with a chief complaint of a right scrotal mass, which was diagnosed as scrotal hydrocele but without treatment or follow-up. Eight years later, the patient complained of abdominal distension, and a computed tomography scan revealed the presence of retroperitoneal and right scrotal masses. The right scrotal mass was removed, and histopathology revealed DDLPS. The patient was diagnosed with unresectable PDDLPS metastasising to the retroperitoneum, and the left pleura was treated with doxorubicin. After an initial response, pleural effusion and ascites increased during the sixth cycle of chemotherapy. The patient subsequently received eribulin but died 5 months after the initial DDLPS diagnosis.

Conclusion

It is difficult to distinguish PLPS from benign inguinal hernia and hydrocele testis on physical examination. PLPS generally has a considerably good prognosis. However, failure to diagnose WDLPS can be dangerous as it might lead to malignant transformation to DDLPS, which has a poor prognosis. Physicians should consider this malignancy when examining patients with hernias or hydroceles of the inguinal region and should perform ultrasonography or magnetic resonance imaging.
A novel approach for dose painting radiotherapy of brain metastases guided by mr perfusion images
Authors: Hou Chuanke , Yin Hanjing , Gong Guanzhong , Wang Lizhen , Su Ya , Lu Jie , Yin Yong
Published: December 2022

Purpose

To investigate the feasibility and dosimetric index features of dose painting guided by perfusion heterogeneity for brain metastasis (BMs) patients.

Methods

A total of 50 patients with single BMs were selected for this study. CT and MR simulation images were obtained, including contrast-enhanced T1-weighted images (T1WI+C) and cerebral blood flow (CBF) maps from 3D-arterial spin labeling (ASL). The gross tumor volume (GTV) was determined by fusion of CT and T1WI+C images. Hypoperfused subvolumes (GTVH) with less than 25% of the maximum CBF value were defined as the dose escalation region. The planning target volume (PTV) and PTVH were calculated from GTV and GTVH respectively. The PTVN was obtained by subtracting PTVH from PTV, and conventional dose was given. Three kinds of radiotherapy plans were designed based on the CBF values. Plan 1 was defined as the conventional plan with an arbitrary prescription dose of 60 Gy for PTV. For dose painting, Plan 2 and Plan 3 escalated the prescription dose for PTVH to 72 Gy based on Plan 1, but Plan 3 removed the maximum dose constraint. Dosimetric indices were compared among the three plans.

Results

The mean GTV volume was 34.5 (8.4-118.0) cm3, and mean GTVH volume was 17.0 (4.5-58.3) cm3, accounting for 49.3% of GTV. Both conventional plan and dose painting plans achieved 98% target coverage. The conformity index of PTVH were 0.44 (Plan1), 0.64 and 0.72 (Plan 2 and Plan 3, P<0.05). Compared to Plan 1, the D2%, D98% and Dmean values of the PTVH escalated by 20.50%, 19.32%, and 19.60% in Plan 2 and by 24.88%, 17.22% and 19.22% in Plan 3 respectively (P<0.05). In the three plans, the index of achievement value for PTVH was between 1.01 and 1.03 (P<0.05). The dose increment rates of Plan 2 and Plan 3 for each organs at risk (OARs) was controlled at 2.19% - 5.61% compared with Plan 1. The doses received by OARs did not significantly differ among the three plans (P >0.05).

Conclusions

BMs are associated with significant heterogeneity, and effective escalation of the dose delivered to target subvolumes can be achieved with dose painting guided by 3D-ASL without extra doses to OARs.
Practical nomogram based on comprehensive CT texture analysis to preoperatively predict peritoneal occult metastasis of gastric cancer patients
Authors: Chen Shuxiang , Zhang Huijuan , Wei Hong , Tong Yongxiu , Chen Xiaofang
Published: December 2022

Objectives

This study aims to evaluate whether a nomogram based on comprehensive CT texture analysis of primary tumor and peritoneotome combined with conventional CT signs can preoperatively predict peritoneal occult metastasis in gastric cancer patients.

Methods

A total of 1,251 patients with gastric cancer (GC) were retrospectively analyzed in Fujian Province Hospital between 2008 and 2020. Patients from the occult peritoneal metastasis (PM) group were initially diagnosed as PM-negative on CT and later confirmed as PM-positive through laparoscopy or surgery. The group without PM was randomly sampled from patients without PM. The preoperative CT signs and texture features and clinical characteristics of patients were retrospectively analyzed. Hazard factors of occult PM were identified by univariate analysis and multivariate logistic regression analysis, which were intended for creating prediction models. A nomogram was established based on the model with the highest predictive efficacy and clinical application value.

Results

A total of 31 patients with occult PM and 165 patients without PM were enrolled in this study. The maximum size, thickness, enhancement, serous involvement of primary GC tumor and ascites on CT, and texture features such as inhomogeneity of the primary tumor, standard deviation, and inhomogeneity of the peritoneum were determined as independent predictors that could be jointly applied to predict occult PM. We separately constructed five forecast models using CT signs, primary tumor texture, peritoneum texture, primary tumor texture + peritoneum texture, and their combination for predicting occult PM. These five prediction models achieved an AUC value of 0.832, 0.70, 0.784, 0.838, and 0.941, respectively. The DeLong test and Decision Curve Analysis (DCA) showed that the joint model, containing three meaningful CT signs (maximum size, thickness, and ascites) and two meaningful texture parameters (inhomogeneity of the primary tumor and inhomogeneity of the peritoneum), possessed the best predictive performance and clinical application (p<0.05). A forecast nomogram was subsequently established from the model above-mentioned. The calibration curves of the nomogram indicated a good consistency (a concordance index of 0.807) between the projection and the actual observation of occult PM.

Conclusions

A practical projection nomogram based on the comprehensive CT texture analysis of a primary tumor and peritoneotome combined with conventional CT signs was constructed in our study, which can be conveniently used in preoperative personalized prediction of occult PM for GC patients, and acts as a recommendation for the optimization of clinical management.
CDK4/6 inhibitor resistance: A bibliometric analysis
Authors: Pang Jiayuecheng , Li Hengyu , Sheng Yuan
Published: December 2022

Background

Cyclin-dependent kinases (CDKs) 4/6 inhibitors are a type of cell cycle regulation that prevents cell proliferation by blocking retinoblastoma protein (Rb) phosphorylation in the G1 to S phase transition. CDK 4/6 inhibitors are currently used mainly in patients with hormone receptor-positive/human epidermal growth factor receptor 2 (HER2) negative breast cancer in combination with endocrine therapy. However, primary or acquired resistance to drugs severely affect drug efficacy. Our study aims at summarizing and visualizing the current research direction and development trend of CDK4/6 inhibitor resistance to provide clinicians and research power with a summary of the past and ideas for the future.

Methods

The Web of Science Core Collection and PubMed was searched for all included articles on CDK4/6 inhibitor resistance for bibliometric statistics and graph plotting. The metrological software and graphing tools used were R language version 4.2.0, Bibliometrix 4.0.0, Vosviewer 1.6.18, GraphPad Prism 9, and Microsoft Excel 2019.

Results

A total of 1278 English-language articles related to CDK4/6 inhibitor resistance were included in the Web of Science core dataset from 1996-2022, with an annual growth rate of14.56%. In PubMed, a total of 1123 articles were counted in the statistics, with an annual growth rate of 17.41% Cancer Research is the most included journal (102/1278, 7.98%) with an impact factor of 13.312 and is the Q1 of the Oncology category of the Journal Citation Reports. Professor Malorni Luca from Italy is probably the most contributing author in the current field (Publications 21/1278, 1.64%), while Prof. Turner Nicholas C from the USA is perhaps the most authoritative new author in the field of CDK4/6 inhibitor resistance (Total Citations2584, M-index 1.429). The main research efforts in this field are currently focused on Palbociclib and Abemaciclib. Studies on drug resistance mechanisms or post-drug resistance therapies focus on MEK inhibitors and related pathways, PI3K-AKT-MTOR pathways or inhibitors, EGFR-related pathways, EGFR inhibitors, TKI inhibitors, MAPK pathways and inhibitors, and so on.

Conclusion

This study provides researchers with a reliable basis and guidance for finding authoritative references, understanding research trends, and mining research neglect directions.
Efficacy and safety profile of corticosteroids and non-steroidal anti-inflammatory drugs in COVID-19 management: A narrative review
Authors: Amponsah Seth Kwabena , Tagoe Benjamin , Adams Ismaila , Bugyei Kwasi Agyei
Published: December 2022

Due to the fact that coronavirus disease 2019 (COVID-19) is still prevalent, and current reports show that some parts of the world have seen increase in incidence, it is relevant that health professionals and scientists know about recent or novel trends, especially drug treatments. Additionally, the safety profiles of these drug treatments need to be documented and shared with the public. Some studies have demonstrated the clinical benefits of non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids in COVID-19 treatment. On the contrary, others have also reported that NSAIDs and corticosteroids may worsen symptoms associated with COVID-19. While some researchers have suggested that corticosteroids may be helpful if used in the early stages of COVID-19, there are still some conflicting findings regarding the use of corticosteroids in certain viral infections. Our review suggests that methylprednisolone, dexamethasone, and ibuprofen have therapeutic potential in reducing mortality due to COVID-19 among hospitalized patients. This review also highlights the fact that the use of NSAIDs is not associated with adverse outcomes of COVID-19. In reality, evidence suggests that NSAIDs do not increase the risk of COVID-19 infections. Also, the literature reviewed suggests that corticosteroid treatment in COVID-19 was linked with a decrease in all-cause mortality and disease progression, without increase in adverse events when compared to no corticosteroid treatment.
Comprehensive serum metabolomics and network analysis to reveal the mechanism of gypenosides in treating lung cancer and enhancing the pharmacological effects of cisplatin
Authors: Qi Yan-Shuang , Xiao Man-Yu , Xie Peng , Xie Jin-Bo , Guo Mei , Li Fang-Fang , Piao Xiang-Lan
Published: December 2022

Gypenosides (GYP) exerted anticancer activity against various cancers. However, the mechanism of GYP against lung cancer (LC) in vivo remains unclear. This study aims to reveal the potential mechanism of GYP against LC and enhancing cisplatin efficacy using a comprehensive analysis of metabolomics, network analysis. Pharmacodynamic results showed that GYP inhibited tumor growth, reduced tumor volume and tumor weight, and alleviated pathological symptoms in Lewis tumor-bearing mice, and GYP could enhance the anti-LC effects of cisplatin. Using serum metabolomics methods, 53 metabolites were found to be significantly altered in the model group, and the levels of 23 biomarkers were significantly restored after GYP treatment. GYP-related metabolic pathways involved six pathways, including alpha-linolenic acid metabolism, glutathione metabolism, sphingolipid metabolism, glycerophospholipid metabolism, tryptophan metabolism, and primary bile acid biosynthesis. 57 genes associated with differential metabolites of GYP recovery and 7 genes of 11 saponins of GYP against LC were screened by network analysis, the STRING database was used to find the association between 57 genes and 7 genes, and a compound-intersection gene-metabolite related gene-metabolite-pathway network was constructed, and STAT3, MAPK14, EGFR and TYMS might be the crucial targets of GYP against LC. Western blot results showed that GYP restored the levels of STA3, MAPK14, EGFR, and TYMS in the model group, and GYP also restored the levels of STAT3 and MAPK14 in the cisplatin group, indicating that GYP might exert anti-LC effects and enhance the pharmacological effects of cisplatin through MAPK14/STAT3 signaling pathway. Our method revealed the effect and mechanism of GYP on LC and the pharmacological effects of GYP-enhanced chemotherapeutic agent cisplatin, which provided some reference for the development of anti-cancer drugs.
The botanical drug PBI-05204, a supercritical CO2 extract of Nerium oleander, sensitizes alveolar and embryonal rhabdomyosarcoma to radiotherapy in vitro and in vivo
Authors: Vaccaro Sara , Rossetti Alessandra , Porrazzo Antonella , Camero Simona , Cassandri Matteo , Pomella Silvia , Tomaciello Miriam , Macioce Giampiero , Pedini Francesca , Barillari Giovanni , Marchese Cinzia , Rota Rossella , Cenci Giovanni , Tombolini Mario , Newman Robert A. , Yang Peiying , Codenotti Silvia , Fanzani Alessandro , Megiorni Francesca , Festuccia Claudio , Minniti Giuseppe , Gravina Giovanni Luca , Vulcano Francesca , Milazzo Luisa , Marampon Francesco
Published: December 2022

Treatment of rhabdomyosarcoma (RMS), the most common a soft tissue sarcoma in childhood, provides intensive multimodal therapy, with radiotherapy (RT) playing a critical role for local tumor control. However, since RMS efficiently activates mechanisms of resistance to therapies, despite improvements, the prognosis remains still largely unsatisfactory, mainly in RMS expressing chimeric oncoproteins PAX3/PAX7-FOXO1, and fusion-positive (FP)-RMS. Cardiac glycosides (CGs), plant-derived steroid-like compounds with a selective inhibitory activity of the Na+/K+-ATPase pump (NKA), have shown antitumor and radio-sensitizing properties. Herein, the therapeutic properties of PBI-05204, an extract from Nerium oleander containing the CG oleandrin already studied in phase I and II clinical trials for cancer patients, were investigated, in vitro and in vivo, against FN- and FP-RMS cancer models. PBI-05204 induced growth arrest in a concentration dependent manner, with FP-RMS being more sensitive than FN-RMS, by differently regulating cell cycle regulators and commonly upregulating cell cycle inhibitors p21Waf1/Cip1 and p27Cip1/Kip1. Furthermore, PBI-05204 concomitantly induced cell death on both RMS types and senescence in FN-RMS. Notably, PBI-05204 counteracted in vitro migration and invasion abilities and suppressed the formation of spheroids enriched in CD133+ cancer stem cells (CSCs). PBI-05204 sensitized both cell types to RT by improving the ability of RT to induce G2 growth arrest and counteracting the RT-induced activation of both Non‐Homologous End‐Joining and homologous recombination DSBs repair pathways. Finally, the antitumor and radio-sensitizing proprieties of PBI-05204 were confirmed in vivo. Notably, both in vitro and in vivo evidence confirmed the higher sensitivity to PBI-05204 of FP-RMS. Thus, PBI-05204 represents a valid radio-sensitizing agent for the treatment of RMS, including the intrinsically radio-resistant FP-RMS.
Circular RNA-related CeRNA network and prognostic signature for patients with oral squamous cell carcinoma
Authors: He Yaodong , Yang Dengcheng , Li Yunshan , Xiang Junwei , Wang Liecheng , Wang Yuanyin
Published: December 2022

Background: Circular RNA (circRNA) has an important influence on oral squamous cell carcinoma (OSCC) progression as competing endogenous RNAs (ceRNAs). However, the link between ceRNAs and the OSCC immune microenvironment is unknown. The research aimed to find circRNAs implicated in OSCC carcinogenesis and progression and build a circRNA-based ceRNA network to create a reliable OSCC risk prediction model.

Methods: The expression profiles of circRNA in OSCC tumors and normal tissues were assessed through RNA sequencing. From the TCGA database, clinicopathological data and expression patterns of microRNAs (miRNAs) and mRNAs were obtained. A network of circRNA-miRNA-mRNA ceRNA was prepared according to these differentially expressed RNAs and was analyzed through functional enrichment. Subsequently, based on the mRNA in the ceRNA network, the influence of the model on prognosis was then evaluated using a risk prediction model. Finally, considering survival, tumor-infiltrating immune cells (TICs), clinicopathological features, immunosuppressive molecules, and chemotherapy efficacy were analyzed.

Results: Eleven differentially expressed circRNAs were found in cancer tissues relative to healthy tissues. We established a network of circRNA-miRNA-mRNA ceRNA, and the ceRNA network includes 123 mRNAs, six miRNAs, and four circRNAs. By the assessment of Genomes pathway and Kyoto Encyclopedia of Genes, it is found that in the cellular senescence, PI3K-AKT and mTOR signaling pathway mRNAs were mainly enrichment. An immune-related signature was created utilizing seven immune-related genes in the ceRNA network after univariate and multivariate analysis. The receiver operating characteristic of the nomogram exhibited satisfactory accuracy and predictive potential. According to a Kaplan-Meier analysis, the high-risk group’s survival rate was signally lower than the group with low-risk. In addition, risk models were linked to clinicopathological characteristics, TICs, immune checkpoints, and antitumor drug susceptibility.

Conclusion: The profiles of circRNAs expression of OSCC tissues differ significantly from normal tissues. Our study established a circRNA-associated ceRNA network associated with OSCC and identified essential prognostic genes. Furthermore, our proposed immune-based signature aims to help research OSCC etiology, prognostic marker screening, and immune response evaluation.
Red blood cell proteomics reveal remnant protein biosynthesis and folding pathways in PIEZO1-related hereditary xerocytosis
Authors: Caulier Alexis , Jankovsky Nicolas , Gautier Emilie Fleur , El Nemer Wassim , Guitton Corinne , Ouled-Haddou Hakim , Guillonneau François , Mayeux Patrick , Salnot Virginie , Bruce Johanna , Picard Véronique , Garçon Loïc
Published: December 2022

Hereditary xerocytosis is a dominant red cell membrane disorder characterized by an increased leak of potassium from the inside to outside the red blood cell membrane, associated with loss of water leading to red cell dehydration and chronic hemolysis. 90% of cases are related to heterozygous gain of function mutations in PIEZO1, encoding a mechanotransductor that translates a mechanical stimulus into a biological signaling. Data are still required to understand better PIEZO1-HX pathophysiology. Recent studies identified proteomics as an accurate and high-input tool to study erythroid progenitors and circulating red cell physiology. Here, we isolated red blood cells from 5 controls and 5 HX patients carrying an identified and pathogenic PIEZO1 mutation and performed a comparative deep proteomic analysis. A total of 603 proteins were identified among which 56 were differentially expressed (40 over expressed and 16 under expressed) between controls and HX with a homogenous expression profile within each group. We observed relevant modifications in the protein expression profile related to PIEZO1 mutations, identifying two main “knots”. The first contained both proteins of the chaperonin containing TCP1 complex involved in the assembly of unfolded proteins, and proteins involved in translation. The second contained proteins involved in ubiquitination. Deregulation of proteins involved in protein biosynthesis was also observed in in vitro-produced reticulocytes after Yoda1 exposure. Thus, our work identifies significant changes in the protein content of PIEZO1-HX erythrocytes, revealing a “PIEZO1 signature” and identifying potentially targetable pathways in this disease characterized by a heterogeneous clinical expression and contra-indication of splenectomy.
Differential activity of wheat antioxidant defense system and alterations in the accumulation of osmolytes at different developmental stages as influenced by marigold (Tagetes erecta L.) leachates
Authors: Mir Rayees Ahmad , Argal Surendra , Ahanger Mohammad Abass , Jatav Keshav Singh , Agarwal Rajiv Mohan
Published: December 2022

Experiments were conducted to evaluate the effectivity of Tagetes erecta L. leachates on various growth, physiological, and biochemical parameters of wheat at different stages of growth. Results suggested that Triticum aestivum L. seedlings/plants when exposed to higher concentrations of marigold leachates (10%, 20%, and 30% w/v of fresh parts and 5% and 10% w/v of dry parts) exhibited enhanced lipid peroxidation along with an increase in the activity of protease and phenylalanine ammonia lyase. Treatment with higher concentrations of leachates of fresh (30% w/v) and dry (10% w/v) T. erecta upregulated the activity of superoxide dismutase, catalase, ascorbate peroxidase, guaiacol peroxidase, glutathione S-transferase, and glutathione reductase and also increased the non-enzymatic components of antioxidant defense such as glutathione, ascorbic acid, and total phenols along with osmotic constituents comprising free proline, free sugars, and free amino acids in wheat. The growth and yield attributes of wheat exhibited a slight increase at treatments with lower concentrations (1% w/v) of dry leachates, whereas a decrease was recorded at higher concentrations (10% w/v). In general, treatments with flower leachates (higher concentrations) showed greater influence as compared with those with leaf leachates. Identification and understanding the mechanism of function of allelochemicals in these leachates may pave a way for further experimentation on Tagetes erecta L crop while it is cultivated and decomposed in the field.
Compensatory growth as a response to post-drought in grassland
Authors: Zhou Huailin , Hou Lulu , Lv Xiaomin , Yang Guang , Wang Yuhui , Wang Xu
Published: December 2022

Grasslands are structurally and functionally controlled by water availability. Ongoing global change is threatening the sustainability of grassland ecosystems through chronic alterations in climate patterns and resource availability, as well as by the increasing frequency and intensity of anthropogenic perturbations. Compared with many studies on how grassland ecosystems respond during drought, there are far fewer studies focused on grassland dynamics after drought. Compensatory growth, as the ability of plants to offset the adverse effects of environmental or anthropogenic perturbations, is a common phenomenon in grassland. However, compensatory growth induced by drought and its underlying mechanism across grasslands remains not clear. In this review, we provide examples of analogous compensatory growth from different grassland types across drought characteristics (intensity, timing, and duration) and explain the effect of resource availability on compensatory growth and their underlying mechanisms. Based on our review of the literature, a hypothetic framework for integrating plant, root, and microbial responses is also proposed to increase our understanding of compensatory growth after drought. This research will advance our understanding of the mechanisms of grassland ecosystem functioning in response to climate change.