bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive factors for delayed hyponatremia after transsphenoidal surgery in patients with Rathke’s cleft cysts
Authors: Lin Kunzhe , Pei Zhijie , Zhang Yibin , Feng Tianshun , Wang Shousen
Published: September 2022

Purpose

We aimed to assess factors influencing the occurrence of delayed hyponatremia after transsphenoidal surgery in patients with Rathke’s cleft cysts (RCCs).

Methods

We retrospectively collected the clinical data of patients who underwent transsphenoidal surgery for RCCs from January 2014 to January 2022. Univariate and multivariate analyses were used to determine the factors influencing the occurrence of postoperative delayed hyponatremia.

Results

Of the 78 microscopic transsphenoidal surgery recipients with RCCs, 15 experienced postoperative delayed hyponatremia. There were 35 men and 43 women, and mean age was 43.75 ± 14.95 years. The clinical manifestations of RCCs were headache (62 cases, 79.5%), visual dysfunction (35 cases, 44.9%), endocrine dysfunction symptoms (12 cases, 15.4%). After transsphenoidal surgery, 93.5% (58/62) had improvements in headache, and 97.1% (34/35) had improved or resolved compressive visual symptoms. Delayed hyponatremia occurred on average on day 6.46 and lasted on average for 4.40 days. Logistic regression analysis showed that the independent influencing factor of delayed hyponatremia after transsphenoidal surgery in patients with RCCs was postoperative diaphragma sellae height.

Conclusion

Postoperative diaphragma sellae height was identified as an independent influencing factor for delayed hyponatremia after transsphenoidal surgery in patients with RCCs.
PD-1 inhibitors plus lenvatinib versus PD-1 inhibitors plus regorafenib in patients with advanced hepatocellular carcinoma after failure of sorafenib
Authors: Xu Yongkang , Fu Shumin , Shang Kai , Zeng Jiayu , Mao Ye
Published: September 2022

Background

Lenvatinib, regorafenib and anti-programmed cell death protein-1 (PD-1) immunotherapy have shown promising clinical outcomes in patients with advanced hepatocellular carcinoma (HCC) after sorafenib failure, respectively. However, the combination of the two treatments has not been reported. We compared the efficacy of PD-1 inhibitors with lenvatinib (PL) and PD-1 inhibitors plus regorafenib (PR) in patients with advanced HCC in this study.

Methods

We conducted a retrospective study of advanced HCC patients who undergone PD-1 inhibitors combined with lenvatinib or regorafenib after failure of sorafenib at Second Affiliated Hospital of Nanchang University from July 2018 and December 2020. The overall survival (OS), progression-free survival (PFS), effective rates and treatment-related adverse events (TRAEs) were investigated.

Results

In total, 61 patients met the criteria and were included in the present study, and they were divided into the PL group (n = 32) and PR group (n = 29). The overall response rate (ORR) (12.5%vs. 10.3%, respectively; p = 0.557) and disease control rate (DCR) (71.9%vs. 58.6%, respectively; p < 0.207) were higher in the PL group than in the PR group, but there was no statistical difference.

Furthermore, median PFS and OS were not significantly different between the two groups in Kaplan-Meier survival analysis (PFS: 5.3 months vs 4.0 months, p = 0.512; OS: 14.1 months vs 13.7 months, p = 0.764 for the PL group vs PR group). The most common treatment-related adverse events (TRAEs) were hand -foot skin reaction (24/61,39.3%), hypertension (20/61,32.8%) and hypothyroidism (13/61,21.3%). The frequent TRAEs (≥Grade 3) during PD-1 inhibitors plus lenvatinib or regorafenib treatment were hand-foot skin reaction (5/29,12.4%), thrombocytopenia (2/29 6.90%) and proteinuria (n =2/32,6.25%).

Conclusions

Combination of lenvatinib/regorafenib and PD-1 inhibitors is a promising therapy for HCC patients after sorafenib failure.
Frontiers and hotspots of 18F-FDG PET/CT radiomics: A bibliometric analysis of the published literature
Authors: Liu Xinghai , Hu Xianwen , Yu Xiao , Li Pujiao , Gu Cheng , Liu Guosheng , Wu Yan , Li Dandan , Wang Pan , Cai Jiong
Published: September 2022

Objective

To illustrate the knowledge hotspots and cutting-edge research trends of 18F-FDG PET/CT radiomics, the knowledge structure of was systematically explored and the visualization map was analyzed.

Methods

Studies related to 18F-FDG PET/CT radiomics from 2013 to 2021 were identified and selected from the Web of Science Core Collection (WoSCC) using retrieval formula based on an interview. Bibliometric methods are mainly performed by CiteSpace 5.8.R3, which we use to build knowledge structures including publications, collaborative and co-cited studies, burst analysis, and so on. The performance and relevance of countries, institutions, authors, and journals were measured by knowledge maps. The research foci were analyzed through research of keywords, as well as literature co-citation analysis. Predicting trends of 18F-FDG PET/CT radiomics in this field utilizes a citation burst detection method.

Results

Through a systematic literature search, 457 articles, which were mainly published in the United States (120 articles) and China (83 articles), were finally included in this study for analysis. Memorial Sloan-Kettering Cancer Center and Southern Medical University are the most productive institutions, both with a frequency of 17. 18F-FDG PET/CT radiomics–related literature was frequently published with high citation in European Journal of Nuclear Medicine and Molecular Imaging (IF9.236, 2020), Frontiers in Oncology (IF6.244, 2020), and Cancers (IF6.639, 2020). Further cluster profile of keywords and literature revealed that the research hotspots were primarily concentrated in the fields of image, textural feature, and positron emission tomography, and the hot research disease is a malignant tumor. Document co-citation analysis suggested that many scholars have a co-citation relationship in studies related to imaging biomarkers, texture analysis, and immunotherapy simultaneously. Burst detection suggests that adenocarcinoma studies are frontiers in 18F-FDG PET/CT radiomics, and the landmark literature put emphasis on the reproducibility of 18F-FDG PET/CT radiomics features.

Conclusion

First, this bibliometric study provides a new perspective on 18F-FDG PET/CT radiomics research, especially for clinicians and researchers providing scientific quantitative analysis to measure the performance and correlation of countries, institutions, authors, and journals. Above all, there will be a continuing growth in the number of publications and citations in the field of 18F-FDG PET/CT. Second, the international research frontiers lie in applying 18F-FDG PET/CT radiomics to oncology research. Furthermore, new insights for researchers in future studies will be adenocarcinoma-related analyses. Moreover, our findings also offer suggestions for scholars to give attention to maintaining the reproducibility of 18F-FDG PET/CT radiomics features.
Endocrine therapy for metastatic solid pseudopapillary neoplasm of the pancreas: A case report
Authors: Kornietskaya Anna , Evdokimova Sevindzh , Kachmazov Andrei , Fedenko Alexander. , Bolotina Larisa , Sidorov Dmitriy , Volchenko Nadezhda , Goeva Natalia , Govaleshko Anastasia , Kaprin Andrey
Published: September 2022

Solid pseudopapillary neoplasm (SPN) of the pancreas is an extremely rare tumor, associated with favorable prognosis and long-term survival in patients with advanced disease. However, limited data exist on systemic therapy for such patients. Herein, we present a case of a young woman with a history of SPN, who progressed after multiple surgical resections and chemotherapy regimens. The immunohistochemistry (IHC) showed overexpression of estrogen receptors (ER) and progesterone receptors (PR) in tumor tissue. The patient started to receive tamoxifen and showed a durable response to endocrine therapy.
Alpha-2-macroglobulin as a novel diagnostic biomarker for human bladder cancer in urinary extracellular vesicles
Authors: Lee Jisu , Park Hyun Sik , Han Seung Ro , Kang Yun Hee , Mun Ji Young , Shin Dong Wook , Oh Hyun-Woo , Cho Yoon-Kyoung , Lee Myung-Shin , Park Jinsung
Published: September 2022

Extracellular vesicles (EVs) derived from urine are promising tools for the diagnosis of urogenital cancers. Urinary EVs (uEVs) are considered potential biomarkers for bladder cancer (BC) because urine is in direct contact with the BC tumor microenvironment and thus reflects the current state of the disease. However, challenges associated with the effective isolation and analysis of uEVs complicate the clinical detection of uEV-associated protein biomarkers. Herein, we identified uEV-derived alpha-2-macroglobulin (a2M) as a novel diagnostic biomarker for BC through comparative analysis of uEVs obtained from patients with BC pre- and post-operation using an antibody array. Furthermore, enzyme-linked immunosorbent assay of uEVs isolated from patients with BC (n=60) and non-cancer control subjects (n=23) validated the significant upregulation of a2M expression in patient uEVs (p<0.0001). There was no significant difference in whole urine a2M levels between patients with BC and controls (p=0.317). We observed that compared to classical differential centrifugation, ExoDisc, a centrifugal microfluidic tangential flow filtration device, was a significantly more effective separation method for uEV protein analysis. We expect that our approach for EV analysis will provide an efficient route for the identification of clinically meaningful uEV-based biomarkers for cancer diagnosis.
Governing HPV-related carcinoma using vaccines: Bottlenecks and breakthroughs
Authors: Bhattacharjee Rahul , Kumar Lamha , Dhasmana Archna , Mitra Tamoghni , Dey Abhijit , Malik Sumira , Kim Bonglee , Gundamaraju Rohit
Published: September 2022

Human papillomavirus (HPV) contributes to sexually transmitted infection, which is primarily associated with pre-cancerous and cancerous lesions in both men and women and is among the neglected cancerous infections in the world. At global level, two-, four-, and nine-valent pure L1 protein encompassed vaccines in targeting high-risk HPV strains using recombinant DNA technology are available. Therapeutic vaccines are produced by early and late oncoproteins that impart superior cell immunity to preventive vaccines that are under investigation. In the current review, we have not only discussed the clinical significance and importance of both preventive and therapeutic vaccines but also highlighted their dosage and mode of administration. This review is novel in its way and will pave the way for researchers to address the challenges posed by HPV-based vaccines at the present time.
Successful conversion therapy for unresectable hepatocellular carcinoma is getting closer: A systematic review and meta-analysis
Authors: Pei Yinxuan , Li Weiwei , Wang Zixiang , Liu Jinlong
Published: September 2022

Background

Conversion therapy provides selected patients with unresectable hepatocellular carcinoma the opportunity to undergo a curative hepatectomy and achieve long-term survival. Although various regimens have been used for conversion therapy, their conversion rate and safety remain uncertain. Therefore, we conducted some meta-analyses to evaluate the efficacy and safety of several conversion regimens in order to elucidate the optimal regimen.

Method

We performed systematic literature research on PubMed, Embase, and the Web of Science until July 30, 2022. Chemotherapy, transcatheter arterial chemoembolization (TACE), molecular therapy (targeted therapy, immunotherapy, or a combination of both), and combined locoregional-systemic therapy were the conversion regimens we targeted.

Results

Twenty-four studies were included. The pooled conversion rates for chemotherapy, TACE, molecular therapy, and combined locoregional-systemic therapy were 13% (95% confidence interval [CI], 7%–20%; I² = 82%), 12% (95% CI, 9%–15%; I² = 60%), 10% (95% CI, 3%–20%; I² = 90%), and 25% (95% CI, 13%–38%; I² = 89%), respectively. The pooled objective response rates (ORR) for chemotherapy, TACE, molecular therapy, and combined locoregional-systemic therapy were 19% (95% CI, 12%–28%; I² = 77%), 32% (95% CI, 15%–51%; I² = 88%), 30% (95% CI, 15%–46%; I² = 93%), and 60% (95% CI, 41%–77%; I² = 91%), respectively. The pooled grade ≥3 AEs for chemotherapy, TACE, molecular therapy, and combined locoregional-systemic therapy were 67% (95% CI, 55%–78%; I² = 79%), 34% (95% CI, 8%–66%; I²= 92%), 30% (95% CI, 18%–43%; I² = 84%), and 40% (95% CI, 23%–58%; I² = 89%), respectively. Subgroup analyses showed the conversion rate, ORR and grade ≥3 AE rate for tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI) and locoregional therapy (LRT) were 33% (95% CI, 17%-52%; I² = 89%), 73% (95% CI, 51%–91%; I² = 90%), 31% (95% CI, 10%-57%; I² = 89%), respectively.

Conclusion

Combined locoregional-systemic therapy, especially TKI combined with ICI and LRT, may be the most effective conversion therapy regimen, associated with a significant ORR, conversion potential, and an acceptable safety profile.
A metabolic reprogramming-related prognostic risk model for clear cell renal cell carcinoma: From construction to preliminary application
Authors: Zhang Qian , Ding Lei , Zhou Tianren , Zhai Qidi , Ni Chenbo , Liang Chao , Li Jie
Published: September 2022

Metabolic reprogramming is one of the characteristics of clear cell renal cell carcinoma (ccRCC). Although some treatments associated with the metabolic reprogramming for ccRCC have been identified, remain still lacking. In this study, we identified the differentially expressed genes (DEGs) associated with clinical traits with a total of 965 samples via DEG analysis and weighted correlation network analysis (WGCNA), screened the prognostic metabolism-related genes, and constructed the risk score prognostic models. We took the intersection of DEGs with significant difference coexpression modules and received two groups of intersection genes that were connected with metabolism via functional enrichment analysis. Then we respectively screened prognostic metabolic-related genes from the genes of the two intersection groups and constructed the risk score prognostic models. Compared with the predicted effect of clinical grade and stage for ccRCC patients, finally, we selected the model constructed with genes of ABAT, ALDH6A1, CHDH, EPHX2, ETNK2, and FBP1. The risk scores of the prognostic model were significantly related to overall survival (OS) and could serve as an independent prognostic factor. The Kaplan-Meier analysis and ROC curves revealed that the model efficiently predicts prognosis in the TCGA-KIRC cohort and the validation cohort. Then we investigated the potential underlying mechanism and sensitive drugs between high- and low-risk groups. The six key genes were significantly linked with worse OS and were downregulated in ccRCC, we confirmed the results in clinical samples. These results demonstrated the efficacy and robustness of the risk score prognostic model, based on the characteristics of metabolic reprogramming in ccRCC, and the key genes used in constructing the model also could develop into targets of molecular therapy for ccRCC.
Loss of the Fbw7 tumor suppressor rewires cholesterol metabolism in cancer cells leading to activation of the PI3K-AKT signalling axis
Authors: Bengoechea-Alonso Maria T. , Aldaalis Arwa , Ericsson Johan
Published: September 2022

The sterol regulatory-element binding proteins (SREBPs) are transcription factors controlling cholesterol and fatty acid synthesis and metabolism. There are three SREBP proteins, SREBP1a, SREBP1c and SREBP2, with SREBP1a being the strongest transcription factor. The expression of SREBP1a is restricted to rapidly proliferating cells, including cancer cells. The SREBP proteins are translated as large, inactive precursors bound to the endoplasmic reticulum (ER) membranes. These precursors undergo a two-step cleavage process that releases the amino terminal domains of the proteins, which translocate to the nucleus and function as transcription factors. The nuclear forms of the SREBPs are rapidly degraded by the ubiquitin-proteasome system in a manner dependent on the Fbw7 ubiquitin ligase. Consequently, inactivation of Fbw7 results in the stabilization of active SREBP1 and SREBP2 and enhanced expression of target genes. We report that the inactivation of Fbw7 in cancer cells blocks the proteolytic maturation of SREBP2. The same is true in cells expressing a cancer-specific loss-of-function Fbw7 protein. Interestingly, the activation of SREBP2 is restored in response to cholesterol depletion, suggesting that Fbw7-deficient cells accumulate cholesterol. Importantly, inactivation of SREBP1 in Fbw7-deficient cells also restores the cholesterol-dependent regulation of SREBP2, suggesting that the stabilization of active SREBP1 molecules could be responsible for the blunted activation of SREBP2 in Fbw7-deficient cancer cells. We suggest that this could be an important negative feedback loop in cancer cells with Fbw7 loss-of-function mutations to protect these cells from the accumulation of toxic levels of cholesterol and/or cholesterol metabolites. Surprisingly, we also found that the inactivation of Fbw7 resulted in the activation of AKT. Importantly, the activation of AKT was dependent on SREBP1 and on the accumulation of cholesterol. Thus, we suggest that the loss of Fbw7 rewires lipid metabolism in cancer cells to support cell proliferation and survival.
The top 100 cited studies on bacterial persisters: A bibliometric analysis
Authors: Ju Yuan , Long Haiyue , Zhao Ping , Xu Ping , Sun Luwei , Bao Yongqing , Yu Pingjing , Zhang Yu
Published: September 2022

Background: Bacterial persisters are thought to be responsible for the recalcitrance and relapse of persistent infections, and they also lead to antibiotic treatment failure in clinics. In recent years, researches on bacterial persisters have attracted worldwide attention and the number of related publications is increasing. The purpose of this study was to better understand research trends on bacterial persisters by identifying and bibliometrics analyzing the top 100 cited publications in this field.

Methods: The Web of Science Core Collection was utilized to retrieve the highly cited publications on bacterial persisters, and these publications were cross-matched with Google Scholar and Scopus. The top 100 cited publications were identified after reviewing the full texts. The main information of each publication was extracted and analyzed using Excel, SPSS, and VOSviewer.

Results: The top 100 cited papers on bacterial persisters were published between 1997 and 2019. The citation frequency of each publication ranged from 147 to 1815 for the Web of Science Core Collection, 153 to 1883 for Scopus, and 207 to 2,986 for Google Scholar. Among the top 100 cited list, there were 64 original articles, 35 review articles, and 1 editorial material. These papers were published in 51 journals, and the Journal of Bacteriology was the most productive journal with 8 papers. A total of 14 countries made contributions to the top 100 cited publications, and 64 publications were from the United States. 15 institutions have published two or more papers and nearly 87% of them were from the United States. Kim Lewis from Northeastern University was the most influential author with 18 publications. Furthermore, keywords co-occurrence suggested that the main topics on bacterial persisters were mechanisms of persister formation or re-growth. Finally, “Microbiology” was the most frequent category in this field.

Conclusion: This study identified and analyzed the top 100 cited publications related to bacterial persisters. The results provided a general overview of bacterial persisters and might help researchers to better understand the classic studies, historical developments, and new findings in this field, thus providing ideas for further research.
A real-world cost-effectiveness analysis of nebulized budesonide and intravenous methylprednisolone in acute exacerbation of chronic obstructive pulmonary disease
Authors: Gu Yong-Li , Sun Zeng-Xian , Sun Ying , Wen Yan , Guan Xin , Jiang Dao-Li , Cheng Cong , Gu Huan
Published: September 2022

Objective: To assess the cost-effectiveness of nebulized budesonide and intravenous methylprednisolone in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in a real-world setting.

Materials and methods: Data from 291 patients with AECOPD were collected from the information system of a tertiary hospital in China. Patients were categorized into two groups: those treated with nebulized budesonide (n = 148) and those treated with intravenous methylprednisolone (n = 143). Clinical efficacy and the rate of no readmission within 1 year after discharge were used as effect indicators, and a cost-effectiveness analysis was conducted from the perspective of the Chinese healthcare system. Logistic regression, generalized linear regression, and bootstrap methods were used for sensitivity analyses.

Results: There was no statistical difference between the budesonide and methylprednisolone groups in clinical efficacy rates (94.6% vs. 93.7%). The cost-minimization analysis shows that budesonide is not cost-effective owing to higher total cost. In terms of readmission rates, budesonide was again not cost-effective, with an incremental cost-effectiveness ratio (ICER) of 22276.62 CNY, which is higher than the willingness to pay (WTP) of 20206.20 CNY, the mean per admission expenditure in China. The sensitivity analyses confirm that these results are robust.

Conclusion: Compared with intravenous methylprednisolone, nebulized budesonide is not a cost-effective strategy for AECOPD patients in China.
Active Peptide AR-9 From Eupolyphaga sinensis Reduces Blood Lipid and Hepatic Lipid Accumulation by Restoring Gut Flora and Its Metabolites in a High Fat Diet–Induced Hyperlipidemia Rat
Authors: Wang Hong , Dong Pingping , Liu Xin , Zhang Zhen , Li Huajian , Li Yanan , Zhang Jiayu , Dai Long , Wang Shaoping
Published: September 2022

The dysbiosis of gut flora and its metabolites plays important roles in the progression of hyperlipidemia (HL), and some bioactive peptides are available for HL treatment. In this study, we aimed to isolate an active peptide (AR-9) from active peptides of E. sinensis (APE) and determine whether AR-9 could improve many symptoms of a HL rat induced by a high-fat diet (HFD) by modulating gut flora and its metabolites. Above all, AR-9 was derived from APE using ion-exchange chromatography, and its structure was deconstructed by Fourier transform infrared spectrometer (FT-IR), circular dichroism (CD) spectroscopy, and UHPLC-Q-Exactive-Orbitrap MS. Then, an HFD-induced HL model in SD rats was established and used to clarify the regulatory effects of AR-9 (dose of 3 mg/kg) on HL. Normal diet–fed rats were taken as the control. The plasma samples and liver were harvested for biochemical and histopathological examinations. 16S rRNA gene sequencing and untargeted metabolomics were sequenced to assess changes in gut flora and its metabolites from rat fecal samples. Finally, Spearman’s correlation analysis was used to assess the relationship between lipid-related factors, gut flora, and its metabolites so as to evaluate the mechanism of AR-9 against HL. The results of the separation experiments showed that the amino acid sequence of AR-9 was AVFPSIVGR, which was a fragment of the actin protein from Blattaria insects. Moreover, HFD rats developed exaltation of index factors, liver lipid accumulation, and simple fibrosis for 8 weeks, and the profiles of gut flora and its metabolites were significantly altered. After treatment, AR-9 decreased the levels of lipid factors in plasma and the extent of liver damage. 16S rRNA gene sequencing results indicated that AR-9 significantly increased the relative abundance of beneficial bacteria Bacteroidetes and reduced the relative abundance of the obesity-associated bacteria Firmicutes. Furthermore, AR-9 changed gut microbiota composition and increased the relative abundance of beneficial bacteria: Lactobacillus, Clostridium, Dehalobacterium, and Candidatus arthromitus. Fecal metabolomics showed that the pathway regulated by AR-9 was “arginine biosynthesis”, in which the contents were citrulline and ornithine. Spearman’s correlation analysis revealed that two metabolites (ornithine and citrulline) showed significantly negative correlations with obesity-related parameters and positive correlations with the gut genera (Clostridium) enriched by AR-9. Overall, our results suggested interactions between gut microbial shifts and fecal amino acid/lipid metabolism and revealed the mechanisms underlying the anti-HL effect of AR-9. The abovementioned results not only reveal the initial anti-HL mechanism of AR-9 but also provide a theoretical basis for the continued development of AR-9.
Revealing the mechanism of raw and vinegar-processed Curcuma aromatica Salisb. [Zingiberaceae] regulates primary dysmenorrhea in rats via integrated metabolomics
Authors: Su Lianlin , Tong Huangjin , Zhang Jiuba , Hao Min , Fei Chenghao , Ji De , Gu Wei , Bian Zhenhua , Mao Chunqin , Lu Tulin
Published: September 2022

Primary dysmenorrhea (PDM) is a common disorder among women around the world. Two processed products of Curcuma aromatica Salisb. [Zingiberaceae] (CAS) are traditional Chinese medicine (TCM) that have long been used to treat gynecological blood stasis syndrome such as primary dysmenorrhea. The mechanisms and active substances of CAS are still largely unknown. The study aimed to establish a rat model of primary dysmenorrhea which investigates the differences between the pharmacodynamics and mechanisms of raw CAS (RCAS) and vinegar-processed CAS (VCAS). Histopathology, cytokinetics, and metabolomics were adopted to evaluate the anti-blood stasis effect of RCAS and VCAS. In metabolomics, endogenous differential metabolites in plasma, urine, and feces are the essential steps to evaluate the effect of RCAS and VCAS. In this study, the rat model of primary dysmenorrhea was successfully established. After RCAS and VCAS intervention, the uterine tissue morphology of dysmenorrhea model rats was improved, and gland hypertrophy and myometrial hyperplasia were reduced as well as neutrophil content. Compared with the RCAS group, the VCAS group had better uterine morphology, few inflammatory factors, and significantly improved amino acid and lipid metabolism. The aforementioned results support the conclusion that VCAS performed better than RCAS in primary dysmenorrhea and that vinegar processing increases the efficacy of CAS.
Icariin protects vertebral endplate chondrocytes against apoptosis and degeneration via activating Nrf-2/HO-1 pathway
Authors: Shao Yuandong , Sun Lei , Yang Guihe , Wang Wenchao , Liu Xiaoyang , Du Ting , Chen Feifei , Jing Xingzhi , Cui Xingang
Published: September 2022

Cartilage endplate (CEP) plays important roles in the onset and progression of intervertebral disc degeneration (IVDD). Icariin (ICA) is the major active ingredient of Herba Epimedii and has various biological activities such as anti-inflammatory and antioxidant, which is used to treat many degenerative diseases. However, the effects and mechanism of ICA on endplate chondrocytes are still unclear. Herein, we studied the effects of ICA on CEP degeneration and elucidated the underlying mechanisms. Endplate chondrocytes were isolated, and TNF-α and TBHP were applied to mimic an IVDD pathological environment. Also, an IVDD mice model was established by transection of bilateral facet joints to investigate the protective effect of ICA in vivo. We found that ICA treatment inhibited the chondrocytes apoptosis and the decrease of extracellular matrix production in a dose-dependent manner. Our in vivo experiments demonstrated that ICA could ameliorate IVDD development and CEP calcification. We also found that the ICA-activated Nrf-2/HO-1 pathway thus promoted the Parkin-mediated mitophagy process and inhibited chondrocytes ferroptosis, thus alleviated redox imbalance and mitochondrial dysfunction and eventually improved cell survival. Knockdown of Nrf-2 using siRNA reversed the protective effect of ICA on endplate chondrocytes apoptosis and degeneration. In conclusion, our study demonstrated that ICA could protect against CEP degeneration and calcification under IVDD pathological conditions, the associated mechanism may be related to Nrf-2/HO-1-mediated mitophagy activation and ferroptosis inhibition. Our results suggest that ICA may be a potential effective medicine for IVDD prevention and treatment.
Ensuring equity: Pharmacogenetic implementation in rural and tribal communities
Authors: Leitch Tianna M. , Killam Shayna R. , Brown Karen E. , Katseanes Kirk C. , George Kathleen M. , Schwanke Corbin , Loveland Joshua , Elias Abdallah F. , Haney Kerry , Krebsbach Kate , Muzquiz LeeAnna I. , Trinidad Susan B. , Woodahl Erica L.
Published: September 2022

Implementation strategies for pharmacogenetic testing have been largely limited to major academic medical centers and large health systems, threatening to exacerbate healthcare disparities for rural and tribal populations. There exists a need in Montana (United States)—a state where two-thirds of the population live in rural areas and with a large proportion of tribal residents—to develop novel strategies to make pharmacogenetic testing more broadly available. We established partnerships between University of Montana (UM) and three early adopter sites providing patient-centered care to historically neglected populations. We conducted 45 semi-structured interviews with key stakeholders at each site and solicited participant feedback on the utility of a centralized pharmacogenetic service at UM offering consultations to patients and providers statewide via telehealth. For settings serving rural patients—tribal and non-tribal—participants described healthcare facilities without adequate infrastructure, personnel, and funding to implement pharmacogenetic services. Participants serving tribal communities stressed the need for ethical practices for collecting biospecimens and returning genetic results to patients, largely due to historical and contemporary traumas experienced by tribal populations with regard to genetic research. Participants expressed that pharmacogenetic testing could benefit patients by achieving therapeutic benefit sooner, reducing the risk of side effects, and improving adherence outcomes for patients with limited access to follow-up services in remote areas. Others expressed concern that financial barriers to pharmacogenetic testing for patients of lower socioeconomic status would further exacerbate inequities in care. Participants valued the role of telehealth to deliver pharmacogenetic consults from a centralized service at UM, describing the ability to connect providers and patients to resources and expertise as imperative to driving successful pharmacogenetic implementation. Our results support strategies to improve access to pharmacogenetic testing for neglected patient populations and create opportunities to reduce existing healthcare inequities. By exploring critical challenges for pharmacogenetic implementation focused on serving underserved communities, this work can help guide equitable frameworks to serve as a model for other resource-limited settings looking to initiate pharmacogenetic testing.
Single-cell sequencing of brain tissues reveal the central nervous system’s susceptibility to SARS-CoV-2 and the drug
Authors: Lu Zhichao , Wang Ziheng , Song Zhuhuan , Chen Chen , Ma He , Gong Peipei , Xu Yunzhao
Published: September 2022

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the current COVID-19 pandemic, resulting in a public health crisis that required immediate action. The SARS-CoV-2 virus enters human cells via three receptors, namely cathepsin, angiotensin-converting enzyme 2 (ACE2) and SARS-CoV receptors. Cathepsin destroys the spike protein (S protein), thereby allowing the entry of viral nucleic acid into human host cells.

Methods: Utilizing single-cell transcriptome analysis of brain tissues, the vulnerability of the central nervous system to infection with SARS-CoV-2 in humans was investigated.

Results: ACE2 is mainly expressed in endothelial cells, with the highest levels found in ageing endothelial cells. Drug prediction suggests that (-)-catechin reduces the effects of COVID-19 on the nervous system. Immunohistochemistry analysis showed that ACE2 was mainly expressed in cerebral vessels. Immunofluroscenceresults showed the co-expression of CD31 and ACE2 in human tissues. Western blot further showed that ACE2 expression was higher in old rats than in young rats.

Conclusion: This study provides insight into the mechanism of SARS-CoV-2 brain invasion. Accordingly, patients with neurological symptoms who are infected with SARS-CoV-2 should be given individualised care.
Research progress in endothelial cell injury and repair
Authors: Huang Yongpan , Song Chong , He Jianbin , Li Min
Published: September 2022

Endothelial cells, which are important metabolic and endocrine cells, play an important role in regulating vascular function. The occurrence and development of various cardiovascular and cerebrovascular diseases are associated with endothelial dysfunction. However, the underlying mechanism of vascular endothelial injury is not fully understood. It has been reported that the mechanism of endothelial injury mainly involves inflammation and oxidative stress. Moreover, endothelial progenitor cells are regarded as important contributors in repairing damaged endothelium. Multiple interventions (including chemical drugs and traditional Chinese medicines) exert endothelial protection by decreasing the release of inducing factors, suppressing inflammation and oxidative stress, and preventing endothelial cell senescence.
Identification and verification of hub genes associated with the progression of non-small cell lung cancer by integrated analysis
Authors: Mengyan Xie , Kun Ding , Xinming Jing , Yutian Wei , Yongqian Shu
Published: September 2022

Objectives: Lung cancer is one of the most common cancers worldwide and it is the leading cause of cancer-related mortality. Despite the treatment of patients with non-small cell lung carcinoma (NSCLC) have improved, the molecular mechanisms of NSCLC are still to be further explored.

Materials and Methods: Microarray datasets from the Gene Expression Omnibus (GEO) database were selected to identify the candidate genes associated with tumorigenesis and progression of non-small cell lung carcinoma. The differentially expressed genes (DEGs) were identified by GEO2R. Protein-protein interaction network (PPI) were used to screen out hub genes. The expression levels of hub genes were verified by GEPIA, Oncomine and The Human Protein Atlas (HPA) databases. Survival analysis and receiver operating characteristic (ROC) curve analysis were performed to value the importance of hub genes in NSCLC diagnosis and prognosis. ENCODE and cBioPortal were used to explore the upstream regulatory mechanisms of hub genes. Analysis on CancerSEA Tool, CCK8 assay and colony formation assay revealed the functions of hub genes in NSCLC.

Results: A total of 426 DEGs were identified, including 93 up-regulated genes and 333 down-regulated genes. And nine hub genes (CDC6, KIAA0101, CDC20, BUB1B, CCNA2, NCAPG, KIF11, BUB1 and CDK1) were found to increase with the tumorigenesis, progression and cisplatin resistance of NSCLC, especially EGFR- or KRAS-mutation driven NSCLC. Hub genes were valuable biomarkers for NSCLC, and the overexpression of hub genes led to poor survival of NSCLC patients. Function analysis showed that hub genes played roles in cell cycle and proliferation, and knockdown of hub genes significantly inhibited A549 and SPCA1 cell growth. Further exploration demonstrated that copy number alterations (CNAs) and transcription activation may account for the up-regulation of hub genes.

Conclusion: Hub genes identified in this study provided better understanding of molecular mechanisms within tumorigenesis and progression of NSCLC, and provided potential targets for NSCLC treatment as well.
Pathophysiology and genetics of salt-sensitive hypertension
Authors: Maaliki Dina , Itani Maha M. , Itani Hana A.
Published: September 2022

Most hypertensive cases are primary and heavily associated with modifiable risk factors like salt intake. Evidence suggests that even small reductions in salt consumption reduce blood pressure in all age groups. In that regard, the ACC/AHA described a distinct set of individuals who exhibit salt-sensitivity, regardless of their hypertensive status. Data has shown that salt-sensitivity is an independent risk factor for cardiovascular events and mortality. However, despite extensive research, the pathogenesis of salt-sensitive hypertension is still unclear and tremendously challenged by its multifactorial etiology, complicated genetic influences, and the unavailability of a diagnostic tool. So far, the important roles of the renin-angiotensin-aldosterone system, sympathetic nervous system, and immune system in the pathogenesis of salt-sensitive hypertension have been studied. In the first part of this review, we focus on how the systems mentioned above are aberrantly regulated in salt-sensitive hypertension. We follow this with an emphasis on genetic variants in those systems that are associated with and/or increase predisposition to salt-sensitivity in humans.
Antennae-abundant expression of candidate cytochrome P450 genes associated with odorant degradation in the asian citrus psyllid, Diaphorina citri
Authors: Kuang Yinhui , Xiong Yu , Chen Xue Dong , Yu Xiudao
Published: September 2022

The Asian citrus psyllid, Diaphorina citri, is a notorious pest that is an efficient vector for Candidatus Liberibacter asiaticus (CLas), the causal agent of citrus huanglongbing (HLB). The olfactory system of insects is crucial for foraging and mating behavior. Antennae-abundant odorant degrading enzymes (ODEs), including cytochrome P450 (CYPs), are important in degrading redundant odorant molecules to recover the insect olfactory. In this study, to isolate the antennal CYP genes of D. citri, we generated four transcriptomes from female/male antennae and body through deep sequencing of RNA libraries. Seven DcCYP genes preferentially expressed in antennae were first identified by comparing the antennal and body transcriptomes. Phylogenetic analysis grouped four DcCYPs (DcCYP6a13, DcCYP6j1, DcCYP6k1, and DcCYP6a2) into the CYP3 class, whereas DcCYP4d2, DcCYP4c62, and DcCYP4d8 were clustered in the CYP4 clade. qRT-PCR analyses across developmental stages and tissues showed they were antennae-abundant in both genders and constantly expressed from the first instar nymph to the adult. The results presented here highlight the isolation and expression of CYP genes in D. citri antennae, providing valuable insights into their putative role in odorant degradation.
Beauty and the pathogens: A leaf-less control presents a better image of Cymbidium orchids defense strategy
Authors: Ahmad Sagheer , Chen Guizhen , Huang Jie , Yang Kang , Hao Yang , Zhou Yuzhen , Zhao Kai , Lan Siren , Liu Zhongjian , Peng Donghui
Published: September 2022

Biological control is a safe way of combating plant diseases using the living organisms. For the precise use of microbial biological control agents, the genetic information on the hypersensitive response (HR), and defense-related gene induction pathways of plants are necessary. Orchids are the most prominent stakeholders of floriculture industry, and owing to their long-awaited flowering pattern, disease control is imperative to allow healthy vegetative growth that spans more than 2 years in most of the orchids. We observed leaf-less flowering in three orchid species (Cymbidium ensifolium, C. goeringii and C. sinense). Using these materials as reference, we performed transcriptome profiling for healthy leaves from non-infected plants to identify genes specifically involved in plant-pathogen interaction pathway. For this pathway, a total of 253 differentially expressed genes (DEGs) were identified in C. ensifolium, 189 DEGs were identified in C. goeringii and 119 DEGs were found in C. sinense. These DEGs were mainly related to bacterial secretion systems, FLS2, CNGCs and EFR, regulating HR, stomatal closure and defense-related gene induction. FLS2 (LRR receptor-like serine/threonine kinase) contained the highest number of DEGs among three orchid species, followed by calmodulin. Highly upregulated gene sets were found in C. sinense as compared to other species. The great deal of DEGs, mainly the FLS2 and EFR families, related to defense and immunity responses can effectively direct the future of biological control of diseases for orchids.
Tonoplast proton pumps regulate nuclear spacing of female gametophytes via mediating polar auxin transport in Arabidopsis
Authors: Jiang Yu-Tong , Zheng Ji-Xuan , Li Rong-Han , Wang Yu-Chen , Shi Jianxin , Ferjani Ali , Lin Wen-Hui
Published: September 2022

The vacuole is an important organelle with multiple functions in plants, and the tonoplast that wraps the vacuole also plays essential roles in intracellular trafficking and ion homeostasis. Previous studies found that tonoplast proton pumps regulate embryo development and morphogenesis through their effects on vacuole biogenesis and distribution, as well as polar auxin transport and concomitant auxin gradient. However, the precise roles of the tonoplast proton pumps in gametophyte development remain unclear. Here we demonstrated that the lack of two types of tonoplast proton pumps or the absence of V-ATPase alone leads to abnormal development and nuclear localization of female gametophyte (FG), and slowed endosperm nuclei division after fertilization of the central cell. We further revealed that V-ATPase regulates auxin levels in ovules through coordinating the content and localization of PIN-FORMED 1 (PIN1) protein, hence influencing nuclear spacing between centra cell and egg cell, and subsequent endosperm development. Collectively, our findings revealed a crucial role of V-ATPase in auxin-mediated FG development in Arabidopsis and expanded our understanding of the functions of tonoplast proton pumps in seed plants reproductive development.
Identification of miRNAs and their target genes associated with improved maize seed vigor induced by gibberellin
Authors: Jin Yunqian , Wang Bin , Tian Lei , Zhao Linxi , Guo Shulei , Zhang Hengchao , Xu Lengrui , Han Zanping
Published: September 2022

High seed vigor is crucial for agricultural production owing to its potential in high quality and yield of crops and a better understanding of the molecular mechanism associated with maize seed vigor is highly necessary. To better understand the involvement and regulatory mechanism of miRNAs correlated with maize seed vigor, small RNAs and degradome sequencing of two inbred lines Yu537A and Yu82 were performed. A total of 791 mature miRNAs were obtained with different expressions, among of which 505 miRNAs were newly identified and the rest miRNAs have been reported before by comparing the miRNAs with the sequences in miRbase database. Analysis of miRNA families showed maize seeds contain fewer miRNA families and larger miRNA families compared with animals, indicating that functions of miRNAs in maize seeds were more synergistic than animals. Degradome sequencing was used to identify the targets of miRNAs and the results showed a total of 6,196 targets were obtained. Function analysis of differentially expressed miRNAs and targets showed Glycan degradation and galactose metabolism were closely correlated with improved maize seed vigor. These findings provide valuable information to understand the involvement of miRNAs with maize seed vigor and these putative genes will be valuable resources for improving the seed vigor in future maize breeding.
Comprehensive analysis of the LHT gene family in tobacco and functional characterization of NtLHT22 involvement in amino acids homeostasis
Authors: Li Zhaowu , Gao Junping , Wang Shuaibin , Xie Xiaodong , Wang Zhangying , Peng Yu , Yang Xiaonian , Pu Wenxuan , Wang Yaofu , Fan Xiaorong
Published: September 2022

Amino acids are vital nitrogen (N) sources for plant growth, development, and yield. The uptake and translocation of amino acids are mediated by amino acid transporters (AATs). The AATs family including lysine-histidine transporters (LHTs), amino acid permeases (AAPs), and proline transporters (ProTs) subfamilies have been identified in various plants. However, little is known about these genes in tobacco. In this study, we identified 23 LHT genes, the important members of AATs, in the tobacco genome. The gene structure, phylogenetic tree, transmembrane helices, chromosomal distribution, cis-regulatory elements, and expression profiles of NtLHT genes were systematically analyzed. Phylogenetic analysis divided the 23 NtLHT genes into two conserved subgroups. Expression profiles confirmed that the NtLHT genes were differentially expressed in various tissues, indicating their potential roles in tobacco growth and development. Cis-elements analysis of promoters and expression patterns after stress treatments suggested that NtLHT genes probable participate in abiotic stress responses of tobacco. In addition, Knock out and overexpression of NtLHT22 changed the amino acids homeostasis in the transgenic plants, the contents of amino acids were significantly decreased in NtLHT22 overexpression plants than wild-type. The results from this study provide important information for further studies on the molecular functions of the NtLHT genes.
The regulatory role of abscisic acid on cadmium uptake, accumulation and translocation in plants
Authors: Shen Chuang , Yang Yu-Mo , Sun Ying-Fang , Zhang Man , Chen Xiao-Jing , Huang Ying-Ying
Published: September 2022

To date, Cd contamination of cropland and crops is receiving more and more attention around the world. As a plant hormone, abscisic acid (ABA) plays an important role in Cd stress response, but its effect on plant Cd uptake and translocation varies among plant species. In some species, such as Arabidopsis thaliana, Oryza sativa, Brassica chinensis, Populus euphratica, Lactuca sativa, and Solanum lycopersicum, ABA inhibits Cd uptake and translocation, while in other species, such as Solanum photeinocarpum and Boehmeria nivea, ABA severs the opposite effect. Interestingly, differences in the methods and concentrations of ABA addition also triggered the opposite result of Cd uptake and translocation in Sedum alfredii. The regulatory mechanism of ABA involved in Cd uptake and accumulation in plants is still not well-established. Therefore, we summarized the latest studies on the ABA synthesis pathway and comparatively analyzed the physiological and molecular mechanisms related to ABA uptake, translocation, and detoxification of Cd in plants at different ABA concentrations or among different species. We believe that the control of Cd uptake and accumulation in plant tissues can be achieved by the appropriate ABA application methods and concentrations in plants.