bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitamin D supplementation improved physical growth and neurologic development of Preterm Infants receiving Nesting Care in the neonatal Intensive Care Unit
Authors: Tang Wei-qin , Ma Ning , Meng Li-ying , Luo Ya-wen , Wang Ying-jie , Zhang Di
Published: May 2023

Objective

To study the effects of vitamin D supplementation on physical growth and neurologic development of very preterm infants receiving nesting intervention in the neonatal intensive care unit (NICU).

Methods

A total of 196 preterm infants had been hospitalized in NICU with the gestational age (GA) between 28 and 32 weeks. Among them, 98 preterm infants received nesting intervention, and the other 98 cases received both nesting and vitamin D supplementation (400 IU). The interventions were continued until 36 weeks postmenstrual age (PMA). The 25(OH)D serum levels, anthropometric parameters, and Premie-Neuro (PN) scores were compared at 36 weeks PMA.

Results

Higher median serum level of 25(OH)D was found in the nesting + vitamin D [38.40 ng/mL (IQR: 17.20 ~ 70.88) ng/mL] as compared to the nesting group [15.95 ng/mL (IQR: 10.80 ~ 24.30) ng/mL] at 36 weeks PMA. Besides, infants receiving combined nesting intervention and vitamin D supplementation had less proportion of vitamin D deficiency [VDD, 25(OH)D levels < 20 ng/mL] than those receiving nesting intervention alone. After intervention, the anthropometric parameters of infants, including weight, length, BMI and head circumference were improved in the nesting + vitamin D group as compared to the nesting group at 36 weeks PMA, with higher scores of neurological, movement and responsiveness.

Conclusions

Vitamin D supplementation effectively decreased the prevalence of VDD and led to higher concentrations of 25(OH)D at 36 weeks PMA. This was one more study that supported the necessity of vitamin D supplementation to improve physical growth and neurologic development of preterm-born newborns who received nesting intervention in the NICU.
The impact of PTSD on risk of cardiometabolic diseases: a national patient cohort study in Norway
Authors: Roer Grethe Emilie , Lien Lars , Bolstad Ingeborg , Aaseth Jan O. , Abebe Dawit Shawel
Published: May 2023

Background

Posttraumatic stress disorder (PTSD) is associated with cardiometabolic diseases, concurrent anxiety, alcohol use disorder and depression. The relationship between PTSD and cardiometabolic diseases are still unclear, and less is known about the effects of socioeconomic status, comorbid anxiety, comorbid alcohol use disorder and comorbid depression. The study, therefore, aims to examine the risk of developing cardiometabolic diseases including type 2 diabetes mellitus over time in PTSD patients, and to what extent socioeconomic status, comorbid anxiety, comorbid alcohol use disorder and comorbid depression attenuate associations between PTSD and risk of developing cardiometabolic diseases.

Method

A retrospective, register-based cohort study with 6-years follow-up of adult (> 18 years) PTSD patients (N = 7 852) compared with the general population (N = 4 041 366), was performed. Data were acquired from the Norwegian Patient Registry and Statistic Norway. Cox proportional regression models were applied to estimate hazard ratios (HRs) (99% confidence intervals) of cardiometabolic diseases among PTSD patients.

Results

Significantly (p < 0.001) higher age and gender adjusted HRs were disclosed for all cardiometabolic diseases among PTSD patients compared to the population without PTSD, with a variation in HR from 3.5 (99% CI 3.1–3.9) for hypertensive diseases to HR = 6.5 (5.7–7.5) for obesity. When adjusted for socioeconomic status and comorbid mental disorders, reductions were observed, especially for comorbid depression, for which the adjustment resulted in HR reduction of about 48.6% for hypertensive diseases and 67.7% for obesity.

Conclusions

PTSD was associated with increased risk of developing cardiometabolic diseases, though attenuated by socioeconomic status and comorbid mental disorders. Health care professionals should be attentive towards the burden and increased risk that low socioeconomic status and comorbid mental disorders may represent for PTSD patients’ cardiometabolic health.
Sedative and adverse effect comparison between oral midazolam and nitrous oxide inhalation in tooth extraction: a meta-analysis
Authors: Li Xia , Liu Yali , Li Chengjun , Wang Jiexue
Published: May 2023

Objective

Oral midazolam and nitrous oxide inhalation were commonly used sedative and analgesic techniques during tooth extraction. It is still controversial whether oral midazolam can replace the nitrous oxide inhalation for sedative and analgesic treatment of tooth extraction. Therefore, we conducted this study in order to provide a reference for doctors to choose effective sedative and analgesic treatment in tooth extraction.

Methods

We searched the Chinese and English databases including PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, Wanfang and VIP information databases.

Results

Through this meta-analysis, we found that the success rate of sedation and analgesia treatment with oral midazolam during tooth extraction was 75.67% and the incidence of adverse reactions was 21.74%. The success rate of sedation and analgesia treatment using nitrous oxide inhalation during tooth extraction was 93.6% and the incidence of adverse reactions was 3.95%.

Conclusion

The use of nitrous oxide inhalation for sedation and analgesia during tooth extraction is very effective, and oral midazolam can be used as an alternative to nitrous oxide inhalation.
Quality of survey-based study reports in dentistry
Authors: Mattos-Vela Manuel Antonio , Evaristo-Chiyong Teresa Angélica , Siquero-Vera Kariem
Published: May 2023

Background

Surveys are a widely used research method in dentistry in different specialities. The study aimed to determine the quality of survey-based research reports published in dentistry journals from 2015 to 2019.

Methods

A cross-sectional descriptive research study was conducted. The report quality assessment was carried out through the SURGE guideline modified by Turk et al. Four journals indexed in the Web of Science were selected: BMC Oral Health, American Journal of Orthodontics and Dentofacial Orthopedics, Journal of Dental Education, and Journal of Applied Oral Science. The selection of articles was made using the PubMed database considering the following search words: questionnaire OR survey, two trained reviewers applied the guideline to the selected articles, and the controversies were solved by discussion and consensus.

Results

A total of 881 articles were identified, of which 99 met the selection criteria and were included in the study. The best-reported items (n = 99) were four: the two that described the introduction of a study, the results reflecting and concerning the study objectives, and the review by an ethics committee. Five items were poorly reported: to declare the incentives to study participants (n = 93), three items on the description of statistical analyses (n = 99, 99, and 94), and information on how nonrespondents differed from respondents (n = 92).

Conclusions

There is a moderate quality of reporting of all aspects that should be considered in survey-based studies in dentistry journals. Poorly reported criteria were found mainly in the statistical analysis.
The survival impact of adjuvant radiotherapy and chemotherapy in patients with non-endometrioid endometrial carcinomas: a PSM-IPTW analysis based on SEER database
Authors: Hao Zhimin , Yu Yangli
Published: May 2023

Purpose

To investigate outcomes of adjuvant treatments for non-endometrioid endometrial carcinomas (NEEC), as previous studies are limited by its rarity and heterogeneity.

Patients and methods

Patients with endometrial serous carcinoma (SC), clear cell carcinoma (CCC) and carcinosarcoma were identified between 2004 and 2018 from SEER database. Propensity score matching (PSM) along with inverse probability treatment weighting (IPTW) technique were employed to balance confounding factors. Multivariate, exploratory subgroup and sensitivity analyses were conducted to evaluate the impact of adjuvant treatment on overall survival (OS) and cause-specific survival (CSS).

Results

The cohort comprised 5577 serous, 977 clear cell, and 959 carcinosarcomas. Combined chemotherapy and radiotherapy (CRT), chemotherapy alone, and radiotherapy alone were respectively administered in 42.21%, 47.27% and 10.58% of the whole cohort. Prior to adjusting, chemotherapy plus brachytherapy yielded the most beneficial effect among various strategies. After PSM-IPTW adjustment, CRT still demonstrated beneficial effect on OS and CSS. Subgroup analysis indicated CRT improved survival among various TNM stages, particularly with uterine carcinosarcoma. In the sensitivity analyses for serous histology, brachytherapy with or without chemotherapy appeared to benefit stage I-II patients. In stage III-IV SC patients, chemotherapy plus brachytherapy was still associated with improved survival outcomes. When nodal metastases were identified, additional external beam radiotherapy (EBRT) to CT was more utilized with survival improvement.

Conclusion

In NEEC patients, combined CRT yielded beneficial effects than any single mode. Both chemotherapy and brachytherapy promoted survival in early stage SC patients. Late stage SC patients may benefit from chemotherapy plus either EBRT or brachytherapy.
Understanding students’ motivations for participating in a mindfulness course: a qualitative analysis of medical students’ views
Authors: Brami Cloé , Sultan Serge , Robieux Léonore , Piot Marie-Aude , Gartili Honorine , Zenasni Franck
Published: May 2023

Objectives

Improving medical students’ wellbeing and empowerment through curricular activities is a topic of interest worldwide. Mindfulness-based interventions (MBIs) are increasingly implemented in medical education often as part of elective courses. To better understand training outcomes and adjust curriculum to students’ needs, we will explore why will medical students participate in meditation-based education?

Methods

We analyzed 29 transcripts from the first session of an 8-week MBSR program offered to medical students in French. Transcripts were coded and analyzed using a qualitative content thematic analysis and the constant comparison method.

Results

Analyses resulted in three themes describing students’ motivation: (1) Medical education and the physician’s role, i.e. improving interpersonal skills, acquiring skills oriented toward a more integrative medicine, being more productive in a highly competitive context. (2) Caring for my health i.e. aiming at stress reduction, emotion regulation, and improving self-compassion. (3) A quest for meaning, i.e. optimizing meaning of care, and meaning of life.

Conclusion

The results highlight the congruence between the perceived motivations and the evidence on the effect of mindfulness on self-care, the development of humanistic medical skills, and the meaning of care. Some findings raise the issue of the limits of using mindfulness to enhance one’s productivity. Notably, participants articulated the need for self-care as in mindfulness training, with the ability to care for others.
Network pharmacology and molecular docking study for biological pathway detection of cytotoxicity of the yellow jasmine flowers
Authors: El-Hawary Seham S. , Albalawi Marzough A , Montasser Ayat O. S. , Ahmed Shaimaa R. , Qasim Sumera , Shati Ali A. , Alfaifi Mohammad Y. , Elbehairi Serag Eldin I. , Hassan Omnia F. , Sadakah Abdelfattah A. , Mokhtar Fatma A.
Published: May 2023

Background

The yellow jasmine flower (Jasminum humile L.) is a fragrant plant belonging to the Oleaceae family with promising phytoconstituents and interesting medicinal uses. The purpose of this study was to characterize the plant metabolome to identify the potential bioactive agents with cytotoxic effects and the underlying mechanism of cytotoxic activity.

Methods

First, HPLC–PDA-MS/MS was used to identify the potential bioactive compounds in the flowers. Furthermore, we assessed the cytotoxic activity of the flower extract against breast cancer (MCF-7) cell line using MTT assay followed by the cell cycle, DNA-flow cytometry, and Annexin V-FITC analyses alongside the effect on reactive oxygen species (ROS). Finally, Network pharmacology followed by a molecular docking study was performed to predict the pathways involved in anti-breast cancer activity.

Results

HPLC–PDA-MS/MS tentatively identified 33 compounds, mainly secoiridoids. J. humile extract showed a cytotoxic effect on MCF-7 breast cancer cell line with IC50 value of 9.3 ± 1.2 µg/mL. Studying the apoptotic effect of J. humile extract revealed that it disrupts G2/M phase in the cell cycle, increases the percentage of early and late apoptosis in Annexin V-FTIC, and affects the oxidative stress markers (CAT, SOD, and GSH-R). Network analysis revealed that out of 33 compounds, 24 displayed interaction with 52 human target genes. Relationship between compounds, target genes, and pathways revealed that J. humile exerts its effect on breast cancer by altering, Estrogen signaling pathway, HER2, and EGFR overexpression. To further verify the results of network pharmacology, molecular docking was performed with the five key compounds and the topmost target, EGFR. The results of molecular docking were consistent with those of network pharmacology.

Conclusion

Our findings suggest that J. humile suppresses breast cancer proliferation and induces cell cycle arrest and apoptosis partly by EGFR signaling pathway, highlighting J. humile as a potential therapeutic candidate against breast cancer.
Identification of three capsule depolymerases in a bacteriophage infecting Klebsiella pneumoniae capsular types K7, K20, and K27 and therapeutic application
Authors: Wu Jia-Wen , Wang Jin-Town , Lin Tzu-Lung , Liu Ya-Zhu , Wu Lii-Tzu , Pan Yi-Jiun
Published: May 2023

Background

Klebsiella pneumoniae capsular types K1, K2, K5, K20, K54, and K57 are prevalent hypervirulent types associated with community infections, and worrisomely, hypervirulent strains that acquired drug resistance have been found. In the search for alternative therapeutics, studies have been conducted on phages that infect K. pneumoniae K1, K2, K5, and K57-type strains and their phage-encoded depolymerases. However, phages targeting K. pneumoniae K20-type strains and capsule depolymerases capable of digesting K20-type capsules have rarely been reported. In this study, we characterized a phage that can infect K. pneumoniae K20-type strains, phage vB_KpnM‐20.

Methods

A phage was isolated from sewage water in Taipei, Taiwan, its genome was analyzed, and its predicted capsule depolymerases were expressed and purified. The host specificity and capsule-digesting activity of the capsule depolymerases were determined. The therapeutic effect of the depolymerase targeting K. pneumoniae K20-type strains was analyzed in a mouse infection model.

Results

The isolated Klebsiella phage, vB_KpnM‐20, infects K. pneumoniae K7, K20, and K27-type strains. Three capsule depolymerases, K7dep, K20dep, and K27dep, encoded by the phage were specific to K7, K20, and K27-type capsules, respectively. K20dep also recognized Escherichia coli K30-type capsule, which is highly similar to K. pneumoniae K20-type. The survival of K. pneumoniae K20-type-infected mice was increased following administration of K20dep.

Conclusions

The potential of capsule depolymerase K20dep for the treatment of K. pneumoniae infections was revealed using an in vivo infection model. In addition, K7dep, K20dep, and K27dep capsule depolymerases could be used for K. pneumoniae capsular typing.
Serum metabolomic signatures of fatty acid oxidation defects differentiate host-response subphenotypes of acute respiratory distress syndrome
Authors: Suber Tomeka L. , Wendell Stacy G. , Mullett Steven J. , Zuchelkowski Benjamin , Bain William , Kitsios Georgios D. , McVerry Bryan J. , Ray Prabir , Ray Anuradha , Mallampalli Rama K. , Zhang Yingze , Shah Faraaz , Nouraie Seyed Mehdi , Lee Janet S.
Published: May 2023

Background

Fatty acid oxidation (FAO) defects have been implicated in experimental models of acute lung injury and associated with poor outcomes in critical illness. In this study, we examined acylcarnitine profiles and 3-methylhistidine as markers of FAO defects and skeletal muscle catabolism, respectively, in patients with acute respiratory failure. We determined whether these metabolites were associated with host-response ARDS subphenotypes, inflammatory biomarkers, and clinical outcomes in acute respiratory failure.

Methods

In a nested case–control cohort study, we performed targeted analysis of serum metabolites of patients intubated for airway protection (airway controls), Class 1 (hypoinflammatory), and Class 2 (hyperinflammatory) ARDS patients (N = 50 per group) during early initiation of mechanical ventilation. Relative amounts were quantified by liquid chromatography high resolution mass spectrometry using isotope-labeled standards and analyzed with plasma biomarkers and clinical data.

Results

Of the acylcarnitines analyzed, octanoylcarnitine levels were twofold increased in Class 2 ARDS relative to Class 1 ARDS or airway controls (P = 0.0004 and < 0.0001, respectively) and was positively associated with Class 2 by quantile g-computation analysis (P = 0.004). In addition, acetylcarnitine and 3-methylhistidine were increased in Class 2 relative to Class 1 and positively correlated with inflammatory biomarkers. In all patients within the study with acute respiratory failure, increased 3-methylhistidine was observed in non-survivors at 30 days (P = 0.0018), while octanoylcarnitine was increased in patients requiring vasopressor support but not in non-survivors (P = 0.0001 and P = 0.28, respectively).

Conclusions

This study demonstrates that increased levels of acetylcarnitine, octanoylcarnitine, and 3-methylhistidine distinguish Class 2 from Class 1 ARDS patients and airway controls. Octanoylcarnitine and 3-methylhistidine were associated with poor outcomes in patients with acute respiratory failure across the cohort independent of etiology or host-response subphenotype. These findings suggest a role for serum metabolites as biomarkers in ARDS and poor outcomes in critically ill patients early in the clinical course.
Drug-coated balloon-based versus drug-eluting stent-only revascularization in patients with diabetes and multivessel coronary artery disease
Authors: Her Ae-Young , Shin Eun-Seok , Kim Sunwon , Kim Bitna , Kim Tae-Hyun , Sohn Chang-Bae , Choi Byung Joo , Park Yongwhi , Cho Jung Rae , Jeong Young-Hoon
Published: May 2023

Background

Data on drug-coated balloon (DCB) treatment in the context of diabetes mellitus (DM) and multivessel coronary artery disease (CAD) are limited. We aimed to investigate the clinical impact of DCB-based revascularization on percutaneous coronary intervention (PCI) in patients with DM and multivessel CAD.

Methods

A total of 254 patients with multivessel disease (104 patients with DM) successfully treated with DCB alone or combined with drug-eluting stent (DES) were retrospectively enrolled (DCB-based group) and compared with 254 propensity-matched patients treated with second-generation DES from the PTRG-DES registry (n = 13,160 patients) (DES-only group). Major adverse cardiovascular events (MACE) comprised cardiac death, myocardial infarction, stroke, stent or target lesion thrombosis, target vessel revascularization, and major bleeding at 2 years.

Results

The DCB-based group was associated with a reduced risk of MACE in patients with DM (hazard ratio [HR] 0.19, 95% confidence interval [CI] 0.05–0.68, p = 0.003], but not in those without DM (HR 0.52, 95% CI 0.20–1.38, p = 0.167) at the 2-year follow-up. In patients with DM, the risk of cardiac death was lower in the DCB-based group than the DES-only group, but not in those without DM. In both patients with or without DM, the burdens of DES and small DES (less than 2.5 mm) used were lower in the DCB-based group than in the DES-only group.

Conclusions

In multivessel CAD, the clinical benefit of a DCB-based revascularization strategy appears to be more evident in patients with DM than in those without DM after 2 years of follow-up. (Impact of Drug-Coated Balloon Treatment in De Novo Coronary Lesion; NCT04619277)
Recent advances in the detection of glioblastoma, from imaging-based methods to proteomics and biosensors: A narrative review
Authors: Hosseini Arianaz , Ashraf Hami , Rahimi Fatemeh , Alipourfard Iraj , Alivirdiloo Vahid , Hashemi Behnam , Yazdani Yalda , Ghazi Farhood , Eslami Majid , Ameri Shah Reza Mahdieh , Dadashpour Mehdi
Published: May 2023

Glioblastoma (GBM) is an aggressive type of cancer that originates in the cells called astrocytes, which support the functioning of nerve cells. It can develop in either the brain or the spinal cord and is also known as glioblastoma multiform. GBM is a highly aggressive cancer that can occur in either the brain or spinal cord. The detection of GBM in biofluids offers potential advantages over current methods for diagnosing and treatment monitoring of glial tumors. Biofluid-based detection of GBM focuses on identifying tumor-specific biomarkers in blood and cerebrospinal fluid. To date, different methods have been used to detect biomarkers of GBM, ranging from various imaging techniques to molecular approaches. Each method has its own strengths and weaknesses. The present review aims to scrutinize multiple diagnostic methods for GBM, with a focus on proteomics methods and biosensors. In other words, this study aims to provide an overview of the most significant research findings based on proteomics and biosensors for the diagnosis of GBM.
Adherence to 14-day radical cure for Plasmodium vivax malaria in Papua, Indonesia: a mixed-methods study
Authors: Rahmalia Annisa , Poespoprodjo Jeanne Rini , Landuwulang Chandra U. R. , Ronse Maya , Kenangalem Enny , Burdam Faustina H. , Thriemer Kamala , Devine Angela , Price Ric N. , Peeters Grietens Koen , Ley Benedikt , Gryseels Charlotte
Published: May 2023

Background

Reducing the risk of recurrent Plasmodium vivax malaria is critical for malaria control and elimination. Primaquine (PQ) is the only widely available drug against P. vivax dormant liver stages, but is recommended as a 14-day regimen, which can undermine adherence to a complete course of treatment.

Methods

This is a mixed-methods study to assess socio-cultural factors influencing adherence to a 14-day PQ regimen in a 3-arm, treatment effectiveness trial in Papua, Indonesia. The qualitative strand, consisting of interviews and participant observation was triangulated with a quantitative strand in which trial participants were surveyed using a questionnaire.

Results

Trial participants differentiated between two types of malaria: tersiana and tropika, equivalent to P. vivax and Plasmodium falciparum infection, respectively. The perceived severity of both types was similar with 44.0% (267/607) perceiving tersiana vs. 45.1% (274/607) perceiving tropika as more severe. There was no perceived differentiation whether malaria episodes were due to a new infection or relapse; and 71.3% (433/607) acknowledged the possibility of recurrence. Participants were familiar with malaria symptoms and delaying health facility visit by 1–2 days was perceived to increase the likelihood of a positive test. Prior to health facility visits, symptoms were treated with leftover drugs kept at home (40.4%; 245/607) or bought over the counter (17.0%; 103/607). Malaria was considered to be cured with ‘blue drugs’ (referring to dihydroartemisinin-piperaquine). Conversely, ‘brown drugs,’ referring to PQ, were not considered malaria medication and instead were perceived as supplements. Adherence to malaria treatment was 71.2% (131/184), in the supervised arm, 56.9% (91/160) in the unsupervised arm and 62.4% (164/263) in the control arm; p = 0.019. Adherence was 47.5% (47/99) among highland Papuans, 51.7% (76/147) among lowland Papuans, and 72.9% (263/361) among non-Papuans; p < 0.001.

Conclusion

Adherence to malaria treatment was a socio-culturally embedded process during which patients (re-)evaluated the characteristics of the medicines in relation to the course of the illness, their past experiences with illness, and the perceived benefits of the treatment. Structural barriers that hinder the process of patient adherence are crucial to consider in the development and rollout of effective malaria treatment policies.
Isoliensinine from Cissampelos pariera rhizomes exhibits potential gametocytocidal and anti-malarial activities against Plasmodium falciparum clinical isolates
Authors: Muema Jackson M. , Mutunga James M. , Obonyo Meshack A. , Getahun Merid N. , Mwakubambanya Ramadhan S. , Akala Hoseah M. , Cheruiyot Agnes C. , Yeda Redemptah A. , Juma Dennis W. , Andagalu Ben , Johnson Jaree L. , Roth Amanda L. , Bargul Joel L.
Published: May 2023

Background

The unmet demand for effective malaria transmission-blocking agents targeting the transmissible stages of Plasmodium necessitates intensive discovery efforts. In this study, a bioactive bisbenzylisoquinoline (BBIQ), isoliensinine, from Cissampelos pariera (Menispermaceae) rhizomes was identified and characterized for its anti-malarial activity.

Methods

Malaria SYBR Green I fluorescence assay was performed to evaluate the in vitro antimalarial activity against D6, Dd2, and F32-ART5 clones, and immediate ex vivo (IEV) susceptibility for 10 freshly collected P. falciparum isolates. To determine the speed- and stage-of-action of isoliensinine, an IC50 speed assay and morphological analyses were performed using synchronized Dd2 asexuals. Gametocytocidal activity against two culture-adapted gametocyte-producing clinical isolates was determined using microscopy readouts, with possible molecular targets and their binding affinities deduced in silico.

Results

Isoliensinine displayed a potent in vitro gametocytocidal activity at mean IC50gam values ranging between 0.41 and 0.69 µM for Plasmodium falciparum clinical isolates. The BBIQ compound also inhibited asexual replication at mean IC50Asexual of 2.17 µM, 2.22 µM, and 2.39 µM for D6, Dd2 and F32-ART5 respectively, targeting the late-trophozoite to schizont transition. Further characterization demonstrated a considerable immediate ex vivo potency against human clinical isolates at a geometric mean IC50IEV = 1.433 µM (95% CI 0.917–2.242). In silico analyses postulated a probable anti-malarial mechanism of action by high binding affinities for four mitotic division protein kinases; Pfnek1, Pfmap2, Pfclk1, and Pfclk4. Additionally, isoliensinine was predicted to possess an optimal pharmacokinetics profile and drug-likeness properties.

Conclusion

These findings highlight considerable grounds for further exploration of isoliensinine as an amenable scaffold for malaria transmission-blocking chemistry and target validation.
EZH2 mediated metabolic rewiring promotes tumor growth independently of histone methyltransferase activity in ovarian cancer
Authors: Chen Jianfeng , Hong Jing Han , Huang Yulin , Liu Shini , Yin Jiaxin , Deng Peng , Sun Yichen , Yu Zhaoliang , Zeng Xian , Xiao Rong , Chan Jason Yongsheng , Guan Peiyong , Wang Yali , Wang Peili , Liu Lizhen , Wen Shijun , Yu Qiang , Ong Choon Kiat , Teh Bin-Tean , Xiong Ying , Tan Jing
Published: May 2023

Background

Enhancer of zeste homolog 2 (EZH2), the key catalytic subunit of polycomb repressive complex 2 (PRC2), is overexpressed and plays an oncogenic role in various cancers through catalysis-dependent or catalysis-independent pathways. However, the related mechanisms contributing to ovarian cancer (OC) are not well understood.

Methods

The levels of EZH2 and H3K27me3 were evaluated in 105 OC patients by immunohistochemistry (IHC) staining, and these patients were stratified based on these levels. Canonical and noncanonical binding sites of EZH2 were defined by chromatin immunoprecipitation sequencing (ChIP-Seq). The EZH2 solo targets were obtained by integrative analysis of ChIP-Seq and RNA sequencing data. In vitro and in vivo experiments were performed to determine the role of EZH2 in OC growth.

Results

We showed that a subgroup of OC patients with high EZH2 expression but low H3K27me3 exhibited the worst prognosis, with limited therapeutic options. We demonstrated that induction of EZH2 degradation but not catalytic inhibition profoundly blocked OC cell proliferation and tumorigenicity in vitro and in vivo. Integrative analysis of genome-wide chromatin and transcriptome profiles revealed extensive EZH2 occupancy not only at genomic loci marked by H3K27me3 but also at promoters independent of PRC2, indicating a noncanonical role of EZH2 in OC. Mechanistically, EZH2 transcriptionally upregulated IDH2 to potentiate metabolic rewiring by enhancing tricarboxylic acid cycle (TCA cycle) activity, which contributed to the growth of OC.

Conclusions

These data reveal a novel oncogenic role of EZH2 in OC and identify potential therapeutic strategies for OC by targeting the noncatalytic activity of EZH2.
Novel plant-derived exosome-like nanovesicles from Catharanthus roseus: preparation, characterization, and immunostimulatory effect via TNF-α/NF-κB/PU.1 axis
Authors: Ou Xiaozheng , Wang Haoran , Tie Huilin , Liao Jiapei , Luo Yuanyuan , Huang Weijuan , Yu Rongmin , Song Liyan , Zhu Jianhua
Published: May 2023

Background

Plant-derived exosomes-like nanovesicles (PDENs) have been found to be advantageous in disease treatment and drug delivery, but research on their biogenesis, compositional analysis, and key marker proteins is still in its infancy, which limits the standardized production of PDENs. Efficient preparation of PDENs continues to be a major challenge.

Results

Novel PDENs-based chemotherapeutic immune modulators, Catharanthus roseus (L.) Don leaves-derived exosome-like nanovesicles (CLDENs) were isolated from apoplastic fluid. CLDENs were membrane structured vesicles with a particle size of 75.51 ± 10.19 nm and a surface charge of −21.8 mV. CLDENs exhibited excellent stability, tolerating multiple enzymatic digestions, resisting extreme pH environments, and remaining stable in the gastrointestinal simulating fluid. Biodistribution experiments showed that CLDENs could be internalized by immune cells, and targeted at immune organs after intraperitoneal injection. The lipidomic analysis revealed CLDENs’ special lipid composition, which contained 36.5% ether-phospholipids. Differential proteomics supported the origin of CLDENs in multivesicular bodies, and six marker proteins of CLDENs were identified for the first time. 60 ~ 240 μg/ml of CLDENs promoted the polarization and phagocytosis of macrophages as well as lymphocyte proliferation in vitro. Administration of 20 mg/kg and 60 mg/kg of CLDENs alleviated white blood cell reduction and bone marrow cell cycle arrest in immunosuppressive mice induced by cyclophosphamide. CLDENs strongly stimulated the secretion of TNF-α, activated NF-κB signal pathway and increased the expression of the hematopoietic function-related transcription factor PU.1 both in vitro and in vivo. To ensure a steady supply of CLDENs, plant cell culture systems of C. roseus were established to provide CLDENs-like nanovesicles which had similar physical properties and biological activities. Gram-level nanovesicles were successfully obtained from the culture medium, and the yield was three times as high as the original.

Conclusions

Our research supports the use of CLDENs as a nano-biomaterial with excellent stability and biocompatibility, and for post-chemotherapy immune adjuvant therapy applications.

Graphical Abstract
Intracorporeal versus extracorporeal anastomosis in laparoscopic right colectomy: a retrospective study
Authors: Chen Fangqian , Lv Zeping , Feng Wenqing , Xu Zhuoqing , Miao Yiming , Xu Zifeng , Zhang Yuchen , Gao Han , Zheng Minhua , Zong Yaping , Zhao Jingkun , Lu Aiguo
Published: May 2023

Background

The surgical procedure for laparoscopic right colectomy (LRC) is not standardized. Some published studies show the superiority of ileocolic anastomosis (IIA), but the evidence so far is insufficient. This study aimed to investigate the potential advantages in postoperative recovery and safety of IIA in LRC.

Methods

A total of 114 patients who underwent LRC with IIA (n = 58) or extracorporeal ileocolic anastomosis (EIA, n = 56) between January 2019 and September 2021 were enrolled. We collected certain factors as clinical features, intraoperative characteristics, oncological outcomes, postoperative recovery, and short-term outcomes. Our primary outcome was time to gastrointestinal (GI) function recovery. Secondary outcomes were postoperative complications within 30 days, postoperative pain, and length of hospital stay.

Results

Faster GI recovery and less postoperative pain were observed in patients with IIA compared to EIA [time to first flatus: (2.4 ± 0.7) vs (2.8 ± 1.0) days, p < 0.01; time to liquid intake: (3.5 ± 0.7) vs (4.0 ± 1.1) days, p = 0.01; postoperative visual analogue scale score: (3.9 ± 1.0) vs (4.3 ± 0.6), p = 0.02]. No significant differences were detected in oncological outcomes or postoperative complications. IIA, rather than EIA, tended to be performed in patients with higher body mass index [(23.93 ± 3.52) vs (22.36 ± 2.87) kg/m2, p = 0.01].

Conclusions

IIA is associated with faster GI function recovery and less postoperative pain and may be more favorable for obese patients.
CEBPG suppresses ferroptosis through transcriptional control of SLC7A11 in ovarian cancer
Authors: Zhang Xiaoqian , Zheng Xiaocui , Ying Xiang , Xie Weiwei , Yin Yujia , Wang Xipeng
Published: May 2023

Background

Ovarian cancer (OC) has high mortality and poor prognosis for lacking of specific biomarkers and typical clinical symptoms in the early stage. CEBPG is an important regulator in tumor development, yet it is unclear exactly how it contributes to the progression of OC.

Methods

TCGA and tissue microarrays with immunohistochemical staining (IHC) were used to examine CEBPG expression in OC. A variety of in vitro assays were conducted, including colony formation, proliferation, migration, and invasion. The orthotopic OC mouse model was established for in vivo studies. Ferroptosis was detected by observing mitochondrial changes with electron microscopy, detecting ROS expression, and detecting cell sensitivity to drugs by CCK8 assay. The interaction between CEBPG and SLC7A11 was confirmed by CUT&Tag and dual luciferase reporter assays.

Results

A significantly higher expression level of CEBPG in OC when compared with benign tissues of ovary, and that high CEBPG expression level was also tightly associated with poor prognosis of patients diagnosed with OC, as determined by analysis of datasets and patient samples. Conversely, knockdown of CEBPG inhibited OC progression using experiments of OC cell lines and in vivo orthotopic OC-bearing mouse model. Importantly, CEBPG was identified as a new participator mediating ferroptosis evasion in OC cells using RNA-sequencing, which could contribute to OC progression. The CUT&Tag and dua luciferase reporter assays further revealed the inner mechanism that CEBPG regulated OC cell ferroptosis through transcriptional control of SLC7A11.

Conclusions

Our findings established CEBPG as a novel transcriptional regulator of OC ferroptosis, with potential value in predicting clinical outcomes and as a therapeutic candidate.
Drug repositioning targeting glutaminase reveals drug candidates for the treatment of Alzheimer’s disease patients
Authors: Bayraktar Abdulahad , Li Xiangyu , Kim Woonghee , Zhang Cheng , Turkez Hasan , Shoaie Saeed , Mardinoglu Adil
Published: May 2023

Background

Despite numerous clinical trials and decades of endeavour, there is still no effective cure for Alzheimer's disease. Computational drug repositioning approaches may be employed for the development of new treatment strategies for Alzheimer’s patients since an extensive amount of omics data has been generated during pre-clinical and clinical studies. However, targeting the most critical pathophysiological mechanisms and determining drugs with proper pharmacodynamics and good efficacy are equally crucial in drug repurposing and often imbalanced in Alzheimer’s studies.

Methods

Here, we investigated central co-expressed genes upregulated in Alzheimer’s disease to determine a proper therapeutic target. We backed our reasoning by checking the target gene’s estimated non-essentiality for survival in multiple human tissues. We screened transcriptome profiles of various human cell lines perturbed by drug induction (for 6798 compounds) and gene knockout using data available in the Connectivity Map database. Then, we applied a profile-based drug repositioning approach to discover drugs targeting the target gene based on the correlations between these transcriptome profiles. We evaluated the bioavailability, functional enrichment profiles and drug-protein interactions of these repurposed agents and evidenced their cellular viability and efficacy in glial cell culture by experimental assays and Western blotting. Finally, we evaluated their pharmacokinetics to anticipate to which degree their efficacy can be improved.

Results

We identified glutaminase as a promising drug target. Glutaminase overexpression may fuel the glutamate excitotoxicity in neurons, leading to mitochondrial dysfunction and other neurodegeneration hallmark processes. The computational drug repurposing revealed eight drugs: mitoxantrone, bortezomib, parbendazole, crizotinib, withaferin-a, SA-25547 and two unstudied compounds. We demonstrated that the proposed drugs could effectively suppress glutaminase and reduce glutamate production in the diseased brain through multiple neurodegeneration-associated mechanisms, including cytoskeleton and proteostasis. We also estimated the human blood–brain barrier permeability of parbendazole and SA-25547 using the SwissADME tool.

Conclusions

This study method effectively identified an Alzheimer’s disease marker and compounds targeting the marker and interconnected biological processes by use of multiple computational approaches. Our results highlight the importance of synaptic glutamate signalling in Alzheimer’s disease progression. We suggest repurposable drugs (like parbendazole) with well-evidenced activities that we linked to glutamate synthesis hereby and novel molecules (SA-25547) with estimated mechanisms for the treatment of Alzheimer’s patients.
Pathological hemodynamic changes and leukocyte transmigration disrupt the blood–spinal cord barrier after spinal cord injury
Authors: Zhou Rubing , Li Junzhao , Chen Zhengyang , Wang Ruideng , Shen Yin , Zhang Rong , Zhou Fang , Zhang Yong
Published: May 2023

Background

Blood–spinal cord barrier (BSCB) disruption is a key event after spinal cord injury (SCI), which permits unfavorable blood-derived substances to enter the neural tissue and exacerbates secondary injury. However, limited mechanical impact is usually followed by a large-scale BSCB disruption in SCI. How the BSCB disruption is propagated along the spinal cord in the acute period of SCI remains unclear. Thus, strategies for appropriate clinical treatment are lacking.

Methods

A SCI contusion mouse model was established in wild-type and LysM-YFP transgenic mice. In vivo two-photon imaging and complementary studies, including immunostaining, capillary western blotting, and whole-tissue clearing, were performed to monitor BSCB disruption and verify relevant injury mechanisms. Clinically applied target temperature management (TTM) to reduce the core body temperature was tested for the efficacy of attenuating BSCB disruption.

Results

Barrier leakage was detected in the contusion epicenter within several minutes and then gradually spread to more distant regions. Membrane expression of the main tight junction proteins remained unaltered at four hours post-injury. Many junctional gaps emerged in paracellular tight junctions at the small vessels from multiple spinal cord segments at 15 min post-injury. A previously unnoticed pathological hemodynamic change was observed in the venous system, which likely facilitated gap formation and barrier leakage by exerting abnormal physical force on the BSCB. Leukocytes were quickly initiated to transverse through the BSCB within 30 min post-SCI, actively facilitating gap formation and barrier leakage. Inducing leukocyte transmigration generated gap formation and barrier leakage. Furthermore, pharmacological alleviation of pathological hemodynamic changes or leukocyte transmigration reduced gap formation and barrier leakage. TTM had very little protective effects on the BSCB in the early period of SCI other than partially alleviating leukocyte infiltration.

Conclusions

Our data show that BSCB disruption in the early period of SCI is a secondary change, which is indicated by widespread gap formation in tight junctions. Pathological hemodynamic changes and leukocyte transmigration contribute to gap formation, which could advance our understanding of BSCB disruption and provide new clues for potential treatment strategies. Ultimately, TTM is inadequate to protect the BSCB in early SCI.
A qualitative investigation into pregnancy experiences and maternal healthcare utilisation among adolescent mothers in Nigeria
Authors: Alex-Ojei Christiana A. , Odimegwu Clifford O. , Ntoimo Lorretta F. C.
Published: May 2023

Background

Adolescent maternal healthcare utilisation is low in Nigeria, and little is understood about the pregnancy experiences and drivers of maternal healthcare utilisation among of adolescent girls. This study investigated the pregnancy experiences and maternal healthcare utilisation among adolescent mothers across Nigeria.

Methods

The study used the qualitative design. Urban and rural communities in Ondo, Imo and Katsina states were selected as research sites. Fifty-five in-depth interviews were conducted with adolescent girls who were currently pregnant or had given birth to a child recently, and nineteen in-depth interviews were conducted with older women who were either mothers or guardians of adolescent mothers. Additionally, key informant interviews were conducted with five female community leaders and six senior health workers. The interviews were transcribed, and resulting textual data were analysed via framework thematic analysis using a semantic and deductive approach, with the aid of NVivo software.

Results

The findings showed that the majority of unmarried participants had unintended pregnancies and stigma against pregnant adolescents was common. Social and financial support from family members, maternal support and influence, as well as healthcare preferences shaped by cultural and religious norms were the major drivers of maternal healthcare use among adolescent mothers, and the choice of their healthcare providers.

Conclusions

Interventions to support adolescent mothers and increase maternal healthcare utilisation among them must focus on ensuring the provision of social and financial support for adolescent mothers, and should be culturally sensitive.
Eggsplorer: a rapid plant–insect resistance determination tool using an automated whitefly egg quantification algorithm
Authors: Devi Micha Gracianna , Rustia Dan Jeric Arcega , Braat Lize , Swinkels Kas , Espinosa Federico Fornaguera , van Marrewijk Bart M. , Hemming Jochen , Caarls Lotte
Published: May 2023

Background

A well-known method for evaluating plant resistance to insects is by measuring insect reproduction or oviposition. Whiteflies are vectors of economically important viral diseases and are, therefore, widely studied. In a common experiment, whiteflies are placed on plants using clip-on-cages, where they can lay hundreds of eggs on susceptible plants in a few days. When quantifying whitefly eggs, most researchers perform manual eye measurements using a stereomicroscope. Compared to other insect eggs, whitefly eggs are many and very tiny, usually 0.2 mm in length and 0.08 mm in width; therefore, this process takes a lot of time and effort with and without prior expert knowledge. Plant insect resistance experiments require multiple replicates from different plant accessions; therefore, an automated and rapid method for quantifying insect eggs can save time and human resources.

Results

In this work, a novel automated tool for fast quantification of whitefly eggs is presented to accelerate the determination of plant insect resistance and susceptibility. Leaf images with whitefly eggs were collected from a commercial microscope and a custom-built imaging system. A deep learning-based object detection model was trained using the collected images. The model was incorporated into an automated whitefly egg quantification algorithm, deployed in a web-based application called Eggsplorer. Upon evaluation on a testing dataset, the algorithm was able to achieve a counting accuracy as high as 0.94, r2 of 0.99, and a counting error of ± 3 eggs relative to the actual number of eggs counted by eye. The automatically collected counting results were used to determine the resistance and susceptibility of several plant accessions and were found to yield significantly comparable results as when using the manually collected counts for analysis.

Conclusion

This is the first work that presents a comprehensive step-by-step method for fast determination of plant insect resistance and susceptibility with the assistance of an automated quantification tool.
Chronic psychological stress promotes breast cancer pre-metastatic niche formation by mobilizing splenic MDSCs via TAM/CXCL1 signaling
Authors: Zheng Yifeng , Wang Neng , Wang Shengqi , Zhang Juping , Yang Bowen , Wang Zhiyu
Published: May 2023

Background

Emerging studies have identified chronic psychological stress as an independent risk factor influencing breast cancer growth and metastasis. However, the effects of chronic psychological stress on pre-metastatic niche (PMN) formation and the underlying immunological mechanisms remain largely unknown.

Methods

The effects and molecular mechanisms of chronic unpredictable mild stress (CUMS) on modulating tumor-associated macrophages (TAMs) and PMN formation were clarified by multiplex immunofluorescence technique, cytokine array, chromatin immunoprecipitation, the dual-luciferase reporter assay, and breast cancer xenografts. Transwell and CD8+ T cytotoxicity detection were used to analyze the mobilization and function of myeloid-derived suppressor cells (MDSCs). mCherry-labeled tracing strategy and bone marrow transplantation were applied to explore the crucial role of splenic CXCR2+/+ MDSCs facilitating PMN formation under CUMS.

Results

CUMS significantly promoted breast cancer growth and metastasis, accompanied by TAMs accumulation in the microenvironment. CXCL1 was identified as a crucial chemokine in TAMs facilitating PMN formation in a glucocorticoid receptor (GR)-dependent manner. Interestingly, the spleen index was significantly reduced under CUMS, and splenic MDSCs were validated as a key factor mediating CXCL1-induced PMN formation. The molecular mechanism study revealed that TAM-derived CXCL1 enhanced the proliferation, migration, and anti-CD8+ T cell functions of MDSCs via CXCR2. Moreover, CXCR2 knockout and CXCR2−/−MDSCs transplantation significantly impaired CUMS-mediated MDSC elevation, PMN formation, and breast cancer metastasis.

Conclusion

Our findings shed new light on the association between chronic psychological stress and splenic MDSC mobilization, and suggest that stress-related glucocorticoid elevation can enhance TAM/CXCL1 signaling and subsequently recruit splenic MDSCs to promote PMN formation via CXCR2.

Graphical Abstract