bluuebunny/crossref_metadata_2025 huggingface dataset:
Myeloid-derived suppressor cell-derived osteoclasts with bone resorption capacity in the joints of arthritic SKG mice
Authors: Fujikawa Yoshikazu , Sendo Sho , del Peral Fanjul Alfonso , Yamada Hirotaka , Uto Kenichi , Yamamoto Yuzuru , Nagamoto Takumi , Morinobu Akio , Saegusa Jun
Published: March 2024

Background

Myeloid-derived suppressor cells (MDSCs) are heterogeneous immature myeloid cells with immunosuppressive functions. It is known that MDSCs are expanded at inflammatory sites after migrating from bone marrow (BM) or spleen (Sp). In chronic inflammatory diseases such as rheumatoid arthritis (RA), previous reports indicate that MDSCs are increased in BM and Sp, but detailed analysis of MDSCs in inflamed joints is very limited.

Objective

The purpose of this study is to characterize the MDSCs in the joints of mice with autoimmune arthritis.

Methods

We sorted CD11b+Gr1+ cells from joints (Jo), bone marrow (BM) and spleen (Sp) of SKG mice with zymosan (Zym)-induced arthritis and investigated differentially expressed genes (DEGs) by microarray analysis. Based on the identified DEGs, we assessed the suppressive function of CD11b+Gr1+ cells from each organ and their ability to differentiate into osteoclasts.

Results

We identified MDSCs as CD11b+Gr1+ cells by flow cytometry and morphological analysis. Microarray analysis revealed that Jo-CD11b+Gr1+ cells had different characteristics compared with BM-CD11b+Gr1+ cells or Sp-CD11b+Gr1+ cells. Microarray and qPCR analysis showed that Jo-CD11b+Gr1+ cells strongly expressed immunosuppressive DEGs (Pdl1, Arg1, Egr2 and Egr3). Jo-CD11b+Gr1+ cells significantly suppressed CD4+ T cell proliferation and differentiation in vitro, which confirmed Jo-CD11b+Gr1+ cells as MDSCs. Microarray analysis also revealed that Jo-MDSCs strongly expressed DEGs of the NF-κB non-canonical pathway (Nfkb2 and Relb), which is relevant for osteoclast differentiation. In fact, Jo-MDSCs differentiated into osteoclasts in vitro and they had bone resorptive function. In addition, intra-articular injection of Jo-MDSCs promoted bone destruction.

Conclusions

Jo-MDSCs possess a potential to differentiate into osteoclasts which promote bone resorption in inflamed joints, while they are immunosuppressive in vitro.
QuantiFERON-TB reversion in children and adolescents with tuberculosis
Authors: Rodríguez-Molino Paula , González Sánchez Araceli , Noguera-Julián Antoni , Soler-García Aleix , Martínez Paz Patricia , Méndez-Echevarría Ana , Baquero-Artigao Fernando , González Muñoz Miguel , Ruíz-Serrano María Jesús , Monsonís Manuel , Sánchez León Rocío , Saavedra-Lozano Jesús , Santiago-García Begoña , Sainz Talía
Published: March 2024

We analyzed 136 children with tuberculosis disease or infection and a positive QuantiFERON-TB (QFT) assay, followed-up for a median of 21 months (0.4-11years). QFT reversed in 16.9% of cases, with significant decreases in TB1 (-1.72 vs. -0.03 IU/ml, p=0.001) and TB2 (-1.65 vs. -0.43 IU/ml, p=0.005) levels compared to non-reverters. We found a higher QFT reversion rate among children under 5 years (25.0% vs 11.9%, p=0.042), and those with TST induration <15mm (29% vs 13.3%, p=0.055). Our data reveal that, although QFT test remained positive in the majority of children, reversion occurred in 16% of cases in a progressive and stable pattern. Younger age and reduced TST induration were associated with QFT reversion.
Mycobacterium bovis BCG as immunostimulating agent prevents the severe form of chronic experimental Chagas disease
Authors: Arce-Fonseca Minerva , Mata-Espinosa Dulce , Aranda-Fraustro Alberto , Rosales-Encina José Luis , Flores-Valdez Mario Alberto , Rodríguez-Morales Olivia
Published: March 2024

Introduction

There is currently no vaccine against Chagas disease (ChD), and the medications available confer multiple side effects. Mycobacterium bovis Bacillus Calmette–Guérin (BCG) produces balanced Th1, Th2, and Th17 modulatory immune responses and has improved efficacy in controlling chronic infections through nonspecific immunity. We aimed to improve the response to infection by inducing a stronger immune response and greater protection against the parasite by trained immunity.

Methods

BALB/c mice were immunized with BCG subcutaneously, and 60 days later, they were infected with Trypanosoma cruzi intraperitoneally. An evaluation of the progression of the disease from the acute to the chronic stage, analyzing various aspects such as parasitemia, survival, clinical status, and humoral and cellular immune response, as well as the appearance of visceral megas and the histopathological description of target organs, was performed.

Results

Vaccination reduced parasitemia by 70%, and 100% survival was achieved in the acute stage; although the presentation of clinical signs was reduced, there was no increase in the antibody titer or in the differential production of the isotypes.

Conclusion

Serum cytokine production indicated a proinflammatory response in infected animals, while in those who received BCG, the response was balanced by inducing Th1/Th2-type cytokines, with a better prognosis of the disease in the chronic stage.
Therapeutic efficacy and safety of JAK inhibitors in treating polymyositis/dermatomyositis: a single-arm systemic meta-analysis
Authors: Ma Chenhang , Liu Mengyao , Cheng Yang , Wang Xinchang , Zhao Yu , Wang Kailu , Wang Weijie
Published: March 2024

Introduction

We performed a single-arm meta-analysis to evaluate the efficacy and safety of JAK inhibitors in the treatment of dermatomyositis (DM)/ polymyositis (PM).

Methods

Relevant studies from four databases were systematically searched until April 25, 2023. The primary endpoint was Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) and other outcomes were Manual Muscle Testing (MMT) and Creatine Kinase (CK). According to the type of JAK and medication regimen, we conducted subgroup analyses. The registration number in PROSPERO was CRD42023416493.

Results

According to the selection criteria, we identified 7 publications with a total of 91 patients. Regarding skin lesions, the CDASI decreased by 17.67 (95% CI: -20.94 ~ -14.41). The CK increased by 8.64 U (95% CI: -28.25 ~ 45.53). About muscle lesions, MMT increased by 10.31 (95% CI: -2.83 ~ 23.46). Subgroup analysis revealed that different types of JAK inhibitors had various degrees of reduction. CDASI in patients treated with RUX had the lowest one [-20.00 (95% CI: -34.9 ~ -5.1)], followed by TOF [-18.29 (95% CI: -21.8 ~ -14.78)] and BAR [-11.2 (95% CI: -21.51 ~ -0.89)]. Additionally, the mean reduction in CDASI in patients treated with TOF alone was 16.16 (95% CI: -21.21 ~ -11.11), in combination with other immunosuppressants was 18.59 (95% CI: -22.74 ~ -14.45). For safety evaluation, one patient developed Orolabial HSV, and two patients developed thromboembolism events.

Discussion

In summary, this meta-analysis demonstrated that JAK inhibitors can potentially treat DM/PM without severe adverse reactions.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42023416493, identifier CRD42023416493.
A rare case of primary cardiac diffuse large B-cell lymphoma imaged with 18F-FDG PET/CT: a case report and literature review
Authors: Huang Wenpeng , Zheng Zuohuan , Zhang Yongbai , Qiu Yongkang , Peng Yushuo , Yang Qi , Wang Wei , Kang Lei
Published: March 2024

Background

One of the exceptionally rare forms of non-Hodgkin’s lymphoma (NHL) is primary cardiac lymphoma (PCL). The principal clinical manifestation in patients with PCL involves cardiac symptoms resulting from myocardial infiltration by lymphoma, including arrhythmias, heart failure, and chest pain. 18F-FDG PET/CT serves as a reliable and indispensable imaging modality for assessing clinically staging NHL.

Case report

We present a rare case involving a 72-year-old woman diagnosed with primary intracardiac diffuse large B-cell lymphoma. For further staging, the patient underwent 18F-FDG PET/CT, revealing multiple nodular soft tissue density lesions in the heart and pericardium exhibiting increased FDG metabolism (SUVmax = 12.1). The supradiaphragmatic and infradiaphragmatic segments of the inferior vena cava exhibited irregular morphology with localized nodular changes and increased FDG metabolism in the surrounding area (SUVmax = 9.7). Additionally, multiple enlarged lymph nodes were identified in the left axilla, mediastinum, and adjacent to the abdominal aorta, displaying heterogeneous FDG uptake with an SUVmax of 9.3, indicating lymphoma involvement. The above imaging findings suggested that the mass was a PCL. Hence, the patient underwent a combination of chemotherapy and immunotherapy using R-CDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone). Following two courses of treatment within a span of 2 months, there was a partial remission observed in the cardiac lymphoma and the enlarged lymph nodes.

Conclusion

The case elucidated in this report contributes to an enhanced understanding of the disease for clinicians, with 18F-FDG PET/CT providing comprehensive insights into the extent of cardiac involvement, as well as the engagement of extracardiac organs and pathologic lymph nodes. The 18F-FDG PET/CT examination not only visually delineates the lesion’s location and extent but also serves as a cornerstone for clinical tumor staging, offering valuable support for treatment monitoring and subsequent follow-up.
Structural neuroimaging markers of normal pressure hydrocephalus versus Alzheimer’s dementia and Parkinson’s disease, and hydrocephalus versus atrophy in chronic TBI—a narrative review
Authors: Kadaba Sridhar Sharada , Dysterheft Robb Jen , Gupta Rishabh , Cheong Scarlett , Kuang Rui , Samadani Uzma
Published: March 2024

Introduction

Normal Pressure Hydrocephalus (NPH) is a prominent type of reversible dementia that may be treated with shunt surgery, and it is crucial to differentiate it from irreversible degeneration caused by its symptomatic mimics like Alzheimer’s Dementia (AD) and Parkinson’s Disease (PD). Similarly, it is important to distinguish between (normal pressure) hydrocephalus and irreversible atrophy/degeneration which are among the chronic effects of Traumatic Brain Injury (cTBI), as the former may be reversed through shunt placement. The purpose of this review is to elucidate the structural imaging markers which may be foundational to the development of accurate, noninvasive, and accessible solutions to this problem.

Methods

By searching the PubMed database for keywords related to NPH, AD, PD, and cTBI, we reviewed studies that examined the (1) distinct neuroanatomical markers of degeneration in NPH versus AD and PD, and atrophy versus hydrocephalus in cTBI and (2) computational methods for their (semi-) automatic assessment on Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) scans.

Results

Structural markers of NPH and those that can distinguish it from AD have been well studied, but only a few studies have explored its structural distinction between PD. The structural implications of cTBI over time have been studied. But neuroanatomical markers that can predict shunt response in patients with either symptomatic idiopathic NPH or post-traumatic hydrocephalus have not been reliably established. MRI-based markers dominate this field of investigation as compared to CT, which is also reflected in the disproportionate number of MRI-based computational methods for their automatic assessment.

Conclusion

Along with an up-to-date literature review on the structural neurodegeneration due to NPH versus AD/PD, and hydrocephalus versus atrophy in cTBI, this article sheds light on the potential of structural imaging markers as (differential) diagnostic aids for the timely recognition of patients with reversible (normal pressure) hydrocephalus, and opportunities to develop computational tools for their objective assessment.
SYN1 variant causes X-linked neurodevelopmental disorders: a case report of variable clinical phenotypes in siblings
Authors: Ren Bin , Wu Xiaoyan , Zhou Yuqiang , Chen Lijuan , Jiang Jingzi
Published: March 2024

The SYN1 gene encodes synapsin I, variants within the SYN1 gene are linked to X-linked neurodevelopmental disorders with high clinical heterogeneity, with reflex epilepsies (REs) being a representative clinical manifestation. This report analyzes a Chinese pedigree affected by seizures associated with SYN1 variants and explores the genotype–phenotype correlation. The proband, a 9-year-old boy, experienced seizures triggered by bathing at the age of 3, followed by recurrent absence seizures, behavioral issues, and learning difficulties. His elder brother exhibited a distinct clinical phenotype, experiencing sudden seizures during sleep at the age of 16, accompanied by hippocampal sclerosis. Whole exome sequencing (WES) confirmed a pathogenic SYN1 variant, c.1647_1650dup (p. Ser551Argfs*134), inherited in an X-linked manner from their mother. Notably, this variant displayed diverse clinical phenotypes in the two brothers and one previously reported case in the literature. Retrospective examination of SYN1 variants revealed an association between truncating variants and the pathogenicity of REs, and non-truncating variants are more related to developmental delay/intellectual disability (DD/ID). In summary, this study contributes to understanding complex neurodevelopmental disorders associated with SYN1, highlighting the clinical heterogeneity of gene variants and emphasizing the necessity for comprehensive genetic analysis in elucidating the pathogenic mechanisms of such diseases.
A brain functional network feature extraction method based on directed transfer function and graph theory for MI-BCI decoding tasks
Authors: Ma Pengfei , Dong Chaoyi , Lin Ruijing , Liu Huanzi , Lei Dongyang , Chen Xiaoyan , Liu Huan
Published: March 2024

Background

The development of Brain-Computer Interface (BCI) technology has brought tremendous potential to various fields. In recent years, prominent research has focused on enhancing the accuracy of BCI decoding algorithms by effectively utilizing meaningful features extracted from electroencephalographic (EEG) signals.

Objective

This paper proposes a method for extracting brain functional network features based on directed transfer function (DTF) and graph theory. The method incorporates the extracted brain network features with common spatial pattern (CSP) to enhance the performance of motor imagery (MI) classification task.

Methods

The signals from each electrode of the EEG, utilizing a total of 32 channels, are used as input signals for the network nodes. In this study, 26 healthy participants were recruited to provide EEG data. The brain functional network is constructed in Alpha and Beta bands using the DTF method. The node degree (ND), clustering coefficient (CC), and global efficiency (GE) of the brain functional network are obtained using graph theory. The DTF network features and graph theory are combined with the traditional signal processing method, the CSP algorithm. The redundant network features are filtered out using the Lasso method, and finally, the fused features are classified using a support vector machine (SVM), culminating in a novel approach we have termed CDGL.

Results

For Beta frequency band, with 8 electrodes, the proposed CDGL method achieved an accuracy of 89.13%, a sensitivity of 90.15%, and a specificity of 88.10%, which are 14.10, 16.69, and 11.50% percentage higher than the traditional CSP method (75.03, 73.46, and 76.60%), respectively. Furthermore, the results obtained with 8 channels were superior to those with 4 channels (82.31, 83.35, and 81.74%), and the result for the Beta frequency band were better than those for the Alpha frequency band (87.42, 87.48, and 87.36%). Similar results were also obtained on two public datasets, where the CDGL algorithm’s performance was found to be optimal.

Conclusion

The feature fusion of DTF network and graph theory features enhanced CSP algorithm’s performance in MI task classification. Increasing the number of channels allows for more EEG signal feature information, enhancing the model’s sensitivity and discriminative ability toward specific activities in brain regions. It should be noted that the functional brain network features in the Beta band exhibit superior performance improvement for the algorithm compared to those in the Alpha band.
Secondary language impairment in posterior cortical atrophy: insights from sentence repetition
Authors: Ahmed Samrah , Caswell Josie , Butler Christopher R. , Bose Arpita
Published: March 2024

Introduction

Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by progressive impairment in visuospatial and perceptual function linked to atrophy of the occipito-parietal cortex. Besides the salient visual impairment, several studies have documented subtle changes in language may also be present. Sentence repetition is a highly constrained linguistic task involving multiple linguistic and cognitive processes and have been shown to be impaired in other AD spectrum disorders, with little consensus on its relevance in PCA. This aim of this study was to further delineate the linguistic and cognitive features of impaired language in PCA using a sentence repetition task.

Method

Seven PCA patients and 16 healthy controls verbally repeated 16 sentences from the Boston Diagnostic Aphasia Examination. Responses were transcribed orthographically and coded for accuracy (percentage accuracy; percentage Correct Information Units; Levenshtein Distance) and for temporal characteristics (preparation duration (ms); utterance duration (ms); silent pause duration (ms); speech duration (ms); dysfluency duration (ms)). The potential modulating effects of attentional control and working memory capacity were explored.

Results

PCA patients showed lower overall accuracy with retained semantic content of the sentences, and lower phonological accuracy. Temporal measures revealed longer preparation and utterance duration for PCA patients compared to controls, alongside longer speech duration but comparable dysfluency duration. PCA patients also showed comparable silent pause duration to controls. Attentional control, measured using the Hayling sentence completion task, predicted accuracy of sentence repetition.

Discussion

The findings suggest that sentence repetition is impaired in PCA and is characterized by phonological, response planning and execution difficulties, underpinned in part by attentional control mechanisms. The emerging profile of language impairment in PCA suggests vulnerability of similar cognitive systems to other Alzheimer’s syndromes, with subtle differences in clinical presentation.
Enhancing children’s nutrition: the influence of rural household technology under China’s home appliances going to the countryside policy
Authors: Du Mingling , Shi Junhui , Shi Songping , Wang Fang
Published: March 2024

This study explores the influence of household technological advancements on children’s nutritional intake, specifically within the context of the Chinese government’s “Home Appliances Going to the Countryside” (HAGC) initiative. Utilizing data from the China Health and Nutrition Surveys of 2006, 2009, and 2011, we employed a Propensity Score Matching Difference-in-Differences (PSM-DID) framework to ascertain the repercussions of enhanced household technology on the dynamics of children’s nutritional consumption patterns. Our analysis reveals that the HAGC-inspired integration of household appliances, including color televisions, washing machines, and refrigerators, has beneficially reshaped the nutritional consumption patterns of children, with a pronounced effect among female children. This finding remains consistent even when employing alternate methodological robustness tests. A deeper examination of the HAGC policy’s mechanisms underscores the pivotal roles of parental time allocation, improved food storage capabilities, and augmented information accessibility as significant drivers bolstering children’s nutritional intake. These insights bear considerable significance for strategizing interventions aimed at elevating the nutritional wellbeing of children in rural settings, offering valuable input for shaping public health policies tailored for such demographies.
Qualitative evaluation of artificial intelligence-generated weight management diet plans
Authors: Kim Dong Wook , Park Ji Seok , Sharma Kavita , Velazquez Amanda , Li Lu , Ostrominski John W. , Tran Tram , Seitter Peréz Robert H. , Shin Jeong-Hun
Published: March 2024

Importance

The transformative potential of artificial intelligence (AI), particularly via large language models, is increasingly being manifested in healthcare. Dietary interventions are foundational to weight management efforts, but whether AI techniques are presently capable of generating clinically applicable diet plans has not been evaluated.

Objective

Our study sought to evaluate the potential of personalized AI-generated weight-loss diet plans for clinical applications by employing a survey-based assessment conducted by experts in the fields of obesity medicine and clinical nutrition.

Design, setting, and participants

We utilized ChatGPT (4.0) to create weight-loss diet plans and selected two control diet plans from tertiary medical centers for comparison. Dietitians, physicians, and nurse practitioners specializing in obesity medicine or nutrition were invited to provide feedback on the AI-generated plans. Each plan was assessed blindly based on its effectiveness, balanced-ness, comprehensiveness, flexibility, and applicability. Personalized plans for hypothetical patients with specific health conditions were also evaluated.

Main outcomes and measures

The primary outcomes measured included the indistinguishability of the AI diet plan from human-created plans, and the potential of personalized AI-generated diet plans for real-world clinical applications.

Results

Of 95 participants, 67 completed the survey and were included in the final analysis. No significant differences were found among the three weight-loss diet plans in any evaluation category. Among the 14 experts who believed that they could identify the AI plan, only five did so correctly. In an evaluation involving 57 experts, the AI-generated personalized weight-loss diet plan was assessed, with scores above neutral for all evaluation variables. Several limitations, of the AI-generated plans were highlighted, including conflicting dietary considerations, lack of affordability, and insufficient specificity in recommendations, such as exact portion sizes. These limitations suggest that refining inputs could enhance the quality and applicability of AI-generated diet plans.

Conclusion

Despite certain limitations, our study highlights the potential of AI-generated diet plans for clinical applications. AI-generated dietary plans were frequently indistinguishable from diet plans widely used at major tertiary medical centers. Although further refinement and prospective studies are needed, these findings illustrate the potential of AI in advancing personalized weight-centric care.
The regulatory process and practical significance of non-coding RNA in the dissemination of prostate cancer to the skeletal system
Authors: Sang Hui , Li Luxi , Zhao Qiang , Liu Yulin , Hu Jinbo , Niu Peng , Hao Zhenming , Chai Keqiang
Published: March 2024

Prostate cancer is a major contributor to male cancer-related mortality globally. It has a particular affinity for the skeletal system with metastasis to bones seriously impacting prognosis. The identification of prostate cancer biomarkers can significantly enhance diagnosis and patient monitoring. Research has found that cancer and metastases exhibit abnormal expression of numerous non-coding RNA. Some of these RNA facilitate prostate cancer bone metastasis by activating downstream signaling pathways, while others inhibit this process. Elucidating the functional processes of non-coding RNA in prostate cancer bone metastasis will likely lead to innovative treatment strategies for this malignant condition. In this review, the mechanistic role of the various RNA in prostate cancer is examined. Our goal is to provide a new avenue of approach to the diagnosis and treatment of bone metastasis in this cancer.
Malignant transformation of primary ameloblastoma of skull: case report and review of current literature
Authors: Xu Haitong , Tan Jialiang , Fu Dongxiang
Published: March 2024

Background

Since 1964, there has been a scarcity of reported cases of primary ameloblastoma (AM) or ameloblastic carcinoma (AMCa) of the skull. The clinical presentation and distinctive features of this uncommon condition at specific anatomical sites remain unclear. We report a case of malignant transformation of a primary AM of the skull situated in the frontal-temporal-parietal region and highlight its similarities to other cases reported in the literature.

Clinical presentation

A 53-year-old female patient presented with a 20-day history of headaches and bilateral lower limb weakness for 10 days. Physical examination revealed slow and unsteady gait. An occupying lesion was observed in the right frontal-temporal-parietal region of the skull on the Cranial imaging. A right cranial bone tumor margin expansion resection was performed. The patient’s motor functions recovered normally after surgery. Postoperative imaging examinations showed10 tumor resection. Follow-up imaging examinations showed tumor recurrence. The patient underwent resection of the recurrent tumor. Postoperative pathological analysis revealed malignant transformation of the AM.Follow-up imaging examinations showed tumor recurrence again. The patient was admitted for stereotactic radiotherapy. Follow-up imaging examinations demonstrated no evidence of tumor recurrence and subsequent chest CT revealed no signs of metastasis.

Conclusion

Primary AM or AMCa of the skull is increasingly being described in the literature, but detailed reports on the malignant transformation of primary AM of the skull are lacking. The pathogenesis of this condition remains unclear. Aggressive treatment and close follow-up may be crucial for preventing disease recurrence and malignant transformation.
Efficacy and safety of consolidation chemotherapy after adjuvant therapy in stage IB-IIA cervical cancer patients with risk factors: a retrospective single-center study
Authors: Wang Jiaxin , Guo Huaijuan , Yang Jingjing , Mao Jingxian , Wang Ying , Gao Ruidong , Yan Xuebing , Wang Jie
Published: March 2024

Objective

Accumulated evidence has suggested a relatively high recurrence rate in early-stage cervical cancer (CC) patients with risk factors. This study aimed to assess the efficacy and safety of consolidation chemotherapy following adjuvant therapy (concurrent chemoradiotherapy (CCRT) or radiotherapy (RT) alone) in stage IB-IIA CC patients with risk factors.

Methods

A total of 237 stage IB-IIA CC patients who received radical surgery between January 2014 and December 2021 were included in the retrospective study. According to the types of adjuvant therapies, the patients were classified into the control group (CCRT or RT alone) and the study group (consolidation chemotherapy following CCRT or RT alone). The propensity score matching (PSM) was used to balance baseline characteristics between the two groups. The primary end points of the study were disease-free survival (DFS) and overall survival (OS).

Results

For the entire cohort, no significant difference was observed in the DFS or OS between the study and control group, which was also confirmed in the PSM cohort (n=124). The multivariate analysis identified the high-risk factor type was an independent adverse prognostic factor for the patients. In patients with high risk factors, consolidation chemotherapy following adjuvant therapy was significantly associated with better clinical outcomes and identified as an independent prognostic favorable factor. Moreover, this association remained statistically significant in high-risk patients with ≥2 metastatic lymph nodes. In patients with intermediate risk factors, consolidation chemotherapy following adjuvant therapy was unrelated to DFS or OS. The safe assessment demonstrated consolidation chemotherapy following adjuvant therapy was significantly correlated with higher rates of ≥ grade 3 hematologic toxicities in both the global and subgroup analysis stratified by risk factor type.

Conclusion

Consolidation chemotherapy after adjuvant therapy provided survival benefits in stage IB-IIA CC patients with high risk factors, particularly those with ≥2 metastatic lymph nodes. However, related hematologic toxicities should be alerted in patient management. The actual efficacy and safety of consolidation chemotherapy still need to be investigated in more well-designed clinical trials.
Case Report: A case of Crohn's disease with right atrial thrombosis
Authors: Hu Zehang , Gao Yi , Fan Shumin
Published: March 2024

Crohn's disease (CD) is a chronic, non-specific inflammatory disease of the intestinal tract with an unknown etiology. It presents with clinical symptoms such as abdominal distension, abdominal pain, diarrhea, bloody stools containing mucus or pus, and other manifestations. CD has a prolonged and chronic course and can lead to various complications that significantly impact patients’ quality of life. Patients with CD have hypercoagulable blood and are prone to thromboembolic diseases, which pose a serious threat to their lives. Several studies have indicated that inflammatory bowel disease is a risk factor for venous thromboembolism. The pathogenesis involves abnormalities in the coagulation-anticoagulation system, fibrinolytic system, platelets, vascular endothelial dysfunction, as well as the effects of therapeutic agents. In this case report, we present a rare case of a 15-year-old female patient with active CD complicated by the presence of a right atrial thrombus. Laboratory tests revealed abnormalities in both the coagulation-anticoagulation system and fibrinolysis system in the patient. The initial diagnosis, based on transthoracic echocardiography and contrast-enhanced echocardiography, confirmed the presence of a thrombus in the right atrium. Subsequent administration of anticoagulant and thrombolytic therapy resulted in gradual reduction in size until complete disappearance, as evidenced by dynamic monitoring. Ultrasound examination is considered as the preferred method for follow-up evaluation in patients with CD due to its ability not only to assess gastrointestinal complications but also to aid early identification of cardiovascular complications, thereby enabling timely intervention and treatment—which remains our primary focus of research and effort.
Decylprodigiosin: a new member of the prodigiosin family isolated from a seaweed-associated Streptomyces
Authors: Girão Mariana , Freitas Sara , Martins Teresa P. , Urbatzka Ralph , Carvalho Maria F. , Leão Pedro N.
Published: March 2024

Bioprospecting actinobacterial secondary metabolism from untapped marine sources may lead to the discovery of biotechnologically-relevant compounds. While studying the diversity and bioactive potential of Actinomycetota associated with Codium tomentosum, a green seaweed collected in the northern Portuguese cost, strain CT-F61, identified as Streptomyces violaceoruber, was isolated. Its extracts displayed a strong anticancer activity on breast carcinoma T-47D and colorectal carcinoma HCT116 cells, being effective as well against a panel of human and fish pathogenic bacteria. Following a bioactivity-guided isolation pipeline, a new analogue of the red-pigmented family of the antibiotics prodigiosins, decylprodigiosin (1), was identified and chemically characterized. Despite this family of natural products being well-known for a long time, we report a new analogue and the first evidence for prodigiosins being produced by a seaweed-associated actinomycete.
Efficacy and safety of Panax notoginseng saponin injection in the treatment of acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trials
Authors: Chen Pengfei , Gao Zhuye , Guo Ming , Pan Deng , Zhang He , Du Jianpeng , Shi Dazhuo
Published: March 2024

Purpose: This study aimed to assess the efficacy and safety of Panax notoginseng saponin (PNS) injection, when combined with conventional treatment (CT), for acute myocardial infarction (AMI).

Methods: Comprehensive searches were conducted in seven databases from inception until 28 September 2023. The search aimed to identify relevant randomized controlled trials (RCTs) focusing on PNS injection in the context of AMI. This meta-analysis adhered to the PRISMA 2020 guidelines, and its protocol was registered with PROSPERO (number: CRD42023480131).

Result: Twenty RCTs involving 1,881 patients were included. The meta-analysis revealed that PNS injection, used adjunctively with CT, significantly improved treatment outcomes compared to CT alone, as evidenced by the following points: (1) enhanced total effective rate [OR = 3.09, p < 0.05]; (2) decreased incidence of major adverse cardiac events [OR = 0.32, p < 0.05]; (3) reduction in myocardial infarct size [MD = −6.53, p < 0.05]; (4) lower ST segment elevation amplitude [MD = −0.48, p < 0.05]; (5) mitigated myocardial injury as indicated by decreased levels of creatine kinase isoenzymes [MD = −11.19, p < 0.05], cardiac troponin T [MD = −3.01, p < 0.05], and cardiac troponin I [MD = −10.72, p < 0.05]; (6) enhanced cardiac function, reflected in improved brain natriuretic peptide [MD = −91.57, p < 0.05], left ventricular ejection fraction [MD = 5.91, p < 0.05], left ventricular end-diastolic dimension [MD = −3.08, p < 0.05], and cardiac output [MD = 0.53, p < 0.05]; (7) reduced inflammatory response, as shown by lower levels of C-reactive protein [MD = −2.99, p < 0.05], tumor necrosis factor-α [MD = −6.47, p < 0.05], interleukin-6 [MD = −24.46, p < 0.05], and pentraxin-3 [MD = −2.26, p < 0.05]; (8) improved vascular endothelial function, demonstrated by decreased endothelin-1 [MD = −20.56, p < 0.05] and increased nitric oxide [MD = 1.33, p < 0.05]; (9) alleviated oxidative stress, evidenced by increased superoxide dismutase levels [MD = 25.84, p < 0.05]; (10) no significant difference in adverse events [OR = 1.00, p = 1.00].

Conclusion: This study highlighted the efficacy and safety of adjunctive PNS injections in enhancing AMI patient outcomes beyond CT alone. Future RCTs need to solidify these findings through rigorous methods.

Systematic Review Registration: (https://www.crd.york.ac.uk/PROSPERO/), identifier (CRD42023480131)
Understanding the role of ursodeoxycholic acid and gut microbiome in non-alcoholic fatty liver disease: current evidence and perspectives
Authors: Mao Qingyi , Lin Beibei , Zhang Wenluo , Zhang Yu , Zhang Yu , Cao Qian , Xu Mengque
Published: March 2024

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, resulting in a huge medical burden worldwide. Accumulating evidence suggests that the gut microbiome and bile acids play pivotal roles during the development of NAFLD. Patients with NAFLD exhibit unique signatures of the intestinal microbiome marked by the priority of Gram-negative bacteria, decreased ratio of Firmicutes/Bacteroidetes (F/B), and increased Prevotella and Lachnospiraceae. The intestinal microbiota is involved in the metabolism of bile acids. Ursodeoxycholic acid (UDCA) is a key determinant in maintaining the dynamic communication between the host and gut microbiota. It generally shows surprising therapeutic potential in NAFLD with several mechanisms, such as improving cellular autophagy, apoptosis, and mitochondrial functions. This action is based on its direct or indirect effect, targeting the farnesoid X receptor (FXR) and various other nuclear receptors. This review aims to discuss the current studies on the involvement of the microbiome–UDCA interface in NAFLD therapy and provide prospective insights into future preventative and therapeutic approaches for NAFLD.
Vasorelaxant and hypotensive effects of an ethanolic extract of Nymphaea pubescens and its main compound quercetin 3-methyl ether 3′-O-β-xylopyranoside
Authors: Panklai Teerapap , Ingkaninan Kornkanok , Chootip Krongkarn , Temkitthawon Prapapan , Suphrom Nungruthai , Tournier-Nappey Maude , Girard Corine , Demougeot Céline , Totoson Perle
Published: March 2024

Aim:Nymphaea plants were traditionally used to treat diseases associated with endothelial dysfunction. The present study investigated the effects of an ethanolic extract of Nymphaea pubescens Willd. (commonly named water lily, WL) and its main compound 1 (quercetin 3-methyl ether 3′-O-β-xylopyranoside) on vascular function in rats.

Materials and methods: The vasorelaxant effects of the WL extract and its main compound 1 and their underlying mechanisms of action were evaluated on isolated mesenteric arteries from Wistar rats. Blood pressure and heart rate were measured in anesthetized rats after infusion (i.v) of vehicle, WL extract, and compound 1 (at 0.01, 0.025, 0.05, 0.1, 0.5, and 1 mg/kg). Nifedipine was used as a positive control.

Results: Both WL extract and compound 1 induced vasorelaxant effects (with EC50 of 0.08 ± 0.01 mg/mL and 42.8 ± 6.3 µM, respectively) that were reduced by endothelium removal. A significant decrease in these relaxations was observed with L-NAME but not with apamin–charybdotoxin or indomethacin. In the endothelium-denuded condition, WL extract-induced relaxation was enhanced by 4-aminopyridine and glibenclamide, while iberiotoxin and ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one) had no effect. In contrast, compound 1-induced relaxation was not changed by any of these inhibitors. Both WL extract and compound 1 enhanced sodium nitroprusside-induced relaxation and inhibited receptor-operated Ca2+ channels. Only the WL extract was able to reduce PE-induced contraction (p < 0.001). As compared to the vehicle, the infusion of WL extract and compound 1 lowered systolic and diastolic blood pressure. Interestingly, the hypotensive effect of the compound was similar to that of nifedipine. The rebound tachycardia found at the highest dose of nifedipine was not observed with the WL extract or compound 1 (p < 0.05).

Conclusion and discussion: Our study demonstrated a vasorelaxant effect of the WL extract and its main compound quercetin 3-methyl ether 3′-O-β-xylopyranoside, relying on the potentiation of the NO-cGMP pathway and calcium inhibitory effects. These vasorelaxant effects were associated with a potent hypotensive effect, providing pharmacological evidence for the traditional use of this plant.
Novel mechanistic study of HDAC6 regulation of rheumatoid arthritis via CMA: exploring potential therapeutic targets
Authors: Lin Duoduo , Lai Weipeng , Zheng Ningning , Luo Hongbin , Chen Xiaole , Que Wenzhong , Zhang Nanwen
Published: March 2024

Objective:

Rheumatoid arthritis (RA) is a systemic autoimmune disease. Its pathogenesis has not yet been clarified, so it is urgent to explore therapeutic targets. Here, we clarified the role of HDAC6 in the mechanism of action of RA through mediating chaperone-mediated autophagy (CMA) to provide a clinical treatment of RA.

Methods:

We used rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and collagen-induced arthritis mice (CIA mice) as models of RA and pharmacological inhibitors as well as genetic interference with adeno-associated viruses to reduce the expression of HDAC6. We explored the influence of CAY10603 on RA-FLS proliferation and inflammation, as well as the expression of proteins related to the CMA signaling pathway. CIA model was constructed using DBA/1J mice. Arthritis symptoms in CIA mice were evaluated, and the expression and localization of CMA-related proteins in mouse ankle joints were examined.

Results:

CAY10603 inhibited proliferation as well as the level of the molecular chaperone autophagy in RA-FLS. HDAC6 shRNA significantly reduced the clinical signs of arthritis in CIA mice, as did the expression of HDAC6 in the serum and ankle synovial tissues of CIA mice. Finally, it significantly inhibited the level of Hsc70 and LAMP-2A, which are involved in the CMA signaling pathway, in ankle joint tissues.

Conclusion:

Downregulation of HDAC6 may inhibit CMA and thereby ameliorate RA.
Skeletons in the closet? Using a bibliometric lens to visualise phytochemical and pharmacological activities linked to Sceletium, a mood enhancer
Authors: Reddy Kaylan , Stafford Gary I. , Makunga Nokwanda P.
Published: March 2024

Plants from the Sceletium genus (Aizoaceae) have been traditionally used for millennia by the Khoe and Khoen people in southern Africa, as an appetite suppressant as well as a mood elevator. In more recent times, this mood-elevating activity has been commercialised in the South African natural products industry for the treatment of anxiety and depression, with several products available both locally and abroad. Research on this species has seen rapid growth with advancements in analytical and pharmacological tools, in an effort to understand the composition and biological activity. The Web of Science (WoS) database was searched for articles related to ‘Sceletium’ and ‘Mesembrine’. These data were additionally analysed by bibliometric software (VOSviewer) to generate term maps and author associations. The thematic areas with the most citations were South African Traditional Medicine for mental health (110) and anxiolytic agents (75). Pioneer studies in the genus focused on chemical structural isolation, purification, and characterisation and techniques such as thin layer chromatography, liquid chromatography (HPLC, UPLC, and more recently, LC-MS), gas chromatography mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) to study mesembrine alkaloids. Different laboratories have used a diverse range of extraction and preanalytical methods that became routinely favoured in the analysis of the main metabolites (mesembrine, mesembranol, mesembranone, and Sceletium A4) in their respective experimental settings. In contrast with previous reviews, this paper identified gaps in the research field, being a lack of toxicology assays, a deficit of clinical assessments, too few bioavailability studies, and little to no investigation into the minor alkaloid groups found in Sceletium. Future studies are likely to see innovations in analytical techniques like leaf spray mass spectrometry and direct analysis in real-time ionisation coupled with high-resolution time-of-flight mass spectrometry (DART-HR-TOF-MS) for rapid alkaloid identification and quality control purposes. While S. tortuosum has been the primary focus, studying other Sceletium species may aid in establishing chemotaxonomic relationships and addressing challenges with species misidentification. This research can benefit the nutraceutical industry and conservation efforts for the entire genus. At present, little to no pharmacological information is available in terms of the molecular physiological effects of mesembrine alkaloids in medical clinical settings. Research in these fields is expected to increase due to the growing interest in S. tortuosum as a herbal supplement and the potential development of mesembrine alkaloids into pharmaceutical drugs.
Comparative genomics, pangenomics, and phenomic studies of Pectobacterium betavasculorum strains isolated from sugar beet, potato, sunflower, and artichoke: insights into pathogenicity, virulence determinants, and adaptation to the host plant
Authors: Borowska-Beszta Maria , Smoktunowicz Magdalena , Horoszkiewicz Daria , Jonca Joanna , Waleron Michal Mateusz , Gawor Jan , Mika Adriana , Sledzinski Tomasz , Waleron Krzysztof , Waleron Malgorzata
Published: March 2024

Introduction

Bacteria of genus Pectobacterium, encompassing economically significant pathogens affecting various plants, includes the species P. betavasculorum, initially associated with beetroot infection. However, its host range is much broader. It causes diseases of sunflower, potato, tomato, carrots, sweet potato, radish, squash, cucumber, and chrysanthemum. To explain this phenomenon, a comprehensive pathogenomic and phenomic characterisation of P. betavasculorum species was performed.

Methods

Genomes of P. betavasculorum strains isolated from potato, sunflower, and artichoke were sequenced and compared with those from sugar beet isolates. Metabolic profiling and pathogenomic analyses were conducted to assess virulence determinants and adaptation potential. Pathogenicity assays were performed on potato tubers and chicory leaves to confirm in silico predictions of disease symptoms. Phenotypic assays were also conducted to assess the strains ability to synthesise homoserine lactones and siderophores.

Results

The genome size ranged from 4.675 to 4.931 kbp, and GC % was between 51.0% and 51.2%. The pangenome of P. betavasculorum is open and comprises, on average, 4,220 gene families. Of these, 83% of genes are the core genome, and 2% of the entire pangenome are unique genes. Strains isolated from sugar beet have a smaller pangenome size and a higher number of unique genes than those from other plants. Interestingly, genomes of strains from artichoke and sunflower share 391 common CDS that are not present in the genomes of other strains from sugar beet or potato. Those strains have only one unique gene. All strains could use numerous sugars as building materials and energy sources and possessed a high repertoire of virulence determinants in the genomes. P. betavasculorum strains were able to cause disease symptoms on potato tubers and chicory leaves. They were also able to synthesise homoserine lactones and siderophores.

Discussion

The findings underscore the adaptability of P. betavasculorum to diverse hosts and environments. Strains adapted to plants with high sugar content in tissues have a different composition of fatty acids in membranes and a different mechanism of replenishing nitrogen in case of deficiency of this compound than strains derived from other plant species. Extensive phenomics and genomic analyses performed in this study have shown that P. betavasculorum species is an agronomically relevant pathogen.
Phloem anatomy predicts berry sugar accumulation across 13 wine-grape cultivars
Authors: Stanfield Ryan C. , Forrestel Elisabeth J. , Elmendorf Kayla E. , Bagshaw Sophia B. , Bartlett Megan K.
Published: March 2024

Introduction

Climate change is impacting the wine industry by accelerating ripening processes due to warming temperatures, especially in areas of significant grape production like California. Increasing temperatures accelerate the rate of sugar accumulation (measured in ⁰Brix) in grapes, however this presents a problem to wine makers as flavor profiles may need more time to develop properly. To alleviate the mismatch between sugar accumulation and flavor compounds, growers may sync vine cultivars with climates that are most amenable to their distinct growing conditions. However, the traits which control such cultivar specific climate adaptation, especially for ⁰Brix accumulation rate, are poorly understood. Recent studies have shown that higher rates of fruit development and sugar accumulation are predicted by larger phloem areas in different organs of the plant.

Methods

Here we test this phloem area hypothesis using a common garden experiment in the Central Valley of Northern California using 18 cultivars of the common grapevine (Vitis vinifera) and assess the grape berry sugar accumulation rates as a function of phloem area in leaf and grape organs.

Results

We find that phloem area in the leaf petiole organ as well as the berry pedicel is a significant predictor of ⁰Brix accumulation rate across 13 cultivars and that grapes from warm climates overall have larger phloem areas than those from hot climates. In contrast, other physiological traits such as photosynthetic assimilation and leaf water potential did not predict berry accumulation rates.

Discussion

As hot climate cultivars have lower phloem areas which would slow down brix accumulation, growers may have inadvertently been selecting this trait to align flavor development with sugar accumulation across the common cultivars tested. This work highlights a new trait that can be easily phenotyped (i.e., petiole phloem area) and be used for growers to match cultivar more accurately with the temperature specific climate conditions of a growing region to obtain satisfactory sugar accumulation and flavor profiles.