bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world experience with TTFields in glioma patients with emphasis on therapy usage
Authors: Jelgersma Claudius , Alsolivany Joan , Akkas Gülsüm , Wasilewski David , Gastl Bastian , Misch Martin , Capper David , Kaul David , Bullinger Lars , Vajkoczy Peter , Onken Julia
Published: January 2025

Tumor Treating Fields (TTFields) has emerged as a significant adjunctive component in the treatment of high-grade gliomas following the EF-14 trial in 2017. The incorporation of TTFields, alongside cyclic temozolomide therapy, has demonstrated improved patient outcomes when the usage exceeds 18 h per day (75% usage). Post-hoc analysis of the EF-14 trial has demonstrated that therapy usage exceeding 90% is associated with an additional benefit, while rates above 50% have also proven effective in literature. Given the cost-intensive nature and mild- to- moderate constraints associated with the therapy, our objective is to generate real-world data on therapy usage through a retrospective analysis at a high-throughput academic center. Between June 2015 and February 2022, a total of 113 high-grade glioma patients received TTFields therapy. Eight patients discontinued TTFields therapy within 2 months with less than 50% usage and were excluded from further analysis. For the remaining patients, the median age was 51 years (range: 20–76 years) and the mean preoperative Karnofsky index was 80%–90%. Most of the patients (75.2%) initiated therapy concurrently with first-line treatment, of whom 27.6% started TTFields therapy concomitant to the first cycle of temozolomide. 15.2% started TTFields therapy in the second-line and 9.5% in the third-line setting. The study cohort had an average therapy duration of 9.3 months with 3.2 break days per month. The mean therapy usage was 65.5% (SD 17.6%). Usage was highest during the first 3 months, with rates of 77.7%, 72.3%, and 71.6%, and then dropped to around 60% in the following 6 months. Linear regression found no predictors of usage, such as age, timing of therapy initiation, and duration or gender. 55% of patients continued TTFields beyond the first recurrence. Interestingly, no drop in usage rates was observed before tumor recurrence was communicated. However, after diagnosis, patients exhibited a significant drop in usage to an average of 52.3%. This high-volume, real-world TTFields usage data reveal that the extent of usage falls short of the intended 75%. It highlights the importance of monitoring and promoting adherence to maximize its potential benefits in managing high-grade glioma patients. Furthermore, strategies to expedite therapy initiation and improve long-term adherence are warranted.
Interpretable machine learning models for predicting skip metastasis in cN0 papillary thyroid cancer based on clinicopathological and elastography radiomics features
Authors: Yao Xiaohua , Tang Mingming , Lu Min , Zhou Jie , Yang Debin
Published: January 2025

Background

Skip lymph node metastasis (SLNM) in papillary thyroid cancer (PTC) involves cancer cells bypassing central nodes to directly metastasize to lateral nodes, often undetected by standard preoperative ultrasonography. Although multiple models exist to identify SLNM, they are inadequate for clinically node-negative (cN0) patients, resulting in underestimated metastatic risks and compromised treatment effectiveness. Our study aims to develop and validate a machine learning (ML) model that combines elastography radiomics with clinicopathological data to predict pre-surgical SLNM risk in cN0 PTC patients with increased risk of lymph node metastasis (LNM), improving their treatment strategies.

Methods

Our study conducted a retrospective analysis of 485 newly diagnosed primary PTC patients, divided into training and external validation cohorts. Patients were categorized into SLNM and non-SLNM groups based on follow-up outcomes and postoperative pathology. We collected preoperative clinicopathological data and extracted, standardized radiomics features from elastography imaging to develop various ML models. These models were internally validated using radiomics and clinicopathological data, with the optimal model’s feature importance analyzed through the Shapley Additive Explanations (SHAP) approach and subsequently externally validated.

Results

In our study of 485 patients, 67 (13.8%) exhibited SLNM. The extreme gradient boosting (XGBoost) model, integrating elastography radiomics with clinicopathological data, demonstrated superior performance in both internal and external validations. SHAP analysis identified five key determinants of SLNM: three radiomics features from elastography images, one clinical variable, and one pathological variable.

Conclusion

Our evaluation highlights the XGBoost model, which integrates elastography radiomics and clinicopathological data, as the most effective ML approach for the prediction of SLNM in cN0 PTC patients with increased risk of LNM. This innovative model significantly enhances the accuracy of risk assessments for SLNM, enabling personalized treatments that could reduce postoperative metastases in these patients.
Case report: A rare case of three synchronous colon tumors with metastasis to the left inguinal lymph node
Authors: Negrut Roxana Loriana , Cote Adrian , Tica Ovidiu , Maghiar Adrian Marius
Published: January 2025

This study presents a rare case of three synchronous colon tumors with metastasis to the left inguinal lymph node, challenging the conventional understanding of the metastatic pathways and highlighting the exceptional nature of such occurrences. This highlights the importance of considering alternative atypical metastatic routes for the management of colon cancer. A literature search was performed to identify similar cases. Our findings emphasize the need for broader diagnostic evaluations to detect atypical metastasis at early stages. Furthermore, this case highlights the need for potential refinements in follow-up and screening protocols to capture unusual patterns of cancer spread. This case encourages further research into innovative treatments tailored to the unique metastatic behaviors observed in synchronous colon tumors, with a view to improving outcomes in similar cases.
Comparison of outcomes following prepectoral and subpectoral implants for breast reconstruction in patients with breast cancer
Authors: Zhang Jun , An Ran , Yu Zhi-Hao , Zhang Li
Published: January 2025

Background

In recent years, different approaches to implant-based breast reconstruction have increasingly become an important option to meet both the treatment and postoperative aesthetic needs of breast cancer patients. This study selected two commonly used techniques for the prepectoral approach: single-incision, gas-inflated endoscopic prepectoral breast reconstruction (SIE-BR) and open prepectoral implant-based breast reconstruction (C-BR), as well as a commonly used technique for the subpectoral approach: open subpectoral implant-based breast reconstruction (SI-BR). By comparing the clinical efficacy and aesthetic outcomes of these three techniques in the treatment of breast cancer patients, this study aims to summarize the advantages of the prepectoral approach.

Methods

This study screened the clinicopathological data of a total of 136 breast cancer patients from January 2023 to December 2023. Among them, 38 patients underwent SIE-BR, 51 patients underwent C-BR, and 47 patients underwent SI-BR. The patient characteristics, intraoperative and postoperative conditions were analyzed in detail, and satisfaction was assessed using the BREAST-Q questionnaire.

Results

The SIE-BR group had the longest surgery time, followed by the SI-BR group, with the C-BR group having the shortest surgery time. The C-BR group had the least blood loss, while the SIE-BR group had the most. The C-BR group also had the lowest drainage volume, and the SIE-BR group had the highest. Patients were categorized into a prepectoral implant-based reconstruction group (PIBR) and a subpectoral implant-based reconstruction group (SIBR). None of the patients experienced implant loss or flap necrosis. The PIBR group had significantly lower rates of wound infection, capsular contracture, and chest muscle pain compared to the SIBR group. The rates of wound dehiscence and implant wrinkling were statistically similar between the two groups. BREAST-Q scores indicated similar satisfaction in terms of breast appearance and sexual life between the groups, but the PIBR group showed significantly better scores in physical health (chest muscle function preservation) and mental health. Additional advantages of the prepectoral approach, including less postoperative pain, reduced movement-related deformity, and shorter surgery time, have contributed to the steady growth of this technique in recent years.

Conclusion

The three implant-based breast reconstruction techniques mentioned above are safe and feasible. Compared to the previously more common subpectoral approach, the prepectoral approach improves patients’ postoperative physical and psychological comfort, making it an ideal surgical option.
REV7: a small but mighty regulator of genome maintenance and cancer development
Authors: Maggs Lara R. , McVey Mitch
Published: January 2025

REV7, also known as MAD2B, MAD2L2, and FANCV, is a HORMA-domain family protein crucial to multiple genome stability pathways. REV7’s canonical role is as a member of polymerase ζ, a specialized translesion synthesis polymerase essential for DNA damage tolerance. REV7 also ensures accurate cell cycle progression and prevents premature mitotic progression by sequestering an anaphase-promoting complex/cyclosome activator. Additionally, REV7 supports genome integrity by directing double-strand break repair pathway choice as part of the recently characterized mammalian shieldin complex. Given that genome instability is a hallmark of cancer, it is unsurprising that REV7, with its numerous genome maintenance roles, is implicated in multiple malignancies, including ovarian cancer, glioma, breast cancer, malignant melanoma, and small-cell lung cancer. Moreover, high REV7 expression is associated with poor prognoses and treatment resistance in these and other cancers. Promisingly, early studies indicate that REV7 suppression enhances sensitivity to chemotherapeutics, including cisplatin. This review aims to provide a comprehensive overview of REV7’s myriad roles in genome maintenance and other functions as well as offer an updated summary of its connections to cancer and treatment resistance.
Advances and current concepts on Eph receptors and ephrins in upper digestive tract cancers
Authors: Lavareze Luccas , Kimura Talita de Carvalho , Scarini João Figueira , de Lima-Souza Reydson Alcides , Gonçalves Moisés Willian Aparecido , Sales de Sá Raisa , Aquino Iara Gonçalves , Fernandes Patricia Maria , Ribeiro Fernanda Cristina Poscai , Altemani Albina , Mariano Fernanda Viviane , Fillmore Gary Chris , Egal Erika Said Abu
Published: January 2025

Erythropoietin-producing hepatocellular (Eph) receptors comprise the largest group of surface receptors and are responsible for cellular signals. Eph/ephrin signaling has been identified to play a role in key cancer development and progression processes, especially in the upper gastrointestinal tract. The Eph/ephrin system has been described as a tumor suppressor in duodenal cancer, while in esophageal, gastric, hepatic, and pancreatic cancer, the system has been related to tumor progression. For their significant role in developing a wide range of malignancies, Eph receptors and their ligands have proven to be an important target for new anticancer therapies. In this review, we present an overview of the literature and highlight evidence supporting the role of the Eph/ephrin system in upper digestive tract cancers. In addition, we discuss molecular findings that represent promising therapeutic targets for these cancers.
Narcolepsy in early childhood: a case report and a Mini review
Authors: Liu Guorui , Li Guanxiong , Wang Yihao , Yin Ming , Pan Wen , Zhao Yu , Gao Shigeng , Shi Peiqi , Wen Jing , Pan Xiao , Wang Yajing , Zhang Yanfei
Published: January 2025

Narcolepsy is a sleep-wake disorder with an onset commonly seen in individuals aged 10–30 years. Due to various reasons, the diagnosis of narcolepsy often experiences a delay of at least ten years. Diagnosing narcolepsy in children is particularly challenging due to atypical symptoms, leading to frequent misdiagnosis or missed diagnoses. We report a case of narcolepsy in a four-year-old girl to provide insights into the early diagnosis and treatment of narcolepsy in children. As a chronic condition, narcolepsy can lead to decreased quality of life, including psychological issues such as depression and anxiety. Furthermore, there are few randomized controlled trials involving pediatric narcolepsy patients. To provide a comprehensive treatment approach for pediatric narcolepsy, we review the current progress in the treatment of narcolepsy in children.
Prevalence of overweight and obesity among preschool children in Hainan: a cross-sectional study in China's largest free-trade zone
Authors: Wu Wei-Jia , Chen Ping-Hao , Huang Zhen-Ning , Lei Xue-Lu , Wang Chen , Zhang Chun-hui , Wang Ping , Huang Chui-can , Luo Qing , Fan Li-Chun
Published: January 2025

Background and aims

Childhood obesity leads to significant health risks, emphasizing the critical need for effective preventive measures during the preschool years. However, there is a lack of comprehensive studies on overweight and obesity among preschool children in Hainan Island, China's largest free-trade zone. Our study assessed the prevalence of overweight and obesity among preschool children across Hainan Island using Chinese, World Health Organization (WHO), and International Obesity Task Force (IOTF) criteria. Additionally, the potential factors influencing overweight and obesity among preschool children in Hainan Island were further explored.

Methods

We conducted a cross-sectional survey of children aged 3–6 years covering 18 cities and counties in China's largest free trade zone. The survey primarily involved anthropometric data collection and questionnaires on children's information and the sociodemographic characteristics of their parents or guardians. We recorded the height and weight of each child and calculated their body mass index (BMI). The z-score for BMI-for-age was calculated using the WHO-recommended Anthro and AnthroPlus software, and diagnoses of overweight and obesity were determined separately according to the Chinese, WHO, and IOTF criteria. The chi-squared test, t-test, or rank-sum test was applied to describe and statistically analyze the baseline characteristics of the participating children. Additionally, potential factors affecting overweight and obesity were analyzed using a multifactor binary logistic regression model.

Results

The prevalence of overweight and obesity among preschool children in Hainan Island was 11.30% based on the Chinese criteria, significantly higher than the rates of 5.80% and 5.40% observed according to the WHO and IOTF criteria, respectively (χ2 = 12,870.368, P < 0.001). After multifactorial adjusted analyses, we found that according to the three growth criteria, having overweight fathers or mothers, family incomes of more than 100,000 Yuan, fully active eating, and higher birth weights increased the risk of overweight and obesity among preschool children in Hainan Island.

Conclusion

The prevalence of overweight and obesity among preschool children in Hainan Island was lower compared to rates reported in other regions. Considering that the growth and development indicators for children under 7 years old in Hainan Island are generally lower than international standards, the use of Chinese standards may be more suitable for detecting overweight and obesity among preschool children in this area. Based on the risk factors identified in this study, preventive measures can be targeted in the future to reduce the risk of overweight and obesity in preschool children in Hainan Island.
Association of vitamin D deficiency and insufficiency with uncontrolled type 1 diabetes Mellitus among Saudi pediatric patients; a hospital-based retrospective study
Authors: Almansour Salman , Alsalamah Abdullrahman , Almutlaq Mohammad , Sheikh Ahmed , Hamdan Hamdan Z. , Al-Nafeesah Abdullah , AlEed Ashwaq , Adam Ishag , Al-Wutayd Osama
Published: January 2025

Background

The association between 25-hydroxy-vitamin D [25(OH)D] levels and glycemic control in pediatric patients with type 1 diabetes mellitus (T1DM) is unclear. In this study, we aimed to investigate the association between 25(OH)D levels and glycemic control in Saudi pediatric patients' with T1DM in a region that is sunny year-round.

Materials and methods

A retrospective study was conducted in the Pediatric Department of King Saud Hospital in Unaizah, Saudi Arabia. A total of 218 children with T1DM were enrolled in the study and grouped according to their glycated hemoglobin (HbA1C) levels into the controlled T1DM (HbA1C ≤ 7.5%) and the uncontrolled T1DM (HbA1C > 7.5%). Their 25(OH)D levels and thyroid function were measured using standard methods.

Results

Of the 218 children in this study, 182 (83.5%) had uncontrolled T1DM, while only 36 (16.5%) had controlled T1DM. The median (interquartile range) of 25(OH)D levels was significantly lower in the uncontrolled T1DM group compared with the controlled group [45.4 (31.2–59.7) nmol/L vs. 56.1 (37.5–77.6) nmol/L; p = 0.007], respectively. Vitamin D deficiency (<50.0 nmol/L) and insufficiency (50–74 nmol/L) were detected in 55.0% and 31.1% of all the enrolled children, respectively. Vitamin D deficiency was detected in 86.6% of the uncontrolled T1DM patients and in 16.5% of the controlled T1DM patients (p = 0.012). The multivariable analysis showed that both vitamin D deficiency [adjusted odds ratio (aOR) = 2.92, p = 0.048] and insufficiency [aOR = 3.17, p = 0.042] were risk factors for uncontrolled diabetes.

Conclusion

Vitamin D deficiency was highly prevalent in the studied group. Both vitamin D deficiency and insufficiency are associated with uncontrolled T1DM. Further study is needed.
Vitamin D protects spermatogonia and Sertoli cells from heat stress damage by inhibiting NLRP3
Authors: Chu Han , Deng Qi-Fei , Fang Yuan
Published: January 2025

Introduction

Cryptorchidism can damage cells in the cryptorchid testes due to elevated local temperatures, potentially impacting the fertility of the child in adulthood. Research indicates that vitamin D enhances sperm quality in adult males. This study aimed to explore whether vitamin D inhibits NLRP3 activation, thus helping to mitigate heat stress damage to testicular spermatogenic and Sertoli cells.

Materials and methods

Five cases of normal testicular tissue adjacent to a tumor (testis removed due to tumorous growth) and five cases of atrophied cryptorchid testicular tissue (testis removed) were analyzed for immunohistochemistry to determine NLRP3 expression in cryptorchid tissue. In Phase I, spermatogonia (GC-1) and Sertoli cells (TM4) were separated into blank and heat stress groups. Apoptosis, inflammatory factor levels, and the expression of Bcl-2 and NLRP3 genes and proteins were measured at 2, 6, and 10 h after heat stress treatment. In Phase II, the cells were re-cultured and divided into three groups: heat stress, siRNA + heat stress, and VD + heat stress. After 10 h, the apoptosis, inflammatory factor levels, and gene and protein expressions of Bcl-2 and NLRP3 were reassessed in each group.

Results

Immunohistochemistry indicated NLRP3 expression in cryptorchid tissue. Phase I, extending heat stress duration led to increased apoptosis in spermatogonia (GC-1) and testicular Sertoli cells (TM4), heightened levels of inflammatory factors, reduced BCL-2 expression, and elevated NLRP3 expression compared to the control group. Phase II, both the siRNA + heat stress and VD + heat stress groups showed decreased apoptosis in spermatogonia and Sertoli cells, lower inflammatory factor levels, increased BCL-2 expression, and decreased NLRP3 expression compared to the heat stress-only group, with statistically significant differences (P < 0.05).

Conclusions

This is the first time we found the expression of NLRP3 in cryptorchidism. Vitamin D can inhibit the expression of NLRP3 and reduce the damage of heat stress on testicular spermatogenic cells and Sertoli cells, and play a protective role for testicular spermatogenic cells and Sertoli cells. This provides a theoretical basis for preserving testicular function during the “treatment gap” in boys with cryptorchidism who have not received surgical treatment.
SOCS1 deficiency—crossroads of autoimmunity and autoinflammation—two case reports
Authors: Trojovsky Kajetan , Seidl Maximilian , Babor Florian , Ehl Stephan , Lee-Kirsch Min Ae , Friedt Michael , Laws Hans-Juergen , Naami Nibras , Oommen Prasad Thomas , Ghosh Sujal
Published: January 2025

Suppressors of cytokine signaling (SOCS) proteins play a critical role in regulating immune signaling pathways. Deficiency of SOCS1 leads to various autoimmune pathologies. We present two unrelated patients with distinct clinical manifestations. Patient 1, a 16-year-old male from Guinea, presented with Evans Syndrome, musculoskeletal pain and elevated liver enzymes. Patient 2, a 6-year-old German boy, developed recurrent oral aphthous ulcers, mild inflammatory bowel disease and chronic recurrent multifocal osteomyelitis. Both patients were diagnosed with SOCS1 deficiency by genetic testing. Treatment strategies included steroids, JAK inhibition and colchicine. These cases emphasize the importance of considering SOCS1 deficiency in patients with autoimmune or autoinflammatory diseases but also in patients with unexplained elevated IgE levels. They highlight the need for further research in ongoing multicenter registries to better understand this condition.
Nature’s magic: how natural products work hand in hand with mitochondria to treat stroke
Authors: Cheng Lin , Lv Shangbin , Wei Chengkai , Li Sucheng , Liu Hao , Chen Yong , Luo Zhaoliang , Cui Hongyan
Published: January 2025

Background

Mitochondria, as the energy factories of cells, are involved in a wide range of vital activities, including cell differentiation, signal transduction, the cell cycle, and apoptosis, while also regulating cell growth. However, current pharmacological treatments for stroke are challenged by issues such as drug resistance and side effects, necessitating the exploration of new therapeutic strategies.

Objective

This review aims to summarize the regulatory effects of natural compounds targeting mitochondria on neuronal mitochondrial function and metabolism, providing new perspectives for stroke treatment.

Main findings

Numerous in vitro and in vivo studies have shown that natural products such as berberine, ginsenosides, and baicalein protect neuronal mitochondrial function and reduce stroke-induced damage through multiple mechanisms. These compounds reduce neuronal apoptosis by modulating the expression of mitochondrial-associated apoptotic proteins. They inhibit the activation of the mitochondrial permeability transition pore (mPTP), thereby decreasing ROS production and cytochrome C release, which helps preserve mitochondrial function. Additionally, they regulate ferroptosis, mitochondrial fission, and promote mitochondrial autophagy and trafficking, further enhancing neuronal protection.

Conclusion

As multi-target chemical agents, natural products offer high efficacy with fewer side effects and present promising potential for innovative stroke therapies. Future research should further investigate the effectiveness and safety of these natural products in clinical applications, advancing their development as a new therapeutic strategy for stroke.
Disproportionate adverse event signals of selumetinib in neurofibromatosis type I: insights from FAERS
Authors: Li Lin
Published: January 2025

Background

Neurofibromatosis type 1 (NF1) is a rare neurogenetic disorder with limited treatment options. Selumetinib, a MEK1/2 inhibitor, has emerged as a promising therapy for inoperable NF1-related plexiform neurofibromas.

Methods

Our retrospective pharmacovigilance study utilized the FDA Adverse Event Reporting System (FAERS) to comprehensively evaluate Selumetinib’s safety profile in real-world settings. Data from the third quarter of 2020 to the fourth quarter of 2023 were analyzed, identifying 498 adverse event reports with Selumetinib as the primary suspect drug.

Results

Statistical analysis revealed disproportionate signals for skin and subcutaneous tissue disorders, eye disorders, and various congenital, familial, and genetic disorders. The most common adverse events were elevated blood creatine phosphokinase, rash, and acneiform dermatitis. Notably, several adverse events, including rhabdomyolysis, were identified but not listed on the Selumetinib product label, based on a comparison with the FDA drug labeling.

Conclusion

The study underscores the importance of early detection and management of adverse reactions associated with Selumetinib, particularly within the initial month of treatment. These findings provide valuable insights for clinicians and regulators to ensure the safe and effective use of Selumetinib in NF1 patients.
Recent advances in the anti-tumor activities of saponins through cholesterol regulation
Authors: Jiang Min , Hong Chao , Zou Wenkui , Ye Zheng , Lu Lu , Liu Yun , Zhang Tong , Ding Yue
Published: January 2025

Abnormal cholesterol metabolism has become a popular therapeutic target in cancer therapy. In recent years there has been a surge in interest in the anti-tumor activities of saponins, particularly their ability to disrupt cholesterol homeostasis in tumor cells. Cholesterol regulation by saponins is a complex process that involves multiple mechanisms. However, there are now a notable dearth of comprehensive reviews addressing their anti-tumor effects through cholesterol modulation. This review will explore the intricate mechanisms by which saponins regulate cholesterol, including modulation of synthesis, metabolism, and uptake, as well as complex formation with cholesterol. It will also outline how saponins exert their anti-cancer activities through cholesterol regulation, enhancing cytotoxicity, inhibiting tumor cell metastasis, reversing drug resistance, inducing immunotoxin macromolecule escape, and ferroptosis. This comprehensive analysis offers insights into the potential for the use of saponins anti-tumor therapies and their combinations with other drugs, advancing the understanding of their effects on cancer cells.
Identification of ALEKSIN as a novel multi-IRF inhibitor of IRF- and STAT-mediated transcription in vascular inflammation and atherosclerosis
Authors: Antonczyk Aleksandra , Kluzek Katarzyna , Herbich Natalia , Boroujeni Mahdi Eskandarian , Krist Bart , Wronka Dorota , Karlik Anna , Przybyl Lukasz , Plewinski Adam , Wesoly Joanna , Bluyssen Hans A. R.
Published: January 2025

Cardiovascular diseases (CVDs) include atherosclerosis, which is an inflammatory disease of large and medium vessels that leads to atherosclerotic plaque formation. The key factors contributing to the onset and progression of atherosclerosis include the pro-inflammatory cytokines interferon (IFN)α and IFNγ and the pattern recognition receptor (PRR) Toll-like receptor 4 (TLR4). Together, they trigger the activation of IFN regulatory factors (IRFs) and signal transducer and activator of transcription (STAT)s. Based on their promoting role in atherosclerosis, we hypothesized that the inhibition of pro-inflammatory target gene expression through multi-IRF inhibitors may be a promising strategy to treat CVDs. Using comparative in silico docking of multiple IRF–DNA-binding domain (DBD) models on a multi-million natural compound library, we identified the novel multi-IRF inhibitor, ALEKSIN. This compound targets the DBD of IRF1, IRF2, and IRF8 with the same affinity and simultaneously inhibits the expression of multiple IRF target genes in human microvascular endothelial cells (HMECs) in response to IIFNα and IFNγ. Under the same conditions, ALEKSIN also inhibited the phosphorylation of STATs, potentially through low-affinity STAT-SH2 binding but with lower potency than the known multi-STAT inhibitor STATTIC. This was in line with the common inhibition of ALEKSIN and STATTIC observed on the genome-wide expression of pro-inflammatory IRF/STAT/NF-κB target genes, as well as on the migration of HMECs. Finally, we identified a novel signature of 46 ALEKSIN and STATTIC commonly inhibited pro-atherogenic target genes, which was upregulated in atherosclerotic plaques in the aortas of high-fat diet-fed ApoEKO mice and associated with inflammation, proliferation, adhesion, chemotaxis, and response to lipids. Interestingly, the majority of these genes could be linked to macrophage subtypes present in aortic plaques in HFD-fed LDLR-KO mice. Together, this suggests that ALEKSIN represents a novel class of multi-IRF inhibitors, which inhibits IRF-, STAT-, and NF-κB-mediated transcription and could offer great promise for the treatment of CVDs. Furthermore, the ALEKSIN and STATTIC commonly inhibited pro-inflammatory gene signature could help monitor plaque progression during experimental atherosclerosis.
Current research status and trends of potassium-competitive acid blockers in the treatment of acid-related diseases: a bibliometric analysis
Authors: Zhu Baoqiang , Chen Long , Tao Xue , Zheng Hong , Li Xia , Wu Qingfang , Long Enwu , Lin Haixia
Published: January 2025

Objective

To explore the current research status and trends of potassium-competitive acid blockers (P-CABs) in the treatment of acid related diseases (ARDs) using bibliometric analysis.

Materials and methods

We collected publications related to P-CAB in the treatment of acid-related diseases in the Web of Science (WOS) Core Collection from the establishment of the database to 30 June 2024. We evaluated the publication volume and citation status over the years using the WOS platform, and visualized the authors, countries, institutions, keywords, and citations of the publications using CiteSpace and VOSviewer.

Results

This study included a total of 455 articles. The number of publications and citations related to research has been increasing year by year. The results show that the scholars with the highest number of publications mainly come from South Korea and Japan. Scholars such as Geun Seog Song, Bongtae Kim, and Nobuhiro Inatomi produced many works in related fields. The most popular drug in this field was vonoprazan, and research on this drug mainly focused on the effectiveness and safety evaluation of ARDs such as Helicobacter pylori infection, gastroesophageal reflux disease, peptic ulcers, etc. Researchers were concerned about the evaluation of treatment regimens and efficacy comparison between P-CABs and traditional proton pump inhibitors (PPIs) in the treatment of ARDs. At the same time, researchers are also closely monitoring the potential adverse reactions and long-term adverse outcomes of clinical application of P-CABs for ARDs.

Conclusion

The clinical application of P-CABs, represented by vonoprazan, in ARDs is receiving widespread attention from researchers. The exploration of the application of this type of drug in ARDs is constantly expanding, and it is a research field with great clinical value and research potential.
Oxyberberine alleviates lipopolysaccharide-induced intestinal barrier disruption and inflammation in human colonic Caco-2 cells in vitro
Authors: Li Cailan , Wang Jiahao , Yang Hongmei , Luo Shuang , Lu Qiang
Published: January 2025

Background

Oxyberberine (OBB) is a naturally occurring isoquinoline alkaloid that is believed to possess various health-promoting properties, including anti-fungus, hepatoprotection, anti-inflammation, and anti-intestinal mucositis effects. Despite several studies reporting the health benefits of OBB in treating ulcerative colitis (UC), its specific mechanism of action has yet to be fully elucidated.

Purpose

This investigation is designed to explore the potential protective efficacy of OBB and the latent mechanism using an in vitro model of UC-like inflammatory intestinal cells.

Methods

Caco-2 cells were pretreated with OBB and subsequently exposed to lipopolysaccharide (LPS). The transepithelial electrical resistance (TEER), paracellular permeability, and the distribution and expression of tight- and adherent junction proteins were determined to assess barrier integrity. The levels of proinflammatory cytokines, reactive oxygen species (ROS), Nrf2, and NF-κB signaling cascade were analyzed via ELISA, qRT-PCR, immunofluorescence, or Western blotting.

Results

OBB was found to mitigate the effects of LPS on Caco-2 cell monolayers, as evidenced by the improvement in TEER and the decrease in FITC-dextran flux. Moreover, OBB ameliorated the LPS-induced decrease in the distribution and expression of several tight junction markers, including ZO-1, occludin, and E-cadherin. In addition, OBB treatment effectively inhibited LPS-induced increases in ROS, apoptosis, and Keap1 and decreases in Nrf2 and HO-1. LPS-induced elevations in nuclear NF-κB p65 and p-IκBα were suppressed by OBB. In addition, ML385, an antagonist of Nrf2, abolished the protective role of OBB.

Conclusion

OBB has a pronounced beneficial effect on LPS-induced damage to enteral barrier function, and the regulation of the Nrf2/NF-κB pathway is an important mechanism responsible for the protection afforded by OBB.
Uvaol attenuates TGF-β1-induced epithelial-mesenchymal transition in human alveolar epithelial cells by modulating expression and membrane localization of β-catenin
Authors: Patrícia Gonçalves Tenório Liliane , Xavier Felipe Henrique da Cunha , Silveira Wagner Mônica , Moreira Bagri Kayo , Alves Ferreira Erick Gabriel , Galvani Romulo , Mermelstein Claudia , Bonomo Adriana Cesar , Savino Wilson , Barreto Emiliano
Published: January 2025

The epithelial-mesenchymal transition (EMT) is a biological process in which epithelial cells change into mesenchymal cells with fibroblast-like characteristics. EMT plays a crucial role in the progression of fibrosis. Classical inducers associated with the maintenance of EMT, such as TGF-β1, have become targets of several anti-EMT therapeutic strategies. Natural products from the pentacyclic triterpene class have emerged as promising elements in inhibiting EMT. Uvaol is a pentacyclic triterpene found in olive trees (Olea europaea L.) known for its anti-inflammatory, antioxidant, and antiproliferative properties. Yet, its effect on the TGF-β1-induced EMT in alveolar epithelial cells is unknown. The present study aimed to investigate the impact of uvaol upon TGF-β1-induced EMT in a cultured A549 human alveolar epithelial cell line, a classic in vitro model for studies of EMT. Changes in cell shape were measured using phase-contrast and confocal microscopy, whereas protein expression levels were measured using immunofluorescence, flow cytometry, and Western blotting. We also performed wound scratch experiments to explore its effects on cell migration. Uvaol had no significant cytotoxic effects on A549 cells. By contrast, the changes in the cell morphology consistent with TGF-β1-induced EMT were largely suppressed by treatment with uvaol. In addition, increased contents of mesenchymal markers, namely, vimentin, N-cadherin, and fibronectin in TGF-β1-induced A549 cells, were downregulated by uvaol treatment. Furthermore, the TGF-β1-induced migration of A549 cells was significantly suppressed by uvaol. Mechanistically, uvaol prevented the nuclear translocation of β-catenin and reduced the TGF-β1-induced levels of ZEB1 in A549 cells. These results provide compelling evidence that uvaol inhibits EMT by regulating proteins related to the mesenchymal profile in human alveolar epithelial cells, likely by modulating β-catenin and ZEB1 levels.
Ponatinib alleviates non-alcoholic steatohepatitis through TFEB-mediated autophagy
Authors: Lin Zhuomiao , Yang Meiqing , Yu Xihui , Tan Guozhu , Zhong Jiahong
Published: January 2025

Objective

Non-alcoholic steatohepatitis (NASH) is a progressive liver disease with lipid accumulation, inflammation, and liver fibrosis. Ponatinib, a third-generation tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia, was found to improve metabolic disorders in mice. However, the role of ponatinib in liver inflammation and fibrosis remains to be elucidated. Here we aimed to determine the effect of ponatinib in non-alcoholic steatohepatitis.

Methods

We explored the function and mechanism of ponatinib using a mouse model of NASH induced by a methionine and choline deficient (MCD) diet and LO2 cells cultured in MCD mimic medium.

Results

Here, we found that ponatinib reduced liver lipid deposition, fibrosis, and inflammation induced by MCD diet without affecting body weight and blood glucose. Meanwhile, we found that ponatinib attenuated steatohepatitis and inflammation in LO2 cells induced by MCD mimic medium. We further discovered that the expression levels of LC3II and lysosomal associated membrane protein 1 (LAMP1) were reduced and the expression level of p62 was upregulated in both mouse and cell models, suggesting that autophagy was inhibited, which was restored by ponatinib treatment. In addition, transcription factor EB (TFEB) is a major regulator of autophagy and lysosome biogenesis and the transcription and protein expression levels of TFEB were decreased in steatosis hepatocytes, which could be ameliorated by ponatinib treatment.

Conclusion

These results revealed that the beneficial effects of ponatinib on NASH via TFEB-mediated autophagy.
Identification of Salvia miltiorrhiza germplasm resources based on metabolomics and DNA barcoding
Authors: He Gaojie , Man Jinhui , Chen Ying , Zhang Xiaoqin , Wang Xin , An Kelu , Amu Laha , Chen Wenqin , Wang Baowei , Shi Yue , Wang Xiaohui , Wei Shengli
Published: January 2025

Introduction

Salvia miltiorrhiza radix et rhizoma (Danshen) is a crucial medicinal material for treating cardiovascular and cerebrovascular diseases. However, the presence of adulterants and intraspecific variability poses challenges to its clinical safety.

Methods

This study collected samples of S. miltiorrhiza from various regions and commonly encountered adulterants. The composition differences of S. miltiorrhiza radix and its adulterants were analyzed by fingerprint and broad-target metabolomics. Chloroplast genome was used to distinguish intra-genus species and DNA barcoding was used to identify germplasm sources.

Results

The fingerprinting analysis proved that there is no chemical composition consistency between S. miltiorrhiza radix and its adulterants. Broad-targeted metabolomics can distinguish S. miltiorrhiza radix from Salvia yunnanensis radix, Dipsacus asperoides radix, and Arctium lappa radix. Additionally, comparative chloroplast genome analysis indicated that atpF and rps4-trnT-UGU were the potential DNA barcodes for S. miltiorrhiza. 259 samples from 13 provinces and 21 origins were amplified and sequenced, resulting in the identification of 62 haplotypes. The unique haplotypes found in Shanxi Luoyang, Shandong Qingdao and other places can be used as molecular geographic markers for the identification of the germplasm source of S. miltiorrhiza.

Discussion

This study systematically differentiates S. miltiorrhiza from its adulterants and highlights the potential of unique haplotypes as markers for sourcing. The findings provide strong scientific evidence for the clinical safety of S. miltiorrhiza, emphasizing the importance of proper cultivation, selection, and breeding of varieties.
Expression of secondary sexual dimorphism in photosynthetic performance of Ilex paraguariensis under contrasted light availability of monoculture and agroforestry during annual rhythmic growth
Authors: Rakocevic Miroslava , Batista Eunice Reis , de Almeida Rafael Leonardo , Wendling Ivar , Ribeiro Rafael Vasconcelos
Published: January 2025

Plants have developed specific mechanisms to tackle environmental challenges. During one annual period, a dioecious yerba mate with rhythmic growth can present two growth units (GU1 and GU2) intercalated with two rest periods (R1 and R2). We hypothesized that photosynthetic performance will be much higher under monoculture (MO, high light) than under an agroforestry system (AFS, low light) over annual growth and that secondary sexual dimorphism (SSD) will be more expressed during rest than during growth periods. We evaluated the maximum net photosynthesis (Amax), apparent quantum efficiency of CO2 assimilation (Ф), respiration rate in the dark (Rd) and in the light (RL), RL/Rd ratio, maximum apparent rate of electron transport (Jmax), maximum apparent RuBisCO carboxylation rate (Vcmax), Jmax/Vcmax ratio, and chlorophyll indexes in four (two male and two female) clones. Light was reduced by 92%–95% in AFS compared to MO. Photosynthetic traits generally varied over the annual rhythmic growth and revealed higher photosynthetic performance under MO than AFS. Lower Amax and Rd in all clones under AFS than MO occurred together with higher inhibition of respiration by light (low RL/Rd) under AFS than MO. Despite the strong effect of cultivation systems and growth rhythmicity on photosynthetic traits, our data did not suggest that the frequency of SSD in photosynthetic performance (with the exception of the Jmax/Vcmax ratio) was related to the cultivation system or period of rhythmic growth. The SSD was expressed in a higher Chl b index and lower Chl a/b ratio in female than male plants during R2 and GU2, indicating lower sensitivity of females to extreme light conditions of two cultivation systems than males. Higher Amax and similar respiration rates (Rd and RL) in females compared to in males in early vegetative phases after pruning (herein R1 and GU1) could be considered as a fitness strategy of female plants in their additional effort to produce fruits and seeds in latter phases. Our results additionally revealed the importance of the evaluation period when assessing photosynthesis in plant species with rhythmic growth.
Effects of aerobic training with blood flow restriction on aerobic capacity, muscle strength, and hypertrophy in young adults: a systematic review and meta-analysis
Authors: Gao Zhendong , Li Yan , Zhang Jinjin , Li Liqiang , Wang Tao , Wang Xiaolin , Wang Hao
Published: January 2025

Aerobic training with blood flow restriction (AT-BFR) has shown promise in enhancing both aerobic capacity and exercise performance. The aim of this review was to systematically analyze the evidence regarding the effectiveness of this novel training method on aerobic capacity, muscle strength, and hypertrophy in young adults. Studies were identified through a search of databases including PubMed, Scopus, Web of Science, SPORTDiscus, CINAHL, Cochrane Library, and EMBASE. A total of 16 studies, involving 270 subjects, were included in the meta-analysis. The results revealed that AT-BFR induced greater improvements in VO2max (SMD = 0.27, 95%CI: [0.02, 0.52], p < 0.05), and muscle strength (SMD = 0.39, 95%CI: [0.09, 0.69], p < 0.05), compared to aerobic training with no blood flow restriction (AT-noBFR). However, no significant effect was observed on muscle mass (SMD = 0.23, 95%CI: [-0.09, 0.56], p = 0.162). Furthermore, no moderating effects on the outcomes were found for individual characteristics or training factors. In conclusion, AT-BFR is more effective than AT-noBFR in improving aerobic capacity and muscle strength, making it a promising alternative to high-intensity training.

Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024559872.
Association between phase angle and daily creatinine excretion changes in critically ill patients: an approach to muscle mass
Authors: Vargas-Errázuriz Patricio , Dreyse Natalia , López René , Cano-Cappellacci Marcelo , Graf Jerónimo , Guerrero Julia
Published: January 2025

Assessing muscle mass in critically ill patients remains challenging. This retrospective cohort study explores the potential of phase angle (PA°) derived from bioelectrical impedance analysis (BIA) as a surrogate marker for muscle mass monitoring by associating it with daily creatinine excretion (DCE), a structural and metabolic muscle mass marker. In 20 ICU patients, we observed a linear relationship between PA° and DCE at initial (S1) and follow-up (S2) points, with Rho values of 0.78 and 0.65, respectively, as well as between their percentage changes (Rho = 0.80). Multivariate analysis confirmed a strong association between changes in PA° and DCE (adjusted R2 of 0.73), while changes in the extracellular water to total body water (ECW/TBW) ratio showed no significant association. This study establishes a relationship between a BIA-derived independent-weight parameter and DCE, highlighting the potential of PA° for muscle mass monitoring during acute changes, such as those seen in ICU settings. Integrating PA° into clinical practice could provide a non-invasive and reliable tool to enhance muscle assessment and support targeted interventions in critically ill patients.
Cross-education: motor unit adaptations mediate the strength increase in non-trained muscles following 8 weeks of unilateral resistance training
Authors: Lecce Edoardo , Conti Alessandra , Del Vecchio Alessandro , Felici Francesco , Scotto di Palumbo Alessandro , Sacchetti Massimo , Bazzucchi Ilenia
Published: January 2025

Introduction

Early increases in muscle strength following unilateral resistance training are typically accompanied by strength gains in the contralateral untrained muscles, a phenomenon known as cross-education. However, the specific motor unit adaptations responsible for this gain transfer remain poorly understood. To address this gap, we recorded myoelectrical activity from the biceps brachii using high-density electromyography.

Methods

Nine participants performed 8-week unilateral resistance training and were compared to nine control individuals who did no intervention. Discharge characteristics of longitudinally tracked motor units were assessed during maximal voluntary contractions and isometric ramp contractions at 35% and 70% of the maximal voluntary force (MVF) at baseline (T0), 4 weeks (T1), and 8 weeks (T2) post-intervention.

Results

MVF increased by 7% in untrained muscles at T1 and 10% at T2 (p < 0.05). These gains were accompanied by significant decreases in motor unit recruitment thresholds (p < 0.01) and higher net discharge rate (i.e., gain in discharge rate from recruitment to peak) following intervention (p < 0.05). Trained muscles presented greater MVF (+11%, T1; +19%, T2) with similar motor unit adaptations, including a lower recruitment threshold (p < 0.01) and a higher net discharge rate (p < 0.01).

Discussion

Our findings indicate that higher strength in untrained muscles is associated with a higher net discharge rate, implying a greater spinal motoneuron output to muscles. The present results underscore the role of motor unit adaptations in the transfer of strength gains to non-trained muscles, offering novel insights into the neural mechanisms underlying cross-education.