bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unique Phenotypes of C1s Deficiency and Abnormality Caused by Two Compound Heterozygosities in a Japanese Family
Authors: Abe Katsuaki , Endo Yuichi , Nakazawa Naomi , Kanno Kazuko , Okubo Mitsuo , Hoshino Tadashi , Fujita Teizo 
Published: April 2014

Abstract
A deficiency in the early components of complement is associated with an increased susceptibility to pyrogenic infections and multiple autoimmune diseases. We previously reported a Japanese case of selective C1s deficiency resulting from a compound heterozygosity for a 4-bp deletion in exon X and a nonsense mutation Glu597X in exon XII of the C1s gene. In this previous case, the patient suffered from unique symptoms including virus-associated hemophagocytic syndrome and died after a long period of loss of consciousness. In the present study, we report another patient from the same family, with C1s abnormality caused by a distinct compound-heterozygous genotype and who had a novel missense mutation Gly630Glu transmitted from the mother’s side and a previously identified nonsense mutation Glu597X from the father’s side. Thus three distinct mutations of the C1s gene were clustered and resulted in two distinct genotypes for C1s deficiency and C1s abnormality within this one family. The present patient showed symptoms that were similar in part to our previous patient, which were different from those of the cases reported in other families. The biochemical properties of C1s in the patient’s serum and the recombinant form were closely related to the undetectable or very low activity of complement activation. These results suggested that the uniqueness and severity of the symptoms observed here in the two patients might be under the control of a common C1s allele and distinct counterparts, respectively.
Phenotypic and Functional Analysis of CD4+CD25−Foxp3+ T Cells in Patients with Systemic Lupus Erythematosus
Authors: Bonelli Michael , Savitskaya Anastasia , Steiner Carl-Walter , Rath Eva , Smolen Josef S. , Scheinecker Clemens 
Published: April 2014

Abstract
CD4+CD25+Foxp3+ regulatory T cells (Treg) that specialize in the suppression of immune responses might be critically involved in the pathogenesis of autoimmune diseases. Recent studies have described increased proportions of CD4+Foxp3+ T cells that lacked expression of CD25 in systemic lupus erythematosus (SLE) patients but the suppressive capacity of these cells has not been analyzed so far. We therefore performed combined phenotypic and functional analyses of CD4+CD25−Foxp3+ T cells in patients with autoimmune diseases and healthy controls (HC). Phenotypic analysis revealed increased proportions of CD4+CD25−Foxp3+ T cells in SLE patients as compared with patients with systemic sclerosis, rheumatoid arthritis, (RA), or HC. In addition, increased proportions of CD4+CD25−Foxp3+ T cells correlated with the clinical disease activity and the daily cortisone dose. According to phenotypic analysis, CD4+CD25−Foxp3+ T cells resembled regulatory T cells rather than activated T cells. For functional analysis, a surrogate surface marker combination to substitute for intracellular Foxp3 was defined: CD4+CD25−CD127− T cells from SLE patients were isolated by FACS sorting and analyzed for their suppressive capacity in vitro. CD4+CD25−CD127− T cells, that contained up to 53% Foxp3+ T cells, were found to suppress T cell proliferation but not IFN-γ production in vitro. In summary, CD4+CD25−Foxp3+ T cells phenotypically and to a certain extent also functionally resemble conventional Treg. Despite increased proportions, however, their selective functional defects might contribute to the failure of Treg to control autoimmune dysregulation in SLE patients.
Oxidative Stress Mediates a Reduced Expression of the Activating Receptor NKG2D in NK Cells from End-Stage Renal Disease Patients
Authors: Peraldi Marie-Noëlle , Berrou Jeannig , Dulphy Nicolas , Seidowsky Alexandre , Haas Philippe , Boissel Nicolas , Metivier Fabien , Randoux Christine , Kossari Niloufar , Guérin Alain , Geffroy Sylvie , Delavaud Guy , Marin-Esteban Viviana , Glotz Denis , Charron Dominique , Toubert Antoine 
Published: April 2014

Abstract
To characterize the immune defect of patients with end-stage renal disease (ESRD), we performed NK cell subset analysis in 66 patients with ESRD treated by hemodialysis (n = 59) or peritoneal dialysis (n = 7). Compared with healthy blood donors, patients undergoing chronic dialysis showed a profound decrease in NKG2D+ cells within both the CD8+ T cell (58% vs 67%, p = 0.03) and NK cell (39% vs 56%, p = 0.002) populations. CD56dim cells, which comprise the majority of NK cells in the periphery, were more affected in this regard than were CD56bright cells. Uremic serum could decrease NKG2D expression on NK cells from healthy donors. Among factors that could contribute to the decrease in NKG2D expression in ESRD patients, reactive oxygen species (ROS) play a major role. We found that catalase could reverse the effects of uremic serum on NKG2D expression (p &lt; 0.001) and that ROS down-regulated NKG2D at the mRNA level and at the NK cell surface. Additionally, ESRD patients had both increased membrane-bound MHC class I-related chain A (MICA) on monocytes (p = 0.04) and increased soluble MICA (203 pg/ml vs 110 pg/ml; p &lt; 0.001). Both ROS and uremic serum could significantly increase in vitro the expression of the NKG2D ligand MICA on the renal epithelial cell line HK-2. Taken together, these studies suggest for the first time that both low NKG2D expression and up-regulation of its ligand MICA are related to ROS production and may be involved in the immune deficiency of ESRD patients.
Nicotinic Attenuation of Central Nervous System Inflammation and Autoimmunity
Authors: Shi Fu-Dong , Piao Wen-Hua , Kuo Yen-Ping , Campagnolo Denise I. , Vollmer Timothy L. , Lukas Ronald J. 
Published: April 2014

Abstract
The expression of nicotinic acetylcholine receptors by neurons, microglia, and astrocytes suggests possibly diverse mechanisms by which natural nicotinic cholinergic signaling and exposure to nicotine could modulate immune responses within the CNS. In this study, we show that nicotine exposure significantly delays and attenuates inflammatory and autoimmune responses to myelin Ags in the mouse experimental autoimmune encephalomyelitis model. In the periphery, nicotine exposure inhibits the proliferation of autoreactive T cells and alters the cytokine profile of helper T cells. In the CNS, nicotine exposure selectively reduces numbers of CD11c+ dendritic and CD11b+ infiltrating monocytes and resident microglial cells and down-regulates the expression of MHC class II, CD80, and CD86 molecules on these cells. The results underscore roles of nicotinic acetylcholine receptors and nicotinic cholinergic signaling in inflammatory and immune responses and suggest novel therapeutic options for the treatment of inflammatory and autoimmune disorders, including those that affect the CNS.
Anti-Endothelial Antibodies Interfere in Apoptotic Cell Clearance and Promote Thrombosis in Patients with Antiphospholipid Syndrome
Authors: Graham Audrey , Ford Isobel , Morrison Rona , Barker Robert N. , Greaves Mike , Erwig Lars-Peter 
Published: April 2014

Abstract
Antiphospholipid syndrome is an important cause of recurrent thrombotic events. The pathogenesis of the thrombosis remains unclear, but it has been suggested that anti-phospholipid Abs, which are laboratory markers for the disease and include species capable of binding to vascular endothelial cells, play an important role. We hypothesized that these anti-endothelial Abs promote thrombosis through interference with clearance of dying cells. We show that healthy endothelial cell monolayers effectively remove apoptotic endothelial cells, but this clearance is markedly inhibited by serum or IgG from patients with antiphospholipid syndrome and anti-endothelial Abs. In addition, patient sera or IgG opsonize apoptotic endothelial cells and cause enhanced Fc-mediated uptake by professional phagocytes. Importantly, the delayed clearance of apoptotic cells by healthy endothelial cells and the enhanced Fc-mediated macrophage uptake each result in procoagulant consequences, as judged by increased thrombin generation. The effects on apoptotic cell clearance were reproduced by a mAb derived from a patient with antiphospholipid syndrome, which binds to endothelial cells and is thrombogenic in experimental models. Taken together, our data support a novel, dual mechanism by which anti-endothelial Abs are prothrombotic in antiphospholipid syndrome by inhibiting removal of procoagulant apoptotic cells and by diverting their clearance to provoke inflammatory and prothrombotic changes in professional phagocytes.
Review on Some Malaysian Traditional Medicinal Plants with Therapeutic Properties
Authors: Ali Alsarhan  , Ahed Al-Khatib  , Naznin Sultana  , Mohammed Rafiq Abdul Kadir  
Published: April 2014

There are many medicinal plants that have been used for thousands of years. These plants can now be found in herbal products and as part of the traditional Malaysian health care system because of their therapeutic efficacy. This paper discusses the use of ten medicinal plants in the traditional medicinal system of Malaysia and related scientific studies on their Pharmaceutical properties, which demonstrate their traditional uses. The plants viewed are Amaranthus spinosus L., Arundina graminifolia (D.Don) Hochr., Callicarpa arborea Roxb., Carica papaya L., Citrus grandis L., Coleus amboinicus Lour., Curcuma domestica Valeton., Psidium guajava L., Garcinia atroviridis Griff. ex T. Anders., and Zingiber officinale Rosc. All the plants mentioned in this paper have therapeutic properties, which explains and validates their uses in traditional medicine.
Multifunctional Bioactive Nanozyme Systems for Enhanced Diabetic Wound Healing
Authors: Gao Suyue , He Xuefeng , Liu Hengdeng , Liu Yiling , Wang Hanwen , Zhou Ziheng , Chen Lei , Ji Xiaoyuan , Yang Ronghua , Xie Julin 
Published: July 2024

AbstractThe protracted transition from inflammation to proliferation in diabetic wound healing poses significant challenges, exacerbated by persistent inflammatory responses and inadequate vascularization. To address these issues, a novel nanozymatic therapeutic approach utilizing asymmetrically structured MnO₂–Au–mSiO₂@aFGF Janus nanoparticles is engineered. Nanozymes featuring a mSiO₂ head and MnO₂ extensions, into which acidic fibroblast growth factor (aFGF) is encapsulated, resulting in MnO₂–Au–mSiO₂@aFGF Janus nanoparticles (mSAM@aFGF), are synthesized. This nanozyme system effectively emulates enzymatic activities of catalase (CAT) and superoxide dismutase (SOD), catalyzing degradation of reactive oxygen species (ROS) and generating oxygen. In addition, controlled release of aFGF fosters tissue regeneration and vascularization. In vitro studies demonstrate that mSAM@aFGF significantly alleviates oxidative stress in cells, and enhances cell proliferation, migration, and angiogenesis. An injectable hydrogel based on photocrosslinked hyaluronic acid (HAMA), incorporating the nanozymatic ROS‐scavenging and growth factor‐releasing system, is developed. The HAMA‐mSAM@aFGF hydrogel exhibits multifaceted benefits in a diabetic wound model, including injectability, wound adhesion, hemostasis, anti‐inflammatory effects, macrophage polarization from M1 to M2 phenotype, and promotion of vascularization. These attributes underscore the potential of this system to facilitate transition from chronic inflammation to the proliferative phase of wound repair, offering a promising therapeutic strategy for diabetic wound management.
Cross‐Species Prediction of Transcription Factor Binding by Adversarial Training of a Novel Nucleotide‐Level Deep Neural Network
Authors: Zhang Qinhu , Wang Siguo , Li Zhipeng , Pan Yijie , Huang De‐Shuang 
Published: July 2024

AbstractCross‐species prediction of TF binding remains a major challenge due to the rapid evolutionary turnover of individual TF binding sites, resulting in cross‐species predictive performance being consistently worse than within‐species performance. In this study, a novel Nucleotide‐Level Deep Neural Network (NLDNN) is first proposed to predict TF binding within or across species. NLDNN regards the task of TF binding prediction as a nucleotide‐level regression task, which takes DNA sequences as input and directly predicts experimental coverage values. Beyond predictive performance, it also assesses model performance by locating potential TF binding regions, discriminating TF‐specific single‐nucleotide polymorphisms (SNPs), and identifying causal disease‐associated SNPs. The experimental results show that NLDNN outperforms the competing methods in these tasks. Then, a dual‐path framework is designed for adversarial training of NLDNN to further improve the cross‐species prediction performance by pulling the domain space of human and mouse species closer. Through comparison and analysis, it finds that adversarial training not only can improve the cross‐species prediction performance between humans and mice but also enhance the ability to locate TF binding regions and discriminate TF‐specific SNPs. By visualizing the predictions, it is figured out that the framework corrects some mispredictions by amplifying the coverage values of incorrectly predicted peaks.
TIPRL Regulates Stemness and Survival in Lung Cancer Stem Cells through CaMKK2‐CaMK4‐CREB Feedback Loop Activation
Authors: Song In‐Sung , Jeong Yu‐Jeong , Yun Jae Kwang , Lee Jimin , Yang Hae‐Jun , Park Young‐Ho , Kim Sun‐Uk , Hong Seung‐Mo , Lee Peter C.W. , Lee Geun Dong , Jang Sung‐Wuk 
Published: July 2024

AbstractFrequent recurrence and metastasis caused by cancer stem cells (CSCs) are major challenges in lung cancer treatment. Therefore, identifying and characterizing specific CSC targets are crucial for the success of prospective targeted therapies. In this study, it is found that upregulated TOR Signaling Pathway Regulator‐Like (TIPRL) in lung CSCs causes sustained activation of the calcium/calmodulin‐dependent protein kinase kinase 2 (CaMKK2) signaling pathway by binding to CaMKK2, thereby maintaining stemness and survival. CaMKK2‐mediated activation of CaM kinase 4 (CaMK4) leads to phosphorylation of cAMP response element‐binding protein (CREB) at Ser129 and Ser133, which is necessary for its maximum activation and the downstream constitutive expression of its target genes (Bcl2 and HMG20A). TIPRL depletion sensitizes lung CSCs to afatinib‐induced cell death and reduces distal metastasis of lung cancer in vivo. It is determined that CREB activates the transcription of TIPRL in lung CSCs. The positive feedback loop consisting of CREB and TIPRL induces the sustained activation of the CaMKK2‐CaMK4‐CREB axis as a driving force and upregulates the expression of stemness‐ and survival‐related genes, promoting tumorigenesis in patients with lung cancer. Thus, TIPRL and the CaMKK2 signaling axis may be promising targets for overcoming drug resistance and reducing metastasis in lung cancer.
Evaluation of preoperative visceral fat area / psoas muscle area ratio and prognosis in patients with colorectal cancer
Authors: Hosoi Nobuhiro , Shiraishi Takuya , Okada Takuhisa , Osone Katsuya , Yokobori Takehiko , Sakai Makoto , Ogawa Hiroomi , Sohda Makoto , Shirabe Ken , Saeki Hiroshi 
Published: July 2024

AbstractBackgroundRecent research has focused on the prognostic relevance of preoperative sarcopenia and sarcopenic obesity in various cancers. In this study we investigated the relationship between visceral fat area (VFA), psoas muscle area (PMA), and the prognosis of patients undergoing colorectal cancer surgery.MethodsPatients with stage III colorectal cancer who underwent surgery between July 2013 and April 2020 were included. The analysis was performed on 151 patients who met the criteria. The VFA and PMA were measured at the level of the third lumbar vertebra on computed tomography (CT) scans, and the ratio of VFA to PMA (V/P ratio) was determined.ResultsPatients with high V/P ratios were significantly older (p = 0.0213), had a higher body mass index (BMI) (p < 0.0001), a higher percentage of sarcopenic obesity (p < 0.0001), and more diabetes complications (p < 0.0001). Prognostic analysis showed that the overall survival (OS) (p = 0.0154) and relapse‐free survival (RFS) (p = 0.0378) were significantly worse in patients with a high V/P ratio. Multivariate analysis revealed that a high V/P ratio was an independent poor prognostic factor for OS. Subgroup analysis was then performed in patients with BMI < 25 kg/m2. OS (p = 0.0259) and RFS (p = 0.0275) were significantly worse in the high V/P ratio group. A high V/P ratio was an independent poor prognostic factor in the multivariate analysis.ConclusionIn colorectal cancer, the preoperative V/P ratio is an independent factor for poor prognosis. Preoperative evaluation of the V/P ratio may identify a wide range of high‐risk patients because it is an independent poor prognostic factor in patients without obesity.
Naturally Occurring Plant‐Based Anticancerous Candidates as Potential ERK2 Inhibitors: In‐Silico Database Mining and Molecular Dynamics Simulations
Authors: Ibrahim Mahmoud A. A. , Ali Sara S. M. , Abdelrahman Alaa H. M. , Abdeljawaad Khlood A. A. , Sidhom Peter A. , Sayed Shaban R. M. , El‐Tayeb Mohamed A. , Paré Paul W. , Hegazy Mohamed‐Elamir F. 
Published: July 2024

AbstractThe evolutionarily conserved extracellular signal‐regulated kinase 2 (ERK2) is involved in regulating cellular signaling in both normal and pathological conditions. ERK2 expression is critical for human development, while hyperactivation is a major factor in tumor progression. Up to now, there have been no approved inhibitors that target ERK2, and as such, here we report on screening of a naturally occurring plant‐based anticancerous compound‐activity‐target (NPACT) database for prospective ERK2 inhibitors. More than 1,500 phytochemicals were screened using in‐silico molecular docking and molecular dynamics (MD) approaches. NPACT compounds with a docking score lower than a co‐crystallized LHZ inhibitor (calc. −10.5 kcal/mol) were subjected to MD simulations. Binding energies (ΔGbinding) of inhibitor‐ERK2 complexes over the MD course were estimated using an MM‐GBSA approach. Based on MM‐GBSA//100 ns MD simulations, the steroid zhankuic acid C (NPACT01034) demonstrated greater binding affinity against ERK2 protein than LHZ, with ΔGbinding values of −50.0 and −47.7 kcal/mol, respectively. Structural and energetical analyses throughout the MD course demonstrated stabilization of zhankuic acid C complexed with ERK2 protein. The anticipated ADMET properties of zhankuic acid C indicated minimal toxicity. Moreover, in‐silico evaluation of fourteen ERK2 inhibitors in clinical trials demonstrated the higher binding affinity of zhankuic acid C towards ERK2 protein.
Seven New Noroleanane Triterpenoids from Mastic and Their NO Inhibitory and Cytotoxic Activities
Authors: An Xue‐rui , Wang Jun‐long , Sun Yu‐wei , Yang Xin , Wu Yan , Liu Wei , Yuan Tao 
Published: July 2024

AbstractMastic is a natural resin produced by Pistacia lentiscus L. (Anacardiaceae) with high medicinal value and have been traditionally used as Uighur imported medicine for centuries. In this study, 16 triterpenoids including seven new noroleanane triterpenoids (1–7), along with nine known oleanane triterpenoids (8–16), were isolated from the mastic. Their chemical structures were determined on the basis of extensive spectroscopic analyses (including IR, UV, ESI‐HR‐MS and NMR spectroscopy) and singlecrystal X‐ray diffraction. Compounds 4–7, 11, 14 and 16 showed strong inhibitory NO production in LPS‐induced RAW264.7 cells with IC50 values 7.44–9.76 μM, respectively (positive control dexamethasone, 9.93±1.17 μM). Furthermore, compounds 3 and 12 significantly inhibited the growth of SW480 cells, compound 3 showed the most pronounced inhibitory effect with an IC50 of 2.30±0.38 μM.
Overview of the Mechanism of Degradation of Pharmaceuticals by Persulfate/Peroxysulfate Catalysts
Authors: Anjorin Excel O. , Alfred Moses O. , Sotunde Babajide , Nnamani Esther A. , Bayode Ajibola A. , Unuabonah Emmanuel I. , Helmreich Brigitte , Omorogie Martins O. 
Published: July 2024

AbstractThe leaching of pharmaceutical ingredients into water bodies poses an escalating threat, demanding urgent remediation strategies. Among several techniques advanced for their remediation, advanced oxidation methods utilizing persulfate (PS) and peroxymonosulfate (PMS) stand out as promising avenues for pharmaceutical degradation in wastewater. This article consolidates the research on photocatalytic degradation of pharmaceutical contaminants, focusing on PMS‐based photoactive composites, and elucidates their efficacy in removing active pharmaceutical ingredients from water. Moreover, it delineates alternative techniques for activating PS and PMS, providing a holistic understanding of the field's advancements. By outlining research limitations and knowledge gaps, this review underscores the imperative for further investigation and innovation in pharmaceutical wastewater treatment.
Tinea capitis (Favus) in a 8‐year‐old child: Case report
Authors: Akbari Negarin , Parhiz Jabbar , Sabzi Zahra 
Published: July 2024

Key Clinical MessageIn examining any scalp itch or skin lesions, especially in children with long hair, fungal lesions under the hair may not be diagnosed in a timely manner. Additionally, fungal infection of the scalp, known as tinea capitis, is considered a chronic condition and if left untreated, it can lead to alopecia (hair loss) and permanent scarring.AbstractTinea capitis (TC) is a common cutaneous fungal infection in childhood. In this report, we describe the case of an 8‐year‐old child presenting with erythematous scalp lesions accompanied by hair loss. Upon examination, palpation revealed a swollen and tender left parotid gland. Notably, the frontal region of the scalp exhibited erythematous lesions and scaly red plaques resembling yellowish paste‐like dough. Subsequent clinical evaluation and culture analysis confirmed the diagnosis of TC. The patient received treatment with Terbinafine 125 mg for a duration of 8 weeks. Follow‐up examinations conducted after 3 months showed no signs of recurrence. Accurate diagnosis and timely treatment, along with adherence to medication regimens, are crucial in cases of TC, and differential diagnoses should be considered. Treatment should commence promptly upon diagnosis to prevent complications such as scalp baldness and transmission to others. This case report underscores the significance of establishing a precise diagnosis and effective treatment for this dermatophytosis to mitigate the risk of recurrences or therapeutic shortcomings, particularly in infants.
Optimization of the Process Parameters of Catalytic Oxygen Removal over CoMo/γ‐Al2O3 Using Design‐of‐Experiment Approaches
Authors: Suh Sung Youn , Giannico Marco , Watermann Clara Maria , Zeidler‐Fandrich Barbara 
Published: July 2024

AbstractCatalytic oxygen removal applying a commercial CoMo‐based catalyst has attracted scientific attention owing to its catalytic stability towards poisoning components and cost‐effectiveness. The catalytic performance of the CoMo catalyst was investigated using statistical optimization techniques. The H2S concentrations in the sulfidation and reaction mixture are the key factors regulating the optimal values of deoxygenation reaction. The sulfidation process is a key step to generate the active species. The catalyst remains active in the presence of sulfur compounds in the reaction mixture, which is poisoning for other catalyst systems. An increase in the H2S content enhances the catalytic activity via in‐situ sulfidation within the meaning of regeneration during the reaction. Concentrations above 450 ppm H2S in the reaction mixture result in a nearly complete oxygen conversion and ensure the catalytic stability. At the same time, an increase in the H2S content favors a high sulfidation degree resulting in the formation of active sites.