bluuebunny/crossref_metadata_2025 huggingface dataset:
Time series clustering of T cell subsets dissects heterogeneity in immune reconstitution and clinical outcomes among MUD-HCT patients receiving ATG or PTCy
Authors: Leserer Saskia , Graf Theresa , Franke Martina , Bogdanov Rashit , Arrieta-Bolaños Esteban , Buttkereit Ulrike , Leimkühler Nils , Fleischhauer Katharina , Reinhardt Hans Christian , Beelen Dietrich W. , Turki Amin T.
Published: March 2023

Introduction

Anti-T-lymphocyte globulin (ATG) or post-transplant cyclophosphamide (PTCy) prevent graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT), yet individual patients benefit differentially.

Methods

Given the sparse comparative data on the impact of cellular immune reconstitution in this setting, we studied flow cytometry and clinical outcomes in 339 recipients of 10/10 matched-unrelated donor (MUD) HCT using either ATG (n=304) or PTCy (n=35) for in vivo T cell manipulation along with a haploidentical PTCy control cohort (n=45). Longitudinal cellular immune reconstitution data were analyzed conventionally and with a data science approach using clustering with dynamic time warping to determine the similarity between time-series of T cell subsets.

Results

Consistent with published studies, no significant differences in clinical outcomes were observed at the cohort level between MUD-ATG and MUD-PTCy. However, cellular reconstitution revealed preferences for distinct T cell subpopulations associating with GVHD protection in each setting. Starting early after HCT, MUD-PTCy patients had higher regulatory T cell levels after HCT (p <0.0001), while MUD-ATG patients presented with higher levels of γδ T- or NKT cells (both p <0.0001). Time-series clustering further dissected the patient population’s heterogeneity revealing distinct immune reconstitution clusters. Importantly, it identified phenotypes that reproducibly associated with impaired clinical outcomes within the same in vivo T cell manipulation platform. Exemplarily, patients with lower activated- and αβ T cell counts had significantly higher NRM (p=0.032) and relapse rates (p =0.01).

Discussion

The improved understanding of the heterogeneity of cellular reconstitution in MUD patients with T cell manipulation both at the cohort and individual level may support clinicians in managing HCT complications.
Urinary complement profile in IgA nephropathy and its correlation with the clinical and pathological characteristics
Authors: Wang Dongqing , Wu Changwei , Chen Sipei , Li Yi , Wang Li , Zhang Yong , Li Guisen
Published: March 2023

Background and objectives

The activated complement profile in IgA nephropathy (IgAN) is still unclear. Our study investigated the profile of urinary complements in IgAN patients and its correlations with clinical and pathological characteristics.

Methods

Urinary protein abundance was detected by liquid chromatography-tandem mass spectrometry (LC–MS/MS) in 50 IgAN, 50 membranous nephropathy (MN), and 68 healthy controls (HC). Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify differentially expressed proteins in IgAN patients. The differentially expressed complement proteins were screened in IgAN patients, and their correlations with laboratory or pathological parameters were analyzed. Thereafter, 7 complement components were validated by enzyme-linked immunosorbent assay (ELISA) in the urine samples of 45 IgAN patients.

Results

There were 786 differentially expressed proteins between IgAN and HC. KEGG analysis showed that differentially expressed urinary proteins in IgAN were enriched with complement. Of these, 67% of urinary complement protein abundance was associated with the estimated glomerular filtration rate. The urinary complement-related protein collectin12 (colec12), complement H factor (CFH), complement H factor-related protein 2 (CFHR2), and complement B factor (CFB) were positively correlated with serum creatinine; colec12, CFHR2, CFB, and C8g were positively correlated with glomerulosclerosis; CFH, CFHR2, C8g, and C9 were positively correlated with tubular atrophy/interstitial fibrosis.

Conclusion

Abnormally increased components of complement pathways significantly correlate with reduced renal function, proteinuria, and renal histological damage in IgAN. It could provide a potential biomarker panel for monitoring IgAN and provide clues for therapeutic choice targeting complement system of IgAN patients.
Potentials of saponins-based adjuvants for nasal vaccines
Authors: Chen Kai , Wang Ning , Zhang Xiaomin , Wang Meng , Liu Yanyu , Shi Yun
Published: March 2023

Respiratory infections are a major public health concern caused by pathogens that colonize and invade the respiratory mucosal surface. Nasal vaccines have the advantage of providing protection at the primary site of pathogen infection, as they induce higher levels of mucosal secretory IgA antibodies and antigen-specific T and B cell responses. Adjuvants are crucial components of vaccine formulation that enhance the immunogenicity of the antigen to confer long-term and effective protection. Saponins, natural glycosides derived from plants, shown potential as vaccine adjuvants, as they can activate the mammalian immune system. Several licensed human vaccines containing saponins-based adjuvants administrated through intramuscular injection have demonstrated good efficacy and safety. Increasing evidence suggests that saponins can also be used as adjuvants for nasal vaccines, owing to their safety profile and potential to augment immune response. In this review, we will discuss the structure-activity-relationship of saponins, their important role in nasal vaccines, and future prospects for improving their efficacy and application in nasal vaccine for respiratory infection.
Multi-faceted role of LRP1 in the immune system
Authors: Sizova Olga , John Lisa St. , Ma Qing , Molldrem Jeffrey J.
Published: March 2023

Graft versus host disease (GVHD) represents the major complication after allogeneic hematopoietic stem cell transplantation (Allo-SCT). GVHD-prone patients rely on GVHD prophylaxis (e.g. methotrexate) and generalized anti-GVHD medical regimen (glucocorticoids). New anti-GVHD therapy strategies are being constantly explored, however there is an urgent need to improve current treatment, since GVHD-related mortality reaches 22% within 5 years in patients with chronic GVHD. This review is an attempt to describe a very well-known receptor in lipoprotein studies – the low-density lipoprotein receptor related protein 1 (LRP1) - in a new light, as a potential therapeutic target for GVHD prevention and treatment. Our preliminary studies demonstrated that LRP1 deletion in donor murine T cells results in significantly lower GVHD-related mortality in recipient mice with MHC (major histocompatibility complex) -mismatched HSCT. Given the importance of T cells in the development of GVHD, there is a significant gap in scientific literature regarding LRP1’s role in T cell biology. Furthermore, there is limited research interest and publications on this classical receptor molecule in other immune cell types. Herein, we endeavor to summarize existing knowledge about LRP1’s role in various immune cells to demonstrate the possibility of this receptor to serve as a novel target for anti-GVHD treatment.
Multiple indices on different habitats and descriptors provide consistent assessments of environmental quality in a marine protected area
Authors: Oprandi Alice , Atzori Fabrizio , Azzola Annalisa , Bianchi Carlo Nike , Cadoni Nicoletta , Carosso Lara , Desiderà Elena , Frau Francesca , Garcia Gutiérrez Maria Leonor , Guidetti Paolo , Morri Carla , Piazzi Luigi , Poli Federica , Montefalcone Monica
Published: March 2023

In the last decades, climate change and human pressures have increasingly and dramatically impacted the ocean worldwide, calling for urgent actions to safeguard coastal marine ecosystems. The European Commission, in particular, has set ambitious targets for member states with two major directives, the Water Framework Directive (WFD) and the Marine Strategy Framework Directive (MSFD), both designed to protect the marine environment in EU waters. Diverse biotic indices have accordingly been developed to assess water and habitat quality. The WFD adopts four Biological Quality Elements (BQEs), whereas the MSFD recommends a set of eleven qualitative descriptors. The borderline between water quality and habitat quality is hard to trace and so far most assessments have involved the use of a few indices and were mainly related to a single BQE or qualitative descriptor. In this study, thanks to the availability of a large dataset encompassing a wide array of descriptors, we compared the performance of 11 biotic indices relative to three habitats/biotic components (reefs, seagrass, and fish) of the Marine Protected Area (MPA) of Capo Carbonara (SE Sardinia, Italy). The aim was to assess whether the indices were consistent in defining the environmental status in the MPA investigated. We used the graphical approach RESQUE (REsilience and QUality of Ecosystem), which enabled us to obtain a single and comprehensive measure of the status of the environment by integrating several metrics. This approach was applied here to different habitats for the first time. All indices were consistent with each other in confirming the good status of Capo Carbonara MPA. The use of RESQUE provided insights to interpret the differences between water quality, defined according to the WFD, and habitat quality, defined according to the MSFD. Differences between the two EU directives, in terms of either requirements or goals, have long been discussed but the present study highlights for the first time that they are congruent in their assessment of the environmental status of marine ecosystems.
Knowledge domain, research hotspots and frontiers in physiology teaching reforms from 2012 to 2021: A bibliometric and knowledge-map analysis
Authors: Xu Jia , Sun Shimeng , Zhao Yadong , Ma Qing
Published: March 2023

Objective

To identify author collaborations and impact; participating countries, institutions, and journals; evaluate the knowledge base; and analyze research hotspots and frontiers in teaching reforms in physiology.

Methods

Articles and reviews related to teaching reforms in physiology published between January 1, 2012, and December 31, 2021, were obtained from the Web of Science Core Collection. Two Scientometric software applications (CiteSpace 5.7 and VOSviewer 1.6.15) were used to perform bibliometric and knowledge-map analysis, generate network maps, and identify research trends and top keywords, authors, co-cited authors, institutions, countries, journals, and references.

Results

The search identified a total of 2,882 papers in 466 academic journals by 13,895 authors from 4,072 organizations in 67 countries/regions. Physiology teaching reform-related publications increased rapidly over time. Arango-Lasprilla and Rivera published the most papers, while Moseley had the most co-citations. Active collaborations among physiology researchers were noted. Advances in Physiology Education published the most papers on physiology teaching reforms and was also the top co-cited journal in the Medicine/Medical/Clinical, Psychology/Education/Health, and Neurology/Sports/Ophthalmology fields. The United States and University of California published the most physiology teaching publications in the search criteria. Ten references (research articles and reviews) on mechanisms and diseases were identified as the knowledge base. The mainstream research directions were education, Alzheimer’s disease, performance, physiology, and risk factors. Mental health and emotion regulation are increasing in significance and may become new hotspots. The research trend to move from the field of pain pathogenesis to the field of neuropsychiatry has become increasingly clear. This tendency away from peripheral system-based disorders to central system-based orders is inextricably linked to further developments in physiological understanding of the brain.

Conclusion

This study analyzed the research hot spots and frontiers of teaching reforms on in physiology using bibliometric and visual methods. Based on the results, rehabilitation, neurosciences, and infectious disease are hot topics in physiology. In particular, the pathogenesis of neurological diseases, treatment strategies, and technology updates have gradually become research hotspots. We predict that this trend is closely related to the implementation of brain research programs in various countries. These findings provide helpful references for scholars focusing on physiology education.
Long-term outcomes of anatomic vs. non-anatomic resection in intrahepatic cholangiocarcinoma with hepatolithiasis: A multicenter retrospective study
Authors: Wu Jun-Yi , Huang Wen-Tao , He Wen-bin , Dai Gao-Fan , Lv Jia-Hui , Qiu Fu-Nan
Published: March 2023

Background

The benefits of anatomic resection (AR) vs. non-anatomic resection (NAR) in patients with primary intrahepatic cholangiocarcinoma (ICC) with hepatolithiasis (HICC) are unclear. This study aimed to compare the long-term outcomes of AR vs. NAR in patients with HICC.

Methods

A total of 147 consecutive patients with HICC who underwent R0 hepatectomy were included. Overall survival (OS) and recurrence-free survival (RFS) following AR vs. NARs were compared using a 1:1 propensity score matching (PSM) analysis. A subgroup analysis was also conducted according to whether there are lymph node metastases (LNM).

Results

In a multivariate analysis, CA 19-9 (>39 U/L), microvascular invasion, LNM, and NAR were independent risk factors for poor RFS and OS rates, whereas multiple tumors were independent risk factors for OS. AR had better 1-, 3-, and 5-year RFS and OS rates than NAR (OS: 78.7, 58.9, and 28.5%, respectively, vs. 61.2, 25.4, and 8.8%, respectively; RFS: 59.5, 36.5, and 20.5%, respectively, vs. 38.2, 12.1, and 6.9%, respectively). After PSM, 100 patients were enrolled. The NAR group also had significantly poorer OS and RFS (OS: 0.016; RFS: p = 0.010) than the AR group. The subgroup analysis demonstrated that in HICC without LNM, OS and RFS were significantly poorer in the NAR group than the AR group, while no significant differences were observed in HICC with LNM before or after PSM.

Conclusion

Anatomic resection was associated with better long-term survival outcomes than NAR in patients with HICC, except for patients with LNM.
Enteroaggregative Escherichia coli as etiological agent of endemic diarrhea in Spain: A prospective multicenter prevalence study with molecular characterization of isolates
Authors: Llorente María Teresa , Escudero Raquel , Ramiro Raquel , Remacha María Antonia , Martínez-Ruiz Rocío , Galán-Sánchez Fátima , de Frutos Mónica , Elía Matilde , Onrubia Isabel , Sánchez Sergio
Published: March 2023

Background

EnteroaggregativeEscherichia coli(EAEC) is increasingly associated with domestically acquired diarrheal episodes in high-income countries, particularly among children. However, its specific role in endemic diarrhea in this setting remains under-recognized and information on molecular characteristics of such EAEC strains is limited. We aimed to investigate the occurrence of EAEC in patients with non-travel related diarrhea in Spain and molecularly characterize EAEC strains associated with illness acquired in this high-income setting.

Methods

In a prospective multicenter study, stool samples from diarrheal patients with no history of recent travel abroad (n = 1,769) were collected and processed for detection of EAEC and other diarrheagenicE. coli(DEC) pathotypes by PCR. An additional case–control study was conducted among children ≤5 years old. Whole-genome sequences (WGS) of the resulting EAEC isolates were obtained.

Results

Detection of DEC in the study population. DEC was detected in 23.2% of patients aged from 0 to 102 years, with EAEC being one of the most prevalent pathotypes (7.8%) and found in significantly more patients ≤5 years old (9.8% vs. 3.4%,p < 0.001). Although not statistically significant, EAEC was more frequent in cases than in controls. WGS-derived characterization of EAEC isolates. Sequence type (ST) 34, ST200, ST40, and ST10 were the predominant STs. O126:H27, O111:H21, and O92:H33 were the predominant serogenotypes. Evidence of a known variant of aggregative adherence fimbriae (AAF) was found in 89.2% of isolates, with AAF/V being the most frequent. Ten percent of isolates were additionally classified as presumptive extraintestinal pathogenicE. coli(ExPEC), uropathogenicE. coli(UPEC), or both, and belonged to clonal lineages that could be specifically associated with extraintestinal infections.

Conclusion

EAEC was the only bacterial enteric pathogen detected in a significant proportion of cases of endemic diarrhea in Spain, especially in children ≤5 years old. In particular, O126:H27-ST200, O111:H21-ST40, and O92:H33-ST34 were the most important subtypes, with all of them infecting both patients and asymptomatic individuals. Apart from this role as an enteric pathogen, a subset of these domestically acquired EAEC strains revealed an additional urinary/systemic pathogenic potential.
Brain vitamin D3-auto/paracrine system in relation to structural, neurophysiological, and behavioral disturbances associated with glucocorticoid-induced neurotoxicity
Authors: Lisakovska Olha , Labudzynskyi Dmytro , Khomenko Anna , Isaev Dmytro , Savotchenko Alina , Kasatkina Ludmila , Savosko Serhii , Veliky Mykola , Shymanskyi Ihor
Published: March 2023

Introduction

Vitamin D3 (VD3) is a potent para/autocrine regulator and neurosteroid that can strongly influence nerve cell function and counteract the negative effects of glucocorticoid (GC) therapy. The aim of the study was to reveal the relationship between VD3 status and behavioral, structural-functional and molecular changes associated with GC-induced neurotoxicity.

Methods

Female Wistar rats received synthetic GC prednisolone (5 mg/kg b.w.) with or without VD3 (1000 IU/kg b.w.) for 30 days. Behavioral, histological, physiological, biochemical, molecular biological (RT-PCR, Western blotting) methods, and ELISA were used.

Results and discussion

There was no difference in open field test (OFT), while forced swim test (FST) showed an increase in immobility time and a decrease in active behavior in prednisolone-treated rats, indicative of depressive changes. GC increased the perikaryon area, enlarged the size of the nuclei, and caused a slight reduction of cell density in CA1-CA3 hippocampal sections. We established a GC-induced decrease in the long-term potentiation (LTP) in CA1-CA3 hippocampal synapses, the amplitude of high K+-stimulated exocytosis, and the rate of Ca2+-dependent fusion of synaptic vesicles with synaptic plasma membranes. These changes were accompanied by an increase in nitration and poly(ADP)-ribosylation of cerebral proteins, suggesting the development of oxidative-nitrosative stress. Prednisolone upregulated the expression and phosphorylation of NF-κB p65 subunit at Ser311, whereas downregulating IκB. GC loading depleted the circulating pool of 25OHD3 in serum and CSF, elevated VDR mRNA and protein levels but had an inhibitory effect on CYP24A1 and VDBP expression. Vitamin D3 supplementation had an antidepressant-like effect, decreasing the immobility time and stimulating active behavior. VD3 caused a decrease in the size of the perikaryon and nucleus in CA1 hippocampal area. We found a recovery in depolarization-induced fusion of synaptic vesicles and long-term synaptic plasticity after VD3 treatment. VD3 diminished the intensity of oxidative-nitrosative stress, and suppressed the NF-κB activation. Its ameliorative effect on GC-induced neuroanatomical and behavioral abnormalities was accompanied by the 25OHD3 repletion and partial restoration of the VD3-auto/paracrine system.

Conclusion

GC-induced neurotoxicity and behavioral disturbances are associated with increased oxidative-nitrosative stress and impairments of VD3 metabolism. Thus, VD3 can be effective in preventing structural and functional abnormalities in the brain and behavior changes caused by long-term GC administration.
Pediatric immune-mediated necrotizing myopathy
Authors: Wang Chen-Hua , Liang Wen-Chen
Published: March 2023

Immune-mediated necrotizing myopathy (IMNM) is a type of inflammatory myopathy. Most patients with IMNM produce anti-3-hydroxy-3-methylglutaryl coenzyme A reductase or anti-signal-recognition particle autoantibodies. IMNM is much rarer in children than in adults. We conducted this mini review focusing on pediatric IMNM to present current evidence regarding its epidemiology, clinical characteristics, diagnosis, and treatment. Our findings indicate that pediatric IMNM often causes severe muscle weakness and is refractory to corticosteroids alone. Furthermore, delayed diagnosis is common because of the clinicopathological similarity between IMNM and inherited myopathy. Raising awareness regarding pediatric IMNM may facilitate early diagnosis and effective treatment.
Somatostatin neuron contributions to cortical slow wave dysfunction in adult mice exposed to developmental ethanol
Authors: Wilson Donald A. , Fleming G. , Williams C. R. O. , Teixeira C. M. , Smiley J. F. , Saito Mariko
Published: March 2023

Introduction

Transitions between sleep and waking and sleep-dependent cortical oscillations are heavily dependent on GABAergic neurons. Importantly, GABAergic neurons are especially sensitive to developmental ethanol exposure, suggesting a potential unique vulnerability of sleep circuits to early ethanol. In fact, developmental ethanol exposure can produce long-lasting impairments in sleep, including increased sleep fragmentation and decreased delta wave amplitude. Here, we assessed the efficacy of optogenetic manipulations of somatostatin (SST) GABAergic neurons in the neocortex of adult mice exposed to saline or ethanol on P7, to modulate cortical slow-wave physiology.

Methods

SST-cre × Ai32 mice, which selectively express channel rhodopsin in SST neurons, were exposed to ethanol or saline on P7. This line expressed similar developmental ethanol induced loss of SST cortical neurons and sleep impairments as C57BL/6By mice. As adults, optical fibers were implanted targeting the prefrontal cortex (PFC) and telemetry electrodes were implanted in the neocortex to monitor slow-wave activity and sleep-wake states.

Results

Optical stimulation of PFC SST neurons evoked slow-wave potentials and long-latency single-unit excitation in saline treated mice but not in ethanol mice. Closed-loop optogenetic stimulation of PFC SST neuron activation on spontaneous slow-waves enhanced cortical delta oscillations, and this manipulation was more effective in saline mice than P7 ethanol mice.

Discussion

Together, these results suggest that SST cortical neurons may contribute to slow-wave impairment after developmental ethanol.
Optical neuroimaging and neurostimulation in surgical training and assessment: A state-of-the-art review
Authors: Goble Mary , Caddick Virginia , Patel Ronak , Modi Hemel , Darzi Ara , Orihuela-Espina Felipe , Leff Daniel R.
Published: March 2023

Introduction

Functional near-infrared spectroscopy (fNIRS) is a non-invasive optical neuroimaging technique used to assess surgeons' brain function. The aim of this narrative review is to outline the effect of expertise, stress, surgical technology, and neurostimulation on surgeons' neural activation patterns, and highlight key progress areas required in surgical neuroergonomics to modulate training and performance.

Methods

A literature search of PubMed and Embase was conducted to identify neuroimaging studies using fNIRS and neurostimulation in surgeons performing simulated tasks.

Results

Novice surgeons exhibit greater haemodynamic responses across the pre-frontal cortex than experts during simple surgical tasks, whilst expert surgical performance is characterized by relative prefrontal attenuation and upregulation of activation foci across other regions such as the supplementary motor area. The association between PFC activation and mental workload follows an inverted-U shaped curve, activation increasing then attenuating past a critical inflection point at which demands outstrip cognitive capacity Neuroimages are sensitive to the impact of laparoscopic and robotic tools on cognitive workload, helping inform the development of training programs which target neural learning curves. FNIRS differs in comparison to current tools to assess proficiency by depicting a cognitive state during surgery, enabling the development of cognitive benchmarks of expertise. Finally, neurostimulation using transcranial direct-current-stimulation may accelerate skill acquisition and enhance technical performance.

Conclusion

FNIRS can inform the development of surgical training programs which modulate stress responses, cognitive learning curves, and motor skill performance. Improved data processing with machine learning offers the possibility of live feedback regarding surgeons' cognitive states during operative procedures.
Single cell metabolic imaging of tumor and immune cells in vivo in melanoma bearing mice
Authors: Heaton Alexa R. , Rehani Peter R. , Hoefges Anna , Lopez Angelica F. , Erbe Amy K. , Sondel Paul M. , Skala Melissa C.
Published: March 2023

Introduction

Metabolic reprogramming of cancer and immune cells occurs during tumorigenesis and has a significant impact on cancer progression. Unfortunately, current techniques to measure tumor and immune cell metabolism require sample destruction and/or cell isolations that remove the spatial context. Two-photon fluorescence lifetime imaging microscopy (FLIM) of the autofluorescent metabolic coenzymes nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD) provides in vivo images of cell metabolism at a single cell level.

Methods

Here, we report an immunocompetent mCherry reporter mouse model for immune cells that express CD4 either during differentiation or CD4 and/or CD8 in their mature state and perform in vivo imaging of immune and cancer cells within a syngeneic B78 melanoma model. We also report an algorithm for single cell segmentation of mCherry-expressing immune cells within in vivo images.

Results

We found that immune cells within B78 tumors exhibited decreased FAD mean lifetime and an increased proportion of bound FAD compared to immune cells within spleens. Tumor infiltrating immune cell size also increased compared to immune cells from spleens. These changes are consistent with a shift towards increased activation and proliferation in tumor infiltrating immune cells compared to immune cells from spleens. Tumor infiltrating immune cells exhibited increased FAD mean lifetime and increased protein-bound FAD lifetime compared to B78 tumor cells within the same tumor. Single cell metabolic heterogeneity was observed in both immune and tumor cells in vivo.

Discussion

This approach can be used to monitor single cell metabolic heterogeneity in tumor cells and immune cells to study promising treatments for cancer in the native in vivo context.
Mechanism of inflammasomes in cancer and targeted therapies
Authors: Gu Qingdan , Zou Jiazhen , Zhou Ying , Deng Qiuchan
Published: March 2023

Inflammasomes, composed of the nucleotide-binding oligomerization domain(NOD)-like receptors (NLRs), are immune-functional protein multimers that are closely linked to the host defense mechanism. When NLRs sense pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), they assemble into inflammasomes. Inflammasomes can activate various inflammatory signaling pathways, including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, and produce a large number of proinflammatory cytokines, which are closely associated with multiple cancers. They can also accelerate the occurrence and development of cancer by providing suitable tumor microenvironments, promoting tumor cell proliferation, and inhibiting tumor cell apoptosis. Therefore, the exploitation of novel targeted drugs against various inflammasomes and proinflammatory cytokines is a new idea for the treatment of cancer. In recent years, more than 50 natural extracts and synthetic small molecule targeted drugs have been reported to be in the research stage or have been applied to the clinic. Herein, we will overview the mechanisms of inflammasomes in common cancers and discuss the therapeutic prospects of natural extracts and synthetic targeted agents.
Superiority of integrated cervicothoracic immobilization in the setup of lung cancer patients treated with supraclavicular station irradiation
Authors: Wan Bao , Luo Shihong , Feng Xin , Qin Wenhua , Sun Haifan , Hou Lu , Zhang Kun , Wu Shiyu , Zhou Zongmei , Xiao Zefen , Chen Dongfu , Feng Qinfu , Wang Xin , Huan Fukui , Bi Nan , Wang Jianyang
Published: March 2023

Objective

To investigate the superiority of the integrated cervicothoracic immobilization devices (ICTID) on the mobility of the supraclavicular station in lung cancer patients requiring both primary lung lesion and positive supraclavicular lymph nodes irradiation.

Methods

One hundred patients with lung cancer were prospectively enrolled in the study. The following four different fixation methods are used for CT simulation positioning: thoracoabdominal flat immobilization device fixation with arms lifting (TAFID group), head-neck-shoulder immobilization device fixation with arms on the body sides (HNSID group), ICTID fixation with arms on the body sides (ICTID arms-down group), and n ICTID fixation with arms lifting (ICTID arms-up group). Cone-beam computed tomography (CBCT) images are taken daily or weekly before treatment, to assess anatomical changes during the radiotherapy course.

Results

The translation errors in X (left-right direction), Y (head-foot direction), and Z (abdomen-back direction) directions of the ICTID arms-up, TAFID, ICTID arms-down and HNSID groups were (0.15 ± 0.18) cm, (0.15 ± 0.16) cm, (0.16 ± 0.16) cm, and (0.15 ± 0.20) cm; (0.15 ± 0.15) cm, (0.21 ± 0.25) cm, (0.28 ± 0.23) cm, and (0.27 ± 0.21) cm; (0.13 ± 0.14) cm, (0.15 ± 0.14) cm, (0.17 ± 0.13) cm, and (0.16 ± 0.14) cm, respectively. Among them, the ICTID arms-up group had the minimal setup errors in X direction than those in ICTID arms-down (p=0.001) and HNSID groups (p=0.001), and in Y direction than those in TAFID (p<0.001), and in Z direction than those in ICTID arms-down (p<0.001) and TAFID groups (p=0.034). For the rotational errors of the four groups in the directions of sagittal plane, transverse plane, and coronal plane, the ICTID arms-up group had the smallest setup errors in the sagittal plane than that of TAFID groups and similar rotation setup errors with those of the other three groups.

Conclusion

For patients requiring radiation of primary lung lesion and positive supraclavicular lymph nodes, an integrated frame fixation device is preferred the ICTID arms-up methods provide the smallest set up error and satisfied repeatability of body position, compared with TAFID and HNSID.
CT radiomics model combined with clinical and radiographic features for discriminating peripheral small cell lung cancer from peripheral lung adenocarcinoma
Authors: Wang Jingting , Zhong Feiyang , Xiao Feng , Dong Xinyang , Long Yun , Gan Tian , Li Ting , Liao Meiyan
Published: March 2023

Purpose

Exploring a non-invasive method to accurately differentiate peripheral small cell lung cancer (PSCLC) and peripheral lung adenocarcinoma (PADC) could improve clinical decision-making and prognosis.

Methods

This retrospective study reviewed the clinicopathological and imaging data of lung cancer patients between October 2017 and March 2022. A total of 240 patients were enrolled in this study, including 80 cases diagnosed with PSCLC and 160 with PADC. All patients were randomized in a seven-to-three ratio into the training and validation datasets (170 vs. 70, respectively). The least absolute shrinkage and selection operator regression was employed to generate radiomics features and univariate analysis, followed by multivariate logistic regression to select significant clinical and radiographic factors to generate four models: clinical, radiomics, clinical-radiographic, and clinical-radiographic-radiomics (comprehensive). The Delong test was to compare areas under the receiver operating characteristic curves (AUCs) in the models.

Results

Five clinical-radiographic features and twenty-three selected radiomics features differed significantly in the identification of PSCLC and PADC. The clinical, radiomics, clinical-radiographic and comprehensive models demonstrated AUCs of 0.8960, 0.8356, 0.9396, and 0.9671 in the validation set, with the comprehensive model having better discernment than the clinical model (P=0.036), the radiomics model (P=0.006) and the clinical–radiographic model (P=0.049).

Conclusions

The proposed model combining clinical data, radiographic characteristics and radiomics features could accurately distinguish PSCLC from PADC, thus providing a potential non-invasive method to help clinicians improve treatment decisions.
Diagnostic value of serum LDH in children with refractory Mycoplasma pneumoniae pneumoniae: A systematic review and meta-analysis
Authors: Wang Shumin , Jiang Zhiyan , Li Xuejun , Sun Chenghui , Zhang Yixing , Xiao Zhen
Published: March 2023

Background

To investigate the relationship between serum Lactate dehydrogenase (LDH) and refractory Mycoplasma pneumoniae pneumonia (RMPP) in juvenile individuals.

Methods

Search Chinese databases and English databases. The retrieval time limit is from the establishment of the database to 2022-04-27. And screening and inclusion of relevant diagnostic test literature. The QUADAS-2 method was used to evaluate the quality of the included literature. The random effects model was used to combine sensitivity, specificity, likelihood ratio, diagnostic odds ratio, summary receiver operating characteristic curve, and area under summary receiver operating characteristic curve to evaluate the prediction value of LDH for RMPP. Subgroup analyses were used to explore sources of heterogeneity.

Results

① A total of 29 literatures that met the criteria were included in the study, and the quality of the literature was medium and high, with a total of 702,2 patients. ② The combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve of the studies were: 0.75 (95% CI = 0.73–0.76), 0.73 (95% CI = 0.72–0.74), 3.61 (95% CI = 2.86–4.56), 0.30 (95% CI = 0.23–0.39), 13.04 (95% CI = 8.24–20.63), and 0.85(95% CI = 0.82–0.88). ③ The results of subgroup analysis showed that Compared with the subgroup with LDH threshold ≤400 IU/L, the AUC increased from 0.84 (95% CI = 0.80–0.87) to 0.89 (95% CI = 0.86–0.91).

Conclusions

The serum LDH has good accuracy for the diagnosis of RMPP and can serve as a diagnostic marker for RMPP.
Acute effect of antiseizure drugs on background oscillations in Scn1aA1783V Dravet syndrome mouse model
Authors: Quinn Shir , Brusel Marina , Ovadia Mor , Rubinstein Moran
Published: March 2023

Dravet syndrome (Dravet) is a rare and severe form of developmental epileptic encephalopathy. Antiseizure medications (ASMs) for Dravet patients include valproic acid (VA) or clobazam (CLB), with or without stiripentol (STP), while sodium channel blockers like carbamazepine (CBZ) or lamotrigine (LTG) are contraindicated. In addition to their effect on epileptic phenotypes, ASMs were shown to modify the properties of background neuronal activity. Nevertheless, little is known about these background properties alterations in Dravet. Here, utilizing Dravet mice (DS, Scn1aA1783V/WT), we tested the acute effect of several ASMs on background electrocorticography (ECoG) activity and frequency of interictal spikes. Compared to wild-type mice, background ECoG activity in DS mice had lower power and reduced phase coherence, which was not corrected by any of the tested ASMs. However, acute administration of Dravet-recommended drugs, VA, CLB, or a combination of CLB + STP, caused, in most mice, a reduction in the frequency of interictal spikes, alongside an increase in the relative contribution of the beta frequency band. Conversely, CBZ and LTG increased the frequency of interictal spikes, with no effect on background spectral properties. Moreover, we uncovered a correlation between the reduction in interictal spike frequency, the drug-induced effect on the power of background activity, and a spectral shift toward higher frequency bands. Together, these data provide a comprehensive analysis of the effect of selected ASMs on the properties of background neuronal oscillations, and highlight a possible correlation between their effect on epilepsy and background activity.
Emerging roles of i-motif in gene expression and disease treatment
Authors: Luo Xiaoqing , Zhang Jianye , Gao Yue , Pan Weifei , Yang Yayuan , Li Xu , Chen Lingfei , Wang Chang , Wang Yuqing
Published: March 2023

As non-canonical nucleic acid secondary structures consisting of cytosine-rich nucleic acids, i-motifs can form under certain conditions. Several i-motif sequences have been identified in the human genome and play important roles in biological regulatory functions. Due to their physicochemical properties, these i-motif structures have attracted attention and are new targets for drug development. Herein, we reviewed the characteristics and mechanisms of i-motifs located in gene promoters (including c-myc, Bcl-2, VEGF, and telomeres), summarized various small molecule ligands that interact with them, and the possible binding modes between ligands and i-motifs, and described their effects on gene expression. Furthermore, we discussed diseases closely associated with i-motifs. Among these, cancer is closely associated with i-motifs since i-motifs can form in some regions of most oncogenes. Finally, we introduced recent advances in the applications of i-motifs in multiple areas.
Effects of frog skin peptide temporin-1CEa and its analogs on ox-LDL induced macrophage-derived foam cells
Authors: Yang Xue-Feng , Liu Xin , Yan Xiao-Yi , Shang De-Jing
Published: March 2023

Purpose: Atherosclerosis is one of the most important pathological foundations of cardiovascular and cerebrovascular diseases with high morbidity and mortality. Studies have shown that macrophages play important roles in lipid accumulation in the vascular wall and thrombosis formation in atherosclerotic plaques. This study aimed to explore the effect of frog skin antimicrobial peptides (AMPs) temporin-1CEa and its analogs on ox-LDL induced macrophage-derived foam cells.

Methods: CCK-8, ORO staining, and intracellular cholesterol measurements were used to study cellular activity, lipid droplet formation and cholesterol levels, respectively. ELISA, real-time quantitative PCR, Western blotting and flow cytometry analysis were used to study the expression of inflammatory factors, mRNA and proteins associated with ox-LDL uptake and cholesterol efflux in macrophage-derived foam cells, respectively. Furthermore, the effects of AMPs on inflammation signaling pathways were studied.

Results: Frog skin AMPs could significantly increase the cell viability of the ox-LDL-induced foaming macrophages and decrease the formation of intracellular lipid droplets and the levels of total cholesterol and cholesterol ester (CE). Frog skin AMPs inhibited foaming formation by reducing the protein expression of CD36, which regulates ox-LDL uptake but had no effect on the expression of efflux proteins ATP binding cassette subfamily A/G member 1 (ABCA1/ABCG1). Then, decreased mRNA expression of NF-κB and protein expression of p-NF-κB p65, p-IκB, p-JNK, p-ERK, p-p38 and the release of TNF-α and IL-6 occurred after exposure to the three frog skin AMPs.

Conclusion: Frog skin peptide temporin-1CEa and its analogs can improve the ox-LDL induced formation of macrophage-derived foam cells, in addition, inhibit inflammatory cytokine release through inhibiting the NF-κB and MAPK signaling pathways, thereby inhibiting inflammatory responses in atherosclerosis.
Updates on the anticancer potential of garlic organosulfur compounds and their nanoformulations: Plant therapeutics in cancer management
Authors: Pandey Pratibha , Khan Fahad , Alshammari Nawaf , Saeed Amir , Aqil Farrukh , Saeed Mohd
Published: March 2023

Garlic (Allium sativum L.) possesses numerous pharmacological potential, including antibacterial, antiarthritic, antithrombotic, anticancer, hypoglycemic, and hypolipidemic effects. The anti-cancer action of garlic is likely the best researched of the many advantageous pharmacological effects, and its use offers significant protection against the risk of developing cancer. A few active metabolites of garlic have been reported to be essential in the destruction of malignant cells due to their multi-targeted activities and lack of significant toxicity. The bioactive compounds in garlic having anticancer properties include diallyl trisulfide, allicin, allyl mercaptan diallyl disulfide, and diallyl sulphide. Different garlic-derived constituents and their nanoformulations have been tested for their effects against various cancers including skin, ovarian, prostate, gastric, breast, and lung, colorectal, liver, oral, and pancreatic cancer. The objective of this review is to summarize the antitumor activity and associated mechanisms of the organosulfur compounds of garlic in breast carcinoma. Breast cancer continues to have a significant impact on the total number of cancer deaths worldwide. Global measures are required to reduce its growing burden, particularly in developing nations where incidence is increasing quickly and fatality rates are still high. It has been demonstrated that garlic extract, its bioactive compounds, and their use in nanoformulations can prevent breast cancer in all of its stages, including initiation, promotion, and progression. Additionally, these bioactive compounds affect cell signaling for cell cycle arrest and survival along with lipid peroxidation, nitric oxide synthase activity, epidermal growth factor receptor, nuclear factor kappa B (NF-κB), and protein kinase C in breast carcinoma. Hence, this review deciphers the anticancer potential of garlic components and its nanoformulations against several breast cancer thereby projecting it as a potent drug candidate for efficient breast cancer management.
Chrysin ameliorates synovitis and fibrosis of osteoarthritic fibroblast-like synoviocytes in rats through PERK/TXNIP/NLRP3 signaling
Authors: Ding Liang , Liao Taiyang , Yang Nan , Wei Yibao , Xing Runlin , Wu Peng , Li Xiaochen , Mao Jun , Wang Peimin
Published: March 2023

Objective: Synovitis and fibrosis are common pathological features of knee osteoarthritis (KOA). The interaction of synovitis and fibrosis can promote KOA progression. Chrysin (CHR), a natural flavonoid, may treat inflammation and prevent fibrosis. However, the effect and mechanism of CHR in KOA synovitis and fibrosis remains unclear.

Methods: The KOA model was established in male SD rats by anterior cruciate ligament transection (ACLT), and histological analysis was used to evaluate synovitis and fibrosis. IL-6, IL-1β and TNF-α mRNA expression in synovial tissue was measured by qRT‒PCR. Immunohistochemistry (IHC) was performed to detect GRP78, ATF-6 and TXNIP expression in vivo. Synovial fibroblasts (SFs) were treated with TGF-β1 to stimulate the inflammatory response and fibrosis. CCK-8 assays were used to detect the viability of CHR-treated SFs. The IL-1β level was detected by immunofluorescence analysis. Coimmunoprecipitation (Co-IP) and double immunofluorescence colocalization were used to detect the physiological interaction between TXNIP and NLRP3. The expression of fibrosis-related mediators and PERK/TXNIP/NLRP3 signaling molecules was detected by western blotting and qRT-PCR.

Results: Four weeks after CHR treatment, pathological sections and associated scores showed that CHR improved synovitis and fibrosis in the ACLT model. In vitro, CHR attenuated the TGF-β1-induced inflammatory response and fibrosis in SFs. Moreover, CHR suppressed the expression of synovial fibrosis markers and PERK/TXNIP/NLRP3 signaling molecules in the synovial tissue of rats with ACLT and cultured SFs. More importantly, we found that CHR inhibited TXNIP-NLRP3 interactions in TGF-β-induced SFs.

Conclusion: Our findings indicate that CHR can ameliorate synovitis and fibrosis in KOA. The underlying mechanism may be related to the PERK/TXNIP/NLRP3 signaling pathway.
Real-time effects of lateral positioning on regional ventilation and perfusion in an experimental model of acute respiratory distress syndrome
Authors: Mlček Mikuláš , Borges João Batista , Otáhal Michal , Alcala Glasiele Cristina , Hladík Dominik , Kuriščák Eduard , Tejkl Leoš , Amato Marcelo , Kittnar Otomar
Published: March 2023

Low-volume lung injury encompasses local concentration of stresses in the vicinity of collapsed regions in heterogeneously ventilated lungs. We aimed to study the effects on ventilation and perfusion distributions of a sequential lateral positioning (30°) strategy using electrical impedance tomography imaging in a porcine experimental model of early acute respiratory distress syndrome (ARDS). We hypothesized that such strategy, including a real-time individualization of positive end-expiratory pressure (PEEP) whenever in lateral positioning, would provide attenuation of collapse in the dependent lung regions. A two-hit injury acute respiratory distress syndrome experimental model was established by lung lavages followed by injurious mechanical ventilation. Then, all animals were studied in five body positions in a sequential order, 15 min each: Supine 1; Lateral Left; Supine 2; Lateral Right; Supine 3. The following functional images were analyzed by electrical impedance tomography: ventilation distributions and regional lung volumes, and perfusion distributions. The induction of the acute respiratory distress syndrome model resulted in a marked fall in oxygenation along with low regional ventilation and compliance of the dorsal half of the lung (gravitational-dependent in supine position). Both the regional ventilation and compliance of the dorsal half of the lung greatly increased along of the sequential lateral positioning strategy, and maximally at its end. In addition, a corresponding improvement of oxygenation occurred. In conclusion, our sequential lateral positioning strategy, with sufficient positive end-expiratory pressure to prevent collapse of the dependent lung units during lateral positioning, provided a relevant diminution of collapse in the dorsal lung in a porcine experimental model of early acute respiratory distress syndrome.