bluuebunny/crossref_metadata_2025 huggingface dataset:
Engineered procyanidin-Fe nanoparticle alleviates intestinal inflammation through scavenging ROS and altering gut microbiome in colitis mice
Authors: Chang Yongliang , Wu Xiawei , Lu Shengwei , Du Jiahao , Long Yixiu , Zhu Yefei , Qin Huanlong
Published: March 2023

Inflammatory bowel disease (IBD) is an idiopathic chronic inflammatory bowel disease characterized by inflammation, intestinal barrier injury, and imbalance of gut microbiota. Excess accumulation of reactive oxygen species (ROS) is closely correlated with the development and reoccurrence of IBD. Previous researches demonstrate that procyanidin, as a natural antioxidant, exhibits strong ability of eliminating ROS, thus showing good therapeutic effects in the inflammation-related diseases. Non-etheless, its poor stability and solubility always limits the therapeutic outcomes. Here, we typically designed an antioxidant coordination polymer nanoparticle using the engineering of procyanidin (Pc) and free iron (Fe), named Pc-Fe nanozyme, for effectively scavenging ROS and further inhibiting inflammation while altering the gut microbiome for the treatment of colitis. Furthermore, in vitro experiments uncover that Pc-Fe nanoparticles exert strong multi biomimic activities, including peroxidase, and glutathione peroxidase, for the scavenging of ROS and protecting cells from oxidative injury. In addition, the colon accumulation of Pc-Fe nanozyme effectively protects the intestinal mucosa from oxidative damage while significantly downregulates pro-inflammatory factors, repairs the intestinal barriers and alternates gut microbiome after orally administrated in sodium dextran sulfate (DSS) induced colitis mice. The results collectively illustrate that the multienzyme mimicking Pc-Fe nanozyme owns high potential for treating IBD through scavenging ROS, inhibiting inflammation, repairing gut barriers and alternating gut microbiome, which further promising its clinical translation on IBD treatment and other ROS induced intestinal diseases.
Imaging the uptake of deuterated methionine in Drosophila with stimulated Raman scattering
Authors: Spratt Spencer J. , Mizuguchi Takaha , Akaboshi Hikaru , Kosakamoto Hina , Okada Rina , Obata Fumiaki , Ozeki Yasuyuki
Published: March 2023

Introduction: Visualizing small individual biomolecules at subcellular resolution in live cells and tissues can provide valuable insights into metabolic activity in heterogeneous cells, but is challenging.

Methods: Here, we used stimulated Raman scattering (SRS) microscopy to image deuterated methionine (d-Met) incorporated into Drosophila tissues in vivo.

Results: Our results demonstrate that SRS can detect a range of previously uncharacterized cell-to-cell differences in d-Met distribution within a tissue at the subcellular level.

Discussion: These results demonstrate the potential of SRS microscopy for metabolic imaging of less abundant but important amino acids such as methionine in tissue.
Senotherapeutics: An emerging approach to the treatment of viral infectious diseases in the elderly
Authors: Li Zhiqiang , Tian Mingfu , Wang Guolei , Cui Xianghua , Ma Jun’e , Liu Siyu , Shen Bingzheng , Liu Fang , Wu Kailang , Xiao Xuan , Zhu Chengliang
Published: March 2023

In the context of the global COVID-19 pandemic, the phenomenon that the elderly have higher morbidity and mortality is of great concern. Existing evidence suggests that senescence and viral infection interact with each other. Viral infection can lead to the aggravation of senescence through multiple pathways, while virus-induced senescence combined with existing senescence in the elderly aggravates the severity of viral infections and promotes excessive age-related inflammation and multiple organ damage or dysfunction, ultimately resulting in higher mortality. The underlying mechanisms may involve mitochondrial dysfunction, abnormal activation of the cGAS-STING pathway and NLRP3 inflammasome, the role of pre-activated macrophages and over-recruited immune cells, and accumulation of immune cells with trained immunity. Thus, senescence-targeted drugs were shown to have positive effects on the treatment of viral infectious diseases in the elderly, which has received great attention and extensive research. Therefore, this review focused on the relationship between senescence and viral infection, as well as the significance of senotherapeutics for the treatment of viral infectious diseases.
Characterization of resistance genes and plasmids from sick children caused by Salmonella enterica resistance to azithromycin in Shenzhen, China
Authors: Wang Hongmei , Cheng Hang , Huang Baoxing , Hu Xiumei , Chen Yunsheng , Zheng Lei , Yang Liang , Deng Jikui , Wang Qian
Published: March 2023

Introduction

Samonella is 1 of 4 key global causes of diarrhoeal diseases, sometimes it can be serious, especially for yong children. Due to the extensive resistance of salmonella serotypes to conventional first-line drugs, macrolides (such as azithromycin) have been designated as the most important antibiotics for the treatment of salmonella. Antimicrobial resistance is a major public health problem in the world, and the mechanism of azithromycin resistance is rarely studied.

Methods

This study determined the azithromycin resistance and plasmids of Salmonella enterica isolates from children attending the Shenzhen Children’s Hospital. The susceptibility of ampicillin (AMP), ciprofloxacin (CIP), ceftriaxone (CRO), sulfamethoxazole (SMZ), chloramphenicol (CL), and azithromycin (AZM) were detected and the genes and plasmids from azithromycin-resistant Salmonella were detected by Illumina hi-seq and Nanopore MinIone whole genome sequencing (WGS) using a map-based method, and the genomic background of these factors was evaluated using various bioinformatics tools.

Results

In total, 15 strains of nontyphoid Salmonella strains that were isolated (including S. typhimurium, S.London, S. Goldcoast, and S.Stanley) demonstrated resistance to azithromycin (minimum inhibitory concentration,MIC from 32 to >256 µg/mL), and the resistance rate was 3.08% (15/487). The sensitivity test to other antibiotics demonstrated 100% resistance to AMP, and the resistance to SMZ and CL was 86.7% and 80.0%, respectively. Through WGS analysis, all isolates were positive for a plasmid-encoded mphA gene. Plasmid incompatibility typing identified five IncFIB(K), five IncHI2/HI2A/Q1, two IncC, one IncHI2/HI2A/N, one IncR, one IncFII and one IncHI2/HI2A plasmids. Sequence analyses of plasmids revealed extensive homology to various plasmids or transposons in regions involved in plasmid replication/maintenance functions and/or in antibiotic resistance gene clusters.

Conclusion

mphA is the main gene involved in azithromycin, a macrolide, and resistance to Salmonella. It is usually located on plasmids and easily spreads, hence posing a great threat to the current treatment of Salmonella infection. The plasmid sequence similarities suggest that the plasmids acquired resistance genes from a variety of enterica bacteria and underscore the importance of a further understanding of horizontal gene transfer among enterica bacteria.
Heart-brain axis: Association of congenital heart abnormality and brain diseases
Authors: Sha Leihao , Li Yajiao , Zhang Yunwu , Tang Yusha , Li Baichuan , Chen Yucheng , Chen Lei
Published: March 2023

Brain diseases are a major burden on human health worldwide, and little is known about how most brain diseases develop. It is believed that cardiovascular diseases can affect the function of the brain, and many brain diseases are associated with heart dysfunction, which is called the heart-brain axis. Congenital heart abnormalities with anomalous hemodynamics are common treatable cardiovascular diseases. With the development of cardiovascular surgeries and interventions, the long-term survival of patients with congenital heart abnormalities continues to improve. However, physicians have reported that patients with congenital heart abnormalities have an increased risk of brain diseases in adulthood. To understand the complex association between congenital heart abnormalities and brain diseases, the paper reviews relevant clinical literature. Studies have shown that congenital heart abnormalities are associated with most brain diseases, including stroke, migraine, dementia, infection of the central nervous system, epilepsy, white matter lesions, and affective disorders. However, whether surgeries or other interventions could benefit patients with congenital heart abnormalities and brain diseases remains unclear because of limited evidence.
Effects of recreational SCUBA diving practiced once a week on neurohormonal response and myokines-mediated communication between muscles and the brain
Authors: Njire Braticevic Marina , Zarak Marko , Simac Brankica , Perovic Antonija , Dumic Jerka
Published: March 2023

Objective

During physical activity, activation of muscular, endocrine, and nervous systems, results in intensive crosstalk between muscles and other organs, which enables response to physiological stress. In SCUBA diving, extreme environmental conditions represent an additional challenge for homeostasis maintenance, but underlying mechanisms are largely unknown. We aimed to contribute to the understanding of neurohormonal response and muscle-brain crosstalk by measuring the concentrations of the selected hormones secreted by the pituitary-target organ axis and myokines involved in the muscle-brain endocrine loop in recreational SCUBA (rSCUBA) divers.

Methods

Fourteen male divers performed five open-water recreational dives (one per week, depth of 20–30 m, lasting 30 min, between 9 and 10 am), after a winter non-diving period of 5 months. Blood samples were collected immediately before and after the first, third, and fifth dives. Adrenocorticotropic hormone (ACTH), cortisol, thyroid-stimulating hormone (TSH), free thyroxine (fT4), prolactin, total testosterone, growth hormone (GH), insulin-like growth factor-1 (IGF-1), irisin, brain-derived neurotrophic factor (BDNF), S100B, glial fibrillary acidic protein (GFAP), and neuron-specific enolase (NSE) were measured using commercially available immunoassays.

Results

Cortisol and ACTH levels decreased after every dive, while total testosterone decreased only after the first dive. No significant changes in post-dive values, as well as the cumulative effect on any other measured hormone, were observed. Although irisin and BDNF levels decreased after the first and third dives, the fifth dive caused a significant increase in both myokines. Changes in IGF-1 levels were not observed. All three dives caused a significant increase in S100B levels. A statistically significant decrease in GFAP concentration was observed after every dive, while NSE pre-dive concentration declined over the studied period. The cumulative effect on myokine levels was reflected in a continuous decline in irisin and BDNF pre-dive levels throughout the studied period, but an increasing trend after the fifth dive was observed.

Conclusions

Observed changes in myokines and hormone levels point to a specific response to rSCUBA practiced once a week, most likely due to extreme environmental conditions. Further studies on communication between muscles and other organ systems, particularly on the muscle-brain endocrine loop, are required for a deeper understanding of the adaptation mechanisms to this kind of physiological stress.
Identification and validation of key genes associated with atrial fibrillation in the elderly
Authors: Liu Chuanbin , Zeng Jing , Wu Jin , Wang Jing , Wang Xin , Yao Minghui , Zhang Minghua , Fan Jiao
Published: March 2023

Background

Atrial fibrillation (AF) is the most common cardiac arrhythmia and significantly increases the risk of stroke and heart failure (HF), contributing to a higher mortality rate. Increasing age is a major risk factor for AF; however, the mechanisms of how aging contributes to the occurrence and progression of AF remain unclear. This study conducted weighted gene co-expression network analysis (WGCNA) to identify key modules and hub genes and determine their potential associations with aging-related AF.

Materials and methods

WGCNA was performed using the AF dataset GSE2240 obtained from the Gene Expression Omnibus, which contained data from atrial myocardium in cardiac patients with permanent AF or sinus rhythm (SR). Hub genes were identified in clinical samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were also performed.

Results

Green and pink were the most critical modules associated with AF, from which nine hub genes, PTGDS, COLQ, ASTN2, VASH1, RCAN1, AMIGO2, RBP1, MFAP4, and ALDH1A1, were hypothesized to play key roles in the AF pathophysiology in elderly and seven of them have high diagnostic value. Functional enrichment analysis demonstrated that the green module was associated with the calcium, cyclic adenosine monophosphate (cAMP), and peroxisome proliferator-activated receptors (PPAR) signaling pathways, and the pink module may be associated with the transforming growth factor beta (TGF-β) signaling pathway in myocardial fibrosis.

Conclusion

We identified nine genes that may play crucial roles in the pathophysiological mechanism of aging-related AF, among which six genes were associated with AF for the first time. This study provided novel insights into the impact of aging on the occurrence and progression of AF, and identified biomarkers and potential therapeutic targets for AF.
Safety and efficacy of intracoronary artery administration of human bone marrow-derived mesenchymal stem cells in STEMI of Lee-Sung pigs—A preclinical study for supporting the feasibility of the OmniMSC-AMI phase I clinical trial
Authors: Chen Wannhsin , Hou Chun-Hsiang , Chen Yi-Ling , Shen Hsin-Hsin , Lin Chen-Hsuan , Wu Cheng-Yi , Lin Meng-Hsueh , Liao Chih-Ching , Huang Jun-Jae , Yang Chi-Yu , Li Yi-Chen , Yip Hon-Kan
Published: March 2023

Background

This study tested whether early left intracoronary arterial (LAD) administration of human bone marrow-derived mesenchymal stem cells (hBMMSCs, called OmniMSCs) in acute ST-segment elevation myocardial infarction (STEMI) of Lee-Sung pigs induced by 90 min balloon-occluded LAD was safe and effective.

Methods and results

Young male Lee-Sung pigs were categorized into SC (sham-operated control, n = 3), AMI-B (STEMI + buffer/21 cc/administered at 90 min after STEMI, n = 6), and AMI-M [acute myocardial infarction (AMI) + hBMMSCs/1.5 × 107/administered at 90 min after STEMI, n = 6] groups. By 2 and 5 months after STEMI, the cardiac magnetic resonance imaging demonstrated that the muscle scar score (MSS) and abnormal cardiac muscle exercise score in the infarct region were significantly increased in the AMI-B than in the SC group that were significantly reversed in the AMI-M group, whereas the left ventricular ejection function by each month (from 1 to 5) displayed an opposite pattern of MSS among the groups (all p < 0.001). By 5 months, histopathological findings of infarct and fibrosis areas and isolectin-B4 exhibited an identical pattern, whereas the cellular expressions of troponin-I/troponin-T/von Willebrand factor exhibited an opposite pattern of MSS among the groups (all p < 0.001). The ST-segment resolution (>80%) was significantly earlier (estimated after 6-h AMI) in the AMI-M group than in the AMI-B group (p < 0.001). The protein expressions of inflammation (IL-1β/TNF-α/NF-κB)/oxidative stress (NOX-1/NOX-2/oxidized protein)/apoptosis (cleaved caspase-3/cleaved PARP)/DNA damage (γ-H2AX) displayed an identical pattern to MSS among the groups, whereas the protein expressions of angiogenesis factors (SDF-1α/VEGF) were significantly and progressively increased from SC, AMI-B, to AMI-M groups (all p < 0.001).

Conclusion

Early intra-LAD transfusion of OmniMSC treatment effectively reduced the infarct size and preserved LV function in porcine STEMI.
Reduction in cardiolipin reduces expression of creatine transporter-1 and creatine transport in growing hCMEC/D3 human brain microvessel endothelial cells
Authors: Miller Donald W. , Hatch Grant M.
Published: March 2023

The phospholipid cardiolipin (CL) regulates mitochondrial energy production. Endothelial cells of the blood-brain barrier (BBB) play a vital role in uptake of metabolites into the brain and are enriched in mitochondria. We examined how deficiency in BBB endothelial cell CL regulates the expression of selected drug and metabolite transporters and their function. Cardiolipin synthase-1 (hCLS1) was knocked down in a human brain microvessel endothelial cell line, hCMEC/D3, and CL levels and the mRNA expression of selected BBB drug and metabolite transporters examined. Mock transfected hCMEC/D3 cells served as controls. Incorporation of (14C)creatine and (14C)oleate into hCMEC/D3 cells was determined as a measure of solute metabolite transport. In addition, protein expression of the creatine transporter was determined. Knockdown of hCLS1 in hCMEC/D3 reduced CL and the mRNA expression of creatine transporter-1, p-glycoprotein and breast cancer resistance protein compared to controls. In contrast, mRNA expression of ATP binding cassette subfamily C members-1, -3, multidrug resistance-associated protein-4 variants 1, -2, and fatty acid transport protein-1 were unaltered. Although ATP production was unaltered by hCLS1 knockdown, incorporation of (14C)creatine into hCMEC/D3 cells was reduced compared to controls. The reduction in (14C)creatine incorporation was associated with a reduction in creatine transporter-1 protein expression. In contrast, incorporation of (14C)oleic acid into hCMEC/D3 cells and the mRNA expression of fatty acid transport protein-1 was unaltered by knockdown of hCLS1 compared to controls. Thus, knockdown of hCLS1 in hCMEC/D3, with a corresponding reduction in CL, results in alteration in expression of specific solute membrane transporters.
Response to pioglitazone in non-alcoholic fatty liver disease patients with vs. without type 2 diabetes: A meta-analysis of randomized controlled trials
Authors: Wang Zeyu , Du Huiqing , Zhao Ying , Ren Yadi , Ma Cuihua , Chen Hongyu , Li Man , Tian Jiageng , Xue Caihong , Long Guangfeng , Xu Meidong , Jiang Yong
Published: March 2023

Background

Pioglitazone is considered a potential therapy for non-alcoholic fatty liver disease (NAFLD). However, different effects of pioglitazone on NAFLD have been demonstrated in diabetic and non-diabetic patients. Herein, a meta-analysis of randomized, placebo-controlled trials was carried out to indirectly compare pioglitazone in NAFLD patients with vs. without type 2 diabetes.

Methods

Randomized controlled trials (RCTs) of pioglitazone vs. placebo involving NAFLD patients with or without type 2 diabetes/prediabetes collected from databases were enrolled into this analysis. Methodological quality was employed to evaluate the domains recommended by the Cochrane Collaboration. The analysis covered the changes in histology (fibrosis, hepatocellular ballooning, inflammation, steatosis), liver enzymes, blood lipids, fasting blood glucose (FBS), homeostasis model assessment-IR (HOMA-IR), weight and body mass index (BMI) before and after treatment, and adverse events.

Results

The review covered seven articles, with 614 patients in total, of which three were non-diabetic RCTs. No difference was found in patients with vs. without type 2 diabetes in histology, liver enzymes, blood lipids, HOMA-IR, weight, BMI, and FBS. Moreover, no significant difference was revealed in adverse effects between NAFLD patients with diabetes and without DM, except the incidence of edema that was found to be higher in the pioglitazone group than in the placebo group in NAFLD patients with diabetes.

Conclusions

Pioglitazone could exert a certain effect on alleviating NAFLD, which was consistent between non-diabetic NAFLD patients and diabetic NAFLD patients in improving histopathology, liver enzymes, and HOMA-IR and reducing blood lipids. Furthermore, there were no adverse effects, except the incidence of edema which is higher in the pioglitazone group in NAFLD patients with diabetes. However, large sample sizes and well-designed RCTs are required to further confirm these conclusions.
The expression of glucocorticoid and mineralocorticoid receptors in pituitary tumors causing Cushing’s disease and silent corticotroph tumors
Authors: Kober Paulina , Rusetska Natalia , Mossakowska Beata J. , Maksymowicz Maria , Pękul Monika , Zieliński Grzegorz , Styk Andrzej , Kunicki Jacek , Działach Łukasz , Witek Przemysław , Bujko Mateusz
Published: March 2023

Objective

Pituitary neuroendocrine corticotroph tumors commonly cause Cushing’s disease (CD) that results from increased adrenocorticotropic hormone (ACTH) secretion by the pituitary tumor and consequent increase of cortisol levels in blood. However, in some patients, corticotroph tumors remain clinically non-functioning. Cortisol secretion is regulated by the hypothalamic–pituitary–adrenal axis and includes a negative feedback between cortisol and ACTH secretion. Glucocorticoids reduce ACTH level both by hypothalamic regulation and acting on corticotrophs via glucocorticoid (GR) and mineralocorticoid (MR) receptors. The aim of the study was to determine the role of GR and MR expression at mRNA and protein levels in both functioning and silent corticotroph tumors.

Methods

Ninety-five patients were enrolled, including 70 with CD and 25 with silent corticotroph tumors. Gene expression levels of NR3C1 and NR3C2 coding for GR and MR, respectively, were determined with qRT-PCR in the two tumor types. GR and MR protein abundance was assessed with immunohistochemistry.

Results

Both GR and MR were expressed in corticotroph tumors. Correlation between NR3C1 and NR3C2 expression levels was observed. NR3C1 expression was higher in silent than in functioning tumors. In CD patients NR3C1 and NR3C2 levels were negatively correlated with morning plasma ACTH levels and tumor size. Higher NR3C2 was confirmed in patients with remission after surgery and in densely granulated tumors. Expression of both genes and GR protein was higher in USP8-mutated tumors. Similar relationship between USP8 mutations and expression levels were observed in analysis of silent tumors that also revealed a negative correlation between GR and tumor size and higher NR3C1 expression in densely granulated tumors.

Conclusions

Although the associations between gene/protein expression and patients clinical features are not strong, they consistently show an evident trend in which higher receptor expression corresponds to more favorable clinical characteristics.
The impact of high-tech industrial agglomeration on China’s green innovation efficiency: A spatial econometric analysis
Authors: Liu Shucheng , Wu Peijin
Published: March 2023

Eco-efficiency is an important factor in assessing the quality of development, and high-tech industries are crucial for countries to forge green innovation paths. However, few studies have examined whether and how high-tech industrial agglomeration affects green innovation efficiency. To fill this gap, we measure the degree of high-tech industrial agglomeration and the level of specialized and diversified agglomeration using the location entropy index and agglomeration factor, and calculate green innovation efficiency using the super-SBM model with undesirable outputs. Based on Chinese provincial panel data from 2006 to 2020, a dynamic spatial Durbin model was constructed to explore the impact of high-tech industrial agglomeration and different agglomeration patterns on green innovation efficiency. Our study found that high-tech industrial agglomeration is a significant contributor to green innovation efficiency. There is an inverted U-shaped relationship between specialized agglomeration and green innovation efficiency, and diversified agglomeration contributes to green innovation efficiency. Given the regionally uneven nature of China’s economic development, there is some variation in the impact effects within different economic regions. We demonstrated the leading role of scientific high-tech industrial agglomeration patterns and appropriate levels of agglomeration in green innovation, providing theoretical guidance for the formulation of China’s high-quality development policies.
Use of pain-related gene features to predict depression by support vector machine model in patients with fibromyalgia
Authors: Wang Fengfeng , Cheung Chi Wai , Wong Stanley Sau Ching
Published: March 2023

The prevalence rate of depression is higher in patients with fibromyalgia syndrome, but this is often unrecognized in patients with chronic pain. Given that depression is a common major barrier in the management of patients with fibromyalgia syndrome, an objective tool that reliably predicts depression in patients with fibromyalgia syndrome could significantly enhance the diagnostic accuracy. Since pain and depression can cause each other and worsen each other, we wonder if pain-related genes can be used to differentiate between those with major depression from those without. This study developed a support vector machine model combined with principal component analysis to differentiate major depression in fibromyalgia syndrome patients using a microarray dataset, including 25 fibromyalgia syndrome patients with major depression, and 36 patients without major depression. Gene co-expression analysis was used to select gene features to construct support vector machine model. The principal component analysis can help reduce the number of data dimensions without much loss of information, and identify patterns in data easily. The 61 samples available in the database were not enough for learning based methods and cannot represent every possible variation of each patient. To address this issue, we adopted Gaussian noise to generate a large amount of simulated data for training and testing of the model. The ability of support vector machine model to differentiate major depression using microarray data was measured as accuracy. Different structural co-expression patterns were identified for 114 genes involved in pain signaling pathway by two-sample KS test (p < 0.001 for the maximum deviation D = 0.11 > Dcritical = 0.05), indicating the aberrant co-expression patterns in fibromyalgia syndrome patients. Twenty hub gene features were further selected based on co-expression analysis to construct the model. The principal component analysis reduced the dimension of the training samples from 20 to 16, since 16 components were needed to retain more than 90% of the original variance. The support vector machine model was able to differentiate between those with major depression from those without in fibromyalgia syndrome patients with an average accuracy of 93.22% based on the expression levels of the selected hub gene features. These findings would contribute key information that can be used to develop a clinical decision-making tool for the data-driven, personalized optimization of diagnosing depression in patients with fibromyalgia syndrome.
Exploring immune interactions in triple negative breast cancer: IL-1β inhibition and its therapeutic potential
Authors: Wilson Brooke E. , Shen Qiang , Cescon David W. , Reedijk Michael
Published: March 2023

Triple negative breast cancer (TNBC) has poor prognosis when compared to other breast cancer subtypes. Despite pre-clinical data supporting an immune targeted approach for TNBCs, immunotherapy has failed to demonstrate the impressive responses seen in other solid tumor malignancies. Additional strategies to modify the tumor immune microenvironment and potentiate response to immunotherapy are needed. In this review, we summarise phase III data supporting the use of immunotherapy for TNBC. We discuss the role of IL-1β in tumorigenesis and summarize pre-clinical data supporting IL-1β inhibition as a potential therapeutic strategy in TNBC. Finally, we present current trials evaluating IL-1β in breast cancer and other solid tumor malignancies and discuss future studies that may provide a strong scientific rationale for the combination of IL-1β and immunotherapy in the neoadjuvant and metastatic setting for people with TNBC.
Analysis in Proceratophrys boiei genome illuminates the satellite DNA content in a frog from the Brazilian Atlantic forest
Authors: João Da Silva Marcelo , Gazoni Thiago , Haddad Célio Fernando Baptista , Parise-Maltempi Patricia Pasquali
Published: March 2023

Satellite DNAs (satDNAs) are one of the most abundant elements in genomes. Characterized as tandemly organized sequences that can be amplified into multiple copies, mainly in heterochromatic regions. The frog P. boiei (2n = 22, ZZ♂/ZW♀) is found in the Brazilian Atlantic forest and has an atypical pattern of heterochromatin distribution when compared to other anuran amphibians, with large pericentromeric blocks on all chromosomes. In addition, females of Proceratophrys boiei have a metacentric sex chromosome W showing heterochromatin in all chromosomal extension. In this work, we performed high-throughput genomic, bioinformatic, and cytogenetic analyses to characterize the satellite DNA content (satellitome) in P. boiei, mainly due to high amount of C-positive heterochromatin and the highly heterochromatic W sex chromosome. After all the analyses, it is remarkable that the satellitome of P. boiei is composed of a high number of satDNA families (226), making P. boiei the frog species with the highest number of satellites described so far. Consistent with the observation of large centromeric C-positive heterochromatin blocks, the genome of P. boiei is enriched with high copy number of repetitive DNAs, with total satDNA abundance comprising 16.87% of the genome. We successfully mapped via Fluorescence in situ hybridization the two most abundant repeats in the genome, PboSat01-176 and PboSat02-192, highlighting the presence of certain satDNAs sequences in strategic chromosomal regions (e.g., centromere and pericentromeric region), which leads to their participation in crucial processes for genomic organization and maintenance. Our study reveals a great diversity of satellite repeats that are driving genomic organization in this frog species. The characterization and approaches regarding satDNAs in this species of frog allowed the confirmation of some insights from satellite biology and a possible relationship with the evolution of sex chromosomes, especially in anuran amphibians, including P. boiei, for which data were not available.
Whole exome sequencing reveals novel variants associated with diminished ovarian reserve in young women
Authors: Li Na , Xu Wanxue , Liu Huimin , Zhou Rui , Zou Siqi , Wang Shiqing , Li Siyu , Yang Zexin , Piao Yongjun , Zhang Yunshan
Published: March 2023

Background: Diminished ovarian reserve is one of the most important causes of female infertility. In the etiology study of DOR, besides age, it is known that chromosomal abnormality, radiotherapy, chemotherapy and ovarian surgery can result in DOR. For young women without obvious risk factors, gene mutation should be considered as a possible cause. However, the specific molecular mechanism of DOR has not been fully elucidated.

Methods: In order to explore the pathogenic variants related to DOR, twenty young women under 35 years old affected by DOR without definite factors damaging ovarian reserve were recruited as the research subjects, and five women with normal ovarian reserve were recruited as the control group. Whole exome sequencing was applied as the genomics research tool.

Results: As a result, we obtained a set of mutated genes that may be related to DOR, where the missense variant on GPR84 was selected for further study. It is found that GPR84Y370H variant promotes the expression of proinflammatory cytokines (TNF-α, IL12B, IL-1β) and chemokines (CCL2, CCL5), as well as the activation of NF-κB signaling pathway.

Conclusion: In conclusion, GPR84Y370H variant was identified though analysis for WES results of 20 DOR patients. The deleterious variant of GPR84 could be the potential molecular mechanism of non-age-related pathological DOR through its role in promoting inflammation. The findings of this study can be used as a preliminary research basis for the development of early molecular diagnosis and treatment target selection of DOR.
Impact of COVID-19 stress on the psychological health of sexual & gender minority individuals: A systematic review
Authors: Datta Sumona , Mukherjee Tilottama
Published: March 2023

Introduction

The differential effect of the Covid-19 pandemic on the mental health of the population around the globe is well documented. Social isolation, loss of job, financial crisis, and fear of infection due to the pandemic have widely affected people across countries, and the sexual and gender minority (SGM) group is no exception. However, the additional stressors like stigma, discrimination, rejection, non-acceptance, and violence associated with diverse sexual orientation complicated the situation for the SGM group in the context of the Covid-19 pandemic.

Method

The present study conducted a systematic review of research (n = 16) investigating the impact of Covid-19 stress on the psychological health of SGM individuals. The review had two objectives: (a) to explore the effect of the stress associated with the pandemic on the psychological health of the SGM individuals; and (b) to identify potential stressors associated with the Covid-19 pandemic affecting the mental health of SGM individuals. Studies were selected following a PRISMA protocol and several inclusion criteria.

Results

The review provided new insights into the mental health issues of the SGM individual in the Covid-19 context. The outcome of the review focused on five aspects: (a) depression and anxiety symptoms related to Covid-19 symptoms; (b) perceived social support and Covid-19 stress; (c) family support and psychological distress related to Covid-19; (d) Covid-19 stress and disordered eating, and (e) problem drinking and substance abuse associated with Covid-19 stress.

Discussion

The present review indicated a negative association between Covid-19 stress and psychological distress among sexual and gender minority individuals. The findings have important implications for psychologists and social workers working with this population and policymakers around the globe.
HPV-related anal cancer is associated with changes in the anorectal microbiome during cancer development
Authors: Elnaggar Jacob H. , Huynh Victoria O. , Lin Daniel , Hillman R. Tyler , Abana Chike O. , El Alam Molly B. , Tomasic Katarina C. , Karpinets Tatiana V. , Kouzy Ramez , Phan Jae L. , Wargo Jennifer , Holliday Emma B. , Das Prajnan , Mezzari Melissa P. , Ajami Nadim J. , Lynn Erica J. , Minsky Bruce D. , Morris Van K. , Milbourne Andrea , Messick Craig A. , Klopp Ann H. , Futreal P. Andrew , Taniguchi Cullen M. , Schmeler Kathleen M. , Colbert Lauren E.
Published: March 2023

Background

Squamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines and approaches for anal dysplasia are less clear than for cervical dysplasia. One potential contributing factor is the anorectal microbiome. In this study, we aimed to identify differences in anal microbiome composition in the settings of HPV infection, anal dysplasia, and anal cancer in this rare disease.

Methods

Patients were enrolled in two prospective studies. Patients with anal dysplasia were part of a cross-sectional cohort that enrolled women with high-grade lower genital tract dysplasia. Anorectal tumor swabs were prospectively collected from patients with biopsy-confirmed locally advanced SCCA prior to receiving standard-of-care chemoradiotherapy (CRT). Patients with high-grade lower genital tract dysplasia without anal dysplasia were considered high-risk (HR Normal). 16S V4 rRNA Microbiome sequencing was performed for anal swabs. Alpha and Beta Diversity and composition were compared for HR Normal, anal dysplasia, and anal cancer.

Results

60 patients with high-grade lower genital tract dysplasia were initially enrolled. Seven patients had concurrent anal dysplasia and 44 patients were considered HR Normal. Anorectal swabs from 21 patients with localized SCCA were included, sequenced, and analyzed in the study. Analysis of weighted and unweighted UniFrac distances demonstrated significant differences in microbial community composition between anal cancer and HR normal (p=0.018). LEfSe identified that all three groups exhibited differential enrichment of specific taxa. Peptoniphilus (p=0.028), Fusobacteria (p=0.0295), Porphyromonas (p=0.034), and Prevotella (p=0.029) were enriched in anal cancer specimens when compared to HR normal.

Conclusion

Although alpha diversity was similar between HR Normal, dysplasia and cancer patients, composition differed significantly between the three groups. Increased anorectal Peptoniphilus, Fusobacteria, Porphyromonas, and Prevotella abundance were associated with anal cancer. These organisms have been reported in various gastrointestinal cancers with roles in facilitating the proinflammatory microenvironment and neoplasia progression. Future work should investigate a potential role of microbiome analysis in screening for anal dysplasia and investigation into potential mechanisms of how these microbial imbalances influence the immune system and anal carcinogenesis.
Identification and validation of hub genes in drug induced acute kidney injury basing on integrated transcriptomic analysis
Authors: Deng Yi-Xuan , Liu Kun , Qiu Qun-Xiang , Tang Zhi-Yao , Que Rui-Man , Li Dian-Ke , Gu Xu-Rui , Zhou Guang-Liang , Wu Yi-Feng , Zhou Ling-Yun , Yin Wen-Jun , Zuo Xiao-Cong
Published: March 2023

Background

Drug-induced acute kidney damage (DI-AKI) is a clinical phenomenon of rapid loss of kidney function over a brief period of time as a consequence of the using of medicines. The lack of a specialized treatment and the instability of traditional kidney injury markers to detect DI-AKI frequently result in the development of chronic kidney disease. Thus, it is crucial to continue screening for DI-AKI hub genes and specific biomarkers.

Methods

Differentially expressed genes (DEGs) of group iohexol, cisplatin, and vancomycin’s were analyzed using Limma package, and the intersection was calculated. DEGs were then put into String database to create a network of protein-protein interactions (PPI). Ten algorithms are used in the Cytohubba plugin to find the common hub genes. Three DI-AKI models’ hub gene expression was verified in vivo and in vitro using PCR and western blot. To investigate the hub gene’s potential as a biomarker, protein levels of mouse serum and urine were measured by ELISA kits. The UUO, IRI and aristolochic acid I-induced nephrotoxicity (AAN) datasets in the GEO database were utilized for external data verification by WGCNA and Limma package. Finally, the Elisa kit was used to identify DI-AKI patient samples.

Results

95 up-regulated common DEGs and 32 down-regulated common DEGs were obtained using Limma package. A PPI network with 84 nodes and 24 edges was built with confidence >0.4. Four hub genes were obtained by Algorithms of Cytohubba plugin, including TLR4, AOC3, IRF4 and TNFAIP6. Then, we discovered that the protein and mRNA levels of four hub genes were significantly changed in the DI-AKI model in vivo and in vitro. External data validation revealed that only the AAN model, which also belonged to DI-AKI model, had significant difference in these hub genes, whereas IRI and UUO did not. Finally, we found that plasma TLR4 levels were higher in patients with DI-AKI, especially in vancomycin-induced AKI.

Conclusion

The immune system and inflammation are key factors in DI-AKI. We discovered the immunological and inflammatory-related genes TLR4, AOC3, IRF4, and TNFAIP6, which may be promising specific biomarkers and essential hub genes for the prevention and identification of DI-AKI.
Tracking of activated cTfh cells following sequential influenza vaccinations reveals transcriptional profile of clonotypes driving a vaccine-induced immune response
Authors: Currenti Jennifer , Simmons Joshua , Oakes Jared , Gaudieri Silvana , Warren Christian M. , Gangula Rama , Alves Eric , Ram Ramesh , Leary Shay , Armitage Jesse D. , Smith Rita M. , Chopra Abha , Halasa Natasha B. , Pilkinton Mark A. , Kalams Spyros A.
Published: March 2023

Introduction

A vaccine against influenza is available seasonally but is not 100% effective. A predictor of successful seroconversion in adults is an increase in activated circulating T follicular helper (cTfh) cells after vaccination. However, the impact of repeated annual vaccinations on long-term protection and seasonal vaccine efficacy remains unclear.

Methods

In this study, we examined the T cell receptor (TCR) repertoire and transcriptional profile of vaccine-induced expanded cTfh cells in individuals who received sequential seasonal influenza vaccines. We measured the magnitude of cTfh and plasmablast cell activation from day 0 (d0) to d7 post-vaccination as an indicator of a vaccine response. To assess TCR diversity and T cell expansion we sorted activated and resting cTfh cells at d0 and d7 post-vaccination and performed TCR sequencing. We also single cell sorted activated and resting cTfh cells for TCR analysis and transcriptome sequencing.

Results and discussion

The percent of activated cTfh cells significantly increased from d0 to d7 in each of the 2016-17 (p < 0.0001) and 2017-18 (p = 0.015) vaccine seasons with the magnitude of cTfh activation increase positively correlated with the frequency of circulating plasmablast cells in the 2016-17 (p = 0.0001) and 2017-18 (p = 0.003) seasons. At d7 post-vaccination, higher magnitudes of cTfh activation were associated with increased clonality of cTfh TCR repertoire. The TCRs from vaccine-expanded clonotypes were identified and tracked longitudinally with several TCRs found to be present in both years. The transcriptomic profile of these expanded cTfh cells at the single cell level demonstrated overrepresentation of transcripts of genes involved in the type-I interferon pathway, pathways involved in gene expression, and antigen presentation and recognition. These results identify the expansion and transcriptomic profile of vaccine-induced cTfh cells important for B cell help.
Controversial role of ILC3s in intestinal diseases: A novelty perspective on immunotherapy
Authors: Zhang Yunshu , Feng Xuefei , Chen Juan , Liu Jiahao , Wu Jianmin , Tan Hongpei , Mi Ze , Rong Pengfei
Published: March 2023

ILC3s have been identified as crucial immune regulators that play a role in maintaining host homeostasis and modulating the antitumor response. Emerging evidence supports the idea that LTi cells play an important role in initiating lymphoid tissue development, while other ILC3s can promote host defense and orchestrate adaptive immunity, mainly through the secretion of specific cytokines and crosstalk with other immune cells or tissues. Additionally, dysregulation of ILC3-mediated overexpression of cytokines, changes in subset abundance, and conversion toward other ILC subsets are closely linked with the occurrence of tumors and inflammatory diseases. Regulation of ILC3 cytokines, ILC conversion and LTi-induced TLSs may be a novel strategy for treating tumors and intestinal or extraintestinal inflammatory diseases. Herein, we discuss the development of ILCs, the biology of ILC3s, ILC plasticity, the correlation of ILC3s and adaptive immunity, crosstalk with the intestinal microenvironment, controversial roles of ILC3s in intestinal diseases and potential applications for treatment.
γδ T cells recruitment and local proliferation in brain parenchyma benefit anti-neuroinflammation after cerebral microbleeds
Authors: Su Xin , Yang Shuxian , Li Yanxiang , Xiang Zongqin , Tao Qiao , Liu Shengde , Yin Zhinan , Zhong Liyun , Lv Xiaoxu , Zhou Libing
Published: March 2023

Background

Cerebral microbleeds (CMBs) are an early sign of many neurological disorders and accompanied by local neuroinflammation and brain damage. As important regulators of immune response and neuroinflammation, the biological behavior and role of γδ T cells after CMBs remain largely unknown.

Methods

We made a spot injury of microvessel in the somatosensory cortex to mimic the model of CMBs by two-photon laser and in vivo tracked dynamical behaviors of γδ T cells induced by CMBs using TCR-δGFP transgenic mice. Biological features of γδ T cells in the peri-CMBs parenchyma were decoded by flow cytometry and Raman spectra. In wildtype and γδ T cell-deficient mice, neuroinflammation and neurite degeneration in the peri-CMBs cortex were studied by RNAseq, immunostaining and in vivo imaging respectively.

Results

After CMBs, γδ T cells in the dural vessels were tracked to cross the meningeal structure and invade the brain parenchyma in a few days, where the division process of γδ T cells were captured. Parenchymal γδ T cells were highly expressed by CXCR6 and CCR6, similar to meningeal γδ T cells, positive for IL-17A and Ki67 (more than 98%), and they contained abundant substances for energy metabolism and nucleic acid synthesis. In γδ T cell-deficient mice, cortical samples showed the upregulation of neuroinflammatory signaling pathways, enhanced glial response and M1 microglial polarization, and earlier neuronal degeneration in the peri-CMBs brain parenchyma compared with wildtype mice.

Conclusion

CMBs induce the accumulation and local proliferation of γδ T cells in the brain parenchyma, and γδ T cells exert anti-neuroinflammatory and neuroprotective effects at the early stage of CMBs.
The macrophages regulate intestinal motility dysfunction through the PGE2 Ptger3 axis during Klebsiella pneumonia sepsis
Authors: Yao Hua , Fu Xin , Xu Qian , Li Tingting , Li Yao , Kang Yan , Wu Qin
Published: March 2023

Introduction

Gut motility dysfunction, the most common complication of post-septic organ dysfunction, depends on immune and neuronal cells. This study aimed to investigate the mechanisms that activate these cells and the contribution of macrophages to the recovery of intestinal motility dysfunction after sepsis.

Materials and methods

Postoperative gut motility dysfunction was induced by establishing Klebsiella pneumonia sepsis in mice with selective deletion of neutrophils and macrophages in the gut. The distribution of orally administered fluorescein isothiocyanate-dextran and carmine excretion time was used to determine the severity of small bowel disease. The effect of macrophages on intestinal motility was evaluated after prostaglandin E2 therapy.

Results

We found that muscular neutrophil infiltration leading to neuronal loss in the intestine muscle triggered intestinal motility dysfunction after pneumonia sepsis; however, reduced neutrophil infiltration did not improve intestinal motility dysfunction. Moreover, macrophage depletion aggravated gut motility dysfunction. The addition of macrophages directly to a smooth muscle was responsible for the recovery of intestinal motility.

Conclusion

Our results suggest that a direct interaction between macrophages and smooth muscle is neurologically independent of the restoration of intestinal dysmotility.