bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the microbiota composition in the genital tract of infertile patients with chronic endometritis or endometrial polyps
Authors: Liang Junhua , Li Meng , Zhang Lei , Yang Yang , Jin Xia , Zhang Qiongqiong , Lv Tao , Huang Zhenyu , Liao Qinping , Tong Xiaowen 
Published: May 2023

BackgroundThe previous researches show that infertile patients have a higher incidence of endometritis and endometrial polyps, and the occurrence of these two diseases is related to changes in the microbiota of the genital tract. We aim to determine the composition and changing characteristics of the microbiota in the genital tract (especially the endometrium) of infertile patients with chronic endometritis or endometrial polyps, and find the correlation between it and the occurrence of diseases.MethodsThis is a prospective study. We collected genital tract biopsy samples from 134 asymptomatic infertile patients receiving assisted reproductive therapy before embryo transfer. Through pathological examination and 16S ribosomal RNA(16S rRNA) sequencing, we determined the distribution of chronic endometritis and endometrial polyps in these patients, as well as their distribution of reproductive tract microorganisms.ResultsCompared with the normal control group, the microbial group of reproductive tract in patients with chronic endometritis and endometrial polyps is changed, and there are significant species differences and relative abundance differences in the vagina, cervix and uterine cavity. Lactobacillus, the dominant flora of female genital tract, showed a change in abundance in patients with endometrial diseases. Endometrial microbiota composed of Staphylococcus, Gardnerella, Atopobium, Streptococcus, Peptostreptococcus, Chlamydia, Fusobacterium, Acinetobacter, etc. are related to chronic endometritis and endometrial polyps.ConclusionThe results showed that, compared with the normal control group, the endometrial microbiota of infertile patients with chronic endometritis or endometrial polyps did have significant changes in the relative abundance distribution of species, suggesting that changes in local microecology may be an important factor in the occurrence of disease, or even adverse pregnancy outcomes. The further study of endometrial microecology may provide a new opportunity to further improve the diagnosis and treatment strategy of chronic endometritis.
Genome-wide profiling of miRNA-gene regulatory networks in mouse postnatal heart development—implications for cardiac regeneration
Authors: Chaudhari Umesh , Pohjolainen Lotta , Ruskoaho Heikki , Talman Virpi 
Published: May 2023

BackgroundAfter birth, mammalian cardiomyocytes substantially lose proliferative capacity with a concomitant switch from glycolytic to oxidative mitochondrial energy metabolism. Micro-RNAs (miRNAs) regulate gene expression and thus control various cellular processes. Their roles in the postnatal loss of cardiac regeneration are however still largely unclear. Here, we aimed to identify miRNA-gene regulatory networks in the neonatal heart to uncover role of miRNAs in regulation of cell cycle and metabolism.Methods and resultsWe performed global miRNA expression profiling using total RNA extracted from mouse ventricular tissue samples collected on postnatal day 1 (P01), P04, P09, and P23. We used the miRWalk database to predict the potential target genes of differentially expressed miRNAs and our previously published mRNA transcriptomics data to identify verified target genes that showed a concomitant differential expression in the neonatal heart. We then analyzed the biological functions of the identified miRNA-gene regulatory networks using enriched Gene Ontology (GO) and KEGG pathway analyses. Altogether 46 miRNAs were differentially expressed in the distinct stages of neonatal heart development. For twenty miRNAs, up- or downregulation took place within the first 9 postnatal days thus correlating temporally with the loss of cardiac regeneration. Importantly, for several miRNAs, including miR-150-5p, miR-484, and miR-210-3p there are no previous reports about their role in cardiac development or disease. The miRNA-gene regulatory networks of upregulated miRNAs negatively regulated biological processes and KEGG pathways related to cell proliferation, while downregulated miRNAs positively regulated biological processes and KEGG pathways associated with activation of mitochondrial metabolism and developmental hypertrophic growth.ConclusionThis study reports miRNAs and miRNA-gene regulatory networks with no previously described role in cardiac development or disease. These findings may help in elucidating regulatory mechanism of cardiac regeneration and in the development of regenerative therapies.
Relevance of PUFA-derived metabolites in seminal plasma to male infertility
Authors: Chen Xiangfeng , Wu Bin , Shen XiaoRong , Wang Xin , Ping Ping , Miao Maohua , Liang Ningning , Yin Huiyong , Shi Huijuan , Qian Jun , Zhang Tiancheng 
Published: May 2023

AimThis study aims to investigate the biological effects of polyunsaturated fatty acid (PUFA)-derived metabolites in seminal plasma on male fertility and to evaluate the potential of PUFA as a biomarker for normozoospermic male infertility.MethodsFrom September 2011 to April 2012, We collected semen samples from 564 men aged 18 to 50 years old (mean=32.28 years old)ch., residing in the Sandu County, Guizhou Province, China. The donors included 376 men with normozoospermia (fertile: n=267; infertile: n=109) and 188 men with oligoasthenozoospermia (fertile: n=121; infertile: n=67). The samples thus obtained were then analyzed by liquid chromatography-mass spectrometry (LC-MS) to detect the levels of PUFA-derived metabolites in April 2013. Data were analyzed from December 1, 2020, to May 15, 2022.ResultsOur analysis of propensity score-matched cohorts revealed that the concentrations of 9/26 and 7/26 metabolites differed significantly between fertile and infertile men with normozoospermia and oligoasthenozoospermia, respectively (FDR &lt; 0.05). In men with normozoospermia, higher levels of 7(R)-MaR1 (HR: 0.4 (95% CI [0.24, 0.64]) and 11,12-DHET (0.36 (95% CI [0.21, 0.58]) were significantly associated with a decreased risk of infertility, while higher levels of 17(S)-HDHA (HR: 2.32 (95% CI [1.44, 3.79]), LXA5 (HR: 8.38 (95% CI [4.81, 15.24]), 15d-PGJ2 (HR: 1.71 (95% CI [1.06, 2.76]), and PGJ2 (HR: 2.28 (95% CI [1.42, 3.7]) correlated with an increased risk of infertility. Our ROC model using the differentially expressed metabolites showed the value of the area under the curve to be 0.744.ConclusionThe PUFA-derived metabolites 7(R)-MaR1, 11,12-DHET, 17(S)-HDHA, LXA5, and PGJ2 might be considered as potential diagnostic biomarkers of infertility in normozoospermic men.
Causality between sarcopenia and diabetic nephropathy: a bidirectional Mendelian randomization study
Authors: Ren Linan , Wang Yao , Ju Feng , Sun Meixin , Gang Xiaokun , Wang Guixia 
Published: May 2023

Background and purposeObservational studies have shown that sarcopenia and diabetic nephropathy (DN), are closely related; however, the causal relationship is unclear. This study aims to address this issue using a bidirectional Mendelian randomization (MR) study.MethodologyWe data from genome-wide association studies including appendicular lean mass (n = 244,730), grip strength (right: n = 461,089, left: n = 461026), walking speed (n = 459,915), and DN (3283 cases and 181,704 controls) to conduct a bidirectional MR study. First, we conducted a Forward MR analysis to evaluate the causality of sarcopenia on the risk of DN from the genetic perspective with appendicular lean mass, grip strength, and walking speed as exposure and DN as the outcome. Then, DN as the exposure, we performed a Reverse MR analysis to determine whether DN impacted the appendicular lean mass, grip strength, and walking speed of the appendices. Finally, a series of sensitivity studies, such as heterogeneity tests, pleiotropy evaluations, and Leave-one-out analyses, were conducted to assess the MR analysis’s accuracy further.ResultsAccording to a forward MR analysis, a genetically predicted decrease in appendicular lean mass is associated with an increased risk of developing DN risk (inverse variance weighting[IVW]: odd ratio [OR] = 0.863, 95% confidence interval [CI] 0.767-0.971; P = 0.014). According to reverse MR results, grip strength decreased as DN progressed (IVW: right β = 0.003, 95% CI: - 0.021 to - 0.009, P = 5.116e-06; left β = 0.003, 95% CI: - 0.024 to - 0.012, P = 7.035e-09). However, the results of the other MR analyses were not statistically different.ConclusionNotably, our findings suggest that the causal relationship between sarcopenia and DN cannot be generalized. According to analysis of the individual characteristic factors of sarcopenia, reducing in appendicular lean mass increases the risk of developing DN and DN is linked to reduced grip strength. But overall, there is no causal relationship between sarcopenia and DN, because the diagnosis of sarcopenia cannot be determined by one of these factors alone.
Acute and chronic lung inflammation drives changes in epithelial glycans
Authors: Alvarez Carlos A. , Qian Emily , Glendenning Leandre M. , Reynero Kalob M. , Kukan Emily N. , Cobb Brian A. 
Published: May 2023

IntroductionAsthma is the most common chronic inflammatory disease and it is characterized by leukocyte infiltration and tissue remodeling, with the latter generally referring to collagen deposition and epithelial hyperplasia. Changes in hyaluronin production have also been demonstrated, while mutations in fucosyltransferases reportedly limit asthmatic inflammation.MethodsGiven the importance of glycans in cellular communication and to better characterize tissue glycosylation changes associated with asthma, we performed a comparative glycan analysis of normal and inflamed lungs from a selection of murine asthma models.ResultsWe found that among other changes, the most consistent was an increase in fucose-α1,3-N-acetylglucosamine (Fuc-α1,3-GlcNAc) and fucose-α1,2-galactose (Fuc-α1,2-Gal) motifs. Increases in terminal galactose and N-glycan branching were also seen in some cases, whereas no overall change in O-GalNAc glycans was observed. Increased Muc5AC was found in acute but not chronic models, and only the more human-like triple antigen model yielded increased sulfated galactose motifs. We also found that human A549 airway epithelial cells stimulated in culture showed similar increases in Fuc-α1,2-Gal, terminal galactose (Gal), and sulfated Gal, and this matched transcriptional upregulation of the α1,2-fucosyltransferase Fut2 and the α1,3-fucosyltransferases Fut4 and Fut7.ConclusionsThese data suggest that airway epithelial cells directly respond to allergens by increasing glycan fucosylation, a known modification important for the recruitment of eosinophils and neutrophils.
Differential effect of lactate on synovial fibroblast and macrophage effector functions
Authors: Pucino Valentina , Nefla Meriam , Gauthier Vincent , Alsaleh Ghada , Clayton Sally A. , Marshall Jennifer , Filer Andrew , Clark Andy R. , Raza Karim , Buckley Christopher D. 
Published: May 2023

IntroductionThe synovial membrane is the main site of inflammation in rheumatoid arthritis (RA). Here several subsets of fibroblasts and macrophages, with distinct effector functions, have been recently identified. The RA synovium is hypoxic and acidic, with increased levels of lactate as a result of inflammation. We investigated how lactate regulates fibroblast and macrophage movement, IL-6 secretion and metabolism via specific lactate transporters.MethodsSynovial tissues were taken from patients undergoing joint replacement surgery and fulfilling the 2010 ACR/EULAR RA criteria. Patients with no evidence of degenerative or inflammatory disease were used as control. Expression of the lactate transporters SLC16A1 and SLC16A3 on fibroblasts and macrophages was assessed by immunofluorescence staining and confocal microscopy. To test the effect of lactate in vitro we used RA synovial fibroblasts and monocyte-derived macrophages. Migration was assessed via scratch test assays or using trans-well inserts. Metabolic pathways were analysed by Seahorse analyser. IL-6 secretion was determined by ELISA. Bioinformatic analysis was performed on publicly available single cell and bulk RNA sequencing datasets.ResultsWe show that: i) SLC16A1 and SLC16A3 which regulate lactate intake and export respectively, are both expressed in RA synovial tissue and are upregulated upon inflammation. SLC16A3 is more highly expressed by macrophages, while SLC16A1 was expressed by both cell types. ii) This expression is maintained in distinct synovial compartments at mRNA and protein level. iii) Lactate, at the concentration found in RA joints (10 mM), has opposite effects on the effector functions of these two cell types. In fibroblasts, lactate promotes cell migration, IL-6 production and increases glycolysis. In contrast macrophages respond to increases in lactate by reducing glycolysis, migration, and IL-6 secretion.DiscussionIn this study, we provide the first evidence of distinct functions of fibroblasts and macrophages in presence of high lactate levels, opening new insights in understanding the pathogenesis of RA and offering novel potential therapeutic targets.
Synovial monocytes contribute to chronic inflammation in childhood-onset arthritis via IL-6/STAT signalling and cell-cell interactions
Authors: Schmidt Tobias , Dahlberg Alma , Berthold Elisabet , Król Petra , Arve-Butler Sabine , Rydén Emilia , Najibi Seyed Morteza , Mossberg Anki , Bengtsson Anders A. , Kahn Fredrik , Månsson Bengt , Kahn Robin 
Published: May 2023

IntroductionMonocytes are key effector cells in inflammatory processes. We and others have previously shown that synovial monocytes in childhood-onset arthritis are activated. However, very little is known about how they contribute to disease and attain their pathological features. Therefore, we set out to investigate the functional alterations of synovial monocytes in childhood-onset arthritis, how they acquire this phenotype, and whether these mechanisms could be used to tailorize treatment.MethodsThe function of synovial monocytes was analysed by assays believed to reflect key pathological events, such as T-cell activation-, efferocytosis- and cytokine production assays using flow cytometry in untreated oligoarticular juvenile idiopathic arthritis (oJIA) patients (n=33). The effect of synovial fluid on healthy monocytes was investigated through mass spectrometry and functional assays. To characterize pathways induced by synovial fluid, we utilized broad-spectrum phosphorylation assays and flow cytometry, as well as inhibitors to block specific pathways. Additional effects on monocytes were studied through co-cultures with fibroblast-like synoviocytes or migration in transwell systems.ResultsSynovial monocytes display functional alterations with inflammatory and regulatory features, e.g., increased ability to induce T-cell activation, resistance to cytokine production following activation with LPS and increased efferocytosis. In vitro, synovial fluid from patients induced the regulatory features in healthy monocytes, such as resistance to cytokine production and increased efferocytosis. IL-6/JAK/STAT signalling was identified as the main pathway induced by synovial fluid, which also was responsible for a majority of the induced features. The magnitude of synovial IL-6 driven activation in monocytes was reflected in circulating cytokine levels, reflecting two groups of low vs. high local and systemic inflammation. Remaining features, such as an increased ability to induce T-cell activation and markers of antigen presentation, could be induced by cell-cell interactions, specifically via co-culture with fibroblast-like synoviocytes.ConclusionsSynovial monocytes in childhood-onset arthritis are functionally affected and contribute to chronic inflammation, e.g., via promoting adaptive immune responses. These data support a role of monocytes in the pathogenesis of oJIA and highlight a group of patients more likely to benefit from targeting the IL-6/JAK/STAT axis to restore synovial homeostasis.
Glabridin inhibited the spread of polymyxin-resistant Enterobacterium carrying ICEMmoMP63
Authors: Fu Jiafang , Liu Yayu , Wang Fengtian , Zong Gongli , Wang Zhen , Zhong Chuanqing , Cao Guangxiang 
Published: May 2023

IntroductionThe role of integrative and conjugative elements (ICEs) in antibiotic resistance in Morganella morganii is unknown. This study aimed to determine whether an ICE identified in the M. morganii genome contributed to the polymyxin resistance.MethodsWhole-genome sequencing was performed followed by bioinformatics analyses to identify ICEs and antibiotic resistance genes. Conjugation assays were performed to analyze the transferability of a discovered ICE. A drug transporter encoded on the ICE was heterogeneously expressed in Escherichia coli, minimum inhibitory concentrations of antibiotics were determined, and a traditional Chinese medicine library was screened for potential efflux pump inhibitors.ResultsAn antibiotic resistance-conferring ICE, named ICEMmoMP63, was identified. ICEMmoMP63 was verified to be horizontally transferred among Enterobacteriaceae bacteria. G3577_03020 in ICEMmoMP63 was found to mediate multiple antibiotic resistances, especially polymyxin resistance. However, natural compound glabridin was demonstrated to inhibit polymyxin resistance.DiscussionOur findings support the need for monitoring dissemination of ICEMmoMP63 in Enterobacteriaceae bacteria. Combined glabridin and polymyxin may have therapeutic potential for treating infections from multi-drug resistant bacteria carrying ICEMmoMP63.
[18F]AlF-NOTA-ADH-1: A new PET molecular radiotracer for imaging of N-cadherin-positive tumors
Authors: Liu Zhenfeng , Wen Guanghua , Huang Yuqiao , Dong Yanzhao , Wang Zewei , Alhaskawi Ahmad , Zhang Shuyi , Wang GuoLin , Ye Qianni , Zhou Haiying , Lu Hui , Dong Mengjie 
Published: May 2023

BackgroundThe cell adhesion molecule (CAM) N-cadherin has become an important target for tumor therapy. The N-cadherin antagonist, ADH-1, exerts significant antitumor activity against N-cadherin-expressing cancers.MethodsIn this study, [18F]AlF-NOTA-ADH-1 was radiosynthesized. An in vitro cell binding test was performed, and the biodistribution and micro-PET imaging of the probe targeting N-cadherin were also studied in vivo.ResultsRadiolabeling of ADH-1 with [18F]AlF achieved a yield of up to 30% (not decay-corrected) with a radiochemical purity of &gt;97%. The cell uptake study showed that Cy3-ADH-1 binds to SW480 cells but weakly binds to BXPC3 cells in the same concentration range. The biodistribution results demonstrated that [18F]AlF-NOTA-ADH-1 had a good tumor/muscle ratio (8.70±2.68) in patient-derived xenograft (PDX) tumor xenografts but a lower tumor/muscle ratio (1.91±0.69) in SW480 tumor xenografts and lowest tumor/muscle ratio (0.96±0.32) in BXPC3 tumor xenografts at 1 h post-injection (p.i.) These findings were in accordance with the immunohistochemistry results. The micro PET imaging results revealed good [18F]AlF-NOTA-ADH-1 tumor uptake in pancreatic cancer PDX xenografts with strong positive N-calcium expression, while lower tumor uptake in SW480 xenografts with positive expression of N-cadherin, and significantly lower tumor uptake in BXPC3 xenografts with low expression of N-cadherin, which was consistent with the biodistribution and immunohistochemistry results. The N-cadherin-specific binding of [18F]AlF-NOTA-ADH-1 was further verified by a blocking experiment involving coinjection of a non radiolabeled ADH-1 peptide, resulting in a significant reduction in tumor uptake in PDX xenografts and SW480 tumor.Conclusion[18F]AlF-NOTA-ADH-1 was successfully radiosynthesized, and Cy3-ADH-1 showed favorable N-cadherin-specific targeting ability by in vitro data. The biodistribution and microPET imaging of the probe further showed that [18F]AlF-NOTA-ADH-1 could discern different expressions of N-cadherin in tumors. Collectively, the findings demonstrated the potential of [18F]AlF-NOTA-ADH-1 as a PET imaging probe for non-invasive evaluation of the N-cadherin expression in tumors.
Assessing lung aeration using ultrasound after birth in near-term lambs at risk of respiratory distress
Authors: Pryor E. J. , Davies I. M. , Crossley K. J. , Thiel A. M. , McGillick E. V. , Rodgers K , Nitsos I , Kitchen M. J. , Blank D. A. , Hooper S. B. 
Published: May 2023

BackgroundOptimizing respiratory support after birth requires real-time feedback on lung aeration. We hypothesized that lung ultrasound (LUS) can accurately monitor the extent and progression of lung aeration after birth and is closely associated with oxygenation.MethodsNear-term (140 days gestation, term ∼147 days), spontaneously breathing lambs with normal (controls; n = 10) or elevated lung liquid levels (EL; n= 9) were delivered by Caesarean section and monitored for four hours after birth. LUS (Phillips CX50, L3–12 transducer) images and arterial blood gases were taken every 5–20 min. LUS images were analyzed both qualitatively (grading) and quantitatively (using the coefficient of variation of pixel intensity (CoV) to estimate the degree of lung aeration), which was correlated with the oxygen exchange capacity of the lungs (Alveolar-arterial difference in oxygen; AaDO2).ResultsLung aeration, measured using LUS, and the AaDO2 improved over the first 4 h after birth. The increase in lung aeration measured using CoV of pixel intensity, but not LUS grade, was significantly reduced in EL lambs compared to controls (p = 0.02). The gradual decrease in AaDO2 after birth was significantly correlated with increased lung aeration in both control (grade, r2 = 0.60, p &lt; 0.0001; CoV, r2 = 0.54, p &lt; 0.0001) and EL lambs (grade, r2 = 0.51, p &lt; 0.0001; CoV, r2 = 0.44, p &lt; 0.0001).ConclusionsLUS can monitor lung aeration and liquid clearance after birth in spontaneously breathing near-term lambs. Image analysis techniques (CoV) may be able detect small to moderate differences in lung aeration in conditions with lung liquid retention which are not readily identified using qualitative LUS grading.
Feasibility, and barriers to use escitalopram in functional gastrointestinal disorders
Authors: Alkhowaiter Saad S. , Alshahrani Amani H. , Almarzouqi Hala F. , Alonazi Gadah K. , Alhawassi Tariq M. , AlRasheed Maha M. 
Published: May 2023

Background and study aims: The feasibility and barriars of escitalopram use in patients with functional gastrointestinal disorders (FGIDs) are still debated. We aimed to evaluate the feasibility, safety and efficacy and barriars of escitalopram use in managing FGIDs in the Saudi population.Patients and Methods: We included 51 patients who received escitalopram for irritable bowel syndrome (n = 26), functional heartburn (n = 10), globus sensation (n = 10) or combined disorders (n = 5). We used an irritable bowel syndrome-severity scoring system IBS-SSS), GerdQ questionnaire and Glasgow Edinburg Throat Scale (GETS) to assess disease severity change before and after treatment.Results: The median age was 33 years (25th- 75th percentiles: 29–47), and 26 (50.98%) were males. Forty-one patients experienced side effects (80.39%), but most side effects were mild. The most common side effects were drowsiness/fatigue/dizziness (54.9%), xerostomia (23.53%), nausea/vomiting (21.57%) and weight gain (17.65%). IBS-SSS was 375 (255–430) and 90 (58–205) before and after treatment, respectively (p &lt; 0.001). GerdQ score was 12 (10–13) before treatment and 7 (6–10) after treatment (p = 0.001). GETS score before treatment was 32.5 (21–46) and after treatment became 22 (13–31) (p = 0.002). Thirty-five patients refused to take the medications, and seven patients discontinued the medication. Possible causes of the poor compliance were fear of the medications and not being convinced of taking psychiatric medications for functional disorders (n = 15).Conclusion: Escitalopram could be a safe and effective treatment for functional gastrointestinal disorders. Targeting and managing factors leading to poor compliance could further improve the treatment outcome.