bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiological Changes and Interactions Between Microbiome and the Host During Pregnancy
Authors: Zakaria Zain Zaki , Al-Rumaihi Shouq , Al-Absi Rana S. , Farah Huda , Elamin Muram , Nader Rahaf , Bouabidi Salma , Suleiman Sara Elgaili , Nasr Shahd , Al-Asmakh Maha
Published: February 2022

In recent years, it has become clear that microbiome play a variety of essential roles in human metabolism, immunity, and overall health and that the composition of these microbiome is influenced by our environment, diet, weight, hormones, and other factors. Indeed, numerous physiological and pathological conditions, including obesity and metabolic syndrome, are associated with changes in our microbiome, referred to as dysbiosis. As a result, it is not surprising that such changes occur during pregnancy, which includes substantial weight gain and significant changes in metabolism and immune defenses. The present review relates physiological changes during pregnancy to alterations in the microbial composition at various sites, including the gut, oral cavity, and vagina. Pregnancy has been linked to such microbial changes, and we believe that, in contrast to certain disease states, these microbial changes are vital for a healthy pregnancy, probably through their influence on the mother’s immunological, endocrinological, and metabolic status.
Similarities in Hypertension Status but Differences in Mortality Risk: A Comparison of 2017 ACC/AHA and 2018 Chinese Hypertension Guidelines
Authors: Chen Kangyu , Su Hao , Wang Qi , Wu Zhenqiang , Shi Rui , Yu Fei , Yan Ji , Yuan Xiaodan , Qin Rui , Zhou Ziai , Hou Zeyi , Li Chao , Chen Tao
Published: February 2022

Background

Few studies investigated the concordance in hypertension status and antihypertensive treatment recommendations between the 2018 Chinese Hypertension League (CHL) guidelines and the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines and assessed the change of premature mortality risk with hypertension defined by the ACC/AHA guidelines.

Methods

We used the baseline data of the China Health and Retirement Longitudinal Study (CHARLS) to estimate the population impact on hypertension management between CHL and ACC/AHA guidelines. Mortality risk from hypertension was estimated using the data from China Health and Nutrition Survey (CHNS). Cox proportional hazards model was used to estimate the hazard ratios (HRs) and their 95% confidence intervals(CIs).

Results

Among 13,704 participants analyzed from the nationally representative data of CHARLS, 42.64% (95% CI: 40.35, 44.96) of Chinese adults were diagnosed by both CHL and ACC/AHA guidelines. 41.25% (39.17, 43.36) did not have hypertension according to either guideline. Overall, the concordance in hypertension status was 83.89% (81.69, 85.57). A high percentage of agreement was also found for recommendation to initiate treatment among untreated subjects (87.62% [86.67, 88.51]) and blood pressure (BP) above the goal among treated subjects (71.68% [68.16, 74.95]). Among 23,063 adults from CHNS, subjects with hypertension by CHL had a higher risk of premature mortality (1.75 [1.50, 2.04]) compared with those without hypertension. The association diminished for hypertension by ACC/AHA (1.46 [1.07, 1.30]). Moreover, the excess risk was not significant for the newly defined Grade 1 hypertension by ACC/AHA (1.15 [0.95, 1.38]) when compared with BP <120/80 mmHg. This contrasted with the estimate from CHL (1.54 [1.25, 1.89]). The same pattern was observed for total mortality.

Conclusions

If ACC/AHA guidelines were adopted, a high degree of concordance in hypertension status and initiation of antihypertensive treatment was found with CHL guidelines. However, the mortality risk with hypertension was reduced with a non-significant risk for Grade 1 hypertension defined by the ACC/AHA.
Plasma Proteome Profiling of Patients With In-stent Restenosis by Tandem Mass Tag-Based Quantitative Proteomics Approach
Authors: Hou Jingyuan , Deng Qiaoting , Liu Sudong , Qiu Xiaohong , Deng Xunwei , Zhong Wei , Zhong Zhixiong
Published: February 2022

Background

Despite the widespread application of new drug-eluting stents, a considerable portion of patients experience in-stent restenosis (ISR). To date, the pathophysiologic mechanisms of ISR remain poorly understood.

Methods

In this study, we collected plasma samples from ISR patients (n = 29) and non-ISR patients (n = 36) after drug-eluting stent implantation, as well as from healthy controls (HCs) (n = 32). Our goal was to investigate differences in plasma protein profiles using tandem mass tag (TMT) labeling coupled with liquid chromatography and tandem mass spectrometry. The proteomic data were validated by enzyme-linked immunosorbent assay (ELISA). Bioinformatic analyses were conducted to analyze potential pathways and protein-protein interaction (PPI) involved in ISR.

Results

A total of 1,696 proteins were identified, of which 278 differed in protein abundance between non-ISR and HCs, 497 between ISR and HCs, and 387 between ISR and non-ISR, respectively. Bioinformatic analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and PPI, further demonstrated that differentially abundant proteins between ISR and non-ISR are involved in several crucial biological processes and signaling pathways, such as focal adhesion, platelet activation, Rap1 signaling, regulation of actin cytoskeleton, and cholesterol metabolism. Among the identified differentially abundant proteins in ISR, 170 were increased in abundance relative to both non-ISR patients and HCs. Some of these proteins were identified to have critical functions for atherosclerosis development and might be involved in ISR pathology. Among these proteins, 3 proteins with increased abundance including fetuin-B, apolipoprotein C-III (APOC3), and cholesteryl ester transfer protein (CETP) were confirmed by ELISA.

Conclusions

This is the first study provided a comprehensive proteomic profile to understand ISR pathology, which may help identify early diagnostic biomarkers and therapeutic targets.
Regulation of Ion Channel Function in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes by Cancer Cell Secretion Through DNA Methylation
Authors: Zhong Rujia , Zhang Feng , Yang Zhen , Li Yingrui , Xu Qiang , Lan Huan , Lang Siegfried , Cyganek Lukas , Burgermeister Elke , El-Battrawy Ibrahim , Zhou Xiaobo , Akin Ibrahim , Borggrefe Martin
Published: February 2022

Background

Cardiac dysfunction including arrhythmias appear frequently in patients with cancers, which are expected to be caused mainly by cardiotoxic effects of chemotherapy. Experimental studies investigating the effects of cancer cell secretion without chemotherapy on ion channel function in human cardiomyocytes are still lacking.

Methods

The human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) generated from three healthy donors were treated with gastrointestinal (GI) cancer (AGS and SW480 cells) medium for 48 h. The qPCR, patch-clamp, western blotting, immunostaining, dot blotting, bisulfite sequence, and overexpression of the ten-eleven translocation (TET) enzyme were performed for the study.

Results

After treated with cancer cell secretion, the maximum depolarization velocity and the action potential amplitude were reduced, the action potential duration prolonged, peak Na+ current, and the transient outward current were decreased, late Na+ and the slowly activating delayed rectifier K+ current were increased. Changes of mRNA and protein level of respective channels were detected along with altered DNA methylation level in CpG island in the promoter regions of ion channel genes and increased protein levels of DNA methyltransferases. Phosphoinositide 3-kinase (PI3K) inhibitor attenuated and transforming growth factor-β (TGF-β) mimicked the effects of cancer cell secretion.

Conclusions

GI cancer cell secretion could induce ion channel dysfunction, which may contribute to occurrence of arrhythmias in cancer patients. The ion channel dysfunction could result from DNA methylation of ion channel genes via activation of TGF-β/PI3K signaling. This study may provide new insights into pathogenesis of arrhythmia in cancer patients.
SAR Offset Tracking Based on Feature Points
Authors: Peng Lincai , Wang Hua , Ng Alex Hay-Man , Yang Xiaoge
Published: February 2022

The offset tracking approach has been widely used to measure large ground deformation as a complement to Interferometric Synthetic Aperture Radar (InSAR) when its coherence is poor and/or the deformation gradient is large. The standard offset tracking procedures estimate deformation of tie points, which are uniformly distributed over two SAR images, resulting in many unsatisfactory measurements. In this paper, we propose a feature point offset tracking (FPOT) procedure to overcome the limitation of the standard method. First, we identify feature points using the Speeded Up Robust Feature (SURF) algorithm. Improper feature points are masked using external land coverage information like water coverages. Then, we use the standard cross-correlation algorithm to find offsets of the remaining feature points between reference and secondary images. The offset outliers are removed using a quadtree filtering. Finally, the resultant deformation field is generated by removing systematic offsets estimated with far-field feature points. We assess the effectiveness of our proposed procedure using the 2016 Mw 7.8 Kaikōura earthquake in New Zealand. In far-field where deformation is expected to be negligible, histograms of offset distribution show that the root-mean-square error (RMSE) is decreased from 0.07 pixels to 0.02–0.03 pixels for regular points and feature points, respectively, after quadtree filtering. The RMSE between our FPOT-derived offsets and GPS measurements are 0.14 and 0.48 m for range and azimuth offsets, respectively. The results show that our proposed procedure can significantly improve the efficiency, accuracy, and reliability with respect to the standard regular point offset tracking (RPOT).
Albedo Parametrizations for the Laohugou Glacier No.12 in the Qilian Mountains—Previous Models and an Alternative Approach
Authors: Wang Lihui , Zhang Dongwei , Steiner Jakob F. , He Xiaobo , Chen Jizu , Liu Yushuo , Li Yanzhao , Jin Zizhen , Qin Xiang
Published: February 2022

Accurate estimates of albedo can be crucial for energy balance models of glaciers. A number of algorithms exist which are often site dependent and rely on accurate measurements or estimates of snow depth. Using the well-established COSIMA model we simulate the energy and mass balance of the Laohugou Glacier No.12 in the Qilian Mountains, on the northern fringe of the Qinghai-Tibetan Plateau, a glacier that has been well studied in the past. Using energy flux and mass balance measurements between 2010 and 2015 we were able to validate the model over multiple seasons. Using the original albedo parametrization, the model fails to reproduce the observed mass balance. We show that this is due to the failure to estimate snow depth accurately. We therefore applied two alternative albedo algorithms, one well established example and one new parametrization only dependent on temperature and time since last snow fall. As a result, mass balance simulations improve considerably from a RMSE of 0.53 m w.e. for the original parametrization to 0.39 and 0.19 m w.e. for the uncalibrated established and the new calibrated model respectively. Modelled albedo during the ablation period (NSE = 0.05, R2 = 0.33) is more accurate than during the accumulation period (NSE = −0.37, R2 = 0.04). Testing the new model at another glacier on the Tibetan Plateau shows that a local recalibration of parameters remains necessary to achieve satisfying results. Investigations into the effect of impurities in snow, regional moisture sources and changing surface characteristics with rising temperatures will be crucial for accurate projections into the future.
Interval Safety Layer Coupled With an Impulsive MPC for Artificial Pancreas to Handle Intrapatient Variability
Authors: Villa-Tamayo María F. , García-Jaramillo Maira , León-Vargas Fabian , Rivadeneira Pablo S.
Published: February 2022

The aim of control strategies for artificial pancreas systems is to calculate the insulin doses required by a subject with type 1 diabetes to regulate blood glucose levels by reducing hyperglycemia and avoiding the induction of hypoglycemia. Several control formulations developed for this end involve a safety constraint given by the insulin on board (IOB) estimation. This constraint has the purpose of reducing hypoglycemic episodes caused by insulin stacking. However, intrapatient variability constantly changes the patient’s response to insulin, and thus, an adaptive method is required to restrict the control action according to the current situation of the subject. In this work, the control action computed by an impulsive model predictive controller is modulated with a safety layer to satisfy an adaptive IOB constraint. This constraint is established with two main steps. First, upper and lower IOB bounds are generated with an interval model that accounts for parameter uncertainty, and thus, define the possible system responses. Second, the constraint is selected according to the current value of glycemia, an estimation of the plant-model mismatch, and their corresponding first and second time derivatives to anticipate the changes of both glucose levels and physiological variations. With this strategy satisfactory results were obtained in an adult cohort where random circadian variability and sensor noise were considered. A 92% time in normoglycemia was obtained, representing an increase of time in range compared to previous MPC strategies, and a reduction of time in hypoglycemia to 0% was achieved without dangerously increasing the time in hyperglycemia.
The Role of Sex Hormones on Bone Mineral Density, Marrow Adiposity, and Muscle Adiposity in Middle-Aged and Older Men
Authors: Xu Li , Zhao Qian , Li Kai , Zhang Yong , Wang Chao , Hind Karen , Wang Ling , Liu Yandong , Cheng Xiaoguang
Published: February 2022

Purpose

The etiology of age-related bone loss is less clear in men. This study is aimed to observe the variations of endogenous sex hormone concentrations with increasing of age in men, and investigate their relations to bone mass, marrow adiposity, and muscle adiposity.

Methods

A total of 199 community-dwelling Chinese men (aged 41 to 82 years) were included and measured of serum total estradiol, total testosterone, and follicle-stimulating hormone (FSH) concentrations by enzyme-linked immunosorbent assay (ELISA). Vertebral trabecular volumetric bone mineral density (vBMD) was measured by quantitative computed tomography for all participants, and vertebral marrow fat content and erector muscle fat content were quantified by Chemistry-shift-encoding magnetic resonance imaging in 62 participants.

Results

In this population, FSH concentration increased (p < 0.001) gradually with aging. Lower vBMD was independently associated with higher FSH concentration (β = -0.216, p < 0.001), but not with total estradiol or total testosterone. For each standard deviation increase in FSH there was a 50% higher risk of an individual having osteopenia or osteoporosis (vBMD < 120 mg/cm3). Marrow fat content and erector muscle fat content were greater in osteopenic and osteoporotic men, but there were no associations with sex hormones concentrations.

Conclusion

In summary, FSH but not total estradiol or total testosterone is related to vertebral trabecular vBMD in middle-aged and older Chinese men. Neither marrow adiposity nor muscle adiposity is associated with sex hormones.
Kynurenic Acid Acts as a Signaling Molecule Regulating Energy Expenditure and Is Closely Associated With Metabolic Diseases
Authors: Zhen Delong , Liu Junjun , Zhang Xu Dong , Song Zehua
Published: February 2022

Kynurenic acid (KYNA) is an important bio-active product of tryptophan metabolism. In addition to its well-known neuroprotective effects on mental health disorders, it has been proposed as a bio-marker for such metabolic diseases as atherosclerosis and diabetes. Emerging evidence suggests that KYNA acts as a signaling molecule controlling the networks involved in the balance of energy store and expenditure through GPR35 and AMPK signaling pathway. KYNA plays an important role in the pathogenesis and development of several endocrine and metabolic diseases. Exercise training promotes KYNA production in skeletal muscles and increases thermogenesis in the long term and limits weight gain, insulin resistance and inflammation. Additionally, KYNA is also present in breast milk and may act as an anti-obesity agent in infants. Although we are far from fully understanding the role of KYNA in our body, administration of KYNA, enzyme inhibitors or metabolites may serve as a potential therapeutic strategy for treating metabolic diseases. The present review provides a perspective on the current knowledge regarding the biological effects of KYNA in metabolic diseases and perinatal nutrition.
Comprehensive Transcriptome Profiling of NAFLD- and NASH-Induced Skeletal Muscle Dysfunction
Authors: Guo Mingwei , Xiang Liping , Yao Jing , Zhang Jun , Zhu Shuangshuang , Wang Dongmei , Liu Caizhi , Li Guoqiang , Wang Jiawen , Gao Yuqing , Xie Cen , Ma Xinran , Xu Lingyan , Zhou Jian
Published: February 2022

Nonalcoholic fatty liver disease (NAFLD), characterized by extensive triglyceride accumulation in hepatocytes, may progress to nonalcoholic steatohepatitis (NASH) with liver fibrosis and inflammation and increase the risk of cirrhosis, cancer, and death. It has been reported that physical exercise is effective in ameliorating NAFLD and NASH, while skeletal muscle dysfunctions, including lipid deposition and weakness, are accompanied with NAFLD and NASH. However, the molecular characteristics and alterations in skeletal muscle in the progress of NAFLD and NASH remain unclear. In the present study, we provide a comprehensive analysis on the similarity and heterogeneity of quadriceps muscle in NAFLD and NASH mice models by RNA sequencing. Importantly, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway functional enrichment analysis revealed that NAFLD and NASH led to impaired glucose and lipid metabolism and deteriorated functionality in skeletal muscle. Besides this, we identified that myokines possibly mediate the crosstalk between muscles and other metabolic organs in pathological conditions. Overall, our analysis revealed a comprehensive understanding of the molecular signature of skeletal muscles in NAFLD and NASH, thus providing a basis for physical exercise as an intervention against liver diseases.
A Study of Protection Method for Hybrid Multiterminal UHVDC Lines Based on CEEMDAN–Teager Energy Operator
Authors: Xing Chao , Wang Long , Bi Guihong , Chen Shilong , Gao Jingye , Che Yanbo
Published: February 2022

In the research, a protection scheme for hybrid multiterminal UHVDC lines based on the CEEMDAN and Teager energy operator is proposed. The fault direction criterion is proposed according to the polarity difference of the sudden variable of the mode component of the current line on both sides of the T-zone after the fault of the EHV multiterminal hybrid DC system. When the fault is located on the left or right side of the T-zone, CEEMDAN is used to decompose the mode component of the fault transient current and obtain the intrinsic mode function (IMF component) at different local characteristic time scales. Then, the Teager energy operator is used to calculate the instantaneous energy of the current high-frequency IMF1 component. Finally, the faults inside and outside the line are judged by comparing the maximum value of current high-frequency IMF1 instantaneous energy with the setting value. When the fault is located in the T-zone, it is determined as a fault outside the line zone. The protection scheme of hybrid multiterminal UHVDC lines is given. The simulation model of the Kunliulong hybrid multiterminal UHVDC line system is built in a PSCAD/EMTDC simulation platform, and the proposed protection method is verified. A large number of simulation results show that the protection scheme has certain anti-transition resistance ability and high reliability.
Potentials and Integrated Suitability Pre-assessment of Wastewater Treatment Plants as Local Energy Cells
Authors: Neugebauer Georg , Lichtenwoehrer Peter , Huber Franz , Stoeglehner Gernot , Kretschmer Florian
Published: February 2022

In 2018 the European Union has recognized wastewater as a renewable energy source, particularly due to its thermal energy content. To create and further develop knowledge on the possible role that wastewater could play in the energy transition, this article pursues two objectives: 1) it presents an overview on the electric and thermal energy potentials available at the wastewater treatment plants (WWTPs) in the Central European area also taking their spatial context to adjacent settlement structures into account. 2) It introduces a small number of easy to apply criteria to (pre-)assess the suitability of WWTPs for being integrated into local energy (heat) supply concepts from an integrated perspective (considering energetic, spatial and environmental aspects). The investigations address the energy generation potentials of 3,315 WWTPs (with a treatment capacity of at least 5,000 population equivalents) in the area under survey. Analysis reveal, that notable amounts of heat ranging to almost 26 TWh/a are available. Their exploitation appears very promising, as investigations also show, that about 73% of the considered WWTPs are situated near or even within existing settlement structures implying very advantageous heat supply distances. Following the estimation of energy potentials, which is made available in the supplementary material, the presented suitability criteria can then be used to identify the most promising WWTPs in a specific regional/local context, in the investigated Central European area and beyond.
The Relationship Between Low-Density Lipoprotein Cholesterol and Progression of Mild Cognitive Impairment: The Influence of rs6859 in PVRL2
Authors: Xiao Qianyi , Xi Jianxiong , Wang Ruru , Zhao Qianhua , Liang Xiaoniu , Wu Wanqing , Zheng Li , Guo Qihao , Hong Zhen , Fu Hua , Ding Ding
Published: February 2022

Background: Genome-wide association studies have identified many Alzheimer’s disease (AD) genetic-risk single nucleotide polymorphisms (SNPs) and indicated the important role of the cholesterol/lipid metabolism pathway in AD pathogenesis. This study aims to investigate the effects of cholesterol and genetic risk factors on progression of mild cognitive impairment (MCI) to AD.

Methods: We prospectively followed 316 MCI participants aged ≥50 years with a baseline cholesterol profile and SNP genotyping data for 4.5 years on average in a sub-cohort of the Shanghai Aging Study. Total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol in serum were measured at baseline. SNP genotyping was performed using a MassARRAY system. At follow-up, consensus diagnosis of incident dementia and AD were established based on medical, neurological, and neuropsychological examinations. Cox regression models were used to assess the association of cholesterol and SNP with incident AD.

Results: The AG/AA genotypes of PVRL2 rs6859 were significantly associated with increased incident AD in MCI participants, compared with GG genotype (adjusted hazard ratio [HR] 2.75, 95% confidence interval [CI] 1.32–5.76, p = .007, false discovery rate–adjusted p = .030). In PVRL2 rs6859 AG/AA carriers, each-1 mmol/L higher level of LDL-C was significantly associated with a 48% decreased risk of AD (adjusted HR 0.52, 95%CI 0.33–0.84, p = .007). Consistent results were obtained when using LDL-C as the categorical variable (P for trend = 0.016).

Conclusion: The relationship between LDL-C and progression of MCI may be influenced by genetic variants.
RNASE2 Mediates Age-Associated B Cell Expansion Through Monocyte Derived IL-10 in Patients With Systemic Lupus Erythematosus
Authors: Zhu Yantong , Tang Xiaojun , Xu Yang , Wu Si , Liu Weilin , Geng Linyu , Ma Xiaolei , Tsao Betty P. , Feng Xuebing , Sun Lingyun
Published: February 2022

Systemic lupus erythematosus (SLE) is characterized by the production of pathogenic autoantibodies. Ribonuclease A family member 2 (RNase2) is known to have antiviral activity and immunomodulatory function. Although RNASE2 level has been reported to be elevated in SLE patients based on mRNA microarray detection, its pathologic mechanism remains unclear. Here, we confirmed that RNASE2 was highly expressed in PBMCs from SLE patients and associated with the proportion of CD11c+T-bet+ B cells, a class of autoreactive B cells also known as age-associated B cells (ABCs). We showed that reduction of RNASE2 expression by small interfering RNA led to the decrease of ABCs in vitro, accompanied by total IgG and IL-10 reduction. In addition, we demonstrated that both RNASE2 and IL-10 in peripheral blood of lupus patients were mainly derived from monocytes. RNASE2 silencing in monocytes down-regulated IL-10 production and consequently reduced ABCs numbers in monocyte-B cell co-cultures, which could be restored by the addition of recombinant IL-10. Based on above findings, we concluded that RNASE2 might induce the production of ABCs via IL-10 secreted from monocytes, thus contributing to the pathogenesis of SLE.
T Cells and CDDO-Me Attenuate Immunosuppressive Activation of Human Melanoma-Conditioned Macrophages
Authors: Torres Gretel M. , Yang Heetaek , Park Chanhyuk , Spezza Paul A. , Khatwani Nikhil , Bhandari Rajan , Liby Karen T. , Pioli Patricia A.
Published: February 2022

Melanoma tumors are highly immunogenic, making them an attractive target for immunotherapy. However, many patients do not mount robust clinical responses to targeted therapies, which is attributable, at least in part, to suppression of immune responses by tumor-associated macrophages (TAMs) in the tumor microenvironment (TME). Using a human in vitro tri-culture system of macrophages with activated autologous T cells and BRAFV600E mutant melanoma cells, we now show that activated T cells and the synthetic triterpenoid the methyl ester of 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO-Me) attenuate immune suppression. Surface expression of CD206, CD16 and CD163 on melanoma-conditioned macrophages was inhibited by the addition of T cells, suggesting relief of immuno-suppressive macrophage activation. We also demonstrated that addition of CDDO-Me to tri-cultures enhanced T cell-mediated reductions in CCL2, VEGF and IL-6 production in a contact-independent manner. Because these results suggest CDDO-Me alters melanoma-conditioned macrophage activation, we interrogated CDDO-Me-mediated changes in macrophage signaling pathway activation. Our results indicated that CDDO-Me inhibited phosphorylation of STAT3, a known inducer of TAM activation. Collectively, our studies suggest that activated T cells and CDDO-Me synergistically relieve immune suppression in melanoma cultures and implicate the potential utility of CDDO-Me in the treatment of melanoma.
Update on Tenosynovial Giant Cell Tumor, an Inflammatory Arthritis With Neoplastic Features
Authors: Robert Marie , Farese Helena , Miossec Pierre
Published: February 2022

Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to joint destruction and bone erosion. Even if many treatments were developed with success in the last decades, some patients fail to respond, and disease chronicity is still a burden. Mechanisms involved in such resistance may include molecular changes in stromal cells. Other explanations can come from observations of tenosynovial giant cell tumor (TGCT), first considered as an inflammatory arthritis, but with unusual neoplastic features. TGCT leads to synovium hypertrophy and hyperplasia with hemosiderin deposition. It affects young adults, resulting in secondary osteoarthritis and increased morbidity. TGCT shows clinical, histological and genetic similarities with RA but affecting a single joint. However, the monoclonality of some synoviocytes, the presence of translocations and rare metastases also suggest a neoplastic disease, with some features common with sarcoma. TGCT is more probably in an intermediate situation between an inflammatory and a neoplastic process, with a main involvement of the proinflammatory cytokine CSF-1/CSF1R signaling axis. The key treatment option is surgery. New treatments, derived from the RA and sarcoma fields, are emerging. The tyrosine kinase inhibitor pexidartinib was recently FDA-approved as the first drug for severe TGCT where surgery is not an option. Options directly targeting the excessive proliferation of synoviocytes are at a preclinical stage.
Unspecific CTL Killing Is Enhanced by High Glucose via TNF-Related Apoptosis-Inducing Ligand
Authors: Yang Wenjuan , Denger Andreas , Diener Caroline , Küppers Frederic , Soriano-Baguet Leticia , Schäfer Gertrud , Yanamandra Archana K. , Zhao Renping , Knörck Arne , Schwarz Eva C. , Hart Martin , Lammert Frank , Roma Leticia Prates , Brenner Dirk , Christidis Grigorios , Helms Volkhard , Meese Eckart , Hoth Markus , Qu Bin
Published: February 2022

TNF-related apoptosis inducing ligand (TRAIL) is expressed on cytotoxic T lymphocytes (CTLs) and TRAIL is linked to progression of diabetes. However, the impact of high glucose on TRAIL expression and its related killing function in CTLs still remains largely elusive. Here, we report that TRAIL is substantially up-regulated in CTLs in environments with high glucose (HG) both in vitro and in vivo. Non-mitochondrial reactive oxygen species, NFκB and PI3K/Akt are essential in HG-induced TRAIL upregulation in CTLs. TRAILhigh CTLs induce apoptosis of pancreatic beta cell line 1.4E7. Treatment with metformin and vitamin D reduces HG-enhanced expression of TRAIL in CTLs and coherently protects 1.4E7 cells from TRAIL-mediated apoptosis. Our work suggests that HG-induced TRAILhigh CTLs might contribute to the destruction of pancreatic beta cells in a hyperglycemia condition.
Nano vaccines for T. gondii Ribosomal P2 Protein With Nanomaterials as a Promising DNA Vaccine Against Toxoplasmosis
Authors: Yu ZhengQing , He Ke , Cao WanDi , Aleem Muhammad Tahir , Yan RuoFeng , Xu LiXin , Song XiaoKai , Li XiangRui
Published: February 2022

Caused by Toxoplasma gondii, toxoplasmosis has aroused great threats to public health around the world. So far, no effective vaccine or drug is commercially available, and the demands for a safe and effective therapeutic strategy have become more and more urgent. In the current study, we constructed a DNA vaccine encoding T. gondii ribosomal P2 protein (TgP2) and denoted as TgP2-pVAX1 plasmid. To improve the immunoprotection, nanomaterial poly-lactic-co-glycolic acid (PLGA) and chitosan were used as the delivery vehicle to construct TgP2-pVAX1/PLGA and TgP2-pVAX1/CS nanospheres. Before vaccinations in BALB/c mice, TgP2-pVAX1 plasmids were transiently transfected into Human Embryonic Kidney (HEK) 293-T cells, and the expression of the eukaryotic plasmids was detected by laser confocal microscopy and Western blotting. Then the immunoprotection of naked DNA plasmids and their two nano-encapsulations were evaluated in the laboratory animal model. According to the investigations of antibody, cytokine, dendritic cell (DC) maturation, molecule expression, splenocyte proliferation, and T lymphocyte proportion, TgP2-pVAX1 plasmid delivered by two types of nanospheres could elicit a mixed Th1/Th2 immune response and Th1 immunity as the dominant. In addition, TgP2-pVAX1/PLGA and TgP2-pVAX1/CS nanospheres have great advantages in enhancing immunity against a lethal dose of T. gondii RH strain challenge. All these results suggested that TgP2-pVAX1 plasmids delivered by PLGA or chitosan nanomaterial could be promising vaccines in resisting toxoplasmosis and deserve further investigations and applications.
Emerging Insights on Caspases in COVID-19 Pathogenesis, Sequelae, and Directed Therapies
Authors: Premeaux Thomas A. , Yeung Stephen T. , Bukhari Zaheer , Bowler Scott , Alpan Oral , Gupta Raavi , Ndhlovu Lishomwa C.
Published: February 2022

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a significant global health emergency with new variants in some cases evading current therapies and approved vaccines. COVID-19 presents with a broad spectrum of acute and long-term manifestations. Severe COVID-19 is characterized by dysregulated cytokine release profile, dysfunctional immune responses, and hypercoagulation with a high risk of progression to multi-organ failure and death. Unraveling the fundamental immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and design of more effective therapeutic interventions for individuals at the highest risk of severe outcomes. Caspases are expressed in both immune and non-immune cells and mediate inflammation and cell death, including apoptosis and pyroptosis. Here we review accumulating evidence defining the importance of the expression and activity of caspase family members following SARS-CoV-2 infection and disease. Research suggests SARS-CoV-2 infection is linked to the function of multiple caspases, both mechanistically in vitro as well as in observational studies of individuals with severe COVID-19, which may further the impact on disease severity. We also highlight immunological mechanisms that occur in severe COVID-19 pathology upstream and downstream of activated caspase pathways, including innate recognition receptor signaling, inflammasomes, and other multiprotein complex assembly, inflammatory mediators IL-1β and IL-18, and apoptotic and pyroptotic cell death. Finally, we illuminate discriminate and indiscriminate caspase inhibitors that have been identified for clinical use that could emerge as potential therapeutic interventions that may benefit clinical efforts to prevent or ameliorate severe COVID-19.
Depletion and Dysfunction of Dendritic Cells: Understanding SARS-CoV-2 Infection
Authors: Chang Teding , Yang Jingzhi , Deng Hai , Chen Deng , Yang XiangPing , Tang Zhao-Hui
Published: February 2022

Uncontrolled severe acute respiratory syndrome-coronavirus (SARS-CoV)-2 infection is closely related to disorders of the innate immune and delayed adaptive immune systems. Dendritic cells (DCs) “bridge” innate immunity and adaptive immunity. DCs have important roles in defending against SARS-CoV-2 infection. In this review, we summarize the latest research concerning the role of DCs in SARS-CoV-2 infection. We focus on the complex interplay between DCs and SARS-CoV-2: pyroptosis-induced activation; activation of the renin–angiotensin–aldosterone system; and activation of dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin. We also discuss the decline in DC number, the impaired antigen-presentation capability, and the reduced production of type-I interferon of DCs in severe SARS-CoV-2 infection. In addition, we discuss the potential mechanisms for pathological activation of DCs to understand the pattern of SARS-CoV-2 infection. Lastly, we provide a brief overview of novel vaccination and immunotherapy strategies based on DC targeting to overcome SARS-CoV-2 infection.
Transcriptome Profiling of Porcine Naïve, Intermediate and Terminally Differentiated CD8+ T Cells
Authors: Lagumdzic Emil , Pernold Clara , Viano Marta , Olgiati Simone , Schmitt Michael W. , Mair Kerstin H. , Saalmüller Armin
Published: February 2022

The pig has the potential to become a leading research model for human diseases, pharmacological and transplantation studies. Since there are many similarities between humans and pigs, especially concerning anatomy, physiology and metabolism, there is necessity for a better understanding of the porcine immune system. In adaptive immunity, cytotoxic T lymphocytes (CTLs) are essential for host defense. However, most data on CTLs come from studies in mice, non-human primates and humans, while detailed information about porcine CD8+ CTLs is still sparse. Aim of this study was to analyze transcriptomes of three subsets of porcine CD8β+ T-cell subsets by using next-generation sequencing technology. Specifically, we described transcriptional profiles of subsets defined by their CD11a/CD27 expression pattern, postulated as naïve (CD8β+CD27+CD11alow), intermediate differentiated (CD8β+CD27dimCD11a+), and terminally differentiated cells (CD8β+CD27-CD11ahigh). Cells were analyzed in ex vivo condition as well as upon in vitro stimulation with concanavalin A (ConA) and PMA/ionomycin. Our analyses show that the highest number of differentially expressed genes was identified between naïve and terminally differentiated CD8+ T-cell subsets, underlining their difference in gene expression signature and respective differentiation stages. Moreover, genes related to early (IL7-R, CCR7, SELL, TCF7, LEF1, BACH2, SATB1, ZEB1 and BCL2) and late (KLRG1, TBX21, PRDM1, CX3CR1, ZEB2, ZNF683, BATF, EZH2 and ID2) stages of CD8+ T-cell differentiation were highly expressed in the naïve and terminally differentiated CD8+ T-cell subsets, respectively. Intermediate differentiated CD8+ T-cell subsets shared a more comparable gene expression profile associated with later stages of T-cell differentiation. Genes associated with cytolytic activity (GNLY, PRF1, GZMB, FASL, IFNG and TNF) were highly expressed in terminally and intermediate differentiated CD8+ T-cell subsets, while naïve CD8+ T cells lacked expression even after in vitro stimulation. Overall, PMA/ionomycin stimulation induced much stronger upregulation of genes compared to stimulation with ConA. Taken together, we provided comprehensive results showing transcriptional profiles of three differentiation stages of porcine CD8+ T-cell subsets. In addition, our study provides a powerful toolbox for the identification of candidate markers to characterize porcine immune cell subsets in more detail.
Case Report: Microincision Vitreous Surgery Induces Bleb Failure in Eyes With Functional Filtering Bleb
Authors: Oogi Satomi , Nakakura Shunsuke , Asaoka Ryo , Terao Etsuko , Dote Saki , Matsuya Kanae , Kimura Yui
Published: February 2022

Purpose

To investigate the effect of microincision vitreous surgery (MIVS) on intraocular pressure (IOP) control in glaucomatous eyes with functional filtering bleb.

Methods

We enrolled 18 patients (15 males; median age, 73 years) who previously had filtering surgery and underwent MIVS with functional filtering bleb. Kaplan–Meier method was used to calculate the survival rate with defined the failure as when more number of preoperative antiglaucoma medication was started or additional glaucoma surgery including bleb revisions were performed, and IOP increase of 20% (criteria 1) and 30% (criteria 2) from preoperative levels after 2 weeks of MIVS.

Results

The median follow-up duration was 970 days. Preoperative IOP was 13.3 ± 3.8 mmHg (mean ± SD). Postoperative IOP were 14.7 ± 4.9 (P=0.365), 15.2 ± 3.5 (P=0.137), 16.4 ± 5.6 (P = 0.073), 17.6 ± 6.1(P = 0.020), and 14.5 ± 4.0 (P = 0.402) mmHg at 3, 6, 12, and 15 months and final visit, respectively (compared to preoperative IOP). The number of antiglaucoma medications was a median of 1.0 (range 0–4) preoperatively and 0 (0–4) at the final visit (P = 0.238). The survival rates were 55%/61% at 3 months, 50%/61% at 6 months, and 38%/55% at 12 months with criteria 1 and 2, respectively. Four eyes (22%) received additional glaucoma surgery during follow-up.

Conclusion

After several months of MIVS, IOP was likely to increase. We should focus on IOP control by conducting long-term follow-ups.
Virulence and Antibiotic Resistance Genes in Listeria monocytogenes Strains Isolated From Ready-to-Eat Foods in Chile
Authors: Parra-Flores Julio , Holý Ondrej , Bustamante Fernanda , Lepuschitz Sarah , Pietzka Ariane , Contreras-Fernández Alejandra , Castillo Claudia , Ovalle Catalina , Alarcón-Lavín María Paula , Cruz-Córdova Ariadnna , Xicohtencatl-Cortes Juan , Mancilla-Rojano Jetsi , Troncoso Miriam , Figueroa Guillermo , Ruppitsch Werner
Published: February 2022

Listeria monocytogenes is causing listeriosis, a rare but severe foodborne infection. Listeriosis affects pregnant women, newborns, older adults, and immunocompromised individuals. Ready-to-eat (RTE) foods are the most common sources of transmission of the pathogen This study explored the virulence factors and antibiotic resistance in L. monocytogenes strains isolated from ready-to-eat (RTE) foods through in vitro and in silico testing by whole-genome sequencing (WGS). The overall positivity of L. monocytogenes in RTE food samples was 3.1% and 14 strains were isolated. L. monocytogenes ST8, ST2763, ST1, ST3, ST5, ST7, ST9, ST14, ST193, and ST451 sequence types were identified by average nucleotide identity, ribosomal multilocus sequence typing (rMLST), and core genome MLST. Seven isolates had serotype 1/2a, five 1/2b, one 4b, and one 1/2c. Three strains exhibited in vitro resistance to ampicillin and 100% of the strains carried the fosX, lin, norB, mprF, tetA, and tetC resistance genes. In addition, the arsBC, bcrBC, and clpL genes were detected, which conferred resistance to stress and disinfectants. All strains harbored hlyA, prfA, and inlA genes almost thirty-two the showed the bsh, clpCEP, hly, hpt, iap/cwhA, inlA, inlB, ipeA, lspA, mpl, plcA, pclB, oat, pdgA, and prfA genes. One isolate exhibited a type 11 premature stop codon (PMSC) in the inlA gene and another isolate a new mutation (deletion of A in position 819). The Inc18(rep25), Inc18(rep26), and N1011A plasmids and MGEs were found in nine isolates. Ten isolates showed CAS-Type II-B systems; in addition, Anti-CRISPR AcrIIA1 and AcrIIA3 phage-associated systems were detected in three genomes. These virulence and antibiotic resistance traits in the strains isolated in the RTE foods indicate a potential public health risk for consumers.
Microbial Community Succession and Organic Pollutants Removal During Olive Mill Waste Sludge and Green Waste Co-composting
Authors: Bouhia Youness , Hafidi Mohamed , Ouhdouch Yedir , El Boukhari Mohammed El Mehdi , El Fels Loubna , Zeroual Youssef , Lyamlouli Karim
Published: February 2022

Olive mill wastewater sludge (OMWS) is the main by-product of the olive industry. OMWS is usually dumped in landfills without prior treatment and may cause several eco-environmental hazards due to its high toxicity, which is mainly attributed to polyphenols and lipids. OMWS is rich in valuable biocompounds, which makes it highly desirable for valorization by composting. However, there is a need to understand how microbial communities evolve during OMWS composting with respect to physicochemical changes and the dynamics of pollutant degradation. In this study, we addressed the relationship between microbial community, physicochemical variations and pollutants degradation during the co-composting of OMWS and green wastes using metagenomic- and culture-dependent approaches. The results showed that in raw OMWS, Pichia was the most represented genus with almost 53% of the total identified fungal population. Moreover, the bacteria that dominated were Zymobacter palmae (20%) and Pseudomonas sp. (19%). The addition of green waste to OMWS improved the actinobacterial diversity of the mixture and enhanced the degradation of lipids (81.3%) and polyphenols (84.54%). Correlation analysis revealed that Actinobacteria and fungi (Candida sp., Galactomyces sp., and Pichia manshurica) were the microorganisms that had the greatest influence on the composting process. Overall, these findings provide for the first time some novel insights into the microbial dynamics during OMWS composting and may contribute to the development of tailored inoculum for process optimization.
Characterization of an Aspergillus niger for Efficient Fatty Acid Ethyl Ester Synthesis in Aqueous Phase and the Molecular Mechanism
Authors: Xu Youqiang , Huang Huiqin , Lu Hongyun , Wu Mengqin , Lin Mengwei , Zhang Chunsheng , Zhao Zhigang , Li Weiwei , Zhang Chengnan , Li Xiuting , Sun Baoguo
Published: February 2022

Fatty acid ethyl esters are important flavor chemicals in strong-flavor baijiu. Microorganisms are the main contributors to ester synthesis during baijiu manufacture. However, the ester synthesis was unstable between batches. This was owing to a limited knowledge of the mechanisms for ester synthesis by microorganisms. In this work, a fatty acid ethyl ester synthesizing Aspergillus niger strain CGMCC (China General Microbiological Culture Collection) 3.4309 was identified. The conversion ratios of ethyl valerate, ethyl caproate, ethyl caprylate, and ethyl caprate were 7.87, 29.20, 94.80, and 85.20%, respectively, under the optimized conditions. A comparison of transcriptomes under the initial and optimized ester synthetic conditions indicated that 23 genes were upregulated in transcription level and encoded enzymes with potential abilities for ester synthesis. Eleven of the enzymes were expressed, and three of them, numbered An605, An1097, and An3131, showed the ability to catalyze fatty acid ethyl ester synthesis under aqueous phase, with capric acid as the preferred substrate. The possible enzymatic catalytic mechanism was proposed based on homology modeling and molecular docking. This study reported for the first time that A. niger showed the ability to efficiently catalyze the synthesis of short- and medium-chain fatty acid ethyl esters in aqueous phase, identified the key enzymes, and analyzed the basic enzymatic properties. This is helpful to promote the application of related microorganisms and enzyme resources in the baijiu industry.
Functional Genomics Uncovers Pleiotropic Role of Rhomboids in Corynebacterium glutamicum
Authors: Luenenschloss Andrea , ter Veld Frank , Albaum Stefan P. , Neddermann Tobias M. , Wendisch Volker F. , Poetsch Ansgar
Published: February 2022

The physiological role of ubiquitous rhomboid proteases, membrane-integral proteins that cleave their substrates inside the lipid bilayer, is still ill-defined in many prokaryotes. The two rhomboid genes cg0049 and cg2767 of Corynebacterium glutamicum were mutated and it was the aim of this study to investigate consequences in respect to growth phenotype, stress resistance, transcriptome, proteome, and lipidome composition. Albeit increased amount of Cg2767 upon heat stress, its absence did not change the growth behavior of C. glutamicum during exponential and stationary phase. Quantitative shotgun mass spectrometry was used to compare the rhomboid mutant with wild type strain and revealed that proteins covering diverse cellular functions were differentially abundant with more proteins affected in the stationary than in the exponential growth phase. An observation common to both growth phases was a decrease in ribosomal subunits and RNA polymerase, differences in iron uptake proteins, and abundance changes in lipid and mycolic acid biosynthesis enzymes that suggested a functional link of rhomboids to cell envelope lipid biosynthesis. The latter was substantiated by shotgun lipidomics in the stationary growth phase, where in a strain-dependent manner phosphatidylglycerol, phosphatidic acid, diacylglycerol and phosphatidylinositol increased irrespective of cultivation temperature.