bluuebunny/crossref_metadata_2025 huggingface dataset:
Yiqi-Bushen-Tiaozhi Recipe Attenuated High-Fat and High-Fructose Diet Induced Nonalcoholic Steatohepatitis in Mice via Gut Microbiota
Authors: Yan Junbin , Nie Yunmeng , Liu Yuan , Li Jingya , Wu Liyan , Chen Zhiyun , He Beihui
Published: April 2022

Aim

To investigate the treating effect of Yiqi-Bushen-Tiaozhi (YBT) recipe on nonalcoholic steatohepatitis (NASH) mice, determine whether the outcome was associated with gut microbiota, and clarify the regulating mechanism.

Methods

NASH mice were induced by high-fat and high-fructose diets (HFFD). In the fifth week, mice in the YBT group were orally administrated YBT (22.12g·kg-1·d-1) daily for 12 weeks. Fresh stool of mice was collected at the 16th week for fecal 16S rDNA analysis. Hepatic pathology and biochemical indicators were used to reflect the improvement of YBT on hepatic inflammation and lipid metabolism in NASH mice. Quantitative real-time PCR (qRT-PCR) was used to verify the results of PICRUSt analysis.

Results

Results of the pathological and biochemical index showed that YBT could improve NASH mice. Compared with improving inflammation and hepatocyte damage, YBT may be more focused on enhancing metabolic disorders in mice, such as increasing HDL-c level. The diversity and richness of the gut microbiota of NASH mice induced by HFFD are significantly different from the normal control (NC) group. After YBT treatment, the diversity and richness of the mice microbiota will be increased to similar NC mice. Intestinimonas, Acetatifactor, Alistipes, Intestinimonas, Acetatifactor, and Alistipes have the most significant changes in the class level. PICRUSt analysis was performed to predict genomic functions based on the 16S rDNA results and reference sequencing. The efficacy of YBT in the treatment of NASH can be achieved by regulating the diversity and richness of gut microbiota. PICRUSt analysis results showed that the most relevant function of the microbiota construction variations is α- Linolenic acid (ALA) metabolism. Results of qRT-PCR showed significant differences between groups in the expression of Fatty acid desaturase 1 (FADS1), Fatty acid desaturase 2 (FADS2), Acyl-CoA Oxidase 1 (ACOX1), and Acyl-CoA Oxidase 2 (ACOX2) related to ALA metabolism. The expression of the above genes will be inhibited in the liver and small intestine of the HFFD group mice, and the expression can be restored after YBT treatment.

Conclusion

YBT could treat NASH mice by improving the diversity and richness of gut microbiota and further the improvement of ALA metabolism.
Healthy Lifetime (HL): An Internet-Based Behavioral Health Coaching Protocol for Older Adults
Authors: Flaherty-Robb Marna , Calarco Margaret , Butterworth Susan , Struble Laura , Harden Karen , Franklin Mary , Potempa Stacia , Laughlin Candia , Schmidt Patricia , Policicchio Judith , Yakusheva Olga , Isaman Deanna , Gallagher Nancy Ambrose , Furspan Philip , Potempa Kathleen
Published: April 2022

By 2060, the number of Americans 65 years and older will more than double, comprising nearly one-quarter of the population in the United States. While there are many advantages to living longer, a byproduct of aging is also a growing incidence of chronic illness and functional health limitations associated with a concurrent rise in chronic disease and disability that impair independent living in the community. We describe a personalized, behavioral health coaching protocol for early intervention that is delivered online to enhance a participant's independent functioning and to increase their self-care capacity with a goal to maintain independent living throughout aging. The electronic platform provides secure access to fillable surveys, health tracking, “just in time” communication with coaches and scheduling of two-way videos launched from the platform site. The 2-month protocol used two-way video conferencing which allowed high fidelity communication to sustain a complex behavioral intervention. Participants indicate high satisfaction with the intervention, the use of the platform, and the technology. While many health systems across the U.S. have ramped up virtual delivery of care in a proactive manner with now more than 70% of out-patient visits conducted through virtual delivery modes in some health systems, there remains much unevenness in this capability across the U.S. Our approach is to create a stable, interoperable, virtual outreach system for personalized professional health coaching that is complementary to medically oriented services that supports the health and functioning of participants as they age.
Case Report: Micro-RNAs in Plasma From Bilateral Inferior Petrosal Sinus Sampling and Peripheral Blood From Corticotroph Pituitary Neuroendocrine Tumors
Authors: Niedra Helvijs , Peculis Raitis , Konrade Ilze , Balcere Inga , Romanovs Mihails , Steina Liva , Stukens Janis , Sokolovska Jelizaveta , Klovins Janis , Rovite Vita
Published: April 2022

Objective

Circulating miRNAs are found in bodily fluids including plasma and can serve as biomarkers for diseases. The aim of this study was to provide the first insight into the landscape of circulating miRNAs in close proximity to the adrenocorticotropic hormone (ACTH) secreting PitNET. To achieve this objective next-generation sequencing of miRNAs in plasma from bilateral inferior petrosal sinus sampling (BIPSS) - a gold standard in diagnosing ACTH-secreting PitNETs was carried out and selected miRNA candidates were further tested by RT-qPCR in independent patient cohorts.

Methods

Sinistral (left) and dextral (right) BIPSS blood samples of the patient were collected in three time points: before the administration of corticotropin-releasing hormone, 5 and 15 minutes after stimulation. In differential expression analysis, sinistral plasma was compared with dextral. The selected miRNA candidates were tested in plasma by RT-qPCR in two patient groups: 1) in five ACTH secreting PitNET patients with plasma samples taken before and 24 hours after surgery, 2) in 12 ACTH secreting PitNET patients vs. 9 non-functioning PitNET patients.

Results

BIPSS concluded that the highest amount of ACTH was released in the sinistral side at the 5th minute mark indicating a presence of a tumor. The highest amount of differentially expressed miRNAs was observed 5 minutes after stimulation (20 upregulated, 14 downregulated). At the 5th minute mark in sinistral plasma, two miRNAs were identified: hsa-miR-7-5p and hsa-miR-375-3p that were highly upregulated compared to other BIPSS samples and peripheral plasma samples. Further testing by qPCR revealed significant reduction of miR-7-5p in plasma 24 hours after surgery and upregulation in plasma of ACTH secreting PitNET patients compared to non-functioning PitNET patients (P =0.0013).

Conclusions

By stimulating the ACTH secreting PitNET with CRH a rapid increase of two miRNAs (hsa-mir-7-5p, hsa-mir-375-3p) and ACTH can be observed in sinistral inferior petrosal (tumor side). A decrease of miR-7-5p in plasma after surgery and upregulation in plasma of ACTH secreting PitNET patients was discovered implying that further studies of this miRNA as diagnostic marker is needed.
A Prognostic Model of Differentiated Thyroid Cancer Based on Up-Regulated Glycolysis-Related Genes
Authors: Wu Min , Ou-yang Deng-jie , Wei Bo , Chen Pei , Shi Qi-man , Tan Hai-long , Huang Bo-qiang , Liu Mian , Qin Zi-en , Li Ning , Hu Hui-yu , Huang Peng , Chang Shi
Published: April 2022

Objective

This study aims to identify reliable prognostic biomarkers for differentiated thyroid cancer (DTC) based on glycolysis-related genes (GRGs), and to construct a glycolysis-related gene model for predicting the prognosis of DTC patients.

Methods

We retrospectively analyzed the transcriptomic profiles and clinical parameters of 838 thyroid cancer patients from 6 public datasets. Single factor Cox proportional risk regression analysis and Least Absolute Shrinkage and Selection Operator (LASSO) were applied to screen genes related to prognosis based on 2528 GRGs. Then, an optimal prognostic model was developed as well as evaluated by Kaplan-Meier and ROC curves. In addition, the underlying molecular mechanisms in different risk subgroups were also explored via The Cancer Genome Atlas (TCGA) Pan-Cancer study.

Results

The glycolysis risk score (GRS) outperformed conventional clinicopathological features for recurrence-free survival prediction. The GRS model identified four candidate genes (ADM, MKI67, CD44 and TYMS), and an accurate predictive model of relapse in DTC patients was established that was highly correlated with prognosis (AUC of 0.767). In vitro assays revealed that high expression of those genes increased DTC cancer cell viability and invasion. Functional enrichment analysis indicated that these signature GRGs are involved in remodelling the tumour microenvironment, which has been demonstrated in pan-cancers. Finally, we generated an integrated decision tree and nomogram based on the GRS model and clinicopathological features to optimize risk stratification (AUC of the composite model was 0.815).

Conclusions

The GRG signature-based predictive model may help clinicians provide a prognosis for DTC patients with a high risk of recurrence after surgery and provide further personalized treatment to decrease the chance of relapse.
Sex Differences in Memory: Do Female Reproductive Factors Explain the Differences?
Authors: Li Jie , Hao Wenting , Fu Chunying , Zhou Chengchao , Zhu Dongshan
Published: April 2022

Background

The sex differences in memory impairment were inconclusive, and the effect of female reproductive factors (age at menarche, age at menopause, and reproductive period) on the differences was not clear. We aimed to examine the sex differences in objective and subjective memory impairment in postmenopausal women and age- and education-matched men and explore whether the differences were differed by female reproductive factors.

Methods

Data were obtained from the China Health and Retirement Longitudinal Study. Using the case–control matching method, 3,218 paired postmenopausal women and men matched for age and education were selected. Memory was assessed using the three-word recall task and a self-rated question. Poisson regression models with a robust error variance were used.

Results

The relative risk was 1.22 (95% confidence interval 1.08–1.38) for objective memory impairment in women compared with men (23.87% vs. 27.36%), and 1.51 (1.36–1.67) for subjective memory impairment (39.34% vs. 28.25%) after adjusting the confounders. The higher risk of objective memory impairment in women was different among groups of age at menarche in a linear pattern, with younger age at menarche associated with higher risks of objective memory impairment (p < 0.001 for trend). It was also different among groups of menopausal age and reproductive period in an approximate U-shaped pattern, with a similar risk of objective memory with men in women menopause at 52–53 years and having a reproductive period of 31–33 years and higher risks in women with earlier or later menopause (RRs raging form 1.17 to1.41) and a shorter or longer period of reproduction (RR, 1.23–1.29). The higher risks of subjective memory impairment in women were not different among different groups of reproductive factors.

Conclusions

Postmenopausal women were at an increased risk of objective and subjective memory impairment than men. The higher risks in objective memory, but not subjective memory, were varied by age at menarche, age at menopause, and reproductive periods, which may help understand the underlying mechanisms of sex differences in cognitive ageing and guide precise intervention to preventing dementia among older women and men.
Hashimoto Thyroiditis, Anti-Parietal Cell Antibodies: Associations With Autoimmune Diseases and Malignancies
Authors: Boutzios Georgios , Koukoulioti Eleni , Goules Andreas V. , Kalliakmanis Ioannis , Giovannopoulos Ilias , Vlachoyiannopoulos Panayiotis , Moutsopoulos Haralampos M. , Tzioufas Athanasios G.
Published: April 2022

Background

Hashimoto thyroiditis (HT) is an autoimmune disease which may result in extensive damage of the thyroid gland. Chronic atrophic gastritis (CAG), is the most frequent HT-associated disorder, with anti-parietal cell autoantibodies (APCA) being a screening test for autoimmune CAG. The aim of this study was to investigate, in a cohort of HT patients: a) the prevalence of APCA in an attempt to define their clinical phenotype and b) any possible associations of APCA with other autoimmune diseases and malignancies.

Methods

This is a single-center, case-control study, conducted at a University Hospital. The study included patients with HT diagnosed between November 2017 and November 2020. Excluded were patients <18 years old, with sonographic features of HT but negative thyroid peroxidase (TPOAbs) or thyroglobulin autoantibodies (TgAbs), Graves’ disease, Down or Turner’s syndrome.

Results

A total of 840 patients with HT were included in the study, from whom 180 (21.4%) had positive APCA. A total of 79 patients (9.4%) had one or more organ-specific autoimmune diseases and 61 (7.3%) had a systemic autoimmune disease. Autoimmune diseases were more frequent in female than in male patients (17.9% versus 10.9%, p = 0.05). APCA-positive patients were older than APCA-negative (54.1 ± 13.5 versus 49.0 ± 14.6, p <0.001) and had more often positive TPOAbs (93.3% versus 83.9%, p=0.001). Gastric neoplasms were documented only in APCA-positive patients (p <0.001). A higher frequency of organ-specific autoimmune diseases was observed in the APCA-positive group (14.4% versus 8%, p = 0.024). In the subgroup of patients with additional autoimmune diseases (n = 140), younger age and positive APCA were independently associated with the presence of organ-specific autoimmunity (OR 0.954, 95% CI 0.927–0.982 and OR 3.100, 95% CI 1.256–7.652, respectively). Papillary thyroid cancer (PTC) occurred in 3.5% of patients (26/29 women). Positive family history for thyroid autoimmunity and negative TPOAbs were the only independent risk factors for PTC among women (OR 3.228, 95% CI 1.173–8.887 and 0.315, 95% 0.113–0.881, respectively).

Conclusion

This study reveals for the first time an association of APCA with organ-specific autoimmunity in HT patients. APCA together with patient age were independently associated with the presence of organ-specific autoimmunity. Finally, this study showed an association between APCA and gastric neoplasms in these patients.
Use of Continuous Glucose Monitoring in the Assessment and Management of Patients With Diabetes and Chronic Kidney Disease
Authors: Ling James , Ng Jack K. C. , Chan Juliana C. N. , Chow Elaine
Published: April 2022

In developed countries, diabetes is the leading cause of chronic kidney disease (CKD) and accounts for 50% of incidence of end stage kidney disease. Despite declining prevalence of micro- and macrovascular complications, there are rising trends in renal replacement therapy in diabetes. Optimal glycemic control may reduce risk of progression of CKD and related death. However, assessing glycemic control in patients with advanced CKD and on dialysis (G4-5) can be challenging. Laboratory biomarkers, such as glycated haemoglobin (HbA1c), may be biased by abnormalities in blood haemoglobin, use of iron therapy and erythropoiesis-stimulating agents and chronic inflammation due to uraemia. Similarly, glycated albumin and fructosamine may be biased by abnormal protein turnover. Patients with advanced CKD exhibited heterogeneity in glycemic control ranging from severe insulin resistance to ‘burnt-out’ beta-cell function. They also had high risk of hypoglycaemia due to reduced renal gluconeogenesis, frequent use of insulin and dysregulation of counterregulatory hormones. Continuous glucose monitoring (CGM) systems measure glucose in interstitial fluid every few minutes and provide an alternative and more reliable method of glycemic assessment, including asymptomatic hypoglycaemia and hyperglycaemic excursions. Recent international guidelines recommended use of CGM-derived Glucose Management Index (GMI) in patients with advanced CKD although data are scarce in this population. Using CGM, patients with CKD were found to experience marked glycemic fluctuations with hypoglycemia due to loss of glucose and insulin during haemodialysis (HD) followed by hyperglycemia in the post-HD period. On the other hand, during peritoneal dialysis, patients may experience glycemic excursions with influx of glucose from dialysate solutions. These undesirable glucose exposure and variability may accelerate decline of residual renal function. Although CGM may improve the quality of glycemic monitoring and control in populations with CKD, further studies are needed to confirm the accuracy, optimal mode and frequency of CGM as well as their cost-effectiveness and user-acceptability in patients with advanced CKD and dialysis.
Prevalence and Associated Factors of Sexual Dysfunction in Patients With Inflammatory Bowel Disease
Authors: Zhang Jinzhi , Nie Jiao , Zou Min , Zeng Qishan , Feng Yue , Luo Zhenyi , Gan Huatian
Published: April 2022

Background

Sexual dysfunction (SD) in patients who suffer from inflammatory bowel disease (IBD) has not attracted widespread attention, and thus research studies are scarce.

Objective

This study aims to evaluate the rates of SD in IBD compared with healthy individuals and elucidate the associated factors.

Methods

In this cross-sectional study, the Female Sexual Function Index (FSFI) and the simplified version of the International Index of Erectile Function (IIEF-5) were filled by IBD patients, as well as healthy control individuals.

Results

A total of 208 IBD patients, including 133 with Crohn’s disease (CD) and 75 with ulcerative colitis (UC), and 190 healthy individuals filled out the questionnaires. In women, SD rates were 61.9% in the patients with IBD vs. 24.4% in the healthy controls (p < 0.01). In men, the rates of erectile dysfunction (ED) were 43.5% in the patients with IBD vs. 12.5% in the healthy controls (p < 0.01). Anxiety (OR, 3.092; 95%CI: 1.033-9.252, p = 0.044) and active perianal disease (OR, 4.481; 95%CI: 1.055-19.029, p = 0.042) were independent risk factors for SD in female IBD patients. age (OR, 1.050; 95%CI: 1.007-1.095, p = 0.022), depression (OR, 5.763; 95%CI: 1.864-17.821, p = 0.002) and active perianal disease (OR, 7.117; 95%CI: 1.747-28.983, p = 0.006) were independent risk factors for ED in male patients.

Conclusions

In the IBD patients, 62% of women reported having SD, and 44% of men reported having ED. These higher rates, as compared to the healthy controls, are mostly driven by active perianal disease and psychological factors.
Novel Biomarkers in Membranous Nephropathy
Authors: Liu Qiuying , Liu Jianhua , Lin Baoxu , Zhang Yue , Ma Meichen , Yang Mei , Qin Xiaosong
Published: April 2022

Membranous nephropathy (MN) is the main cause of adult nephrotic syndrome (NS). The pathogenesis of MN is complex and involves subepithelial immune complex deposition. Approximately one-third of patients with MN develop end-stage renal disease (ESRD). Timely diagnosis and reasonable intervention are the keys to improving prognosis. In recent years, with the development of high-throughput technologies, such as mass spectrometry (MS), microarray, and sequencing technologies, the discovery of biomarkers for MN has become an important area of research. In this review, we summarize the significant progress in biomarker identification. For example, a variety of podocyte target antigens and their autoantibodies have been reported. Phospholipase A2 receptor (PLA2R) is the most well-established target antigen in MN. PLA2R and its autoantibodies have clinical significance, with both diagnostic and therapeutic value for MN. In addition, a variety of new biomarkers, including proteins, metabolites, noncoding RNAs (ncRNAs), and immune cells, have recently been found. These MN-related biomarkers have great significance in the diagnosis, progression, prognosis, and treatment response of MN.
Novel Therapeutic Targeting of CCL3-CCR4 Axis Mediated Apoptotic Intesitnal Injury in Necrotizing Enterocolitis
Authors: Yuan Xi , Xiong Zihan , Liu Wei , Li Yue , Li Hongdong , Zhang Xuemei , Yin Yibing , Xu Pingyong , Cao Ju , Chen Dapeng , Song Zhixin
Published: April 2022

Background

Necrotizing enterocolitis (NEC) is the leading cause of neonatal gastrointestinal-related death, while the etiology and pathogenesis are poorly understood.

Methods

The levels of CCL3 in intestinal tissue from modeling mice and patients were measured and analyzed. HE staining, TUNEL, Annexin and FCM were used to assess pathological changes and apoptosis in intestinal tissue and epithelial cells. CCL3, CCR4, cytokines, tight junction protein ZO-1, apoptosis-related genes and ERK1/2-NF-κB signaling pathway were detected by ELISA, Q-PCR, Western blotting and immunofluorescence.

Results

CCL3 levels in the intestinal tissue significantly elevated in patients with NEC and mouse models. Blockade of CCL3 significantly alleviated NEC-related intestinal tissue damage, while administration of recombinant CCL3 aggravated intestinal injury by exacerbating intestinal epithelial cell apoptosis in NEC mice. Importantly, CCR4 blockade reversed CCL3-mediated damage to intestinal tissue and intestinal epithelial cell apoptosis both in vivo and in vitro. Further mechanistic studies showed that CCL3 regulated apoptosis-related BAX/BCL-2 expression through the activation of the ERK1/2 and NF-κB pathways, which could be reversed by anti-CCR4 treatment. Furthermore, ERK1/2 inhibition reduced CCL3-mediated phosphorylation of NF-κB in IEC-6 cells, while inhibition of NF-κB had no obvious effect on ERK1/2 phosphorylation. As expected, inhibition of NF-κB regulated BAX/BCL-2 expression and alleviated CCL3-induced epithelial cell apoptosis. These results indicate that high expression of CCL3 in NEC lesions promotes intestinal epithelial apoptosis through the CCL3-CCR4-ERK1/2-NFκB-BAX/BCL2 signalling axis, thereby exacerbating NEC-related intestinal injury.

Conclusions

Our study represents an important conceptual advance that CCL3 may be one of the key culprits of intestinal tissue damage in NEC patients, and blocking either CCL3, CCR4, or NF-κB may represent a novel effective immunotherapy for NEC.
Propionic Acid, Induced in Gut by an Inulin Diet, Suppresses Inflammation and Ameliorates Liver Ischemia and Reperfusion Injury in Mice
Authors: Kawasoe Junya , Uchida Yoichiro , Kawamoto Hiroshi , Miyauchi Tomoyuki , Watanabe Takeshi , Saga Kenichi , Tanaka Kosuke , Ueda Shugo , Terajima Hiroaki , Taura Kojiro , Hatano Etsuro
Published: April 2022

Liver ischemia and reperfusion injury (IRI) is one of the obstacles in liver surgery such as liver resection and transplantation. In this study, we investigated the preventive effect on mouse liver IRI by feeding mice with inulin, which is a heterogeneous blend of indigestible fructose polymer. Mice were fed either a control ordinary diet (CD) or an inulin diet (ID) containing 5% inulin in the CD, for 14 days before the ischemia and reperfusion (IR) maneuver. IR induced-liver damages were significantly ameliorated in the ID group, compared with those in the CD group. Feeding mice with an ID, but not a CD, elevated levels of Bacteroidetes among gut microbiota, and especially increased Bacteroides acidifaciens in mouse feces, which resulted in significant elevation of short-chain fatty acids (SCFAs) in the portal vein of mice. Among SCFAs, propionic acid (PA) was most significantly increased. The microbial gene functions related to PA biosynthesis were much higher in the fecal microbiome of the ID group compared to the CD. However, the action of PA on liver IRI has not been yet clarified. Direct intraperitoneal administration of PA alone prior to the ischemia strongly suppressed liver cell damages as well as inflammatory responses caused by liver IR. Furthermore, PA suppressed the secretion of inflammatory cytokines from peritoneal macrophages stimulated in vitro through TLR-4 with high-mobility group box 1 protein (HMGB-1), known to be released from apoptotic liver cells during the IR insult. The present study shows that PA may play a key role in the inulin-induced amelioration of mouse liver IRI.
Long-Lasting T Cell Responses in BNT162b2 COVID-19 mRNA Vaccinees and COVID-19 Convalescent Patients
Authors: Hurme Antti , Jalkanen Pinja , Heroum Jemna , Liedes Oona , Vara Saimi , Melin Merit , Teräsjärvi Johanna , He Qiushui , Pöysti Sakari , Hänninen Arno , Oksi Jarmo , Vuorinen Tytti , Kantele Anu , Tähtinen Paula A. , Ivaska Lauri , Kakkola Laura , Lempainen Johanna , Julkunen Ilkka
Published: April 2022

The emergence of novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made it more difficult to prevent the virus from spreading despite available vaccines. Reports of breakthrough infections and decreased capacity of antibodies to neutralize variants raise the question whether current vaccines can still protect against COVID-19 disease. We studied the dynamics and persistence of T cell responses using activation induced marker (AIM) assay and Th1 type cytokine production in peripheral blood mononuclear cells obtained from BNT162b2 COVID-19 mRNA vaccinated health care workers and COVID-19 patients. We demonstrate that equally high T cell responses following vaccination and infection persist at least for 6 months against Alpha, Beta, Gamma, and Delta variants despite the decline in antibody levels.
miRNA Profile Based on ART Delay in Vertically Infected HIV-1 Youths Is Associated With Inflammatory Biomarkers and Activation and Maturation Immune Levels
Authors: Tarancon-Diez Laura , Consuegra Irene , Vazquez-Alejo Elena , Ramos-Ruiz Ricardo , Ramos José Tomás , Navarro María Luisa , Muñoz-Fernández Mª Ángeles
Published: April 2022

Early antiretroviral treatment (ART) in vertically acquired HIV-1-infection is associated with a rapid viral suppression, small HIV-1 reservoir, reduced morbimortality and preserved immune functions. We investigated the miRNA profile from vertically acquired HIV-1-infected young adults based on ART initiation delay and its association with the immune system activation. Using a microRNA panel and multiparametric flow cytometry, miRNome profile obtained from peripheral blood mononuclear cells and its association with adaptive and innate immune components were studied on vertically HIV-1-infected young adults who started ART early (EARLY, 0-53 weeks after birth) and later (LATE, 120-300 weeks). miR-1248 and miR-155-5p, were significantly upregulated in EARLY group compared with LATE group, while miR-501-3p, miR-548d-5p, miR-18a-3p and miR-296-5p were significantly downregulated in EARLY treated group of patients. Strong correlations were obtained between miRNAs levels and soluble biochemical biomarkers and immunological parameters including CD4 T-cell count and maturation by CD69 expression on CD4 T-cells and activation by HLA-DR on CD16high NK cell subsets for miR-1248 and miR-155-5p. In this preliminary study, a distinct miRNA signature discriminates early treated HIV-1-infected young adults. The role of those miRNAs target genes in the modulation of HIV-1 replication and latency may reveal new host signaling pathways that could be manipulated in antiviral strategies. Correlations between miRNAs levels and inflammatory and immunological markers highlight those miRNAs as potential biomarkers for immune inflammation and activation in HIV-1-infected young adults who initiated a late ART.
S100A8 in Serum, Urine, and Saliva as a Potential Biomarker for Systemic Lupus Erythematosus
Authors: Kim Ji-Won , Jung Ju-Yang , Lee Sang-Won , Baek Wook-Young , Kim Hyoun-Ah , Suh Chang-Hee
Published: April 2022

Objectives

This study aimed to elucidate the potential of serum, urine, and saliva S100 calcium-binding protein A8 protein (S100A8) levels as biomarkers for systemic lupus erythematosus (SLE).

Methods

Serum, urine, and saliva samples were obtained from 249 patients with SLE from the Ajou lupus cohort and 52 age- and sex-matched healthy controls (HCs). The concentrations of S100A8 were quantified using an ELISA, and a receiver operating characteristic curve was used to analyze whether they may be used as biomarkers for diagnosing SLE.

Results

Among 249 SLE patients included in our study, the mean SLE disease activity index (SLEDAI)-2K was 7.16 ± 5.61, and the number of patients with lupus flare was 11. Patients with SLE showed a 2.7-fold increase in serum S100A8 levels compared with that in HCs (1,890.6 vs. 709 pg/ml, p < 0.001). In urine and saliva, the average S100A8 levels were significantly higher in patients with SLE compared with those in HCs (urine, 2,029.4 vs. 1,096.7 pg/ml, p = 0.001; saliva, 290,496.3 vs. 47,742 pg/ml, p < 0.001). For SLE diagnosis, the area under the receiver operating characteristic curve was 0.831 for serum S100A8 (95% CI, 0.765–0.897), 0.751 for urine S100A8 (95% CI, 0.648–0.854), and 0.729 for salivary S100A8 (95% CI, 0.646–0.812). Pearson’s correlation analysis showed that S100A8 in serum, urine, and saliva was significantly associated with the SLEDAI (r = 0.267, p < 0.001; r = 0.274, p < 0.001; and r = 0.629, p < 0.001, respectively). Among the clinical manifestations, nephritis was the most influential factor related to SLE in the concentration of S100A8 in serum, urine, and saliva.

Conclusion

This is the first study to show that the expression of S100A8 in serum, urine, and saliva is significantly higher in patients with SLE than in HCs and is associated with disease activity markers. Therefore, we suggest that S100A8 protein could be a potential biomarker for SLE.
Sediment-Derived Dissolved Organic Matter Stimulates Heterotrophic Prokaryotes Metabolic Activity in Overlying Deep Sea in the Ulleung Basin, East Sea
Authors: Hyun Jung-Ho , Kim Bomina , Han Heejun , Baek Yong-Jae , Lee Hyeonji , Cho Hyeyoun , Yoon Seok-Hyun , Kim Guebuem
Published: April 2022

The effects of benthic dissolved organic carbon (DOC) flux on the dynamics of DOC in the deep continental margins (200 – 2000 m depth) is poorly understood. We investigated heterotrophic prokaryotes (hereafter bacteria) production (BP) and the bio-reactive properties of sediment-derived dissolved organic matter (SDOM) to elucidate microbially mediated cause-effect relationships regarding the rapid consumption of dissolved oxygen (DO) and accumulation of humic-like fluorescent DOM (FDOMH) in the deep-water column (750 – 2000 m depth range) of the Ulleung Basin (UB) in the East Sea. BP in the deep water (2.2 μmol C m-3 d-1) of the UB was among the highest reported for various deep-sea sites. The high DOC concentration (55 μM) likely supported the high BP seen in the deep-water column of the UB. Concentrations of DOC and C1 component of the FDOMH, which is indicative of microbial metabolic by-products, were 13-fold and 20-fold greater, respectively, in pore water than in the overlying bottom water, indicating that the sediment in the continental margins is a significant source of DOM in the overlying water column. Fine-scale water sampling revealed that BP near the sediment (0 – 30 m above the seafloor; 2.78 μmol C m-3 d-1) was 1.67 times higher than that measured in the water column above (30 – 100 m above the seafloor; 1.67 μmol C m-3 d-1). In addition, BP increased in the bottom water incubation amended with SDOM-containing pore water (PW). The results demonstrated that SDOM contains bio-reactive forms of DOM that stimulate heterotrophic microbial metabolism at the expense of oxygen in the bottom water layer. The accumulation of C1 component in both PW-amended and unamended bottom water incubation (i.e., without an extra DOM supply from sediment) further indicated that refractory DOM is produced autochthonously in the water column via heterotrophic metabolic activity. This explains in part the microbially mediated accumulation of excess FDOMH in the deep-water column of the UB. Overall results suggest that the benthic release of bio-reactive DOM may be of widespread significance in controlling microbial processes in the deep-water layer of marginal seas.
Diversity of Giant Viruses Infecting Vermamoeba vermiformis
Authors: Geballa-Koukoulas Khalil , La Scola Bernard , Blanc Guillaume , Andreani Julien
Published: April 2022

The discovery of Acanthamoeba polyphaga mimivirus in 2003 using the free-living amoeba Acanthamoeba polyphaga caused a paradigm shift in the virology field. Twelve years later, using another amoeba as a host, i.e., Vermamoeba vermiformis, novel isolates of giant viruses have been discovered. This amoeba–virus relationship led scientists to study the evolution of giant viruses and explore the origins of eukaryotes. The purpose of this article is to review all the giant viruses that have been isolated from Vermamoeba vermiformis, compare their genomic features, and report the influence of these viruses on the cell cycle of their amoebal host. To date, viruses putatively belonging to eight different viral taxa have been described: 7 are lytic and 1 is non-lytic. The comparison of giant viruses infecting Vermamoeba vermiformis has suggested three homogenous groups according to their size, the replication time inside the host cell, and the number of encoding tRNAs. This approach is an attempt at determining the evolutionary origins and trajectories of the virus; therefore, more giant viruses infecting Vermamoeba must be discovered and studied to create a comprehensive knowledge on these intriguing biological entities.
Treadmill Training for Common Marmoset to Strengthen Corticospinal Connections After Thoracic Contusion Spinal Cord Injury
Authors: Kondo Takahiro , Saito Risa , Sato Yuta , Sato Kenta , Uchida Akito , Yoshino-Saito Kimika , Shinozaki Munehisa , Tashiro Syoichi , Nagoshi Narihito , Nakamura Masaya , Ushiba Junichi , Okano Hideyuki
Published: April 2022

Spinal cord injury (SCI) leads to locomotor dysfunction. Locomotor rehabilitation promotes the recovery of stepping ability in lower mammals, but it has limited efficacy in humans with a severe SCI. To explain this discrepancy between different species, a nonhuman primate rehabilitation model with a severe SCI would be useful. In this study, we developed a rehabilitation model of paraplegia caused by a severe traumatic SCI in a nonhuman primate, common marmoset (Callithrix jacchus). The locomotor rating scale for marmosets was developed to accurately assess the recovery of locomotor functions in marmosets. All animals showed flaccid paralysis of the hindlimb after a thoracic contusive SCI, but the trained group showed significant locomotor recovery. Kinematic analysis revealed significantly improved hindlimb stepping patterns in trained marmosets. Furthermore, intracortical microstimulation (ICMS) of the motor cortex evoked the hindlimb muscles in the trained group, suggesting the reconnection between supraspinal input and the lumbosacral network. Because rehabilitation may be combined with regenerative interventions such as medicine or cell therapy, this primate model can be used as a preclinical test of therapies that can be used in human clinical trials.
Correlation Between Resting Theta Power and Cognitive Performance in Patients With Schizophrenia
Authors: Cao Yanxiang , Han Chuanliang , Peng Xing , Su Ziyao , Liu Gan , Xie Yixi , Zhang Yiting , Liu Jun , Zhang Pei , Dong Wen , Gao Michel , Sha Sha , Zhao Xixi
Published: April 2022

Objective

Schizophrenia is a mental disorder that is characterized by progressive cognitive impairment. Objective measures of cognitive function may provide reliable neurobiomarkers for patients with schizophrenia. The goal of the current work is to explore the correlation between resting theta power and cognitive performance in patients with schizophrenia.

Methods

Twenty-two patients with schizophrenia and 23 age-, sex-, and education-matched healthy controls were included in this study. The MATRICS Consensus Cognitive Battery (MCCB) was used for cognitive evaluation and the Positive and Negative Syndrome Scale (PANSS) for evaluation of clinical symptoms. EEGs were acquired in the resting state with closed and opened eyes. Between the two groups, we compared the relative theta power and examined their relationship with cognitive performance.

Results

Compared to healthy controls, patients with schizophrenia showed significantly higher theta power, both with eyes closed and open (P < 0.05). When the eyes were open, negative correlations were found in patients with schizophrenia between theta power in the central and parietal regions with processing speed scores, and between the theta power of the Pz electrode and verbal learning and reasoning and problem-solving scores (r ≥ −0.446). In the control group, theta power over the Fz electrode was negatively correlated with processing speed (r = −0.435).

Conclusions

Our findings showed that theta activity increased in certain brain regions during resting state in schizophrenia. Negative associations between resting theta power (increased) over the parietal-occipital regions with MCCB domains scores (decreased) suggest that altered theta activity can be used as a neurobiological indicator to predict cognitive performance.
Imatinib Mesylate Reduces Neurotrophic Factors and pERK and pAKT Expression in Urinary Bladder of Female Mice With Cyclophosphamide-Induced Cystitis
Authors: Perkins Megan , Girard Beatrice M. , Campbell Susan E. , Hennig Grant W. , Vizzard Margaret A.
Published: April 2022

Imatinib mesylate is a tyrosine kinase inhibitor that inhibits platelet-derived growth factor receptor (PDGFR)-α, -β, stem cell factor receptor (c-KIT), and BCR-ABL. PDGFRα is expressed in a subset of interstitial cells in the lamina propria (LP) and detrusor muscle of the urinary bladder. PDGFRα + interstitial cells may contribute to bladder dysfunction conditions such as interstitial cystitis/bladder pain syndrome (IC/BPS) or overactive bladder (OAB). We have previously demonstrated that imatinib prevention via oral gavage or treatment via intravesical infusion improves urinary bladder function in mice with acute (4 hour, h) cyclophosphamide (CYP)-induced cystitis. Here, we investigate potential underlying mechanisms mediating the bladder functional improvement by imatinib using a prevention or treatment experimental design. Using qRT-PCR and ELISAs, we examined inflammatory mediators (NGF, VEGF, BDNF, CCL2, IL-6) previously shown to affect bladder function in CYP-induced cystitis. We also examined the distribution of phosphorylated (p) ERK and pAKT expression in the LP with immunohistochemistry. Imatinib prevention significantly (0.0001 ≤ p ≤ 0.05) reduced expression for all mediators examined except NGF, whereas imatinib treatment was without effect. Imatinib prevention and treatment significantly (0.0001 ≤ p ≤ 0.05) reduced pERK and pAKT expression in the upper LP (U. LP) and deeper LP (D. LP) in female mice with 4 h CYP-induced cystitis. Although we have previously demonstrated that imatinib prevention or treatment improves bladder function in mice with cystitis, the current studies suggest that reductions in inflammatory mediators contribute to prevention benefits of imatinib but not the treatment benefits of imatinib. Differential effects of imatinib prevention or treatment on inflammatory mediators may be influenced by the route and frequency of imatinib administration and may also suggest other mechanisms (e.g., changes in transepithelial resistance of the urothelium) through which imatinib may affect urinary bladder function following CYP-induced cystitis.
Comparison of Radiofrequency Ablation Versus Cryoablation For T1 Renal Tumors: An Evidence-Based Analysis of Comparative Outcomes
Authors: Shi Hongjin , Li Jinze , Fan Zhinan , Yang Jing , Fu Shi , Wang Haifeng , Wang Jiansong , Zhang Jinsong
Published: April 2022

Objective

To discuss the differences in the effectiveness and security for T1 renal tumors by radiofrequency ablation (RFA) and cryoablation (CA).

Methods

We systematically searched the Cochrane Library, PubMed, Embase, CNKI databases, and Science databases, and the date was from the above database establishment to August 2021. Controlled trials on RFA and CA for T1 renal tumors were included. The meta-analysis was conducted with the Review Manager 5.4 software.

Results

A total of ten studies with 2,367 patients were included in the analysis. There were no significant differences in complications (odds ratio [OR], 1.23; 95% CI, 0.80 to 1.90; p=0.35), primary technique efficacy rate (OR, 1.01; 95% CI, 0.33 to 3.14; p=0.98), changes in serum creatinine (weighted mean difference [WMD], 0.53; 95% CI, -0.50 to 1.57; p=0.31), or 5-year survival rate (hazard ratio [HR], 1.11; 95% CI, 0.41 to 3.00; p=0.84) among patients undergoing RFA and CA. However, compared with patients who underwent RFA, patients who underwent CA had a lower Local recurrence (OR: 2.25; 95% CI: 1.38 to 3.67; p = 0.001).

Conclusion

The analysis demonstrated that in the treatment of T1 renal tumors, CA may be associated with lower local recurrence rates. However, no differences were observed in terms of primary technique efficacy rate, 5-year survival rate, changes in serum creatinine, and complication rate between groups.

Systematic Review Registration

[https://www.crd.york.ac.uk/PROSPERO/], identifier PROSPERO (CRD42021295160).
Comprehensive Target Screening and Cellular Profiling of the Cancer-Active Compound b-AP15 Indicate Abrogation of Protein Homeostasis and Organelle Dysfunction as the Primary Mechanism of Action
Authors: Gubat Johannes , Selvaraju Karthik , Sjöstrand Linda , Kumar Singh Dhananjay , Turkina Maria V. , Schmierer Bernhard , Sabatier Pierre , Zubarev Roman A. , Linder Stig , D’Arcy Pádraig
Published: April 2022

Dienone compounds have been demonstrated to display tumor-selective anti-cancer activity independently of the mutational status of TP53. Previous studies have shown that cell death elicited by this class of compounds is associated with inhibition of the ubiquitin-proteasome system (UPS). Here we extend previous findings by showing that the dienone compound b-AP15 inhibits proteasomal degradation of long-lived proteins. We show that exposure to b-AP15 results in increased association of the chaperones VCP/p97/Cdc48 and BAG6 with proteasomes. Comparisons between the gene expression profile generated by b-AP15 to those elicited by siRNA showed that knock-down of the proteasome-associated deubiquitinase (DUB) USP14 is the closest related to drug response. USP14 is a validated target for b-AP15 and we show that b-AP15 binds covalently to two cysteines, Cys203 and Cys257, in the ubiquitin-binding pocket of the enzyme. Consistent with this, deletion of USP14 resulted in decreased sensitivity to b-AP15. Targeting of USP14 was, however, found to not fully account for the observed proteasome inhibition. In search for additional targets, we utilized genome-wide CRISPR/Cas9 library screening and Proteome Integral Solubility Alteration (PISA) to identify mechanistically essential genes and b-AP15 interacting proteins respectively. Deletion of genes encoding mitochondrial proteins decreased the sensitivity to b-AP15, suggesting that mitochondrial dysfunction is coupled to cell death induced by b-AP15. Enzymes known to be involved in Phase II detoxification such as aldo-ketoreductases and glutathione-S-transferases were identified as b-AP15-targets using PISA. The finding that different exploratory approaches yielded different results may be explained in terms of a “target” not necessarily connected to the “mechanism of action” thus highlighting the importance of a holistic approach in the identification of drug targets. We conclude that b-AP15, and likely also other dienone compounds of the same class, affect protein degradation and proteasome function at more than one level.
Human Tumor Targeted Cytotoxic Mast Cells for Cancer Immunotherapy
Authors: Fereydouni Mohammad , Ahani Elnaz , Desai Parth , Motaghed Mona , Dellinger Anthony , Metcalfe Dean D. , Yin Yuzhi , Lee Sung Hyun , Kafri Tal , Bhatt Aadra P. , Dellinger Kristen , Kepley Christopher L.
Published: April 2022

The diversity of autologous cells being used and investigated for cancer therapy continues to increase. Mast cells (MCs) are tissue cells that contain a unique set of anti-cancer mediators and are found in and around tumors. We sought to exploit the anti-tumor mediators in MC granules to selectively target them to tumor cells using tumor specific immunoglobin E (IgE) and controllably trigger release of anti-tumor mediators upon tumor cell engagement. We used a human HER2/neu-specific IgE to arm human MCs through the high affinity IgE receptor (FcεRI). The ability of MCs to bind to and induce apoptosis of HER2/neu-positive cancer cells in vitro and in vivo was assessed. The interactions between MCs and cancer cells were investigated in real time using confocal microscopy. The mechanism of action using cytotoxic MCs was examined using gene array profiling. Genetically manipulating autologous MC to assess the effects of MC-specific mediators have on apoptosis of tumor cells was developed using siRNA. We found that HER2/neu tumor-specific IgE-sensitized MCs bound, penetrated, and killed HER2/neu-positive tumor masses in vitro. Tunneling nanotubes formed between MCs and tumor cells are described that parallel tumor cell apoptosis. In solid tumor, human breast cancer (BC) xenograft mouse models, infusion of HER2/neu IgE-sensitized human MCs co-localized to BC cells, decreased tumor burden, and prolonged overall survival without indications of toxicity. Gene microarray of tumor cells suggests a dependence on TNF and TGFβ signaling pathways leading to apoptosis. Knocking down MC-released tryptase did not affect apoptosis of cancer cells. These studies suggest MCs can be polarized from Type I hypersensitivity-mediating cells to cytotoxic cells that selectively target tumor cells and specifically triggered to release anti-tumor mediators. A strategy to investigate which MC mediators are responsible for the observed tumor killing is described so that rational decisions can be made in the future when selecting which mediators to target for deletion or those that could further polarize them to cytotoxic MC by adding other known anti-tumor agents. Using autologous human MC may provide further options for cancer therapeutics that offers a unique anti-cancer mechanism of action using tumor targeted IgE’s.