CXCL9 may serve as a potential biomarker for primary Sjögren's syndrome with extra-glandular manifestations.

BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune condition that causes harm to exocrine glands and also has extra-glandular manifestations (EGM). pSS patients with EGM have a worse prognosis than those with only sicca symptoms. Previous studies have shown that the minor salivary glands (MSG) of pSS patients exhibit a unique profile of cytokines and chemokines compared to healthy controls. However, there is a lack of research comparing pSS with EGM (pSS-EGM) and pSS without EGM (pSS-non-EGM). This study aims to explore potential biomarkers associated with pSS, particularly pSS with EGM. METHODS: By utilizing RNA sequencing, we conducted an analysis on the gene expression profiles of MSG in 63 patients diagnosed with pSS, as well as 12 non-pSS individuals. Furthermore, we also investigated the MSG of pSS patients, both with and without EGM. Through bioinformatics analysis, we identified genes with differential expression (DEGs) and determined the core hub genes using PPI network. We then analyzed the top 20 DEGs and their correlation with the patients' clinical characteristics, and validated our findings using peripheral blood plasma. RESULTS: A total of 725 differentially expressed genes (DEGs) were identified in the comparison between pSS and non-pSS groups, and 727 DEGs were observed between pSS-EGM and pSS-non-EGM. It is noteworthy that the expression levels of CXCL9 were higher in both pSS patients and pSS-EGM when compared to the control group. Taking into consideration the significance of the top 20 DEGs in relation to clinical parameters and the central hub genes, we ultimately chose CXCL9. In comparison to the non-pSS group, pSS patients exhibited notably greater expression of the CXCL9 gene in the MSG, as well as higher levels of CXCL9 protein in their plasma (p < 0.001). Furthermore, the expression of the CXCL9 gene and levels of CXCL9 protein were notably higher in pSS patients accompanied by EGM and those with SSA antibodies. Additionally, a correlation was found between the expression of the CXCL9 gene and the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI), as well as with immunoglobulin G (IgG) levels and erythrocyte sedimentation rate (ESR). Meanwhile, the protein levels of CXCL9 were found to be correlated with IgG levels and ESSDAI. CONCLUSION: CXCL9 proves to be a valuable biomarker in pSS, specifically due to its strong ability to differentiate between pSS patients with EGM and those without EGM. There is a significant correlation between CXCL9 and various clinical parameters both at the gene and protein level. Therefore, CXCL9 could be a potential target for future treatment of pSS.

Microbiota dysbiosis in primary Sjögren's syndrome and the ameliorative effect of hydroxychloroquine.

The human microbiome plays an important role in autoimmune diseases. However, there is limited knowledge regarding the microbiota in individuals with primary Sjögren's syndrome (pSS). Here, we perform 16S ribosomal RNA gene sequencing of fecal, oral, and vaginal samples from a cohort of 133 individuals with pSS, 56 with non-pSS, and 40 healthy control (HC) individuals. Dysbiosis in the gut, oral, and vaginal microbiome is evident in patients with pSS, and oral samples demonstrate the greatest extent of microbial variation. Multiple key indicator bacteria and clinical characteristics are identified across different body sites, implying that microbial dysbiosis has important roles in the pathogenesis of pSS. Furthermore, we observe pSS-like dysbiosis in individuals with pre-clinical pSS or non-pSS-related disease, revealing that microbial shifts could appear prior to pSS. After hydroxychloroquine (HCQ) treatment, microbial dysbiosis in individuals with pSS is partially resolved, although the microbiota composition remain disordered. These results contribute to the overall understanding of the relationship between the microbiome and pSS.

Metagenomic Analysis Reveals A Possible Association Between Respiratory Infection and Periodontitis.

Periodontitis is an inflammatory disease that is characterized by progressive destruction of the periodontium and causes tooth loss in adults. Periodontitis is known to be associated with dysbiosis of the oral microflora, which is often linked to various diseases. However, the complexity of plaque microbial communities of periodontitis, antibiotic resistance, and enhanced virulence make this disease difficult to treat. In this study, using metagenomic shotgun sequencing, we investigated the etiology, antibiotic resistance genes (ARGs), and virulence genes (VirGs) of periodontitis. We revealed a significant shift in the composition of oral microbiota as well as several functional pathways that were represented significantly more abundantly in periodontitis patients than in controls. In addition, we observed several positively selected ARGs and VirGs with the Ka/Ks ratio > 1 by analyzing our data and a previous periodontitis dataset, indicating that ARGs and VirGs in oral microbiota may be subjected to positive selection. Moreover, 5 of 12 positively selected ARGs and VirGs in periodontitis patients were found in the genomes of respiratory tract pathogens. Of note, 91.8% of the background VirGs with at least one non-synonymous single-nucleotide polymorphism for natural selection were also from respiratory tract pathogens. These observations suggest a potential association between periodontitis and respiratory infection at the gene level. Our study enriches the knowledge of pathogens and functional pathways as well as the positive selection of antibiotic resistance and pathogen virulence in periodontitis patients, and provides evidence at the gene level for an association between periodontitis and respiratory infection.

Characteristic dysbiosis in gout and the impact of a uric acid-lowering treatment, febuxostat on the gut microbiota.

Gut dysbiosis is suggested to play a critical role in the pathogenesis of gout. The aim of our study was to identify the characteristic dysbiosis of the gut microbiota in gout patients and the impact of a commonly used uric acid-lowering treatment, febuxostat on gut microbiota in gout. 16S ribosomal RNA sequencing and metagenomic shotgun sequencing was performed on fecal DNA isolated from 38 untreated gout patients, 38 gout patients treated with febuxostat, and 26 healthy controls. A restriction of gut microbiota biodiversity was detected in the untreated gout patients, and the alteration was partly restored by febuxostat. Biochemical metabolic indexes involved in liver and kidney metabolism were significantly associated with the gut microbiota composition in gout patients. Functional analysis revealed that the gut microbiome of gout patients had an enriched function on carbohydrate metabolism but a lower potential for purine metabolism, which was comparatively enhanced in the febuxostat treated gout patients. A classification microbial model obtained a high mean area under the curve up to 0.973. Therefore, gut dysbiosis characterizings gout could potentially serve as a noninvasive diagnostic tool for gout and may be a promising target of future preventive interventions.

CXCR2 May Serve as a Useful Index of Disease Activity in Interstitial Lung Disease Associated With Primary Sjögren's Syndrome.

Background: Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease characterized by typical autoantibody production and lymphocytic-mediated exocrine gland damage. Interstitial lung disease (ILD) is a common complication of pSS and can be associated with a poor prognosis. However, the pathogenesis of ILD in pSS is still unclear. Methods: In this study, we used RNA sequencing to investigate the gene-expression profile of the minor salivary glands (MSGs) from 36 patients with ILD-pSS and 128 patients with non-ILD-pSS. Results: In the remarkably enriched chemokine-mediated signaling pathway, C-X-C motif chemokine receptor 2 (CXCR2), a receptor for interleukin-8, which participates in the activation of neutrophils, was found to be significantly elevated in both MSG and plasma from pSS patients with vs. without ILD (p < 0.001). Furthermore, the CXCR2 expression level in MSG and plasma was significantly associated with the diffusing capacity of the lungs for carbon monoxide, erythrocyte sedimentation rate, and EULAR Sjögren's Syndrome disease Activity Index in ILD-pSS. Conclusion: Therefore, with its potential role in ILD progression in patients with pSS and its strong association with clinical manifestations of the disease, CXCR2 may serve as a useful index for disease activity in ILD associated with pSS.

Dysbiosis of urine microbiota in obstructive urinary retention patients revealed by next-generation sequencing.

BACKGROUND: Urinary retention (UR) is a common urinary system disease can be caused by urinary tract obstruction with numerous reasons, however, the role of urine microbes in these disorders is still poorly understood. The aim of this study was to identify the urine microbial features of two common types of obstructive UR, caused by urinary stones or urinary tract tumors, with comparison to healthy controls. METHODS: Urine samples were collected from a cohort of 32 individuals with stone UR, 25 subjects with tumor UR and 25 healthy controls. The urine microbiome of all samples was analyzed using high-throughput 16S rRNA (16S ribosomal RNA) gene sequencing. RESULTS: We observed dramatically increased urine microbial richness and diversity in both obstructive UR groups compared to healthy controls. Despite different origins of UR, bacteria such as Pseudomonas, Acinetobacter and Sphingomonas were enriched, while Lactobacillus, Streptococcus, Gardnerella, Prevotella and Atopobium were decreased in both UR groups in comparison with healthy controls, exhibited an approximate urine microbial community and functional characteristics of two types of obstructive UR. Furthermore, disease classifiers were constructed using specific enriched genera in UR, which can distinguish stone UR or tumor UR patients from healthy controls with an accuracy of 92.29% and 97.96%, respectively. CONCLUSION: We presented comprehensive microbial landscapes of two common types of obstructive urinary retention and demonstrated that urine microbial features of these patients are significantly different from that of healthy people. The urine microbial signatures would shed light on the pathogenesis of these types of urinary retention and might be used as potential classification tools in the future.

The potential involvement of JAK-STAT signaling pathway in the COVID-19 infection assisted by ACE2.

COVID-19, a novel identified coronavirus disease due to Severe Acute Respiratory Syndrome coronaviruses 2 (SARS-Cov-2) infection, has posed a significant threat to public health worldwide. It has been reported COVID-19 keeps substantial nucleotide similarity and shares common receptor, Angiotensin-converting enzyme 2 (ACE2) with Severe Acute Respiratory Syndrome coronaviruses (SARS-Cov). Here, we investigated the gene expression of ACE2 and identified associated pathways of SARS-Cov as a useful reference for a deepening understanding of COVID-19. The results indicated the ACE2 was overexpressed in human airway epithelial cells (HAEs), especially at 72 h after SARS-Cov infection. We found ACE2 might regulate immune response through immunological activation-associated pathways in the process of in both SARS-Cov and SARS-Cov-2 infection, where the activation of B cells, macrophages, helper T cells 1 (Th1 cells) and the inhibition of Foxp3 + regulatory T (Treg) cells and CD8 + T cells were found to be prominent. Finally, significant correlation between ACE2 and JAK-STAT signaling pathway was identified which indicate that JAK-STAT signaling pathway might involve in the downstream action of the overactivation of ACE2. These findings are expected to gain a further insight into the action mechanism of COVID-19 infection and provide a promising target for designing effective therapeutic strategies.

Integrative analyses of gene expression profile reveal potential crucial roles of mitotic cell cycle and microtubule cytoskeleton in pulmonary artery hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a life-threatening condition. The aim of this study was to explore potential crucial genes and pathways associated with PAH based on integrative analyses of gene expression and to shed light on the identification of biomarker for PAH. METHODS: Gene expression profile of pulmonary tissues from 27 PAH patients and 22 normal controls were downloaded from public database (GSE53408 and GSE113439). After the identification of differentially expressed genes (DEGs), hub pathways and genes were identified based on the comprehensive evaluation of protein-protein interaction (PPI) network analysis, modular analysis and cytohubba's analysis, and further validated in another PAH transcriptomic dataset (GSE33463). Potentially associated micro-RNAs (miRNAs) were also predicted. RESULTS: A total of 521 DEGs were found between PAH and normal controls, including 432 up-regulated DEGs and 89 down-regulated DEGs. Functional enrichment analysis showed that these DEGs were mainly enriched in mitotic cell cycle process, mitotic cell cycle and microtubule cytoskeleton organization. Moreover, five key genes (CDK1, SMC2, SMC4, KIF23, and CENPE) were identified and then further validated in another transcriptomic dataset associated with special phenotypes of PAH. Furthermore, these hub genes were mainly enriched in promoting mitotic cell cycle process, which may be closely associated with the pathogenesis of PAH. We also found that the predicted miRNAs targeting these hub genes were found to be enriched in TGF-ß and Hippo signaling pathway. CONCLUSION: These findings are expected to gain a further insight into the development of PAH and provide a promising index for the detection of PAH.

The potential role of TNFα in 2019 novel coronavirus pneumonia.

The outbreak of 2019 novel coronavirus has spread rapidly in multiple countries. We report the first case of 2019-nCoV infection in a patient with Ankylosing Spondylitis (AS), who was a biological agent (anti-TNFα) user in Wenzhou, China, and describe the clinical course and management of the case.

[Preparation and Comparison of Arsenic Removal Granular Adsorbent Based on Iron-Manganese Sludge].

Backwashing sludge is an efficient adsorbent for arsenic removal. However, considering the practical application, it is unfavorable for solid-liquid separation. To overcome this disadvantage, a high-temperature baking method was used to prepare a granular adsorbent (GA) with iron-manganese sludge, along with an embedding method with drying (H-GA) and lyophilization (D-GA). The characterization results showed that the surface of the three adsorbents were rough, with specific surface areas of 43.830, 110.30, and 129.18 m2·g-1, respectively. The adsorption experiments showed that the adsorption of arsenic by H-GA and D-GA was much higher than that of GA. The maximum adsorption capacities of GA, H-GA, and D-GA were 5.05, 14.95, and 13.45 mg·g-1, respectively. The Langmuir model fit the adsorption process of arsenic by H-GA and D-GA better, whereas the Freundlich model fit the adsorption process of GA better. The Pseudo-first order model and Pseudo-second order model were suitable to describe the kinetic curves of the three adsorbents. The acidic environment was more conducive to the adsorption of arsenic. The particle adsorbents prepared by the embedding method, H-GA and D-GA, retained the original structure of iron-manganese sludge, and the specific surface area was much larger than that of GA; thus, the adsorption capacity was greater than that of GA. Drying and lyophilization had no significant effect on the adsorption performance of granular adsorbents prepared by embedding.

[Start-up and Operation of Biofilter Coupled Nitrification and CANON for the Removal of Iron, Manganese and Ammonia Nitrogen].

A pilot-scale bio-filter coupled nitrification and CANON was started up to remove iron, manganese and ammonia nitrogen from groundwater in a plant, and the main removal route of ammonia nitrogen was analyzed. The experiment showed that the bio-filter could be started up successfully and achieved stable operation after 164 days of culture development. The value of △NH4+-N/△NO3--N was 1.49, and the oxidation and removal of Fe(Ⅱ), Mn(Ⅱ), and NH4+-N were (9.87±1.17), (2.25±0.06), and (1.51±0.06) mg·L-1, respectively. The calculation based on the quantitative relationship between nitrogen conservation and dissolved oxygen (DO) measurement indicated that the contribution of CANON to NH4+-N removal was 33.48%-38.87%, and the average ratio of ammonia nitrogen removal amount to DO was 1:3.79-1:3.94. The removal ratio of ammonia nitrogen was lower with lower temperature.

[Effect of Intermediate-Setting Aeration on the CANON Granular Sludge Process in the AUSB Reactor].

The impact of different aeration positions on startup and operation of the continuous flow CANON granular sludge process was considered by inoculating flocculent ANAMMOX activated sludge at room temperature (25±1)℃ in two sets of AUSB reactors. The aeration unit of R1 was installed 0.3 m above the base, while the aeration unit of R2 was set at the bottom. R1 and R2 successfully developed the granule CANON process on the 43rd d and 56th d, respectively. The mean particle diameter of R1 granular sludge increased to 214.79 µm, and the eigenvalue (△NO3--N/△TN) was maintained at 0.128; whereas, the granular sludge size of R2 rose to 205.27 µm with an eigenvalue maintained at 0.129. The nitrogen loading rate (NLR) was gradually increased in the low ammonia-nitrogen (90 mg·L-1) wastewater within R1 and R2. This was more beneficial in R1, resulting in the persistent growth of CANON granular sludge and the enhancement of the systematic nitrogen removal rate (NRR). The average particle diameter of R1 rose to 507.46 µm in 88 d, while NRR reached up to 0.277 kg·(m3·d)-1. R2 granule sludge particle size was 467.72 µm after 108 d of cultivation, and achieved a 0.243 kg·(m3·d)-1NRR, which was 87.73% of that in R1. During the course of steady operation, the specific anoxic/aerobic mode of R1 effectively suppressed NOB microbial activity, the eigenvalue remained around 0.127±0.003, and the NRR of R1 was maintained at about (0.262±0.019) kg·(m3·d)-1. However, NOB was propagated observably in the continuously aerobic R2, whose eigenvalue rose to 0.136±0.004, while NRR was merely (0.231±0.015) kg·(m3·d)-1 after 125 d of long-term operation. During the whole experiment period, the intermediate-setting aerated AUSB accelerated the formation of CANON granular sludge evolving from flocculent ANAMMOX sludge, and better nitrogen removal performance and operational stability were achieved.

[Arsenic(â ¤) Removal by Granular Adsorbents Made from Backwashing Residuals from Biofilters for Iron and Manganese Removal].

Granular adsorbents for arsenic removal (GA) made from the backwashing residuals from iron and manganese removal biofilters for groundwater were characterized and examined as an arsenate sorbent. The GA were characterized by SEM-EDS microscopy, X-ray diffraction (XRD), and BET surface area measurement. The results showed that the GA had rough surfaces, developed pores, and were mainly amorphous, with small fractions of crystalline quartz and hematite. The surface area of the GA, which consists of many mesopores, was 43.8 m2·g-1. The kinetic studies revealed that arsenate adsorption on the GA was described by a pseudo-second-order kinetic equation, and the Freundlich isotherm equation fit the arsenate adsorption well (R2=0.994). The maximum adsorption capacity calculated by the Langmuir isotherm equation for As(Ⅴ) was 5.05 mg·g-1. Further studies showed that the GA operated well for As(Ⅴ) removal over a broad range in pH from 1.1 to 9.5. The coexistence of HCO3- and SO42- had no great influence on arsenic adsorption, while the H2PO4- and SiO32- showed negative effects. The GA can be regenerated well, and 82% of the original adsorption capacity was maintained after three regeneration cycles.