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1.
Bioresour Technol ; 333: 125205, 2021 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-33932808

RESUMEN

High solid anaerobic digestion has become the mainstream technology for sustainable on-farm treatment of solid wastes but has not been optimized with respect to increasing solid content in cow manure (CM). In the present study, CM was batch digested at total solid (TS) of 5%, 10%, 15% and 20% and microbial communities were investigated. The process remained stable up to 15% TS. The biomethane production rate at TS of 10% and 15% was reported to be 352.2 mL g-1 VS and 318.6 mL g-1 VS, reaching up to 83% and 75% of TS 5% biomethane, respectively. Kinetics results disclosed that the biodegradable organics could be utilized at increasing solid content with decreasing hydrolysis rate. The abundances of hydrogenotrophic and methylotrophic methanogens increased significantly with increasing solid content. This study is of great importance for understanding and application of high solid anaerobic digestion of cow manure.

2.
Waste Manag ; 127: 121-129, 2021 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-33933869

RESUMEN

High solid anaerobic digestion (HSAD) is a promising technology for the treatment of organic waste. Mixing process in HSAD is quite difficult with long mixing time, poor homogenization, significant short-circuiting and stagnant zones. However, the mass transfer in mixing process in HSAD has not been visualized due to the lack of a proper method. In this study, a novel approach for experimentally quantifying the mass transfer in HSAD's mixing process was proposed in a mixing tank equipped with multistage impellers by means of the Laser Induced Fluorescence (LIF) technique. Flow field was investigated for better illustrating the mass transfer, thus Particle Image Velocimetry (PIV) and Computational Fluid Dynamics (CFD) technique were conducted for flow field measurement. The obtained results revealed that the feedstock tended to accumulate around the impeller in the HSAD system, especially near the 1st stage. The tracer diffused rapidly around the 1st impeller in t = 10 s, but the diffusion around the 2nd impeller was quite tough even after 4 h 08 min 23 s. And prolonging mixing time could not significantly improve the flow pattern along with the mixing. In this study, new insight was thrown into the visualization of the mass transfer in mixing process within a HSAD reactor. The visualization of mass transfer in the mixing process in HSAD could offer reference information to the study of the mixing process of HSAD even in full-scale.

3.
Drug Metab Dispos ; 2021 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-33941543

RESUMEN

Givosiran is a N-acetylgalactosamine (GalNAc)-conjugated RNA interference (RNAi) therapeutic that targets 5'-aminolevulinate synthase 1 (ALAS1) messenger RNA (mRNA) in the liver and is currently marketed for the treatment of acute hepatic porphyria (AHP). Herein, nonclinical pharmacokinetic (PK) and absorption, distribution, metabolism, and excretion (ADME) properties of givosiran were characterized. Givosiran was completely absorbed after subcutaneous (SC) administration with relatively short plasma elimination t1/2 (less than 4 hours). Plasma exposure increased approximately dose proportionally with no accumulation after repeat doses. Plasma protein binding (PPB) was concentration dependent across all species tested and was around 90% at clinically relevant concentration in human. Givosiran predominantly distributed to the liver by asialoglycoprotein receptor (ASGPR)-mediated uptake, and the elimination t1/2 in the liver was significantly longer (~1 week). Givosiran was metabolized by nucleases, not cytochrome P450 (CYP) isozymes, across species with no human unique metabolites. Givosiran metabolized to form one primary active metabolite with the loss of 1 nucleotide from the 3' end of antisense strand, AS(N­1)3' givosiran which was equipotent to givosiran. Renal and fecal excretion were minor routes of elimination of givosiran as approximately 10% and 16% of the dose was recovered intact in excreta of rats and monkeys, respectively. Givosiran is not a substrate, inhibitor, or inducer of CYP isozymes, and it is not a substrate or inhibitor of uptake and most efflux transporters. Thus, givosiran has a low potential of mediating drug-drug interactions involving CYP isozymes and drug transporters. Significance Statement Nonclinical PK and ADME properties of givosiran, the first approved GalNAc-conjugated RNAi therapeutic, were characterized. Givosiran shows similar PK and ADME properties across rats and monkeys in vivo and across human and animal matrices in vitro. SC administration results in adequate exposure of givosiran to the target organ (liver). These studies support the interpretation of toxicology studies, help characterize the disposition of givosiran in humans, and support the clinical use of givosiran for the treatment of AHP.

4.
Am J Epidemiol ; 2021 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-33949658

RESUMEN

No epidemiological studies have been conducted to assess the association of dietary vitamin K intake with the risk of pancreatic cancer. We used prospective data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial between 1993 and 2009 to fill this gap. A total of 101695 subjects were identified. Dietary intakes of phylloquinone (vitamin K1), menaquinones (vitamin K2), and dihydrophylloquinone (dihydrovitamin K1) were assessed with a food frequency questionnaire. Cox regression was applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). During a mean follow-up of 8.86 years (900744.57 person-years), 361 pancreatic cancer cases were documented. In the fully adjusted model, dietary intakes of phylloquinone (HRquartile 4 versus 1: 0.57; 95% CI: 0.39, 0.83; Ptrend=0.002) and dihydrophylloquinone (HRquartile 4 versus 1: 0.59; 95% CI: 0.41, 0.85; Ptrend=0.006), but not menaquinones (HRquartile 4 versus 1: 0.93; 95% CI: 0.65, 1.33; Ptrend=0.816), were found to be inversely associated with the risk of pancreatic cancer in a nonlinear dose-response manner (all Pnonlinearity<0.05), which were not modified by predefined stratification factors and remained in sensitivity analyses. In conclusion, dietary intakes of phylloquinone and dihydrophylloquinone, but not menaquinones, confer a reduced risk of pancreatic cancer. Future studies should confirm our findings.

6.
Sci Total Environ ; 773: 145668, 2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-33940754

RESUMEN

Combustion-derived black carbon (BC) is increasingly recognized as a significant pollutant that can have adverse effects on the atmospheric environment, human health, and regional climate. Fossil fuel combustion is the main source of BC, yet understanding of the relative contributions to BC from coal and liquid fuel combustion remains incomplete. Moreover, few studies have assessed the relative contributions based on long-term continuous daily field observations. This study adopted a Bayesian model of a three-dimensional array of a stable carbon isotope and the ratios of non-sea-salt K+ to BC and ΔBC/ΔCO of one year's daily observations (from September 1, 2017 to August 31, 2018) to constrain source apportionment of BC in Beijing (China). Results showed that both the BC and the carbon isotope concentrations exhibited strong seasonal variability, and that the annual BC concentration has decreased significantly in recent years. The Bayesian model results also revealed that the relative contributions from the combustion of coal, liquid fuel, and biomass were 42% ± 18%, 42% ± 18%, and 16% ± 11%, respectively, with a larger contribution from coal (liquid fuel) combustion in winter and spring (summer and autumn). The seasonal variation of source appointment was attributed to local and regional fuel combustion coupled with meteorological conditions. With increasing PM2.5 level, the BC concentration derived from biomass burning increased fastest, followed by that derived from coal combustion. But concentration of secondary inorganic ions increased faster than BC as PM2.5 increased.

7.
Sci Rep ; 11(1): 9430, 2021 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-33941804

RESUMEN

This study aimed to characterize the key survival-specific genes for lung adenocarcinoma (LUAD) using machine-based learning approaches. Gene expression profiles were download from gene expression omnibus to analyze differentially expressed genes (DEGs) in LUAD tissues versus healthy lung tissue and to construct protein-protein interaction (PPI) networks. Using high-dimensional datasets of cancer specimens from clinical patients in the cancer genome atlas, gene set enrichment analysis was employed to assess the independent effect of meiotic nuclear divisions 1 (MND1) expression on survival status, and univariate and multivariate Cox regression analyses were applied to determine the associations of clinic-pathologic characteristics and MND1 expression with overall survival (OS). A set of 495 DEGs (145 upregulated and 350 downregulated) was detected, including 63 hub genes with ≥ 10 nodes in the PPI network. Among them, MND1 was participated in several important pathways by connecting with other genes via 17 nodes in lung cancer, and more frequently expressed in LUAD patients with advancing stage (OR = 1.68 for stage III vs. stage I). Univariate and multivariate Cox analyses demonstrated that the expression level of MND1 was significantly and negatively correlated with OS. Therefore, MND1 is a promising diagnostic and therapeutic target for LUAD.

9.
Artículo en Inglés | MEDLINE | ID: mdl-33935257

RESUMEN

OBJECTIVES: The clinical safety, efficacy and feasibility of laparoscopic appendectomy (LA) compared with open appendectomy (OA) in pregnancy are still controversial. Herein, we are aiming to compare the clinical outcomes of LA and OA in patients with acute appendicitis during their pregnancy. MATERIALS AND METHODS: This was a systematic review and meta-analysis of studies comparing laparoscopic and OA in pregnancy identifying using PubMed, Web of science, Embase, The Cochrane Library, Ovid and Scopus. Two independent reviewers extracted data on surgical complication, fetal loss, preterm delivery, hospital stay, Apgar score in both groups. RESULTS: Twenty-seven studies with total of 6497 patients (4464 in open and 2031 in laparoscopic group) were included. LA was associated with lower rate of wound infection [odds risk (OR)=3.13, 95% confidence interval (CI): 1.77-5.56, P<0.0001] overall complications (OR=2.15, 95% CI: 1.47-3.14, P<0.0001) and shorter hospitalization (mean difference=0.72, 95% CI: 0.43-1.02, P<0.00001) compared with open group. LA was in a lower risk for 5-minute Apgar score (mean difference=0.09, 95% CI: 0.02-0.17, P=0.01) group than open group. No difference was found regarding preterm delivery between 2 groups. LA was associated with higher fetal loss (OR=0.57, 95% CI: 0.41-0.79, P=0.0007) compared with open surgery. However, laparoscopy was not associated with increased fetal loss after 2010 (OR=0.74, 95% CI: 0.44-1.24, P=0.26) compared with open group. CONCLUSIONS: LA in pregnancy seems to be feasible with acceptable outcome, especially in patients with early and mid-trimester period, with sophisticated hands and experienced centers.

10.
PLoS One ; 16(4): e0249915, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33831101

RESUMEN

Ultraviolet (UV) filters are used in cosmetics, personal care products and packaging materials to provide sun protection for human skin and other substances. Little is known about these substances, but they continue to be released into the environment. The acute toxicity of 4,4'-dihydroxybenzophenone, 2,4,4'-trihydroxybenzophenone and 4-MBC to Chlorella vulgaris and Daphnia magna were analyzed in this study. The 96 h-EC50 values of 4,4'-dihydroxybenzophenone, 2,4,4'-trihydroxybenzophenone and 4-MBC on C. vulgaris were 183.60, 3.50 and 0.16874 mg/L, respectively. The 48 h-LC50 of 4,4'-dihydroxybenzophenone, 2,4,4'-trihydroxybenzophenone and 4-MBC on D. magna were 12.50, 3.74 and 0.54445 mg/L, respectively. The toxicity of a mixture of 4,4'-dihydroxybenzophenone and 4-MBC showed addictive effect on C. vulgaris, while the toxicity of mixtures of 4,4'-dihydroxybenzophenone and 2,4,4'-trihydroxybenzophenone, 2,4,4'-trihydroxybenzophenone and 4-MBC as well as 4,4'-dihydroxybenzophenone, 2,4,4'-trihydroxybenzophenone and 4-MBC all showed antagonistic effect on C. vulgaris. The induced no-effect concentrations of 4,4'-dihydroxybenzophenone, 2,4,4'-trihydroxybenzophenone and 4-MBC by the assessment factor (AF) method were 0.0125, 0.00350 and 0.000169 mg/L, respectively.

11.
DNA Repair (Amst) ; 102: 103112, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33838550

RESUMEN

Ovarian cancer has a poor prognosis due to drug resistance, relapse and metastasis. In recent years, immunotherapy has been applied in numerous cancers clinically. However, the effect of immunotherapy monotherapy in ovarian cancer is limited. DNA damage response (DDR) is an essential factor affecting the efficacy of tumor immunotherapy. Defective DNA repair may lead to carcinogenesis and tumor genomic instability, but on the other hand, it may also portend particular vulnerability of tumors and can be used as biomarkers for immunotherapy patient selection. Programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway mediates tumor immune escape, which may be a promising target for immunotherapy. Therefore, further understanding of the mechanism of PD-L1 expression after DDR may help guide the development of immunotherapy in ovarian cancer. In this review, we present the DNA damage repair pathway and summarize how DNA damage repair affects the PD-1/PD-L1 pathway in cancer cells. And then we look for biomarkers that affect efficacy or prognosis. Finally, we review the progress of PD-1/PD-L1-based immunotherapy in combination with other therapies that may affect the DDR pathway in ovarian cancer.

12.
Mar Drugs ; 19(3)2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33809116

RESUMEN

With the widespread occurrence of aquaculture diseases and the broad application of antibiotics, drug-resistant pathogens have increasingly affected aquatic animals' health. Marine probiotics, which live under high pressure in a saltwater environment, show high potential as a substitute for antibiotics in the field of aquatic disease control. In this study, twenty strains of non-hemolytic bacteria were isolated from the intestine of wild oysters and perch, and a model of Caenorhabditis elegans infected by Vibrio anguillarum was established. Based on the model, ML1206, which showed a 99% similarity of 16S rRNA sequence to Planococcus maritimus, was selected as a potential marine probiotic, with strong antibacterial capabilities and great acid and bile salt tolerance, to protect Caenorhabditis elegans from being damaged by Vibrio anguillarum. Combined with plate counting and transmission electron microscopy, it was found that strain ML1206 could significantly inhibit Vibrio anguillarum colonization in the intestinal tract of Caenorhabditis elegans. Acute oral toxicity tests in mice showed that ML1206 was safe and non-toxic. The real-time qPCR results showed a higher expression level of genes related to the antibacterial peptide (ilys-3) and detoxification (ugt-22, cyp-35A3, and cyp-14A3) in the group of Caenorhabditis elegans protected by ML1206 compared to the control group. It is speculated that ML1206, as a potential probiotic, may inhibit the infection caused by Vibrio anguillarum through stimulating Caenorhabditis elegans to secrete antibacterial effectors and detoxification proteins. This paper provides a new direction for screening marine probiotics and an experimental basis to support the potential application of ML1206 as a marine probiotic in aquaculture.

13.
Front Cell Infect Microbiol ; 11: 638785, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33842388

RESUMEN

Background: Dengue fever is a mosquito-borne febrile illness. Southeast Asia experienced severe dengue outbreaks in 2019, and over 1000 cases had been reported in Jiangxi, a previously known low-epidemic region in China. However, the emergence of a dengue virus epidemic in a non-epidemic region remains unclear. Methods: We enrolled 154 dengue fever patients from four hospitals in Jiangxi, from April 2019 to September 2019. Real-time PCR, NS1 antigen rapid test, and IgM, IgG tests were performed, and 14 samples were outsourced to be sequenced metagenomically. Results: Among the 154 cases, 42 were identified as imported and most of them returned from Cambodia. A total of 113 blood samples were obtained and 106 were identified as DENV-1, two as DENV-2, and five were negative through RT-PCR. All DENV-1 strains sequenced in this study were all classified to one cluster and owned a high similarity with a Cambodia strain isolated in 2019. The evolutionary relationships of amino acid were consistent with that of nucleotide genome result. The sequence-based findings of Jiangxi strains were consistent with epidemiological investigation. Conclusion: Epidemiological analysis demonstrated that the emergence of dengue cases led to autochthonous transmission in several cities in Jiangxi, a low-epidemic region before. This study emphasized future prevention and control of dengue fever in both epidemic and non-epidemic regions.

14.
Sci Rep ; 11(1): 7294, 2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33790390

RESUMEN

Nasopharyngeal carcinoma (NPC) is a rare malignancy, with the unique geographical and ethnically characteristics of distribution. Gene chip and bioinformatics have been employed to reveal regulatory mechanisms in current functional genomics. However, a practical solution addressing the unresolved aspects of microarray data processing and analysis have been long pursuit. This study developed a new method to improve the accuracy of identifying key biomarkers, namely Unit Gamma Measurement (UGM), accounting for multiple hypotheses test statistics distribution, which could reduce the dependency problem. Three mRNA expression profile of NPC were selected to feed UGM. Differentially expressed genes (DEGs) were identified with UGM and hub genes were derived from them to explore their association with NPC using functional enrichment and pathway analysis. 47 potential DEGs were identified by UGM from the 3 selected datasets, and affluent in cysteine-type endopeptidase inhibitor activity, cilium movement, extracellular exosome etc. also participate in ECM-receptor interaction, chemical carcinogenesis, TNF signaling pathway, small cell lung cancer and mismatch repair pathway. Down-regulation of CAPS and WFDC2 can prolongation of the overall survival periods in the patients. ARMC4, SERPINB3, MUC4 etc. have a close relationship with NPC. The UGM is a practical method to identify NPC-associated genes and biomarkers.

15.
Small ; : e2100246, 2021 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-33818015

RESUMEN

The introduction of patterned sapphire substrates (PSS) has been regarded as an effective method to improve the photoelectric performance of 2D layered materials in recent years. Molybdenum disulfide (MoS2 ), an intriguing transition metal 2D materials with splendid photoresponse owing to a direct-indirect bandgap transition at monolayer, shows promising optoelectronics applications. Here, a large-scale, continuous multilayer MoS2 film is prepared on a SiO2 /Si substrate and transferred to flat sapphire substrate and PSS, respectively. An enhanced dynamic distribution of local electric field and concentrated photon excitons across the interface between MoS2 and patterned sapphire substrates are revealed by the finite-difference time-domain simulation. The photoelectric performance of the MoS2 /PSS photodetector is improved under the three lasers of 365, 460, and 660 nm. Under the 365 nm laser, the photocurrent increased by 3 times, noise equivalent power (NEP) decreases to 1.77 × 10-14 W/Hz1/2 and specific detectivity (D*) increases to 1.2 × 1010 Jones. Meanwhile, the responsivity is increased by 7 times at 460 nm, and the response time of the MoS2 /PSS photodetector is also shortened under three wavelengths. The work demonstrates an effective method for enhancing the optical properties of photodetectors and enabling simultaneous detection of broad-spectrum emissions.

16.
Biol Trace Elem Res ; 2021 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-33797704

RESUMEN

Essential metal elements (EMEs) have essential roles in neurological development and maintenance of human homeostasis. We performed a case-control study to explore association between the risk of autism spectrum disorder (ASD) and the 11 EMEs [Calcium (Ca), potassium (K), magnesium (Mg), sodium (Na), manganese (Mn), selenium (Se), cobalt (Co), Molybdenum (Mo), copper (Cu), zinc (Zn), and iron (Fe)] in serum. Ninety-two autistic subjects (cases) and age-sex-matched healthy subjects (controls = 91) from Beijing, China were recruited. In addition, totally 109 mothers of recruited children participated in this study. ICP-AES and ICP-MS were applied to determine the concentration of 11 EMEs in serum. The concentrations of Ca, K, and Mg were significantly higher in the cases than in the controls (OR [95% CI]: 1.031 [1.006-1.058] for Ca; 1.081 [1.046-1.118] for K; 1.161 [1.012-1.331] for Mg), while the concentrations of Zn and Cu were significantly lower (0.997 [0.995-0.999] for Cu; 0.996 [0.992-1.000] for Zn). Clear dose-response relationships between EMEs concentrations and the risk of ASD, as well as the correlation between EME concentrations and the severity of ASD were observed for most of the above EMEs. Six and seven specific correlated pairs between mothers and children were found in the cases and controls separately. The overall profiles of the EMEs were changed in the cases as compared to the controls. This study suggested that the higher levels of Ca, K, and Mg and lower levels of Zn and Cu may be associated with an elevated risk of ASD.

17.
Circ Res ; 128(7): 1021-1039, 2021 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-33793338

RESUMEN

Nuclear receptors represent a large family of ligand-activated transcription factors which sense the physiological environment and make long-term adaptations by mediating changes in gene expression. In this review, we will first discuss the fundamental mechanisms by which nuclear receptors mediate their transcriptional responses. We will focus on the PPAR (peroxisome proliferator-activated receptor) family of adopted orphan receptors paying special attention to PPARγ, the isoform with the most compelling evidence as an important regulator of arterial blood pressure. We will review genetic data showing that rare mutations in PPARγ cause severe hypertension and clinical trial data which show that PPARγ activators have beneficial effects on blood pressure. We will detail the tissue- and cell-specific molecular mechanisms by which PPARs in the brain, kidney, vasculature, and immune system modulate blood pressure and related phenotypes, such as endothelial function. Finally, we will discuss the role of placental PPARs in preeclampsia, a life threatening form of hypertension during pregnancy. We will close with a viewpoint on future research directions and implications for developing novel therapies.

18.
BMC Pulm Med ; 21(1): 116, 2021 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-33832474

RESUMEN

Extracorporeal life support treatments such as extracorporeal membrane oxygenation (ECMO) have been recommended for the treatment of severe acute respiratory distress syndrome (ARDS) patients with coronavirus disease 2019 (COVID-19). To date, many countries, including China, have adopted ECMO as a treatment for severe COVID-19. However, marked differences in patient survival rates have been reported, and the underlying reasons are unclear. This study aimed to summarize the experience of using ECMO to treat severe COVID-19 and provide suggestions for improving ECMO management. The effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the pathophysiology of COVID-19 and the effects of ECMO on the clinical outcomes in patients with severe cases of COVID-19 were reviewed. Recent data from frontline workers involved in the use of ECMO in Wuhan, China, and those experienced in the implementation of artificial heart and lung support strategies were analysed. There is evidence that ECMO may complicate the pathophysiological state in COVID-19 patients. However, many studies have shown that the appropriate application of ECMO improves the prognosis of such patients. To expand our understanding of the benefits of ECMO for critically ill patients with COVID-19, further prospective, multicentre clinical trials are needed.


Asunto(s)
/terapia , Cuidados Críticos , Oxigenación por Membrana Extracorpórea , /complicaciones , Humanos
19.
Nucleic Acid Ther ; 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33861634

RESUMEN

Serum protein interactions are evaluated during the drug development process since they determine the free drug concentration in blood and thereby can influence the drug's pharmacokinetic and pharmacodynamic properties. While the impact of serum proteins on the disposition of small molecules is well understood, it is not yet well characterized for a new modality, RNA interference therapeutics. When administered systemically, small interfering RNAs (siRNAs) conjugated to the N-acetylgalactosamine (GalNAc) ligand bind to proteins present in circulation. However, it is not known if these protein interactions may impact the GalNAc-conjugated siRNA uptake into hepatocytes mediated through the asialoglycoprotein receptor (ASGPR) and thereby influence the activity of GalNAc-conjugated siRNAs. In this study, we assess the impact of serum proteins on the uptake and activity of GalNAc-conjugated siRNAs in primary human hepatocytes. We found that a significant portion of the GalNAc-conjugated siRNAs is bound to serum proteins. However, ASGPR-mediated uptake and activity of GalNAc-conjugated siRNAs were minimally impacted by the presence of serum relative to their uptake and activity in the absence of serum. Therefore, in contrast to small molecules, serum proteins are expected to have minimal impact on pharmacokinetic and pharmacodynamic properties of GalNAc-conjugated siRNAs.

20.
Cell Mol Life Sci ; 2021 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-33880615

RESUMEN

Rheumatoid arthritis (RA) is a chronic autoimmune disease with joint and systemic inflammation that is accompanied by the production of autoantibodies, such as rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Follicular helper T (Tfh) cells, which are a subset of CD4+ T cells, facilitate germinal center (GC) reactions by providing signals required for high-affinity antibody production and the generation of long-lived antibody-secreting plasma cells. Uncontrolled expansion of Tfh cells is observed in various systemic autoimmune diseases. Particularly, the frequencies of circulating Tfh-like (cTfh-like) cells, their subtypes and synovial-infiltrated T helper cells correlate with disease activity in RA patients. Therefore, reducing autoantibody production and restricting excessive Tfh cell responses are ideal ways to control RA pathogenesis. The present review summarizes current knowledge of the involvement of Tfh cells in RA pathogenesis and highlights the potential of these cells as therapeutic targets.

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