bluuebunny/crossref_metadata_2025 huggingface dataset:
REV1: A novel biomarker and potential therapeutic target for various cancers
Authors: Zhu Ning , Zhao Yingxin , Mi Mi , Lu Yier , Tan Yinuo , Fang Xuefeng , Weng Shanshan , Yuan Ying
Published: September 2022

Background: REV1 is a member of the translesion synthesis DNA polymerase Y family. It is an essential player in a variety of DNA replication activities, and perform major roles in the production of both spontaneous and DNA damage-induced mutations. This study aimed to explore the role of REV1 as a prognostic biomarker and its potential function regulating the sensitivity of anti-tumor drugs in various cancers.

Methods: We analyzed the impact of REV1 gene alterations on patient prognosis and the impact of different REV1 single nucleotide polymorphisms (SNP) on protein structure and function using multiple online prediction servers. REV1 expression was assessed using data from Oncomine, TCGA, and TIMER database. The correlation between REV1 expression and patient prognosis was performed using the PrognoScan and Kaplan-Meier plotter databases. The IC50 values of anti-cancer drugs were downloaded from the Genomics of Drug Sensitivity in Cancer database and the correlation analyses between REV1 expression and each drug pathway’s IC50 value in different tumor types were conducted.

Results: Progression free survival was longer in REV1 gene altered group comparing to unaltered group [Median progression free survival (PFS), 107.80 vs. 60.89 months, p value = 7.062e-3]. REV1 SNP rs183737771 (F427L) was predicted to be deleterious SNP. REV1 expression differs in different tumour types. Low REV1 expression is associated with better prognosis in colorectal disease specific survival (DSS), disease-free survival (DFS), gastric overall survival (OS), post progression survival (PPS) and ovarian (OS, PPS) cancer while high REV1 expression is associated with better prognosis in lung [OS, relapse free survival (RFS), first progession (FP), PPS] and breast (DSS, RFS) cancer. In colon adenocarcinoma and rectum adenocarcinoma and lung adenocarcinoma, low expression of REV1 may suggest resistance to drugs in certain pathways. Conversely, high expression of REV1 in acute myeloid leukemia, brain lower grade glioma, small cell lung cancer and thyroid carcinoma may indicate resistance to drugs in certain pathways.

Conclusion: REV1 plays different roles in different tumor types, drug susceptibility, and related biological events. REV1 expression is significantly correlated with different prognosis in colorectal, ovarian, lung, breast, and gastric cancer. REV1 expression can be used as predictive marker for various drugs of various pathways in different tumors.
External validation of biomarkers for immune-related adverse events after immune checkpoint inhibition
Authors: Glehr Gunther , Riquelme Paloma , Yang Zhou Jordi , Cordero Laura , Schilling Hannah-Lou , Kapinsky Michael , Schlitt Hans J. , Geissler Edward K. , Burkhardt Ralph , Schmidt Barbara , Haferkamp Sebastian , Hutchinson James A. , Kronenberg Katharina
Published: September 2022

Immune checkpoint inhibitors have revolutionized treatment of advanced melanoma, but commonly cause serious immune-mediated complications. The clinical ambition of reserving more aggressive therapies for patients least likely to experience immune-related adverse events (irAE) has driven an extensive search for predictive biomarkers. Here, we externally validate the performance of 59 previously reported markers of irAE risk in a new cohort of 110 patients receiving Nivolumab (anti-PD1) and Ipilimumab (anti-CTLA-4) therapy. Alone or combined, the discriminatory value of these routine clinical parameters and flow cytometry biomarkers was poor. Unsupervised clustering of flow cytometry data returned four T cell subsets with higher discriminatory capacity for colitis than previously reported populations, but they cannot be considered as reliable classifiers. Although mechanisms predisposing some patients to particular irAEs have been described, we are presently unable to capture adequate information from pre-therapy flow cytometry and clinical data to reliably predict risk of irAE in most cases.
Specific circulating neutrophils subsets are present in clinically stable adults with cystic fibrosis and are further modulated by pulmonary exacerbations
Authors: Martin Clémence , Dhôte Théo , Ladjemi Maha Zohra , Andrieu Muriel , Many Souganya , Karunanithy Vaarany , Pène Frédéric , Da Silva Jennifer , Burgel Pierre-Régis , Witko-Sarsat Véronique
Published: September 2022

The progressive lung destruction in cystic fibrosis (CF) is tightly associated with chronic bacterial infection and neutrophil-dominated airway inflammation. CF pulmonary disease is complicated by episodes of acute exacerbations, contributing to irreversible lung damage. We hypothesized that circulating subsets of neutrophils from clinically stable adults with CF present some phenotypic specificities that could amplify their activation during an infectious episode. The aim of the present study was to examine the different neutrophil subsets in whole blood and in the low density neutrophils (LDN) that co-purify with peripheral blood mononuclear cells (PBMC) in clinically stable adults with CF and in CF adults during pulmonary exacerbations compared to healthy donors. Blood samples were obtained from 22 adults with CF (16 in stable state and 6 during pulmonary exacerbations) and from 20 healthy donors. Flow cytometry analysis of 13 different markers related to lineage (CD45, CD15), maturity (CD16, CD10, and CD33), activation (CD62L, CD11b, CD66b, and CD114), metabolism (GLUT-1, LOX1) and immunosuppression (PD1, PD-L1) was carried out within whole blood and within the LDN fraction. Unsupervised analysis of flow cytometry data was performed using visual t-distributed stochastic neighbor embedding (vi-tSNE). A significant increase in the CD11b expression in neutrophils from CF patients during exacerbations was observed compared to neutrophils from stable CF patients or to healthy donors, indicative of a circulating activation state due to an infectious status. The percentage of LDN was not increased in stable CF patients but increased during exacerbations. Analysis of neutrophil subsets using the double CD16/CD62L labeling revealed a significant increase in the CD16high/CD62Llow subset in all CF patients compared to healthy donors. In contrast, an increase in the CD16low/CD62Lhigh subset was observed only in CF patients during exacerbations. Unsupervised analysis identified a PD-L1high/CD114high population that was present in stable CF patients and as well as in CF patients during exacerbations.
Single Domain Antibody application in bacterial infection diagnosis and neutralization
Authors: Qin Qian , Liu Hao , He Wenbo , Guo Yucheng , Zhang Jiaxin , She Junjun , Zheng Fang , Zhang Sicai , Muyldermans Serge , Wen Yurong
Published: September 2022

Increasing antibiotic resistance to bacterial infections causes a serious threat to human health. Efficient detection and treatment strategies are the keys to preventing and reducing bacterial infections. Due to the high affinity and antigen specificity, antibodies have become an important tool for diagnosis and treatment of various human diseases. In addition to conventional antibodies, a unique class of “heavy-chain-only” antibodies (HCAbs) were found in the serum of camelids and sharks. HCAbs binds to the antigen through only one variable domain Referred to as VHH (variable domain of the heavy chain of HCAbs). The recombinant format of the VHH is also called single domain antibody (sdAb) or nanobody (Nb). Sharks might also have an ancestor HCAb from where SdAbs or V-NAR might be engineered. Compared with traditional Abs, Nbs have several outstanding properties such as small size, high stability, strong antigen-binding affinity, high solubility and low immunogenicity. Furthermore, they are expressed at low cost in microorganisms and amenable to engineering. These superior properties make Nbs a highly desired alternative to conventional antibodies, which are extensively employed in structural biology, unravelling biochemical mechanisms, molecular imaging, diagnosis and treatment of diseases. In this review, we summarized recent progress of nanobody-based approaches in diagnosis and neutralization of bacterial infection and further discussed the challenges of Nbs in these fields.
Identification of cross-talk pathways and ferroptosis-related genes in periodontitis and type 2 diabetes mellitus by bioinformatics analysis and experimental validation
Authors: Pan Shengyuan , Hu Bo , Sun Jicheng , Yang Zun , Yu Wenliang , He Zangmin , Gao Xiang , Song Jinlin
Published: September 2022

Purpose

There is a bidirectional relationship between periodontitis and type 2 diabetes mellitus (T2DM). The aim of this study was to further explore the pathogenesis of this comorbidity, screen out ferroptosis-related genes involved in the pathological process, and predict potential drug targets to develop new therapeutic strategies.

Methods

Common cross-talk genes were identified from periodontitis datasets (GSE16134, GSE10334 and GSE106090) and T2DM databases (DisGeNET and GeneCard). Then, GO and KEGG enrichment analyses, PPI network analysis and hub gene identification were performed. The association between ferroptosis and periodontitis with T2DM was investigated by Pearson correlation analysis. Core ferroptosis-related cross-talk genes were identified and verified by qRT-PCR. Potential drugs targeting these core genes were predicted via DGIDB.

Results

In total, 67 cross-talk genes and two main signalling pathways (immuno-inflammatory pathway and AGE-RAGE signalling pathway) were identified. Pearson correlation analysis indicated that ferroptosis served as a crucial target in the pathological mechanism and treatment of periodontitis with T2DM. IL-1β, IL-6, NFE2L2 and ALOX5 were identified as core ferroptosis-related genes and the qRT-PCR detection results were statistically different. In total, 13 potential drugs were screened out, among which, Echinacea and Ibudilast should be developed first.

Conclusions

This study contributes to a deeper understanding of the common pathogenesis of periodontitis and T2DM and provides new insights into the role of ferroptosis in this comorbidity. In addition, two drugs with potential clinical application value were identified. The potential utility of these drugs requires further experimental investigation.
Enlarged perivascular spaces, neuroinflammation and neurological dysfunction in NMOSD patients
Authors: Yao Xiao-Ying , Gao Mei-Chun , Bai Shu-Wei , Xie Li , Song Ya-Ying , Ding Jie , Wu Yi-Fan , Xue Chun-Ran , Hao Yong , Zhang Ying , Guan Yang-Tai
Published: September 2022

Background and objectives

Cerebrospinal fluid (CSF) and interstitial fluid exchange along a brain-wide network of perivascular spaces (PVS) termed the ‘glymphatic system’. The aquaporin-4 (AQP4) water channels abundantly expressed on astrocytic endfeet play a key role in the CSF circulation in the glymphatic system. Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating autoimmune disease of the central nervous system (CNS) featured with a specific autoantibody directed against AQP4 in most of patients. Anti-AQP4 antibodies are likely resulting in the impairment of the brain glymphatic system and the enlargement of PVS in NMOSD patients. In the current study, we aimed to demonstrate the features of EPVS detected by MRI and its association with the CSF anti-AQP4 antibody titer, CNS inflammatory markers, and disease severity in NMOSD patients.

Methods

We conducted a retrospective review of a consecutive cohort of 110 patients with NMOSD who had brain MRI. We assessed the correlation of EPVS with markers of neuroinflammation, blood-brain barrier (BBB) function and severity of neurological dysfunction in patients. We used multivariate logistic regression analysis to determine the independent variables associated with disease severity.

Results

The median number of total-EPVS was 15.5 (IQR, 11-24.2) in NMOSD patients. The number of total-EPVS was significantly related to EDSS score after correcting for the effects of age and hypertension (r=0.353, p<0.001). The number of total-EPVS was also significantly associated with the titer of CSF anti-AQP4 antibody, the albumin rate (CSF/serum ratios of albumin), the CSF albumin, IgG and IgA levels. Logistic regression analysis showed that total-EPVS and serum albumin level were two independent factors to predict disease severity in NMOSD patients (OR=1.053, p=0.028; OR=0.858, p=0.009 respectively). Furthermore, ROC analysis achieved AUC of 0.736 (0.640-0.831, p<0.001) for total-EPVS to determine severe NMOSD (EDSS 4.5-9.5).

Discussion

In our cohort, we found a relationship between EPVS and neuroinflammation and BBB function in NMOSD. Moreover, EPVS might independently predict neurological dysfunction in patients with NMOSD.
Neutralization effect of plasma from vaccinated COVID-19 convalescents on SARS-CoV-2 Omicron variants
Authors: Xie Yudi , Liu Lei , Wang Jue , Zheng Yaqiong , Luo Chen , Ni Wenxu , He Zhihang , Zhao Xin , Liu Yan , He Yingyu , Zheng Shangen , Li Ling , Liu Zhong
Published: September 2022

Background

COVID-19 has caused a global pandemic and the death toll is increasing. With the coronavirus continuously mutating, Omicron has replaced Delta as the most widely reported variant in the world. Studies have shown that the plasma of some vaccinated people does not neutralize the Omicron variant. However, further studies are needed to determine whether plasma neutralizes Omicron after one- or two-dose vaccine in patients who have recovered from infection with the original strain.

Methods

The pseudovirus neutralization assays were performed on 64 plasma samples of convalescent COVID-19 patients, which were divided into pre-vaccination group, one-dose vaccinated group and two-dose vaccinated group.

Results

In the three groups, there were significant reductions of sera neutralizing activity from WT to Delta variant (B.1.617.2), and from WT to Omicron variant (B.1.1.529) (ps<0.001), but the difference between Delta and Omicron variants were not significant (p>0.05). The average neutralization of the Omicron variant showed a significant difference between pre-vaccination and two-dose vaccinated convalescent individuals (p<0.01).

Conclusions

Among the 64 plasma samples of COVID-19 convalescents, whether vaccinated or not, Omicron (B.1.1.529) escaped the neutralizing antibodies, with a significantly decreased neutralization activity compared to WT. And two-dose of vaccine could significantly raise the average neutralization of Omicron in convalescent individuals.
MSC-EVs transferring mitochondria and related components: A new hope for the treatment of kidney disease
Authors: Mao Jueyi , Li Cuifang , Wu Feifeng , She Zhou , Luo Senlin , Chen Xiaoyu , Wen Chuan , Tian Jidong
Published: September 2022

Kidney disease is a serious hazard to human health. Acute or chronic renal disease will have a significant negative impact on the body’s metabolism. The involvement of mitochondria in renal illness has received a lot of interest as research on kidney disease has advanced. Extracellular vesicles are gaining popularity as a means of intercellular communication in recent years. They have a close connection to both the nephropathy process and the intercellular transfer of mitochondria. The goal of this review is to present the extracellular vesicle transport mitochondria and its related biologically active molecules as new therapeutic options for the treatment of clinical kidney disease. This review focuses on the extracellular vesicles through the transfer of mitochondria and its related bioactive molecules, which affect mitochondrial energy metabolism, take part in immune regulation, and secrete outside the body.
Antithrombin activity levels for predicting long-term outcomes in the early phase of isolated traumatic brain injury
Authors: Takahashi Masaki , Wada Takeshi , Nakae Ryuta , Fujiki Yu , Kanaya Takahiro , Takayama Yasuhiro , Suzuki Go , Naoe Yasutaka , Yokobori Shoji
Published: September 2022

Coagulopathy management is an important strategy for preventing secondary brain damage in patients with traumatic brain injury (TBI). Antithrombin (AT) is a natural anticoagulant that controls coagulation and inflammation pathways. However, the significance of AT activity levels for outcomes in patients with trauma remains unclear. This study aimed to investigate the relationship between AT activity levels and long-term outcomes in patients with TBI; this was a sub-analysis of a prior study that collected blood samples of trauma patients prospectively in a tertiary care center in Kawaguchi City, Japan. We included patients with isolated TBI (iTBI) aged ≥16 years admitted directly to our hospital within 1 h after injury between April 2018 and March 2021. General coagulofibrinolytic and specific molecular biomarkers, including AT, were measured at 1, 3, 6, 12, and 24 h after injury. We analyzed changes in the AT activity levels during the study period and the impact of the AT activity levels on long-term outcomes, the Glasgow Outcome Scale-Extended (GOSE), 6 months after injury. 49 patients were included in this study; 24 had good neurological outcomes (GOSE 6–8), and 25 had poor neurological outcomes (GOSE 1–5). Low AT activity levels were shown within 1 h after injury in patients in the poor GOSE group; this was associated with poor outcomes. Furthermore, AT activity levels 1 h after injury had a strong predictive value for long-term outcomes (area under the receiver operating characteristic curve of 0.871; 95% CI: 0.747–0.994). Multivariate logistic regression analysis with various biomarkers showed that AT was an independent factor of long-term outcome (adjusted odds ratio: 0.873; 95% CI: 0.765–0.996; p=0.043). Another multivariate analysis with severity scores showed that low AT activity levels were associated with poor outcomes (adjusted odds ratio: 0.909; 95% CI: 0.822–1.010; p=0.063). We demonstrated that the AT activity level soon after injury could be a predictor of long-term neurological prognosis in patients with iTBI.
miR-210-3p protects against osteoarthritis through inhibiting subchondral angiogenesis by targeting the expression of TGFBR1 and ID4
Authors: Tang Han , Zhu Wenrun , Cao Lu , Zhang Jin , Li Juncheng , Ma Duan , Guo Changan
Published: September 2022

Excessive subchondral angiogenesis is a key pathological feature of osteoarthritis (OA), as it alters the balance of subchondral bone remodeling and causes progressive cartilage degradation. We previously found that miR-210-3p correlates negatively with angiogenesis, though the specific mechanism of miR-210-3p-related angiogenesis in subchondral bone during OA progression remains unclear. This study was conducted to identify the miR-210-3p-modulating subchondral angiogenesis mechanism in OA and investigate its therapeutic effect. We found that miR-210-3p expression correlated negatively with subchondral endomucin positive (Emcn+) vasculature in the knee joints of OA mice. miR-210-3p overexpression regulated the angiogenic ability of endothelial cells (ECs) under hypoxic conditions in vitro. Mechanistically, miR-210-3p inhibited ECs angiogenesis by suppressing transforming growth factor beta receptor 1 (TGFBR1) mRNA translation and degrading DNA-binding inhibitor 4 (ID4) mRNA. In addition, TGFBR1 downregulated the expression of ID4. Reduced ID4 levels led to a negative feedback regulation of TGFBR1, enhancing the inhibitory effect of miR-210-3p on angiogenesis. In OA mice, miR-210-3p overexpression in ECs via adeno-associated virus (AAV) alleviated cartilage degradation, suppressed the type 17 immune response and relieved symptoms by attenuating subchondral Emcn+ vasculature and subchondral bone remodeling. In conclusion, we identified a miR-210-3p/TGFBR1/ID4 axis in subchondral ECs that modulates OA progression via subchondral angiogenesis, representing a potential OA therapy target.
PTPRD/PTPRT mutation as a predictive biomarker of immune checkpoint inhibitors across multiple cancer types
Authors: Shang Xiaoling , Zhang Wengang , Zhang Xun , Yu Miao , Liu Jingwen , Cheng Yufeng , Cheng Bo
Published: September 2022

Background

Immune checkpoint inhibitors (ICIs) are dramatically changing the treatment landscape of a variety of cancers. Nevertheless, the variability in ICI responses highlight the importance in identifying predictive biomarkers. PTPRD and PTPRT (PTPRD/PTPRT) are the phosphatases of JAK-STAT signaling, a critical pathway in anti-cancer immunity regulation. However, the pan-cancer association between PTPRD/PTPRT mutation and the efficacy of ICIs remains unclear across pan-cancer patients.

Methods

We analyzed the association between PTPRD/PTPRT mutations and patient outcomes using clinical data and genomic mutations from TCGA pan-cancer cohort. Furthermore, the ICI-treatment cohort was used to evaluate the relationship between PTPRD/PTPRT mutation and the efficacy of ICIs. Another ICIs-treatment cohort was used to validate the findings. The TCGA pan-cancer dataset was analyzed to explore the correlation between PTPRD/PTPRT mutations and immune signatures. Moreover, we combined four factors to construct a nomogram model that could be used to predict the survival of pan-cancer patients receiving ICI treatment. The calibration curves and area under the curve were applied to assess the performance of the model.

Results

PTPRD/PTPRT mutations were shown to be associated with a worse prognosis in TCGA cohort (P < 0.05). In the Samstein cohort, prolonged overall survival (OS) was observed in PTPRD/PTPRT mutant cancers, compared with wild-type cancers (mOS: 40.00 vs 16.00 months, HR = 0.570, 95%CI: 0.479-0.679, P < 0.0001). In the validation cohort, significant OS advantage was observed in PTPRD/PTPRT mutant patients (mOS: 31.32 vs 15.53 months, HR = 0.658, 95%CI: 0.464-0.934, P = 0.0292). Furthermore, PTPRD/PTPRT mutations were associated with a higher tumor mutational burden, MSI score, and TCR score (P < 0.0001). Enhanced immune signatures were found in the PTPRD/PTPRT mutant cancers (P < 0.05). Finally, we successfully established a nomogram model that could be used to predict the survival of NSCLC patients who received ICI treatment. Based on the risk score of the model, patients in the low-risk group showed a better mOS than those in the high-risk group (mOS: 2.75 vs 1.08 years, HR = 0.567, 95%CI: 0.492-0.654; P < 0.001).

Conclusions

PTPRD/PTPRT mutations may be a potential biomarker for predicting ICI treatment responsiveness in multiple cancer types.
An allergenic plant calmodulin from Artemisia pollen primes human DCs leads to Th2 polarization
Authors: Zhang Yue , Hu Wenzhi , Chen Dongbo , Ding Ming , Wang Tao , Wang Yaojun , Chi Jiaoni , Li Zhimin , Li Qiang , Li Chengxin
Published: September 2022

Artemisiapollen is the major cause of seasonal allergic respiratory diseases in the northern hemisphere. About 28.57% ofArtemisiaallergic patients’ IgE can recognize ArtCaM, a novel allergenic calmodulin fromArtemisiaidentified in this study. These patients exhibited stronger allergic reactions and a longer duration of allergic symptoms. However, the signaling mechanism that triggers these allergic reactions is not fully understood. In this study, we found that extracellular ArtCaM directly induces the maturation of human dendritic cells (DCs), which is attributed to a series of Ca2+relevant cascades, including Ca2+/NFAT/CaMKs. ArtCaM alone induces inflammatory response toward Th1, Th17, and Treg. Interestingly, a combination of ArtCaM and anti-ArtCaM IgE led to Th2 polarization. The putative mechanism is that anti-ArtCaM IgE partially blocks the ArtCaM-induced ERK signal, but does not affect Ca2+-dependent cascades. The crosstalk between ERK and Ca2+signal primes DCs maturation and Th2 polarization. In summary, ArtCaM related to clinical symptoms when combined with anti-ArtCaM IgE, could be a novel allergen to activate DCs and promote Th2 polarization. Such findings provide mechanistic insights into Th2 polarization in allergic sensitization and pave the way for novel preventive and therapeutic strategies for efficient management of such pollen allergic disease.
Knowledge mapping of targeted immunotherapy for myasthenia gravis from 1998 to 2022: A bibliometric analysis
Authors: Su Yue , Ruan Zhe , Wang Rui , Hao Sijia , Tang Yonglan , Huang Xiaoxi , Gao Ting , Li Zhuyi , Chang Ting
Published: September 2022

Background

The treatment of myasthenia gravis (MG) has advanced from steroids and traditional immunosuppressants to targeted immunotherapy. Targeted immunotherapy has been successfully employed in clinical practice in recent years. This study aimed to explore the emerging trend of targeted immunotherapy in MG and summarize the knowledge structure through bibliometric methods.

Methods

The Web of Science Core Collection database (WoSCC) was chosen to retrieve the literature on targeted immunotherapy for MG. Two bibliometric analysis software, VOSviewer and CiteSpace, and bibliometric online platform were mainly used to evaluate the contributions from countries/regions, institutions, journals, and authors through the construction and visualization of bibliometric networks. By systematically reviewing a knowledge domain, future research developments were determined. The R version 4.1.2 and Microsoft Excel 365 were used for statistical analysis.

Results

A total of 562 original articles and 262 reviews relevant to MG targeted immunotherapy were included. The number of publications on targeted immunotherapy for MG exhibited a two-phase advancement. The first stage showed a steady growth trend from 1998 to 2016, with an annual number of no more than 35 publications. The second stage revealed an explosive growth trend from 2017, reaching a peak number of publications in 2020. The United States ranked first in the number of publications, citations, and h-index. The author with the highest citation and h-index was Vincent A. And 28.03% of the articles were published in the top 10 journals. In addition to “myasthenia gravis”, the keyword with the highest consideration was “rituximab”, followed by “double-blind”, which indicate research hotspots gradually from basic research to clinical research over time, especially in the field of targeted immunotherapy. The MG treatment has entered a personalized precision treatment phase. Exploration into new target molecules and conducting high-quality randomized controlled trials on existing biological agents are the further research direction.

Conclusion

The current study summarized the global research trends concerning targeted immunotherapy for MG. Research interests gradually advanced from basic research to clinical research. MG treatment has entered a personalized precision treatment phase. Further investigations into new target molecules and high-quality randomized controlled trials on existing biological agents are required urgently to direct future immunotherapy research.
Interleukin-17 as a potential therapeutic target for chronic pain
Authors: Jiang Xiaojuan , Zhou Ruihao , Zhang Yujun , Zhu Tao , Li Qian , Zhang Weiyi
Published: September 2022

Chronic pain remains to be a clinical challenge and is recognized as a major health problem with varying impacts on quality of life. Currently, the first-line therapy for chronic pain is opioids, which are often accompanied by unwanted psychoactive side effects. Thus, new and effective treatments for chronic pain are urgently needed and eagerly pursued. Inflammatory cytokines, especially interleukin-17 (IL-17), are reportedly potential therapeutic targets owing to their pivotal role in chronic pain from the neuroinflammation perspective. Recently, substantial evidence confirmed that IL-17 and IL-17 receptors (IL-17Rs) were increased in neuropathic, inflammatory, and cancer pain models. Notably, IL-17/IL-17R antibodies also reportedly relieve or cure inflammatory- and pain-related diseases. However, existing studies have reported controversial results regarding IL-17/IL-17Rs as potential therapeutic targets in diverse animal models of chronic pain. In this review, we present a summary of published studies and discuss the evidence, from basic to clinical to research, regarding the role and mechanism of action between IL-17 and diverse kinds of chronic pain in animal models and clinical patients. Furthermore, we evaluated IL-17-based therapy as a potential therapeutic strategy for inflammatory- and pain-related disease. Importantly, we also discussed clinical trials of IL-17/IL-17R targeting monoclonal antibodies. Overall, we found that IL-17 is a potential therapeutic target for chronic pain from the perspective of neuroinflammation.
CMIP6 projections of ocean warming and the impact on dimethylsulfide emissions from the Great Barrier Reef, Australia
Authors: Jackson Rebecca L. , Woodhouse Matthew T. , Gabric Albert J. , Cropp Roger A.
Published: September 2022

Coral reefs are important regional sources of biogenic sulfur to the tropical marine atmosphere, through stress-induced emissions of dimethylsulfide (DMS). Recent estimates suggest that the Great Barrier Reef (GBR), Australia emits 0.02-0.05 Tg yr-1 of DMS (equivalent to 0.010-0.026 Tg yr-1 S), with potential implications for local aerosol-cloud processes. However, the impact of ocean warming on DMS emissions from coral reefs remains uncertain, complicating efforts to improve the representation of coral reefs in DMS climatologies and climate models. We investigate the influence of predicted changes in sea surface temperature (SST), photosynthetically active radiation (PAR) and wind speed on contemporary DMS emissions from the GBR using model output from the Coupled Model Intercomparison Project Phase 6 (CMIP6). A multiple linear regression is used to calculate seawater surface DMS (DMSw) concentration in the GBR in a contemporary (2001-2020) and end-of-century (2081-2100) scenario, as simulated by CMIP6 models under a SSP2-4.5 and SSP5-8.5 Shared Socioeconomic Pathway. By the end of this century, a 1.5-3.0°C rise in annual mean SST and a 1.1-1.7 mol m-2 d-1 increase in PAR could increase DMSw concentration in the GBR by 9.2-14.5%, leading to an increase in DMS flux of 9.5-14.3%. Previous model studies have suggested that the aerosol system has a low sensitivity to relatively large changes in coral reef-derived DMS. Therefore, the predicted change in contemporary DMS emissions is unlikely to influence the regional atmosphere. Further research is needed to understand the combined effects of temperature, light, pH, salinity and ecosystem structure on DMS production in coral reefs to better predict potential changes in emissions. Nevertheless, the findings provide insight into how predicted ocean warming may affect present-day DMS emissions and the source-strength of the GBR to the atmospheric sulfur budget.
Modeling and optimization of multiple tuned mass dampers for a barge-type floating offshore wind turbine
Authors: Wang Bin , Han Dongdong , Wang Wenhua , Li Xin , Shen Kanmin , Li Ying
Published: September 2022

Significant structural responses pose potential hazards to the safe operation of floating offshore wind turbines (FOWTs). To effectively mitigate the motion of FOWTs using conventional passive vibration control methods such as tuned mass damper (TMD) and multiple tuned mass damper (MTMD), an optimization method for TMD and MTMD in a barge-type FOWT is proposed in this study. A simplified dynamic model of a barge FOWT with MTMD, which includes the tower first bending and floating platform degrees of freedom (DOFs), in addition to the simplified DOF of the MTMD, is derived. The corresponding fully coupled numerical model is established using the updated simulation tool FAST-SC. Subsequently, the unknown parameters and accuracy of the simplified dynamic model are validated via comparison with the results of the coupled numerical model. Moreover, an optimization method is proposed based on the simplified dynamic model considering the prominent coupling effects of FOWT and computational expense, and the GA algorithm is used for TMD and MTMD optimization. Furthermore, the effectiveness of the optimized TMDs and MTMD is evaluated based on the reduction in the coupled responses of the barge FOWT under the selected environmental conditions. Compared with the optimized TMD in the nacelle, the optimized TMD in the platform and MTMD are proven to be more feasible for vibration mitigation under complex environmental loads. Moreover, an improved steady output is obtained using the optimized vibration control methods, in addition to the excellent mitigation effects on structural responses.
Prevalence and Clinical Profiling of Dysglycemia and HIV Infection in Persons With Pulmonary Tuberculosis in Brazil
Authors: Arriaga María B. , Araújo-Pereira Mariana , Barreto-Duarte Beatriz , Sales Caio , Miguez-Pinto João Pedro , Nogueira Evelyn B. , Nogueira Betânia M. F. , Rocha Michael S. , Souza Alexandra B. , Benjamin Aline , de Oliveira Jamile G. , Moreira Adriana S. R. , Queiroz Artur T. L. , Rodrigues Moreno M. S. , Spener-Gomes Renata , Figueiredo Marina C. , Durovni Betina , Cavalcante Solange , Lapa-e-Silva José R. , Kristki Afrânio L. , Cordeiro-Santos Marcelo , Sterling Timothy R. , Rolla Valeria C. , Andrade Bruno B. ,   the RePORT-Brazil consortium
Published: September 2022

Background

There are scarce data on the prevalence and disease presentation of HIV in patients with tuberculosis (TB) and dysglycemia (diabetes [DM] and prediabetes [PDM]), especially in TB-endemic countries.

Methods

We assessed the baseline epidemiological and clinical characteristics of patients with culture-confirmed pulmonary TB, enrolled in a multicenter prospective cohort in Brazil (RePORT-Brazil) during 2015–2019. Dysglycemia was defined by elevated glycated hemoglobin and stratified as PDM or DM. Additionally, we used data from TB cases obtained through the Brazilian National Notifiable Diseases Information System (SINAN), during 2015–2019. In SINAN, diagnosis of diabetes was based on self-report. Logistic regression models were performed to test independent associations between HIV, dysglycemia status, and other baseline characteristics in both cohorts.

Results

In the RePORT-Brazil cohort, the prevalence of DM and of PDM was 23.7 and 37.8%, respectively. Furthermore, the prevalence of HIV was 21.4% in the group of persons with TB-dysglycemia and 20.5% in that of patients with TBDM. In the SINAN cohort, the prevalence of DM was 9.2%, and among the TBDM group the prevalence of HIV was 4.1%. Logistic regressions demonstrated that aging was independently associated with PDM or DM in both the RePORT-Brazil and SINAN cohorts. In RePORT-Brazil, illicit drug use was associated with PDM, whereas a higher body mass index (BMI) was associated with DM occurrence. Of note, HIV was not associated with an increased risk of PDM or DM in patients with pulmonary TB in both cohorts. Moreover, in both cohorts, the TBDM-HIV group presented with a lower proportion of positive sputum smear and a higher frequency of tobacco and alcohol users.

Conclusion

There is a high prevalence of dysglycemia in patients with pulmonary TB in Brazil, regardless of the HIV status. This reinforces the idea that DM should be systematically screened in persons with TB. Presence of HIV does not substantially impact clinical presentation in persons with TBDM, although it is associated with more frequent use of recreational drugs and smear negative sputum samples during TB screening.
Follow-up of young adult monozygotic twins after simultaneous critical coronavirus disease 2019: a case report
Authors: de Castro Mateus V. , Silva Monize V. R. , Soares Flávia B. , Cória Vivian R. , Naslavsky Michel S. , Scliar Marilia O. , Castelli Erick C. , de Oliveira Jamile R. , de Medeiros Giuliana X. , Sasahara Greyce L. , Santos Keity S. , Cunha-Neto Edecio , Kalil Jorge , Zatz Mayana
Published: September 2022

Background

The influence of the host genome on coronavirus disease 2019 (COVID-19) susceptibility and severity is supported by reports on monozygotic (MZ) twins where both were infected simultaneously with similar disease outcomes, including several who died due to the SARS-CoV-2 infection within days apart. However, successive exposures to pathogens throughout life along with other environmental factors make the immune response unique for each individual, even among MZ twins.

Case presentation and methods

Here we report a case of a young adult monozygotic twin pair, who caught attention since both presented simultaneously severe COVID-19 with the need for oxygen support despite age and good health conditions. One of the twins, who spent more time hospitalized, reported symptoms of long-COVID even 7 months after infection. Immune cell profile and specific responses to SARS-CoV-2 were evaluated as well as whole exome sequencing.

Conclusion

Although the MZ twin brothers shared the same genetic mutations which may be associated with their increased risk of developing severe COVID-19, their clinical progression was different, reinforcing the role of both immune response and genetics in the COVID-19 presentation and course. Besides, post-COVID syndrome was observed in one of them, corroborating an association between the duration of hospitalization and the occurrence of long-COVID symptoms.
Comparison of the risk of gastrointestinal perforation between patients with and without rheumatoid arthritis: A nationwide cohort study in Asia
Authors: Chang Ting-Chia , Kan Wei-Chih , Cheng Kuo-Chen , Ho Chung-Han , Chen Yi-Chen , Chu Chin-Chen , Hsu Chien-Chin , Kuo Hsing-Tao , Lin Hung-Jung , Huang Chien-Cheng
Published: September 2022

Objectives

Patients with rheumatoid arthritis (RA) may have an increased risk for gastrointestinal perforation (GIP) caused by medications or chronic inflammation. However, the risk of GIP between patients with and without RA remains unclear. Therefore, we conducted this study to clarify it.

Methods

Using the Taiwan National Health Insurance Research Database, we identified patients with and without RA matched at 1:1 ratio by age, sex, and index date between 2000 and 2013 for this study. Comparison of the risk of GIP between the two cohorts was performed by following up until 2014 using Cox proportional hazard regression analyses.

Results

In total, 11,666 patients with RA and an identical number of patients without RA were identified for this study. The mean age (±standard deviation) and female ratio were 55.3 (±15.2) years and 67.6% in both cohorts. Patients with RA had a trend of increased risk for GIP than patients without RA after adjusting for underlying comorbidities, medications, and monthly income [adjusted hazard ratio (AHR) 1.42; 95% confidence interval (CI) 0.99–2.04, p = 0.055]. Stratified analyses showed that the increased risk was significant in the female population (AHR 2.06; 95% CI 1.24–3.42, p = 0.005). Older age, malignancy, chronic obstructive pulmonary disease, and alcohol abuse were independent predictors of GIP; however, NSAIDs, systemic steroids, and DMARDs were not.

Conclusion

RA may increase the risk of GIP, particularly in female patients. More attention should be paid in female population and those with independent predictors above for prevention of GIP.
Predictors of stress in patients with Lupus
Authors: Jolly Meenakshi , Katz Patricia
Published: September 2022

Background

Stress is common in patients with Systemic Lupus Erythematosus (SLE), and is associated with depression, fatigue, and disease flares. Stress may be modifiable and identifying those at high risk allows clinicians and allied health care professionals to develop a multidisciplinary management plan to direct appropriate resources. This study is aimed at identifying predictors of high stress over time among patients with SLE.

Methods

Longitudinal data from two interviews of the Lupus Outcomes Study 2 years apart from 726 patients with SLE were analyzed for stress, measured using the Perceived Stress Scale (PSS; high-stress PSS ≥6). T-test and Chi-square analyses compared patient characteristics by high-stress status. Logistic regressions were conducted with high stress as the dependent variable. Covariates included demographics, disease features, quality of life (QOL), health care utilization (HCU), and comorbidities. QoL was measured using the SF-36 form (Physical Component Score, PCS; Mental Component Score, MCS) and MOS Cognitive Functioning Scale (CFS). HCU indicated having established care with a rheumatologist, use of an emergency room or hospitalization, and quality of care. P ≤ 0.05 were considered significant.

Results

The mean age of the cohort was 50.6 (12.5) years, 92% were women and 68% were Caucasian. The mean (SD) PSS was 5.3 (3.6), and high stress (PSS >6) was noted in 253 participants. Those with high stress were more frequently below the poverty line and less commonly employed. They had a greater prevalence of comorbidities and HCU; and worse disease severity (activity, flare, damage) and QOL. In regression analyses, high stress (baseline) was associated with younger age, married status, worse QOL, and presence of diabetes. Better QOL (PCS, MCS) independently predicted decreased odds of high stress, while high stress (baseline) predicted high stress (OR 3.16, 95% CI 1.85, 5.37, p < 0.0001) at follow-up, after adjusting for demographics, disease features, HCU, and comorbidities.

Conclusion

Patients with SLE should be routinely screened for QOL and stress during their clinical care, to identify those at risk for poor health outcomes. This information can facilitate multidisciplinary management for those at risk for worse health outcomes.
A rapid colorimetric lateral flow test strip for detection of live Salmonella Enteritidis using whole phage as a specific binder
Authors: Charlermroj Ratthaphol , Makornwattana Manlika , Phuengwas Sudtida , Karoonuthaisiri Nitsara
Published: September 2022

Specific antibodies are essential components of immunoassay, which can be applied for the detection of pathogens. However, producing an antibody specific to live bacterial pathogens by the classical method of immunizing animals with live pathogens can be impractical. Phage display technology is an effective alternative method to obtain antibodies with the desired specificity against selected antigenic molecules. In this study, we demonstrated the power of a microarray-based technique for obtaining specific phage-derived antibody fragments against Salmonella, an important foodborne pathogen. The selected phage-displayed antibody fragments were subsequently employed to develop a lateral flow test strip assay for the detection of live Salmonella. The test strips showed specificity to Salmonella Enteritidis without cross-reactivity to eight serovars of Salmonella or other bacteria strains. The test strip assay requires 15 min, whereas the conventional biochemical and serological confirmation test requires at least 24 h. The microarray screening technique for specific phage-based binders and the test strip method can be further applied to other foodborne pathogens.
A reporter cell line for the automated quantification of SARS-CoV-2 infection in living cells
Authors: Desmarets Lowiese , Callens Nathalie , Hoffmann Eik , Danneels Adeline , Lavie Muriel , Couturier Cyril , Dubuisson Jean , Belouzard Sandrine , Rouillé Yves
Published: September 2022

The SARS-CoV-2 pandemic and the urgent need for massive antiviral testing highlighted the lack of a good cell-based assay that allowed for a fast, automated screening of antivirals in high-throughput content with minimal handling requirements in a BSL-3 environment. The present paper describes the construction of a green fluorescent substrate that, upon cleavage by the SARS-CoV-2 main protease, re-localizes from the cytoplasm in non-infected cells to the nucleus in infected cells. The construction was stably expressed, together with a red fluorescent nuclear marker, in a highly susceptible clone derived from Vero-81 cells. With this fluorescent reporter cell line, named F1G-red, SARS-CoV-2 infection can be scored automatically in living cells by comparing the patterns of green and red fluorescence signals acquired by automated confocal microscopy in a 384-well plate format. We show the F1G-red system is sensitive to several SARS-CoV-2 variants of concern and that it can be used to assess antiviral activities of compounds in dose–response experiments. This high-throughput system will provide a reliable tool for antiviral screening against SARS-CoV-2.
Potential roles of gut microbes in biotransformation of natural products: An overview
Authors: Zhao Yucui , Zhong Xinqin , Yan Junyuan , Sun Congying , Zhao Xin , Wang Xiaoying
Published: September 2022

Natural products have been extensively applied in clinical practice, characterized by multi-component and multi-target, many pharmacodynamic substances, complex action mechanisms, and various physiological activities. For the oral administration of natural products, the gut microbiota and clinical efficacy are closely related, but this relationship remains unclear. Gut microbes play an important role in the transformation and utilization of natural products caused by the diversity of enzyme systems. Effective components such as flavonoids, alkaloids, lignans, and phenols cannot be metabolized directly through human digestive enzymes but can be transformed by enzymes produced by gut microorganisms and then utilized. Therefore, the focus is paid to the metabolism of natural products through the gut microbiota. In the present study, we systematically reviewed the studies about gut microbiota and their effect on the biotransformation of various components of natural products and highlighted the involved common bacteria, reaction types, pharmacological actions, and research methods. This study aims to provide theoretical support for the clinical application in the prevention and treatment of diseases and provide new ideas for studying natural products based on gut biotransformation.
Rhodococcus strains as a good biotool for neutralizing pharmaceutical pollutants and obtaining therapeutically valuable products: Through the past into the future
Authors: Ivshina Irina , Bazhutin Grigory , Tyumina Elena
Published: September 2022

Active pharmaceutical ingredients present a substantial risk when they reach the environment and drinking water sources. As a new type of dangerous pollutants with high chemical resistance and pronounced biological effects, they accumulate everywhere, often in significant concentrations (μg/L) in ecological environments, food chains, organs of farm animals and humans, and cause an intense response from the aquatic and soil microbiota. Rhodococcus spp. (Actinomycetia class), which occupy a dominant position in polluted ecosystems, stand out among other microorganisms with the greatest variety of degradable pollutants and participate in natural attenuation, are considered as active agents with high transforming and degrading impacts on pharmaceutical compounds. Many representatives of rhodococci are promising as unique sources of specific transforming enzymes, quorum quenching tools, natural products and novel antimicrobials, biosurfactants and nanostructures. The review presents the latest knowledge and current trends regarding the use of Rhodococcus spp. in the processes of pharmaceutical pollutants’ biodegradation, as well as in the fields of biocatalysis and biotechnology for the production of targeted pharmaceutical products. The current literature sources presented in the review can be helpful in future research programs aimed at promoting Rhodococcus spp. as potential biodegraders and biotransformers to control pharmaceutical pollution in the environment.