bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heat shock protein 90 inhibition attenuates inflammation in models of atopic dermatitis: a novel mechanism of action
Authors: Ben Abdallah Hakim , Bregnhøj Anne , Ghatnekar Gautam , Iversen Lars , Johansen Claus 
Published: January 2024

BackgroundHeat shock protein 90 (HSP90) is an important chaperone supporting the function of many proinflammatory client proteins. Recent studies indicate HSP90 inhibition may be a novel mechanism of action for inflammatory skin diseases; however, this has not been explored in atopic dermatitis (AD).ObjectivesOur study aimed to investigate HSP90 as a novel target to treat AD.MethodsExperimental models of AD were used including primary human keratinocytes stimulated with cytokines (TNF/IFNγ or TNF/IL-4) and a mouse model established by MC903 applications.ResultsIn primary human keratinocytes using RT-qPCR, the HSP90 inhibitor RGRN-305 strongly suppressed the gene expression of Th1- (TNF, IL1B, IL6) and Th2-associated (CCL17, CCL22, TSLP) cytokines and chemokines related to AD. We next demonstrated that topical and oral RGRN-305 robustly suppressed MC903-induced AD-like inflammation in mice by reducing clinical signs of dermatitis (oedema and erythema) and immune cell infiltration into the skin (T cells, neutrophils, mast cells). Interestingly, topical RGRN-305 exhibited similar or slightly inferior efficacy but less weight loss compared with topical dexamethasone. Furthermore, RNA sequencing of skin biopsies revealed that RGRN-305 attenuated MC903-induced transcriptome alterations, suppressing genes implicated in inflammation including AD-associated cytokines (Il1b, Il4, Il6, Il13), which was confirmed by RT-qPCR. Lastly, we discovered using Western blot that RGRN-305 disrupted JAK-STAT signaling by suppressing the activity of STAT3 and STAT6 in primary human keratinocytes, which was consistent with enrichment analyses from the mouse model.ConclusionHSP90 inhibition by RGRN-305 robustly suppressed inflammation in experimental models mimicking AD, proving that HSP90 inhibition may be a novel mechanism of action in treating AD.
A viral-specific CD4+ T cell response protects female mice from Coxsackievirus B3 infection
Authors: Pattnaik Aryamav , Dhalech Adeeba H. , Condotta Stephanie A. , Corn Caleb , Richer Martin J. , Snell Laura M. , Robinson Christopher M. 
Published: January 2024

BackgroundBiological sex plays an integral role in the immune response to various pathogens. The underlying basis for these sex differences is still not well defined. Here, we show that Coxsackievirus B3 (CVB3) induces a viral-specific CD4+ T cell response that can protect female mice from mortality.MethodsWe inoculated C57BL/6 Ifnar-/- mice with CVB3. We investigated the T cell response in the spleen and mesenteric lymph nodes in male and female mice following infection.ResultsWe found that CVB3 can induce expansion of CD62Llo CD4+ T cells in the mesenteric lymph node and spleen of female but not male mice as early as 5 days post-inoculation, indicative of activation. Using a recombinant CVB3 virus expressing a model CD4+ T cell epitope, we found that this response is due to viral antigen and not bystander activation. Finally, the depletion of CD4+ T cells before infection increased mortality in female mice, indicating that CD4+ T cells play a protective role against CVB3 in our model.ConclusionsOverall, these data demonstrated that CVB3 can induce an early CD4 response in female but not male mice and further emphasize how sex differences in immune responses to pathogens affect disease.
Low grade of satisfaction related to the use of current systemic therapies among pustular psoriasis patients: a therapeutic unmet need to be fulfilled
Authors: Coscarella Giulia , Falco Gennaro Marco , Palmisano Gerardo , Ippoliti Elena , De Luca Eleonora , Gori Niccolò , Di Nardo Lucia , Caldarola Giacomo , De Simone Clara , Chiricozzi Andrea , Peris Ketty 
Published: January 2024

IntroductionPustular psoriasis is considered a separate entity from plaque psoriasis and can be categorized as generalized pustular psoriasis (GPP), acrodermatitis continua of Hallopeau, or palmoplantar pustulosis (PPP). Current guidelines mostly include treatment options that have not been specifically developed for the treatment of pustular psoriasis. The majority of them does not have indication for the treatment of pustular psoriasis. Their effectiveness and safeness have been described in small cohort-based studies or case series with a low level of evidence. Previous studies evaluated treatment response through physician-based assessment but none reported patient satisfaction to treatment, quality of life and patient perception of disease severity during systemic therapies, particularly with biologics commonly used in plaque psoriasis. This study aimed to investigate patient satisfaction to treatment and patients’ quality of life during treatment, correlating patient-reported outcomes with residual disease severity.MethodsA cross-sectional, cohort-based, single center study included patients affected by pustular psoriasis undergoing treatment with systemic agents. Demographic, clinical characteristics were collected. Treatment satisfaction as well as disease severity were assessed through dedicated assessment scores.ResultsA total of 31 patients affected by GPP or PPP were included. Despite biologic treatment, 80.6% of patients continued to experience mild-to-severe disease activity, with discrepancies between patient and physician assessments. Patients reported a substantial impairment in their quality of life, with notable limitations in physical activity and emotional distress. Mental health conditions, such as depression and anxiety disorders, were common. Treatment satisfaction varied, with moderate scores for effectiveness and convenience. Only a small proportion of patients (41.9%) reported complete or high overall treatment satisfaction. GPP and PPP subcohorts exhibited similar quality of life and treatment satisfaction levels.DiscussionThis study highlights the suboptimal control of PP despite biologic therapies, resulting in a significant impact on patients’ quality of life and treatment satisfaction. The findings highlight the need for specific therapies and standardized guidelines for managing PP. New targeted therapies, such as spesolimab, hold promise for optimizing treatment satisfaction and improving patients’ quality of life in this challenging condition. Future research should focus on refining treatment strategies to address the unmet needs of PP patients comprehensively.
Association between gut microbiota and peptic ulcer disease, particularly gastric ulcer and duodenal ulcer: a two-sample Mendelian randomization study
Authors: Dong Zhenhua , Yu Kai , Xin Yuchao , Gao Xulei , Bu Fan , Zhao Dingliang , Ren Donghui , Lu Ji , Wang Daguang 
Published: January 2024

BackgroundRecent an observational study has suggested a potential connection between gut microbiota (GM) and peptic ulcer diseases (PUDs), particularly gastric ulcer (GU) and duodenal ulcer (DU). However, the causal connection remains unsure.MethodsA two-sample Mendelian randomization (MR) is carried out to explore the connection between the GM and DU or GU. Data on the GM comes from the MiBioGend database, and GU or DU data are based on the FinnGen database. One group of single nucleotide polymorphisms (SNPs) (P &lt; 5 × 10−8) are served as instrumental variables (IVs). To obtain a more comprehensive conclusion, the other SNPs (P &lt; 1 × 10−5) are selected as IVs. Inverse variance weighting (IVW) is used to determine the causal relationship.ResultsAt the level of P &lt; 1 × 10−5, the IVW analysis suggests that Clostridiaceae1, Butyriccoccus, and Peptcoccus have harmful effects on GU, while LachnospiraceaeUCG004 and MollicutesRF9 have beneficial effects on GU. Then, in the case of DU, the IVW analysis suggested that Lentisphaeria, Negativicutes, Clostridiaceae1, ClostridiumseMnsustricto1, ErysipelotrichaceaeUCG003, LachnospiraceaeNC2004group, Selenomonadale, Victivallales, and Lentisphaerae have harmful effects, while Catenibacterium, Escherichia.Shigella, LachnospiraceaeUCG008, and Sutterella have beneficial effects. When P &lt; 5 × 10−8, IVW analysis suggests that GM has no significant influence on GU or DU.ConclusionThis two-sample MR indicates a causal relationship between GM and GU or DU.
Unlocking the potential of Rosa roxburghii Tratt polyphenol: a novel approach to treating acute lung injury from a perspective of the lung-gut axis
Authors: Tang Li , Zhang Shuo , Zhang Min , Wang Pengjiao , Liang Guiyou , Gan Zhitong , Gao Xiuli 
Published: January 2024

IntroductionAcute lung injury (ALI) is a serious respiratory disease characterized by progressive respiratory failure with high morbidity and mortality. It is becoming increasingly important to develop functional foods from polyphenol-rich medicinal and dietary plants in order to prevent or alleviate ALI by regulating intestinal microflora. Rosa roxburghii Tratt polyphenol (RRTP) has significant preventive and therapeutic effects on lipopolysaccharide-induced ALI mice, but its regulatory effects on gut homeostasis in ALI mice remains unclear.MethodsThis study aims to systematically evaluate the ameliorative effects of RRTP from the perspective of “lung-gut axis” on ALI mice by intestine histopathological assessment, oxidative stress indicators detection and short-chain fatty acids (SCFAs) production, and then explore the modulatory mechanisms of RRTP on intestinal homeostasis by metabolomics and gut microbiomics of cecal contents.ResultsThe results showed that RRTP can synergistically exert anti-ALI efficacy by significantly ameliorating intestinal tissue damage, inhibiting oxidative stress, increasing SCFAs in cecal contents, regulating the composition and structure of intestinal flora, increasing Akkermansia muciniphila and modulating disordered intestinal endogenous metabolites.DiscussionThis study demonstrated that RRTP has significant advantages in adjuvant therapy of ALI, and systematically clarified its comprehensive improvement mechanism from a new perspective of “lung-gut axis”, which provides a breakthrough for the food and healthcare industries to develop products from botanical functional herbs and foods to prevent or alleviate ALI by regulating intestinal flora.
Pan-cancer analysis of SERPINE family genes as biomarkers of cancer prognosis and response to therapy
Authors: Liu Yating , Li Xinyu , Chen Shanshan , Zhu Changyu , Shi Yijun , Dang Shoutao , Zhang Weitao , Li Wei 
Published: January 2024

Background: Serine protease inhibitor E (SERPINE) family genes participate in the tumor growth, cancer cell survival and metastasis. However, the SERPINE family members role in the prognosis and their clinical therapeutic potentials in various human cancer types have not been elaborately explored.Methods: We preliminarily analyzed expression levels and prognostic values of SERPINE family genes, and investigated the correlation between SERPINEs expression and tumor microenvironment (TME), Stemness score, clinical characteristic, immune infiltration, tumor mutational burden (TMB), immune subtype, and drug sensitivity in pan-cancer, which based on updated public databases and integrated some bioinformatics analysis methods. In addition, we conducted the enrichment analysis of SERPINEs from DAVID and KOBAS databases.Results: SERPINE1, SERPINE2, and SERPINE3 expression were upregulated in nine cancers, twelve cancers, and six cancers, respectively. The expression of SERPINE family genes was associated with the prognosis in several cancers from The Cancer Genome Atlas (TCGA). Furthermore, SERPINE family genes expression also had a significant relation to stromal and immune scores, and RNA stemness score and DNA stemness score in pan-cancer. SERPINE1 and SERPINE2 expression significantly increased in tumor advanced stage in colon adenocarcinoma (COAD). Results showed that SERPINE1 and SERPINE2 expression were negatively related with B cells and Monocytes, respectively. SERPINE2 expression had a significantly positive relation with B cells and Macrophages. In terms of TMB, SERPINE1, SERPINE2, and SERPINE3 were found to associated with TMB in seven cancers, fourteen cancers, and four cancers, respectively. Moreover, all SERPINE gene family members were significantly correlated with immune subtypes. SERPINE1 expression had a significantly positive or negative correlation with drug sensitivity.Conclusion: The study indicated the great potential of SERPINE family genes as biomarkers for prognosis and provided valuable strategies for further investigation of SERPINE family genes as potential targets in cancer.
Loss of filamentous actin, tight junction protein expression, and paracellular barrier integrity in frataxin-deficient human brain microvascular endothelial cells—implications for blood-brain barrier physiology in Friedreich’s ataxia
Authors: Smith Frances M. , Kosman Daniel J. 
Published: January 2024

Introduction: Friedreich’s Ataxia (FRDA) is the most prevalent inherited ataxia. FRDA results from loss of Frataxin (FXN), an essential mitochondrial iron trafficking protein. FRDA starts with an early burst of neurodegeneration of the dorsal root ganglion and cerebellar dentate nuclei, followed by progressive brain iron accumulation in the latter. End stage disease includes cardiac fibrosis that contributes to hypertrophic cardiomyopathy. The microvasculature plays an essential barrier role in both brain and heart homeostasis, thus an investigation of this tissue system in FRDA is essential to the delineation of the cellular dysfunction in this genetic disorder. Previous reports have identified cytoskeletal alterations in non-barrier forming FRDA cell models, but physiological consequences are limited.Methods: We investigated brain microvascular endothelial cell integrity in FRDA in a model of the blood-brain barrier (BBB). We have knocked down FXN in immortalized human brain microvascular endothelial cells (hBMVEC), which compose the microcapillaries of the BBB, by using shRNA. We confirmed known cellular pathophysiologies of FXN-knockdown including decreased energy metabolism, markers of oxidative stress, and increased cell size.Results: We investigated cytoskeletal architecture, identifying decreased filamentous actin and Occludin and Claudin-5 tight junction protein expression in shFXN hBMVECs. This was consistent with decreased transendothelial electrical resistance (TEER) and increased paracellular tracer flux during early barrier formation. shFXN hBMVEC start with only 67% barrier integrity of the controls, and flux a paracellular tracer at 800% of physiological levels.Discussion: We identified that insufficient FXN levels in the hBMVEC BBB model causes changes in cytoskeletal architecture and tight junction protein abundance, co-incident with increased barrier permeability. Changes in the integrity of the BBB may be related to patient brain iron accumulation, neuroinflammation, neurodegeneration, and stroke. Furthermore, our findings implicate other barrier cells, e.g., the cardiac microvasculature, loci of disease pathology in FRDA.
Exploring the inhibitory potential of in silico-designed small peptides on Helicobacter pylori Hp0231 (DsbK), a periplasmic oxidoreductase involved in disulfide bond formation
Authors: Roszczenko-Jasińska Paula , Giełdoń Artur , Mazur Dominika , Spodzieja Marta , Plichta Maciej , Czaplewski Cezary , Bal Wojciech , Jagusztyn-Krynicka Elzbieta K. , Bartosik Dariusz 
Published: January 2024

Introduction:Helicobacter pylori is a bacterium that colonizes the gastric epithelium, which affects millions of people worldwide. H. pylori infection can lead to various gastrointestinal diseases, including gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. Conventional antibiotic therapies face challenges due to increasing antibiotic resistance and patient non-compliance, necessitating the exploration of alternative treatment approaches. In this study, we focused on Hp0231 (DsbK), an essential component of the H. pylori Dsb (disulfide bond) oxidative pathway, and investigated peptide-based inhibition as a potential therapeutic strategy.Methods: Three inhibitory peptides designed by computational modeling were evaluated for their effectiveness using a time-resolved fluorescence assay. We also examined the binding affinity between Hp0231 and the peptides using microscale thermophoresis.Results and discussion: Our findings demonstrate that in silico-designed synthetic peptides can effectively inhibit Hp0231-mediated peptide oxidation. Targeting Hp0231 oxidase activity could attenuate H. pylori virulence without compromising bacterial viability. Therefore, peptide-based inhibitors of Hp0231 could be candidates for the development of new targeted strategy, which does not influence the composition of the natural human microbiome, but deprive the bacterium of its pathogenic properties.
One-year retention of gait speed improvement in stroke survivors after treatment with a wearable home-use gait device
Authors: Darcy Brianne , Rashford Lauren , Tsai Nancey T. , Huizenga David , Reed Kyle B. , Bamberg Stacy J. M. 
Published: January 2024

BackgroundGait impairments after stroke are associated with numerous physical and psychological consequences. Treatment with the iStride® gait device has been shown to facilitate improvements to gait function, including gait speed, for chronic stroke survivors with hemiparesis. This study examines the long-term gait speed changes up to 12 months after treatment with the gait device.MethodsEighteen individuals at least one-year post-stroke completed a target of 12, 30-minute treatment sessions with the gait device in their home environment. Gait speed was measured at baseline and five follow-up sessions after the treatment period: one  week, one  month, three months, six months, and 12 months. Gait speed changes were analyzed using repeated-measures ANOVA from baseline to each follow-up time frame. Additional analysis included comparison to the minimal clinically important difference (MCID), evaluation of gait speed classification changes, and review of subjective questionnaires.ResultsParticipants retained an average gait speed improvement &gt;0.21 m/s compared to baseline at all post-treatment time frames. Additionally, 94% of participants improved their gait speed beyond the MCID during one or more post-treatment measurements, and 88% subjectively reported a gait speed improvement.ConclusionTreatment with the gait device may result in meaningful, long-term gait speed improvement for chronic stroke survivors with hemiparetic gait impairments.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03649217, identifier NCT03649217.
The relationship between obstructive sleep apnea and visual hallucinations in PD patients: a polysomnography study
Authors: Zhu Jun , Zhao Yang , Jiang Yinyin , Pan Yang , Jiang Xu , Wang Yaxi , Li Dongfong , Zhang Li 
Published: January 2024

PurposeParkinson's disease (PD) patients frequently experience visual hallucinations (VHs) and obstructive sleep apnea (OSA). The aim of this study was to describe the prevalence and clinical correlates of VHs and OSA in the Chinese population with PD.Materials and methodsA sample of 489 PD patients was recruited for the present study. Patients were categorized as having formed VHs (FVHs) or minor VHs (MVHs) or as non-hallucinators (NVHs) according to the Unified Parkinson's Disease Rating Scale (UPDRS) and an initial questionnaire. Polysomnography (PSG) was used for objective assessment of sleep.ResultsVHs were observed in 143 (29.2%) patients. Among them, 75 of the hallucinators experienced MVHs, and 68 experienced FVHs. The disease duration, UPDRS Part III score, Hoehn and Yahr (H–Y) stage, Pittsburgh Sleep Quality Index (PSQI) score and rapid eye movement (REM) sleep behavior disorder (RBD) score of hallucinators were significantly greater than those of non-hallucinators (P &lt; 0.05). We also observed OSA in 38.7, 54.7, and 63.3% of the NVH, MVH, and FVH groups, respectively. PSG showed that the VH groups had a lower total sleep time, lower sleep efficiency, higher arousal index, lower sleep latency, lower N1%, higher apnea-hypopnea index (AHI), higher average duration of apnea, higher respiratory-related arousal (RRA), and lower values of the lowest O2 and mean O2. The forward binary logistic regression model showed that AHI, N1%, RRA and lowest O2 were independently associated with VHs in PD patients.ConclusionsOur results confirm the high prevalence of VHs and OSA as well as their relationship in patients with PD.
Metabolic alterations in the right anterior insula among patients with cirrhosis without overt hepatic encephalopathy: a magnetic resonance spectroscopy study
Authors: Huang Nao-Xin , Huang Hui-Wei , Dong Qiu-Yi , Wen Yu-Lin , Li Dan , Li Jian-Qi , Chen Hua-Jun 
Published: January 2024

PurposeWe investigated metabolic alterations in the right anterior insula (rAI) in cirrhotic patients and determined its association with patients' cognitive dysfunction.MethodsIn this study, 31 healthy controls (HCs) and 32 cirrhotic patients without overt hepatic encephalopathy participated. Both blood ammonia level and Child-Pugh score were measured. The psychometric hepatic encephalopathy score (PHES) was used to evaluate cognitive function. 1H-magnetic resonance spectroscopy (MRS) data located in the rAI were recorded on a commercially available 3T magnetic resonance imaging scanner. The ratios of metabolites were measured, including N-acetylaspartate (NAA)/total creatine (tCr), glutamate plus glutamine (Glx)/tCr, myo-inositol (mI)/tCr, and total choline (tCho)/tCr. We adopted the non-parametric Mann–Whitney U-test for intergroup comparison of metabolic ratios. To determine the association between metabolite concentration and clinical parameters, we performed Spearman correlation analyses.ResultsPatients with cirrhosis performed worse on PHES in comparison with HCs (P &lt; 0.001). Patients with cirrhosis had significantly decreased mI/tCr (0.87 ± 0.07 vs. 0.74 ± 0.19, P = 0.025) and increased Glx/tCr (1.79 ± 0.17 vs. 2.07 ± 0.29, P &lt; 0.001) in the rAI. We did not observe any significant between-group differences in tCho/tCr and NAA/tCr. The blood ammonia level was correlated with Glx/tCr (r = 0.405, P = 0.022) and mI/tCr (r = −0.398, P = 0.024) of the rAI. In addition, PHES was negatively correlated with Glx/tCr of the rAI (r = −0.379, P = 0.033).ConclusionMetabolic disturbance of the rAI, which is associated with ammonia intoxication, might account for the neural substrate of cirrhosis-related cognitive dysfunction to some extent.