bluuebunny/crossref_metadata_2025 huggingface dataset:
Intestinal immune responses to commensal and pathogenic protozoa
Authors: Sardinha-Silva Aline , Alves-Ferreira Eliza V. C. , Grigg Michael E.
Published: September 2022

The physical barrier of the intestine and associated mucosal immunity maintains a delicate homeostatic balance between the host and the external environment by regulating immune responses to commensals, as well as functioning as the first line of defense against pathogenic microorganisms. Understanding the orchestration and characteristics of the intestinal mucosal immune response during commensal or pathological conditions may provide novel insights into the mechanisms underlying microbe-induced immunological tolerance, protection, and/or pathogenesis. Over the last decade, our knowledge about the interface between the host intestinal mucosa and the gut microbiome has been dominated by studies focused on bacterial communities, helminth parasites, and intestinal viruses. In contrast, specifically how commensal and pathogenic protozoa regulate intestinal immunity is less well studied. In this review, we provide an overview of mucosal immune responses induced by intestinal protozoa, with a major focus on the role of different cell types and immune mediators triggered by commensal (Blastocystisspp. andTritrichomonasspp.) and pathogenic (Toxoplasma gondii,Giardia intestinalis,Cryptosporidium parvum) protozoa. We will discuss how these various protozoa modulate innate and adaptive immune responses induced in experimental models of infection that benefit or harm the host.
An intranasal stringent response vaccine targeting dendritic cells as a novel adjunctive therapy against tuberculosis
Authors: Karanika Styliani , Gordy James T. , Neupane Pranita , Karantanos Theodoros , Ruelas Castillo Jennie , Quijada Darla , Comstock Kaitlyn , Sandhu Avinaash K. , Kapoor Aakanksha R. , Hui Yinan , Ayeh Samuel K. , Tasneen Rokeya , Krug Stefanie , Danchik Carina , Wang Tianyin , Schill Courtney , Markham Richard B. , Karakousis Petros C.
Published: September 2022

Lengthy tuberculosis (TB) treatment is required to overcome the ability of a subpopulation of persistentMycobacterium tuberculosis(Mtb) to remain in a non-replicating, antibiotic-tolerant state characterized by metabolic remodeling, including induction of the RelMtb-mediated stringent response. We developed a novel therapeutic DNA vaccine containing a fusion of therelMtbgene with the gene encoding the immature dendritic cell-targeting chemokine, MIP-3α/CCL20. To augment mucosal immune responses, intranasal delivery was also evaluated. We found that intramuscular delivery of theMIP-3α/relMtb(fusion) vaccine or intranasal delivery of therelMtb(non-fusion) vaccine potentiate isoniazid activity more than intramuscular delivery of the DNA vaccine expressingrelMtbalone in a chronic TB mouse model (absolute reduction ofMtbburden: 0.63 log10and 0.5 log10colony-forming units, respectively; P=0.0002 and P=0.0052), inducing pronouncedMtb-protective immune signatures. The combined approach involving intranasal delivery of the DNAMIP-3α/relMtbfusion vaccine demonstrated the greatest mycobactericidal activity together with isoniazid when compared to each approach alone (absolute reduction ofMtbburden: 1.13 log10, when compared to the intramuscular vaccine targetingrelMtbalone; P<0.0001), as well as robust systemic and local Th1 and Th17 responses. This DNA vaccination strategy may be a promising adjunctive approach combined with standard therapy to shorten curative TB treatment, and also serves as proof of concept for treating other chronic bacterial infections.
Telomere-related gene risk model for prognosis and drug treatment efficiency prediction in kidney cancer
Authors: Li Song-Chao , Jia Zhan-Kui , Yang Jin-Jian , Ning Xiang-hui
Published: September 2022

Kidney cancer is one of the most common urological cancers worldwide, and kidney renal clear cell cancer (KIRC) is the major histologic subtype. Our previous study found that von-Hippel Lindau (VHL) gene mutation, the dominant reason for sporadic KIRC and hereditary kidney cancer-VHL syndrome, could affect VHL disease-related cancers development by inducing telomere shortening. However, the prognosis role of telomere-related genes in kidney cancer has not been well discussed. In this study, we obtained the telomere-related genes (TRGs) from TelNet. We obtained the clinical information and TRGs expression status of kidney cancer patients in The Cancer Genome Atlas (TCGA) database, The International Cancer Genome Consortium (ICGC) database, and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. Totally 353 TRGs were differential between tumor and normal tissues in the TCGA-KIRC dataset. The total TCGA cohort was divided into discovery and validation TCGA cohorts and then using univariate cox regression, lasso regression, and multivariate cox regression method to conduct data analysis sequentially, ten TRGs (ISG15, RFC2, TRIM15, NEK6, PRKCQ, ATP1A1, ELOVL3, TUBB2B, PLCL1, NR1H3) risk model had been constructed finally. The kidney patients in the high TRGs risk group represented a worse outcome in the discovery TCGA cohort (p<0.001), and the result was validated by these four cohorts (validation TCGA cohort, total TCGA cohort, ICGC cohort, and CPTAC cohort). In addition, the TRGs risk score is an independent risk factor for kidney cancer in all these five cohorts. And the high TRGs risk group correlated with worse immune subtypes and higher tumor mutation burden in cancer tissues. In addition, the high TRGs risk group might benefit from receiving immune checkpoint inhibitors and targeted therapy agents. Moreover, the proteins NEK6, RF2, and ISG15 were upregulated in tumors both at the RNA and protein levels, while PLCL1 and PRKCQ were downregulated. The other five genes may display the contrary expression status at the RNA and protein levels. In conclusion, we have constructed a telomere-related genes risk model for predicting the outcomes of kidney cancer patients, and the model may be helpful in selecting treatment agents for kidney cancer patients.
Improving the ischemia-reperfusion injury in vascularized composite allotransplantation: Clinical experience and experimental implications
Authors: He Jiqiang , Khan Umar Zeb , Qing Liming , Wu Panfeng , Tang Juyu
Published: September 2022

Long-time ischemia worsening transplant outcomes in vascularized composite allotransplantation (VCA) is often neglected. Ischemia-reperfusion injury (IRI) is an inevitable event that follows reperfusion after a period of cold static storage. The pathophysiological mechanism activates local inflammation, which is a barrier to allograft long-term immune tolerance. The previous publications have not clearly described the relationship between the tissue damage and ischemia time, nor the rejection grade. In this review, we found that the rejection episodes and rejection grade are usually related to the ischemia time, both in clinical and experimental aspects. Moreover, we summarized the potential therapeutic measures to mitigate the ischemia-reperfusion injury. Compare to static preservation, machine perfusion is a promising method that can keep VCA tissue viability and extend preservation time, which is especially beneficial for the expansion of the donor pool and better MHC-matching.
Pre-existing humoral immunity and complement pathway contribute to immunogenicity of adeno-associated virus (AAV) vector in human blood
Authors: Smith Corinne J. , Ross Nikki , Kamal Ali , Kim Kevin Y. , Kropf Elizabeth , Deschatelets Pascal , Francois Cedric , Quinn William J. , Singh Inderpal , Majowicz Anna , Mingozzi Federico , Kuranda Klaudia
Published: September 2022

AAV gene transfer is a promising treatment for many patients with life-threatening genetic diseases. However, host immune response to the vector poses a significant challenge for the durability and safety of AAV-mediated gene therapy. Here, we characterize the innate immune response to AAV in human whole blood. We identified neutrophils, monocyte-related dendritic cells, and monocytes as the most prevalent cell subsets able to internalize AAV particles, while conventional dendritic cells were the most activated in terms of the CD86 co-stimulatory molecule upregulation. Although low titers (≤1:10) of AAV neutralizing antibodies (NAb) in blood did not have profound effects on the innate immune response to AAV, higher NAb titers (≥1:100) significantly increased pro-inflammatory cytokine/chemokine secretion, vector uptake by antigen presenting cells (APCs) and complement activation. Interestingly, both full and empty viral particles were equally potent in inducing complement activation and cytokine secretion. By using a compstatin-based C3 and C3b inhibitor, APL-9, we demonstrated that complement pathway inhibition lowered CD86 levels on APCs, AAV uptake, and cytokine/chemokine secretion in response to AAV. Together these results suggest that the pre-existing humoral immunity to AAV may contribute to trigger adverse immune responses observed in AAV-based gene therapy, and that blockade of complement pathway may warrant further investigation as a potential strategy for decreasing immunogenicity of AAV-based therapeutics.
Reef effect of offshore structures on the occurrence and foraging activity of harbour porpoises
Authors: Fernandez-Betelu Oihane , Graham Isla M. , Thompson Paul M.
Published: September 2022

With increasing numbers of offshore structures being installed and decommissioned, a better understanding of their effect on marine predators is timely. There is some evidence that oil and gas platforms may attract marine mammals, acting as artificial reefs. However, it is unclear whether different man-made structure designs have similar effects or whether artificial structures modify the diel patterns of occurrence and foraging of marine mammals. Here, we used passive acoustics to investigate the occurrence and foraging activity of harbour porpoises (Phocoena phocoena) around four artificial structures of different age and complexity. We deployed an array of echolocation click detectors (CPODs) in 2021, along a gradient of distances to these structures and assessed the extent to which porpoises were attracted to them and their effect on porpoises’ diel patterns of occurrence and foraging activity. The probability of porpoise occurrence and foraging activity decreased with distance from offshore structures. A significant increase in porpoise occurrence and foraging was detected during night-time compared to daytime around all four offshore structures (< 200 m). Comparing pre- and post-installation porpoise detections, the daily patterns of occurrence and foraging activity shifted from a weak diel pattern before the structure was installed, to a strong nocturnal pattern when the structure was present. These findings provide evidence that marine mammals are attracted to man-made structures and that porpoises modify their diel patterns of occurrence and foraging activity around them. This research suggests that offshore structures play an important role as foraging areas for some marine mammals and provides key information for decommissioning considerations and the planning of decommissioning activities.
Effects of dietary pyrroloquinoline quinone on growth performance, serum biochemical parameters, antioxidant status, and growth-related genes expressions in juvenile yellow catfish, Pelteobagrus fulvidraco
Authors: Shi Qingchao , Wen Zhengyong , Wang Jun , Hu Peng , Zou Yuanchao , Wang Shuqi , Qin Chuanjie
Published: September 2022

This study aimed to evaluate the impacts of dietary pyrroloquinoline quinone (PQQ) supplement on growth performance, serum biochemical parameters, antioxidant status, and growth-related genes expressions in juvenile yellow catfish, Pelteobagrus fulvidraco. Triplicate groups of fish (n = 40) with an average weight of 5 g were fed with five gradient levels PQQ-incorporated diets (0 (basal), 1.5 mg/kg; 3.0 mg/kg; 4.5 mg/kg, 6.0 mg/kg) for 56 days. Our findings revealed that fish fed with the diets containing PQQ at the level of 3.0-6.0 mg/kg showed significantly higher final body weight, weight gain rate, and specific growth rate than those of that in the control group (P < 0.05). The activities of protease were observed significantly increased in fish fed with diets containing 4.5 mg/kg and 6 mg/kg PQQ (P < 0.05). Meanwhile, fish in 4.5 mg/kg PQQ group showed significantly lower levels of serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol, and significantly higher level of the high-density lipoprotein cholesterol (P < 0.05). The antioxidant-related parameters of superoxide dismutase and total antioxidant capacity were markedly elevated (P < 0.05), while malondialdehyde content was significantly reduced in 3.0-6.0 mg/kg PQQ group (P < 0.05). Meanwhile, the mRNA expression levels of growth-related genes (growth hormone, insulin-like growth factor 1, and insulin-like growth factor 2) were dramatically up-regulated in the liver of fish fed with the diets containing 3-6 mg/kg PQQ in comparison with the control group (P < 0.05). In conclusion, dietary PQQ could improve the growth performance, serum biochemical parameters, antioxidant status, and growth-related genes expressions in juvenile yellow catfish, and the optimal dietary PQQ level was evaluated to be 4.92 mg/kg of dry diet for juvenile yellow catfish.
Effect of coconut shell nanopowder reinforcement in the development of palm fiber composites
Authors: Raja Dhas J. Edwin , Savio Lewise K. Anton , Kumar K. Naveen , Raja Vijayanandh , AL-bonsrulah Hussein A. Z. , Ahmad Hijaz , Yao Shao-Wen , Al-Bahrani Mohammed
Published: September 2022

Lightweight materials are being employed in aeronautical and automobile industries for high strength, lower weight, and energy consumption. Attention is needed to control pollution through the usage of harmful synthetic composites globally. In this work, coconut shell nanofillers are reinforced in the development of various palm fiber (leaf stalk, leaf sheath, leaf-spine, and fruit) composites using the hand layup technique. Mechanical and morphological effects of the addition of nano-coconut-shell-powder to the composites are addressed. The palm fibers are sandwiched within the glass fiber to improve the strength of composites. The addition of coconut shell nanoparticles in the composites improves the tensile, flexural, impact, hardness, and water absorption characteristics. SEM image observations on the composite indicate the buildup of nanomodified matrix residues around the fiber bundle. The adhesive property of the composite is confirmed by Fourier transform infrared spectroscopy examination, which reveals the presence of one additional alcohol/phenol OH stretch, one less alkyl CH stretch, and aromatic CH bending functional groups. The inclusion of palm fibers during the fabrication of composites facilitated the pushing of curves to higher temperatures with considerable degradation temperatures, thereby increasing thermal stability and making them suitable for thermal applications. Development of the eco-composite changes environmental impact factors aiming sustainability.
Peptides derived from hookworm anti-inflammatory proteins suppress inducible colitis in mice and inflammatory cytokine production by human cells
Authors: Cobos Claudia , Bansal Paramjit S. , Wilson David T. , Jones Linda , Zhao Guangzu , Field Matthew A. , Eichenberger Ramon M. , Pickering Darren A. , Ryan Rachael Y. M. , Ratnatunga Champa N. , Miles John J. , Ruscher Roland , Giacomin Paul R. , Navarro Severine , Loukas Alex , Daly Norelle L.
Published: September 2022

A decline in the prevalence of parasites such as hookworms appears to be correlated with the rise in non-communicable inflammatory conditions in people from high- and middle-income countries. This correlation has led to studies that have identified proteins produced by hookworms that can suppress inflammatory bowel disease (IBD) and asthma in animal models. Hookworms secrete a family of abundant netrin-domain containing proteins referred to as AIPs (Anti-Inflammatory Proteins), but there is no information on the structure-function relationships. Here we have applied a downsizing approach to the hookworm AIPs to derive peptides of 20 residues or less, some of which display anti-inflammatory effects when co-cultured with human peripheral blood mononuclear cells and oral therapeutic activity in a chemically induced mouse model of acute colitis. Our results indicate that a conserved helical region is responsible, at least in part, for the anti-inflammatory effects. This helical region has potential in the design of improved leads for treating IBD and possibly other inflammatory conditions.
Valproic-induced Fanconi syndrome: Clinical features, risk factors, diagnosis and management
Authors: Wang Chunjiang , Zhou Yulu , Song Liying , Deng Zhenzhen , Fang Weijin
Published: September 2022

Objective

Although Fanconi syndrome (FS) induced by valproate (VPA) has occasionally been reported, the detailed clinical features of the disease remain unclear. The aim of this study was to elucidate the clinical features of patients with VPA-induced FS.

Methods

We searched Chinese and English databases for all original studies, clinical reports, and case reports on VPA-induced FS published before March 2022.

Results

A total of 29 articles including 54 patients (28 males and 24 females) were included. The patients had a median age of 7 years (range 2–34 years), had severely disabled (87.0%), tube feeding (64.8%), and received an average of 1.8 medications other than VPA. The median duration of VPA treatment was 4 years (range 0.7–15.5). Pathological fractures (25.9%), unexplained fever (11.1%), muscle weakness (9.3%), and edema (9.3%) were the most common symptoms, while 18 patients were diagnosed in incidental laboratory tests. Blood tests revealed hypokalemia (69.2%), hypophosphatemia (98.0%), and hypouricemia (93.3%). Urinalysis revealed glucosuria (96.1%), proteinuria (100.0%), generalized hyperaminoaciduria (100.0 %), β2 macroglobulin (100.0%). Decreased percent total reabsorption of phosphate (%TRP) found in 94.1% of patients, and increased fractional excretion of uric acid (FEUA) were found in 100% of patients. The median time to resolution of FS after discontinuation of drug therapy was 3 months (range 0.25–18).

Conclusions

The possibility of FS needs to be considered with long-term VPA administration, especially in young, tube-fed, severely disabled patients who are co-administered with anticonvulsants. Patients receiving VPA should have regular blood and urine tests. Abnormal laboratory values returned to normal levels after VPA discontinuation.
At the limits of digital education. The importance of practical education for clinical competencies learning in the field of emergency medicine: A controlled non-randomized interventional study
Authors: Vogt Lina , Schauwinhold Michael , Rossaint Rolf , Schenkat Henning , Klasen Martin , Sopka Saša
Published: September 2022

Introduction

A high-quality education of future physicians is essential. Modern approaches interlock the acquisition of theoretical knowledge and practical skills in a spiral curriculum, leading to a mutual learning benefit for knowledge and application. This model was challenged by the elimination of hands-on trainings during the pandemic, which were often replaced by purely digital teaching models. Given the holistic nature of the spiral curriculum, we assumed that a purely digital model would have an impact on knowledge acquisition due to missing hands-on learning opportunities. The aim of the study was to investigate, using an emergency seminar as an example, whether purely digital training leads to a difference in theoretical knowledge compared to the traditional model.

Materials and methods

Study design: We used a two-groups design comparing a sample of medical students taught in 2020 with a purely digital teaching format (DF;n= 152) with a historical control group taught with a traditional format (TF;n= 1060). Subject of investigation was a seminar on emergency medicine, taking place in the 4th year. Outcome parameters: The primary outcome parameter was the students' acquired knowledge, measured by the score achieved in the final exams. Students' evaluation of the seminar was used as a secondary outcome parameter.

Results

Students in the DF group scored significantly lower than students in the TF group in the final exams. Students in the DF group rated the course significantly worse than students in the TF group.

Discussion

The study results illustrate that purely digital education leads to inferior knowledge acquisition compared to the traditional spiral curriculum. A possible explanation may lie in a deeper processing of the information (e.g., understanding the information by experience and analysis) and accordingly a better memory recall. Moreover, the students' critical appraisal of the DF may have had an unfavorable effect on learning performance. Moderating factors may be lower learning motivation or the “zoom fatigue” effect.

Conclusion

These study results clearly illustrate the importance of hands-on teaching for knowledge acquisition. The interlocking of theoretical knowledge and practical skills, as ensured by the spiral curriculum, is essential.
Transmission of anelloviruses to HIV-1 infected children
Authors: Kaczorowska Joanna , Cicilionytė Aurelija , Wahdaty Annet Firouzi , Deijs Martin , Jebbink Maarten F. , Bakker Margreet , van der Hoek Lia
Published: September 2022

Anelloviruses (AVs) are widespread in the population and infect humans at the early stage of life. The mode of transmission of AVs is still unknown, however, mother-to-child transmission, e.g., via breastfeeding, is one of the likely infection routes. To determine whether the mother-to-child transmission of AVs may still occur despite the absence of natural birth and breastfeeding, 29 serum samples from five HIV-1-positive mother and child pairs were Illumina-sequenced. The Illumina reads were mapped to an AV lineage database “Anellometrix” containing 502 distinct ORF1 sequences. Although the majority of lineages from the mother were not shared with the child, the mother and child anellomes did display a significant similarity. These findings suggest that AVs may be transmitted from mothers to their children via different routes than delivery or breastfeeding.
A circulating miR-19b-based model in diagnosis of human breast cancer
Authors: Zhao Qian , Shen Lei , Lü Jinhui , Xie Heying , Li Danni , Shang Yuanyuan , Huang Liqun , Meng Lingyu , An Xuefeng , Zhou Jieru , Han Jing , Yu Zuoren
Published: September 2022

Abstract Objective: Breast cancer (BC) is becoming the leading cause of cancer-related death in women all over the word. Identification of diagnostic biomarkers for early detection of BC is one of the most effective ways to reduce the mortality.

Methods: Plasma samples from BC patients (n = 120) and normal controls (n = 50) were collected to determine the differentially expressed circulating miRNAs in BC patients. Binary logistic regression was applied to develop miRNA diagnostic models. Receiver operating characteristic (ROC) curves were applied to calculate the area under the curve (AUC). MMTV-PYMT mammary tumor mice were used to validate the expression change of those circulating miRNAs. Plasma samples from patients with other tumor types were collected to determine the specificity of the model in diagnosis of BC.

Results: In the screening phase, 5 circulating miRNAs (miR-16, miR-17, miR-19b, miR-27a, and miR-106a) were identified as the most significantly upregulated miRNAs in plasma of BC patients. In consistence, the 5 miRNAs showed upregulation in the circulation of additional 80 BC patients in a tumor stage-dependent manner. Application of a tumor-burden mice model further confirmed upregulation of the 5 miRNAs in circulation. Based on these data, five models with diagnostic potential of BC were developed. Among the 5 miRNAs, miR-19b ranked at the top position with the highest specificity and the biggest contribution. In combination with miR-16 and miR-106a, a miR-19b-based 3-circulating miRNA model was selected as the best for further validation. Taken the samples together, the model showed 92% of sensitivity and 90% of specificity in diagnosis of BC. In addition, three other tumor types including prostate cancer, thyroid cancer and colorectal cancer further verified the specificity of the BC diagnostic model. Conclusion: The current study developed a miR-19b-based 3-miRNA model holding potential for diagnosis of BC using blood samples.
Type 2 diabetes is associated with increased risk of dementia, but not mild cognitive impairment: a cross-sectional study among the elderly in Chinese communities
Authors: Liu Guojun , Li Yong , Xu Yuzhen , Li Wei
Published: September 2022

Background: Previous studies have confirmed that diabetes is associated with cognitive impairment, but there is little data on this among older Chinese.

Methods: This study included 192 dementia patients, 610 patients with mild cognitive impairment (MCI), and 2,218 normal controls. Their general demographic information (such as gender, age, education, etc.), disease-related information (hypertension), and diabetes information (such as whether you have diabetes, course of the disease, etc) were collected by standardized questionnaires. The mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess their overall cognitive function, Moreover, 84 healthy, randomly selected older adults also underwent brain MRI scans at the same time, and the target brain regions included the hippocampus, the third, fourth, and fifth ventricles.

Results: The proportion of type 2 diabetes was significantly higher in the dementia group (25.5%) than that in the normal elderly group (15.6%) and the MCI group (17.7%). By using stepwise multiple logistics regression analysis, we found that type 2 diabetes was associated with dementia (p = 0.005*, OR = 1.805, 95%CI: 1.199–2.761), but not with MCI (p > 0.05). The volume of the fourth ventricle of the healthy elderly with diabetes was significantly larger than that of the healthy elderly without diabetes (p < 0.05), but there was no statistical difference (p > 0.05) in the volume of the hippocampus, the third ventricle, and the fifth ventricle between the two groups. However, we did not find an association between the fourth ventricle and cognitive scores (MMSE and MoCA).

Conclusions: In conclusion, type 2 diabetes in elderly Chinese people is associated with dementia, but not MCI. Type 2 diabetes may impair cognitive function by affecting the volume of the fourth ventricle. However, larger longitudinal follow-up studies are needed to confirm these conclusions.
Role of the renin-angiotensin system in the development of COVID-19-associated neurological manifestations
Authors: Méndez-García Lucía A. , Escobedo Galileo , Minguer-Uribe Alan Gerardo , Viurcos-Sanabria Rebeca , Aguayo-Guerrero José A. , Carrillo-Ruiz José Damián , Solleiro-Villavicencio Helena
Published: September 2022

SARS-CoV-2 causes COVID-19, which has claimed millions of lives. This virus can infect various cells and tissues, including the brain, for which numerous neurological symptoms have been reported, ranging from mild and non-life-threatening (e.g., headaches, anosmia, dysgeusia, and disorientation) to severe and life-threatening symptoms (e.g., meningitis, ischemic stroke, and cerebral thrombosis). The cellular receptor for SARS-CoV-2 is angiotensin-converting enzyme 2 (ACE2), an enzyme that belongs to the renin-angiotensin system (RAS). RAS is an endocrine system that has been classically associated with regulating blood pressure and fluid and electrolyte balance; however, it is also involved in promoting inflammation, proliferation, fibrogenesis, and lipogenesis. Two pathways constitute the RAS with counter-balancing effects, which is the key to its regulation. The first axis (classical) is composed of angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and angiotensin type 1 receptor (AT1R) as the main effector, which -when activated- increases the production of aldosterone and antidiuretic hormone, sympathetic nervous system tone, blood pressure, vasoconstriction, fibrosis, inflammation, and reactive oxygen species (ROS) production. Both systemic and local classical RAS’ within the brain are associated with cognitive impairment, cell death, and inflammation. The second axis (non-classical or alternative) includes ACE2, which converts Ang II to Ang-(1–7), a peptide molecule that activates Mas receptor (MasR) in charge of opposing Ang II/AT1R actions. Thus, the alternative RAS axis enhances cognition, synaptic remodeling, cell survival, cell signal transmission, and antioxidant/anti-inflammatory mechanisms in the brain. In a physiological state, both RAS axes remain balanced. However, some factors can dysregulate systemic and local RAS arms. The binding of SARS-CoV-2 to ACE2 causes the internalization and degradation of this enzyme, reducing its activity, and disrupting the balance of systemic and local RAS, which partially explain the appearance of some of the neurological symptoms associated with COVID-19. Therefore, this review aims to analyze the role of RAS in the development of the neurological effects due to SARS-CoV-2 infection. Moreover, we will discuss the RAS-molecular targets that could be used for therapeutic purposes to treat the short and long-term neurological COVID-19-related sequelae.
Genetic and molecular features of seizure-freedom following surgical resections for focal epilepsy: A pilot study
Authors: Louis Shreya , Busch Robyn M. , Lal Dennis , Hockings Jennifer , Hogue Olivia , Morita-Sherman Marcia , Vegh Deborah , Najm Imad , Ghosh Chaitali , Bazeley Peter , Eng Charis , Jehi Lara , Rotroff Daniel M.
Published: September 2022

Objective

Seizure outcomes after brain surgery for drug-resistant epilepsy (DRE) are very heterogeneous and difficult to predict with models utilizing the current clinical, imaging, and electrophysiological variables. In this pilot study, we investigated whether genetic and molecular biomarkers (e.g., genomic, transcriptomic) can provide additional insight into differential response to surgery.

Methods

Post-operative seizure-outcomes were collected at last follow-up (>6 months) for 201 adult patients with DRE who underwent surgery between 2004 and 2020. Resected tissue was sent for miRNA sequencing (n = 132) and mRNA sequencing (n = 135). Following the selection of 10 genes (SCN1A, NBEA, PTEN, GABRA1, LGL1, DEPDC5, IL1A, ABCB1, C3, CALHM1), we investigated SNPs in those 10 genes from previously acquired exome sequencing data (n = 106). Logistic regression was performed to test for associations between individual features (mRNAs, miRNAs, and SNPs) and post-operative seizure-outcome with an exploratory FDR P < 0.25 as the threshold for significance. Post-operative time-to-seizure analyses were performed for each SNP using a Cox proportional hazards model.

Results

The majority of patients (83%) had temporal lobe epilepsy. Mean age at surgery was 38.3 years, and 56% were female. Three SNPs (rs10276036, rs11975994, rs1128503) in multi-drug resistance gene, ABCB1, were associated with post-operative seizure outcomes. Patients with alternate alleles in ABCB1 were more likely to be seizure-free at last follow-up (52–56% reduction in seizure recurrence; FDR P = 0.24). All three SNPs were in linkage disequilibrium and highly correlated with each other. Median post-operative time-to-seizure was 63 months for patients with 2 alternate alleles, 24–33 months with 1 alternate allele, and 10–11 months with 0 alternate alleles. These SNPs improved outcome prediction beyond MRI and sex alone. No independent miRNAs or mRNAs were significantly associated with seizure-outcome (P > 0.05). However, pathway analysis identified “cancer drug resistance by drug efflux” (mir-154 and mir-379) as enriched (P = 0.02), supporting the role of drug response genes in post-operative seizure recurrence.

Significance

ABCB1 may have a role in epileptogenesis and surgery outcomes independent of its drug efflux activity necessitating further investigation. SNPs in ABCB1 may serve as independent predictors of post-operative outcome.
Case report: Combined acute revascularization in early bilateral carotid stent occlusion
Authors: Černík David , Bartoš Robert , Neradová Jarmila , Frenštátská Nicol , Cihlář Filip , Brušáková Štěpánka , Sameš Martin
Published: September 2022

Introduction

The introduction of a carotid stent involves the use of effective antiplatelet therapy to maintain stent patency. We present a case report of combined acute revascularization in a patient with occlusion in recently introduced stents of both carotid arteries.

Methods

The patient (male, 73 years) was admitted for stroke recurrence upon discontinuation of antiplatelet therapy. According to the CTA, the closure of implanted stents of both carotid arteries was confirmed. Intravenous thrombolysis and mechanical thrombectomy were performed with complete recanalization of the left carotid stent. At 3 days apart, clinical deterioration was found with progressive stent restenosis. Percutaneous transluminal stent angioplasty, mechanical embolectomy and prolonged low-dose intravenous thrombolysis have been used repeatedly.

Results

With the impossibility of maintaining the patency of carotid stents even on the maximum drug therapy and despite endovascular procedures, bilateral neurosurgical revascularization of the middle cerebral arteries using ECIC bypasses was successfully performed. Prolonged low-dose intravenous thrombolysis (20 mg recombinant plasminogen aktivator (rTPA)/10 h) has proven to be an acute bridging therapy until surgery.

Conclusion

Early occlusion of the carotid stent is a significant complication of endovascular treatment of stenotic arteries. ECIC bypass revascularization of the middle cerebral artery can be a highly effective therapeutic procedure.
Tetramethylpyrazine in Chinese baijiu: Presence, analysis, formation, and regulation
Authors: Shi Xiaoshan , Zhao Shumiao , Chen Shenxi , Han Xinglin , Yang Qiang , Zhang Long , Xia Xian , Tu Junming , Hu Yuanliang
Published: September 2022

Traditional Chinese fermented baijiu is one of the six major distilled spirits consumed worldwide. It plays an important role in people's daily life and social interactions because of its taste, nutritional value, and various health functions. Tetramethylpyrazine (TMP), also known as ligustrazine, is not only an important compound related to the flavor of Chinese baijiu but also has special pharmacological effects. It gives the baijiu a nutty and baked aroma and provides baijiu with important health benefits. Recently, the nutritional, drinking, and health aspects of baijiu have attracted significant attention. Therefore, the study of TMP in baijiu is an important aspect of baijiu health research. This mini novel review summarizes the formation mechanism of TMP, along with the current research progress, analytical methods used, and regulation strategies associated with TMP in Chinese baijiu in recent years.
Removing the sporoderm from the sporoderm-broken spores of Ganoderma lucidum improves the anticancer and immune-regulatory activity of the water-soluble polysaccharide
Authors: Fang Liu , Zhao Qian , Guo Cuiling , Guo Dandan , Li Zhenhao , Xu Jing , Guo Chengjie , Sang Tingting , Wang Ying , Chen Jiajun , Chen Chaojie , Chen Rong , Wu Jianjun , Wang Xingya
Published: September 2022

Plant-derived polysaccharides have demonstrated promising anti-cancer effects via immune-regulatory activity. The aim of the current study was to compare the chemical property and the anticancer effects of polysaccharides extracted from the sporoderm-removed spores of the medicinal mushroom Ganoderma lucidum (RSGLP), which removed the sporoderm completely, with polysaccharides extracted from the sporoderm-broken spores of G. lucidum (BSGLP). We found that RSGLP has a higher extraction yield than BSGLP. HPGPC and GC-MS results revealed that both RSGLP and BSGLP are heteropolysaccharides, but RSGLP had a higher molecular weight and a different ratio of monosaccharide composition than BSGLP. MTT and flow cytometry results demonstrated that RSGLP exhibited much higher dose-efficacy in inhibiting cell viability and inducing apoptosis than BSGLP in 8 cancer cell lines representing colon (HCT116 and HT29), liver (HepG2 and Huh-7), breast (MDA-MB-231 and MCF-7), and lung cancers (NCI-H460 and A549). Furthermore, RSGLP is more effective in inhibiting HCT116 and NCI-H460 xenograft tumor growth and inhibiting tumor-induced splenomegaly than BSGLP in nude mice, suggesting a better effect on regulating immunity of RSGLP. Next, we found that RSGLP is more potent in inhibiting the level of serum inflammatory cytokines in nude mice, and in inhibiting the activation of macrophage RAW264.7 and the expression of the inflammatory mediators IL-1β, TNF-α, iNOS, and COX-2 in vitro. This is the first study to compare the chemical properties, anti-cancer, and immune-regulatory effects of RSGLP and BSGLP using multiple cancer cell lines. Our results revealed that the sporoderm-removed spores of G. lucidum (RSGL) and RSGLP may serve as new anticancer agents for their promising immune-regulatory activity.
Effects of a natural nutritional supplement on immune cell infiltration and immune gene expression in exercise-induced injury
Authors: Jiang Feng , Yang Rongfeng , Xue Diya , Li Rong , Tan Meiling , Zeng Zhicong , Xu Luhua , Liu Linling , Song Yinzhi , Lin Fengxia
Published: September 2022

Inflammatory immune response plays a key role in exercise-induced injury and healing; however, the relevant regulatory mechanisms of immune infiltration in exercise-induced injuries remain less studied. In the present study, a highly efficient system for screening immunity-related biomarkers and immunomodulatory ability of natural nutritional supplements was developed by integrating intelligent data acquisition, data mining, network pharmacology, and computer-assisted target fishing. The findings demonstrated that resting natural killer cells showed a higher rate of infiltration after exercise, whereas naive B cells and activated dendritic cells showed higher rate of infiltration before exercise. Four key genes, namely PRF1, GZMB, CCL4, and FASLG, were associated with exercise-induced injuries and inflammatory immune response. In total, 26 natural compounds including echinacoside, eugenol, tocopherol, and casuariin were predicted by using the HERB databases. Molecular docking analysis showed that GZMB, FASLG, and CCL4 bound to echinacoside. In vivo experiments in mice showed that after 30 min swimming, natural killer (NK) cells showed high infiltration rates, and the key genes (GZMB, PRF1, FASLG, and CCL4) were highly expressed; however, echinocandin significantly reduced the level of NK cells and decreased the expression of the four key genes post exercise. This natural nutritional supplement may act to protect against inflammatory injury after exercise by suppressing specific immune infiltration.
Study on preparation of chickpea peptide and its effect on blood glucose
Authors: Ma Xuemei , Fan Xing , Wang Deping , Li Xianai , Wang Xiaoyun , Yang Jiangyong , Qiu Chenggong , Liu Xiaolu , Pang Guangxian , Abra Redili , Wang Liang
Published: September 2022

Chickpeas are the third largest bean in the world and are rich in protein. In this study, chickpea peptides were prepared by the enzyme-bacteria synergy method. Taking the peptide yield as the index, we first screened 8 strains suitable for the fermentation of chickpea peptides from 16 strains, carried out sodium dodecyl sulfate polyacrylamide gel electrophoresis, and then screened 4 strains with the best decomposition effect of chickpea protein. The molecular weight, amino acid content, and α-glucosidase inhibitory activity of the chickpea peptides fermented by these four strains were detected. Finally, the strains with the best α-glucosidase inhibitory activity were obtained, and the inhibitory activities of the different molecular weight components of the chickpea peptides fermented by the strains with the best α-glucosidase inhibitory were detected. It was found that Bifidobacterium species had the best fermentation effect, and the highest peptide yield was 52.99 ± 0.88%. Lactobacillus thermophilus had the worst fermentation effect, and the highest peptide yield was 43.22 ± 0.47%. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that Bifidobacterium species, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Lactobacillus paracasei have a better effect on the decomposition of chickpea protein in the fermentation process, and the molecular weight of their fermented peptides is basically below 20 KDa. Among the four strains, the α-glycosidase inhibition of chickpea peptide fermented by Lactobacillus acidophilus was the best, which was 58.22 ± 1.10% when the peptide concentration was 5.0 mg/ml. In chickpea peptide fermented by Lactobacillus acidophilus, the influence of molecular weight on the inhibitory activity is not obvious when the molecular weight is <10 kD, and the molecular weight range of the best inhibitory effect is 3–10 kD, and the inhibitory rate of α-glucosidase is 37 ± 1.32% at 2.0 mg/ml. This study provides a theoretical basis for the study of a new preparation method for chickpea peptide and its hypoglycemic effect.
Clinical features and outcomes of patients with follicular lymphoma: A real-world study of 926 patients in China
Authors: Gao Fenghua , Zhang Tingting , Liu Xia , Qu Zhenjie , Liu Xianming , Li Lanfang , Qiu Lihua , Qian Zhengzi , Zhou Shiyong , Gong Wenchen , Meng Bin , Ren Xiubao , Wang Xianhuo , Zhang Huilai
Published: September 2022

Background

The data about the clinical features and outcomes of Chinese patients with follicular lymphoma (FL) are limited. Here, we conducted a retrospective study to explore the initial treatment strategies and clinical outcomes of Chinese patients with FL in the real world.

Method

This study included FL patients who were newly diagnosed in Tianjin Medical University Cancer Institute and Hospital from March 2002 to August 2020.

Results

A total of 926 FL patients were enrolled. The median age was 54 years old, and the majority of the Chinese FL patients had advanced-stage disease and Eastern Cooperative Oncology Group(ECOG) <1 but less frequently infiltrated bone marrow. After a median of 38-month follow-up, the 5-year progressive-free survival (PFS) and overall survival (OS) of grade1–3a were 57.8% and 88.7%, respectively, which both are similar to those reported in previous Chinese and Western studies. The co-existence at diagnosis of FL and diffuse large B-cell lymphoma (DLBCL) components (FL/DLBCL) was associated with poor outcomes. The FL grades and proportion of DLBCL component in FL/DLBCL did not have an impact on PFS and OS. The most common regimen with great efficacy and risk–benefit was RCHOP-like followed by R maintenance regimen. The 5-year cumulative hazard of histological transformation (HT) was 4.7% (95% CI, 3.5–5.9); median time to transformation was 23.5 months (range, 2–146 months) after diagnosis. Three-year survival following transformation was 55% (95% CI, 40–70). Patients with stage III–IV, elevated β2 microglobulin (β2-MG), and B symptoms seemed to be more prone to progress within 24 months of frontline therapy (POD24). The FLIPI-2 showed the highest specificity to predict POD24, reflecting the prediction of correctly classifying as low-risk patients, but the FLIPI had the highest sensitivity to predict the risk of progression for critical patients.

Conclusions

We revealed the clinical characteristics and outcomes of FL patients in the real world in China, which may provide novel data on prognostic factors and primary treatment of FL, applicable to routine clinical practice.
CT-based radiomic nomogram for preoperative prediction of DNA mismatch repair deficiency in gastric cancer
Authors: Zeng Qingwen , Zhu Yanyan , Li Leyan , Feng Zongfeng , Shu Xufeng , Wu Ahao , Luo Lianghua , Cao Yi , Tu Yi , Xiong Jianbo , Zhou Fuqing , Li Zhengrong
Published: September 2022

Background

DNA mismatch repair (MMR) deficiency has attracted considerable attention as a predictor of the immunotherapy efficacy of solid tumors, including gastric cancer. We aimed to develop and validate a computed tomography (CT)-based radiomic nomogram for the preoperative prediction of MMR deficiency in gastric cancer (GC).

Methods

In this retrospective analysis, 225 and 91 GC patients from two distinct hospital cohorts were included. Cohort 1 was randomly divided into a training cohort (n = 176) and an internal validation cohort (n = 76), whereas cohort 2 was considered an external validation cohort. Based on repeatable radiomic features, a radiomic signature was constructed using the least absolute shrinkage and selection operator (LASSO) regression analysis. We employed multivariable logistic regression analysis to build a radiomics-based model based on radiomic features and preoperative clinical characteristics. Furthermore, this prediction model was presented as a radiomic nomogram, which was evaluated in the training, internal validation, and external validation cohorts.

Results

The radiomic signature composed of 15 robust features showed a significant association with MMR protein status in the training, internal validation, and external validation cohorts (both P-values <0.001). A radiomic nomogram incorporating a radiomic signature and two clinical characteristics (age and CT-reported N stage) represented good discrimination in the training cohort with an AUC of 0.902 (95% CI: 0.853–0.951), in the internal validation cohort with an AUC of 0.972 (95% CI: 0.945–1.000) and in the external validation cohort with an AUC of 0.891 (95% CI: 0.825–0.958).

Conclusion

The CT-based radiomic nomogram showed good performance for preoperative prediction of MMR protein status in GC. Furthermore, this model was a noninvasive tool to predict MMR protein status and guide neoadjuvant therapy.