Miracle-dz/UniFAR-FTUs huggingface dataset:
Network pharmacology identify intersection genes of quercetin and Alzheimer’s disease as potential therapeutic targets

Background Currently, there are no efficient therapies for Alzheimer’s disease (AD) among the elderly, although it is the most common etiology of dementia among the elderly. Quercetin, which has a variety of therapeutic properties, may pave the way for novel approaches to AD treatment. In the AD patients’ frontal cortex, current study aims to identify the potential mechanisms of quercetin’s pharmacological targets. Materials and methods The pharmacological targets of quercetin have been studied from DrugBank and SwissTarget. In order to distinguish AD-associated genes targeted by quercetin (Q-ADGs), we utilized an integrated intersection of gene expressions of the frontal cortex in combination with transcriptome analysis. To detect cortex-related Q-ADGs and immune-related Q-ADGs, a drug screening database and the immune infiltration analysis was utilized. The Q-ADGs were then linked with the AD severity scores (MMSE scores) to find severity-associated Q-ADGs. In addition, the miRNA-seq datasets were examined to identify severity-associated Q-ADG-miRNAs. Twelve genes, more frequently related to AD by previous studies among all the genes identified in the present study, were subjected to the verification of qRT-PCR in AD cell model. Results In the frontal lobe of AD, 207 Q-ADGs were discovered and found that axonogenesis, glial differentiation, and other biological processes had been enriched. There were 155 immune-related Q-ADGs (e.g., COX2, NOS2, HMGB1) and 65 cortex-related Q-ADGs (e.g., FOXO1, CXCL16, NOTCH3). Sixteen Q-ADGs (e.g., STAT3, RORA, BCL6) and 28 miRNAs (e.g., miR-142-5p, miR-17-5p) were found to be related to MMSE scores. In the qRT-PCR results, six out of twelve genes were significantly regulated by quercetin. DYRK1A, FOXO1, NOS2, NGF, NQO1, and RORA genes were novel target of quercetin in AD. DYRK1A, NOS2, and NQO1 genes targeted by quercetin have benefits in the treatment of AD. However, FOXO1, NGF, and RORA genes targeted by quercetin might have a negative impact on AD. Conclusion The role of quercetin in AD appears to be multifaceted, and it can affect patients’ frontal cortex in a variety of pathways, such as axonogenesis, immune infiltration, and glial cell differentiation. DYRK1A, NOS2, and NQO1 might be potential novel effective drug targets for quercetin in AD.
Maternal well-being and family adaptation during COVID-19 in fragile X syndrome

Mothers of children with fragile X syndrome are at increased risk of experiencing anxiety and depression due to potential genetic risk and to stress associated with parenting a child with significant behavioral, emotional, and educational support needs. During the initial shutdown and subsequent restrictions of the COVID-19 pandemic, mothers of children with fragile X reported experiencing elevated levels of anxiety and depression relative to their usual levels of well-being. Many indicated that the negative consequences of exposure to COVID-19 and related stressors, as well as the impacts of the pandemic on their family, directly affected their anxiety and depression. Mothers reported on specific sources of distress as well as potential sources of resilience and positive adaptation that occurred during the first year of the COVID-19 pandemic.
Integrated co-expression network analysis uncovers novel tissue-specific genes in major depressive disorder and bipolar disorder

Tissue-specific gene expression has been found to be associated with multiple complex diseases including cancer, metabolic disease, aging, etc. However, few studies of brain-tissue-specific gene expression patterns have been reported, especially in psychiatric disorders. In this study, we performed joint analysis on large-scale transcriptome multi-tissue data to investigate tissue-specific expression patterns in major depressive disorder (MDD) and bipolar disorder (BP). We established the strategies of identifying tissues-specific modules, annotated pathways for elucidating biological functions of tissues, and tissue-specific genes based on weighted gene co-expression network analysis (WGCNA) and robust rank aggregation (RRA) with transcriptional profiling data from different human tissues and genome wide association study (GWAS) data, which have been expanded into overlapping tissue-specific modules and genes sharing with MDD and BP. Nine tissue-specific modules were identified and distributed across the four tissues in the MDD and six modules in the BP. In general, the annotated biological functions of differentially expressed genes (DEGs) in blood were mainly involved in MDD and BP progression through immune response, while those in the brain were in neuron and neuroendocrine response. Tissue-specific genes of the prefrontal cortex (PFC) in MDD-, such as IGFBP2 and HTR1A, were involved in disease-related functions, such as response to glucocorticoid, taste transduction, and tissue-specific genes of PFC in BP-, such as CHRM5 and LTB4R2, were involved in neuroactive ligand-receptor interaction. We also found PFC tissue-specific genes including SST and CRHBP were shared in MDD-BP, SST was enriched in neuroactive ligand-receptor interaction, and CRHBP shown was related to the regulation of hormone secretion and hormone transport.
Biofilm aggregates and the host airway-microbial interface

Biofilms are multicellular microbial aggregates that can be associated with host mucosal epithelia in the airway, gut, and genitourinary tract. The host environment plays a critical role in the establishment of these microbial communities in both health and disease. These host mucosal microenvironments however are distinct histologically, functionally, and regarding nutrient availability. This review discusses the specific mucosal epithelial microenvironments lining the airway, focusing on: i) biofilms in the human respiratory tract and the unique airway microenvironments that make it exquisitely suited to defend against infection, and ii) how airway pathophysiology and dysfunctional barrier/clearance mechanisms due to genetic mutations, damage, and inflammation contribute to biofilm infections. The host cellular responses to infection that contribute to resolution or exacerbation, and insights about evaluating and therapeutically targeting airway-associated biofilm infections are briefly discussed. Since so many studies have focused on Pseudomonas aeruginosa in the context of cystic fibrosis (CF) or on Haemophilus influenzae in the context of upper and lower respiratory diseases, these bacteria are used as examples. However, there are notable differences in diseased airway microenvironments and the unique pathophysiology specific to the bacterial pathogens themselves.
Composition and diversity of gut microbiota in diabetic retinopathy

Objective Diabetic retinopathy (DR) is one of the most common complications of type 2 diabetes mellitus. The current study investigates the composition, structure, and function of gut microbiota in DR patients and explores the correlation between gut microbiota and clinical characteristics of DR. Methods A total of 50 stool samples were collected from 50 participants, including 25 DR patients and 25 healthy controls (HCs). 16S ribosomal RNA gene sequencing was used to analyze the gut microbial composition in these two groups. DNA was extracted from the fecal samples using the MiSeq platform. Results The microbial structure and composition of DR patients were different from that of HCs. The microbial richness of gut microbiota in DR was higher than that of normal individuals. The alterations of microbiome of DR patients were associated with disrupted Firmicutes, Bacteroidetes, Synergistota, and Desulfobacterota phyla. In addition, increased levels of Bacteroides, Megamonas, Ruminococcus_torques_group, Lachnoclostridium, and Alistipes, and decreased levels of Blautia, Eubacterium_ hallii_group, Collinsella, Dorea, Romboutsia, Anaerostipes, and Fusicatenibacter genera were observed in the DR groups. Additionally, a stochastic forest model was developed to identify a set of biomarkers with seven bacterial genera that can differentiate patients with DR from those HC. The microbial communities exhibited varied functions in these two groups because of the alterations of the above-mentioned bacterial genera. Conclusion The altered composition and function of gut microbiota in DR patients indicated that gut microbiome could be used as non-invasive biomarkers, improve clinical diagnostic methods, and identify putative therapeutic targets for DR.
Peptide profile of Parmigiano Reggiano cheese after simulated gastrointestinal digestion: From quality drivers to functional compounds

Time of ripening has a strong impact on shaping the valuable and recognizable characteristics of long-ripened types of cheese such as Parmigiano Reggiano (PR) due to the interrelationship between microbiota and proteolysis that occurs during ripening. The derived peptide profile is linked to cheese quality and represents the canvas for enzymes upon digestion, which could be responsible for the release of potentially bioactive peptides (BPs). In this study, we aimed at investigating the presence of BP in 72 PR cheese samples of different ripening times, from curd to 24 months of ripening, produced in six different dairies, and following their fate after simulated gastrointestinal digestion. A small number of peptide sequences sharing 100% similarity with known antimicrobial, antioxidant, and ACE-inhibitor sequences were found in PR cheeses, while a higher number of potential BPs were found after their simulated gastrointestinal digestion, in different amounts according to ripening time. Taking advantage of the complex organization of the sampling plan, we were able to follow the fate of peptides considered quality drivers during cheese ripening to their release as functional compounds upon digestion.
Myeloid Wls expression is dispensable for skin wound healing and blood vessel regeneration

Wnt signaling controls blood vessel growth, regression and patterning during embryonic and postnatal life. Macrophages are major producers of Wnt ligands and angiogenic growth factors. It regulates vascular development and specification during embryogenesis and wound healing. Macrophage dysregulation in wound healing impairs vessel regeneration and delay wound closure. During cutaneous wound healing, the endovascular progenitors (EVPs) proliferate and differentiate into mature endothelial (D) cells in response to signals produced by perivascular cells, including macrophages, governing blood vessels regeneration. However, the role of macrophage’s Wnt production on endothelial cells, especially the EVPs during wound healing is currently unknown. Here we used a cutaneous excisional wound model in mice with conditional deletion of Wnt secretion by myeloid cells (Wlsfl/flLysM-Cre+ ) to assess the kinetics of endothelial subpopulations (including EVP), myeloid infiltration, collagen deposition and wound closure. Deletion of Wls expression by myeloid cells did not affect wound closure and collagen deposition, indicating that myeloid Wls expression does not promote wound healing and regeneration. Myeloid-specific Wls deletion elevated the EVP population during the peak of angiogenesis, yet without affecting blood vessel density. Wounds in Wlsfl/flLysM-Cre+ animals showed unperturbed myeloid infiltration and differentiation. Overall, our data indicate that macrophage Wnt production shapes EVP kinetics without major relevance to wound healing. These findings extend the knowledge of macrophage and endothelial molecular crosstalk and position myeloid-derived Wnt production as a regulator of endovascular progenitor.
Can improved cassava genotypes from the breeding program substitute the adopted variety for gari production? Biophysical and textural attributes approach

The use of the biophysical and textural attributes of gari/eba to determine the possible substitution of an adopted cassava variety (TMBE419) with the improved genotypes from the breeding program was evaluated in this study. Standard methods were used for the characterization of the biophysical and textural attributes of the gari/eba from different cassava roots. It was observed that the mean of the biophysical attributes of the gari is swelling power (SWP) 12.46%, dispersibility 59.70%, water absorption capacity (WAC) 474.60%, peak 355.82 RVU, breakdown 111.02 RVU, and final 423.07 RVU viscosities, peak time 4.91 min, pasting temperature 80.14°C, moisture content 3.92%, ash content 0.98%, starch content 71.98%, amylose content 31.47% and cyanogenic potential (CNP) content 0.47 mg HCN/kg. There were significant differences (p < 0.05) in all the biophysical attributes of the gari samples. The instrumental texture attribute of the eba is hardness 40.46 N/m2, mouldability 0.93, and stretchability 1.04. The sensory texture attributes depict that all the eba was moderately soft, sticky, and mouldable. Significant differences (p < 0.05) exist in the instrumental and sensory texture attributes of the eba samples. The PCA shows that gari made from TMS14F1285P0006 and TMS13F1053P0010 genotypes may have similar behavior in terms of dispersibility, SWP, and peak and breakdown viscosities to that of the TMBE419 variety. Also, the stickiness of the eba prepared from the TMS14F1285P0006 and TMS13F1053P0010 genotypes may be the same as that of the TMBE419 variety. Therefore, TMS14F1285P0006 and TMS13F1053P0010 genotypes may be good replacements for producing gari/eba in place of the TMBE419 variety.
TRPM4 and TRPV2 are two novel prognostic biomarkers and promising targeted therapy in UVM

Uveal melanoma (UVM) is the most common primary intraocular malignancy tumor in adults. Almost 50% of UVM patients develop metastatic disease, and is usually fatal within 1 year. However, the mechanism of etiology remains unclear. The lack of prognostic, diagnostic and therapeutic biomarkers is a main limitation for clinical diagnosis and treatment. The transient receptor potential (TRP) channels play important roles in the occurrence and development of tumors, which may have the potential as a therapeutic target for UVM. This current study aimed to identify the potential effect and function of the TRPs that could provide survival prediction and new insight into therapy for UVM. Based on the transcriptome data and potential key genes of UVM were screened using the Cancer Genome Atlas (TCGA) databases, Gene expression analysis showed the expression of TRPM4, TRPV2 and other TRPs was high levels in UVM. Using survival analysis, we screened out that the high expression of TRPM4 and TRPV2 was negatively correlated with the prognosis of UVM patients. Cox regression analysis and functional enrichment analysis further indicated that TRPM4 and TRPV2 were the most convincing therapeutic targets of UVM, and the majority of genes involved in ferroptosis pathways in UVM showed positively correlated with the expression levels of TRPM4 and TRPV2. In conclusion, TRPM4 and TRPV2 were considered as two novel prognostic biomarkers and a promising targeted therapy in UVM.
Acute retinal necrosis: A mini review

Acute retinal necrosis is a rare but potentially devastating disease. Even in the era of modern medicine, retinal detachment is a frequent complication leading to vison loss, as well as phthisis bulbi. Whereas IV acyclovir still remains the standard of care, high doses of valacyclovir with/without additional intravitreal injections of foscarnet have been used. In an attempt to reduce the retinal detachment rate, prophylactic laser treatment and early vitrectomy have been proposed. In this article, we aim to review current diagnostic and treatment modalities.
Neuroimaging in Frontotemporal Lobar Dementia: Research and Clinical Utility

Frontotemporal Lobar Dementia (FTLD) is a clinically and pathologically complex disease. Advances in neuroimaging techniques have provided a specialized set of tools to investigate underlying pathophysiology and identify clinical biomarkers that aid in diagnosis, prognostication, monitoring, and identification of appropriate endpoints in clinical trials. In this chapter, we review data discussing the utility of neuroimaging biomarkers in sporadic FTLD, with an emphasis on current and future clinical applications. Among those modalities readily utilized in clinical settings, T-1 weighted structural magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) are best supported in differential diagnosis and as targets for clinical trial endpoints. However, a number of non-clinical neuroimaging modalities, including diffusion tensor imaging and resting state functional connectivity MRI, show promise as biomarkers to predict progression and as clinical trial endpoints. Other neuroimaging modalities including amyloid PET, Tau PET, and arterial spin labeling MRI are also discussed, though more work is required to establish their utility in FTLD in clinical settings.
Effects of Coenzyme Q10 on Skeletal Muscle Oxidative Metabolism in Statin Users Assessed Using 31 P Magnetic Resonance Spectroscopy: a Randomized Controlled Study

Objectives— Statins partially block the production of coenzyme Q10 (CoQ10), an essential component for mitochondrial function. Reduced skeletal muscle mitochondrial oxidative capacity has been proposed to be a cause of statin myalgia and can be measured using 31 phosphorus magnetic resonance spectroscopy ( 31 P-MRS). The purpose of this study is to assess the effect of CoQ10 oral supplementation on mitochondrial function in statin users using 31 P-MRS. Design/Setting— In this randomized, double-blind, placebo-controlled pilot study, 21 adults aged 47–73 were randomized to statin+placebo (n=9) or statin+CoQ10 (n=12). Phosphocreatine (PCr) recovery kinetics of calf muscles were assessed at baseline (off statin and CoQ10) and 4 weeks after randomization to either statin+CoQ10 or statin+placebo. Results— Baseline and post-treatment PCr recovery kinetics were assessed for 19 participants. After 4 weeks of statin+ CoQ10 or statin+placebo, the overall relative percentage change (100*(baseline−follow up)/baseline) in PCr recovery time was −15.1% compared with baseline among all participants, (p-value=0.258). Participants randomized to statin+placebo (n=9) had a relative percentage change in PCr recovery time of −18.9%, compared to −7.7% among participants (n=10) receiving statin+CoQ10 (p-value=0.448). Conclusions— In this pilot study, there was no significant change in mitochondrial function in patients receiving 4 weeks of statin+CoQ10 oral therapy when compared to patients on statin +placebo. impairment of mitochondrial oxidation is reflected in prolonged (slower) post-exercise PCr recovery. We previously used 31 P-MRS to show that post-exercise PCr recovery times were significantly prolonged after four weeks of statin therapy when compared to baseline measures off statins The purpose of this study is to assess the effects of CoQ10 oral supplementation on calf muscle post-exercise PCr recovery kinetics in patients on statin therapy using 31 P-MRS. In addition, we also explored if there are differences among those with a history of statin myalgia compared to those with a history of tolerating statins, and evaluated correlations between plasma CoQ10 levels and PCr recovery kinetics.
Zinc Finger Transcription Factor Zn 3 -Sp1 Reactions with Cd 2+

Cadmium is recognized as a major pollutant and threat to health in industrialized countries (1,2). In humans, chronic Cd2+ exposure causes toxicity that targets kidney and bone (1-3). Suggestive evidence implicates other sites such as lung (4). Experimental toxicological studies have largely focused on the role of metallothionein (MT) in the protection of tissues against Cd2+-induced injury (5). 1 Using a variety of approaches including investigations with mice that bear the MT null genotype or contain extra, transgenic MT, it is clear that metallothionein induction by Cd2+ protects against acute exposure to Cd2+ and probably chronic exposure as well (5,6).
Occupational Exposure and Health Risks of Volatile Organic Compounds (VOCs) of Hotel Housekeepers Field Measurements of Exposure and Health Risks

Hotel housekeepers represent a large, low-income, predominantly minority, and high-risk workforce. Little is known about their exposure to chemicals, including volatile organic compounds (VOCs). This study evaluates VOC exposures of housekeepers, sources and factors affecting VOC levels, and provides preliminary estimates of VOC-related health risks. We utilized indoor and personal sampling at two hotels, assessed ventilation, and characterized the VOC composition of cleaning agents. Personal sampling of hotel staff showed a total target VOC concentration of 57 ± 36 μg/m 3 (mean ± standard deviation), about twice that of indoor samples. VOCs of greatest health significance included chloroform and formaldehyde. Several workers had exposure to alkanes that could cause non-cancer effects. VOC levels were negatively correlated with estimated air change rates. The composition and concentrations of the tested products and air samples helped identify possible emission sources, which included building sources (for formaldehyde), disinfection byproducts in the laundry room, and cleaning products. VOC levels and the derived health risks in this study were at the lower range found in the US buildings. The excess lifetime cancer risk (average of 4.1 × 10 −5 ) still indicates a need to lower exposure by reducing or removing toxic constituents, especially formaldehyde, or by increasing ventilation rates.
LETTER TO THE EDITOR ARSA variants in a -synucleinopathies

1 Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA 2 Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA 3 Fundació Docència i Recerca MútuaTerrassa and Movement Disorders Unit, Department of Neurology, University Hospital MútuaTerrassa, Terrassa 08221, Barcelona, Spain 4 Department of Human Genetics, McGill University, Montréal, Québec, Canada 5 Montreal Neurological Institute, McGill University, Montréal, Québec, Canada 6 Department of Neurology, Oslo University Hospital, Oslo, Norway 7 Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK 8 Department of Neurology and Neurosurgery, McGill University, Montréal, Québec, Canada