Postoperative Maxillary Cyst Following Maxillary Tooth Extraction: A Rare Surgical Predicament.

A postoperative maxillary cyst (POMC) is an epithelium-lined cyst that can develop following surgery or trauma in the maxillary antral region. This condition arises from the entrapment of the sinonasal mucosa in the maxilla, and rarely in the mandible, due to trauma or instrumentation near the maxillary sinus. Literature indicates that POMCs, or surgical ciliated cysts, can appear as delayed complications from five months to 56 years after trauma or surgical procedures in the sinus area. Despite its potential for aggressive local destruction, it often presents incidentally with minimal symptoms. This clinical case report describes the occurrence of such a cyst in a 30-year-old male and discusses the diagnosis and management of this rare pathology.

Synthesis, Optical Spectroscopy, and Laser and Biomedical Imaging Application Potential of 2,4,6-Triphenylpyrylium Tetrachloroferrate and Its Derivatives.

Synthesis, optical spectroscopic properties, two-photon (TP) absorption-induced fluorescence, and laser and bioimaging application potentials of 2,4,6-triphenylpyrylium tetrachloroferrate (1),4-(4-methoxyphenyl)-2,6-diphenylpyrylium tetrachloroferrate (2), 2,6-bis(4-methoxyphenyl)-4-phenylpyrylium tetrachloroferrate (3), and 2,4,6-tris(4-methoxyphenyl)pyrylium tetrachloroferrate (4) are presented. The synthesis involves the conversion of pyrylium tosylates to pyrylium chlorides, followed by transformation into 1-4 on heating to reflux with FeCl3 in acetonitrile. They are characterized using 1H and 13C NMR spectra in CD3OD, and FTIR and Raman spectroscopic techniques. The salts dissolve in organic solvents and water (pH = 7 to 3) even at high concentrations (10-3 M). These solutions absorb light strongly from 500-300 nm. Solutions of 1, 3, and 4 fluoresce with high quantum yield in the 500-700 nm spectral range. Salts 1 and 4 exhibit fluorescence lifetime shortening, line width narrowing, and free-running laser action under intense pulsed laser excitation. Toxicity and cell imaging studies using human cancer cell lines reveal that salts 1 and 3 function as cellular fluorophores in vitro and have no adverse effects on cellular viability at nanomolar ranges. Furthermore, acetonitrile and methanol solutions of salts 1, 3, and 4 exhibit strong two-photon absorption-induced fluorescence, opening potential applications in biomedical imaging and microscopy.

Metaboepigenetic regulation of gene expression in obesity and insulin resistance.

INTRODUCTION: Variation in DNA methylation (DNAm) in adipose tissue is associated with the pathogenesis of obesity and insulin resistance. The activity of enzymes involved in altering DNAm levels is dependent on several metabolite cofactors. OBJECTIVES: To understand the role of metabolites as mechanistic regulators of epigenetic marks, we tested the association between selected plasma metabolites and DNAm levels in the adipose tissue of African Americans. METHODS: In the AAGMEx cohort (N = 256), plasma levels of metabolites were measured by untargeted liquid chromatography-mass spectrometry; adipose tissue DNAm and transcript levels were measured by reduced representation bisulfite sequencing, and expression microarray, respectively. RESULTS: Among the 21 one-carbon metabolism pathway metabolites evaluated, six were associated with gluco-metabolic traits (PFDR < 0.05, for BMI, SI, or Matsuda index) in AAGMEx. Methylation levels of 196, 116, and 180 CpG-sites were associated (P < 0.0001) with S-adenosylhomocysteine (SAH), cystine, and hypotaurine, respectively. Cis-expression quantitative trait methylation (cis eQTM) analyses suggested the role of metabolite-level-associated CpG sites in regulating the expression of adipose tissue transcripts, including genes in G-protein coupled receptor signaling pathway. Plasma SAH level-associated CpG sites chr19:3403712 and chr19:3403735 were also associated with the expression of G-protein subunit alpha 15 (GNA15) in adipose. The expression of GNA15 was significantly correlated with BMI (ß = 1.87, P = 1.9 × 10-16) and SI (ß = -1.61, P = 2.49 × 10-5). CONCLUSION: Our study suggests that a subset of metabolites modulates the methylation levels of CpG sites in specific loci and, in turn, regulates the expression of transcripts involved in obesity and insulin resistance.

Studies on in vivo antithrombotic activity of quercetin, a natural flavonoid isolated from a traditional medicinal plant, African eggplant (Solanum indicum).

ETHNOPHARMACOLOGICAL RELEVANCE: Every year, cardiovascular diseases (CVDs) account for about 17.9 million deaths, making them the primary cause of both morbidity and mortality. Conventional drugs, which are often prescribed to treat cardiovascular diseases, are costly and have adverse effects. Consequently, dietary modifications and other medications are needed. Traditional use of Solanum indicum as cardiotonic to treat hypertension and anticoagulant potency has been reported but poorly evaluated scientifically. AIM OF THE STUDY: This study investigated the in vivo anticoagulant activity and mechanism of anticoagulation of quercetin (QC), a bioactive compound isolated from S. indicum (SI) hydroethanolic fruit extract. MATERIALS AND METHODS: Bioassay-guided fractionation (anticoagulant activity) extracted QC from hydroethanolic SI extract. QC was extensively characterized biochemically and pharmacologically. The interaction between QC and thrombin was investigated using spectrofluorometric and isothermal calorimetric methods. Cytotoxicity, antiplatelet, and thrombolytic studies were carried out in vitro. The Swiss albino mice were used to assess the in vivo, anticoagulant, and antithrombotic activities of QC. RESULTS: QC exhibits anticoagulant activity via (i) uncompetitive inhibition of thrombin but not FXa with a Ki value of 33.11 ± 4.2 µM and (ii) a partial inhibition of thrombin-catalyzed platelet aggregation with an IC50 value of 13.2 ± 1.2 µM. The experimental validation of the in silico study's prediction of QC's binding to thrombin was confirmed by spectrofluorometric and isothermal calorimetric analyses. QC was nontoxic to mammalian, non-hemolytic cells and demonstrated thrombolytic activity by activating plasminogen. QC demonstrated in vivo anticoagulant efficacy, preventing k-carrageen-induced thrombus formation in mice's tails. In the acute circulatory stasis paradigm in mice, QC reduces thromboxane B2 (TXB2) and endothelin-1 (ET-1) while increasing nitric oxide synthase (eNOS) and 6-keto prostaglandin F1α (6-keto-PGF1 α). CONCLUSION: Effective in vivo anticoagulant and antithrombotic properties of S. indicum's bioactive component QC point to the plant's potential use as a herbal anticoagulant medication for preventing and treating cardiovascular diseases linked to thrombosis.

Stereodivergent sila-germylenation vs. sila-stannylenation of an internal alkyne.

We report on the insertion of electron deficient alkyne, dimethyl acetylene dicarboxylate (DMAD), into the E-Si bond of hypersilyl tetrylenes, PhC(NtBu)2ESi(SiMe3)3 (E = Ge and Sn), at room temperature. Uniquely, the germylene leads to cis alkenes, while the stannylene gives access to trans alkenes, and the insight into divergent stereoselectivity has been obtained by DFT studies.

Chirality of CsPbBr3 Nanocrystals with Varying Dimensions in the Presence of Chiral Molecules.

Chiral lead halide perovskite (LHP) nanocrystals (NCs) have been attracting considerable interest for circularly polarized luminescence (CPL)-based optoelectronic applications. This study combined experimental and computational analyses to investigate how the dimensionality of 3D (cubic) to 0D (quantum dots) influences the tunable chiral emission of CsPbBr3 LHP NCs. The circular dichroism (CD) spectra have a significant blue shift from 508 to 406 nm. The dissymmetry factors for CD (gCD) change from ±2.5 × 10-3 to ±7.5 × 10-3 as dimensionality varies from 3D to 0D in the presence of the chiral molecule (cyclohexylethylamine, CHEA). A significant luminescence dissymmetry factor (glum) of ±5.6 × 10-4 is observed in the 0D CsPbBr3 NCs. Theoretical calculations using structural distortion parameters, the extent of charge transfer, and electrostatic potential profiles have revealed that the most significant enhancement of the chirality transfer occurs from the CHEA molecules to 0D NCs, and the order of chirality transfer from CHEA to CsPbBr3 NCs is 0D (quantum dots) > 2D (nanoplatelet) > 3D (cubic).

Metabolism and Excretion of [14C]Mobocertinib, a Selective Covalent Inhibitor of Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations, in Healthy Male Subjects.

Mobocertinib (formerly known as TAK-788) is a targeted covalent tyrosine kinase inhibitor of epidermal growth factor receptor with exon 20 insertion mutations. This article describes the metabolism and excretion of mobocertinib in healthy male subjects after a single oral administration of [14C]mobocertinib. Mobocertinib-related materials were highly covalently bound to plasma proteins such as human serum albumin. The mean extraction recovery of total radioactivity was only 3.9% for six individual Hamilton pooled plasma samples. After extraction, mobocertinib was the most abundant component accounting for 7.7% of total extracted circulating radioactivity (TECRA) in the supernatant. Each of identified metabolites accounted for <10% of TECRA. Mobocertinib underwent extensive first-pass metabolism with the fraction of the dose absorbed estimated to be approximately 91.7%. Fecal excretion of mobocertinib metabolites was the major elimination route. Mobocertinib was mainly eliminated via oxidative metabolism with a fraction of approximately 88% metabolized by CYP3A4/5. The other minor elimination pathways included cysteine conjugation, metabolism by other cytochrome P450s, and renal excretion of unchanged mobocertinib. SIGNIFICANCE STATEMENT: This article describes the metabolism and excretion of a targeted covalent inhibitor mobocertinib in humans after a single oral administration of [14C]mobocertinib. Mobocertinib was highly covalently bound to human plasma proteins. No metabolite accounted for >10% of total extracted circulating radioactivity in human plasma. Mobocertinib was mainly eliminated via CYP3A4/5 mediated oxidative metabolism followed by fecal excretion after approximately 91.7% of the dose was absorbed.

Deciphering Pauling's Third Rule: Uncovering Strong Anharmonicity and Exceptionally Low Thermal Conductivity in TlAgSe for Thermoelectrics.

Pauling's third empirical rule deals with the cationic repulsion due to proximity in the face or edge shared polyhedra in a crystal structure, can bring about the lattice instability required to suppress the lattice thermal conductivity (κL). Here, we demonstrate the presence of such instability in TlAgSe, leading to a ultra-low κL of 0.17 W/m.K at 573 K. Our study reveals the instability arising from Ag-Ag repulsion within edge-shared AgSe4 tetrahedra through investigation of the local structure using synchrotron X-ray pair distribution function (PDF)  and supported by density functional theory. We observe correlation between weakening in the Ag  and the Tl-sublattice, providing direct experimental evidence of Pauling's third rule. The correlated rattling of Ag and Tl induces a highly anharmonic lattice and low energy optical phonons, resulting in suppressed sound velocity and ultralow κL. The electronic origin of soft and anharmonic lattice is the presence of filled antibonding states in the valence band near the Fermi level constructed by Ag(4d)-Se(4p) and Tl(6s)-Se(4p) interactions. This work demonstrates that the evidence of dynamic distortion in a crystal lattice is governed by the third empirical rule given by Pauling, which can act as a potential new strategy for diminishing κL in crystalline solids.

High Ammonia Yield Rate from Dilute Nitrate Solutions Using a Cu(100)-Rich Foil: A Step Closer to Large-Scale Production.

The electrochemical reduction of nitrate (NO3-) ions to ammonia (NH3) provides an alternative method to eliminate harmful NO3- pollutants in water as well as to produce highly valuable NH3 chemicals. The NH3 yield rate however is still limited to the µmol h-1 cm-2 range when dealing with dilute NO3- concentrations found in waste streams. Copper (Cu) has attracted much attention because of its unique ability to effectively convert NO3- to NH3. We have reported a simple and scalable electrochemical method to produce a Cu foil having its surface covered with a porous Cu nanostructure enriched with (100) facets, which efficiently catalyzes NO3- to NH3. The Cu(100)-rich electrocatalyst showed a very high NH3 production rate of 1.1 mmol h-1 cm-2 in NO3- concentration as low as 14 mM NO3-, which is 4-5 times higher than the best-reported values. Increasing the NO3- concentration (140 mM) resulted in an NH3 production yield rate of 3.34 mmol h-1 cm-2. The durability test conducted for this catalyst foil in a flow cell system showed greater than 100 h stability with a Faradaic efficiency greater than 98%, demonstrating its potential to be used on an industrially relevant scale. Further, density functional theory (DFT) calculations have been performed to understand the better catalytic activity of Cu(100) compared to Cu(111) facets toward NO3-RR.

Synthesis and catalytic application of a donor-free bismuthenium cation.

Herein, we report the synthesis and catalytic application of a new N,N'-dineopentyl-1,2-phenylenediamine-based bismuthenium cation (3). 3 has been synthesized via the treatment of chlorobismuthane LBiCl [L = 1,2-C6H4{N(CH2tBu)}2] (2) with AgSbF6, and was further used as a robust catalyst for the cyanosilylation of ketones under mild reaction conditions. Experimental studies and DFT calculations were performed to understand the mechanistic pathway.

Long-Lived Interlayer Excitons in WS2/Ruddlesden-Popper Perovskite van der Waals Heterostructures.

Two-dimensional (2D) transition metal dichalcogenides (TMDs) and perovskites hold substantial promise for various optoelectronic applications such as light emission, photodetection, and energy harvesting. However, each of these materials possesses certain limitations that can be overcome by synergistically combining them to form heterostructures, thereby unveiling intriguing optical properties. In this study, we present an uncomplicated technique for crafting a van der Waals (vdW) heterojunction comprising monolayer WS2 and a Ruddlesden-Popper (RP) perovskite, namely (TEA)2PbI4. By utilizing ultrafast transient absorption (TA) spectroscopy, we explored the charge carrier dynamics within the WS2/(TEA)2PbI4 heterostructure. Our findings uncover a type-II band alignment in the heterostructure, facilitating rapid (within 260 fs) hole transfer from WS2 to the perovskite and leading to the formation of interlayer excitons (IXs) with a much longer lifetime (728 ps). This strategic approach has the potential to contribute to the development of hybrid systems aimed at achieving high-performance optoelectronic devices.

Integrated multi-omic analyses uncover the effects of aging on cell-type regulation in glucose-responsive tissues.

Aging significantly influences cellular activity and metabolism in glucose-responsive tissues, yet a comprehensive evaluation of the impacts of aging and associated cell-type responses has been lacking. This study integrates transcriptomic, methylomic, single-cell RNA sequencing, and metabolomic data to investigate aging-related regulations in adipose and muscle tissues. Through coexpression network analysis of the adipose tissue, we identified aging-associated network modules specific to certain cell types, including adipocytes and immune cells. Aging upregulates the metabolic functions of lysosomes and downregulates the branched-chain amino acids (BCAAs) degradation pathway. Additionally, aging-associated changes in cell proportions, methylation profiles, and single-cell expressions were observed in the adipose. In the muscle tissue, aging was found to repress the metabolic processes of glycolysis and oxidative phosphorylation, along with reduced gene activity of fast-twitch type II muscle fibers. Metabolomic profiling linked aging-related alterations in plasma metabolites to gene expression in glucose-responsive tissues, particularly in tRNA modifications, BCAA metabolism, and sex hormone signaling. Together, our multi-omic analyses provide a comprehensive understanding of the impacts of aging on glucose-responsive tissues and identify potential plasma biomarkers for these effects.

Highly Stable Self-Regenerating Organic Multi-Redox Systems derived from Bicyclic (Alkyl)(amino)carbenes (BICAACs).

An extended class of organic multi-redox systems was derived from bicyclic(alkyl)amino carbenes (BICAACs). The highly-conjugated system undergoes a total of 4 redox events spanning a 1.8 V redox range. These organic compounds exhibited four different stable redox states (dication, radical cation, neutral and radical anion), and all of them were characterized either by single crystal X-ray study and/or various spectroscopic studies. Three of the four redox states are stable to air and moisture. The availability of stable multiple redox states demonstrated promise towards their efficacy in the symmetric H-cell charge/discharge cycling. Among various redox states, the dication/neutral state works efficiently and continuously for 1500 cycles in 2e- charge/discharge process outside glovebox in commercially available DMF with minimum capacity loss (retaining nearly 90 % Coulombic efficiency). Surprisingly, the efficiency of the redox cycle was retained even if the system was exposed to air for 30 days when it slowly regenerated to the initial deep blue radical cation, and it exhibited another 100 charge/discharge cycles with a minimal capacity loss. Such a stable H-cell cycling ability is not well known among organic molecule-based systems.

TUNEL-n-DIFL Method for Detection and Estimation of Apoptosis Specifically in Neurons and Glial Cells in Mixed Culture and Animal Models of Central Nervous System Diseases and Injuries.

Detection of merely apoptosis does not reveal the type of central nervous system (CNS) cells that are dying in the CNS diseases and injuries. In situ detection and estimation of amount of apoptosis specifically in neurons or glial cells (astrocytes, oligodendrocytes, and microglia) can unveil valuable information for designing therapeutics for protection of the CNS cells and functional recovery. A method was first developed and reported from our laboratory for in situ detection and estimation of amount of apoptosis precisely in neurons and glial cells using in vitro and in vivo models of CNS diseases and injuries. This is a combination of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and double immunofluorescent labeling (DIFL) or simply TUNEL-n-DIFL method for in situ detection and estimation of amount of apoptosis in a specific CNS cell type. An anti-digoxigenin (DIG) IgG antibody conjugated with 7-amino-4-methylcoumarin-3-acetic acid (AMCA) for blue fluorescence, fluorescein isothiocyanate (FITC) for green fluorescence, or Texas Red (TR) for red fluorescence can be used for in situ detection of apoptotic cell DNA, which is earlier labeled with TUNEL using alkali-stable DIG-11-dUTP. A primary anti-NeuN (neurons), anti-GFAP (astrocytes), anti-MBP (oligodendrocytes), or anti-OX-42 (microglia) IgG antibody and a secondary IgG antibody conjugated with one of the above fluorophores (other than that of ani-DIG antibody) are used for in situ detection of apoptosis in a specific CNS cell type in the mixed culture and animal models of the CNS diseases and injuries.

Chromatographic Separation and Quantitation of Sphingolipids from the Central Nervous System or Any Other Biological Tissue.

Chromatographic separation and purification of an individual lipid to homogeneity have long been introduced. Using this concept, a more precise method has been developed to identify and characterize the sphingolipid composition(s) using a small amount (30 mg) of biological sample. Sphingolipids (lipids containing sphingosine or dihydrosphingosine) are well-known regulators of the central nervous system development and play a critical role in neurodegenerative diseases. Introducing a silicic acid column chromatography, sphingolipid components have been separated to individual fractions such as ceramide, glucosyl/galactosylceramide, other neutral and acidic glycosphingolipids, including (dihydro)sphingosine and psychosine; as well as phospholipids from which individual components are quantified employing a single or combination of other advanced chromatography procedures such as thin-layer chromatography, gas chromatography-mass spectrometry, and high-performance liquid chromatography-mass spectrometry.

Computational approach to enhance thermoelectric performance of Ag2Se by S and Te substitutions.

Designing an n-type thermoelectric material with a high thermoelectric figure of merit at near room temperature is extremely challenging. Generally, pristine Ag2Se reveals unusually low thermal conductivity along with a high electrical conductivity and Seebeck coefficient, which leads to high thermoelectric performance (n-type) at room temperature. Herein, we report a pseudo-ternary phase (Ag2Se0.5Te0.25S0.25) that exhibits significantly high thermoelectric performance (zT ∼ 2.1) even at 400 K. First-principles calculation reveals that the Rashba type of spin-dependent band spitting, which originates due to sulfur and tellurium substitution, helps to improve the thermopower magnitude. We also show that the intrinsic carrier mobility is not only controlled by the carrier effective mass but is substantially limited by longitudinal acoustic and optical phonon modes, which is an extension of the deformation potential theory. Locally off-center sulfur atoms, together with the increase in configurational entropy via substitution of Te and S atoms in Ag2Se, lead to a drastic reduction in the lattice thermal conductivity (klat ∼ 0.34 W m-1 K-1 at 400 K). The Rashba effect coupled with the configurational entropy synergistically results in a high thermoelectric figure of merit in the n-type thermoelectric material working in the near-room-temperature regime.

Hydrogen Evolution in Neutral Media by Differential Intermediate Binding at Charge-Modulated Sites of a Bimetallic Alloy Electrocatalyst.

The energy barrier to dissociate neutral water has been lowered by the differential intermediate binding on the charge-modulated metal centers of Co85Mo15 sheets supported on Ni-foam (NF), where the overpotential for hydrogen evolution reaction (HER) in 1 M phosphate buffer solution (PBS) is only 50±9 mV at -10 mA cm-2. It has a turnover frequency (TOF) of 0.18 s-1, mass activity of 13.2 A g-1 at -200 mV vs. reversible hydrogen electrode (RHE), and produces 16 ml H2 h-1 at -300 mV vs. RHE, more than double that of 20 % Pt/C. The Moδ+ and Coδ- sites adsorb OH*, and H*, respectively, and the electron injection from Co to H-O-H cleaves the O-H bond to form the Mo-OH* intermediate. Operando spectral analyses indicate a weak H-bonded network for facilitating the H2O*/OH* transport, and a potential-induced reversal of the charge density from Co to the more electronegative Mo, because of the electron withdrawing Co-H* and Mo-OH* species. Co85Mo15/NF can also drive the complete electrolysis of neutral water at only 1.73 V (10 mA cm-2). In alkaline, and acidic media, it demonstrates a Pt-like HER activity, accomplishing -1000 mA cm-2 at overpotentials of 161±7, and 175±22 mV, respectively.

A Multilayered Post-Genome-Wide Association Study Analysis Pipeline Defines Functional Variants and Target Genes for Systemic Lupus Erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE), an autoimmune disease with incompletely understood etiology, has a strong genetic component. Although genome-wide association studies (GWASs) have revealed multiple SLE susceptibility loci and associated single-nucleotide polymorphisms (SNPs), the precise causal variants, target genes, cell types, tissues, and mechanisms of action remain largely unknown. METHODS: Here, we report a comprehensive post-GWAS analysis using extensive bioinformatics, molecular modeling, and integrative functional genomic and epigenomic analyses to optimize fine-mapping. We compile and cross-reference immune cell-specific expression quantitative trait loci (cis- and trans-expression quantitative trait loci) with promoter capture high-throughput capture chromatin conformation (PCHi-C), allele-specific chromatin accessibility, and massively parallel reporter assay data to define predisposing variants and target genes. We experimentally validate a predicted locus using CRISPR/Cas9 genome editing, quantitative polymerase chain reaction, and Western blot. RESULTS: Anchoring on 452 index SNPs, we selected 9,931 high linkage disequilibrium (r2 > 0.8) SNPs and defined 182 independent non-human leukocyte antigen (HLA) SLE loci. The 3,746 SNPs from 143 loci were identified as regulating 564 unique genes. Target genes are enriched in lupus-related tissues and associated with other autoimmune diseases. Of these, 329 SNPs (106 loci) showed significant allele-specific chromatin accessibility and/or enhancer activity, indicating regulatory potential. Using CRISPR/Cas9, we validated reference SNP identifier 57668933 (rs57668933) as a functional variant regulating multiple targets, including SLE-risk gene ELF1 in B cells. CONCLUSION: We demonstrate and validate post-GWAS strategies for using multidimensional data to prioritize likely causal variants with cognate gene targets underlying SLE pathogenesis. Our results provide a catalog of significantly SLE-associated SNPs and loci, target genes, and likely biochemical mechanisms to guide experimental characterization.

KLF2 enhancer variant rs4808485 increases lupus risk by modulating inflammasome machinery and cellular homoeostasis.

OBJECTIVE: A recent genome-wide association study linked KLF2 as a novel Asian-specific locus for systemic lupus erythematosus (SLE) susceptibility. However, the underlying causal functional variant(s), cognate target gene(s) and genetic mechanisms associated with SLE risk are unknown. METHODS: We used bioinformatics to prioritise likely functional variants and validated the best candidate with diverse experimental techniques, including genome editing. Gene expression was compared between healthy controls (HCs) and patients with SLE with or without lupus nephritis (LN+, LN-). RESULTS: Through bioinformatics and expression quantitative trait locus analyses, we prioritised rs4808485 in active chromatin, predicted to modulate KLF2 expression. Luciferase reporter assays and chromatin immunoprecipitation-qPCR demonstrated differential allele-specific enhancer activity and binding of active histone marks (H3K27ac, H3K4me3 and H3K4me1), Pol II, CTCF, P300 and the transcription factor PARP1. Chromosome conformation capture-qPCR revealed long-range chromatin interactions between rs4808485 and the KLF2 promoter. These were directly validated by CRISPR-based genetic and epigenetic editing in Jurkat and lymphoblastoid cells. Deleting the rs4808485 enhancer in Jurkat (KO) cells disrupted NLRP3 inflammasome machinery by reducing KLF2 and increasing CASPASE1, IL-1ß and GSDMD levels. Knockout cells also exhibited higher proliferation and cell-cycle progression than wild type. RNA-seq validated interplay between KLF2 and inflammasome machinery in HC, LN+ and LN-. CONCLUSIONS: We demonstrate how rs4808485 modulates the inflammasome and cellular homoeostasis through regulating KLF2 expression. This establishes mechanistic connections between rs4808485 and SLE susceptibility.

Epigallocatechin-3-Gallate and Genistein for Decreasing Gut Dysbiosis, Inhibiting Inflammasomes, and Aiding Autophagy in Alzheimer's Disease.

There are approximately 24 million cases of Alzheimer's disease (AD) worldwide, and the number of cases is expected to increase four-fold by 2050. AD is a neurodegenerative disease that leads to severe dementia in most patients. There are several neuropathological signs of AD, such as deposition of amyloid beta (Aß) plaques, formation of neurofibrillary tangles (NFTs), neuronal loss, activation of inflammasomes, and declining autophagy. Several of these hallmarks are linked to the gut microbiome. The gastrointestinal (GI) tract contains microbial diversity, which is important in regulating several functions in the brain via the gut-brain axis (GBA). The disruption of the balance in the gut microbiota is known as gut dysbiosis. Recent studies strongly support that targeting gut dysbiosis with selective bioflavonoids is a highly plausible solution to attenuate activation of inflammasomes (contributing to neuroinflammation) and resume autophagy (a cellular mechanism for lysosomal degradation of the damaged components and recycling of building blocks) to stop AD pathogenesis. This review is focused on two bioflavonoids, specifically epigallocatechin-3-gallate (EGCG) and genistein (GS), as a possible new paradigm of treatment for maintaining healthy gut microbiota in AD due to their implications in modulating crucial AD signaling pathways. The combination of EGCG and GS has a higher potential than either agent alone to attenuate the signaling pathways implicated in AD pathogenesis. The effects of EGCG and GS on altering gut microbiota and GBA were also explored, along with conclusions from various delivery methods to increase the bioavailability of these bioflavonoids in the body.