Fabrication of SrTiO3 anchored rGO/g-C3N4 photocatalyst for the removal of mixed dye from wastewater: dual photocatalytic mechanism.

A metal-free combination of rGO/g-C3N4-coupled SrTiO3 (SRN) ternary nanocomposite prepared via a wet impregnation method for UV-Vis light photocatalytic applications. Various physicochemical properties of the samples were investigated by several spectroscopic techniques including X-ray diffraction (XRD), FT-IR, Raman, field emission scanning electron microscopy with energy dispersive X-ray spectroscopy (FE-SEM-EDX), high-resolution transmission electron microscopy (HR-TEM), UV-Vis, photoluminescence (PL), X-ray photoelectron spectroscopy (XPS) and Brunauer-Emmett-Teller (BET) surface area analysis. The data suggest agglomerated SRT nanoparticles are dispersed and distributed throughout the surface of the rGO sheets and GCN nanostructures. The photocatalytic performance of the SRN towards combined mixed dye and its degradation activities were evaluated towards the most common industrial effluents, Rhodamine B (RhB) and Methylene blue (MB), under UV-Vis light illumination. The results revealed that the degradation efficiency of the SRN photocatalyst shows excellent performance compared with that of the binary composition and the pure SrTiO3 (SRT) sample. The reaction rate constant for RhB was estimated to be 0.0039 min-1 and for MB to be 0.0316 min-1, which are 3.26 (RhB) and 4.21 (MB) times faster than the pure SRT sample. The enhanced degradation efficiency was attained not only by interfacial formation but also by the speedy transportation of electrons across the heterojunction. After 5 runs of the photocatalytic recylic process, the SRN photocatalyst exhibited ultimate stability without structural changes, and no noticeable degradation was observed. The outcomes of the ternary SRN nanocomposite manifest a dual photocatalytic scheme, the photocatalytic enrichment could be caused by the Z-scheme charge transfer process between GCN, SRT, and rGO nanocomposite, which helps effectual charge separation and keeps a high redox potential. From the results, SRN sample provides insight into the integration of an effective and potential photocatalyst for wastewater treatment toward real-time environmental remediation applications.

Leprosy: Comprehensive insights into pathology, immunology, and cutting-edge treatment strategies, integrating nanoparticles and ethnomedicinal plants.

Mycobacterium leprae is the causative agent responsible for the chronic disease known as leprosy. This condition is characterized by dermal involvement, often leading to peripheral nerve damage, sensory-motor loss, and related abnormalities. Both innate and acquired immunological responses play a role in the disease, and even in individuals with lepromatous leprosy, there can be a transient increase in T cell immunity during lepromatous reactions. Diagnosing of early-stage leprosy poses significant challenges. In this context, nanoparticles have emerged as a promising avenue for addressing various crucial issues related to leprosy. These include combatting drug resistance, mitigating adverse effects of conventional medications, and enhancing targeted drug delivery. This review serves as a comprehensive compilation, encompassing aspects of pathology, immunology, and adverse effects of multidrug delivery systems in the context of leprosy treatment. Furthermore, the review underscores the significance of ethnomedicinal plants, bioactive secondary metabolites, and nanotherapeutics in the management of leprosy. It emphasizes the potential to bridge the gap between existing literature and ongoing research efforts, with a profound scope for validating traditional claims, developing herbal medicines, and formulating nanoscale drug delivery systems that are safe, effective, and widely accepted.

Sesamol: A lignan in sesame seeds with potent anti-inflammatory and immunomodulatory properties.

Inflammation is associated with the development and progression of a plethora of diseases including joint, metabolic, neurological, hepatic, and renal disorders. Sesamol, derived from the seeds of Sesamum indicum L., has received considerable attention due to its well-documented multipotent phytotherapeutic effects, including its anti-inflammatory and immunomodulatory properties. However, to date, no comprehensive review has been established to highlight or summarize the anti-inflammatory and immunomodulatory properties of sesamol. Herein, we aim to address this gap in the literature by presenting a thorough review encapsulating evidence surrounding the range of inflammatory mediators and cytokines shown to be targeted by sesamol in modulating its anti-inflammatory actions against a range of inflammatory disorders. Additionally, evidence highlighting the role that sesamol has in modulating components of adaptive immunity including cellular immune responses and Th1/Th2 balance is underscored. Moreover, the molecular mechanisms and the signaling pathways underlying such effects are also highlighted. Findings indicate that this seemingly potent lignan mediates its anti-inflammatory actions, at least in part, via suppression of various pro-inflammatory cytokines like IL-1ß and TNFα, and downregulation of a multitude of signaling pathways including NF-κB and MAPK. In conclusion, we anticipate that sesamol may be employed in future therapeutic regimens to aid in more effective drug development to alleviate immune-related and inflammatory conditions.

High-sensitive detection and quantitation of thyroid-stimulating hormone (TSH) from capillary/fingerstick and venepuncture whole-blood using fluorescence-based rapid lateral flow immunoassay (LFIA).

Background: In the last decade, point of care testing (POCT) such as lateral flow immunoassays (LFIA) were developed for rapid TSH measurement. Most of these TSH-LFIAs are designed for qualitative measurements (i.e., if TSH values > 5, or >15 IU/L) and as screening tests for primary hypothyroidism in children and adults. Serum or plasma, but not venepuncture whole-blood or fingerstick/capillary, are usually used to quantify TSH accurately. Studies on performance evaluation of TSH-LFIAs POCT using venepuncture or fingerstick whole-blood are limited. Additionally, limited studies evaluated the performance and validity of TSH-LFIAs POCT compared to valid and reliable reference methods. To our knowledge, this is the first study to evaluate three different blood withdrawal techniques for evaluating POCT of TSH. Aim: We aim to evaluate the performance of a new fluorescence-based LFIA and its Finecare™ fluorescent reader for quantitative measurement of TSH from a fingerstick, venepuncture whole-blood, and serum. Methods: 102 fingerstick, venepuncture whole-blood, and serum samples (with normal and abnormal TSH values) were analyzed by Finecare™ Rapid Quantitative LFIA test and Roche CobasPro-c503 as a reference test. Results: Using serum, when compared to CobasPro-c503 reference method, Finecare™ showed high sensitivity [90.5 % (69.6-98.8)] and specificity [96.3 % (89.6-99.2)] for diagnosis of thyroid abnormalities (<0.35 or >4.5 mIU/L). The actual test values (mIU/L) of Finecare™ showed excellent agreement (Cohen's Kappa = 0.85) and strong correlation (r = 0.93, p < 0.0001) with CobasPro-c503. Using venepuncture whole-blood samples, Finecare™ showed similar results to serum with high sensitivity [95.2 % (76.2-99.9)], specificity [97.5 % (91.4-99.7)], excellent agreement (Cohen's Kappa = 0.91), and very strong correlation (r = 0.95, p < 0.0001) with CobasPro-c503. These results suggest that Finecare™ can be used for quantitative measurement of TSH using serum or venepuncture whole-blood. These key performance indicators were slightly decreased when fingerstick whole-blood samples were used: sensitivity [85.7 %(63.7-97)], specificity [90.0 %,(81.5-96)], good agreement (Cohen's Kappa = 0.7) and very strong correlation (r = 0.9, p < 0.0001) with CobasPro-c503. A subgroup analysis of abnormal TSH samples revealed a strong and significant correlation between the reference, Finecare™ whole-blood (r = 0.692; p = 0.0015), and fingerstick test Finecare™ (r = 0.66; p = 0.0025). A very strong correlation was also observed between Cobaspro-c508 serum and Finecare™ serum (r = 0.88; p < 0.0001). Conclusion: In comparison to the reference assay, our study demonstrates that Finecare™ exhibits high sensitivity, specificity, agreement, and a strong correlation. These findings provide evidence that Finecare™ is a reliable, valid, and accurate point-of-care test for TSH screening and quantitative measurement, especially in non- or small laboratory settings.

Hypolipidemic and Anti-Atherogenic Effects of Sesamol and Possible Mechanisms of Action: A Comprehensive Review.

Sesamol is a phenolic lignan isolated from Sesamum indicum seeds and sesame oil. Numerous studies have reported that sesamol exhibits lipid-lowering and anti-atherogenic properties. The lipid-lowering effects of sesamol are evidenced by its effects on serum lipid levels, which have been attributed to its potential for significantly influencing molecular processes involved in fatty acid synthesis and oxidation as well as cholesterol metabolism. In this review, we present a comprehensive summary of the reported hypolipidemic effects of sesamol, observed in several in vivo and in vitro studies. The effects of sesamol on serum lipid profiles are thoroughly addressed and evaluated. Studies highlighting the ability of sesamol to inhibit fatty acid synthesis, stimulate fatty acid oxidation, enhance cholesterol metabolism, and modulate macrophage cholesterol efflux are outlined. Additionally, the possible molecular pathways underlying the cholesterol-lowering effects of sesamol are presented. Findings reveal that the anti-hyperlipidemic effects of sesamol are achieved, at least in part, by targeting liver X receptor α (LXRα), sterol regulatory element binding protein-1 (SREBP-1), and fatty acid synthase (FAS) expression, as well as peroxisome proliferator-activated receptor α (PPARα) and AMP activated protein kinase (AMPK) signaling pathways. A detailed understanding of the molecular mechanisms underlying the anti-hyperlipidemic potential of sesamol is necessary to assess the possibility of utilizing sesamol as an alternative natural therapeutic agent with potent hypolipidemic and anti-atherogenic properties. Research into the optimal sesamol dosage that may bring about such favorable hypolipidemic effects should be further investigated, most importantly in humans, to ensure maximal therapeutic benefit.

Performance Evaluation of a New Fluorescent-Based Lateral Flow Immunoassay for Quantification of Hemoglobin A1c (HBA1c) in Diabetic Patients.

BACKGROUND: Rapid hemoglobin A1C (HbA1c) level monitoring is essential in slowing the progression of diabetes. This need becomes challenging in low resources countries where the social burden of the disease is overwhelming. Recently, fluorescent-based lateral flow immunoassays (LFIAs) gained wide attention for small laboratories and population surveillance. AIM: We aim to evaluate the performance of Finecare™ HbA1c Rapid Test, certified by CE, NGSP, and IFCC, for the quantitative measurement of hemoglobin A1C (HbA1c) along with its reader. METHODS: A total of 100 (fingerstick and venepuncture whole blood) samples were analyzed by Wondfo Finecare™ HbA1c Rapid Quantitative Test and the results were compared with the reference assay Cobas Pro c503. RESULTS: A strong correlation was observed between Finecare™/Cobas Pro c503 with fingerstick (r > 0.93, p < 0.0001) and venous (r > 0.97, p < 0.0001) blood samples. Finecare™ measurements showed excellent agreement and compliance with Roche Cobas Pro c503 as the mean bias was negligible; 0.05 (Limits-of-agreement: -0.58-0.68) with fingerstick and 0.003 (Limits-of-agreement: -0.49-0.50) with venous blood. Interestingly, a very small mean bias (0.047) was also shown between the fingerstick and the venepuncture data, indicating that the type of sample used does not affect the results and the high reproducibility of the assay. Finecare™ showed 92.0% (95% CI: 74.0-99.0) sensitivity and 94.7% (95% CI: 86.9-98.5) specificity compared to the Roche Cobas Pro c503 using fingerstick whole blood samples. Finecare™ showed 100% (95% CI: 86.3-100) sensitivity and 98.7% (95% CI: 92.8-100) specificity compared to the Cobas Pro c503 using venepuncture samples. Cohen's Kappa denoted excellent agreement with Cobas Pro c503; 0.84 (95% CI: 0.72-0.97) and 0.97 (95% CI: 0.92-1.00) using fingerstick and venous blood samples, respectively. Most importantly, Finecare™ showed a significant difference between normal, pre-diabetic, and diabetic samples (p < 0.0001). Similar results were obtained when an additional 47 samples (from different participants; mainly diabetic) were analyzed in a different lab using different Finecare™ analyzer and different kit lot number. CONCLUSIONS: Finecare™ is a reliable and rapid assay (5 min) which can be easily implemented for long-term monitoring of HbA1c in diabetic patients, particularly in small laboratory settings.

Discovery of novel papain-like protease inhibitors for potential treatment of COVID-19.

The recent emergence of different SARS-CoV-2 variants creates an urgent need to develop more effective therapeutic agents to prevent COVID-19 outbreaks. Among SARS-CoV-2 essential proteases is papain-like protease (SARS-CoV-2 PLpro), which plays multiple roles in regulating SARS-CoV-2 viral spread and innate immunity such as deubiquitinating and deISG15ylating (interferon-induced gene 15) activities. Many studies are currently focused on targeting this protease to tackle SARS-CoV-2 infection. In this context, we performed a phenotypic screening using an in-house pilot compounds collection possessing a diverse skeleta against SARS-CoV-2 PLpro. This screen identified SIMR3030 as a potent inhibitor of SARS-CoV-2. SIMR3030 has been shown to exhibit deubiquitinating activity and inhibition of SARS-CoV-2 specific gene expression (ORF1b and Spike) in infected host cells and possessing virucidal activity. Moreover, SIMR3030 was demonstrated to inhibit the expression of inflammatory markers, including IFN-α, IL-6, and OAS1, which are reported to mediate the development of cytokine storms and aggressive immune responses. In vitro absorption, distribution, metabolism, and excretion (ADME) assessment of the drug-likeness properties of SIMR3030 demonstrated good microsomal stability in liver microsomes. Furthermore, SIMR3030 demonstrated very low potency as an inhibitor of CYP450, CYP3A4, CYP2D6 and CYP2C9 which rules out any potential drug-drug interactions. In addition, SIMR3030 showed moderate permeability in Caco2-cells. Critically, SIMR3030 has maintained a high in vivo safety profile at different concentrations. Molecular modeling studies of SIMR3030 in the active sites of SARS-CoV-2 and MERS-CoV PLpro were performed to shed light on the binding modes of this inhibitor. This study demonstrates that SIMR3030 is a potent inhibitor of SARS-CoV-2 PLpro that forms the foundation for developing new drugs to tackle the COVID-19 pandemic and may pave the way for the development of novel therapeutics for a possible future outbreak of new SARS-CoV-2 variants or other Coronavirus species.

Stereodivergent Desymmetrization of Phenols En Route to Modular Access to Densely Functionalized Quinazoline and Oxazine Scaffolds.

The de novo assembly of stereochemically and skeletally diverse scaffolds is a powerful tool for the discovery of novel chemotypes. Hence, the development of modular, step- and atom-economic synthetic methods to access stereochemically and skeletally diverse compound collection is particularly important. Herein, we show a metal-free, stereodivergent build/couple/pair strategy that allows access to a unique collection of benzo[5,6][1,4]oxazino[4,3-a]quinazoline, quinolino[1,2-a]quinazoline and benzo[b]benzo [4,5]imidazo[1,2-d][1,4]oxazine scaffolds with complete diastereocontrol and wide distribution of molecular architectures. This metal-free process proceeds via desymmetrization of phenol derivatives. The cascade unites Mannich with aza-Michael addition reactions, providing expeditious entries to diverse classes of molecular shapes in a single operation.

Validation of a Novel Fluorescent Lateral Flow Assay for Rapid Qualitative and Quantitative Assessment of Total Anti-SARS-CoV-2 S-RBD Binding Antibody Units (BAU) from Plasma or Fingerstick Whole-Blood of COVID-19 Vaccinees.

Background: Limited commercial LFA assays are available to provide a reliable quantitative measurement of the total binding antibody units (BAU/mL) against the receptor-binding domain of the SARS-CoV-2 spike protein (S-RBD). Aim: This study aimed to evaluate the performance of the fluorescence LFA FinecareTM 2019-nCoV S-RBD test along with its reader (Model No.: FS-113) against the following reference methods: (i) the FDA-approved GenScript surrogate virus-neutralizing assay (sVNT); and (ii) three highly performing automated immunoassays: BioMérieux VIDAS®3, Ortho VITROS®, and Mindray CL-900i®. Methods: Plasma from 488 vaccinees was tested by all aforementioned assays. Fingerstick whole-blood samples from 156 vaccinees were also tested by FinecareTM. Results and conclusions: FinecareTM showed 100% specificity, as none of the pre-pandemic samples tested positive. Equivalent FinecareTM results were observed among the samples taken from fingerstick or plasma (Pearson correlation r = 0.9, p < 0.0001), suggesting that fingerstick samples are sufficient to quantitate the S-RBD BAU/mL. A moderate correlation was observed between FinecareTM and sVNT (r = 0.5, p < 0.0001), indicating that FinecareTM can be used for rapid prediction of the neutralizing antibody (nAb) post-vaccination. FinecareTM BAU results showed strong correlation with VIDAS®3 (r = 0.6, p < 0.0001) and moderate correlation with VITROS® (r = 0.5, p < 0.0001) and CL-900i® (r = 0.4, p < 0.0001), suggesting that FinecareTM can be used as a surrogate for the advanced automated assays to measure S-RBD BAU/mL.

Immunomodulatory and Anti-Inflammatory Effects of Berberine in Lung Tissue and its Potential Application in Prophylaxis and Treatment of COVID-19.

Natural products with known safety profiles are a promising source for the discovery of new drug leads. Berberine presents an example of one such phytochemical that has been extensively studied for its anti-inflammatory and immunomodulatory properties against myriads of diseases, ranging from respiratory disorders to viral infections. A growing body of research supports the pluripotent therapeutic role berberine may play against the dreaded disease COVID-19. The exact pathophysiological features of COVID-19 are yet to be elucidated. However, compelling evidence suggests inflammation and immune dysregulations as major features of this disease. Being a potent immunomodulatory and anti-inflammatory agent, berberine may prove to be useful for the prevention and treatment of COVID-19. This review aims to revisit the pharmacological anti-inflammatory and immunomodulatory benefits of berberine on a multitude of respiratory infections, which like COVID-19, are known to adversely affect the airways and lungs. We speculate that berberine may help alleviate COVID-19 via preventing cytokine storm, restoring Th1/Th2 balance, and enhancing cell-mediated immunity. Furthermore, the role this promising phytochemical plays on other important inflammatory mediators involved in respiratory disorders will be underscored. We further highlight the role of berberine against COVID-19 by underscoring direct evidence from in silico, in vitro, and in vivo studies suggesting the inhibitory potential berberine may play against three critical SARS-CoV-2 targets, namely main protease, spike protein, and angiotensin-converting enzyme 2 receptor. Further preclinical and clinical trials are certainly required to further substantiate the efficacy and potency of berberine against COVID-19 in humans.

JC-10 probe as a novel method for analyzing the mitochondrial membrane potential and cell stress in whole zebrafish embryos.

BACKGROUND: A sensitive method to investigate cellular stress and cytotoxicity is based on measuring mitochondrial membrane potential. Recently, JC-10, was developed to measure mitochondrial membrane potential in vitro and used as an indicator for cytotoxicity. Yet, JC-10 has never been used in vivo (whole organism). In normal cells, JC-10 concentrates in the mitochondrial matrix, where it forms red fluorescent aggregates. However, in apoptotic/necrotic cells, JC-10 diffuses out of the mitochondria, changes to monomeric form, and stains cells in green. Here, we aimed to develop and optimize a JC-10 assay to measure cytotoxicity in zebrafish embryo. We also investigated the effectiveness of JC-10 assay by comparing it to common cytotoxicity assays. METHODS: Zebrafish embryos were exposed to a toxic surfactant AEO-7 at no observed effect concentration (6.4 µg/L), and then cytotoxicity was measured using (i) JC-10 mitochondrial assay, (ii) acridine orange (AO), (iii) TUNEL assay, and (iv) measuring the level of Hsp70 by western blotting. RESULTS: As compared to the negative control, embryos treated with NOEC of AEO-7 did not show significant cytotoxicity when assessed by AO, TUNEL or western blotting. However, when JC-10 was used under the same experimental conditions, a significant increase of green:red fluorescent ratio signal was detected in the AEO-7 treated embryos, indicating mitochondrial damage and cellular cytotoxicity. Noteworthy, the observed green: red ratio increase was dose dependent, suggesting specificity of the JC-10 assay. CONCLUSION: JC-10 is a sensitive in vivo method, thus, can be used as surrogate assay to measure cytotoxicity in whole zebrafish embryos.

Stereodivergent Complexity-to-Diversity Strategy en Route to the Synthesis of Nature-Inspired Skeleta.

The complexity-to-diversity (CtD) strategy has become one of the most powerful tools used to transform complex natural products into diverse skeleta. However, the reactions utilized in this process are often limited by their compatibility with existing functional groups, which in turn restricts access to the desired skeletal diversity. In the course of employing a CtD strategy en route to the synthesis of natural product-inspired compounds, our group has developed several stereodivergent strategies employing indoloquinolizine natural product analogues as starting materials. These transformations led to the rapid and diastereoselective synthesis of diverse classes of natural product-like architectures, including camptothecin-inspired analogues, azecane medium-sized ring systems, arborescidine-inspired systems, etc. This manifestation required a drastic modification of the synthetic design that ultimately led to modular and diastereoselective access to a diverse collection of various classes of biologically significant natural product analogues. The reported strategies provide a unique platform that will be broadly applicable to other late-stage natural product transformation approaches.

Immunomodulatory and anti-inflammatory effects of sesamin: mechanisms of action and future directions.

Inflammation is associated with the development and progression of various disorders including atherosclerosis, diabetes mellitus and cancer. Sesamin, a fat-soluble lignan derived from Sesamum indicum seeds and oil, has received increased attention due to its wide array of pharmacological properties including its immunomodulatory and anti-inflammatory potential. To date, no review has been conducted to summarize or analyze the immunomodulatory and anti-inflammatory roles of sesamin. Herein, we provide a comprehensive review of experimental findings that were reported with regards to the ability of sesamin to modulate inflammation, cellular and humoral adaptive immune responses and Th1/Th2 paradigm. The potential influence of sesamin on the cytotoxic activity of NK cells against cancer cells is also highlighted. The molecular mechanisms and the signal transduction pathways underlying such effects are underscored. The metabolism, pharmacokinetics, absorption, tissue distribution and bioavailability of sesamin in different species, including humans, are reviewed. Moreover, we propose future preclinical and clinical investigations to further validate the potential preventive and/or therapeutic efficacy of sesamin against various immune-related and inflammatory conditions. We anticipate that sesamin may be employed in future therapeutic regimens to enhance the efficacy of treatment and dampen the adverse effects of synthetic chemical drugs currently used to alleviate immune-related and inflammatory conditions.

Thymoquinone, a major constituent in Nigella sativa seeds, is a potential preventative and treatment option for atherosclerosis.

Atherosclerosis is a widespread and progressive chronic arterial disease that remains the leading cause of mortality and morbidity worldwide. It is generally accepted that atherosclerosis is a multifactorial disease characterized by dyslipidemia and inflammation in the vessel walls. Nonpharmacological interventions to treat chronic diseases like atherosclerosis have gained considerable attention in recent years. Thymoquinone (TQ), the major bioactive constituent of Nigella sativa seeds, presents one such example of a natural therapeutic agent that has captured the attention of many researchers due to its wide array of medicinal properties, including its potent anti-atherosclerotic effects. Various in vitro and in vivo studies support the potential of TQ in ameliorating hyperlipidemia, hypercholesterolemia, oxidative stress, and inflammation, all of which are key hallmarks of atherosclerosis. However, to date, no review has been conducted to substantiate the role of TQ in preventing and/or treating atherosclerosis. This comprehensive review aims to examine recent in vitro and in vivo experimental findings reported on the potential anti-atherosclerotic effects of TQ. The roles of TQ in combatting hyperlipidemia, oxidative stress, and inflammation in atherosclerosis are highlighted. We also shed light on the role of TQ in preventing foam cell formation by decreasing low-density lipoprotein (LDL) availability and oxidation. Moreover, recent findings on the protective role of TQ on early markers of atherosclerosis, including homocysteinemia and endothelial dysfunction, are also underscored. Experimental evidence suggests that TQ can potentially be employed as a natural therapeutic agent with minimal side effects against the development and/or progression of atherosclerosis and its associated complications.

Bioluminescence Imaging Applications in Cancer: A Comprehensive Review.

Bioluminescence imaging (BLI), an optical preclinical imaging modality, is an invaluable imaging modality due to its low-cost, high throughput, fast acquisition times, and functional imaging capabilities. BLI is being extensively used in the field of cancer imaging, especially with the recent developments in genetic-engineering, stem cell, and gene therapy treatments. The purpose of this paper is to provide a comprehensive review of the principles, developments, and current status of BLI in cancer research. This paper covers the fundamental BLI concepts including BLI reporters and enzyme-substrate systems, data acquisition, and image characteristics. It reviews the studies discussing the use of BLI in cancer research such as imaging tumor-characteristic phenomena including tumorigenesis, metastasis, cancer metabolism, apoptosis, hypoxia, and angiogenesis, and response to cancer therapy treatments including chemotherapy, radiotherapy, immunotherapy, gene therapy, and stem cell therapy. The key advantages and disadvantages of BLI compared to other common imaging modalities are also discussed.

Health benefits of sesamin on cardiovascular disease and its associated risk factors.

Sesamin, a major lignin isolated from sesame (Sesamum indicum) seeds and sesame oil, is known to possess antioxidant and anti-inflammatory properties. Several studies have revealed that oxidative stress and inflammation play a major role in a variety of cardiovascular diseases (CVDs). This comprehensive review summarizes the evidence on the effects of sesamin on CVD and its risk factors, principally due to its antioxidant properties. Specifically, this review highlights the mechanisms underlying the anti-hypertensive, anti-atherogenic, anti-thrombotic, anti-diabetic, and anti-obesity, lipolytic effects of sesamin both in vivo and in vitro, and identifies the signaling pathways targeted by sesamin and its metabolites. The data indicates that RAS/MAPK, PI3K/AKT, ERK1/2, p38, p53, IL-6, TNFα, and NF-κB signaling networks are all involved in moderating the various effects of sesamin on CVD and its risk factors. In conclusion, the experimental evidence suggesting that sesamin can reduce CVD risk is convincing. Thus, sesamin can be potentially useful as an adjuvant therapeutic agent to combat CVD and its multitude of risk factors.

Organ-specific toxicity evaluation of stearamidopropyl dimethylamine (SAPDMA) surfactant using zebrafish embryos.

Surfactants are widely used in the industry of detergents, household products, and cosmetics. SAPDMA is a cationic surfactant that is used mostly in cosmetics, conditioning agents and has recently gained attention as a corrosion inhibitor in the sea pipelines industry. In this regard, literature concerning the ecotoxicological classification of SAPDMA on aquatic animals is lacking. This study aims to evaluate the potential ecotoxicity of SAPDMA using the aquatic zebrafish embryo model. The potential toxic effects of SAPDMA were assessed by different assays. This includes (i) mortality/survival assay to assess the median lethal concentration (LC50); (ii) teratogenicity assay to assess the no observed effect concentration (NOEC); (iii) organ-specific toxicity assays including cardiotoxicity, neurotoxicity (using locomotion assay), hematopoietic toxicity (hemoglobin synthesis using o-dianisidine staining), hepatotoxicity (liver steatosis and yolk retention using Oil Red O (ORO) stain); (iv) cellular cytotoxicity (mitochondrial membrane potential) by measuring the accumulation of JC-1 dye into mitochondria. Exposure of embryos to SAPDMA caused mortality in a dose-dependent manner with a calculated LC50 of 2.3 mg/L. Thus, based on the LC50 value and according to the Fish and Wildlife Service (FWS) Acute Toxicity Rating Scale, SAPDMA is classified as "moderately toxic". The No Observed Effect Concentration (NOEC) concerning a set of parameters including scoliosis, changes in body length, yolk, and eye sizes was 0.1 mg/L. At the same NOEC concentration (0.1 mg/L), no organ-specific toxicity was detected in fish treated with SAPDMA, except hepatomegaly with no associated liver dysfunctions. However, higher SAPDMA concentrations (0.8 mg/L) have dramatic effects on zebrafish organ development (eye, heart, and liver development). Our data recommend a re-evaluation of the SAPDMA employment in the industry setting and its strictly monitoring by environmental and public health agencies.

Divergent Strategy for Diastereocontrolled Synthesis of Small- and Medium-Ring Architectures.

Nitrogen and oxygen medium rings, in particular nine-membered rings, epitomize a unique area of chemical space that occurs in many natural products and biologically appealing compounds. The scarcity of 8- to 12-membered rings among clinically approved drugs is indicative of the difficulties associated with their synthesis, principally owing to the unfavorable entropy and transannular strain. We report here a scandium triflate-catalyzed reaction that allows for a modular access to a diverse collection of nine-membered ring heterocycles in a one-pot cascade and with complete diastereocontrol. This cascade features an intramolecular addition of an acyl group-derived enol to a α,ß-unsaturated carbonyl moiety, leading to N- and O-derived medium-ring systems. Computational studies using the density functional theory support the proposed mechanism. Additionally, a one-pot cascade leading to hexacyclic chromeno[3',4':2,3]indolizino[8,7-b]indole architectures, with six fused rings and four contiguous chiral centers, is reported. This novel cascade features many concerted events, including the formation of two azomethine ylides, [3 + 2]-cycloaddition, 1,3-sigmatropic rearrangement, Michael addition, and Pictet-Spengler reaction among others. Phenotypic screening of the resulting oxazonine collection identified chemical probes that regulate mitochondrial membrane potential, adenosine 5'-triphosphate contents, and reactive oxygen species levels in hepatoma cells (Hepa1-6), a promising approach for targeting cancer and metabolic disorders.

Effects of sesamin on fatty acid and cholesterol metabolism, macrophage cholesterol homeostasis and serum lipid profile: A comprehensive review.

Sesamin is the major lignan constituent derived from Sesamum indicum seeds and sesame oil. Various studies have reported that sesamin possesses potent lipid-lowering properties. The lipid-lowering effects of sesamin have been mainly attributed to its ability in affecting key events in fatty acid and cholesterol metabolism and in lowering atherogenesis-triggering LDL, VLDL and TG levels, as well as in increasing atheroprotective HDL levels. In this review, we provide a comprehensive summary of the reported anti-hyperlipidemic effects of sesamin, presented both in vitro and in vivo. The molecular anti-hyperlipidemic properties of sesamin that underlie its well-documented anti-atherogenic effects are thoroughly discussed and analyzed. Studies focusing on the ability of sesamin to inhibit fatty acid synthesis, induce fatty acid oxidation, inhibit cholesterol synthesis and absorption and maintain macrophage cholesterol homeostasis are outlined. The effects of sesamin on circulating serum and liver lipid levels are also highlighted. Moreover, the anti-hyperlipidemic effects of sesamin are compared to those of other important sesame lignans like sesamolin and episesamin. Findings reveal that sesamin mainly exerts its anti-hyperlipidemic effects by targeting Δ5 desaturase, HMGCR, ABCA1 and ABCG1 through PPARα, PPARγ, LXRα, and SREBP signaling pathways. Overall, the amount of evidence supporting the anti-hyperlipidemic potential of sesamin in vitro and in vivo is compelling. A thorough understanding of the mechanisms underlying the anti-hyperlipidemic properties of sesamin is imperative for the possible employment of sesamin as an anti-hyperlipidemic and anti-atherogenic agent with minimal side effects.

AEBP1 is a Novel Oncogene: Mechanisms of Action and Signaling Pathways.

Adipocyte enhancer-binding protein 1 (AEBP1) is a transcriptional repressor involved in the regulation of critical biological processes including adipogenesis, mammary gland development, inflammation, macrophage cholesterol homeostasis, and atherogenesis. Several years ago, we first reported the ability of AEBP1 to exert a positive control over the canonical NF-κB pathway. Indeed, AEBP1 positively regulates NF-κB activity via its direct interaction with IκBα, a key NF-κB inhibitor. AEBP1 overexpression results in uncontrollable activation of NF-κB, which may have severe pathogenic outcomes. Recently, the regulatory relationship between AEBP1 and NF-κB pathway has been of great interest to many researchers primarily due to the implication of NF-κB signaling in critical cellular processes such as inflammation and cancer. Since constitutive activation of NF-κB is widely implicated in carcinogenesis, AEBP1 overexpression is associated with tumor development and progression. Recent studies sought to explore the effects of the overexpression of AEBP1, as a potential oncogene, in different types of cancer. In this review, we analyze the effects of AEBP1 overexpression in a variety of malignancies (e.g., breast cancer, glioblastoma, bladder cancer, gastric cancer, colorectal cancer, ovarian cancer, and skin cancer), with a specific focus on the AEBP1-mediated control over the canonical NF-κB pathway. We also underscore the ability of AEBP1 to regulate crucial cancer-related events like cell proliferation and apoptosis in light of other key pathways (e.g., PI3K-Akt, sonic hedgehog (Shh), p53, parthanatos (PARP-1), and PTEN). Identifying AEBP1 as a potential biomarker for cancer prognosis may lead to a novel therapeutic target for the prevention and/or treatment of various types of cancer.