Proguanil Suppresses Breast Tumor Growth In Vitro and In Vivo by Inducing Apoptosis via Mitochondrial Dysfunction.

Breast cancer, ranking as the second leading cause of female cancer-related deaths in the U.S., demands the exploration of innovative treatments. Repurposing FDA-approved drugs emerges as an expedited and cost-effective strategy. Our study centered on proguanil, an antimalarial drug, reveals notable anti-proliferative effects on diverse breast cancer cell lines, including those derived from patients. Proguanil-induced apoptosis was associated with a substantial increase in reactive oxygen species (ROS) production, leading to reduced mitochondrial membrane potential, respiration, and ATP production. Proguanil treatment upregulated apoptotic markers (Bax, p-H2AX, cleaved-caspase 3, 9, cleaved PARP) and downregulated anti-apoptotic proteins (bcl-2, survivin) in breast cancer cell lines. In female Balb/c mice implanted with 4T1 breast tumors, daily oral administration of 20 mg/kg proguanil suppressed tumor enlargement by 55%. Western blot analyses of proguanil-treated tumors supported the in vitro findings, demonstrating increased levels of p-H2AX, Bax, c-PARP, and c-caspase3 as compared to controls. Our results collectively highlight proguanil's anticancer efficacy in vitro and in vivo in breast cancer, prompting further consideration for clinical investigations.

Miniature fluorescence sensor for quantitative detection of brain tumour.

Fluorescence-guided surgery has emerged as a vital tool for tumour resection procedures. As well as intraoperative tumour visualisation, 5-ALA-induced PpIX provides an avenue for quantitative tumour identification based on ratiometric fluorescence measurement. To this end, fluorescence imaging and fibre-based probes have enabled more precise demarcation between the cancerous and healthy tissues. These sensing approaches, which rely on collecting the fluorescence light from the tumour resection site and its "remote" spectral sensing, introduce challenges associated with optical losses. In this work, we demonstrate the viability of tumour detection at the resection site using a miniature fluorescence measurement system. Unlike the current bulky systems, which necessitate remote measurement, we have adopted a millimetre-sized spectral sensor chip for quantitative fluorescence measurements. A reliable measurement at the resection site requires a stable optical window between the tissue and the optoelectronic system. This is achieved using an antifouling diamond window, which provides stable optical transparency. The system achieved a sensitivity of 92.3% and specificity of 98.3% in detecting a surrogate tumour at a resolution of 1 × 1 mm2. As well as addressing losses associated with collecting and coupling fluorescence light in the current 'remote' sensing approaches, the small size of the system introduced in this work paves the way for its direct integration with the tumour resection tools with the aim of more accurate interoperative tumour identification.

Evaluation of urinary limonene metabolites as biomarkers of exposure to greenness.

Exposure to plants is known to improve physical and mental health and living in areas of high vegetation is associated with better health. The addition of quantitative measures of greenness exposure at individual-level to other objective and subjective study measures will help establish cause-and-effect relationships between greenspaces and human health. Because limonene is one of the most abundant biogenic volatile organic compounds emitted by plants, we hypothesized that urinary metabolites of inhaled limonene can serve as biomarkers of exposure to greenness. To test our hypothesis, we analyzed urine samples collected from eight human volunteers after limonene inhalation or after greenness exposure using liquid chromatography-high resolution mass spectrometry-based profiling. Eighteen isomers of nine metabolites were detected in urine after limonene inhalation, and their kinetic parameters were estimated using nonlinear mixed effect models. Urinary levels of most abundant limonene metabolites were elevated after brief exposure to a forested area, and the ratio of urinary limonene metabolites provided evidence of recent exposure. The identities and structures of these metabolites were validated using stable isotope tracing and tandem mass spectral comparison. Together, these data suggest that urinary metabolites of limonene, especially uroterpenol glucuronide and dihydroperillic acid glucuronide, could be used as individualized biomarkers of greenness exposure.

Metabolic Pathways for Removing Reactive Aldehydes are Diminished in Atrophic Muscle During Heart Failure.

Background: Muscle wasting is a serious complication in heart failure patients, and oxidative stress is involved in the pathogenesis of muscle wasting. Oxidative stress leads to the formation of toxic lipid peroxidation products, such as 4-hydroxy-2-nonenal (HNE) and acrolein, which causemuscle wasting. In tissues, these toxic aldehydes are metabolically removed by enzymes such asaldo keto reductases and endogenous nucleophiles, such as glutathione and carnosine. Whether these metabolic pathways could be affected in skeletal muscle during heart failure has never been studied. Methods: Male wild-type C57BL/6J mice were subjected to a pressure overload model of hypertrophy by transaortic constriction (TAC) surgery, and echocardiography was performed after 14 weeks. Different skeletal muscle beds were weighed and analyzed for atrophic and inflammatory markers, Atrogin1 and TRIM63, TNF-α and IL-6, respectively, by RT-PCR. Levels of acrolein and HNE-protein adducts, aldehyde-removing enzymes, aldose reductase (AKR1B1) and aldehyde dehydrogenase 2 (ALDH2) were measured by Western blotting, and histidyl dipeptides and histidyl dipeptide aldehyde conjugates were analyzed by LC/MS-MS in the gastrocnemius and soleus muscles of sham- and TAC-operated mice. Furthermore, histidyl dipeptide synthesizing enzyme carnosine synthase (CARNS) and amino acid transporters (PEPT2 and TAUT)wasmeasured in the gastrocnemius muscles of the sham and TAC-operated mice. Results: TAC-induced heart failure decreases body weight and gastrocnemius and soleus muscle weights. The expression of the atrophic and inflammatory markers Atrogin1 and TNF-α, respectively, wasincreased (~1.5-2-fold), and the formation of HNE and acrolein-protein adducts was increased in the gastrocnemius muscle of TAC-operated mice. The expression of AKR1B1 remained unchanged, whereas ALDH2 was decreased, in the gastrocnemius muscle of TAC mice. Similarly, in the atrophic gastrocnemius muscle, levels of total histidyl dipeptides (carnosine and anserine) and, in particular,carnosine were decreased. Depletion of histidyl dipeptides diminished the aldehyde removal capacity of the atrophic gastrocnemius muscle. Furthermore, the expression of CARNS and TAUT wasdecreased in the atrophic gastrocnemius muscle. Conclusions: Collectively, these results show that metabolic pathways involved in the removal of lipid peroxidation products and synthesis of histidyl dipeptides are diminished in atrophic skeletal muscle during heart failure, which could contribute to muscle atrophy.

The Green Heart Project: Objectives, Design, and Methods.

The Green Heart Project is a community-based trial to evaluate the effects of increasing greenery on urban environment and community health. The study was initiated in 2018 in a low-to-middle-income mixed-race residential area of nearly 28,000 residents in Louisville, KY. The 4 square mile area was surveyed for land use, population characteristics, and greenness, and assigned to 8 paired clusters of demographically- and environmentally matched "target" (T) and adjacent "control" (C), clusters. Ambient levels of ultrafine particles, ozone, oxides of nitrogen, and environmental noise were measured in each cluster. Individual-level data were acquired during in-person exams of 735 participants in Wave 1 (2018-2019) and 545 participants in Wave 2 (2021) to evaluate sociodemographic and psychosocial factors. Blood, urine, nail, and hair samples were collected to evaluate standard cardiovascular risk factors, inflammation, stress, and pollutant exposure. Cardiovascular function was assessed by measuring arterial stiffness and flow-mediated dilation. After completion of Wave 2, more than 8,000 mature, mostly evergreen, trees and shrubs were planted in the T clusters in 2022. Post planting environmental and individual-level data were collected during Wave 3 (2022) from 561 participants. We plan to continue following changes in area characteristics and participant health to evaluate the long-term impact of increasing urban greenery.

Aldose Reductase (AR) Mediates and Perivascular Adipose Tissue (PVAT) Modulates Endothelial Dysfunction of Short-Term High-Fat Diet Feeding in Mice.

Increased adiposity of both visceral and perivascular adipose tissue (PVAT) depots is associated with an increased risk of diabetes and cardiovascular disease (CVD). Under healthy conditions, PVAT modulates vascular tone via the release of PVAT-derived relaxing factors, including adiponectin and leptin. However, when PVAT expands with high-fat diet (HFD) feeding, it appears to contribute to the development of endothelial dysfunction (ED). Yet, the mechanisms by which PVAT alters vascular health are unclear. Aldose reductase (AR) catalyzes glucose reduction in the first step of the polyol pathway and has been long implicated in diabetic complications including neuropathy, retinopathy, nephropathy, and vascular diseases. To better understand the roles of both PVAT and AR in HFD-induced ED, we studied structural and functional changes in aortic PVAT induced by short-term HFD (60% kcal fat) feeding in wild type (WT) and aldose reductase-null (AR-null) mice. Although 4 weeks of HFD feeding significantly increased body fat and PVAT mass in both WT and AR-null mice, HFD feeding induced ED in the aortas of WT mice but not of AR-null mice. Moreover, HFD feeding augmented endothelial-dependent relaxation in aortas with intact PVAT only in WT and not in AR-null mice. These data indicate that AR mediates ED associated with short-term HFD feeding and that ED appears to provoke 'compensatory changes' in PVAT induced by HFD. As these data support that the ED of HFD feeding is AR-dependent, vascular-localized AR remains a potential target of temporally selective intervention.

Exploring quantum computational, molecular docking, and molecular dynamics simulation with MMGBSA studies of ethyl-2-amino-4-methyl thiophene-3-carboxylate.

2-aminothiophenes derivative, Ethyl-2-amino-4-methyl thiophene-3-carboxylate (EAMC) has been synthesized, characterized, and investigated quantum chemically. It was experimentally investigated by different spectroscopic methods like- NMR (1H-NMR and 13C-NMR), FT-IR, and UV-Visible. B3LYP method and 6-311++G(d,p) basis set were employed for optimization of molecular structure and calculation of wave numbers of normal modes of vibrations and various other important parameters. Calculated bond lengths and angles were compared with the experimental bond lengths and Bond Angle Parameters. Optimized bond parameters and experimental bond parameters were found in good agreement. Complete potential energy distribution assignments were done successfully by VEDA. The HOMO/LUMO energy gap emphasizes adequate charge transfer happening within the molecule. A study of donor-acceptor interconnections was done via NBO analysis. MEP surface analysis was done to demonstrate charge distribution and reactive areas qualitatively in the molecule. The degree of relative localization of electrons was analyzed via ELF Diagram. The Fukui function analysis showed possible sites for attacks by different substituents. By using the TD-DFT method and PCM solvent model, the UV-Vis spectrum (gas, methanol, DMSO) and the maximum absorption wavelength was computed and compared with experimental data. 3D and 2D intermolecular interactions in the crystal were analyzed via Hirshfeld surface analysis and fingerprint plots reveal that the EAMC crystal was stabilized by H--H/H--H/C--H bond formation. The molecular docking was done with 7 different protein receptors on the molecule to find the best ligand-protein interactions. Molecular dynamic simulations and MMGBSA calculations were also carried out to find out the best binding of the ligand with the protein.Communicated by Ramaswamy H. Sarma.

The Cell and Gene Therapy Consortium's Perspective on Harmonizing Data Collection for Patient Enrollment, Therapy Ordering and Scheduling, and Cell Collection.

Established in October 2021, the Cell and Gene Therapy (CGT) Consortium convened with the goal to bring together key CGT stakeholders - manufacturers, treatment centers, regulators, services providers, and ecosystem partners - to gain alignment on process definitions, terminology, challenges, and opportunities for process and data standardization from CGT program start-up and patient enrollment to therapy administration. With the recognition that the number of investigational and commercial cell and gene therapies will scale over the next several years, so will the number of manufacturer-specific processes and solutions (e.g., portals). As a result, this will increase the burden on academic medical centers, community hospitals, standalone clinics, collection facilities, and labs. Healthcare professionals (HCPs) and other industry stakeholders agree that a multiplicity of manufacturer portals with varying data requirements and nomenclature is unsustainable and adds unnecessary complexity - risk, cost, and time - in coordinating patient treatment. Following extensive discussions and multiple stakeholder meetings and interviews, we have developed a manuscript reporting on our activities and conclusions. Through the course of the manuscript, we delineate a framework for defining common principles, terminology, and user experiences for enrolling patients, ordering therapies, and collecting starting material in a standardized way. We also provide substantial background information on opportunities to streamline communications between manufacturing and healthcare organizations from the HCP end-user's perspective.

Global Profiling of Urinary Mercapturic Acids Using Integrated Library-Guided Analysis.

Urinary mercapturic acids (MAs) are often used as biomarkers for monitoring human exposures to occupational and environmental xenobiotics. In this study, we developed an integrated library-guided analysis workflow using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry. This method includes expanded assignment criteria and a curated library of 220 MAs and addresses the shortcomings of previous untargeted approaches. We employed this workflow to profile MAs in the urine of 70 participants─40 nonsmokers and 30 smokers. We found approximately 500 MA candidates in each urine sample, and 116 MAs from 63 precursors were putatively annotated. These include 25 previously unreported MAs derived mostly from alkenals and hydroxyalkenals. Levels of 68 MAs were comparable in nonsmokers and smokers, 2 MAs were higher in nonsmokers, and 46 MAs were elevated in smokers. These included MAs of polycyclic aromatic hydrocarbons and hydroxyalkenals and those derived from toxicants present in cigarette smoke (e.g., acrolein, 1,3-butadiene, isoprene, acrylamide, benzene, and toluene). Our workflow allowed profiling of known and unreported MAs from endogenous and environmental sources, and the levels of several MAs were increased in smokers. Our method can also be expanded and applied to other exposure-wide association studies.

Highly Responsive Near-Infrared Si/Sb2Se3 Photodetector via Surface Engineering of Silicon.

The development of imaging technology and optical communication demands a photodetector with high responsiveness. As demonstrated by microfabrication and nanofabrication technology advancements, recent progress in plasmonic sensor technologies can address this need. However, these photodetectors have low optical absorption and ineffective charge carrier transport efficiency. Sb2Se3 is light-sensitive material with a high absorption coefficient, making it suitable for photodetector applications. We developed an efficient, scalable, low-cost near-infrared (NIR) photodetector based on a nanostructured Sb2Se3 film deposited on p-type micropyramidal Si (made via the wet chemical etching process), working on photoconductive phenomena. Our results proved that, at the optimized thickness of the Sb2Se3 layer, the proposed Si micropyramidal substrate enhanced the responsivity nearly two times, compared with that of the Sb2Se3 deposited on a flat Si reference sample and a glass/Sb2Se3 sample at 1064 nm (power density = 15 mW/cm2). More interestingly, the micropyramidal silicon-based device worked at 0 V bias, paving a path for self-bias devices. The highest specific detectivity of 2.25 × 1015 Jones was achieved at 15 mW/cm2 power density at a bias voltage of 0.5 V. It is demonstrated that the enhanced responsivity was closely linked with field enhancement due to the Kretschmann configuration of Si pyramids, which acts as hot spots for Si/Sb2Se3 junction. A high responsivity of 47.8 A W-1 proved it suitable for scalable and cost-effective plasmonic-based NIR photodetectors.

Protein restriction in adults with chronic kidney disease, with or without diabetes: Integrated Diabetes and Endocrine Academy (IDEA) consensus statement for Indian patients.

BACKGROUND AND AIMS: Most guidelines recommend protein restriction in adults with chronic kidney disease (CKD), with or without diabetes. However, advising protein restriction for every person with CKD is controversial. We aim to arrive at a consensus on this topic, especially among Indian adults with CKD. METHODS: A systematic literature search in the PubMed electronic database was undertaken using specific keywords and MeSH terms until May 1, 2022. All the retrieved literature was circulated and rigorously deliberated upon by the panel members. RESULTS: Seventeen meta-analyses that evaluated the outcomes of protein restriction in adults with CKD, with or without diabetes, met our inclusion criteria and were analyzed. A low-protein diet (LPD) in people with stages 3-5 of CKD (who are not on haemodialysis [HD]) reduces the severity of uremic symptoms and the rate of decline in glomerular filtration rate, leading to a delay in dialysis initiation. However, LPD in patients on maintenance HD may not be desirable because HD-induced protein catabolism may lead to protein-energy malnutrition. Since the average protein intake among Indians is much lower than recommended, this must be taken into consideration before recommending LPD for all Indian adults with CKD, particularly those on maintenance HD. CONCLUSION: It is essential to assess the nutritional status of people with CKD, particularly in countries like India where average daily protein intake is poor, before recommending guideline-directed protein restriction. The prescribed diet, including the quantity and quality of proteins, should be tailored to the person's habits, tastes, and needs.

Enhance photoluminescence properties of Ca-Eu:Y2O3@SiO2 core-shell nanomaterial for the advanced forensic and LEDs applications.

The divalent (Ca2+)-doped Eu:Y2O3@SiO2 core-shell luminescent nanophosphors have been synthesised by a cost-effective combustion technique. Various characterizations were carried out to confirm the successful formation of the core-shell structure. The TEM micrograph reveals the thickness of the SiO2 coating over Ca-Eu:Y2O3 as ∼25 nm. The optimal value of silica coating over the phosphor has been obtained as 10 vol%(TEOS) of SiO2, with this value increasing fluorescence intensity by 34 %. Phosphor exhibits CIE coordinates as x = 0.425, y = 0.569 and a CCT value as ∼2115 K with color purity and the respective CRI of 80 % and 98 %, respectively, which make the core-shell nanophosphor suitable for warm LEDs, and other optoelectronic applications. Further, the core-shell nanophosphor has been investigated for the visualisation of latent finger prints and as security ink. The findings point towards the prospective future application of nanophosphor materials for anti-counterfeiting purposes and latent finger prints for forensic purposes.

Interferon stimulated gene 15 (ISG15) in cancer: An update.

Among the plethora of defense mechanisms which a host elicits after pathogen invasion, type 1 interferons play a central role in regulating the immune system's response. They induce several interferon-stimulated genes (ISGs) which play a diverse role once activated. Over the past few decades, there have been several studies exploring the role of ISGs in cancer and ISG15 is among the most studied for its pro and anti-tumorigenic role. In this review, we aim to provide an update on the recent observations and findings related to ISG15 in cancer. We provide a brief overview about the initial observations and important historical findings which helped scientists understand structure and function of ISG15. We aim to provide an overview of ISG15 in cancer with an emphasis on studies which delve into the molecular mechanism of ISG15 in modulating the tumor microenvironment. Further, the dysregulation of ISG15 in cancer and the molecular mechanisms associated with its pro and anti-tumor roles are discussed in respective cancer types. Finally, we discuss multiple therapeutic applications of ISG15 in current cancer therapy.

Associations between residential volatile organic compound exposures and liver injury markers: The role of biological sex and race.

While occupational exposures to volatile organic compounds (VOCs) have been linked to steatohepatitis and liver cancer in industrial workers, recent findings have also positively correlated low-dose, residential VOC exposures with liver injury markers. VOC sources are numerous; factors including biological make up (sex), socio-cultural constructs (gender, race) and lifestyle (smoking) can influence both VOC exposure levels and disease outcomes. Therefore, the current study's objective is to investigate how sex and race influence associations between residential VOC exposures and liver injury markers particularly in smokers vs. nonsmokers. Subjects (n = 663) were recruited from residential neighborhoods; informed consent was obtained. Exposure biomarkers included 16 urinary VOC metabolites. Serological disease biomarkers included liver enzymes, direct bilirubin, and hepatocyte death markers (cytokeratin K18). Pearson correlations and generalized linear models were conducted. Models were adjusted for common liver-related confounders and interaction terms. The study population constituted approximately 60% females (n = 401) and 40% males (n = 262), and a higher percent of males were smokers and/or frequent drinkers. Both sexes had a higher percent of White (75% females, 82% males) vs. Black individuals. Positive associations were identified for metabolites of acrolein, acrylamide, acrylonitrile, butadiene, crotonaldehyde, and styrene with alkaline phosphatase (ALP), a biomarker for cholestatic injury; and for the benzene metabolite with bilirubin; only in females. These associations were retained in female smokers. Similar associations were also observed between these metabolites and ALP only in White individuals (n = 514). In Black individuals (n = 114), the styrene metabolite was positively associated with aspartate transaminase. Interaction models indicated that positive associations for acrylamide/crotonaldehyde metabolites with ALP in females were dose-dependent. Most VOC associations with K18 markers were negative in this residential population. Overall, the findings demonstrated that biological sex, race, and smoking status influence VOC effects on liver injury and underscored the role of biological-social-lifestyle factor(s) interactions when addressing air pollution-related health disparities.

Association of electronic cigarette use with circulating angiogenic cell levels in healthy young adults: Evidence for chronic systemic injury.

BACKGROUND: Circulating angiogenic cells (CACs) are indicative of vascular health and repair capacity; however, their relationship with chronic e-cigarette use is unclear. This study aims to assess the association between e-cigarette use and CAC levels. METHODS: We analyzed CAC levels in 324 healthy participants aged 21-45 years from the cross-sectional Cardiovascular Injury due to Tobacco Use study in four groups: never tobacco users (n = 65), sole e-cigarette users (n = 19), sole combustible cigarette users (n = 212), and dual users (n = 28). A total of 15 CAC subpopulations with four cell surface markers were measured using flow cytometry: CD146 (endothelial), CD34 (stem), CD45 (leukocyte), and AC133 (early progenitor/stem). Generalized linear models with gamma distribution and log-link were generated to assess association between CACs and smoking status. Benjamini-Hochberg were used to adjust p-values for multiple comparisons. RESULTS: The cohort was 47% female, 51% Black/African American, with a mean (± SD) age of 31 ± 7 years. Sole cigarette use was significantly associated with higher levels of two endothelial marker CACs (Q ⩽ 0.05). Dual users had higher levels of four endothelial marker CACs and one early progenitor/stem marker CAC (Q ⩽ 0.05). Sole e-cigarette users had higher levels of one endothelial and one leukocyte marker CAC (Q ⩽ 0.05). CONCLUSION: Dual use of e-cigarettes and combustible cigarettes was associated with higher levels of endothelial origin CACs, indicative of vascular injury. Sole use of e-cigarettes was associated with higher endothelial and inflammatory CACs, suggesting ongoing systemic injury. Distinct patterns of changes in CAC subpopulations suggest that CACs may be informative biomarkers of changes in vascular health due to tobacco product use.

Epsin Nanotherapy Regulates Cholesterol Transport to Fortify Atheroma Regression.

BACKGROUND: Excess cholesterol accumulation in lesional macrophages elicits complex responses in atherosclerosis. Epsins, a family of endocytic adaptors, fuel the progression of atherosclerosis; however, the underlying mechanism and therapeutic potential of targeting Epsins remains unknown. In this study, we determined the role of Epsins in macrophage-mediated metabolic regulation. We then developed an innovative method to therapeutically target macrophage Epsins with specially designed S2P-conjugated lipid nanoparticles, which encapsulate small-interfering RNAs to suppress Epsins. METHODS: We used single-cell RNA sequencing with our newly developed algorithm MEBOCOST (Metabolite-mediated Cell Communication Modeling by Single Cell Transcriptome) to study cell-cell communications mediated by metabolites from sender cells and sensor proteins on receiver cells. Biomedical, cellular, and molecular approaches were utilized to investigate the role of macrophage Epsins in regulating lipid metabolism and transport. We performed this study using myeloid-specific Epsin double knockout (LysM-DKO) mice and mice with a genetic reduction of ABCG1 (ATP-binding cassette subfamily G member 1; LysM-DKO-ABCG1fl/+). The nanoparticles targeting lesional macrophages were developed to encapsulate interfering RNAs to treat atherosclerosis. RESULTS: We revealed that Epsins regulate lipid metabolism and transport in atherosclerotic macrophages. Inhibiting Epsins by nanotherapy halts inflammation and accelerates atheroma resolution. Harnessing lesional macrophage-specific nanoparticle delivery of Epsin small-interfering RNAs, we showed that silencing of macrophage Epsins diminished atherosclerotic plaque size and promoted plaque regression. Mechanistically, we demonstrated that Epsins bound to CD36 to facilitate lipid uptake by enhancing CD36 endocytosis and recycling. Conversely, Epsins promoted ABCG1 degradation via lysosomes and hampered ABCG1-mediated cholesterol efflux and reverse cholesterol transport. In a LysM-DKO-ABCG1fl/+ mouse model, enhanced cholesterol efflux and reverse transport due to Epsin deficiency was suppressed by the reduction of ABCG1. CONCLUSIONS: Our findings suggest that targeting Epsins in lesional macrophages may offer therapeutic benefits for advanced atherosclerosis by reducing CD36-mediated lipid uptake and increasing ABCG1-mediated cholesterol efflux.

Gheirat as a complex emotional reaction to relational boundary violations: A mixed-methods investigation.

People from different cultural backgrounds vary in how they define, perceive, and react to violations of relational boundaries. Muslim cultures are diverse and include nearly one in four people in the world, yet research on their relational and moral norms is scarce. We contribute to narrowing this gap by studying gheirat, a moral-emotional experience ubiquitous in Muslim Middle Eastern cultures. In four mixed-methods studies, we study how gheirat is experienced, what situations elicit it, and its social functions among Iranian adults (N = 1,107) using qualitative interviews, scenario- and prototype-based surveys, and an experiment. The prototypical experience of gheirat consisted of diverse appraisals (including sense of responsibility, insecurity, and low self-worth) and emotional components (including hostility, social fears, and low empowerment). We identified three types of relational violations that elicit gheirat: harm or insult to namoos (people and self-relevant entities one is obliged to protect), romantic betrayal by namoos, and intrusions by a third person. Each violation type led to a distinct variant of the prototype. Contrary to folk theories of gheirat, we did not find support for the idea that gheirat is a predominantly male experience. However, an experiment on the signaling effects of gheirat revealed that gheirat expressors are ascribed both positive and negative traits, but positive traits prevail for men and negative traits prevail for women. We discuss how the results contribute to a better understanding of Iranian social life and intercultural contact, as well as the implications for theories of emotion and the cultural logic of honor. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Effects of electronic cigarette flavorants on human platelet aggregation ex vivo.

Because little is known about the effects of individual flavorants in electronic cigarette (e-cig) fluids on human platelet aggregation, we tested for the direct effects of 15 common e-cig flavorants on adenosine diphosphate (ADP)-induced human platelet aggregation ex vivo. To better understand a potential mechanism of action of flavorants, we quantified 2 phases of aggregation. Human platelet-rich plasma (PRP) was obtained from whole blood of healthy volunteers and used in a platelet aggregometry assay. PRP was incubated with 1 of 15 different flavorant compounds (e.g., benzyl alcohol, eugenol, citronellol, menthol, menthone, diacetyl, maltol, limonene, methylbutyric acid, isoamyl acetate, acetylpyridine, eucalyptol, 2,5-dimethylpyrazine, cinnamaldehyde, and vanillin) at 100 µM for 5 min at 37 °C prior to addition of ADP (10 µM). Subsequent ADP-induced platelet aggregation was tracked for 5 min using an aggregometer. Aggregation curves were analyzed for flavorant-induced effects on total (%) aggregation, Phase 1 and Phase 2 components, and compared with their ADP-only control via One-Way ANOVA. Notably, eugenol significantly inhibited total aggregation; an effect due solely to inhibition of Phase 2. No other flavor tested had any effect on total or phase-specific ADP-induced platelet aggregation. These results indicate that parent flavorant compounds commonly found in e-cig liquids neither activate nor inhibit ADP-induced human platelet aggregation. However, as flavorants are chemically altered during heating of e-cig, thermally-derived products of flavorants (e.g., flavor acetals) also will need to be tested for effects on platelet activation.

Research Trend and Detailed Insights into the Molecular Mechanisms of Food Bioactive Compounds against Cancer: A Comprehensive Review with Special Emphasis on Probiotics.

In an attempt to find a potential cure for cancer, scientists have been probing the efficacy of the food we eat and its bioactive components. Over the decades, there has been an exponentially increasing trend of research correlating food and cancer. This review explains the molecular mechanisms by which bioactive food components exhibit anticancer effects in several cancer models. These bioactive compounds are mainly plant based or microbiome based. While plants remain the primary source of these phytochemicals, little is known about probiotics, i.e., microbiome sources, and their relationships with cancer. Thus, the molecular mechanisms underlying the anticancer effect of probiotics are discussed in this review. The principal mode of cell death for most food bioactives is found to be apoptosis. Principal oncogenic signaling axes such as Akt/PI3K, JAK/STAT, and NF-κB seem to be modulated due to these bioactives along with certain novel targets that provide a platform for further oncogenic research. It has been observed that probiotics have an immunomodulatory effect leading to their chemopreventive actions. Various foods exhibit better efficacy as complete extracts than their individual phytochemicals, indicating an orchestrated effect of the food components. Combining bioactive agents with available chemotherapies helps synergize the anticancer action of both to overcome drug resistance. Novel techniques to deliver bioactive agents enhance their therapeutic response. Such combinations and novel approaches are also discussed in this review. Notably, most of the food components that have been studied for cancer have shown their efficacy in vivo. This bolsters the claims of these studies and, thus, provides us with hope of discovering anticancer agents in the food that we eat.