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Frontiers in Nutrition 20242-Amino-1-methyl-6-phenylimidazole [4,5-b] pyridine (PhIP), a heterocyclic amine (HAA), is found in meat products heated at high temperatures. However, PhIP is a...
INTRODUCTION
2-Amino-1-methyl-6-phenylimidazole [4,5-b] pyridine (PhIP), a heterocyclic amine (HAA), is found in meat products heated at high temperatures. However, PhIP is a mutagenic and potential carcinogenic compound. Cassiae semen, a type of medicine and food homology plant, is abundant in China and has been less applied for inhibiting heterocyclic amines.
METHODS
To investigate the inhibitory effect of cassiae semen extract on PhIP formation within a model system and elucidate the inhibitory mechanism, an ultrasonic-assisted method with 70% ethanol was used to obtain cassiae semen extract, which was added to a model system (0.6 mmol of phenylalanine: creatinine, 1:1). PhIP was analyzed by LC-MS to determine inhibitory effect. The byproducts of the system and the mechanism of PhIP inhibition were verified by adding the extract to a model mixture of phenylacetaldehyde, phenylacetaldehyde and creatinine.
RESULTS
The results indicated that PhIP production decreased as the concentration of cassiae semen extract increased, and the highest inhibition rate was 91.9%. Byproduct (E), with a mass-charge ratio of m/z 199.9, was detected in the phenylalanine and creatinine model system but was not detected in the other systems. The cassiae semen extract may have reacted with phenylalanine to produce byproduct (E), which prevented the degradation of phenylalanine by the Strecker reaction to produce phenylacetaldehyde.
DISCUSSION
Cassiae semen extract consumed phenylalanine, which is the precursor for PhIP, thus inhibiting the formation of phenylacetaldehyde and ultimately inhibiting PhIP formation. The main objective of this study was to elucidate the mechanism by which cassiae semen inhibit PhIP formation and establish a theoretical and scientific foundation for practical control measures.
PubMed: 38903617
DOI: 10.3389/fnut.2024.1407007 -
Frontiers in Immunology 2024Post-transplant cyclophosphamide (PTCy) is becoming the standard prophylaxis for graft-versus-host disease (GVHD) in HLA-haploidentical allogeneic hematopoietic cell... (Review)
Review
Post-transplant cyclophosphamide (PTCy) is becoming the standard prophylaxis for graft-versus-host disease (GVHD) in HLA-haploidentical allogeneic hematopoietic cell transplantation (allo-HCT) and in HLA-matched allo-HCT. Immune reconstitution in the post-transplant setting may influence the graft-versus-tumor (GVT) effect because PTCy has a profound effect on T cell and natural killer cell functions and their reconstitution after allo-HCT. However, many recent studies have shown that the incidence of relapse after allo-HCT with PTCy is comparable to that after conventional allo-HCT. To further improve the outcomes, it is critical to establish a strategy to maintain or effectively induce the GVT effect when using PTCy as a platform for GVHD prophylaxis. However, there is a paucity of studies focusing on the GVT effect in allo-HCT with PTCy. Therefore, focusing on this issue may lead to the establishment of more appropriate strategies to improve transplantation outcomes without exacerbating GVHD, including novel therapies involving cell modification.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Cyclophosphamide; Graft vs Host Disease; Graft vs Tumor Effect; Transplantation, Homologous; Immunosuppressive Agents; Animals
PubMed: 38903503
DOI: 10.3389/fimmu.2024.1403936 -
PLoS Pathogens Jun 2024The AAA-type ATPase VPS4 is recruited by proteins of the endosomal sorting complex required for transport III (ESCRT-III) to catalyse membrane constriction and membrane...
The AAA-type ATPase VPS4 is recruited by proteins of the endosomal sorting complex required for transport III (ESCRT-III) to catalyse membrane constriction and membrane fission. VPS4A accumulates at the cytoplasmic viral assembly complex (cVAC) of cells infected with human cytomegalovirus (HCMV), the site where nascent virus particles obtain their membrane envelope. Here we show that VPS4A is recruited to the cVAC via interaction with pUL71. Sequence analysis, deep-learning structure prediction, molecular dynamics and mutagenic analysis identify a short peptide motif in the C-terminal region of pUL71 that is necessary and sufficient for the interaction with VPS4A. This motif is predicted to bind the same groove of the N-terminal VPS4A Microtubule-Interacting and Trafficking (MIT) domain as the Type 2 MIT-Interacting Motif (MIM2) of cellular ESCRT-III components, and this viral MIM2-like motif (vMIM2) is conserved across β-herpesvirus pUL71 homologues. However, recruitment of VPS4A by pUL71 is dispensable for HCMV morphogenesis or replication and the function of the conserved vMIM2 during infection remains enigmatic. VPS4-recruitment via a vMIM2 represents a previously unknown mechanism of molecular mimicry in viruses, extending previous observations that herpesviruses encode proteins with structural and functional homology to cellular ESCRT-III components.
PubMed: 38900818
DOI: 10.1371/journal.ppat.1012300 -
International Journal of Yoga 2024Infertility, a widespread medical condition affecting numerous couples globally, persists as a challenge despite advances in assisted reproductive technologies (ARTs),... (Review)
Review
Infertility, a widespread medical condition affecting numerous couples globally, persists as a challenge despite advances in assisted reproductive technologies (ARTs), often burdened by financial, physical, and emotional strains. Complementary and alternative approaches, notably yoga, have garnered attention for potentially enhancing fertility outcomes. Studies reveal yoga's influence on factors contributing to infertility, including reduced oxidative stress (OS) and oxidative DNA damage (ODD). OS, linked to mutagenic base formation, higher malondialdehyde levels, abnormal methylation, and altered gene expression, can impair sperm genome integrity. Yoga's efficacy is evident in lowering OS, positively affecting signal transmission, gene expression, and physiological systems. Furthermore, yoga has a positive impact on addressing the dysregulation of apoptosis, resulting in improved processes such as spermatogenesis, sperm maturation, and motility, while also reducing DNA fragmentation. OS correlates with genome-wide hypomethylation, telomere shortening, and mitochondrial dysfunction, contributing to genome instability. Yoga and meditation significantly reduce OS and ODD, ensuring proper reactive oxygen levels and preserving physiological systems. The review explores potential mechanisms underlying yoga's positive impact on infertility, including enhanced blood flow, reduced inflammation, relaxation response, and modulation of the hypothalamic-pituitary-adrenal axis. Furthermore, a comprehensive review of the literature reveals substantial evidence supporting the positive effects of yoga on infertility factors. These include oxidative stress (OS), oxidative DNA damage (ODD), epigenetic changes, hormonal balance, ovarian function, menstrual irregularities, and stress reduction. In summary, yoga emerges as a promising adjunctive therapy for infertility, demonstrating the potential to mitigate key factors influencing reproductive success. Although preliminary evidence indicates the positive effects of yoga on infertility, further clinical research is imperative to define specific benefits, molecular mechanisms associated, optimal protocols, and long-term effects in infertility treatment plans.
PubMed: 38899142
DOI: 10.4103/ijoy.ijoy_211_23 -
Scientific Reports Jun 2024Newly synthesized gemini quaternary ammonium salts (QAS) with different counterions (bromide, hydrogen chloride, methylcarbonate, acetate, lactate), chain lengths (C12,...
Newly synthesized gemini quaternary ammonium salts (QAS) with different counterions (bromide, hydrogen chloride, methylcarbonate, acetate, lactate), chain lengths (C12, C14, C16) and methylene linker (3xCH) were tested. Dihydrochlorides and dibromides with 12 carbon atoms in hydrophobic chains were characterized by the highest biological activity against planktonic forms of yeast and yeast-like fungi. The tested gemini surfactants also inhibited the production of filaments by C. albicans. Moreover, they reduced the adhesion of C. albicans cells to the surfaces of stainless steel, silicone and glass, and slightly to polystyrene. In particular, the gemini compounds with 16-carbon alkyl chains were most effective against biofilms. It was also found that the tested surfactants were not cytotoxic to yeast cells. Moreover, dimethylcarbonate (2xCMeCOG) did not cause hemolysis of sheep erythrocytes. Dihydrochlorides, dilactate and diacetate showed no mutagenic potential.
Topics: Biofilms; Quaternary Ammonium Compounds; Antifungal Agents; Candida albicans; Animals; Sheep; Surface-Active Agents; Hemolysis; Erythrocytes; Microbial Sensitivity Tests; Cell Adhesion; Stainless Steel
PubMed: 38898117
DOI: 10.1038/s41598-024-64859-y -
Chemical & Pharmaceutical Bulletin 2024Dihydrobenzofuran is an important skeleton for bioactive compounds and natural products. Hydroquinones can be easily modified into substituted hydroquinones, which...
Dihydrobenzofuran is an important skeleton for bioactive compounds and natural products. Hydroquinones can be easily modified into substituted hydroquinones, which effectively undergo oxidation to produce the corresponding benzoquinone derivatives. Benzoquinones are reactive electrophiles that are frequently utilized in coupling with olefins to dihydrobenzofurans. Herein, we report the one-pot oxidative coupling of hydroquinones bearing an electron-withdrawing group at the C2 position with olefins to dihydrobenzofurans in the presence of the Lewis acidic FeCl and 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) oxidant. Furthermore, this method was applied to the oxidative coupling of N-electron-withdrawing group-substituted 4-aminophenol.
Topics: Hydroquinones; Benzofurans; Alkenes; Molecular Structure; Oxidative Coupling; Ferric Compounds; Oxidation-Reduction; Chlorides; Benzoquinones
PubMed: 38897954
DOI: 10.1248/cpb.c24-00231 -
BioRxiv : the Preprint Server For... Jun 2024Tanning bed users have a significantly increased risk of melanoma, but it remains unclear how indoor tanning drives melanomagenesis. Tanning bed radiation is often...
BACKGROUND
Tanning bed users have a significantly increased risk of melanoma, but it remains unclear how indoor tanning drives melanomagenesis. Tanning bed radiation is often thought of as a substitute for natural UV radiation despite differences in the maximum doses, UV content, body sites exposed, and patterns of melanoma that arise.
METHODS
To better understand the epidemiologic trends and etiology of melanoma associated with tanning bed use, we described the patterns of melanoma in patients with quantifiable tanning bed usage and performed exome sequencing of 182 melanocytes from normal skin of a subset of these patients.
RESULTS
Tanning bed users were more likely than non-users to have melanoma on body sites with low cumulative levels of sun damage and were more likely to have multiple melanomas. The melanocytes in normal appearing skin from tanning bed users had higher mutation burdens, a higher proportion of melanocytes with pathogenic mutations, and distinct mutational signatures. These differences were most prominent over body sites that experience comparatively less exposure to natural sunlight.
CONCLUSIONS
We conclude that tanning bed radiation induces melanoma by increasing the mutation burden of melanocytes and by mutagenizing a broader field of melanocytes than are typically exposed to natural sunlight. The unique signatures of mutations in skin cells of tanning users may be attributable to the distinct spectra of radiation emitted from solariums.
PubMed: 38895302
DOI: 10.1101/2024.06.04.597225 -
International Journal of Molecular... May 2024While edible algae might seem low in fat, the lipids they contain are crucial for good health and preventing chronic diseases. This study introduces a binary matrix to...
While edible algae might seem low in fat, the lipids they contain are crucial for good health and preventing chronic diseases. This study introduces a binary matrix to analyze all the polar lipids in both macroalgae (Wakame-, Dulse-, and Nori- spp.) and microalgae (Spirulina-, and Chlorella-) using matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). The key lies in a new dual matrix made by combining equimolar amounts of 1,5-diaminonaphthalene (DAN) and 9-aminoacridine (9AA). This combination solves the limitations of single matrices: 9AA is suitable for sulfur-containing lipids and acidic phospholipids, while DAN excels as an electron-transfer secondary reaction matrix for intact chlorophylls and their derivatives. By employing the equimolar binary matrix, a wider range of algal lipids, including free fatty acids, phospholipids, glycolipids, pigments, and even rare arsenosugarphospholipids were successfully detected, overcoming drawbacks related to ion suppression from readily ionizable lipids. The resulting mass spectra exhibited a good signal-to-noise ratio at a lower laser fluence and minimized background noise. This improvement stems from the binary matrix's ability to mitigate in-source decay effects, a phenomenon often encountered for certain matrices. Consequently, the data obtained are more reliable, facilitating a faster and more comprehensive exploration of algal lipidomes using high-throughput MALDI-MS/MS analysis.
Topics: Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Lipids; Seaweed; Microalgae; 2-Naphthylamine; Aminacrine; Pigments, Biological; Spirulina
PubMed: 38892117
DOI: 10.3390/ijms25115919 -
International Journal of Molecular... May 2024Cordycepin, or 3'-deoxyadenosine, is an adenosine analog with a broad spectrum of biological activity. The key structural difference between cordycepin and adenosine...
Cordycepin, or 3'-deoxyadenosine, is an adenosine analog with a broad spectrum of biological activity. The key structural difference between cordycepin and adenosine lies in the absence of a hydroxyl group at the 3' position of the ribose ring. Upon administration, cordycepin can undergo an enzymatic transformation in specific tissues, forming cordycepin triphosphate. In this study, we conducted a comprehensive analysis of the structural features of cordycepin and its derivatives, contrasting them with endogenous purine-based metabolites using chemoinformatics and bioinformatics tools in addition to molecular dynamics simulations. We tested the hypothesis that cordycepin triphosphate could bind to the active site of the adenylate cyclase enzyme. The outcomes of our molecular dynamics simulations revealed scores that are comparable to, and superior to, those of adenosine triphosphate (ATP), the endogenous ligand. This interaction could reduce the production of cyclic adenosine monophosphate (cAMP) by acting as a pseudo-ATP that lacks a hydroxyl group at the 3' position, essential to carry out nucleotide cyclization. We discuss the implications in the context of the plasticity of cancer and other cells within the tumor microenvironment, such as cancer-associated fibroblast, endothelial, and immune cells. This interaction could awaken antitumor immunity by preventing phenotypic changes in the immune cells driven by sustained cAMP signaling. The last could be an unreported molecular mechanism that helps to explain more details about cordycepin's mechanism of action.
Topics: Deoxyadenosines; Humans; Neoplasms; Cyclic AMP; Molecular Dynamics Simulation; Adenosine Triphosphate; Signal Transduction; Computer Simulation; Adenylyl Cyclases
PubMed: 38891880
DOI: 10.3390/ijms25115692 -
BMC Medicine Jun 2024Previous studies have shown that the addition of platinum to neoadjuvant chemotherapy (NAC) improved outcomes for patients with triple-negative breast cancer (TNBC).... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Previous studies have shown that the addition of platinum to neoadjuvant chemotherapy (NAC) improved outcomes for patients with triple-negative breast cancer (TNBC). However, no studies have assessed the efficacy and safety of the combination of taxane and lobaplatin. In this study, we conducted a randomized controlled phase II clinical study to compare the efficacy and safety of taxane combined with lobaplatin or anthracycline.
METHODS
We randomly allocated patients with stage I-III TNBC into Arm A and Arm B. Arm A received six cycles of taxane combined with lobaplatin (TL). Arm B received six cycles of taxane combined with anthracycline and cyclophosphamide (TEC) or eight cycles of anthracycline combined with cyclophosphamide and sequential use of taxane (EC-T). Both Arms underwent surgery after NAC. The primary endpoint was the pathologic complete response (pCR). Secondary endpoints were event-free survival (EFS), overall survival (OS), and safety.
RESULTS
A total of 103 patients (51 in Arm A and 52 in Arm B) were assessed. The pCR rate of Arm A was significantly higher than that of Arm B (41.2% vs. 21.2%, P = 0.028). Patients with positive lymph nodes and low neutrophil-to-lymphocyte ratio (NLR) benefited significantly more from Arm A than those with negative lymph nodes and high NLR (P = 0.001, P = 0.012, respectively). There was no significant difference in EFS (P = 0.895) or OS (P = 0.633) between the two arms. The prevalence of grade-3/4 anemia was higher in Arm A (P = 0.015), and the prevalence of grade-3/4 neutropenia was higher in Arm B (P = 0.044).
CONCLUSIONS
Neoadjuvant taxane plus lobaplatin has shown better efficacy than taxane plus anthracycline, and both regimens have similar toxicity profiles. This trial may provide a reference for a better combination strategy of immunotherapy in NAC for TNBC in the future.
Topics: Humans; Triple Negative Breast Neoplasms; Female; Middle Aged; Neoadjuvant Therapy; Adult; Antineoplastic Combined Chemotherapy Protocols; Cyclobutanes; Anthracyclines; Aged; Taxoids; Organoplatinum Compounds; Treatment Outcome; Cyclophosphamide; Bridged-Ring Compounds
PubMed: 38886794
DOI: 10.1186/s12916-024-03474-0