The effect of photobiomodulation on histamine and Mucuna pruriens-induced pruritus, hyperknesis and alloknesis in healthy volunteers: A double-blind, randomized, sham-controlled study.

BACKGROUND: Photobiomodulation, also referred to as Low-Level Light Therapy (LLLT), has emerged as a promising intervention for pruritus, a prevalent and often distressing symptom. OBJECTIVES: This study investigated the efficacy of low-level light therapy (LLLT) in alleviating pruritus, hyperknesis, and alloknesis induced by histamine and Mucuna pruriens. METHODS: In a double-blind, randomized, sham-controlled trial with a split-body design, healthy volunteers underwent 6 minutes of LLLT and sham treatments in separate upper back quadrants. The histamine model was applied to the upper quadrants, and Mucuna pruriens to the lower quadrants. Pruritus intensity, alloknesis, hyperknesis, flare area, and skin temperature were measured pre and post treatment. RESULTS: Seventeen individuals (eight females, nine males) participated in the study. In the histamine model, LLLT notably reduced itch intensity (difference = 13.9 (95% CI: 10.5 - 17.4), p = 0.001), alloknesis (difference = 0.80 (95% CI: 0.58-1.02), p = 0.001), and hyperknesis (difference = 0.48 (95% CI: 0.09-0.86), p = 0.01). Skin temperature changes were not significantly different between the two groups (difference = -2.0 (95% CI: -6.7-2.6), p = 0.37). For the Mucuna pruriens model, no significant differences were observed in any measures, including itch intensity (difference = 0.8 (95% CI: -2.3 - 3.8), p = 0.61) hyperknesis (difference = 0.08 (95% CI: -0.06-0.33), p = 0.16) and alloknesis (difference = 0. 0.09 (95% CI: -0.08-0.256), p = 0.27). CONCLUSIONS: LLLT effectively reduced histamine-induced pruritus, alloknesis, and hyperknesis; however, LLLT was ineffective against Mucuna pruriens-induced pruritus. Further investigations are required to determine LLLT's effectiveness of LLLT in various pruritus models.

Salivary Histamine Levels in Patients with Oral Lichen Planus Lesions.

Background and Objectives: An oral lichen planus (OLP) chronic lesion refers to a group of oral potentially malignant disorders (OPMDs) that still lack a proper understanding from the point of view of relevant biomarkers for diagnostics and prognosis. The aim of the study was to assess the salivary histamine levels in patients with oral lichen planus lesions. Materials and Methods: The study included a group of 76 patients with oral lichen planus. General diseases and medication taken, smoking habits, severity of pain assessed using a visual analogue scale (VAS), oral hygiene status, and duration of OLP were evaluated. ELISA diagnostics for histamines in saliva levels were assessed. Results: The histamine levels in the OLP group were higher (0.468) in comparison with the control group (0.056), without a statistically significant value p = 0.090 (Mann-Whitney U Test). The median age of 76 OLP patients was 63 years (min 22.0-max. 81), with the biological sex being 80.3% females and 15 19.7% males. The average duration of OLP lesion presence was 29.4 months (SD 37.1) and the median value was 14.5 months. The median of the VAS was 3.0. OLP assessment in accordance with the Malhotra methodology showed the highest frequency-30.3% for only two of the point areas involved and 17.1% for three points. Clinical assessment of the different OLP grades, severity, and oral site involvement and the VAS in correlation with histamine salivary levels showed a lack of statistical significance in the investigated population. Conclusions: Undertaking further research could provide further possibilities for searching for general factors in OLP development.

Itch and Pain Behaviors in Irritant Contact Dermatitis Produced by Sodium Lauryl Sulfate in Mice.

Irritant contact dermatitis (ICD) is a nonspecific skin inflammation caused by irritants, leading to itch and pain. We tested whether differential responses to histamine-dependent and -independent pruritogens can be evoked in ICD induced by sodium lauryl sulfate (SLS). An ICD mouse model was established with 5% SLS in acetone versus a vehicle topically applied for 24 h to the cheek. Site-directed itch- and pain-like behaviors, occurring spontaneously and in response to mechanical, thermal, and chemical stimuli (histamine, ß-alanine, BAM8-22, and bradykinin) applied to the cheek, were recorded before (day 0) and after irritant removal (days 1, 2, 3, and 4). Skin inflammation was assessed through visual scoring, ultrasound, and measurements of skin thickness. SLS-treated mice exhibited hyperalgesia-like behavior in response to mechanical and heat stimuli on day 1 compared to the controls. SLS mice exhibited more spontaneous wipes (pain) but not scratching bouts (itch) on day 1. Pruritogen injections caused more scratching but not wiping in SLS-treated mice compared to the controls. Only bradykinin increased wiping behavior compared to saline. SLS-treated mice developed noticeable erythema, scaling, and increased skin thickness on days 1 and 2. SLS induced cutaneous inflammation and behavioral signs of spontaneous pain and itching, hyperalgesia to mechanical and heat stimuli and a chemical algogen, and enhanced itch response to pruritogens. These sensory reactions preceded the inflammation peak and lasted up to two days.

The role of histamine and its receptors in breast cancer: from pathology to therapeutic targets.

Breast cancer is the most common malignancy in women, and despite the development of new treatment methods and the decreasing mortality rate in recent years, one of the clinical problems in breast cancer treatment is chronic inflammation in the tumor microenvironment. Histamine, an inflammatory mediator, is produced by tumor cells and can induce chronic inflammation and the growth of some tumors by recruiting inflammatory cells. It can also affect tumor physiopathology, antitumor treatment efficiency, and patient survival. Antihistamines, as histamine receptor antagonists, play a role in modulating the effects of these receptors in tumor cells and can affect some treatment methods for breast cancer therapy; in this review, we investigate the role of histamine, its receptors, and antihistamines in breast cancer pathology and treatment methods.

Molecular mechanism of bitter taste receptor agonist-mediated relaxation of airway smooth muscle.

G-protein-coupled receptors (GPCRs) belonging to the type 2 taste receptors (TAS2Rs) family are predominantly present in taste cells to allow the perception of bitter-tasting compounds. TAS2Rs have also been shown to be expressed in human airway smooth muscle (ASM), and TAS2R agonists relax ASM cells and bronchodilate airways despite elevating intracellular calcium. This calcium "paradox" (calcium mediates contraction by pro-contractile Gq-coupled GPCRs) and the mechanisms by which TAS2R agonists relax ASM remain poorly understood. To gain insight into pro-relaxant mechanisms effected by TAS2Rs, we employed an unbiased phosphoproteomic approach involving dual-mass spectrometry to determine differences in the phosphorylation of contractile-related proteins in ASM following the stimulation of cells with TAS2R agonists, histamine (an agonist of the Gq-coupled H1 histamine receptor) or isoproterenol (an agonist of the Gs-coupled ß2-adrenoceptor) alone or in combination. Our study identified differential phosphorylation of proteins regulating contraction, including A-kinase anchoring protein (AKAP)2, AKAP12, and RhoA guanine nucleotide exchange factor (ARHGEF)12. Subsequent signaling analyses revealed RhoA and the T853 residue on myosin light chain phosphatase (MYPT)1 as points of mechanistic divergence between TAS2R and Gs-coupled GPCR pathways. Unlike Gs-coupled receptor signaling, which inhibits histamine-induced myosin light chain (MLC)20 phosphorylation via protein kinase A (PKA)-dependent inhibition of intracellular calcium mobilization, HSP20 and ERK1/2 activity, TAS2Rs are shown to inhibit histamine-induced pMLC20 via inhibition of RhoA activity and MYPT1 phosphorylation at the T853 residue. These findings provide insight into the TAS2R signaling in ASM by defining a distinct signaling mechanism modulating inhibition of pMLC20 to relax contracted ASM.

Stimulation of central histaminergic transmission attenuates diazepam-induced motor disturbance on rota-rod and beam walking tests in mice.

Diazepam administration has been shown to influence the release of histamine in various brain areas involved in motor behavior. Therefore, the present study explored the plausible regulatory role of the central histaminergic system in diazepam-induced deficits in motor performance in mice using the rota-rod and beam walking tests. In this study, several doses of diazepam (0.5, 1, 2, and 3 mg/kg, i.p.) were assessed in mice for changes in motor performance on the rota-rod and beam walking test. In addition, the brain histamine levels were determined after diazepam administration, and the diazepam-induced motor deficits were assessed in mice, pretreated centrally (intracerebroventricular) with histaminergic agents such as histamine (0.1, 10 µg), histamine precursor (L-histidine: 0.1, 2.5 µg), histamine neuronal releaser/H 3 receptor antagonist (thioperamide: 0.5, 10 µg), H 1 and H 2 receptor agonist [2-(3-trifluoromethylphenyl) histamine (FMPH: 0.1, 6.5 µg; amthamine: 0.1, 5 µg)/antagonist (H 1 : cetirizine 0.1 µg) and (H 2 : ranitidine: 50 µg)]. Results indicate that mice treated with diazepam at doses 1, 2 mg/kg, i.p. significantly increased the brain histamine levels. Moreover, in mice pretreated with histaminergic transmission-enhancing agents, the diazepam (2 mg/kg, i.p.)-induced motor incoordination was significantly reversed. Contrastingly, diazepam (1 mg/kg, i.p.) in its subeffective dose produced significant motor deficits in mice preintracerebroventricular injected with histamine H 1 and H 2 receptor antagonists on both the employed tests. Therefore, it is postulated that endogenous histamine operates via H 1 and H 2 receptor activation to alleviate the motor-impairing effects of diazepam.

Histamine deficiency exacerbates cisplatin-induced ferroptosis in cochlea hair cells of HDC knockout mice.

Cisplatin (CDDP) is extensively utilized in the management of diverse types of cancers, but its ototoxicity cannot be ignored, and clinical interventions are not ideal. Histidine decarboxylase (HDC) is the exclusive enzyme for histamine synthesis. Anti-histamine receptor drugs are ubiquitously employed in the therapeutics of allergies and gastrointestinal diseases. Yet, the specific role of histamine and its signaling in the inner ear is not fully understood. This study utilized cisplatin treated mice and HEI-OC1 auditory hair cell line to establish a cisplatin-induced ototoxicity (CIO) model. Histidine decarboxylase knockout (HDC-/-) mice and histamine receptor 1 (H1R) antagonist were utilized to investigate the influence of HDC/histamine/H1R signaling on ototoxicity. The results identified HDC and H1R expression in mouse hair cells. Transcriptomics indicated that the expression levels of oxidative stress-related genes in the cochlea of HDC-/- mice increased. Furthermore, histamine deficiency or suppression of H1R signaling accelerated HC ferroptosis, a pivotal factor underlying the aggravation of CIO in vivo and in vitro, conversely, the supplementation of exogenous histamine reversed these deleterious effects. Mechanistically, this study revealed that the malfunction of HDC/histamine/H1R signaling induced upregulation of NRF2 expression, accompanied by the upregulation of ACSL4 and downregulation of GPX4 expression, which are major regulatory factors of ferroptosis. In summary, histamine deficiency may induce hair cell death by regulating the H1R pathway and exacerbate CIO. Our findings have indicated a potential therapeutic target for CIO.

Single-Nucleotide Polymorphisms of TAS2R46 Affect the Receptor Downstream Calcium Regulation in Histamine-Challenged Cells.

Bitter taste receptors (TAS2Rs) expressed in extraoral tissues represent a whole-body sensory system, whose role and mechanisms could be of interest for the identification of new therapeutic targets. It is known that TAS2R46s in pre-contracted airway smooth muscle cells increase mitochondrial calcium uptake, leading to bronchodilation, and that several SNPs have been identified in its gene sequence. There are very few reports on the structure-function analysis of TAS2Rs. Thus, we delved into the subject by using mutagenesis and in silico studies. We generated a cellular model that expresses native TAS2R46 to evaluate the influence of the four most common SNPs on calcium fluxes following the activation of the receptor by its specific ligand absinthin. Then, docking studies were conducted to correlate the calcium flux results to the structural mutation. The analysed SNPs differently modulate the TAS2R46 signal cascade according to the altered protein domain. In particular, the SNP in the sixth transmembrane domain of the receptors did not modulate calcium homeostasis, while the SNPs in the sequence coding for the fourth transmembrane domain completely abolished the mitochondrial calcium uptake. In conclusion, these results indicate the fourth transmembrane domain of TAS2R46 is critical for the intrinsic receptor activity.

"One-Pot" Readout Cyano-Programmable SERS-Encoded Platform Enables Ultrasensitive and Interference-Free Detection of Multitarget Bioamines.

Surface-enhanced Raman spectroscopy (SERS) detection platforms with high signal-to-noise ratio in the "biological-silent" region (1800-2800 cm-1) are presently being developed for sensing and imaging applications, overcoming the limitations of traditional SERS studies in the "fingerprint" region. Herein, a series of cyano-programmable Raman reporters (RRs) operating in the "biological-silent" region were designed based on 4-mercaptobenzonitrile derivatives and then embedded in core-shell Au@Ag nanostars using a "bottom-up" strategy to provide SERS enhancement and encapsulation protection. The approach enabled the "one-pot" readout interference-free detection of multiple bioamines (histamine, tyramine, and ß-phenethylamine) based on aptamer-driven magnetic-induced technology. Three cyano-encoded SERS tags resulted in separate SERS signals for histamine, tyramine, and ß-phenethylamine at 2220, 2251, and 2150 cm-1, respectively. A target-specific aptamer-complementary DNA competitive binding strategy allowed the formation of microscale core-satellite assemblies between Fe3O4-based magnetic beads and the SERS tags, enabling multiple SERS signals to be observed simultaneously under a 785 nm laser excitation laser. The LODs for detection of the three bioamines were 0.61 × 10-5, 2.67 × 10-5, and 1.78 × 10-5 mg L-1, respectively. The SERS-encoded platform utilizing programmable reporters provides a fast and sensitive approach for the simultaneous detection of multiple biomarkers, paving the way for routine SERS analyses of multiple analytes in complex matrices.

Sensitive detection of histamine utilizing the SERS platform combined with an azo coupling reaction and a composite hydrophobic layer.

Herein, the surface-enhanced Raman scattering (SERS) platform was combined with an azo coupling reaction and an aluminum alloy covered with a hydrophobic layer of praseodymium oxide and stearic acid complexes for the detection of histamine. The praseodymium oxide on aluminum alloy was successfully synthesized by the rare-earth-salt-solution boiling bath method and modified by stearic acid. Its surface exhibits a water contact angle (WCA) of 125.0°. Through the azo derivatization reaction with 3-amino-5-mercapto-1,2,4-triazole (AMTA) diazonium salts, histamine can be converted into the derivatization product with higher Raman activity. The mixture of the derivatization product and ß-cyclodextrin-modified Ag nanoparticles (ß-CD-AgNPs) were dropped onto the surface of an aluminum alloy covered with a hydrophobic layer of praseodymium oxide and stearic acid complexes, and dried for SERS measurement. The intensity ratio between the SERS peaks at 1246 cm-1 and 1104 cm-1 (I1246/I1104) of the derivatization product was used for the quantification of histamine. Under the selected conditions, the limit of detection (LOD) and the limit of quantification (LOQ) for this method were 7.2 nM (S/N = 3) and 24 nM (S/N = 10), respectively. The relative standard deviation (RSD) of this method for the determination of 1 µM histamine was 6.1 % (n = 20). The method was also successfully used for the determination of histamine in fish samples with recoveries ranging from 92 % to 111 %. The present method is simple, sensitive, reliable, and may provide a new approach for preparing the composite hydrophobic layer that can enhance SERS signals through hydrophobic condensation effect. Meanwhile, it may have a promising future in the determination of small molecular compounds containing an imidazole ring.

Evaluation methods using tear volume in a conjunctivitis mice model.

Allergic conjunctival disease is an immune-mediated inflammatory disease of the conjunctiva. To develop clinically useful drugs, it is necessary to develop quantitative evaluation methods that reflect the clinical symptoms in experimental animal models. Allergic conjunctivitis model mice were systemically sensitised with ovalbumin (OVA) administered intraperitoneally and locally sensitised with OVA eye drops between day 14-28. Next, conjunctivitis induced by ocular administration of OVA solution to sensitised mice was evaluated based on tear volume. Additionally, we evaluated increase in tear volume induced by direct ocular instillation of histamine, compound 48/80, and carrageenan. An increase in antigen-induced tear volume was observed in the mice model. Additionally, direct instillation of histamine, compound 48/80, and carrageenan increased tear volume. Furthermore, levocabastine inhibited the increase in tear volume in antigen-induced allergic conjunctivitis and histamine- and compound 48/80-induced conjunctivitis models. In contrast, betamethasone suppressed carrageenan-induced tear volume but not histamine- or compound 48/80-induced tear volume. Histamine may be involved in increased tear volume in allergic conjunctivitis. Betamethasone is not directly involved in the action of histamine and is thought to suppress increase in tear volume. Evaluation of tear volume in a conjunctivitis mice model is highly quantitative; therefore, it is possible to evaluate drug efficacy. This is considered a useful index compared with conventional methods.

Therapeutic Potentials of Medicinal Leech in Chinese Medicine.

The use of medicinal leeches in clinical therapy has been employed for a long time, as it was originally recognized for exerting antithrombin effects. These effects were due to the ability of the leech to continuously suck blood while attached to human skin. According to Chinese Pharmacopoei, leeches used in traditional Chinese medicine mainly consist of Whitmania pigra Whitman, Hirudo nipponia Whitman, and Whitmania acranulata, but the latter two species are relatively scarce. The main constituents of leeches are protein and peptide macromolecules. They can be categorized into two categories based on their pharmacological effects. One group consists of active ingredients that directly target the coagulation system, such as hirudin, heparin, and histamine, which are widely known. The other group comprises protease inhibitor components like Decorsin and Hementin. Among these, hirudin secreted by the salivary glands of the leech is the most potent thrombin inhibitor and served as the sole remedy for preventing blood clotting until the discovery of heparin. Additionally, leeches play a significant role in various traditional Chinese medicine formulations. In recent decades, medicinal leeches have been applied in fields including anti-inflammatory treatment, cardiovascular disease management, antitumor treatment, and many other medical conditions. In this review, we present a comprehensive overview of the historical journey and medicinal applications of leeches in various medical conditions, emphasizing their pharmaceutical significance within traditional Chinese medicine. This review offers valuable insights for exploring additional therapeutic opportunities involving the use of leeches in various diseases and elucidating their underlying mechanisms for future research.

Liposomal nanocarriers of preassembled glycocalyx restore normal venular permeability and shear stress sensitivity in sepsis: assessed quantitatively with a novel microchamber system.

The endothelial glycocalyx (EG), covering the luminal side of endothelial cells, regulates vascular permeability and senses wall shear stress. In sepsis, EG undergoes degradation leading to increased permeability and edema formation. We hypothesized that restoring EG integrity using liposomal nanocarriers of preassembled glycocalyx (LNPG) will restore normal venular permeability in lipopolysaccharide (LPS)-induced sepsis model of mice. To test this hypothesis, we designed a unique perfusion microchamber in which the permeability of isolated venules could be assessed by measuring the concentration of Evans blue dye (EBD) in microliter samples of extravascular solution (ES). Histamine-induced time- and dose-dependent increases in EBD in the ES could be measured, confirming the sensitivity of the microchamber system. Notably, the histamine-induced increase in permeability was significantly attenuated by histamine receptor (H1) antagonist, triprolidine hydrochloride. Subsequently, mice were treated with LPS or LPS + LNPG. When compared with control mice, venules from LPS-treated mice showed a significant increased permeability, which was significantly reduced by LNPG administration. Moreover, in the presence of wall shear stress, intraluminal administration of LNPG significantly reduced the permeability in isolated venules from LPS-treated mice. We have found no sex differences. In conclusion, our newly developed microchamber system allows us to quantitatively measure the permeability of isolated venules. LPS-induced sepsis increases permeability of mesenteric venules that is attenuated by in vivo LNPG administration, which also reestablished endothelial responses to shear stress. Thus, LNPG presents a promising therapeutic potential for restoring EG function and thereby mitigating vasogenic edema due to increased permeability in sepsis.NEW & NOTEWORTHY In sepsis, the degradation of the endothelial glycocalyx leads to increased venular permeability. In this study, we developed a potentially new therapeutic approach by in vivo administration of liposomal nanocarriers of preassembled glycocalyx to mice, which restored venular sensitivity to wall shear stress and permeability in lipopolysaccharide-induced sepsis, likely by restoring the integrity of the endothelial glycocalyx. Using a new microchamber system, the permeability of Evans blue dye could be quantitatively determined.

Exploring factors influencing the levels of biogenic amines in wine and microbiological strategies for controlling their occurrence in winemaking.

Fermented beverages, including wine, can accumulate high concentrations of biogenic amines (BAs), which can pose potential health risks. BAs are produced by various yeasts and lactic acid bacteria (LAB) during winemaking. LAB are the main contributors to the formation of histamine and tyramine, the most toxic and food safety relevant biogenic amines. Numerous factors, ranging from agricultural and oenological practices to sanitation conditions, can contribute to the formation of BAs in wines. Moreover, organic and biodynamic wines impose limitations on the use of common food additives employed to control the proliferation of native and spoilage microorganisms during vinification and storage. To mitigate histamine production, commercial starter cultures incapable of synthesising histamine have been effectively utilised to reduce wine histamine content. Alternative fermentative microorganisms are currently under investigation to enhance the safety, quality, and typicity of wines, including indigenous LAB, non-Saccharomyces yeasts, and BAs degrading strains. Furthermore, exploration of extracts from BAs-degrading microorganisms and their purified enzymes has been undertaken to reduce BAs levels in wines. This review highlights microbial contributors to BAs in wines, factors affecting their growth and BA production, and alternative microorganisms that can degrade or avoid BAs. The aim is to lessen reliance on additives, providing consumers with safer wine choices.

Chemogenetic activation of histamine neurons promotes retrieval of apparently lost memories.

Memory retrieval can become difficult over time, but it is important to note that memories that appear to be forgotten might still be stored in the brain, as shown by their occasional spontaneous retrieval. Histamine in the central nervous system is a promising target for facilitating the recovery of memory retrieval. Our previous study demonstrated that histamine H3 receptor (H3R) inverse agonists/antagonists, activating histamine synthesis and release, enhance activity in the perirhinal cortex and help in retrieving forgotten long-term object recognition memories. However, it is unclear whether enhancing histaminergic activity alone is enough for the recovery of memory retrieval, considering that H3Rs are also located in other neuron types and affect the release of multiple neurotransmitters. In this study, we employed a chemogenetic method to determine whether specifically activating histamine neurons in the tuberomammillary nucleus facilitates memory retrieval. In the novel object recognition test, control mice did not show a preference for objects based on memory 1 week after training, but chemogenetic activation of histamine neurons before testing improved memory retrieval. This selective activation did not affect the locomotor activity or anxiety-related behavior. Administering an H2R antagonist directly into the perirhinal cortex inhibited the recovery of memory retrieval induced by the activation of histamine neurons. Furthermore, we utilized the Barnes maze test to investigate whether chemogenetic activation of histamine neurons influences the retrieval of forgotten spatial memories. Control mice explored all the holes in the maze equally 1 week after training, whereas mice with chemogenetically activated histamine neurons spent more time around the target hole. These findings indicate that chemogenetic activation of histamine neurons in the tuberomammillary nucleus can promote retrieval of seemingly forgotten object recognition and spatial memories.

Histamine-Responsive Hydrogel Biosensors Based on Aptamer Recognition and DNA-Driven Swelling Hydrogels.

Detection of chemical substances is essential for living a healthy and cultural life in the modern world. One type of chemical sensing technology, biosensing, uses biological components with molecular recognition abilities, enabling a broad spectrum of sensing targets. Short single-stranded nucleic acids called aptamers are one of the biological molecules used in biosensing, and sensing methods combining aptamers and hydrogels have been researched for simple sensing applications. In this research, we propose a hydrogel-based biosensor that uses aptamer recognition and DNA-driven swelling hydrogels for the rapid detection of histamine. Aptamer recognition and DNA-driven swelling hydrogels are directly linked via DNA molecular reactions, enabling rapid sensing. We selected histamine, a major food poisoning toxin, as our sensing target and detected the existence of histamine within 10 min with significance. Because this sensing foundation uses aptamers, which have a vast library of targets, we believe this system can be expanded to various targets, broadening the application of hydrogel-based biosensors.

Histamine-related genes participate in the establishment of an immunosuppressive microenvironment and impact the immunotherapy response in hepatocellular carcinoma.

Chronic inflammation is pivotal in the pathogenesis of hepatocellular carcinoma (HCC). Histamine is a biologically active substance that amplifies the inflammatory and immune response and serves as a neurotransmitter. However, knowledge of histamine's role in HCC and its effects on immunotherapy remains lacking. We focused on histamine-related genes to investigate their potential role in HCC. The RNA-seq data and clinical information regarding HCC were obtained from The Cancer Genome Atlas (TCGA). After identifying the differentially expressed genes, we constructed a signature using the univariate Cox proportional hazard regression and least absolute shrinkage and selection operator (LASSO) analyses. The signature's predictive performance was evaluated using a receiver operating characteristic curve (ROC) analysis. Furthermore, drug sensitivity, immunotherapy effects, and enrichment analyses were conducted. Histamine-related gene expression in HCC was confirmed using quantitative real-time polymerase chain reaction (qRT-PCR). A histamine-related gene prognostic signature (HRGPS) was developed in TCGA. Time-dependent ROC and Kaplan-Meier survival analyses demonstrated the signature's strong predictive power. Importantly, patients in high-risk groups exhibited a higher frequency of TP53 mutations, elevated immune checkpoint-related gene expression, and increased infiltration of immunosuppressive cells-indicating a potentially favorable response to immunotherapy. In addition, drug sensitivity analysis revealed that the signature could effectively predict chemotherapy efficacy and sensitivity. qRT-PCR results validated histamine-related gene overexpression in HCC. Our findings demonstrate that inhibiting histamine-related genes and signaling pathways can impact the therapeutic effect of anti-PD-1/PD-L1. The precise predictive ability of our signature in determining the response to different therapeutic options highlights its potential clinical significance.

Evaluation of the therapeutic effect of Sacha inchi oil in atopic dermatitis mice.

Atopic dermatitis (AD) is a prevalent inflammatory skin condition characterized by a multifaceted pathogenesis, which encompasses immune system signaling dysregulation, compromised skin barrier function, and genetic influencers. Sacha inchi (Plukenetia volubilis L.) oil (SIO) has demonstrated potent anti-inflammatory and antioxidant properties, however, the mechanism underlying the beneficial effects of SIO on AD remains unclear. This study aims to investigate the anti-AD effect of SIO and its possible molecular mechanism in mice with AD. The results demonstrated that SIO significantly reduced the degree of skin lesions and scratching, and improved the skin thickness and mast cell infiltration in AD mice. Furthermore, SIO significantly reduced the levels of immunoglobulin E, histamine and thymic stromal lymphopoietin in serum of AD mice. Additionally, it inhibited the expression of tumor necrosis factor-γ, interferon-γ, interleukin-2, interleukin-4, interleukin 1ß and other inflammatory cytokines in the lesions skin of mice. The Western blotting analysis revealed that SIO exhibited an upregulatory effect on the protein expression of filaggrin and loricrin, while concurrently exerting inhibitory effects on the protein expression and phosphorylation levels of P38, ERK, NF-κB, and IκBα within their respective signaling pathways. Consequently, it can be inferred that SIO exerts a significant anti-atopic dermatitis effect by modulating the P38, ERK, NF-κB, and IκBα signaling pathways. This study contributes to expand the research and development potential of SIO, and provides novel insights and potential therapeutic strategies for AD treatment.

Recognition and detection of histamine in foods using aptamer modified fluorescence polymer dots sensors.

Histamine has been known as a momentous cause of biogenic amine poisoning. Therefore, the content of histamine in foods is strictly required to be controlled within a certain range. Here, an aptamer fluorescent sensor was developed for detection of histamine. Poly [(9, 9-di-n-octylfluorenyl-2, 7-diyl)-alt-(benzo [2,1,3] thiadia-zol-4, 8-diyl)] (PF8BT) and the styrene maleic anhydride copolymer (PSMA) were used for the preparation of PF8BT-Polymer dots (PF8BT-Pdots). PF8BT-Pdots and the cyanine3-phosphoramidite (Cy3) were linked through aptamer to achieve the ratiometric detection for histamine. PF8BT-Pdots were partly quenched by Cy3 due to the fluorescence resonance energy transfer (FRET), when the histamine molecule was recognized by aptamer on the surface of PF8BT-Pdots. A linear range (3-21 µmol/L) was obtained for histamine detection with a low limit of detection (LOD = 0.38 µmol/L). PF8BT aptamer Pdots (PF8BT-A) were used to detect histamine in simply treated aquaculture water and tuna. The cell imaging of HeLa cells presented a good biosecurity and outstanding fluorescent imaging capability of PF8BT-A. The aptamer fluorescent sensors provided a new platform for rapid and accurate detection of histamine in aquatic products and had great potential for the application in food safety and quality control.

Ultraviolet Protection From a Patented Amino Acid Complex Technology.

OBJECTIVE:   This study aimed to investigate the ultraviolet (UV) protection/repair benefits of a patented Amino Acid Complex (AAComplex). METHODS: I) AAComplex was incubated with dermal fibroblasts, with/without UVA, and collagen I was measured with a GlasBoxPlus device. II) A lotion, with/without AAComplex (1%) was applied topically to skin explants, following UVA irradiation, and quantified for health-related biomarkers (TNFalpha, histamine, and MMP-1). III) A broad spectrum sunscreen with SPF 46 and a skincare serum containing AAComplex (2%) were assessed using epidermal equivalents, in the presence of UV irradiation, for effects on IL-1alpha, thymine dimers, Ki-67, filaggrin and Nrf2. RESULTS: I) Collagen I synthesis in dermal fibroblasts was significantly decreased after UVA compared to without UV. The presence of AAComplex prevented this decrease. II) UVA irradiation of skin explants increased histamine, TNFα, and MMP-1. Hydrocortisone aceponate cream significantly decreases all 3 biomarkers. AAComplex contained lotion also significantly decreased all 3 biomarkers, the no AAComplex control lotion only reduced histamine. III) With the regimen of sunscreen + AAComplex contained skincare serum, the significant reduction in IL-1alpha was observed along with a complete recovery of Ki-67 and stimulation of filaggrin and Nrf2T. No thymine dimer positive cell was observed indicating the most positive skin impact from the regiment.  Conclusion: This research using different human skin models demonstrated that AAComplex can provide protection and damage repair caused by UV, at the ingredient level also when formulated in a serum or lotion formula. Skin may be best protected from UV damage when the regimen is used.   J Drugs Dermatol. 2024;23(5):366-375. doi:10.36849/JDD.7916.