Histidine Decarboxylase Gene Research Articles

Clinicopathologic and Genomic Features of Invasive Stratified Mucin-producing Carcinoma of the Uterine Cervix Coexisting With High-grade Squamous Intraepithelial Lesion.

Invasive stratified mucin-producing carcinoma (ISMC) is a specific type of adenocarcinoma of the cervix, which is associated with human papillomavirus infection and often coexists with other types of carcinomas. However, given its rarity, understanding of this disease remains insufficient. We present a unique case of ISMC of the cervix coexisting with a high-grade squamous intraepithelial lesion (HSIL). In addition to histologic and immunohistochemical feature observation, genomic profiling of the 2 lesions was performed. Histologically, the ISMC and HSIL lesions were independent of each other. Aside from the typical morphology, various architectural features of ISMC were observed. Immunohistochemically, the ISMC and HSIL lesions were strongly and diffusely positive for p16 and exhibited high Ki-67 expression. The ISMC lesion was also positive for CK7, MUC5AC, and MUC6, while it was negative for PAX-8. The HSIL lesion was positive for CK5/6 and p40. The combined positive score of PD-L1 was 55. The other markers were all negative in both lesions, and the p53 was wild-type. Next-generation sequencing analysis revealed multiple gene mutations in the ISMC and HSIL lesions. A total of 88 gene mutations were identified in the ISMC lesion, while 20 gene mutations were identified in the HSIL lesion. Three mutations (ERBB2, histidine decarboxylase gene [HDC], and BSN) were detected in the ISMC and HSIL lesions. Both lesions had a low tumor mutation burden and microsatellite-stable status. No copy number-associated variants or structural variations were identified in either lesion. These results suggest that patients with ISMC may benefit from PD-L1 immunotherapy and targeted therapy.

Effects of pickle brine and glycine addition on biogenic amine production in pickle fermentation

This study investigated the effects of different pickle brines and glycine additions on biogenic amine formation in pickle fermentation. The results showed that the brines with higher biogenic amine content led to the production of more biogenic amines in the simulated pickle fermentation system. This was related to the abundance of biogenic amine-producing microorganisms in the microbial communities of the brines. Metagenome analysis of the brines and metatranscriptome analysis of the fermentation systems showed that putrescine was primarily from Lactobacillus, Oenococcus, and Pichia, while histamine and tyramine were primarily from Lactobacillus and Tetragenococcus. Addition of glycine significantly reduced the accumulation of biogenic amines in the simulated pickle fermentation system by as much as 70 %. The addition of glycine had no inhibitory effect on the amine-producing microorganisms, but it down-regulated the transcription levels of the genes for enzymes related to putrescine synthesis in Pichia, Lactobacillus, and Oenococcus, as well as the histidine decarboxylase genes in Lactobacillus and Tetragenococcus. Catalytic reaction assay using crude solutions of amino acid decarboxylase extracted from Lactobacillus brevis showed that the addition of glycine inhibited 45 %–55 % of ornithine decarboxylase and tyrosine decarboxylase activities. This study may provide a reference for the study and control of the mechanism of biogenic amine formation in pickle fermentation.

Technological and Enzymatic Characterization of Autochthonous Lactic Acid Bacteria Isolated from Viili Natural Starters.

Viili, a Finnish ropy fermented milk, is traditionally manufactured through spontaneous fermentation, by mesophilic lactic acid bacteria and yeast-like fungi, or back-slopping. This study evaluated four natural viili starters as sources of lactic acid bacteria for dairy production. Back-slopping activation of the studied viili samples was monitored through pH and titratable acidity measurements and enumeration of mesophilic lactic acid bacteria. Sixty lactic acid bacteria isolates were collected, molecularly identified, and assayed for acidification performance, enzymatic activities, production of exopolysaccharides (EPSs), presence of the histidine decarboxylase (hdcA) gene of Gram-positive bacteria, and production of bacteriocins. A neat predominance of Lactococcus lactis emerged among the isolates, followed by Enterococcus faecalis, Enterococcus faecium, Enterococcus durans, Enterococcus lactis, and Lactococcus cremoris. Most isolates exhibited proteolytic activity, whereas only a few enterococci showed lipase activity. Five isolates identified as L. cremoris, L. lactis, and E. faecalis showed a good acidification performance. Most of the isolates tested positive for leucine arylamidase, whereas only one E. durans and two L. lactis isolates were positive for valine arylamidase. A few isolates also showed a positive reaction for beta-galactosidase and alpha- and beta-glucosidase. None of the isolates produced EPSs or bacteriocins. The hdcA gene was detected in five isolates identified as L. lactis and E. faecium. A few L. cremoris and L. lactis isolates for potential use as starter or adjunct cultures for dairy processing were finally identified.

Elucidating the potential of chlorogenic acid for controlling Morganella psychrotolerans growth and histamine formation.

To investigate the inhibitory impact of chlorogenic acid (CGA) on the growth of Morganella psychrotolerans and its ability to form histamine. The antimicrobial effect of CGA on M. psychrotolerans was evaluated using the minimum inhibitory concentration (MIC) method, revealing an MIC value of 10mg ml-1. The alkaline phosphatase (AKP) activity, cell membrane potential, and scanning electron microscopy images revealed that CGA treatment disrupted cell structure and cell membrane. Moreover, CGA treatment led to a dose-dependent decrease in crude histidine decarboxylase (HDC) activity and gene expression of histidine decarboxylase (hdc). Molecular docking analysis demonstrated that CGA interacted with HDC through hydrogen bonds. Furthermore, in situ investigation confirmed the efficacy of CGA in controlling the growth of M. psychrotolerans and significantly reducing histamine formation in raw tuna. CGA had good activity in controlling the growth of M. psychrotolerans and histamine formation.

Insight into a natural novel histidine decarboxylase gene deletion in Enterobacter hormaechei RH3 from traditional Sichuan-style sausage.

Histamine (HIS) is primarily formed from decarboxylated histidine by certain bacteria with histidine decarboxylase (hdc) activity and is the most toxic biogenic amine. Hdc, which is encoded by the hdc gene, serves as a key enzyme that controls HIS production in bacteria. In this paper, we characterized the changes in microbial and biogenic amines content of traditional Sichuan-style sausage before and after storage and demonstrated that Enterobacteriaceae play an important role in the formation of HIS. To screen for Enterobacteriaceae with high levels of HIS production, we isolated strain RH3 which has a HIS production of 2.27mg/mL from sausages stored at 37°C for 180 days, using selective media and high-performance liquid chromatography. The strain RH3 can produce a high level of HIS after 28h of fermentation with a significant hysteresis. Analysis of the physicochemical factors revealed that RH3 still retained its ability to partially produce HIS in extreme environments with pH 3.5 and 10.0. In addition, RH3 exhibited excellent salt tolerance (6.0% NaCl and 1.0% NaNO2 ). Subsequently, RH3 was confirmed as Enterobacter hormaechei with hdc gene deletion by PCR, western blot, and whole-genome sequencing analysis. Furthermore, RH3 exhibited pathogenicity rate of 75.60% toward the organism, indicating that it was not a food-grade safe strain, and demonstrated a high level of conservation in intraspecific evolution. The results of this experiment provide a new reference for studying the mechanism of HIS formation in microorganisms. PRACTICAL APPLICATION: This study provides a new direction for investigating the mechanism of histamine (HIS) formation by microorganisms and provides new insights for further controlling HIS levels in meat products. Further research can control the key enzymes that form HIS to control HIS levels in food.

Insight into the role of lactic acid bacteria in the development of a novel fermented pistachio (Pistacia vera L.) beverage

This study aimed to assess the fermentability of a pistachio-based beverage. The effects of lactic acid fermentation on the odor profile and the stability of the beverage were also assessed. To this end, a procedure for obtaining a pistachio beverage was developed, and the nutritional composition of the beverage was obtained. The beverage was characterized by a high content of fiber (2.9%), fat (4.6%), and protein (2%), and contained high amounts of K and Mg. For the experiment, 43 cultures of the following lactic acid bacteria were used: Companilactibacillus paralimentarius, Companilactibacillus kimchi, Levilactibacillus brevis, Lactiplantibacillu pentosus, Lactiplantibacillus plantarum, Lactiplantibacillus paraplantarum, Latilactobacillus curvatus, Leuconostoc pseudomesenteroides, and Furfurilactobacillus rossiae. The cultures were evaluated for the following technological characteristics: i) growth and acidifying activity, ii) production of exopolysaccharides; iii) presence of histidine decarboxylase (hdcA) gene; iv) antimicrobial activity against Listeria innocua. The cultures were used in model pistachio-based fermentations to assess their ability to grow and acidify. The odor profile of the beverage after 24 h fermentation was assessed using an electronic nose system (E-nose). The pistachio-based beverage resulted an optimal substrate for lactic acid bacteria that reached loads between 8 and 10 log CFU/mL and acidified the beverage to pH values between 4 and 5.5. In the beverage, viable counts of all cultures remained above 8 log CFU/mL after 30 days of storage at 4 °C. The E-nose analysis represented a valid screening method to evaluate the effects of the fermentative activity of microbial starters on the qualitative characteristics of this novel food matrix.

A neurotransmitter histamine mediating phototransduction and photopreference in Callosobruchus maculatus.

The biogenic amine histamine plays a critical role in the phototransduction and photopreference of most insects. Here, we study the function of histamine in Callosobruchus maculatus, a global storage pest. In our experiment, we initially identified the histidine decarboxylase (hdc) gene through bioinformation analysis. We subsequently investigated effects of hdc and histamine on the photopreference of C. maculatus using a combination of RNA interference (RNAi), electroretinograms (ERG), immunostaining, and photopreference behavior approaches. Our results showed that histamine was required for visual signal transduction of C. maculatus, and increased its photopreference regardless of the wavelength. This is the first study analyzing the molecular characteristics of C. maculatus photopreference, which forms the basis for a molecular mechanism for the effects of histamine on its visual transduction and preference. In practice, better understanding the photopreference patterns contributes to IPM (integrated pest management) for this storage pest. © 2023 Society of Chemical Industry.

Effects of different fermentation starter cultures on the quality of fish sauce prepared from deep-sea smelt

This study investigated deep-sea smelt fish sauces made with three types of starter cultures to produce a high-quality product that contains low histamine levels. The starter cultures included lactic acid bacterium Tetragenococcus halophilus for soy sauce and T. halophilus strains 8-25 and 14-1 that do not receive the histidine decarboxylase gene, isolated from fermented marine foods. The addition of these bacteria reduced the pH of the fish sauce mashes (moromis) to below 5.0 in the first 21 days. This pH level was maintained until the end of fermentation. Throughout fermentation, histamine-producing bacterial counts and histamine levels in the moromis were below 9.3 × 10 most probable number (MPN)/g and 113 mg/L, respectively. A principal component analysis of the final products revealed that taste, which was obtained using a taste sensor, and quality indicators (physicochemical and extractive components) differed among the three products.

Diversity and Safety Aspects of Coagulase-Negative Staphylococci in Ventricina del Vastese Italian Dry Fermented Sausage

Ventricina del Vastese is a traditional dry fermented sausage from Central Italy not yet characterized for the occurrence, identity and safety of coagulase-negative staphylococci (CNS), a bacterial group technologically important for this kind of product. Therefore, in this study, 98 CNS isolates from four manufacturers were differentiated using repetitive element palindromic PCR (Rep-PCR) and identified using 16S rRNA gene sequencing. These were examined for genes encoding biogenic amine (BA) production, resistance to aminoglycosides, β-lactams, tetracyclines and staphylococcal enterotoxins (SEs). Staphylococcus succinus (55%) predominated, followed by S. xylosus (30%), S. epidermidis (7.4%), S. equorum (3.1%), S. saprophyticus (3.1%) and S. warneri (1%). One S. succinus subsp. casei isolate was slightly β-hemolytic. SEs and the histidine decarboxylase gene hdcA were not detected, whereas the tyrosine decarboxylase gene tdcA was detected in four S. xylosus isolates. The blaZ beta-lactamase gene in an S. equorum isolate, tetracycline resistance genes tetK in six S. succinus isolates and tetA in one S. succinus isolate also bearing tetK were found. The product examined is characterized by a peculiar CNS species ratio and a low occurrence and diversity of AR transferable genes than found in other studies, as a probable consequence of production only with meat from animals raised in small farms with extensive rearing systems in which antibiotic usage is infrequent.

Histamine Release in the Prefrontal Cortex Excites Fast-Spiking Interneurons while GABA Released from the Same Axons Inhibits Pyramidal Cells.

We studied how histamine and GABA release from axons originating from the hypothalamic tuberomammillary nucleus (TMN) and projecting to the prefrontal cortex (PFC) influence circuit processing. We optostimulated histamine/GABA from genetically defined TMN axons that express the histidine decarboxylase gene (TMNHDC axons). Whole-cell recordings from PFC neurons in layer 2/3 of prelimbic, anterior cingulate, and infralimbic regions were used to monitor excitability before and after optostimulated histamine/GABA release in male and female mice. We found that histamine-GABA release influences the PFC through actions on distinct neuronal types: the histamine stimulates fast-spiking interneurons; and the released GABA enhances tonic (extrasynaptic) inhibition on pyramidal cells (PyrNs). For fast-spiking nonaccommodating interneurons, histamine released from TMNHDC axons induced additive gain changes, which were blocked by histamine H1 and H2 receptor antagonists. The excitability of other fast-spiking interneurons in the PFC was not altered. In contrast, the GABA released from TMNHDC axons predominantly produced divisive gain changes in PyrNs, increasing their resting input conductance, and decreasing the slope of the input-output relationship. This inhibitory effect on PyrNs was not blocked by histamine receptor antagonists but was blocked by GABAA receptor antagonists. Across the adult life span (from 3 to 18 months of age), the GABA released from TMNHDC axons in the PFC inhibited PyrN excitability significantly more in older mice. For individuals who maintain cognitive performance into later life, the increases in TMNHDC GABA modulation of PyrNs during aging could enhance information processing and be an adaptive mechanism to buttress cognition.SIGNIFICANCE STATEMENT The hypothalamus controls arousal state by releasing chemical neurotransmitters throughout the brain to modulate neuronal excitability. Evidence is emerging that the release of multiple types of neurotransmitters may have opposing actions on neuronal populations in key cortical regions. This study demonstrates for the first time that the neurotransmitters histamine and GABA are released in the prefrontal cortex from axons originating from the tuberomammillary nucleus of the hypothalamus. This work demonstrates how hypothalamic modulation of neuronal excitability is maintained throughout adult life, highlighting an unexpected aspect of the aging process that may help maintain cognitive abilities.

Comparative Genomics of Lentilactobacillus parabuchneri isolated from dairy, KEM complex, Makgeolli, and Saliva Microbiomes

BackgroundLentilactobacillus parabuchneri is of particular concern in fermented food bioprocessing due to causing unwanted gas formation, cracks, and off-flavor in fermented dairy foods. This species is also a known culprit of histamine poisonings because of decarboxylating histidine to histamine in ripening cheese. Twenty-eight genomes in NCBI GenBank were evaluated via comparative analysis to determine genomic diversity within this species and identify potential avenues for reducing health associated risks and economic losses in the food industry caused by these organisms.ResultCore genome-based phylogenetic analysis revealed four distinct major clades. Eight dairy isolates, two strains from an unknown source, and a saliva isolate formed the first clade. Three out of five strains clustered on clade 2 belonged to dairy, and the remaining two strains were isolated from the makgeolli and Korean effective microorganisms (KEM) complex. The third and fourth clade members were isolated from Tete de Moine and dairy-associated niches, respectively. Whole genome analysis on twenty-eight genomes showed ~ 40% of all CDS were conserved across entire strains proposing a considerable diversity among L. parabuchneri strains analyzed. After assigning CDS to their corresponding function, ~ 79% of all strains were predicted to carry putative intact prophages, and ~ 43% of the strains harbored at least one plasmid; however, all the strains were predicted to encode genomic island, insertion sequence, and CRISPR-Cas system. A type I-E CRISPR-Cas subgroup was identified in all the strains, with the exception of DSM15352, which carried a type II-A CRISPR-Cas system. Twenty strains were predicted to encode histidine decarboxylase gene cluster that belongs to not only dairy but also saliva, KEM complex, and unknown source. No bacteriocin-encoding gene(s) or antibiotic resistome was found in any of the L. parabuchneri strains screened.ConclusionThe findings of the present work provide in-depth knowledge of the genomics of L. parabuchneri by comparing twenty-eight genomes available to date. For example, the hdc gene cluster was generally reported in cheese isolates; however, our findings in the current work indicated that it could also be encoded in those strains isolated from saliva, KEM complex, and unknown source. We think prophages are critical mobile elements of L. parabuchneri genomes that could pave the way for developing novel tools to reduce the occurrence of this unwanted species in the food industry.

White matter abnormalities in the Hdc knockout mouse, a model of tic and OCD pathophysiology.

An inactivating mutation in the histidine decarboxylase gene (Hdc) has been identified as a rare but high-penetrance genetic cause of Tourette syndrome (TS). TS is a neurodevelopmental syndrome characterized by recurrent motor and vocal tics; it is accompanied by structural and functional abnormalities in the cortico-basal ganglia circuitry. Hdc, which is expressed both in the posterior hypothalamus and peripherally, encodes an enzyme required for the biosynthesis of histamine. Hdc knockout mice (Hdc-KO) functionally recapitulate this mutation and exhibit behavioral and neurochemical abnormalities that parallel those seen in patients with TS. We performed exploratory RNA-seq to identify pathological alterations in several brain regions in Hdc-KO mice. Findings were corroborated with RNA and protein quantification, immunohistochemistry, and ex vivo brain imaging using MRI. Exploratory RNA-Seq analysis revealed, unexpectedly, that genes associated with oligodendrocytes and with myelin production are upregulated in the dorsal striatum of these mice. This was confirmed by qPCR, immunostaining, and immunoblotting. These results suggest an abnormality in myelination in the striatum. To test this in an intact mouse brain, we performed whole-brain ex vivo diffusion tensor imaging (DTI), which revealed reduced fractional anisotropy (FA) in the dorsal striatum. While the DTI literature in individuals with TS is sparse, these results are consistent with findings of disrupted descending cortical projections in patients with tics. The Hdc-KO model may represent a powerful system in which to examine the developmental mechanisms underlying this abnormality.

Histamine production by the gut microbiota induces visceral hyperalgesia through histamine 4 receptor signaling in mice.

The gut microbiota has been implicated in chronic pain disorders, including irritable bowel syndrome (IBS), yet specific pathophysiological mechanisms remain unclear. We showed that decreasing intake of fermentable carbohydrates improved abdominal pain in patients with IBS, and this was accompanied by changes in the gut microbiota and decreased urinary histamine concentrations. Here, we used germ-free mice colonized with fecal microbiota from patients with IBS to investigate the role of gut bacteria and the neuroactive mediator histamine in visceral hypersensitivity. Germ-free mice colonized with the fecal microbiota of patients with IBS who had high but not low urinary histamine developed visceral hyperalgesia and mast cell activation. When these mice were fed a diet with reduced fermentable carbohydrates, the animals showed a decrease in visceral hypersensitivity and mast cell accumulation in the colon. We observed that the fecal microbiota from patients with IBS with high but not low urinary histamine produced large amounts of histamine in vitro. We identified Klebsiella aerogenes, carrying a histidine decarboxylase gene variant, as a major producer of this histamine. This bacterial strain was highly abundant in the fecal microbiota of three independent cohorts of patients with IBS compared with healthy individuals. Pharmacological blockade of the histamine 4 receptor in vivo inhibited visceral hypersensitivity and decreased mast cell accumulation in the colon of germ-free mice colonized with the high histamine-producing IBS fecal microbiota. These results suggest that therapeutic strategies directed against bacterial histamine could help treat visceral hyperalgesia in a subset of patients with IBS with chronic abdominal pain.

Antagonism of histamine H3 receptor promotes angiogenesis following focal cerebral ischemia.

Our previous study showed that H3 receptor antagonists reduced neuronal apoptosis and cerebral infarction in the acute stage after cerebral ischemia, but through an action independent of activation of histaminergic neurons. Because enhanced angiogenesis facilitates neurogenesis and neurological recovery after ischemic stroke, we herein investigated whether antagonism of H3R promoted angiogenesis after brain ischemia. Photothrombotic stroke was induced in mice. We showed that administration of H3R antagonist thioperamide (THIO, 10 mg·kg-1·d-1, i.p., from D1 after cerebral ischemia) significantly improved angiogenesis assessed on D14, and attenuated neurological defects on D28 after cerebral ischemia. Compared with wild-type mice, Hrh3-/- mice displayed more blood vessels in the ischemic boundary zone on D14, and THIO administration did not promote angiogenesis in these knockout mice. THIO-promoted angiogenesis in mice was reversed by i.c.v. injection of H3R agonist immepip, but not by H1 and H2 receptor antagonists, histidine decarboxylase inhibitor α-fluoromethylhistidine, or histidine decarboxylase gene knockout (HDC-/-), suggesting that THIO-promoted angiogenesis was independent of activation of histaminergic neurons. In vascular endothelial cells (bEnd.3), THIO (10-9-10-7 M) dose-dependently facilitated cell migration and tube formation after oxygen glucose deprivation (OGD), and H3R knockdown caused similar effects. We further revealed that H3R antagonism reduced the interaction between H3R and Annexin A2, while knockdown of Annexin A2 abrogated THIO-promoted angiogenesis in bEnd.3 cells after OGD. Annexin A2-overexpressing mice displayed more blood vessels in the ischemic boundary zone, which was reversed by i.c.v. injection of immepip. In conclusion, this study demonstrates that H3R antagonism promotes angiogenesis after cerebral ischemia, which is independent of activation of histaminergic neurons, but related to the H3R on vascular endothelial cells and its interaction with Annexin A2. Thus, H3R antagonists might be promising drug candidates to improve angiogenesis and neurological recovery after ischemic stroke.

Histidine and Humans Disease

Background: Histidine is an important amino acid with important properties that enable it to play a vital part in many activities in the human body, such as proton buffering, metal ion chelation, scavenging of reactive oxygen and nitro-gen species, erythropoiesis and the histaminergic system. This review presents the impact of histidine level fluctuation on the body function, the physiological role and metabolic pathway of histidine in various parts of the human's body. Also, we investigated that histamine produc-tion by Histidine decarboxylase gene and there is relationship between histidine food intake and level of Histamine in blood, which resulting in the obesity, anemia and other nutrition issues. In addition, a neurotrans-mitter is included oin histamine that is widely distributed throughout the human brain; its deficiency could cause problems in the nervous system. This study revealed that deficiency of histidine contributed to mental problems like Parkinson's disease (PD), schizophrenia (SCZ), kidney and prion disease as well. As a result, histidine is important to keep hu-man body healthy, and it is also found that hisidine is used as a suitable drug for people who have schizophrenia. This review revealed that the correlation between histamine and asthma is still not well understood. So, this review will open way for researchers to focuses on this aspect. Keywords: Histidine, Histamine, physiological role, Parkinson's disease and human disease

Identification by means of molecular tools of the microbiota responsible for the formation of histamine accumulated in commercial cheeses in Spain

Histamine intoxication is an important food safety and public health concern. Ripened cheeses are the most common dairy products in which histamine can accumulate. Histamine is formed by the microbiota present in cheese by decarboxylation of histidine, due to the action of the histidine decarboxylase. This study's objective was to identify the responsible for the formation of histamine accumulated in commercial cheeses. The content of histamine of 39 different types of cheeses marketed in Spain, of varying milk origin, was assessed. About one third of the cheeses analysed contained more than 200 mg/kg histamine; two cheeses exceeded 500 mg/kg histamine, the consumption of such cheeses can be harmful or even toxic for consumers. The five cheeses with the highest histamine concentrations were selected for in-depth molecular analysis. Firstly, bacterial and yeast isolates were obtained, and then the total genetic material from the cheeses was analysed, in order to verify the putative presence of the hdc histidine decarboxylase gene. In order to identify the histamine producing microorganisms, the nucleotide sequences of the histidine decarboxylase genes from the cheeses were amplified, and subjected them to Sanger sequencing. In four of the five selected cheeses, the main histamine producer was identified as Lentilactobacillus parabuchneri, whereas in the remaining cheese it was Tetragenococcus halophilus. The hdc gene was located in an unstable plasmid, only present in that cheese sample. Since all histamine producing microorganisms identified in this study are not part of the species used in cheese starter cultures, an improvement of hygienic manufacturing practices and/or thermal treatments for microbial inactivation in milk may be considered to prevent histamine accumulation in cheeses during ripening.

Role of histidine decarboxylase gene in the pathogenesis of Tourette syndrome.

Tourette syndrome (TS) is caused by complex genetic and environmental factors and is characterized by tics. Histidine decarboxylase (HDC) mutation is a rare genetic cause with high penetrance in patients with TS. HDC‐knockout (KO) mice have similar behavioral and neurochemical abnormalities as patients with TS. Therefore, HDC‐KO mice are considered a valuable TS pathophysiological model as it reveals the underlying pathological mechanisms that cannot be obtained from patients with TS, thus advancing the development of treatment strategies for TS and other tic disorders. This review summarizes some of the recent research hotspots and progress in HDC‐KO mice, aiming to deepen our understanding of brain mechanisms relevant to TS. Furthermore, we encapsulate the possible brain nerve cell changes in HDC‐KO mice and their potential roles in TS to provide multiple directions for the future research on tics.

Technological Parameters, Anti-Listeria Activity, Biogenic Amines Formation and Degradation Ability of L. plantarum Strains Isolated from Sheep-Fermented Sausage.

The aim of this work was to identify and characterize, from a technological and safety point of view, the lactic acid bacteria (LAB) isolated from traditional sheep-fermented sausage. First, LABs were identified then were screened for some technological parameters such as acidifying and growth ability, proteolytic and lipolytic activity and for antimicrobial activity. Finally, biogenic amine production and degradation abilities were also evaluated. This research reveals the predominance of Lactiplantibacillus (L.) plantarum on LAB community. Almost all L. plantarum strains were active against Listeria monocytogenes strains (inhibition zone diameters > 1 cm). None of the tested strains were positive in histidine (hdcA), lysine (ldc) and tyrosine (tyrdc) decarboxylase genes and only one (L. plantarum PT9-2) was positive to the agmatine deiminase (agdi) gene. Furthermore, given the positive results of the sufl (multi-copper oxidase) gene detection, all strains showed a potential degradation ability of biogenic amines.

Inhibitory mechanism of cell-free supernatants of Lactobacillus plantarum on Proteus mirabilis and influence of the expression of histamine synthesis-related genes

The purpose of this study was to evaluate the inhibitory mechanism of cell-free supernatants of Lactobacillus plantarum (LCFS) on Proteus mirabilis and estimate the expression of histamine synthesis-related genes. The minimum inhibitory concentration (MIC) of the LCFS and antibacterial curve assay was determined by the tube double-dilution method. The antibacterial mechanism was explored by cell integrity, morphology, and structure of P. mirabilis. Further, the expression of the histidine decarboxylase (hdcA) gene and histidine/histamine antiporter (hdcP) gene of P. mirabilis and the intracellular and extracellular contents of histidine and histamine were determined. The MIC of the LCFS was 12.5 mg/mL, and the antibacterial curve assay showed an inhibited growth of P. mirabilis. The increase in the Alkaline Phosphatase (AKP) content, membrane permeability, and potential indicated the destruction of the cytoplasm, cell membrane, and cell wall of P. mirabilis. The results of SEM and TEM revealed that the LCFS disrupted the normal morphology and structure of the cell. Moreover, differences in the extracellular and intracellular histidine and histamine content between the MIC group and the control group was consistent with the decreased expression of hdcA and hdcP genes in the MIC group observed in the previous antimicrobial studies. Hence, the inhibitory mechanism of LCFS on histamine formation was clarified at cellular and molecular levels.

Acute Intestinal Inflammation Depletes/Recruits Histamine-Expressing Myeloid Cells From the Bone Marrow Leading to Exhaustion of MB-HSCs.

Background & AimsHistidine decarboxylase (HDC), the histamine-synthesizing enzyme, is expressed in a subset of myeloid cells but also marks quiescent myeloid-biased hematopoietic stem cells (MB-HSCs) that are activated upon myeloid demand injury. However, the role of MB-HSCs in dextran sulfate sodium (DSS)-induced acute colitis has not been addressed.MethodsWe investigated HDC+ MB-HSCs and myeloid cells by flow cytometry in acute intestinal inflammation by treating HDC–green fluorescent protein (GFP) male mice with 5% DSS at various time points. HDC+ myeloid cells in the colon also were analyzed by flow cytometry and immunofluorescence staining. Knockout of the HDC gene by using HDC-/-; HDC-GFP and ablation of HDC+ myeloid cells by using HDC-GFP; HDC–tamoxifen-inducible recombinase Cre system; diphtheria toxin receptor (DTR) mice was performed. The role of H2-receptor signaling in acute colitis was addressed by treatment of DSS-treated mice with the H2 agonist dimaprit dihydrochloride. Kaplan–Meier survival analysis was performed to assess the effect on survival.ResultsIn acute colitis, rapid activation and expansion of MB-HSC from bone marrow was evident early on, followed by a gradual depletion, resulting in profound HSC exhaustion, accompanied by infiltration of the colon by increased HDC+ myeloid cells. Knockout of the HDC gene and ablation of HDC+ myeloid cells enhance the early depletion of HDC+ MB-HSC, and treatment with H2-receptor agonist ameliorates the depletion of MB-HSCs and resulted in significantly increased survival of HDC-GFP mice with acute colitis.ConclusionsExhaustion of bone marrow MB-HSCs contributes to the progression of DSS-induced acute colitis, and preservation of quiescence of MB-HSCs by the H2-receptor agonist significantly enhances survival, suggesting the potential for therapeutic utility.