Neurosyphilis complicated by anti-γ-aminobutyric acid-B receptor encephalitis: A case report

BACKGROUND Syphilis is an infectious disease caused by Treponema pallidum that can invade the central nervous system,causing encephalitis.Few cases of anti-N-methyl-Daspartate receptor autoimmune encephalitis(AE)secondary to neurosyphilis have been reported.We report a neurosyphilis patient with anti-γ-aminobutyric acid-B receptor(GABABR)AE.CASE SUMMARY A young man in his 30s who presented with acute epileptic status was admitted to a local hospital.He was diagnosed with neurosyphilis,according to serum and cerebrospinal fluid(CSF)tests for syphilis.After 14 d of antiepileptic treatment and anti-Treponema pallidum therapy with penicillin,epilepsy was controlled but serious cognitive impairment,behavioral,and serious psychiatric symptoms were observed.He was then transferred to our hospital.The Mini-Mental State Examination(MMSE)crude test results showed only 2 points.Cranial magnetic resonance imaging revealed significant cerebral atrophy and multiple fluidattenuated inversion recovery high signals in the white matter surrounding both lateral ventricles,left amygdala and bilateral thalami.Anti-GABABR antibodies were discovered in CSF(1:3.2)and serum(1:100).The patient was diagnosed with neurosyphilis complicated by anti-GABABR AE,and received methylprednisolone and penicillin.Following treatment,his mental symptoms were alleviated.Cognitive impairment was significantly improved,with a MMSE of 8 points.Serum anti-GABABR antibody titer decreased to 1:32.The patient received methylprednisolone and penicillin after discharge.Three months later,the patient’s condition was stable,but the serum anti-GABABR antibody titer was 1:100.CONCLUSION This patient with neurosyphilis combined with anti-GABABR encephalitis benefited from immunotherapy.

Cognitive dysfunction in schizophrenia patients caused by downregulation of γ-aminobutyric acid receptor subunits

BACKGROUND The expression pattern of gamma aminobutyric acid(GABA)receptor subunits are commonly altered in patients with schizophrenia,which may lead to nerve excitation/inhibition problems,affecting cognition,emotion,and behavior.AIM To explore GABA receptor expression and its relationship with schizophrenia and to provide insights into more effective treatments.METHODS This case-control study enrolled 126 patients with schizophrenia treated at our hospital and 126 healthy volunteers who underwent physical examinations at our hospital during the same period.The expression levels of the GABA receptor subunits were detected using 1H-magnetic resonance spectroscopy.The recognized cognitive battery tool,the MATRICS Consensus Cognitive Battery,was used to evaluate the scores for various dimensions of cognitive function.The correlation between GABA receptor subunit downregulation and schizophrenia was also analyzed.RESULTS Significant differences in GABA receptor subunit levels were found between the case and control groups(P<0.05).A significant difference was also found between the case and control groups in terms of cognitive function measures,including attention/alertness and learning ability(P<0.05).Specifically,as the expression levels of GABRA1(α1 subunit gene),GABRB2(β2 subunit gene),GABRD(δsubunit),and GABRE(εsubunit)decreased,the severity of the patients’condition increased gradually,indicating a positive correlation between the downregulation of these 4 receptor subunits and schizophrenia(P<0.05).However,the expression levels of GABRA5(α5 subunit gene)and GABRA6(α6 subunit gene)showed no significant correlation with schizophrenia(P>0.05).CONCLUSION Downregulation of the GABA receptor subunits is positively correlated with schizophrenia.In other words,when GABA receptor subunits are downregulated in patients,cognitive impairment becomes more severe.

γ-aminobutyric acid B2 receptor:A potential therapeutic target for cholangiocarcinoma in patients with diabetes mellitus

BACKGROUND The association between diabetes mellitus(DM)and the increased risk and progression of cholangiocarcinoma(CCA)has been reported with unclear underlying mechanisms.Previous studies showed thatγ-aminobutyric acid(GABA)B2 receptor(GABBR2)was upregulated in CCA cells cultured in high glucose(HG)conditions.Roles of GABA receptors in CCA progression have also been studied,but their association with DM and hyperglycemia in CCA remains unclarified.AIM To investigate the effects of hyperglycemia on GABBR2 expression and the potential use of GABBR2 as a CCA therapeutic target.METHODS CCA cells,KKU-055 and KKU-213A,were cultured in Dulbecco Modified Eagle’s Medium supplemented with 5.6 mmol/L(normal glucose,NG)or 25 mmol/L(HG)glucose and assigned as NG and HG cells,respectively.GABBR2 expression in NG and HG cells was investigated using real-time quantitative polymerase chain reaction and western blot.Expression and localization of GABBR2 in CCA cells were determined using immunocytofluorescence.GABBR2 expression in tumor tissues from CCA patients with and without DM was studied using immunohistochemistry,and the correlations of GABBR2 with the clinicopathological characteristics of patients were analyzed using univariate analysis.Effects of baclofen,a GABA-B receptor agonist,on CCA cell proliferation and clonogenicity were tested using the MTT and clonogenic assays.Phospho-kinases arrays were used to screen the affected signaling pathways after baclofen treatment,and the candidate signaling molecules were validated using the public transcriptomic data and western blot.RESULTS GABBR2 expression in CCA cells was induced by HG in a dose-and time-dependent manner.CCA tissues from patients with DM and hyperglycemia also showed a significantly higher GABBR2 expression compared with tumor tissues from those with euglycemia(P<0.01).High GABBR2 expression was significantly associated with a poorer non-papillary histological subtype but with smaller sizes of CCA tumors(P<0.05).HG cells of both tested CCA cell lines were more sensitive to baclofen treatment.Baclofen significantly suppressed the proliferation and clonogenicity of CCA cells in both NG and HG conditions(P<0.05).Phospho-kinase arrays suggested glycogen synthase kinase 3(GSK3),β-catenin,and the signal transducer and activator of transcription 3(STAT3)as candidate signaling molecules under the regulation of GABBR2,which were verified in NG and HG cells of the individual CCA cell lines.Cyclin D1 and c-Myc,the common downstream targets of GSK3/β-catenin and STAT3 involving cell proliferation,were accordingly downregulated after baclofen treatment.CONCLUSION GABBR2 is upregulated by HG and holds a promising role as a therapeutic target for CCA regardless of the glucose condition.

Relationship of nocturnal concentrations of melatonin, gamma-aminobutyric acid and total antioxidants in peripheral blood with insomnia after stroke： study protocol for a prospective non-randomized controlled trial

Melatonin and gamma-aminobutyric acid（GABA） have been shown to regulate sleep. The nocturnal concentrations of melatonin, GABA and total antioxidants may relate to insomnia in stroke patients. In this prospective single-center non-randomized controlled clinical trial performed in the China Rehabilitation Research Center, we analyzed the relationship of nocturnal concentrations of melatonin, GABA and total antioxidants with insomnia after stroke. Patients during rehabilitation of stroke were recruited and assigned to the insomnia group or non-insomnia group. Simultaneously, persons without stroke or insomnia served as normal controls. Each group contained 25 cases. The primary outcome was nocturnal concentrations of melatonin, GABA and total antioxidants in peripheral blood. The secondary outcomes were Pittsburgh Sleep Quality Index, Insomnia Severity Index, Epworth Sleepiness Scale, Fatigue Severity Scale, Morningness-Eveningness Questionnaire（Chinese version）, and National Institute of Health Stroke Scale. The relationship of nocturnal concentrations of melatonin, GABA and total antioxidants with insomnia after stroke was analyzed and showed that they were lower in the insomnia group than in the non-insomnia group. The severity of stroke was higher in the insomnia group than in the non-insomnia group. Correlation analysis demonstrated that the nocturnal concentrations of melatonin and GABA were associated with insomnia after stroke. This trial was registered at Clinical Trials.gov, identifier： NCT03202121.

The IBI1 Receptor ofβ-Aminobutyric Acid Interacts with VOZ Transcription Factors to Regulate Abscisic Acid Signaling and Callose-Associated Defense

Extemal and internal signals can prime the plant immune system for a faster and/or stronger response to pathogen attack.β-aminobutyric acid(BABA)is an endogenous stress metabolite that induces broad-spectrum disease resistance in plants.BABA perception in Arabidopsis is mediated by the aspartyl tRNA synthetase IBI1,which activates priming of multiple immune responses,including callose-associated cell wall defenses that are under control by abscisic acid(ABA).However,the immediate signaling components after BABA perception by IBI1,as well as the regulatory role of ABA therein,remain unknown.Here,we have studied the early signaling events controlling IBI1-dependent BABA-induced resistance(BABAIR),using untargeted transcriptome and protein interaction analyses.Transcriptome analysis revealed that IBI1-dependent expression of BABA-IR against the biotrophic oomycete Hyaloperonospora arabidopsidis is associated with suppression of ABA-inducible abiotic stress genes.Protein interaction studies identified the VOZ1 and VOZ2 transcription factors(TFs)as IBI1-interacting partners,which are transcrip-tionally induced by ABA but suppress pathogen-induced expression of ABA-dependent genes.Furthermore,we show that VOZ TFs require nuclear localization for their contribution to BABA-IR by mediating augmented expression of callose-associated defense.Collectively,our study indicates that the IBI1-VOZ signaling module channels pathogen-induced ABA signaling toward cell wall defense while simultaneously suppressing abiotic stress-responsive genes.

On-line near-infrared spectroscopy optimizing and monitoring biotransformation process of γ-aminobutyric acid

Near-infrared spectroscopy （NIRS） with its fast and nondestructive advantages can be qualified for the real-time quantitative analysis. This paper demonstrates that NIRS combined with partial least squares （PLS） regression can be used as a rapid analytical method to simultaneously quantify L-glutamic acid （L- GIu） and γ-aminobutyric acid （GABA） in a biotransformation process and to guide the optimization of production conditions when the merits of NIRS are combined with response surface methodology. The high performance liquid chromatography （HPLC） reference analysis was performed by the o-phthaldialdehyde pre-column derivatization. NIRS measurements of two batches of 141 samples were firstly analyzed by PLS with several spectral pre-processing methods. Compared with those of the HPLC reference analysis, the resulting determination coefficients （R2）, root mean square error of prediction （RMSEP） and residual predictive deviation （RPD） of the external validation for the L-GIu concentration were 99.5%, 1.62 g/L, and 11.3, respectively. For the GABA concentration, R2, RMSEP, and RPD were 99.8%, 4.00 g/L, and 16.4, respectively. This NIRS model was then used to optimize the biotransformation process through a Box- Behnken experimental design. Under the optimal conditions without pH adjustment, 200 gjL L-GIu could be catalyzed by 7148 U/L glutamate decarboxylase （GAD） to GABA, reaching 99% conversion at the fifth hour. NIRS analysis provided timely information on the conversion from L-GIu to GABA. The results suggest that the NIRS model can not only be used for the routine profiling of enzymatic conversion, providing a simple and effective method of monitoring the biotransformation process of GABA, but also be considered to be an optimal tool to guide the optimization of production conditions.

Effect of Propofol on Glutamate and γ-aminobutyric Acid Release from Rat Hippocampal Synaptosomes

To investigate the effect of propofol on the release of glutamate and γ-aminobutyric acid （GABA） from rat hippocampal synatosomes, synaptosomes was made from hippocampus and incubated with artificial cerebrospinal fluid （aCSF）. With the experiment of Ca^2＋-dependent release of glutamate and GABA, dihydrokainic acid （DHK） and nipectic acid were added into aCSF. For the observation of Ca^2＋-independent release of glutamate and GABA, no DHK, nipectic acid and Ca^2＋ were added from aCSF. The release of glutamate and GABA were evoked by 20 μmol/L veratridine or 30 mmol/L KCh The concentration of glutamate and GABA in aCSF was measured by using high-performance liquid chromatography （HPLC）. 30, 100 arid 300 μmol/L propofol significantly inhibited veratridine-evoked Ca^2＋-dependent release of glutamate and GABA （P〈0. 01 or P〈0. 05）, However, propofol showed no effect on elevated KCl-evoked Ca^2＋-dependent release of glutamate and GABA （P〉0, 05）, Veratridine or elevated KCI evoked Ca^2＋-independent release of glutamate and GABA was not affected significantly by propofol （P〉0.05）. Propofol could inhibit Ca^2＋- dependent release of glutamate and GABA, However, it has no effect on the Ca^2＋-independent release of glutamate and GABA,

Effect of the pineal gland on 5-hydroxytryptamine and γ-aminobutyric acid secretion in the hippocampus of male rats during the summer and winter

Objective:The present study aimed to investigate the effect of seasonal variation on neurotransmitter release in the hippocampus of normal rats and rats with pineal excision.Methods:Two time points,the summer and winter solstice,which are the longest and shortest days of the year,respectively,were selected.Male Spraguee Dawley rats that underwent a sham operation without pineal excision were included as a control group.The concentrations of 5-hydroxytryptamine(5-HT)andγ-aminobutyric acid(GABA)were determined by radioimmunoassays and enzyme-linked immunosorbent assays,respectively.Results:In the winter,the 5-HT and GABA levels in normal rats exhibited a significant difference compared with those in the operation group(P<.01).A difference was also noted in GABA levels between the normal group and the sham operation group(P<.05).The concentrations of 5-HT and GABA in the hippocampal tissues of the normal group exhibited a seasonal rhythm consisting of elevation during the summer and reduction during the winter(P<.01),while the GABA levels in the sham operation group exhibited a significant difference,with elevation during the summer and reduction during the winter(P<.01).In the operation group,GABA showed the same trend(P<.01).Conclusion:The seasonal rhythm of neurotransmitter secretion by the hippocampus(5-HT and GABA)consisted of elevation during the summer and reduction during the winter.During the winter,the pineal gland exhibited a reverse regulatory effect on the secretion of 5-HT and GABA in the hippocampus,and it exhibited seasonal selectivity with regard to the regulation of 5-HT.

Expression of gamma-aminobutyric acid type A receptor α_2 subunit in the dorsal root ganglion of rats with sciatic nerve injury

The γ-aminobutyric acid neurotransmitter in the spinal cord dorsal horn plays an important role in pain modulation through primary afferent-mediated presynaptic inhibition. The weakening of γ-aminobutyric acid-mediated presynaptic inhibition may be an important cause of neuropathic pain. γ-aminobutyric acid-mediated presynaptic inhibition is related to the current strength of γ-aminobutyric acid A receptor activation. In view of this, the whole-cell patch-clamp technique was used here to record the change in muscimol activated current of dorsal root ganglion neurons in a chronic constriction injury model. Results found that damage in rat dorsal root ganglion neurons following application of muscimol caused concentration-dependent activation of current, and compared with the sham group, its current strength and γ-aminobutyric acid A receptor protein expression decreased. Immunofluorescence revealed that γ-aminobutyric acid type A receptor α2 subunit protein expression decreased and was most obvious at 12 and 15 days after modeling. Our experimental findings confirmed that the y-aminobutyric acid type A receptor α2 subunit in the chronic constriction injury model rat dorsal root ganglion was downregulated, which may be one of the reasons for the reduction of injury in dorsal root ganglion neurons following muscimol-activated currents.

Incorporation ofγ-aminobutyric acid and cesium cations to formamidinium lead halide perovskites for highly efficient solar cells

The stability issue has become one of the main challenges for the commercialization of perovskite solar cells(PSCs).Formamidinium(FA)-based perovskites have shown great promise owing to their improved thermal and moisture stability.However,these perovskites are suffering from phase transition and separation.Here,a method of incorporating of γ-aminobutyric acid(GABA) and cesium cations into FAPbl_(3) is developed to improve the phase stability.It is demonstrated that the crystallinity of α-FAPbl_(3) phase is greatly improved and the phase transition temperature is significantly dropped.The resultant solar cell therefore obtains a champion power conversion efficiency(PCE) of 23.71%,which is one of the highest efficiencies for methylammonium-free PSCs.Furthermore,it shows an impressively enhanced stability under illumination,exhibiting the great potential of FA-based perovskites for efficient and stable solar cells.

Hippocampal and cortical expression of gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein in pentylenetetrazol-induced chronic epileptic rats

BACKGROUND： Gamma-aminobutyric acid transporter plays an important role in gamma-aminobutyric acid metabolism, and is highly associated with epilepsy seizures. Pathologically, astrocytes release active substances that alter neuronal excitability, and it has been demonstrated that astrocytes play a role in epileptic seizures. OBJECTIVE： To observe changes in gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression in the hippocampus and cortex of the temporal lobe in rats with pentylenetetrazol-induced chronic epilepsy. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment was performed at the Department of Neurobiology, Third Military University of Chinese PLA between January 2006 and December 2007. MATERIALS： Pentylenetetrazol was purchased from Sigma, USA; rabbit anti-rat gammaaminobutyric acid transporter 1 and glial fibrillary acidic protein were from Chemicon, USA. METHODS： A total of 40 Sprague Dawley rats were divided into model and control groups. Rat models of chronic epilepsy were created by pentylenetetrazol kindling, and were subdivided into 3-, 7-, and 14-day kindling subgroups. MAIN OUTCOME MEASURES： Gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression, as well as the number of positive cells in the hippocampus and cortex of temporal lobe of rats, were determined by immunohistochemistry and Western blot analyses. RESULTS： Compared with the control group, the number of gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein -positive cells in the hippocampus and cortex of rats with pentylenetetrazol-induced epilepsy significantly increased, gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression increased after 3 days of kindling, reached a peak on day 7, and remained at elevated levels at day 14 （P〈 0.05）. CONCLUSION： Astrocytic activation and gamma-aminobutyric acid transporter 1 overexpression may contribute to pentylenetetrazol-induced epilepsy.

Effects of Gamma-Aminobutyric Acid on Performance of Lactating Sows during Heat Weather

[ Objective] To study the effects of gamma-aminobutyric acid （GABA） on performance of lactating sows during heat stress. [ Metbod] A total of 14 sows at the same parity and with close expected date of childbirth and similar body we：,ght were randomly divided into control group and experimental group. They were fed a common basal diet and a GABA （300 mg/kg） supplementary diet, respectively. The trial lasted for 21 d. [ Result ] The daily feed intake, lactation yield and average daily gain of piglets in the experimental group were increased by 9.4%, 28.5% and 10.7%, respectively. The backfat of lactating sows was decreased less, and the same with the weaning-oestrus interval. The survival ratio of piglets was increased by 4.5%. Compared with the control group, the content of lactose and fat increased significantly, but other components almost did not change. [Conclusien] Supplementing GABA in diet can improve the performance of lactating sows and promote the growth of piglets effectively.

Effects of Rhizoma Acori Tatarinowii extracts on gamma-aminobutyric acid type A receptor alpha 1 subunit brain expression during development in a recurrent seizure rat model

Extracts from Rhizoma Acori Tatarinowii （Grassleaf Sweetflag Rhizome, Shichangpu） have been shown to improve learning and memory, reduce anxiety, allay excitement, and suppress seizures. Rhizoma Acori Tatarinowii extracts interact with y-aminobutyric acid and activate the y-aminobutyric acid type A receptor, although few studies have addressed the precise effects of v-aminobutyric acid type A receptor al subunit. In the present study, y-aminobutyric acid type A receptor al subunit protein expression in the cerebral cortex and hippocampus, and pathological scores of brain injury, were significantly greater following recurrent seizures, but significantly decreased following treatment with Rhizoma Acori Tatarinowii extracts. These results indicated that Rhizoma Acori Tatarinowii extracts down-regulated y-aminobutyric acid type A receptor al subunit protein expression in the cerebral cortex and hippocampus and protected seizure-induced brain injury during development.

A comparison study on structure-function relationship of polysaccharides obtained from sea buckthorn berries using different methods:antioxidant and bile acid-binding capacity

In this study,the structural characters,antioxidant activities and bile acid-binding ability of sea buckthorn polysaccharides(HRPs)obtained by the commonly used hot water(HRP-W),pressurized hot water(HRP-H),ultrasonic(HRP-U),acid(HRP-C)and alkali(HRP-A)assisted extraction methods were investigated.The results demonstrated that extraction methods had significant effects on extraction yield,monosaccharide composition,molecular weight,particle size,triple-helical structure,and surface morphology of HRPs except for the major linkage bands.Thermogravimetric analysis showed that HRP-U with filamentous reticular microstructure exhibited better thermal stability.The HRP-A with the lowest molecular weight and highest arabinose content possessed the best antioxidant activities.Moreover,the rheological analysis indicated that HRPs with higher galacturonic acid content and molecular weight showed higher viscosity and stronger crosslinking network(HRP-C,HRP-W and HRP-U),which exhibited stronger bile acid binding capacity.The present findings provide scientific evidence in the preparation technology of sea buckthorn polysaccharides with good antioxidant and bile acid binding capacity which are related to the structure affected by the extraction methods.

Enabling heterogeneous catalysis to achieve carbon neutrality: Directional catalytic conversion of CO_(2) into carboxylic acids

The increase in anthropogenic carbon dioxide(CO_(2))emissions has exacerbated the deterioration of the global environment,which should be controlled to achieve carbon neutrality.Central to the core goal of achieving carbon neutrality is the utilization of CO_(2) under economic and sustainable conditions.Recently,the strong need for carbon neutrality has led to a proliferation of studies on the direct conversion of CO_(2) into carboxylic acids,which can effectively alleviate CO_(2) emissions and create high-value chemicals.The purpose of this review is to present the application prospects of carboxylic acids and the basic principles of CO_(2) conversion into carboxylic acids through photo-,electric-,and thermal catalysis.Special attention is focused on the regulation strategy of the activity of abundant catalysts at the molecular level,inspiring the preparation of high-performance catalysts.In addition,theoretical calculations,advanced technologies,and numerous typical examples are introduced to elaborate on the corresponding process and influencing factors of catalytic activity.Finally,challenges and prospects are provided for the future development of this field.It is hoped that this review will contribute to a deeper understanding of the conversion of CO_(2) into carboxylic acids and inspire more innovative breakthroughs.

Γ-Aminobutyric acid promotes methionine-choline deficient diet-induced nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis（NASH） is one of the most common liver diseases and a major cause of liver fibrosis worldwide.r-Aminobutyric acid（GABA） is one of the most abundant inhibitory neurotransmitters in the central nervous system.Recently,it has been reported that GABAergic signaling pathways are found in various non-neuronal tissues including the immune system and play a functional role.In the present study,we investigated whether administration of GABA has effects on NASH through its immunomodulatory effects.To test this hypothesis,C57BL/6 mice were fed a methionine-choline-deficient（MCD） diet for 8 weeks.After four weeks into MCD feeding,mice were provided with plain water（control） or water containing 2 mg/mL of GABA for the subsequent 4 weeks.Using this MCD diet-induced NASH model,we found that mice receiving GABA showed more severe steatohepatitis and liver fibrosis than control mice.This increased liver damage was confirmed by higher levels of serum alanine transaminase（ALT） and aspartate aminotransferase（AST） compared to the control group.In accordance with increased liver steatohepatitis,NASH-related and inflammatory gene expression（collagen al,tissue inhibitor of metalloproteinase-1,TNF-α） in the liver was markedly increased in GABA-treated mice.Furthermore,GABA directly enhanced production of inflammatory cytokines including IL-6 and TNF-α in LPS activated RAW macrophage cells and increased TIB-73 hepatocyte death.Such effects were abolished when GABA was treated with bicuculline,a competitive antagonist of GABA receptors.These results suggest that oral administration of GABA may be involved in changes of the liver immune milieu and conferred detrimental effects on NASH progression.

Immunohisto chemical Study on the Effects of Pyrethroids on Gluta-mate and γ-Aminobutyric Acid in Rat Central Nervous System

Objective\ In order to study the effects of pyrethroids on glutamate (Glu) and gamma aminobutyric acid (GABA) in rat central nervous system. Methods\ Male SD rats were treated with permethrin (7 mg/kg, i.p) or cypermethrin (70 mg/kg, i.p) once a day for 3 days. Glu and GABA immunoreactive cells and transmitters in CNS were studied by immunohistochemical method. Results\ The total number, percentage of positive area and integral optical density of glutamate immunoreactive cell in cerebral cortex, hippocampus decreased significantly in permethrin or cypermethrin, while GABA was enhanced. Cypermethrin is more tent than permethrin on either Glu or GABA. Conclusion\ Disturbance of Glu and GABA is likely to play a role in the development of pyrethroids excitatory neurotoxicity.

Abiotic stress treatment reveals expansin like A gene OfEXLA1 improving salt and drought tolerance of Osmanthus fragrans by responding to abscisic acid

Sweet osmanthus(Osmanthus fragrans) is a having general approval aromatic tree in China that is widely applied to landscaping and gardening. However, the evergreen tree adaptability is limited by many environmental stresses. Currently, limited information is available regarding the genetic analysis and functional identification of expansin genes in response to abiotic stress in sweet osmanthus. In this study, a total of 29 expansin genes were identified and divided into four groups by genome-wide analysis from the sweet osmanthus genome. Transcriptome and quantitative Real-time PCR analysis showed that the cell wall-localized protein expansin-like A(OfEXLA1) gene was significantly induced by salt and drought treatment. Histochemical GUS staining of transgenic Arabidopsis lines in which GUS activity was driven with the OfEXLA1 promoter, GUS activity was significantly induced by salt, drought, and exogenous abscisic acid(ABA). In yeast, we found OfEXLA1overexpression significantly improved the population of cells compared with wild-type strains after NaCl and polyethylene glycol(PEG)treatment. Additionally, OfEXLA1 overexpression not only promoted plant growth, but also improved the salt and drought tolerance in Arabidopsis. To gain insight into the role of ABA signaling in the regulation of OfEXLA1 improving abiotic tolerance in sweet osmanthus, four differentially expressed ABA Insensitive 5(ABI5)-like genes(OfABL4, OfABL5, OfABL7, and OfABL8) were identified from transcriptome, and dualluciferase(dual-LUC) and yeast one hybrid(Y1H) assay showed that OfABL4 and OfABL5 might bind to OfEXLA1 promoter to accumulate the OfEXLA1 expression by responding to ABA signaling to improve abiotic tolerance in sweet osmanthus. These results provide the information for understanding the molecular functions of expansin-like A gene and molecular breeding of sweet osmanthus in future.

Bile acids,gut microbiota,and therapeutic insights in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.

Blood glucose-lowering activity of protocatechuic acid is mediated by inhibiting a-glucosidase

α-Glucosidase inhibitors are effective in controlling postprandial hyperglycemia,which play crucial roles in the management of type 2 diabetes.Protocatechuic acid(PCA)is one of phenolic acids existing not only in various plant foods but also as a major microbial metabolite of dietary anthocyanins in the large colon.The present study investigated the inhibitory mechanism of PCA on a-glucosidase in vitro and examined its effect on postprandial blood glucose levels in vivo.Results from in vitro experiments demonstrated that PCA was a mix-type inhibitor of a-glucosidase.Driven by hydrogen bonds and van der Waals interactions,PCA reversibly bound withα-glucosidase to form a stable a-glucosidase-PCA complex in a spontaneous manner.The computational simulation found that PCA could insert into the active cavity of a-glucosidase and establish hydrogen bonds with catalytic amino acid residues.PCA binding aroused the steric hindrance for substrates to enter active sites and caused the structural changes of interacted catalytic amino acid residues.PCA also exhibited postprandial hypoglycemic capacity in diabetic mice.This study may provide the theoretical basis for the application of PCA as an active ingredient of functional foods in dietary management of diabetes.