Olfactory receptors in neural regeneration in the central nervous system

Olfactory receptors are crucial for detecting odors and play a vital role in our sense of smell,influencing behaviors from food choices to emotional memories.These receptors also contribute to our perception of flavor and have potential applications in medical diagnostics and environmental monitoring.The ability of the olfactory system to regenerate its sensory neurons provides a unique model to study neural regeneration,a phenomenon largely absent in the central nervous system.Insights gained from how olfactory neurons continuously replace themselves and reestablish functional connections can provide strategies to promote similar regenerative processes in the central nervous system,where damage often results in permanent deficits.Understanding the molecular and cellular mechanisms underpinning olfactory neuron regeneration could pave the way for developing therapeutic approaches to treat spinal co rd injuries and neurodegenerative diseases like Alzheimer's disease.Olfa ctory receptors are found in almost any cell of eve ry orga n/tissue of the mammalian body.This ectopic expression provides insights into the chemical structures that can activate olfactory receptors.In addition to odors,olfactory receptors in ectopic expression may respond to endogenous compounds and molecules produced by mucosal colonizing microbiota.The analysis of the function of olfactory receptors in ectopic expression provides valuable information on the signaling pathway engaged upon receptor activation and the receptor's role in proliferation and cell differentiation mechanisms.This review explo res the ectopic expression of olfa ctory receptors and the role they may play in neural regeneration within the central nervous system,with particular attention to compounds that can activate these receptors to initiate regenerative processes.Evidence suggests that olfactory receptors could serve as potential therapeutic targets for enhancing neural repair and recovery following central nervous system injuries.

Global trends of purinergic receptors and depression:A bibliometric analysis from 2003 to 2023

BACKGROUND Depression significantly threatens human health.Purinergic receptors are reported to be associated with depression.However,there is no bibliometric research in this field have been published.AIM To provide some reference for the further research in the field of purinergic receptors and depression utilizing bibliometric analysis.METHODS Relevant researches were retrieved from the Web of Science Core Collection database.The period of the search was from January 1,2003 to December 31,2023.The CiteSpace(6.2.R7)and VOSviewer(1.6.19)were applied to identify the main contributors of countries,authors,institutions,references and journals.Besides,we evaluate keywords to assess the hotspots and trends over the previous 2 decades.RESULTS Totally,247 articles were identified,showing an increasing trend over time.The most productive country,institution,and journal in this field are China,Harvard University,and Biological Psychiatry,respectively.Liang SD and Rodrigues,Ana Lucia S were the most prolific authors.Burnstock G ranked first among the cited authors.The cooperation among countries and disciplines is crucial.The P2X7 receptor provides promising prospects for treating depression and further studies are warranted to validate the scope and significance of depression therapeutic strategies.CONCLUSION This study provides an overview of the worldwide research status and future trends in purinergic receptors and depression.P2X7 receptor is considered an appropriate target for the treatment of depression,as well as neurological diseases.It is implied that based on purinergic system,the future prospects for interventions aimed at depression treatment are promising,showing the way for both augmentation strategies and new drug treatments in the context of the pharmacology of depression.

Intricate roles of estrogen and estrogen receptors in digestive system cancers:a systematic review

Gender disparities are evident across different types of digestive system cancers,which are typically characterized by a lower incidence and mortality rate in females compared to males.This finding suggests a potential protective role of female steroid hormones,particularly estrogen,in the development of these cancers.Estrogen is a well-known sex hormone that not only regulates the reproductive system but also exerts diverse effects on non-reproductive organs mediated through interactions with estrogen receptors(ERs),including the classic(ERαand ERβ)and non-traditional ERs[G protein-coupled estrogen receptor(GPER)].Recent advances have contributed to our comprehension of the mechanisms underlying ERs in digestive system cancers.In this comprehensive review we summarize the current understanding of the intricate roles played by estrogen and ERs in the major types of digestive system cancers,including hepatocellular,pancreatic,esophageal,gastric,and colorectal carcinoma.Furthermore,we discuss the potential molecular mechanisms underlying ERα,ERβ,and GPER effects,and propose perspectives on innovative therapies and preventive measures targeting the pathways regulated by estrogen and ERs.The roles of estrogen and ERs in digestive system cancers are complicated and depend on the cell type and tissue involved.Additionally,deciphering the intricate roles of estrogen,ERs,and the associated signaling pathways may guide the discovery of novel and tailored therapeutic and preventive strategies for digestive system cancers,eventually improving the care and clinical outcomes for the substantial number of individuals worldwide affected by these malignancies.

Cortico-striatal gamma oscillations are modulated by dopamine D3 receptors in dyskinetic rats

Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.

Expression of Progesterone and Estrogen Receptors in Human Renal Cell Carcinoma

Progesterone receptor(PR) and estrogen receptor(ER) were investigated in 29 specimens of renal cell carcinoma (RCC) and its autologous kidneys, 12 samples of control kidnerys with high sensitive and specific enzymelabelled histochemical techniques. The positive expression rates of PR in RCC, its autologous kidneys and control kidneys were 31.0%, 82.8% and 83.3% respectively, while the positive expression rates of ER of those tissues were 58.6%, 79.3% and 83.3%, respectively. It showed that the positive rate and the value of PR and ER in RCC were significantly less than those determined in the autologous kidneys and normal tissues(P<0.05) and no significant differences of PR and ER were found between autologous and normal kidneys(P>0.05). The level and positive rate of PR in stage Ⅰ were higher than those in stage Ⅱ to Ⅳ of RCC tissues (P<0.05). There was no relationship between the status of PR, ER and patient sex(P>0.05). Expression of PR in RCC had correlation to Robson stage closely. The positive rate of PR may be treated as a prognostic factor because it decreased as the stage rose. Our result provided an experimental basis for the application of hormonal therapy in RCC and emphasized that patients who may be benefited from hormonal therapy must have sufficient hormone receptors.

Estrogen, estrogen receptors, and hepatocellular carcinoma: Are we there yet?

A protective role of the sex steroid hormone estrogenin hepatocellular carcinoma(HCC) was suggested a few decades ago according to clinical data showing higher HCC morbidity and mortality among males. Several recent studies further confirmed the anti-cancer effects of estrogen in the liver. However, it remains to be identified how to exploit estrogen signalling within clinical settings for HCC treatment. There are several unresolved issues related to the estrogen pathway in liver cells. The main problems include the absence of a clear understanding of which estrogen receptor(ER) isoform is predominantly expressed in normal and malignant liver cells, the ER isoform expression difference between males and females, and which ER isoform should be targeted when designing HCC therapy. Some of those questions were recently addressed by Iyer and coauthors. The current editorial review critically analyses the study by Iyer et al(WJG, 2017) that investigated the expression of ER subtypes in liver samples collected from patients with a healthy liver, hepatitis C virus cirrhosis, and HCC. ER presence was evaluated in association with gender, intracellular localization, inflammation marker NF-kB, and proliferation-related effector cyclin D1. The study limitations and advantages are discussed in light of recent advances in the HCC and estrogen signalling areas.

Metabotropic glutamate receptors(mGluRs)in epileptogenesis:an update on abnormal mGluRs signaling and its therapeutic implications

Epilepsy is a neurological disorder characterized by high morbidity,high recurrence,and drug resistance.Enhanced signaling through the excitatory neurotransmitter glutamate is intricately associated with epilepsy.Metabotropic glutamate receptors(mGluRs)are G protein-coupled receptors activated by glutamate and are key regulators of neuronal and synaptic plasticity.Dysregulated mGluR signaling has been associated with various neurological disorders,and numerous studies have shown a close relationship between mGluRs expression/activity and the development of epilepsy.In this review,we first introduce the three groups of mGluRs and their associated signaling pathways.Then,we detail how these receptors influence epilepsy by describing the signaling cascades triggered by their activation and their neuroprotective or detrimental roles in epileptogenesis.In addition,strategies for pharmacological manipulation of these receptors during the treatment of epilepsy in experimental studies is also summarized.We hope that this review will provide a foundation for future studies on the development of mGluR-targeted antiepileptic drugs.

Ulcerative colitis: From inflammation to cancer. Do estrogen receptors have a role?

Ulcerative colitis(UC) is a condition at increased risk for colorectal carcinoma(CRC) development. Nowadays, screening and follow-up programs are routinely performed worldwide to promote the early detection of CRCs in subjects with well known risk factors(extent, duration and severity of the disorder). The diffusion of these procedures is presumably the main reason for the marked reduction of cancer incidence and mortality in the course of UC. In addition, chemoprevention has been widely investigated and developed in many medical fields, and aspirin has shown a preventive effect against CRC, while mesalazine has been strongly invoked as a potential chemopreventive agent in UC. However, available studies show some limitations due to the obvious ethical implications of drug withdrawal in UC in order to design a control group. The estrogenreceptors(ER) alpha/beta balance seems to have a relevant influence on colorectal carcinogenesis and ER beta appears to parallel apoptosis, and hence an anticarcinogenic effect. Phytoestrogens are compounds acting as ER beta agonists and have shown a promising chemopreventive effect on sporadic as well as genetically inherited CRC. There is evidence suggesting a role for ERs in UC-related carcinogenesis. In this perspective, since these substances can be considered as dietary supplements and are completely free from side effects, phytoestrogens could be an interesting option for CRC prevention, even when the disease is a consequence of long-term chronic inflammation, as in the course of UC. Further studies of their effects are warranted in both the basic research and clinical fields.

Lack of estrogen receptors expression in malignant and pre-malignant colorectal lesions in Egyptian patients

Background: incidence of Colorectal cancer (CRC) is increasing globally. In Egypt, CRC ranks the sixth most common cancer in males and the fifth in females. Aim: To assess the expression of estrogen receptors (alpha and beta) in pre-malignant (adenomatous polyps and IBD), malignant colorectal lesions and normal colonic mucosa in group of Egyptian patients. Methods: This prospective study was done on 45 patients presenting with colonic symptoms, patients were divided into four groups;15 CRC patients, 10 patients with adenomatous polyps, 10 IBD patients and 10 patients in the control group. Patients subjected to: Stool analysis, FOBT, CBC, CEA, Abdominal ultrasound & colonoscopy and biopsy (number = 80), Pathological, immunohistochemistry and RT- PCR quantification of ERα and ERβ were done. Results: Mean age: 39.2 (12 - 73), gender: M/F: 28/17. Bleeding per rectum was the commonest presentation;29/45 (64.4%). CEA was significantly elevated in the CRC group compared with other studied groups (1692 mg/L vs. 4.0, 4.0 and 4.4 mg/L). Ultrasonography of the studied patients showed that metastatic CRC: 3/15 (20%);Colonic wall thickening: 5/15 (33.3%), 1/10 showed colonic polypoidal lesions in adenomatous polyps groups, in IBD group: 4/10 (40%) showed colonic and ileocecal thicknening. All the studied patients showed negative results for estrogen receptors (alpha and beta) by the use of immunohistochemistry staining and RT-PCR technique. Conclusion: Role of estrogen receptors in the colonic mucosa, precancerous and colorectal cancer is doubtful, contradictory results with some literature data could be due to racial and genetic difference in the studied population.

The Effect of Administration of Rutin on Plasma Levels of Estrogen, Prolactin, Growth Hormone and Gene Expression of Their Receptors in Mammary Glands in Ovariectomized Rats

The development of mammary glands, endocrine hormone concentrations and the gene expression of related receptors were measured in ovariectomized virgin rats after adminstration of an estrogen-like plant extract, rutin. Thirty-two ovariectomized virgin Wistar rats were randomly assigned to 4 treatments with 8 animals each： gastric infusion of 2 mL normal saline per unovariectomized rat per day （Sham）, gastric infusion of 2 mL normal saline per ovariectomized rat per day （Ova）, gastric infusion of 60 mg rutin kg-1 body weight （BW） per ovariectomized rat per day （Ova＋Rut）, or intramuscular injection of 60 ug estradiol kg-1 BW per ovariectomized rat weekly （Ova＋Est）. Samples of blood and mammary glands were harvested to determine the levels of estrogen （E2）, prolactin （PRL） and growth hormone （GH）, and the gene expression of estrogen receptors （ER）, prolactin receptors （PRLR） and growth hormone receptors （GHR） with radioimmunoassy （RIA） and RT-PCR technology, respectively. The E2 concentration in plasma and gland tissues from the rats of Ovx＋Rut or Ovx＋Est was higher than that of Ovx （P〈0.05）, but the plasma E2 concentration from the rats of Ovx＋Rut was lower than that of Sham （P〈0.05）. The order of the PRL concentration in plasma and gland tissues was Ovx〈Ovx＋Rut〈Ovx＋Est 〈Sham, and the difference in each treatment （P〈0.05）. The plasma GH concentration was lower in Ovx than in Ovx＋Rut or Ovx＋Est, and lower in Ovx＋Rut than in Sham （P〈0.05）. The GH concentration in gland tissues was lower in Ovx than in Ovx＋Rut or Ovx＋Est （P〈0.05）, and lower in Ovx＋Rut than in Sham （P〈0.05）. The gene expression of ER in gland tissues was increased in an order as Ovx〈Ovx＋Rut〈Ovx＋Est〈Sham （P〈0.05）, and PRLR, GHR showed the same trend. In conclusion, adminstration of rutin increased the E2 concentration in plasma and mammary glands, promoted pituitary PRL and GH release, up-regulated the gene expression of ER, PRLR and GHR, and stimulated mammary development in ovariectomized virgin rats.

Immunomodulation of Proton-activated G Protein-coupled Receptors in Inflammation

Proton-activated G protein-coupled receptors(GPCRs),initially discovered by Ludwig in 2003,are widely distributed in various tissues.These receptors have been found to modulate the immune system in several inflammatory diseases,including inflammatory bowel disease,atopic dermatitis,and asthma.Proton-activated GPCRs belong to the G protein-coupled receptor family and can detect alternations in extracellular pH.This detection triggers downstream signaling pathways within the cells,ultimately influencing the function of immune cells.In this review,we specifically focused on investigating the immune response of proton-activated GPCRs under inflammatory conditions.

Characterization of Domeless receptors and the role of Bd Domeless3 in anti-symbiont-like virus defense in Bactrocera dorsalis

The Janus kinase/signal transducers and activators of transcription(JAK/STAT)signaling pathway play a pivotal role in innate immunity.Among invertebrates,Domeless receptors serve as the key upstream regulators of this pathway.In our study on Bactrocera dorsalis,we identified three cytokine receptors:BdDomeless1,BdDomeless2,and BdDomeless3.Each receptor encompasses five fibronectin-type-III-like(FN III)extracellular domains and a transmembrane domain.Furthermore,these receptors exhibit the increased responsiveness to diverse pathogenic challenges.Notably,only BdDomeless3 is upregulated during symbiont-like viral infections.Moreover,silencing BdDomeless3 enhanced the infectivity of Bactrocera dorsalis cripavirus(BdCV)and B.dorsalis picorna-like virus(BdPLV),underscoring BdDomeless3’s crucial role in antiviral defense of B.dorsalis.Following the suppression of Domeless3 expression,six antimicrobial peptide genes displayed decreased expression,potentially correlating with the rise in viral infectivity.To our knowledge,this is the first study identifying cytokine receptors associated with the JAK/STAT pathway in tephritid flies,shedding light on the immune mechanisms of B.dorsalis.

The Role of Toll-Like Receptors and Nuclear Factor κB p65 Protein in the Pathogenesis of Otitis Media

The role of Toll-like receptor 4 (TLR4) and nuclear factor κB p65 (NF-κB p65) proteins in the pathogenesis of otitis media is explored. In recent years, the incidence of otitis media has been rising globally, becoming a significant threat to human health. More and more studies have found that Toll-like receptor 4 (TLR4), as a member of the Toll-like receptor family, can promote the generation of inflammatory factors and is closely related to the body’s immune response and inflammatory response. Nuclear factor-κB p65 (NF-κB p65) is a nuclear transcription factor that can interact with various cytokines, growth factors, and apoptotic factors, participating in processes such as oxidative stress, apoptosis, and inflammation in the body [1]. This article elaborates on the structure, function, and signaling pathways of TLR4 and NF-κB p65 proteins in the pathogenesis of otitis media, aiming to provide more precise targets and better therapeutic efficacy for the diagnosis and treatment of otitis media. The role of inflammation in disease.

Toll-like receptors 2 polymorphism is associated with psoriasis: A case-control study in the northern Chinese population

Background:Psoriasis is a disease caused by genetics and immune system dysfunction,affecting the skin and joints.Toll-like receptors(TLRs)play an important role in triggering the innate immune response and controlling adaptive immunity.The role of TLR2 in the progression of psoriasis is not well understood.Methods:A case-control study was conducted on a northern Chinese Han population,consisting of psoriasis patients and healthy control subjects.Genotyping was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction(ARMS-PCR),and allele and genotype frequencies of four SNPs in TLR2 were analyzed in 270 psoriasis patients and 246 healthy controls.Results:Four TLR2 SNPs(rs11938228,rs4696480,rs3804099,rs5743699)were genotyped and found to be in linkage disequilibrium.The genotype distributions of rs11938228 and rs4696480 in two groups were in Hardy-Weinberg equilibrium and statistically significant except for the overdominance model.The haplotypes ATTC and ATCC were found to be protective against psoriasis.Conclusion:Our study found a correlation between TLR2 genetic variations and the likelihood of psoriasis in northern China.

Determination of the concentration of estrogen,progestin and androgen cytosol receptors in human uterine tissues

The specific bindings of estrogen,progestin and androgen were determined inthe cytosol fraction of myomatous,adenomyotic and postmenopausal uterine tissues andof the normal endometrium and myometrium as well.It was found that theconcentrations of estrogen,progestin and androgen cytosol receptors were significantlyhigher in myomatous tissue than in normal myometrium;there was also an obvious differ-ence of the concentration of the sex steroid receptors between normal endometrium andadenomyotic tissue;and the uterine tissues of postmenopausal women still retained highlevels of these sex steroid receptors.In addition,the regulation of sex steroids in thepathogenesis of myoma and adenomyosis is discussed.

Epithelial turnover in duodenal familial adenomatous polyposis: A possible role for estrogen receptors?

AIM: To investigate estrogen receptors expression in duodenal familial adenomatous polyposis (FAP) and any relationship with epithelial proliferation/apoptosis markers.METHODS: Twenty-two patients affected by FAP undergoing duodenal resection for malignancies were recruited. Controls were 15 healthy subjects undergoing endoscopy for dyspeptic symptoms. ER-&#x003b1;, ER-&#x003b1;, Ki-67, TUNEL and caspase 3 expression (labeling index: percentage of positive cells) were evaluated by immunohistochemistry or immunofluorescence and examined by light or confocal microscopy. Samples were assigned to four groups: normal tissue, low (LGD) and high-grade dysplasia (HGD), adenocarcinoma (AC). One-way analysis of variance, corrected by Bonferroni&#x02019;s test, and Pearson&#x02019;s correlation test were applied for statistical analysis.RESULTS: ER-beta showed a progressive decline: normal tissue (23.5 &#x000b1; 4.9), LGD (21.1 &#x000b1; 4.8), HGD (9.3 &#x000b1; 3.5), AC (7.1 &#x000b1; 3.1). The normal tissue of FAP subjects expressed ER-beta like the controls (23.9 &#x000b1; 6.2). Conversely, ER-&#x003b1; showed a progressive increase from normal tissue (24.8 &#x000b1; 5.6) to AC (52.0 &#x000b1; 8.2); the expression in normal tissue was similar to controls (22.5 &#x000b1; 5.3). Ki67 demonstrated a statistically significant progressive increase at each disease stage up to AC. TUNEL did not reveal differences between controls and normal tissue of FAP subjects, but progressive decreases were observed in LGD, through HGD to AC. Pearson&#x02019;s correlation test showed a direct relationship between ER-&#x003b2; and TUNEL LI (r = 0.8088, P &#x0003c; 0.0001). Conversely, ER-&#x003b1; was inversely correlated with TUNEL LI (r = - 0.7257, P &#x0003c; 0.0001). The co-expression of ER-&#x003b2; and caspase 3 declined progressively from normal to neoplastic tissue.CONCLUSION: This study confirmed that ER-&#x003b2; is strongly decreased in duodenal FAP carcinomas, declining in a multiple step fashion, thereby suggesting a putative anti-carcinogenic effect. ER-&#x003b1; showed the opposite trend. ER-&#x003b2;/caspase 3 co-expression suggests this hormone&#x02019;s possible involvement in apoptosis. Hormonal influences in FAP duodenal tumorigenesis, and modulation of these as a possible chemoprevention strategy, may be a promising approach.

Nuclear receptors and pathogenesis of pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a median overall survival time of 5 mo and the five years survival less than 5%, a rate essentially unchanged over the course of the years. A well defined progression model of accumulation of genetic alterations ranging from single point mutations to gross chromosomal abnormalities has been introduced to describe the origin of this disease. However, due to the its subtle nature and concurring events PDAC cure remains elusive. Nuclear receptors (NR) are members of a large superfamily of evolutionarily conserved ligand-regulated DNA-binding transcription factors functionally involved in important cellular functions ranging from regulation of metabolism, to growth and development. Given the nature of their ligands, NR are very tempting drug targets and their pharmacological modulation has been widely exploited for the treatment of metabolic and inflammatory diseases. There are now clear evidences that both classical ligand-activated and orphan NR are involved in the pathogenesis of PDAC from its very early stages; nonetheless many aspects of their role are not fully understood. The purpose of this review is to highlight the striking connections that link peroxisome proliferator activated receptors, retinoic acid receptors, retinoid X receptor, androgen receptor, estrogen receptors and the orphan NR Nur, chicken ovalbumin upstream promoter transcription factor II and the liver receptor homologue-1 receptor to PDAC development, connections that could lead to the identification of novel therapies for this disease.

Fluorescent probes for imaging and detection of plant hormones and their receptors

Exploring plant behavior at the cellular scale in a minimally invasive manner is critical to understanding plant adaptation to the environment.Phytohormones play vital regulatory roles in multiple aspects of plant growth and development and acclimation to environmental changes.Since the biosynthesis,modification,transportation,and degradation of plant hormones in plants change with time and space,their content level and distribution are highly dynamic.To monitor the production,transport,perception,and distribution of phytohormones within undamaged tissues,we require qualitative and quantitative tools endowed with remarkably high temporal and spatial resolution.Fluorescent probes are regarded as excellent tools for widespread plant imaging because of their high sensitivity and selectivity,reproducibility,real-time in situ detection,and uncomplicated mechanism elucidation.In this review,we provide a systematical overview of the progress in the sensing and imaging of phytohormone fluorescent probes and fluorescently labeled phytohormones to their receptors in plants.Moreover,forthcoming viewpoints and possible applications of these fluorescent probes within the realm of plants are also presented.We hold the conviction that the new perspective brought by this paper can promote the development of fluorescent probes,enabling them to have better detection performance in plant hormone imaging.

Correlation of estrogen and progesterone receptors ER and PR expression with the growth of endometrial cancer

Objective:To study the correlation of estrogen and progesterone receptors ER and PR expression with the growth of endometrial cancer.Methods: A total of 80 patients with endometrial cancer who were treated collected in the Fourth People's Hospital of Shaanxi and the First Affiliated Hospital of Xi'an Jiaotong University between January 2013 and January 2017 were collected, endometrial cancer tissue and para-carcinoma normal tissue were collected, immunohistochemical method was used to detect positive expression of ER and PR, and fluorescence quantitative PCR was used to detect the mRNA expression of proliferation and apoptosis genes.Results: The positive expression of ER and PR in tumor tissue were significantly lower than those in para-carcinoma tissue;proliferation genes KCC1, RRM2, SRPX2 and Snail mRNA expression in tumor tissue of ER-positive group and PR-positive group were lower than those of ER-negative group and PR-negative group;anti-apoptosis genes Wip-1 and Bcl-2 mRNA expression were lower than those of ER-negative group and PR-negative group respectively while pro-apoptosis genes Bid, Bax and Fas mRNA expression were higher than those of ER-negative group and PR-negative group respectively.Conclusion:Patients with positive expression of endometrial estrogen and progesterone receptors ER and PR are with lower tumor proliferation activity, higher apoptosis activity and lower malignant degree than patients with negative ER and PR expression.

Contribution of altered signal transduction associated to glutamate receptors in brain to the neurological alterations of hepatic encephalopathy

Patients with liver disease may present hepatic enceph- alopathy (HE), a complex neuropsychiatric syndrome covering a wide range of neurological alterations, including cognitive and motor disturbances. HE reduces the quality of life of the patients and is associated with poor prognosis. In the worse cases HE may lead to coma or death. The mechanisms leading to HE which are not well known are being studied using animal models. The neurological alterations in HE are a consequence of impaired cerebral function mainly due to alterations in neurotransmission. We review here some studies indicating that alterations in neurotransmission associated to different types of glutamate receptors are responsible for some of the cognitive and motor alterations present in HE. These studies show that the function of the signal transduction pathway glutamate-nitric oxide-cGMP associated to the NMDA type of glutamate receptors is impaired in brain in vivo in HE animal models as well as in brain of patients died of HE. Activation of NMDA receptors in brain activates this pathway and increases cGMP. In animal models of HE this increase in cGMP induced by activation of NMDA receptors is reduced, which is responsible for the impairment in learning ability in these animal models. Increasing cGMP by pharmacological means restores learning ability in rats with HE and may be a new therapeutic approach to improve cognitive function in patients with HE. However, it is necessary to previously assess the possible secondary effects.Patients with HE may present psychomotor slowing, hypokinesia and bradykinesia. Animal models of HE also show hypolocomotion. It has been shown in rats with HE that hypolocomotion is due to excessive activation of metabotropic glutamate receptors (mGluRs) in substantia nigra pars reticulata. Blocking mGluR1 in this brain area normalizes motor activity in the rats, suggesting that a similar treatment for patients with HE could be useful to treat psychomotor slowing and hypokinesia. However, the possible secondary effects of mGluR1 antagonists should be previously evaluated. These studies are setting the basis for designing therapeutic procedures to specifically treat the individual neurological alterations in patients with HE.