Blood-based microRNA profiling unveils complex molecular dynamics in breast cancer.

BACKGROUND: Breast cancer, a genetically intricate disease with diverse subtypes, exhibits heightened incidence globally. In this study, we aimed to investigate blood-based microRNAs (miRNAs) as potential biomarkers for breast cancer. The primary objectives were to explore the role of miRNAs in cancer-related processes, assess their differential expression between breast cancer patients and healthy individuals, and contribute to a deeper understanding of the molecular underpinnings of breast cancer. METHODS: MiRNA extraction was performed on 40 breast cancer patients and adjacent normal tissues using a commercial RNA isolation kit. Total RNA quantification and quality assessment were conducted with advanced technologies. MiRNA profiling involved reverse transcription, labeling, and hybridization on Agilent human miRNA arrays (V2). Bioinformatics analysis utilized the DIANA system for target gene prediction and the DIANA-mirPath tool for pathway enrichment analysis. Selected miRNAs underwent validation through quantitative real-time PCR. RESULTS: Principal component analysis revealed overlapping miRNA expression patterns in primary and malignant breast tumors, underscoring the genetic complexity involved. Statistical analysis identified 54 downregulated miRNAs in malignant tumors and 38 in primary tumors compared to controls. Bioinformatics analysis implicated several pathways, including Wnt, TGF-b, ErbB, and MAPK signaling. Validation through qRT-PCR confirmed altered expression of hsa-miR-130a, hsa-miR-21, hsa-miR-223, and hsa-let-7c key miRNAs, highlighting their significance in breast cancer. The results from microarray were further validated by qPCR and the expression of which are downregulated in breast cancer was detected. CONCLUSION: This study provides significant insights into distinct miRNA expression patterns in normal and malignant breast tissues. The overlapping miRNA profiles in primary and malignant tumors underscore the complexity of genetic regulation in breast cancer. The identification of deregulated miRNAs and affected pathways contributes to our understanding of breast cancer pathogenesis. The validated miRNAs hold potential as diagnostic and prognostic markers, offering avenues for further clinical exploration in breast cancer research.

Clinical determinants of intestinal failure and death in preterm infants with surgical necrotizing enterocolitis.

OBJECTIVE: We sought to investigate the clinical determinants of intestinal failure and death in preterm infants with surgical NEC. METHODS: Retrospective comparison of clinical information between Group A = intestinal failure (Parenteral nutrition (PN) >90 days) and death and Group B = survivors and with PN dependence < 90 days in preterm infants with surgical NEC. RESULTS: Group A (n = 99/143) had a lower mean gestational age (26.4 weeks [SD3.5] vs. 29.4 [SD 3.5]; p = 0.013), lower birth weight (873 gm [SD 427g] vs. 1425 gm [894g]; p = <0.001), later age of NEC onset (22 days [SD20] vs. 16 days [SD 17]; p = 0.128), received surgery later (276 hours [SD 544] vs. 117 hours [SD 267]; p = 0.032), had cholestasis, received dopamine (80.6% vs. 58.5%; p = 0.010) more frequently and had longer postoperative ileus time (19.8 days [SD 15.4] vs. 11.8 days [SD 6.5]; p = <0.001) and reached full feeds later (93 days [SD 45] vs. 44 [SD 22]; p = <0.001) than Group B.On multivariate logistic regression, higher birth weight was associated with lower risk (OR 0.35, 95% CI 0.15-0.82; p = 0.016) of TPN > 90 days or death. Longer length of bowel resected (OR 1.76, 95% CI 1.02-3.02; p = 0.039) and longer postoperative ileus (OR 2.87, 95% CI 1.26-6.53; p = 0.011) were also independently associated with TPN >90days or death adjusted for gestational age and antenatal steroid treatment. CONCLUSION: In preterm infants with surgical NEC, clinical factors such as lower birth weight, longer bowel loss, and postoperative ileus days were significantly and independently associated with TPN >90 days or death.

The small molecule Erk1/2 signaling pathway inhibitor PD98059 improves DNA repair in an experimental autoimmune encephalomyelitis SJL/J mouse model of multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating disorder in which the myelin sheath covering the central nervous system axons is damaged or lost, disrupting action potential conduction and leading to various neurological complications. The pathogenesis of MS remains unclear, and no effective therapies are currently available. MS is triggered by environmental factors in genetically susceptible individuals. DNA damage and DNA repair failure have been proposed as MS genetic risk factors; however, inconsistent evidence has been found in multiple studies. Therefore, more investigations are needed to ascertain whether DNA damage/repair is altered in this disorder. In this context, therapies that prevent DNA damage or enhance DNA repair could be effective strategies for MS treatment. The overactivation of the extracellular-signal-related kinase 1 and 2 (Erk1/2) pathway can lead to DNA damage and has been linked to MS pathogenesis. In our study, we observed substantially elevated oxidative DNA damage and slower DNA repair rates in an experimentally autoimmune encephalomyelitis animal model of MS (EAE). Moreover, statistical decreases in oxidative DNA strand breaks and faster repair rates were observed in EAE animals injected with the Erk1/2 inhibitor PD98059 (PD). Moreover, the expression of several genes associated with DNA strand breaks and repair changed in EAE mice at both the mRNA and protein levels, as revealed by the RT2 Profiler PCR array and verified by RT-PCR and protein analyses. The treatment with PD mitigated these changes and improved DNA repair gene expression. Our results demonstrate clear associations between Erk1/2 activation, DNA damage/repair, and MS pathology, and further suggest that PD therapy may be a promising adjuvant therapeutic strategy.

Diagnosis of hypercritical chronic pulmonary disorders using dense convolutional network through chest radiography.

Lung-related ailments are prevalent all over the world which majorly includes asthma, chronic obstructive pulmonary disease (COPD), tuberculosis, pneumonia, fibrosis, etc. and now COVID-19 is added to this list. Infection of COVID-19 poses respirational complications with other indications like cough, high fever, and pneumonia. WHO had identified cancer in the lungs as a fatal cancer type amongst others and thus, the timely detection of such cancer is pivotal for an individual's health. Since the elementary convolutional neural networks have not performed fairly well in identifying atypical image types hence, we recommend a novel and completely automated framework with a deep learning approach for the recognition and classification of chronic pulmonary disorders (CPD) and COVID-pneumonia using Thoracic or Chest X-Ray (CXR) images. A novel three-step, completely automated, approach is presented that first extracts the region of interest from CXR images for preprocessing, and they are then used to detects infected lungs X-rays from the Normal ones. Thereafter, the infected lung images are further classified into COVID-pneumonia, pneumonia, and other chronic pulmonary disorders (OCPD), which might be utilized in the current scenario to help the radiologist in substantiating their diagnosis and in starting well in time treatment of these deadly lung diseases. And finally, highlight the regions in the CXR which are indicative of severe chronic pulmonary disorders like COVID-19 and pneumonia. A detailed investigation of various pivotal parameters based on several experimental outcomes are made here. This paper presents an approach that detects the Normal lung X-rays from infected ones and the infected lung images are further classified into COVID-pneumonia, pneumonia, and other chronic pulmonary disorders with an utmost accuracy of 96.8%. Several other collective performance measurements validate the superiority of the presented model. The proposed framework shows effective results in classifying lung images into Normal, COVID-pneumonia, pneumonia, and other chronic pulmonary disorders (OCPD). This framework can be effectively utilized in this current pandemic scenario to help the radiologist in substantiating their diagnosis and in starting well in time treatment of these deadly lung diseases.

Correlation between Sonoelastography and Histopathological Findings in Evaluation of Chronic Renal Allograft Disease.

Background Non-invasive evaluation tool for allograft kidney is important to predict chronic allograft dysfunction as it can be alternative to the invasive biopsy which is prone to so many complications. Sonoelastography can assess the stiffness of the allograft renal parenchyma, which is prone to undergo interstitial fibrosis. Objective To correlate sonoelastography with histopathology findings in the renal allografts. Method Sonoelastography was done in 60 renal allograft recipients prior to their biopsy for various indications. Estimated glomerular filtration rate (eGFR) of the patient were also obtained. Histopathology reports were collected to determine Banff score of interstitial fibrosis. Descriptive measurements (Mean ± standard deviation, Frequencies, Proportions) were calculated. Correlations among the variables were measured using Pearson's correlation, independent sample t-test, and ANOVA. Result The mean strain index (SI) was lower in higher grades of fibrosis. There was significant difference in mean SI (F=18.264; df= 2,57; p < 0.001) among the histological grades of fibrosis. Also a significant difference in SI among mild and moderate (S.E. 0.27, p value < 0.001), mild and severe (S.E. 0.213, p value < 0.001) as well as moderate and severe fibrosis (S.E. 0.244, p value < 0.001) was seen. Significant correlation of eGFR with SI (p < 0.001) was also seen. Conclusion Strain index, measured with sonoelastography, significantly correlated with different grades of tissue fibrosis. Thus it can be used as alternative method for evaluation of renal allograft patients to avoid complications of biopsy.

Synthesis, characterization and evaluation of visible light active cadmium sulfide-graphitic carbon nitride nanocomposite: A prospective solar light harvesting photo-catalyst for the deactivation of waterborne pathogen.

Cadmium sulfide-graphitic carbon nitride nanocomposite was synthesized by pulsed laser ablation in liquid, and it was found from the results of optical and morphological characterizations that the proper anchoring of nanostructured cadmium sulfide on the nano-sheets of graphitic carbon nitride took place, which brought about the positive attributes such as enhanced visible light absorption and reduced photo-generated charge recombination, the key features required for an efficient photo-catalyst by solar light harvesting. The pulsed laser ablation in liquid method adopted for the synthesis of cadmium sulfide-graphitic carbon nitride has the following advantages: the shape and size of the synthesized particles can be controlled by altering the experimental parameters such as laser wavelength, pulse laser duration, the pH of the solution, the surfactants and the temperature of the solution, pulsed laser ablation in liquid method neither requires cumbersome equipment nor does it require intermediate chemicals and catalysts nor does it necessitate the post synthesis purification. The enhancement of photo-catalytic activity of cadmium sulfide-graphitic carbon nitride nanocomposite was tested for the photo-catalytic deactivation of Escherichia coli bacteria in water under visible light radiation. As anticipated, a significant improvement of photo-catalytic deactivation was observed, which is attributed to the enhanced and extended light absorption in the visible spectral region, and the formation of herterojunction between the semiconductors, which is instrumental in inhibiting the undesired recombination of photo-generated charge carriers. Quantitatively, the presence of cadmium sulfide on the graphitic carbon nitride surface contributed to a remarkable 129% increase of photo-catalytic degradation constant compared to pure graphitic carbon nitride, which resulted in the decrease of total depletion time of Escherichia coli from 156 min to 67 min with the cadmium sulfide-graphitic carbon nitride nanocomposite synthesized by pulsed laser ablation in liquid method. Our results on the efficient photo-catalytic deactivation of Escherichia coli under visible light assures that cadmium sulfide-graphitic carbon nitride nanocomposite can very well be used for photo-catalytic water purification by harvesting the abundant solar light.

Investigation of belinostat-induced genomic instability by molecular cytogenetic analysis and pathway-focused gene expression profiling.

Histone deacetylases (HDACs), which regulate transcription and specific functions such as tumor suppression by p53, are frequently altered in tumors and have a contentious role in carcinogenesis. HDAC inhibitors, which have a long history of use in psychiatry and neurology, have recently been tested as possible treatments for tumors. Belinostat received regulatory approval in the USA on July 3, 2014, for use against peripheral T-cell lymphoma. However, the unavailability of information on belinostat genotoxicity in normal cells and the molecular mechanisms involved in the genetic instability after exposure to belinostat encouraged us to conduct this study. Our data showed that the exposure of mice to belinostat at the recommended human doses induced chromosome breakage, whole-chromosome lagging, and oxidative DNA damage in bone marrow cells in a dose-dependent manner. The expression levels of 84 genes involved in the DNA damage signaling pathway were evaluated by using an RT2 Profiler PCR array. Belinostat exposure altered the expression of 25 genes, with statistically significant changes observed in 17 genes. The array results were supported by RT-PCR and western blotting experiments. Collectively, our results showed that belinostat exposure caused oxidative DNA damage and downregulated the expression of genes involved in DNA damage repair, which may be responsible for belinostat-induced genomic instability. Thus, the clinical usage of this drug should be weighed against the hazards of carcinogenesis, and the observed genotoxicity profile of belinostat may support further development of efficient HDAC inhibitors with weaker genotoxicity.

Neuroprotective effect of allopurinol and nimesulide against cerebral ischemic reperfusion injury in diabetic rats.

OBJECTIVES: The main objective of the study was to determine the neuroprotective effect of allopurinol and nimesulide against the cerebral ischemic reperfusion injury in diabetic and nondiabetic rats. MATERIALS AND METHODS: In this study, Wistar albino rats of either sex weighing 150-250 g were procured from authorized suppliers. Rats were anesthetized by giving thiopentone sodium (45 mg/kg) by i.p. Under anesthesia, midline incision was given. Common carotid arteries were identified and isolated carefully from vago-sympathetic nerve. Rats were made ischemic by occluding bicommon carotid arteries with thread for 30 min, followed by reperfusion for 4 h by removing the occlusion. The drugs allopurinol (15, 30 mg/kg) and nimesulide (20, 40 mg/kg) were administered 10 min before reperfusion. Then after 4 h reperfusion, animals were sacrificed and immediately brain was removed, homogenized, centrifuged and supernatant was collected, various enzyme estimations were done and same procedure was followed in streptozotocin (STZ: 45 mg/kg; i.p.) induced diabetic rats. RESULTS: Ischemia reperfusion (I/R) group showed significant increase in malondialdehyde (MDA), myeloperoxidase (MPO) and depletion in catalase (CAT) and superoxide dismutase (SOD) levels. Treatment with allopurinol and nimesulide significantly decreased the MDA and MPO levels whereas increased the SOD and CAT levels when compared I/R group in both non-diabetic and diabetic rats. CONCLUSIONS: These findings suggest the cerebral injury due to over production of free radicals was inhibited by allopurinol and nimesulide that exert a neuroprotective effect probably by radical scavenging and antioxidant activities.

Influence of iron metabolism indices on HbA1c in non-diabetic pregnant women with and without iron-deficiency anemia: effect of iron supplementation.

AIMS: Condition that influence erythrocyte turnover also affect HbA1c. Although many forms of anemia are associated with lowering of HbA1c, iron-deficiency anemia (IDA) tends to increase HbA1c. In this study, we examined the relationship between HbA1c and erythrocyte indices in non-diabetic pregnancy and assessed the effect of iron supplementation on HbA1c. MATERIALS AND METHODS: 150 women were studied (30 non-diabetic), non-pregnant, non-anemic women in child bearing women with varying parity as controls (Gp 1); 30 non-diabetic, non-anemic pregnant women in first trimester of pregnancy (Gp 2a); 30 non-diabetic, non-anemic pregnant women in second trimester of pregnancy (Gp 2b); 30 non-diabetic, non-anemic pregnant women in third trimester of pregnancy (Gp 2c) and 30 non-diabetic pregnant women with IDA (Gp 2d). HbA1c, OGTT, erythrocyte indices and iron metabolic indices were determined in Gp 2d subjects not supplemented with iron and repeated these indices after 3 months of iron-supplementation. RESULTS: The mean fasting and postprandial blood glucose levels (79.9±8.0mg/dl, 108.1±14.1mg/dl) in Gp 1 were found to be significantly lower in first trimester among Gp 2a (74.4±5.3mg/dl and 97.2±11.1mg/dl), in second trimester among Gp 2b (76.2±5.2mg/dl and 103.4±7.9mg/dl) followed by increase in IIIrd trimester among Gp 2c (82.3±5.7mg/dl and 112.5±8.5mg/dl) subjects. A significant difference in HbA1c was also observed among the groups (HbA1c 4.7±0.3% in Gp 1; 4.6±0.4% in Gp 2a; 4.5±0.3 in Gp 2b; 4.7±0.3 in Gp 2c). Among Gp 2d subjects, HbA1c was 5.2±0.3% and the level decreased after iron supplementation to 5.1±0.3%. Significant correlation between erythrocyte indices, iron metabolic indices and HbA1c was also observed. CONCLUSION: We conclude that consideration should be given for performing glucose testing in patients with IDA to ascertain the reliability of HbA1c in the diagnosis of diabetes. HbA1c concentrations in diabetic patients with IDA should be interpreted with caution.

Global developmental delay and its determinants among urban infants and toddlers: a cross sectional study.

OBJECTIVE: To estimate the prevalence of global developmental delay among children under 3 years of age and study the determinant factors. METHODS: Cross sectional descriptive study was conducted in field practice areas of the Department of Community Medicine, JN Medical College, Aligarh, India. A total of 468 (243 boys and 225 girls) children aged 0-3 years were included. Developmental screening was performed for each child. A multitude of biological and environmental factors were analysed. RESULTS: As many as 7.1% of the children screened positive for global developmental delay. Maximum delay was observed in the 0-12 months age group (7.0%). Undernutrition and prematurity were the two most prevalent etiological diagnoses (21% each). Stunting and maternal illiteracy were the microenvironmental predictors on stepwise binary logistic regression while prematurity and a history of seizures emerged significant biological predictors. CONCLUSIONS: Developmental delay can be predicted by specific biological and environmental factors which would help in initiating appropriate interventions.

Cancer diagnosis by discrimination between normal and malignant human blood samples using attenuated total reflectance-Fourier transform infrared spectroscopy.

FTIR spectroscopy is a common technique for cancer diagnosis. Applied tissue samples are heterogeneous and may be damaged in preparation procedures. Easier sampling, more available samples and also easier process with assured results would be interesting. Whole blood samples include all of these qualifications and our hypothesis was the bio-molecular changes in blood which manifest themselves in different optical signatures, detectable by FTIR spectroscopy. Noncancerous blood samples were differentiated from cancerous ones using ATR-FTIR spectroscopy and LDA classification method. Procedure was 100 percent and 90 percent accurate in prediction of cancerous or noncancerous situation for 33 known and 10 unknown samples, respectively.

Larvicidal and mosquito repellent activities of Pine (Pinus longifolia, family: Pinaceae) oil.

BACKGROUND AND OBJECTIVES: Various plant-based products are safe and biodegradable alternatives to synthetic chemicals for use against mosquitoes. Oil of Pinus longifolia is traditionally used for protection against mosquitoes in some rural areas but there is no documented report of its use against mosquitoes. The present study was undertaken to scientifically evaluate the activity of Pine oil against mosquitoes. METHODS: The oil was procured from the market and its contents were chemically analysed. Larvicidal activity of oil was tested in laboratory bioassays, while repellent action was studied during whole night bait collections in field by direct application on the skin and after its impregnation on mats. RESULTS: Results showed varying degree of larvicidal activity of Pine oil against mosquitoes with LC50 values ranging between 82 and 112 ppm. The Pine oil had strong repellent action against mosquitoes as it provided 100% protection against Anopheles culicifacies for 11 h and 97% protection against Culex quinquefasciatus for nine hours respectively. Electrically heated mats prepared from Pine oil provided, 94 and 88% protection against An. culicifacies and Cx. quinquefasciatus for 10 and seven hours respectively. INTERPRETAION AND CONCLUSION: Pine oil is effective against mosquito larvae at very higher doses which are not of any practical utility. However, Pine oil showed strong repellent action against An. culicifacies (malaria vector) and Cx. quinquefasciatus (pest mosquito). Thus its use could be popularised as mosquito repellent.

Evaluation of repellent action of Cymbopogan martinii martinii Stapf var sofia oil against Anopheles sundaicus in tribal villages of Car Nicobar Island, Andaman & Nicobar Islands, India.

A field study was carried out to evaluate the mosquito repellent action of Cymbopogan martinii martinii Stapf var sofia oil in tribal village of Car Nicobar Island. Results revealed that application of 1 ml of the oil provided 98.7% protection in indoor and 96.52% in outdoor conditions during 12 h period of observation from the bites of An. sundaicus. Cymbopogan martinii martinii Stapf var sofia oil is an indigenous product, its application is safe and can be widely used for protection from malaria.

Lessons to be learned: a case study approach. Paraganglioma of the urinary bladder.

Primary paraganglioma arises infrequently in the urinary bladder. We present here the clinicopathological, immunohistochemical and ultrastructural findings in a 23-year-old Saudi female. She was hospitalised because of gross haematuria over the previous seven days. The intravenous urogram revealed a filling defect in the urinary bladder. Cystoscopy disclosed a non-papillary tumour arising from the roof of the bladder neck. Transurethral resection was, accordingly, performed--but marked fluctuation in blood pressure was observed during the procedure. The histopathological findings of trabeculae and small nests of plump oval to spindle cells with a clear to acidophilic cytoplasm, forming an organoid pattern and demonstrating inconspicuous mitotic activity, were diagnostic of paraganglioma of the urinary bladder, the diagnosis was confirmed by means of immunohistochemical and ultrastructural studies. The endocrine markers chromogranin A and neuron-specific enolase were positive in chief cells; sustentacular cells at the periphery of neoplastic cell clusters were positive for S-100 protein. Neurosecretory granules were identified by electron microscopic examination. It is emphasised that, currently, there are no anatomico-pathological criteria to distinguish benign and malignant forms of the disease. Post-surgical recovery was uneventful in this case. Recurrence and metastases, though infrequent, have been reported in the literature; therefore, radiation therapy may be an important adjunct--and long-term follow-up is mandatory.

Correlation between AgNOR count and subjective AgNOR pattern assessment score in cytology and histology of breast lumps.

OBJECTIVE: To find the correlation of argyrophilic nucleolar organizer region (AgNOR) count and subjective AgNOR pattern assessment (SAPA) score in cytology and histology of breast lumps. STUDY DESIGN: The study group consisted of 73 patients (46 malignant, 27 benign) with breast lumps. In all cases, fine needle aspiration cytology (FNAC) samples and histologic specimens were studied by conventional and silver staining for AgNORs. RESULTS: AgNOR count and SAPA score were helpful in differentiating benign from malignant tumors in both the cytologic smear and histologic specimen. AgNOR count was 6.94+/-2.74 in FNAC and 6.57+/-2.73 in histology of malignant tumors, while in benign tumors it was 2.75+/-0.74 in FNAC and 2.68+/-0.77 in histology. SAPA score was 9.02+/-4.60 in FNAC and 8.76+/-2.34 in histology in malignant tumors and 5.87+/-0.93 in FNAC and 5.82+/- 0.83 in histology in benign tumors. CONCLUSION: Both AgNOR count and SAPA score gave similar results, but SAPA score is a more convenient, reproducible and rapid method of AgNOR evaluation.

New flavonoids from Avicennia marina.

In addition to luteolin 7-O-methylether, chrysoeriol 7-O-glucoside and isorhamnetin 3-O-rutinoside, the methanol extract of the aerial parts of Avicennia marina yielded two new flavonoids identified as luteolin 7-O-methylether 3'-O-beta-D-glucoside and its galactoside analogue 2.

Gonadotropin-releasing hormone increases CD4 T-lymphocyte numbers in an animal model of immunodeficiency.

BACKGROUND: Gonadotropin-releasing hormone (GnRH) possesses immunostimulatory properties. We have previously demonstrated that GnRH antagonists decrease lymphocyte numbers in an animal model of autoimmune disease. We speculated that the converse might be true, that GnRH administration would increase lymphocyte numbers or alter lymphocyte subsets in an immunodeficiency state. OBJECTIVE: Our purpose was to test the hypothesis that GnRH agonist would increase IgG and CD4 counts in a rat model of immunodeficiency independently of gonadal steroids. METHODS: We used diabetes-prone (DP) BB rats. This model has been characterized to have an AIDS-like lymphocyte profile, with lymphopenia and depressed CD4 counts. Ovariectomized female DP rats were randomized to receive subcutaneous injections with GnRH or vehicle 6 times weekly. DR rats were ovariectomized and treated with vehicle as controls. We performed flow cytometric analysis and complete blood cell counts at baseline, 3.5 weeks, and 7 weeks of treatment. We also measured total serum IgG and luteinizing hormone levels. RESULTS: GnRH administration significantly increased total serum IgG levels in DP rats compared with vehicle. The percentages of CD4(+) cells in blood were also significantly increased in the GnRH-treated group compared with the vehicle-treated group and compared with baseline. Similarly, the absolute numbers of CD4(+) positive T cells were increased over controls at 7 weeks. The effects of GnRH were specific for the CD4 subset because there were no significant differences in numbers of CD8(+) positive cells between the 2 treatment groups. CONCLUSION: GnRH shows potential utility as an immunostimulatory agent in immunodeficient states manifesting diminished numbers of immunocompetent CD4(+) T lymphocytes.

Gender-specific exacerbation of murine lupus by gonadotropin-releasing hormone: potential role of G alpha(q/11).

We have previously demonstrated that GnRH and its analogues modulate the severity of murine systemic lupus erythematosus. In the present study, we demonstrate that GnRH alters disease severity in a sexually dimorphic fashion, even in gonadectomized mice. GnRH administration leads to an exacerbation of lupus in ovariectomized females, whereas it exerts no effect in castrated males. We initially hypothesized that gender differences in lymphocytic expression of GnRH receptor might explain these observations. Using competitive RT-PCR and binding studies to quantitate GnRH receptor expression in lymphoid organs, we found that GnRH administration led to decreased expression of GnRH receptor messenger RNA (mRNA) and GnRH binding, compared with vehicle, in spleens of ovariectomized females after 2 weeks of treatment. These decreases occurred concurrently with increased expression of interleukin-2 receptor mRNA and protein in females. GnRH administration did not alter GnRH receptor or interleukin-2 receptor mRNA or protein in castrated males. GnRH exerts actions on the pituitary through G protein signal transduction, specifically through G alpha(q/11). Competitive RT-PCR revealed that GnRH administration was associated with increases in the expression of G alpha(q/11) mRNA, compared with vehicle, in spleens in ovariectomized females but not in castrated males. Immunoblot analysis revealed a similar pattern. We conclude that gender differences in expression of G alpha(q/11) may contribute to gender differences in immunity and/or autoimmune disease.