Bibliometrics and visualization analysis of literature on male hypogonadism from 2000 to 2023: research focus and frontiers.

Male hypogonadism can seriously affect male health and fertility, yet comprehensive bibliometric and visualization analyses of research in this area have been lacking. This study aimed to examine the distribution of literature, identify research hotspots, and discern development trends in male hypogonadism by analyzing 4026 English documents published between 2000 and 2023 using bibliometric and visual analyses. The results indicated a significant increase in publications and citations related to male hypogonadism over the past two decades, with the United States, the University of Florence, Maggi M, and the Journal of Clinical Endocrinology & Metabolism recognized as the most productive and highly cited country, institution, author, and journal, respectively. The article titled "The GPR54 gene as a regulator of puberty" received the highest number of citations. The keywords were categorized into four distinct clusters, including the etiology and pathogenesis of male hypogonadism, symptoms of late-onset hypogonadism, testosterone replacement therapy and its contraindications, the correlation between male hypogonadism and metabolic syndrome (MetS), obesity, and the epidemiology of male hypogonadism. The most frequently co-occurring keywords were "hypogonadism", "testosterone", and "men", while "oxidative stress" was the most prominent burst keyword. The analysis also identified "male infertility" and "oxidative stress" as the primary burst keywords in the last five years, indicating their emerging high-interest topics. Overall, this study provides a comprehensive overview of male hypogonadism research, offering valuable insights for researchers interested in this area, including potential collaborators, current research hotspots, and future research directions.

Fixed drug eruption-induced balanoposthitis: a case report.

Fixed Drug Eruptions (FDE) represent a distinctive type of adverse drug reaction, typically characterized by recurring, sharply demarcated skin lesions occurring at identical sites with each administration of the causative drug. A less frequent, albeit significant manifestation of FDE, is balanoposthitis, an inflammatory condition affecting the glans penis and prepuce. This rare case report explores the clinical presentation, diagnosis, and therapeutic management of FDE-induced balanoposthitis in a 34-year-old male patient who developed this condition following azithromycin administration to treat a pulmonary infection. The patient's distinctive symptoms, coupled with a medical history of similar antibiotic-induced reactions, pointed strongly towards an FDE diagnosis. Management entailed immediate discontinuation of the offending drug and initiation of symptomatic treatment, culminating in a positive therapeutic outcome. This case illuminates the potential of commonly prescribed medications, such as antibiotics, to incite balanoposthitis via FDE. It underscores the critical need for healthcare professionals to include FDE in their differential diagnosis for balanoposthitis, especially when patient exposure to high-risk medications is evident. Furthermore, the report emphasizes the pressing requirement for additional research to elucidate the pathogenesis of FDE-induced balanoposthitis and to devise effective therapeutic and preventive measures.

Serum 25-hydroxyvitamin D level is associated with short-term glycemic variability metrics derived from continuous glucose monitoring in T2DM.

This study aims to investigate the association between 25-hydroxyvitamin D (25OHD) and continuous glucose monitoring-assessed short-term glycemic variability (GV) and HbA1c among patients with type 2 diabetes mellitus (T2DM). We conducted a cross-sectional study recruiting 325 patients. The association between 25OHD and GV metrics (mean amplitude of glycemic excursions [MAGE], coefficient of variation [CV], standard deviation of sensor glucose [SD], and TIR) and HbA1c were analyzed using multivariable linear and logistic regression analyses. The 25OHD level and GV metrics showed significant differences among HbA1c groups (P < 0.01). CV, MAGE, SD and HbA1c decreased, and TIR increased with ascending 25OHD tertiles (P < 0.05). Serum 25OHD was inversely associated with CV (ß = - 0.211 [- 0.350 to - 0.071], P < 0.01) and HbA1c (ß = - 0.061 [- 0.114 to - 0.031], P < 0.01), and further multivariable analyses confirmed these results (P < 0.05). However, no association of HbA1c and 25OHD was found with the highest tertile of CV. These findings revealed that increased GV and HbA1c were both associated with lower 25OHD, and the relationship between HbA1c and 25OHD was attenuated with higher glucose CV in T2DM. Taken together, the analyses suggest that increasing vitamin D status has effects on improvements in long-term glycemic control and low glycemic variability.

Comprehensive retinal vascular measurements: time in range is associated with peripheral retinal venular calibers in type 2 diabetes in China.

AIM: Retinal vascular parameters are biomarkers of diabetic microangiopathy. We aimed to investigate the relationship between time in range (TIR) assessed by continuous glucose monitoring (CGM) and retinal vascular parameters in patients with type 2 diabetes in China. METHODS: The TIR assessed by CGM and retinal photographs were obtained at the same time from adults with type 2 diabetes who were recruited. Retinal vascular parameters were extracted from retinal photographs by a validated fully automated computer program, and TIR was defined as between 3.9-7.8 mmol/L over a 24-h period. The association between TIR and caliber of retinal vessels distributed in different zones were analyzed using multivariable linear regression analyses. RESULTS: For retinal vascular parameters measurements, the peripheral arteriovenous and middle venular calibers widen with decreasing TIR quartiles (P < 0.05). Lower TIR was associated with wider peripheral venule after adjusting for potential confounders. Even after further correction for GV, there was still a significant correlation between TIR and peripheral vascular calibers (CV: ß = - 0.015 [- 0.027, - 0.003], P = 0.013; MAGE: ß = - 0.013 [- 0.025, - 0.001], P = 0.038) and SD: ß = - 0.013 [- 0.026, - 0.001], P = 0.004). Similar findings were not found for the middle and central venular calibers or arterial calibers located in different zones. CONCLUSIONS: The TIR was associated with adverse changes to peripheral retinal venules but not central and middle vessels in patients with type 2 diabetes, suggesting that peripheral retinal vascular calibers may be affected by glycemic fluctuations earlier.

Insulin-like growth factor binding protein-1 and insulin in polycystic ovary syndrome: a systematic review and meta-analysis.

Background: Insulin-like growth factor binding protein-1 (IGFBP-1) is considered a decline in polycystic ovary syndrome (PCOS), but it remains controversial that whether such reduction is attributed to obesity. Aims: This systematic review aims to explore whether IGFBP-1 is reduced in PCOS, and whether such reduction is associated with obesity. Results: Our pooled study included 12 studies with a total of 450 participants. IGFBP-1 levels in PCOS were significantly lower than that in non-PCOS (SMD (95%CI)=-0.49(-0.89, -0.09), P=0.02). No significant difference in IGFBP-1 levels between patients with or without PCOS classified by BMI. Whilst, stratification by PCOS status revealed a significant decrease in IGFBP-1 in overweight (SMD (95%CI)=-0.92(-1.46, -0.37), P=0.001). When comparing fasting insulin in the same way, PCOS patients had significantly elevated fasting insulin level but not statistically declined IGFBP-1 after classified by BMI. Conclusion: This meta-analysis provides evidence that the decrease of IGFBP-1 in PCOS was more strongly influenced by comorbid obesity than by PCOS itself. Additionally, contrast to previous findings that insulin significantly suppresses IGFBP-1, our results suggested that the suppression of PCOS-related hyperinsulinemia on IGFBP-1 seemed diminished. Overall, our work may provide a novel perspective on the mechanism between insulin and IGFBP-1 underlying PCOS development.

Needle-free injection of basal insulin improves fasting glucose variability as assessed by continuous glucose monitoring in T2DM: a prospective randomized multicenter open-label crossover study.

BACKGROUND: Fasting glucose variability (FGV) extensively promotes the onset and development of diabetic complications. This study aimed to evaluate the FGV in type 2 diabetes mellitus (T2DM) patients administered basal insulin using a needle-free insulin injector (NFII). RESEARCH DESIGN AND METHODS: This was a prospective randomized multicenter open-label crossover study. We randomly assigned 48 T2DM patients to receive basal insulin by NFII or conventional insulin pen (CIP) for 7-14 days and were then crossed over after washout. We conducted continuous glucose monitoring to investigate the FGV, our primary outcome was a composite parameter of the FGV with a fasting blood glucose target between 4.4 and 6.1 mmol/L. RESULTS: The coefficient of variation for sensor glucose at 6 a.m. with CIP was 11.67 (8.70,14.81)% vs. 9.48 (6.48,12.24)% with NFII (p = 0.003), and the coefficient of variation for mean sensor glucose at 5-6 a.m. with CIP was 12.70 (9.17,16.56)% vs. 9.23 (7.01,11.98)% with NFII (p < 0.001). The overall basal insulin dosage with CIP injection was 18.00 (16.00, 20.00) IU vs. 16.00 (12.00, 19.00) IU during NFII (p < 0.003). CONCLUSION: Compared with CIP, the use of the NFII to inject basal insulin improved FGV in T2DM. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn Identifier is ChiCTR2000034674.

Association between serum low-density neutrophils and acute-onset and recurrent Guillain-Barré syndrome.

BACKGROUND AND AIM: Guillain-Barré syndrome (GBS) is one of the most common causes of acute flaccid paralysis. A timely assessment of this disease condition and its treatments are of vital importance to patients diagnosed with GBS. The purpose of this study is to investigate the variation trend of neutrophils along with disease courses and assess the prognostic value of serum low-density neutrophils (LDNs) in the acute-onset and recurrence of GBS. METHODS: A total of 176 GBS patients were recruited. Patients were evaluated with Medical Research Council (MRC) sum score and the Hughes Functional Grading Scale score upon admission. Peripheral blood samples were collected for routine testing. Flow cytometry analysis was performed to identify LDNs. All patients were followed up to collect disease condition data. RESULTS: The total neutrophil ratios and counts were significantly higher in patients with acute-onset GBS compared to healthy controls (HCs). These counts/ratios decreased during remission and re-elevated in recurrent GBS patients. However, no correlation was observed between the total neutrophil counts/ratios and the MRC sum score. The LDNs collected from different GBS courses were identified using flow cytometry. The counts and ratios were significantly higher in acute-onset GBS and recurrent GBS compared to HCs and patients in remission. The LDN counts/ratios displayed a negative correlation with the MRC sum scores in acute-onset GBS and recurrent GBS. CONCLUSION: Our findings suggest that LDN counts/ratios are positively correlated with the acute-onset and recurrence of GBS and its severity. Therefore, LDNs might serve as an accessible prognostic indicator for disease progression monitoring.

Correlation between retinal vascular parameters and cystatin C in patients with type 2 diabetes.

AIMS: To investigate the relationship between retinal vascular parameters and cystatin C in patients with type 2 diabetes in northwestern China. METHODS: This was a cross-sectional study of 1689 patients with type 2 diabetes. A validated fully automated computer program was used to extract retinal vascular parameters from the entire vascular tree. Multiple logistic regression analyses were conducted to investigate the relationship between these vascular measurements and cystatin C. RESULTS: For retinal vascular geometrical measurements, smaller arteriolar fractal dimension was related to high cystatin C after adjusting for multiple variables (odds ratio [OR] 0.149, 95% CI 0.042-0.532). For retinal vascular caliber measurements, narrower central and middle arteriolar calibers were related to high cystatin C after adjusting for multiple variables (central: OR 0.922, 95% CI 0.886-0.960; middle: OR 0.940, 95% CI 0.901-0.981). Wider central, middle and peripheral venular calibers were associated with high cystatin C after adjusting for multiple variables (central: OR 1.058, 95% CI 1.003-1.117; middle: OR 1.094, 95% CI 1.040-1.150; peripheral: OR 1.075, 95% CI 1.023-1.130). CONCLUSIONS: Multiple retinal vascular geometrical and caliber measurements are associated with cystatin C in type 2 diabetic patients. Further studies are needed to explore whether these retinal vascular changes can predict the incidence and progress of diabetic nephropathy.

Facile preparation and highly efficient sorption of magnetic composite graphene oxide/Fe3O4/GC for uranium removal.

In this work, we reported for the first time a novel magnetic composite graphene oxide/Fe3O4/glucose-COOH (GO/Fe3O4/GC) that was facilely prepared from glucose through the hydrothermal carbonization and further combination with graphene oxide (GO). The chemical and structural properties of the samples were investigated. By the batch uranium adsorption experiments, the magnetic composite GO/Fe3O4/GC exhibits an excellent adsorption performance and fast solid-liquid separation for uranium from aqueous solution. GO/Fe3O4/GC (the maximum adsorption capacity (Qm) was 390.70 mg g-1) exhibited excellent adsorption capacity and higher removal rate (> 99%) for U(VI) than those of glucose-COOH (GC) and magnetic GC (MGC). The effect of the coexisting ions, such as Na+, K+, Mg2+, Ca2+, and Al3+, on the U(VI) removal efficiency of GO/Fe3O4/GC was examined. The equilibrium sorption and sorption rate for the as-prepared adsorbents well fit the Langmuir model and pseudo second-order kinetic model, respectively. The thermodynamic parameters (ΔH0 = 11.57 kJ mol-1 and ΔG0 < 0) for GO/Fe3O4/GC indicate that the sorption process of U(VI) was exothermic and spontaneous. Thus, this research provides a facile strategy for the preparation of the magnetic composite with low cost, high efficiency and fast separation for the U(VI) removal from aqueous solution.

Facile preparation and adsorption performance of low-cost MOF@cotton fibre composite for uranium removal.

A novel composite MOF@cotton fibre (HCF) was prepared and characterized by FTIR, SEM, XPS and TGA. The effect of various parameters on the adsorption efficiency, such as the solution pH, contact time, initial U(VI) concentration and temperature, was studied. The maximal sorption capacity (Qm) is 241.28 mg g-1 at pH 3.0 for U(VI) according to the Langmuir isotherm adsorption model, and the kinetic and thermodynamic data reveal a relatively fast entropy-driven process (ΔH0 = 13.47 kJ mol-1 and ΔS0 = 75.47 J K-1 mol-1). The removal efficiency of U(VI) by HCF is comparable with that of pure cotton fibre and as-prepared MOF (noted as HST). However, the HST composite with cotton fibre significantly improved the treatment process of U(VI) from aqueous solutions in view of higher removal efficiency, lower cost and faster solid-liquid separation. Recycling experiments showed that HCF can be used up to five times with less than 10% efficiency loss.

Tunicamycin promotes metastasis through upregulating endoplasmic reticulum stress induced GRP78 expression in thyroid carcinoma.

BACKGROUND: Thyroid cancer (TC) is the most common type of endocrine malignancy and its incidence is increasing over years. Conventional surgery, radiotherapy and chemotherapy are difficult to improve the significant effects of it due to aggression and metastasis of poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC), and these are regarded as the most malignant types of TC. Glucose-regulated protein (GRP78) is the key molecule of tumor growth, apoptosis and metastasis. However, the underlying mechanisms of GRP78 in TC still require discussion. This study aimed to explore the role of GRP78 and its potential mechanism in TC. RESULTS: GRP78 expression was increased in TC tissues when compared with adjacent normal tissues. Besides, down-regulation of GRP78 significantly inhibited the metastatic and proliferative ability of ATC cells in in vitro studies. In addition, tunicamycin-induced ER stress up-regulated the expression of GRP78, PERK and XBP1 as well as reversed the metastatic ability of GRP78 in ATC cells. Bioinformatics and statistical analysis of gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for RNA-sequencing data with regard to si-GRP78 and si-control showed that GRP78 might regulate the ability of metastasis through extracellular matrix (ECM) remodeling in ATC cells, as well as the expression of ECM components such as COL1A1 and MMP13, which were highly relevant to ATC cells. The analysis of GEPIA database confirmed that high genomic amplification of MMP13 and COL1A1 in TC tissues showed correlation with TNM stage. Further western blotting analysis showed that MMP13 might be the target of GRP78 in ATC cells and ER stress could activate the expression of MMP13 that is suppressed by GRP78 depletion. CONCLUSIONS: GRP78 acts as an important regulator of metastasis under ER stress. In addition, the function of GRP78 might be mediated by ECM remodeling in ATC cells, implicating it as a therapeutic target in TC.

Comprehensive retinal vascular measurements: a novel association with renal function in type 2 diabetic patients in China.

To examine the association between various retinal vascular measurements and microalbuminuria in patients with type 2 diabetes in a northwestern China study. Data from 911 patients with type 2 diabetes were analyzed. Novel retinal vascular measurements from the whole vascular tree were extracted using a validated fully automatic computer program. Retinal vascular measurements were analyzed continuously and categorically for associations with microalbuminuria using multiple logistic regressions, adjusted for related variables. In logistic regression adjusting for multiple variables, microalbuminuria was associated with smaller peripheral arteriolar caliber, larger peripheral venular caliber, larger arteriolar tortuosity, and smaller arteriolar fractal dimension (p = 0.028, p < 0.001, p = 0.038, p = 0.035, respectively). In further categorical analyses, microalbuminuria was related to smaller peripheral arteriolar caliber [T1 vs. T3: odds ratio (OR) 2.029; 95% confidence interval (CI) 1.186-3.473], larger peripheral venular caliber (T1 vs. T3: OR 0.609; 95% CI 0.362-1.024), and smaller arteriolar fractal dimension (T1 vs. T3: OR 1.659; 95% CI 1.028-2.675). Microalbuminuria in type 2 diabetes is associated with both retinal vascular caliber and geometry. These noninvasive vascular measurements serve as potential preclinical markers to identify populations at high risk of early kidney disease in the course of diabetes.

Preparation of a magnetic reduced-graphene oxide/tea waste composite for high-efficiency sorption of uranium.

The preparation and application of adsorptive materials with low cost and high-efficiency recovery of uranium from nuclear waste is necessary for the development of sustainable, clean energy resources and to avoid nuclear pollution. In this work, the capacity of tea waste and tea waste hybrids as inexpensive sorbents for uranium removal from water solutions was investigated. Composites of graphene oxide (GO) and tea waste (TW) exhibited a promising adsorption performance for uranium from aqueous solutions. The composites GOTW and magnetic rGO/Fe3O4/TW show high adsorption capacities (Qm (TW) = 91.72 mg/g, Qm (GOTW) = 111.61 mg/g and Qm (rGO/Fe3O4/TW) = 104.95 mg/g) and removal rates (~99%) for U(VI). The equilibrium sorption of the adsorbents fitted well to the Langmuir model, and the sorption rate fitted well to a pseudo-second-order kinetic model. The thermodynamic parameters indicated that sorption was spontaneous and favourable. The prepared adsorbents were used for the removal of uranium from real water samples as well. The results revealed that GOTW and rGO/Fe3O4/TW can be used to remediate nuclear industrial effluent as a potential adsorbent.

Facile preparation of low-cost HKUST-1 with lattice vacancies and high-efficiency adsorption for uranium.

In this work, we prepared HKUST-1 and HKUST-1 with lattice vacancies (HLV) using benzoic acid (BA) as a low-cost modulator to replace part of the traditional trimesic acid ligand (H3BTC). The structure and morphology of the products were characterized by FTIR, XRD, SEM and XPS. The adsorption performance of the products for uranium from aqueous solutions was investigated. The results showed that the sorption of U(vi) on HKUST-1 and HLV agreed with the Langmuir isotherm model (R HKUST-1 2 = 0.9867 and R HLV 2 = 0.9828) and the maximum adsorption capacity was 430.98 mg g-1 and 424.88 mg g-1, respectively. According to kinetics studies, the adsorption fitted better with a pseudo-second-order model (R HKUST-1 2 = 1.0000 and R HLV 2 = 0.9978). The as-prepared adsorbents were used for the removal of uranium from real water samples as well. The results showed that HLV with lower cost is a promising adsorbent for uranium from aqueous solutions.

Facile preparation and adsorption performance of graphene oxide-manganese oxide composite for uranium.

To overcome the limits of low adsorption capacity and the separation difficulty of solid from liquid phase for graphene oxide (GO), a novel nanocomposite graphene oxide-manganese oxide (GOMO) was facilely fabricated under ultrasonic radiation. The structures and micro-morphology of the products were characterized by fourier transform infrared (FT-IR) spectroscopy, raman shift spectroscopy, X-ray diffraction (XRD) pattern and scanning electron microscopy (SEM). The effect of solution pH, adsorbent dose, contact time, initial uranium concentration, ionic strength and temperature on uranium removal efficiency was studied by batch adsorption experiments. The product GOMO was used to examine the feasibility of the removal of high salt content in uranium-containing wastewater. The adsorption results were fitted using the Langmuir and Freundlich isotherm models. The kinetic parameters in the adsorption process were measured and fitted. Five adsorption/desorption cycles were performed using 3 M HNO3 as the regenerant in order to evaluate the reuse of GOMO.

[Analysis of deafness-related gene mutations in 100 non-syndromic hearing loss patients in Henan province].

OBJECTIVE: To preliminarily determine the gene mutation frequency and the hotspots in Henan province, we analysed the deafness-related gene mutation in patients with non-syndromic hearing loss (NSHL). METHOD: Genomic DNA samples of 100 patients with NSHL in Henan province were extracted from peripheral blood after clinical history inquiry and clinical examination, Four common deafness genes GJB2, SLC26A4, mitochondrial 12SrRNA, and GJB3 were detected by Sanger sequencing method,and then data analysis were conducted. RESULT: Among 100 patients with NSHL. the gene mutation frequency was 44%. In these patients, 29 cases had GJB2 mutations, 13 cases had SLC26A4 gene mutations, and 3 cases had mitochondrial 12SrRNA mutations. CONCLUSION: Among the patients with NSHL in Henan province, the most frequent mutation causing hereditary deafness was mutation in GJB2, followed by SLC26A4,and it will provide a theoretical basis to determine the etiology of deafness in Henan Province.

Facile decolorization of methylene blue with flower-like manganese wads.

Flower-like manganese wads (MWs) were synthesized via a simple and inexpensive ultrasonic irradiation method for the first time. MWs were characterized by X-ray diffraction, scanning electron microscopy, energy dispersive X-ray and transmission electronic microscopy. The decolorization efficiency of MWs for methylene blue (MB) azo dye was examined as a function of pH, stirring time, MW dosage and initial concentration of the MB solution. Results show that MWs have excellent decolorization performance for MB with a higher efficiency (and without using H2O2 or other devises such as UV light and ultrasonic irradiation) compared to other catalysts, such as the mixture of Mn3O4 and H2O2 (with a maximum decolorization rate of 99.7% in 3 h), ZnS and CdS under light irradiation (with a maximum decolorization rate of 73% in 6 h), and sulfate modified titania under solar radiation (with a maximum decolorization rate of nearly 100% in 4 h).

The cathepsin B inhibitor, z-FA-FMK, inhibits human T cell proliferation in vitro and modulates host response to pneumococcal infection in vivo.

The cathepsin B inhibitor, benzyloxycarbonyl-phenyl-alanyl-fluoromethylketone (z-FA-FMK) at nontoxic doses was found to be immunosuppressive and repressed human T cell proliferation induced by mitogens and IL-2 in vitro. We showed that z-FA-FMK suppresses the secretion of IL-2 and IFN-gamma as well as the expression of IL-2R alpha-chain (CD25) in activated T cells, whereas the expression of the early activated T cell marker, CD69, was unaffected. Furthermore, z-FA-FMK blocks NF-kappaB activation, inhibits T cell blast formation, and prevents cells from entering and leaving the cell cycle. z-FA-FMK inhibits the processing of caspase-8 and caspase-3 to their respective subunits in resting T cells stimulated through the Ag receptor, but has no effect on the activation of these caspases during Fas-induced apoptosis in proliferating T cells. When administered in vivo, z-FA-FMK significantly increased pneumococcal growth in both lungs and blood, compared with controls, in a mouse model of intranasal pneumococcal infection. Because host response to bronchopneumonia in mice is T cell dependent, our collective results demonstrated that z-FA-FMK is immunosuppressive in vitro and in vivo.

Statin-induced proinflammatory response in mitogen-activated peripheral blood mononuclear cells through the activation of caspase-1 and IL-18 secretion in monocytes.

Statins, which inhibit 3-hydroxy-3-methylglutaryl CoA reductase, have been shown recently to promote proinflammatory responses. We show in this study that both atorvastatin and simvastatin induced proinflammatory responses in mitogen-activated PBMCs by increasing the number of T cells secreting IFN-gamma. This is abolished by the presence of mevalonate, suggesting that statins act specifically by blocking the mevalonate pathway for cholesterol synthesis to promote the proinflammatory response. Both statins at low concentrations induced a dose-dependent increase in the number of IFN-gamma-secreting T cells in mitogen-activated PBMCs, whereas at higher concentrations the effect was abolished. The proinflammatory effect of statins was not seen in purified T cells per se activated with mitogen. However, conditioned medium derived from statin-treated PBMCs enhanced the number of IFN-gamma-secreting cells in activated purified T cells. This effect was not blocked by mevalonate, but was abolished by neutralizing Abs to IL-18 and IL-12. Similarly, the up-regulation of IFN-gamma-secreting T cells in PBMCs costimulated with statins and mitogens was blocked by the neutralizing anti-IL-18 and anti-IL-12. We showed that simvastatin stimulates the secretion of IL-18 and IL-1beta in monocytes. Active caspase-1, which is required for the processing and secretion of IL-18 and IL-1beta, was activated in simvastatin-treated monocytes. This was blocked by mevalonate and the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone. Taken together, the proinflammatory response mediated by statins in activated PBMCs is mediated mainly via the activation of caspase-1 and IL-18 secretion in the monocytes and to a lesser extent by IL-12.