Selenium supplementation decreases CRP and IL-6 and increases TNF-alpha: A systematic review and meta-analysis of randomized controlled trials.

Inflammation is an initiating cause of infectious and non-infectious diseases. Studies have shown that selenium (Se) has anti-inflammatory effects. However, its' effects on serum c-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) plasma concentrations are equivocal. Therefore, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs), evaluating the effects of per oral (PO) and intravenous (IV) Se supplementation on CRP, TNF-α, and IL-6. A systematic search was conducted using four databases, including PubMed, Google Scholar, Cochrane Library, and Scopus to find randomized clinical trials, published up to April 2023. From 19476 papers, after screening and removing duplicate articles, 24 studies were analyzed in the present meta-analysis. In the pooled analysis, PO Se administration showed no significant effect on CRP (WMD: 0.12; 95 % CI -0.11, 0.38; P-value= 0.30). However, IV Se supplementation had a significant negative association with CRP concentration (-2.24; 95 % CI: -4.24, -0.24; p-value: 0.02). Se administration had no significant association with TNF-α plasma concentration (9.64, 95 % CI: -0.59, 19.88, p-value= 0.06; and heterogeneity: 98 %). However, a significant positive association was present between Se and plasma TNF-α concentrations (0.15, 95 % CI: 0.14, 0.17, P-value<0.0001). Moreover, Se supplementation had a significant negative correlation with IL-6 plasma concentration in PO (-0.54; 95 % CI: -1.61, 0.52; P-value = 0.31) and IV administrations (-4.77; 95 % CI: -7.61, -1.93; P-value<0.0001), respectively. This study demonstrated that IV Se administration reduced CRP and IL-6 plasma concentrations. Conversely, IV Se supplementation increased TNF-α plasma concentration. It is evident that further, well-controlled clinical trials are required.

Evaluation of testicular torsion management in Ogbomoso, South-Western Nigeria and surgical detorsion-augmented treatment with phytochemical fractions of Corchorus olitorius leaf in experimental rats.

Background: There is need to investigate whether phytochemicals along with surgical detorsion could serve as better managements options in TT patients rather than surgical detorsion (SD) alone. Methods: The descriptive cross-sectional part of this study is questionnaire-based addressing sociodemographic characteristics of participants and their experience in management of TT. In the experimental part, male rats (n = 32) were grouped into: sham, Ischemia-reperfusion injury (IRI), dichloromethane (DCM) and ethanol fraction (100 mg/kg) of CO. Evaluation of tissue GPx, total thiol, SOD, MDA and H2O2 was done. Serum estimations of nitrite, TNF-α and IL-6, MPO, sperm motility, count and viability was also carried out. Tissue expression of bax and caspase 3 was assessed. Results: 68.9 % respondents agreed that SD alone is non-effective in the management of TT while 83.6 % reported a need to augment surgery with medications. Oxidative stress markers like H2O2, MDA and nitrite increased by IRI were decreased in post-treatment groups, along with a significant increase in the tissue level of GSH, GST, SOD, GPx, and total thiol. Inflammatory mediators were elevated in IRI while post-treatment rats showed significant decrease. IRI decreased sperm count significantly this was reversed by post-treatment. Bax and caspase 3 was increased in IRI rats and post-treatment with CO fractions reduced them. Conclusions: Quantitative cross-sectional study has revealed through experience of clinicians that surgical detorsion alone is not effective in managing TT. Augmented treatment with CO leaf fractions suppressed testicular IRI through inhibition of pro-apoptotic proteins expression, oxidative stress and inflammation.

[Should we interfere with the interleukin-6 receptor during COVID-19: What do we know?] / Inhibiteurs du récepteur de l'IL-6 dans le traitement de la COVID-19 : que savons-nous ?

COVID-19 is a viral infection with predominant respiratory tropism. In its most severe forms, the initial viral aggression leads to acute respiratory failure due to damage secondary to an exacerbated inflammatory response provoked by the activation of innate, followed by adaptive immunity. The inflammatory response may entail respiratory distress syndrome, if not multivisceral failure and death. IL-6 receptor inhibitors (Tocilizumab and Sarilumab) have been proposed as treatments. Numerous studies have provided new information, which remains heterogeneous and difficult to interpret. This review is aimed at clarifying the potential role of IL-6 receptor inhibitors in severe forms of COVID-19.

The Extracellular Mass to Body Cell Mass Ratio as a Predictor of Mortality Risk in Hemodialysis Patients.

The extracellular mass/body cell mass ratio (ECM/BCM ratio) is a novel indicator of nutritional and hydration status in hemodialysis (HD) patients. This study aimed to explore the ECM/BCM ratio as a predictor of mortality risk with nutritional-inflammatory markers in HD patients. A prospective observational study was conducted in 90 HD patients (male: 52.2%; DM: 25.60%). Clinical and biochemical parameters [serum albumin, serum C-reactive protein (s-CRP), interleukine-6 (IL-6)] were analysed and bioelectrical impedance analysis (BIA) was performed. Protein-energy wasting syndrome (PEW) was diagnosed using malnutrition-inflammation score (MIS). Based on BIA-derived measurements, the ECM/BCM ratio with a cut-off point of 1.20 was used as a PEW-fluid overload indicator. Comorbidity by Charlson index and hospital admissions were measured. Out of 90 HD patients followed up for 36 months, 20 patients (22.22%) died. PEW was observed in 24 survivors (34.28%) and all non-survivors. The ECM/BCM ratio was directly correlated with MIS, s-CRP, Charlson index and hospital admissions but was negatively correlated with phase angle and s-albumin (all, p < 0.001). Values of the ECM/BCM ratio ≥ 1.20 were associated with higher probability of all-cause mortality (p = 0.002). The ECM/BCM ratio ≥ 1.20, IL-6 ≥ 3.1 pg/mL, s-CRP and s-albumin ≥ 3.8 g/dL and Charlson index were significantly associated with all-cause mortality risk in multivariate adjusted analysis. This study demonstrates that the ECM/BCM ratio ≥ 1.20 as a nutritional marker and/or fluid overload indicator had a significant prognostic value of death risk in HD patients.

Approche thérapeutique des maladies de Castleman : l'émergence des thérapies ciblées.

The spectrum of Castleman disease encompasses several different disorders. Nowadays three different forms of the disease are individualized: unicentric Castleman disease, multicentric HHV-8 associated Castleman disease and idiopathic multicentric Castleman disease. In the latter a severe form called TAFRO syndrome (thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly) tend to be individualized. Improvement in the classification and understanding of the physiopathology of CD have allowed improvement in treatment strategies. Treatment of rare but often severe manifestations, such as paraneoplastic pemphigus and bronchiolitis obliterans in unicentric CD and hemophagocytic syndrome and/or Kaposi' sarcoma in HHV8 associated CD, are better adapted. Most of current treatment strategies are based on retrospective and very few prospective studies. Both anti-IL6/6R and anti-CD20 biotherapies have greatly improved the management of certain forms of the disease. We report in this review the most relevant studies and national or international expert consensus statements for the treatment in the different types of CD. © 2022 Published by Elsevier Masson SAS on behalf of Société nationale française de médecine interne (SNFMI).

Validity of IL-6 and Arthrocentesis in the Cause and Management of Internal Derangement of TMJ.

Purpose: The aim of this clinical study was to evaluate the level of Interleukine-6 (IL-6), pre and post arthrocentesis to validate it as a biomarker in the Internal Derangement (ID) of TMJ. Material and Methods: This study included 30 patients (20 females and 10 males) of Temporo-Mandibular Dysfunction (TMD) with Disc displacement without reduction (DDwoR) Wilkes stage III, who were refractory to conservative management. Arthrocentesis was performed as a therapeutic modality. Synovial fluid aspirates were obtained prior to arthrocentesis and post arthrocentesis with 300 ml of Ringer Lactate solution into the superior joint compartment for the assessment of level of IL-6. The clinical parameters used for correlating the level of IL-6 were degree of pain (VAS I), chewing ability (VAS II), Maximal Mouth Opening (MMO) in both pre and post op phase with the follow-up period of 01 day, 01 week, 01 month, 03 month and 06 month and the results were compared. ELISA was performed to analyze the levels of IL-6 in the aspirates. The clinical parameters and the level of IL-6 were recorded and analyzed statistically. Results: The study showed ID of TMJ (Wilkes stage III) s are more prevalent in females especially in the fourth decades of life with the mean age of 38.4 years. The post operative assessment in terms of pain, maximum mouth opening, lateral movements of the mandible and the levels of IL-6 were found to be statistically significant with a P value <0.01. Conclusion: This study validates the role of IL-6 as a definitive biomarker for the pathogenesis of ID of TMJ Wilkes stage III and arthrocentesis proved to be a minimally invasive therapeutic modality for its management.

Expression Levels of Il-6 and Il-18 in Acute Myeloid Leukemia and Its Relation with Response to Therapy and Acute GvHD After Bone Marrow Transplantation.

Cytokines seem to play a crucial role in physiological and pathological conditions of acute myeloid leukemia (AML). The aim of this study was to evaluate the expression levels of interleukins-6 (IL-6) and IL-18 in patients with AML and its correlation with response to therapy and graft versus host disease (GvHD) after bone marrow transplantation. The expression levels of IL-6 and IL-18 genes were done in all patients and compared with matched control. Complete remission (CR) was used for evaluation of the effects of these cytokines on response to treatment in patients group. The expression level of these cytokines was also evaluated in patients who underwent bone marrow transplantation and experienced acute GvHD in compare with patients without aGvHD. Il-6 gene expression level was significantly higher in these patients in comparison with control but Il-18 gene expression level was not statistically significant compared to control group. Il-6 and also Il-18 expression levels were significantly higher in patients without a response to treatment according to CR compared to patient's whit response to treatment as well as patients experienced aGvHD after bone marrow transplantation. IL-6 and Il-18 are important markers in the progression of the disease and could be considered as a prognostic marker in acute leukemia. It is recommended that more studies with larger study groups and more involved cytokines are needed for more evaluation of the cytokine roles in pathophysiology and progression of acute leukemia.

Covid-19 decompensating epilepsy in the elderly: A case report.

The COVID-19 pandemic has had a great impact on chronic diseases, including epilepsy. The imbalance of antiepileptic drugs in case of intercurrent infection with COVID-19 leads to worsening seizures. A 71-year-old man, followed for post-traumatic epilepsy for 30 years, was stabilized with phenobarbital and topiramate. He presented generalized tonic-clonic epileptic seizures without meningitis. He improved well on midazolam combined with the usual treatment before the diagnosis and worsening of the covid-19. The severity of the lung damage led to hypoxia, recurrence of seizures, and poor prognosis. The association between covid-19 and epilepsy remains pejorative despite management. An epileptic seizure should always be considered as a possible manifestation of COVID-19. The article aimed to establish the relationship between covid-19 and the risk of worsening seizures and to demonstrate the severity of the association between covid-19 and epilepsy in elderly patients.

Genetic markers for preeclampsia in Peruvian women.

BACKGROUND: Preeclampsia is a multiorgan disorder associated with maternal and perinatal morbi-mortality. In Peru, incidence is 10% and accounts for 22% of maternal deaths. Genome and genetic epidemiological studies have found an association between preeclampsia and genetic polymorphisms. OBJECTIVE: To determine the association of the vascular endothelial growth factor (VEGF) +936 C/T and +405 G/C, interleukine-6 (IL-6) -174 G/C, IL-1ß-511 C/T, Apo A-1-75 G/A, Apo B-100 2488 C/T (Xbal) polymorphisms with preeclampsia in pregnant Peruvian women. METHODS: Were included preeclamptic and healthy (control) pregnant women. Maternal blood samples were subjected to DNA extraction, and molecular genetic analysis was conducted using the PCR-RFLP technique and following a specific protocol for each gene. Allele and genotypic frequencies in the cases and controls were compared. RESULTS: No association was found between the VEGF+936C/T and VEGF+405 polymorphisms and preeclampsia. The frequencies of the GG genotypes and the G allele of the -174 G/C polymorphism in the IL6 gene in preeclamptic and controls showed significant differences, with higher frequencies in cases. For the -511 C/T polymorphism of the IL-1ß gene, no significant differences were found in the frequencies of TT genotypes compared with CT+CC. The genotypes and alleles of the Apo-A1-75 G/A and Apo-B100 Xbal variants showed no significant differences between cases and controls. CONCLUSION: No association was found between the studied genetic markers and preeclampsia. However, in the -174G/C polymorphism of the IL-6 gene, significant differences were found mainly in the GG genotype and G allele.

Elevated IL-6 and CRP Levels Are Associated With Incident Self-Reported Major Mobility Disability: A Pooled Analysis of Older Adults With Slow Gait Speed.

BACKGROUND: Elevated interleukine-6 (IL-6) and C-reactive protein (CRP) are associated with aging-related reductions in physical function, but little is known about their independent and combined relationships with major mobility disability (MMD), defined as the self-reported inability to walk a quarter mile. METHODS: We estimated the absolute and relative effect of elevated baseline IL-6, CRP, and their combination on self-reported MMD risk among older adults (≥68 years; 59% female) with slow gait speed (<1.0 m/s). Participants were MMD-free at baseline. IL-6 and CRP were assessed using a central laboratory. The study combined a cohort of community-dwelling high-functioning older adults (Health ABC) with 2 trials of low-functioning adults at risk of MMD (LIFE-P, LIFE). Analyses utilized Poisson regression for absolute MMD incidence and proportional hazards models for relative risk. RESULTS: We found higher MMD risk per unit increase in log IL-6 (hazard ratio [HR] = 1.26; 95% confidence interval [95% CI] 1.13-1.41). IL-6 meeting predetermined threshold considered to be high (>2.5 pg/mL) was similarly associated with higher risk of MMD (HR = 1.31; 95% CI 1.12-1.54). Elevated CRP (CRP >3.0 mg/L) was also associated with increased MMD risk (HR = 1.38; 95% CI 1.10-1.74). The CRP effect was more pronounced among participants with elevated IL-6 (HR = 1.62; 95% CI 1.12-2.33) compared to lower IL-6 levels (HR = 1.19; 95% CI 0.85-1.66). CONCLUSIONS: High baseline IL-6 and CRP were associated with an increased risk of MMD among older adults with slow gait speed. A combined biomarker model suggests CRP was associated with MMD when IL-6 was elevated.

Genetic markers for preeclampsia in Peruvian women / Marcadores genéticos de preeclampsia en mujeres peruanas

Abstract Background: Preeclampsia is a multiorgan disorder associated with maternal and perinatal morbi-mortality. In Peru, incidence is 10% and accounts for 22% of maternal deaths. Genome and genetic epidemiological studies have found an association between preeclampsia and genetic polymorphisms. Objective: To determine the association of the vascular endothelial growth factor (VEGF) +936 C/T and +405 G/C, interleukine-6 (IL-6) -174 G/C, IL-1β-511 C/T, Apo A-1-75 G/A, Apo B-100 2488 C/T (Xbal) polymorphisms with preeclampsia in pregnant Peruvian women. Methods: Were included preeclamptic and healthy (control) pregnant women. Maternal blood samples were subjected to DNA extraction, and molecular genetic analysis was conducted using the PCR-RFLP technique and following a specific protocol for each gene. Allele and genotypic frequencies in the cases and controls were compared. Results: No association was found between the VEGF+936C/T and VEGF+405 polymorphisms and preeclampsia. The frequencies of the GG genotypes and the G allele of the -174 G/C polymorphism in the IL6 gene in preeclamptic and controls showed significant differences, with higher frequencies in cases. For the -511 C/T polymorphism of the IL-1β gene, no significant differences were found in the frequencies of TT genotypes compared with CT+CC. The genotypes and alleles of the Apo-A1-75 G/A and Apo-B100 Xbal variants showed no significant differences between cases and controls. Conclusion: No association was found between the studied genetic markers and preeclampsia. However, in the -174G/C polymorphism of the IL-6 gene, significant differences were found mainly in the GG genotype and G allele.

Resumen Antecedentes: La preeclampsia es un trastorno multiorgánico asociado con la morbi-mortalidad materna y perinatal. En el Perú, su incidencia es del 10% y causa el 22% de las muertes maternas. Se encontró una asociación entre la preeclampsia y ciertos polimorfismos. Objetivo: Determinar asociación entre los polimorfismos genéticos del factor de crecimiento endotelial vascular (VEGF) +936 C/T y +405 G/C, interleucina-6 (IL-6) -174G/C, IL-1β -511 C/T, Apo A-1 -75 G/A, Apo B-100 2488 C/T (Xbal), y preeclampsia en gestantes peruanas. Métodos: Se incluyeron gestantes preeclámpticas y sanas (controles). Las muestras de sangre fueron procesadas para extracción del ADN, y el análisis se realizó con la técnica PCR-RFLP con protocolos específicos para cada gen y confirmación con secuenciamiento Sanger. Se compararon las frecuencias alélicas y genotípicas en los casos (preeclampsia) y los controles. Resultados: No se halló asociación entre los polimorfismos VEGF+936-C/T y VEGF+405 y la preeclampsia. Las frecuencias de los genotipos GG y el alelo G del polimorfismo -174-G/C en el gen IL6 en preeclámpticas y controles, mostraron diferencias significativas, con frecuencias más altas en los casos. Para el polimorfismo -511-C/T del gen IL-1β, no se encontraron diferencias significativas en las frecuencias de genotipos TT comparados con CT+CC. Los genotipos y alelos de las variantes Apo-A1-75-G/A y Apo-B100 Xbal no mostraron diferencias significativas entre los grupos Conclusión: No se encontró asociación entre los marcadores genéticos estudiados y la preeclampsia. Sin embargo, el polimorfismo -174-G/C en el gen IL6 mostró diferencias significativas principalmente en el genotipo GG y el alelo G.

The effects of local versus systemic passive heating on the acute inflammatory, vascular and glycaemic response.

The aim of this study was to compare the acute cardiometabolic and perceptual responses between local and whole-body passive heating. Using a water-perfused suit, 10 recreationally active males underwent three 90 min conditions: heating of the legs with upper-body cooling (LBH), whole-body heating (WBH) and exposure to a thermoneutral temperature (CON). Blood samples were collected before and up to 3 h post-session to assess inflammatory markers, while a 2 h oral glucose tolerance test was initiated 1 h post-session. Femoral artery blood flow and perceptual responses were recorded at regular intervals. The interleukin (IL)-6 incremental area under the curve (iAUC) was higher for LBH (1096 ± 851 pg/mL × 270 min) and WBH (833 ± 476 pg/mL × 270 min) compared with CON (565 ± 325 pg/mL × 270 min; p < 0.047). Glucose concentrations were higher after WBH compared with LBH and CON (p < 0.046). Femoral artery blood flow was higher at the end of WBH (1713 ± 409 mL/min) compared with LBH (943 ± 349 mL/min; p < 0.001), and higher in LBH than CON (661 ± 222 mL/min; p = 0.002). Affect and thermal comfort were more negative during WBH compared with LBH and CON (p < 0.010). In conclusion, local passive heating elevated blood flow and the IL-6 iAUC. However, while resulting in more positive perceptual responses, the majority of the included cardiometabolic markers were attenuated compared with WBH. Novelty: The increase in the IL-6 iAUC in response to passive heating is not reduced by upper-body cooling. Upper-body cooling attenuates the plasma nitrite, IL-1ra and femoral artery blood flow response to passive heating. Upper-body cooling leads to more positive perceptual responses to passive heating.

Oxidative Phosphorylation Dysfunction Modifies the Cell Secretome.

Mitochondrial oxidative phosphorylation disorders are extremely heterogeneous conditions. Their clinical and genetic variability makes the identification of reliable and specific biomarkers very challenging. Until now, only a few studies have focused on the effect of a defective oxidative phosphorylation functioning on the cell's secretome, although it could be a promising approach for the identification and pre-selection of potential circulating biomarkers for mitochondrial diseases. Here, we review the insights obtained from secretome studies with regard to oxidative phosphorylation dysfunction, and the biomarkers that appear, so far, to be promising to identify mitochondrial diseases. We propose two new biomarkers to be taken into account in future diagnostic trials.

Silencing of IL-6 and STAT3 by siRNA loaded hyaluronate-N,N,N-trimethyl chitosan nanoparticles potently reduces cancer cell progression.

The immunosuppressive nature of the tumor microenvironment is a critical problem that should be considered before the design of immunotherapies. Interleukin (IL)-6 and its related downstream molecules such as signal transducer and activator of transcription (STAT)3 play an important role in the cancer progression, which can be considered as potential therapeutic targets. In the present study, we generated the active-targeted hyaluronate (HA) recoated N, N, N-trimethyl chitosan (TMC) nanoparticles (NPs) to deliver IL-6- and STAT3-specific small interfering RNAs (siRNAs) to the CD44-expressing cancer cells. We utilized the interaction between HA and CD44 to increase the specificity and efficacy of cellular uptake in NPs. The results showed that the synthesized NPs had efficient physicochemical characteristics, high transfection efficiency, low toxicity, and controlled siRNA release. siRNA-loaded NPs significantly inhibited the IL-6/STAT3 expression, which was associated with blockade of proliferation, colony formation, migration, and angiogenesis in cancer cells. These findings imply the potential of HA-TMC NPs as potent vectors in gene therapy and their application for the silencing of IL-6 and STAT3, as a novel anti-cancer combination therapeutic strategy, for the first time.

Oral supplementation with omega-3 fatty acids and inflammation markers in patients with chronic kidney disease in hemodialysis.

Chronic kidney disease (CKD) is an increasingly common public health problem that increases the risk of death because of cardiovascular complications by 2-3 times compared with the general population. This research concerns a prospective, randomized, double-blind study in patients with CKD undergoing hemodialysis. The participants were assigned to 1 of 2 groups: the study group (group A; 46 patients) received 4 capsules (2.4 g) of omega-3 fatty acids daily during the 12-week intervention, while patients in the control group (group B; 47 patients) received 4 capsules of paraffin oil. The patients' general characteristics, nutritional indicators, renal disease markers and inflammatory markers (C-reactive protein, interleukin (IL)-6, IL-10, and tumour necrosis factor alpha (TNF-α)) were evaluated. No differences were found between the general characteristics of the patients (P < 0.05), and no differences were shown in the nutritional indicators and markers of kidney disease (P < 0.05). Patients in group A showed significant decreases in levels of C-reactive protein, IL-6, TNF-α, and the IL-10/IL-6 ratio after 12 weeks of supplementation (P < 0.05). Patients in group B did not show any significant changes in concentrations of inflammatory markers during the intervention (P < 0.05). In conclusion, oral supplementation with omega-3 fatty acids produces a significant decrease in the concentrations of inflammation markers in patients with chronic kidney disease on hemodialysis. Novelty Oral supplementation with omega-3 fatty acids produced significant decreases in the concentrations of inflammation markers. This supplementation could be given to patients with uremic syndrome and coronary heart disease to reduce cardiovascular risk.

Impact of resistance training program configuration on the circulating brain-derived neurotrophic factor response.

This study examined the acute and resting changes of brain-derived neurotrophic factor (BDNF) and inteleukin-6 (IL-6) and if changes in these biomarkers were correlated during resistance training (RT). Fifteen men with ≥2 years of RT experience (age: 23 ± 3 years, body mass: 84.4 ± 12.3 kg) participated. Subjects performed RT 3×/week for 6 weeks in either a high-repetition (HR; n = 8) or low-repetition (LR; n = 7) group. Protocols during week 1 were HR - Monday: 4 (sets) × 12 (repetitions) at 60% of 1-repetition maximum, Wednesday: 4 × 10 at 65%, Friday: 5 × 8 at 70%; LR - Monday: 8 × 6 at 75%, Wednesday 9 × 4 at 80%, Friday: 10 × 2 at 85%. Total volume was equated for the 6 weeks but not for individual sessions. Greater volume and intensity were performed in LR versus HR (p < 0.01) on Mondays. Plasma was collected immediately before and after exercise of the Monday session. There were no significant interactions or main effects for BDNF (p > 0.05). There was a moderate between-group effect size (0.57) in favor of LR in week 6, suggesting a potentially greater acute increase in BDNF in LR versus HR. For IL-6, a statistically significant main effect was observed for training (p < 0.0001), showing an acute increase in IL-6 in both weeks (p < 0.01); however, no other 3-way or 2-way interactions existed (p > 0.05). A minimum volume threshold of RT may be needed to induce acute elevations in BDNF. Novelty A minimum RT volume threshold may be needed to elicit BDNF. A close proximity to failure may be needed to elicit BDNF. BDNF and IL-6 did not correlate.

Nicotinamide N-Methyltransferase and Its Precursor Substrate Methionine Directly and Indirectly Control Malignant Metabolism During Progression of Renal Cell Carcinoma.

BACKGROUND/AIM: Renal cell carcinoma (RCC) is one of the most common tumor diseases in adults, and new specific biomarkers are urgently needed to define diagnosis and prognosis of patients with RCC as well as monitor the outcome of therapeutic interventions. The enzyme nicotinamide N-methyltransferase (NNMT) is believed to represent such a marker molecule in RCC therapy. MATERIALS AND METHODS: NNMT expression was examined by western blotting in samples from patients with RCC and in RCC cell lines. Effects of NNMT on cell growth and metabolism were assessed using the Hoechst 33342 reagent assay and Vita-Orange cell viability assay. Incubation experiments were performed to study the influence of methionine and interleukin-6 (IL6) on expression of NNMT. RESULTS: In patient samples, NNMT was up-regulated depending on the stage of progression. Investigations in an RCC cell culture model showed that after modulation of NNMT expression, cellular metabolism, but not cell growth was affected. This regulatory function was also dependent on the presence of the NNMT precursor substrate methionine and IL6. CONCLUSION: The metabolism-regulatory activity of NNMT depends on the precursor substrate methionine and the presence of IL6. The function of methionine appears to be dependent on the stage of progression, since in individual RCC cell lines, opposing effects on metabolism were demonstrated. This, in turn, reflects the thoroughly complex situation in the clinic.

Treatment with hydrogen sulfide donor attenuates bone loss induced by modeled microgravity.

The present study was undertaken to explore the therapeutic potential of hydrogen sulfide against bone loss induced by modeled microgravity. Hindlimb suspension (HLS) and rotary wall vessel bioreactor were applied to model microgravity in vivo and in vitro, respectively. Treatment of rats with GYY4137 (a water soluble donor of hydrogen sulfide, 25 mg/kg per day, i.p.) attenuated HLS-induced reduction of bone mineral density in tibiae, and preserved bone structure in tibiae and mechanical strength in femurs. In HLS group, GYY4137 treatment significantly increased levels of osteocalcin in sera. Interestingly, treatment of HLS rats with GYY4137 enhanced osteoblast surface, but had no significant effect on osteoclast surface of proximal tibiae. In MC3T3-E1 cells exposed to modeled microgravity, GYY4137 stimulated transcriptional levels of runt-related transcription factor 2 and enhanced osteoblastic differentiation, as evidenced by increased mRNA expression and activity of alkaline phosphatase. HLS in rats led to enhanced levels of interleukin 6 in sera, skeletal muscle, and tibiae, which could be attenuated by GYY4137 treatment. Our study showed that GYY4137 preserved bone structure in rats exposed to HLS and promoted osteoblastic differentiation in MC3T3-E1 cells under modeled microgravity.

Antimetastatic Potential of Garcinone E in Human Oral Cancer Cells

Objective: Oral cancer presents as a devastating type of malignancy. It is predominant in populations with high use of alcohol and various forms of tobacco as well as poor diets with low intake of fruits and vegetables. The present study focused on the potential of Garcinone E to inhibit HSC-4 oral cancer cell proliferation, migration and invasion. Methods: MTT and colony forming assays were performed to study antiproliferative effects of Garcinone E. Hoechst staining was used to determine levels of apoptosis, with cell invasion and scratch assays conducted for migration and invasion characteristics. The levels of MMPs and cytokines were quantified in Garcinone E treated cells by ELISA. Results: Garcinone E inhibited the proliferation and colony forming potential of HSC-4 cells. It also suppressed migration and invasion with inhibition of MMP-2 and MMP-9 expression. Moreover, it elevated IL-2 and reduced IL-6 expression in HSC-4 cells. Conclusion: Our results demonstrate for the first time that Garcinone E might inhibit metastasis of an oral cancer cell line by blocking invasion, migration and MMP production.