Demodex folliculorum (Trombidiformes: Demodecidae) infestation in medical students with facial dermatoses and healthy groups.

Demodex folliculorum (Simon, 1842) has been associated with various dermatological conditions. This study aimed to assess the prevalence of Demodex infestation in medical students with facial dermatoses compared with healthy medical students serving as controls. A total of 250 participants were enrolled, including 150 individuals with facial dermatoses and 100 healthy controls. Sampling was performed based on the standardized skin surface biopsy method. Demographic characteristics, specifically gender and age, were not statistically different between the patient and control groups. Among the facial dermatosis patients, 25 out of 150 (16.6%) were found to have Demodex infestation, while only three out of the 100 healthy controls (3%) exhibited infestations. The only identified species was D. folliculorum. The rates of Demodex infestation were significantly higher in the patients compared to the control groups. These findings indicate a higher prevalence of Demodex infestation among medical students with facial dermatosis, particularly in those diagnosed with folliculitis, acne vulgaris, and inflammatory papule, when compared to healthy controls. A better understanding of the relationship between D. folliculorum infestation and these dermatological conditions may lead to improved diagnostic and treatment strategies in the future.

Comparison of the differentiation of ovine fetal bone-marrow mesenchymal stem cells towards osteocytes on chitosan/alginate/CuO-NPs and chitosan/alginate/FeO-NPs scaffolds.

In the current study, the creation of a chitosan/alginate scaffold hydrogel with and without FeO-NPs or CuO-NPs was studied. From fetal ovine bone marrow mesenchymal stem cells (BM-MSCs) were isolated and cultivated. Their differentiation into osteocyte and adipose cells was investigated. Also, on the scaffolds, cytotoxicity and apoptosis were studied. To investigate the differentiation, treatment groups include: (1) BM-MSCs were plated in DMEM culture medium with high glucose containing 10% FBS and antibiotics (negative control); (2) BM-MSCs were plated in osteogenic differentiation medium (positive control); (3) positive control group + FeO-NPs, (4) positive control group + CuO-NPs; (5) BM-MSCs were plated in osteogenic differentiation medium on chitosan/alginate scaffold; (6) BM-MSCs were plated in osteogenic differentiation medium on chitosan/alginate/FeO-NPs scaffold; and (7) BM-MSCs were plated in osteogenic differentiation medium on chitosan/alginate/CuO-NPs scaffold. Alkaline phosphatase enzyme concentrations, mineralization rate using a calcium kit, and mineralization measurement by alizarin staining quantification were evaluated after 21 days of culture. In addition, qRT-PCR was used to assess the expression of the ALP, ColA, and Runx2 genes. When compared to other treatment groups, the addition of CuO-NPs in the chitosan/alginate hydrogel significantly increased the expression of the ColA and Runx2 genes (p < 0.05). However, there was no significant difference between the chitosan/alginate hydrogel groups containing FeO-NPs and CuO-NPs in the expression of the ALP gene. It appears that the addition of nanoparticles, in particular CuO-NPs, has made the chitosan/alginate scaffold more effective in supporting osteocyte differentiation.

Chitosan/alginate scaffold enhanced with Berberis vulgaris extract for osteocyte differentiation of ovine fetal stem cells.

Designing biocompatible polymers using plant derivatives can be extremely useful in tissue engineering, nanomedicine, and many other fields of medicine. In this study, it was first looked into how chitosan/alginate scaffolds were made and characterized in the presence of berberine and barberry fruit extract. Second, the process of proliferation and differentiation of ovine fetal BM-MSCs (bone marrow-mesenchymal stem cells) was assessed on these scaffolds after BM-MSCs were extracted and confirmed by developing into osteocyte and adipose cells. To investigate the differentiation, treatment groups include (1) ovine fetal BM-MSCs were plated in Dulbecco's modified eagle medium culture medium with high glucose containing 10% fetal bovine serum and antibiotics (negative control), (2) ovine fetal BM-MSCs were plated in osteogenic differentiation medium (positive control group), (3) positive control group + barberry fruit extract, (4) positive control group + berberine, (5) ovine fetal BM-MSCs were plated in osteogenic differentiation medium on chitosan/alginate scaffold (hydrogel group), (6) ovine fetal BM-MSCs were plated in osteogenic differentiation medium on chitosan/alginate/barberry fruit extract scaffold (hydrogel group containing barberry fruit extract), and (7) ovine fetal BM-MSCs were plated in osteogenic differentiation medium on chitosan/alginate/berberine scaffold (hydrogel group containing berberine). Alkaline phosphatase (ALP) enzyme concentrations, mineralization rate using a calcium kit, and mineralization measurement by alizarin staining quantification were all found after 21 days of culture. In addition, real-time quantitative reverse transcription polymerase chain reaction was used to assess the expression of the ALP, COL1A2, and Runx2 genes. Days 5 and 7 had the lowest water absorption by the hydrogel scaffold containing barberry extract, which was significant in comparison to other groups (p < .05). Among the hydrogel scaffolds under study, the one containing barberry extract exhibited the lowest tensile strength, and this difference was statistically significant (p < .05). The chitosan/alginate hydrogel has the highest tensile strength of all of them. In comparison to the control and other treatment groups, the inclusion of berberine in the chitosan/alginate hydrogel significantly increased the expression of the ALP, Runx2, and COL1A2 genes (p < .05). The osteocyte differentiation of mesenchymal stem cells in in vitro settings appears to have been enhanced by the inclusion of berberine in the chitosan/alginate scaffold.

Reoperation etiologies in the initial hospital stay after liver transplantation: a single-center study from Iran.

Background: Liver transplantation (LT) is widely recognized as a life-saving therapy for patients with end-stage liver disease. However, due to certain posttransplant complications, reoperations or endovascular interventions may be necessary to improve patient outcomes. This study was conducted to examine reasons for reoperation during the initial hospital stay following LT and to identify its predictive factors. Methods: We evaluated the incidence and etiology of reoperation in 133 patients who underwent LT from brain-dead donors over a 9-year period based on our experiences. Results: A total of 52 reoperations were performed for 29 patients, with 17 patients requiring one reoperation, seven requiring two, three requiring three, one requiring four, and one requiring eight. Four patients underwent liver retransplantation. The most common cause of reoperation was intra-abdominal bleeding. Hypofibrinogenemia was identified as the sole predisposing factor for bleeding. Frequencies of comorbidities such as diabetes mellitus and hypertension did not differ significantly between groups. Among patients who underwent reoperation due to bleeding, the mean plasma fibrinogen level was 180.33±68.21 mg/dL, while among reoperated patients without bleeding, it was 240.62±105.14 mg/dL (P=0.045; standard mean difference, 0.61; 95% confidence interval, 0.19-1.03). The initial hospital stay was significantly longer for the reoperated group (47.5±15.5 days) than for the non-reoperated group (22.5±5.5 days). Conclusions: Meticulous pretransplant assessment and postoperative care are essential for the early identification of predisposing factors and posttransplant complications. In order to enhance graft and patient outcomes, any complications should be addressed without hesitation, and appropriate intervention or surgery should not be delayed.

The Effect of 40-Hz White LED Therapy on Structure-Function of Brain Mitochondrial ATP-Sensitive Ca-Activated Large-Conductance Potassium Channel in Amyloid Beta Toxicity.

Photobiomodulation therapy has become the focus of medical research in many areas such as Alzheimer's disease (AD), because of its modulatory effect on cellular processes through light energy absorption via photoreceptors/chromophores located in the mitochondria. However, there are still many questions around the underlying mechanisms. This study was carried out to unravel whether the function-structure of ATP-sensitive mitoBKCa channels, as crucial components for maintenance of mitochondrial homeostasis, can be altered subsequent to light therapy in AD. Induction of Aß neurotoxicity in male Wistar rats was done by intracerebroventricular injection of Aß1-42. After a week, light-treated rats were exposed to 40-Hz white light LEDs, 15 min for 7 days. Electrophysiological properties of mitoBKCa channel were investigated using a channel incorporated into the bilayer lipid membrane, and mitoBKCa-ß2 subunit expression was determined using western blot analysis in Aß-induced toxicity and light-treated rats. Our results describe that conductance and open probability (Po) of mitoBKCa channel decreased significantly and was accompanied by a Po curve rightward shift in mitochondrial preparation in Aß-induced toxicity rats. We also showed a significant reduction in expression of mitoBKCa-ß2 subunit, which is partly responsible for a leftward shift in BKCa Po curve in low calcium status. Interestingly, we provided evidence of a significant improvement in channel conductance and Po after light therapy. We also found that light therapy improved mitoBKCa-ß2 subunit expression, increasing it close to saline group. The current study explains a light therapy improvement in brain mitoBKCa channel function in the Aß-induced neurotoxicity rat model, an effect that can be linked to increased expression of ß2 subunit.

Targeting EGFR Tyrosine Kinase: Design, Synthesis and Biological Evaluation of Novel Quinazolinone Derivatives.

Impaired cell cycle regulation and disturbance in signal transduction pathway are two major causes of a condition defined as cancer, one of the significant reasons for mortality worldwide. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been commonly used as anticancer agents, and the majority of this medications possess quinazoline moiety as a heteroaromatic core. In this study, two novel series of EGFR-TKIs containing quinazolinone core were designed and synthesized. Most compounds showed reasonable inhibitory activity against EGFR-TK compared to that of erlotinib, a reversible inhibitor of this enzyme. Compound 8b, 2-((2-chlorobenzyl)amino)-6-phenoxyquinazolin-4(1H)-one, with an IC50 value of 1.37 nM exhibited the highest potency. Molecular docking study of compound 8b showed that it had the same direction of erlotinib and formed proper hydrogen bonds and hydrophobic interactions with the important amino acid residues of the active site. Based on in-silico calculations of ADME properties, our novel compounds have the potential to be orally active agents.

The 40-Hz White Light-Emitting Diode (LED) Improves the Structure-Function of the Brain Mitochondrial KATP Channel and Respiratory Chain Activities in Amyloid Beta Toxicity.

It has been described that using noninvasive exposure to 40-Hz white light LED reduces amyloid-beta, a peptide thought to initiate neurotoxic events in Alzheimer's disease (AD). However, the mechanisms remain to be identified. Since AD impairs mitochondrial potassium channels and respiratory chain activity, the objectives of the current study were to determine the effect of 40-Hz white light LED on structure-function of mitoKATP channel and brain mitochondrial respiratory chain activity, production of reactive oxygen species (ROS), and ΔΨm in AD. Single mitoKATP channel was considered using a channel incorporated into the bilayer lipid membrane and expression of mitoKATP-Kir6.1 subunit as a pore-forming subunit of the channel was determined using a western blot analysis in Aß1-42 toxicity and light-treated rats. Our results indicated a severe decrease in mito-KATP channel permeation and Kir6.1 subunit expression coming from the Aß1-42-induced neurotoxicity. Furthermore, we found that Aß1-42-induced neurotoxicity decreased activities of complexes I and IV and increased ROS production and ΔΨm. Surprisingly, light therapy increased channel permeation and mitoKATP-Kir6.1 subunit expression. Noninvasive 40-Hz white light LED treatment also increased activities of complexes I and IV and decreased ROS production and ΔΨm up to ~ 70%. Here, we report that brain mito-KATP channel and respiratory chain are, at least in part, novel targets of 40-Hz white light LED therapy in AD.

A novel sensitive laccase biosensor using gold nanoparticles and poly L-arginine to detect catechol in natural water.

In this study, the simple, green, and fast layer-by-layer modification of the glassy carbon electrode was mainly performed by electrodeposition of gold nanoparticles and then, poly-l-arginine, and finally, laccase was covalently bonded to poly-l-arginine using glutaraldehyde. This type of fabrication is used for the first time for catechol detection, which provides a bioelectrocatalytic cycle for electron transport in the presence of laccase that results in sensitive and fast detection of catechol. The scanning electron microscopy, Fourier-transform infrared spectroscopy, and electrochemical studies were performed to confirm successful immobilization of the enzyme. The biosensor response was linear in a wide range of catechol trace concentrations, 24.90-274.00 nM, with the detection limit of 18.00 nM. Values of Km , α, n, and Ks for the immobilized enzyme were calculated to be 1.25 × 10-2  µM, 0.56, 3.19, and 0.28 Sec-1 , respectively. It was examined in real sample successfully confirming it is capable of measuring catechol in natural water.

Hesperidin inhibits insulin-induced phosphoinositide 3-kinase/Akt activation in human pre-B cell line NALM-6.

CONTEXT: It has been shown that hesperidin induces apoptosis in NALM-6 cells through inhibition of nuclear factor-kappa B (NF-κB) activation. AIMS: To investigate the effect of hesperidin on inhibition of NF-κB activation through blocking phosphoinositide 3-kinase (PI3K)/Akt pathway as a main target in cancer treatment, in NALM-6 cells. MATERIALS AND METHODS: NALM-6 cells were incubated with two concentrations of hesperidin (25, 50 µM) in the presence or absence of insulin (100 nM), as a potent activator of Akt. The cytotoxic activity of hesperidin was determined by 3-(4,5-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptotic death was measured by ELISA test using cell death detection ELISA Plus kit. To assay the effect of hesperidin on Akt pathway, the phosphorylation levels of Akt, inhibitor of kappa B alpha (IκBα), and glycogen synthase kinase-3 beta (GSK-3ß) and expression level of IκB kinase alpha (IKKα) were determined by Western blot analysis. RESULTS: Hesperidin (both concentrations) significantly reduced cells survival in the presence and absence of insulin compared to untreated cells in a time-dependent manner (P < 0.05). Hesperidin also significantly increased apoptosis in NALM-6 cells even in hyperinsulinemia condition (P < 0.0001). Hesperidin inhibited insulin-induced phosphorylation and activation of Akt, IκBα, and GSK-3ß and decreased expression of IKKα. CONCLUSION: The results of this study demonstrated that cytotoxic and proapoptotic actions of hesperidin are partly mediated through the suppression of PI3K3/Akt/IKK signaling pathway. So, hesperidin might act as a chemotherapeutic agent by targeting cell survival pathways.

Is the pattern of dietary amino acids intake associated with serum lipid profile and blood pressure among individuals with spinal cord injury?

OBJECTIVE: The probable effect of dietary amino acids intake pattern on serum lipid profile and blood pressure (BP) have not yet been described among individuals with spinal cord injury (SCI). DESIGN: Cross-sectional. SETTING: Tertiary rehabilitation center. PARTICIPANTS: People with SCI referred to Brain and Spinal Cord Injury Research Center between 2011 and 2014. OUTCOME MEASURES: Dietary intakes were assessed by recording consumed foods by 24-hour dietary recall interviews using Nutritionist IV 3.5.3 modified for Iranian foods. Partial correlation test with adjustment for age, weight, body mass index, total energy intake, total fat, cholesterol and carbohydrate intake, and injury-related variables was used. RESULTS: Dietary intake of lysine was positively related to levels of fasting plasma glucose (FPG), triglyceride (TG), systolic blood pressure (SBP) and diastolic blood pressure (DBP) (P < 0.0001, 0.046, 0.002 and 0.009, respectively). There was a positive significant relationship between the intake of cysteine and levels of TG and SBP as well (P : 0.027 and 0.048, respectively). Higher intakes of threonine and leucine had a negative relationship with TG level (P : 0.001 and 0.026, respectively). Furthermore, tyrosine, threonine and leucine were inversely correlated to blood pressure. Total cholesterol level was only related to intake of threonine and leucine (P : 0.004 and 0.012, respectively). FPG was positively associated with intake of all amino acids except for cysteine, glutamic acid, threonine, leucine and histidine. CONCLUSION: In the present study, the pattern of relationships between dietary intake of amino acids and serum lipid profile and BP has been described among people with SCI.

Fingolimod (FTY720) improves hippocampal synaptic plasticity and memory deficit in rats following focal cerebral ischemia.

Fingolimod (FTY720) is a known sphingosine-1-phosphate (S1P) receptor agonist. Several studies have shown the therapeutic efficacy of FTY720 in neurodegenerative disorders. However, the neuroprotective mechanisms in brain ischemia have not been adequately studied. Therefore, the present study aimed to investigate the effects of FTY720 on the impairment of learning and memory and hippocampal synaptic plasticity induced by middle cerebral artery occlusion (MCAO) in ischemic brain injury. Twenty eight male rats were randomly divided into four groups of control (n=7), sham (n=8), ischemic-reperfusion+vehicle (I/R+V; n=7), and I/R+FTY720 (n=6). After 1h of the occlusion of artery, the filament was gently withdrawn to allow reperfusion for the next 7 days. The animals first received a dose of FTY720 (0.5mg/Kg) or its vehicle (intra-peritoneal) twenty-four hours before surgery in I/R+FTY720 and I/R+V groups, respectively. The administration of FTY720 or its vehicle continued every other day. The passive avoidance test and field potential recording were used for evaluation of learning, memory and synaptic plasticity. The brain infarct volume was measured by triphenyltetrazolim hydrochloride (TTC) staining. MCAO caused infarct damage in the rat's brain tissue. The administration of FTY720 significantly reduced the size of the lesion, improved the memory impairment of MCAO rats, and increased the STL time. In addition, the field potential recording demonstrated a marked reduction in induction of long-term potentiation of MCAO animals. However, administration of FTY720 recovers the magnitude of the LTP without any effects on presynaptic plasticity and neurotransmitter release probability. The results of this study demonstrated that MCAO in rats impairs the retention of passive avoidance tasks and multiple injection of FTY720 improved the memory performance after MCAO by LTP induction via post-synaptic mechanisms.

The Relationship Between Dietary Intakes of Amino Acids and Bone Mineral Density Among Individuals with Spinal Cord Injury.

OBJECTIVES: The effect of dietary protein intake on bone mineral density (BMD) has not been explained in patients with spinal cord injury (SCI). In this study, we looked at the relationship between BMD and higher protein intake in patients with SCI while controlling for possible confounders. METHODS: Patients with SCI, who were referred to the Brain and Spinal Cord Injury Research Center between November 2010 and April 2012, were included in the study. In total, the dietary intakes of 103 patients were assessed by 24-hour dietary recall interviews. We used dual-energy X-ray absorptiometry to measure BMD in the femoral neck, trochanter, intertrochanteric zone, hip, and lumbar vertebras. RESULTS: Eighty-six men and 17 women participated in this study. Protein intake was negatively associated with the BMD of lumbar vertebrae (p = 0.001, r = -0.37 for T-score and p = 0.030, r = -0.24 for Z-score). The BMD of lumbar vertebrae were negatively associated with intake of tryptophan, isoleucine, lysine, cysteine, and tyrosine (p = 0.007, 0.005, 0.009, 0.008, and 0.008 for T-score, respectively). Higher intakes of threonine, leucine, methionine, phenylalanine, valine, and histidine were related to a lower BMD of lumbar vertebrae (p = 0.006, 0.010, 0.009, 0.010, 0.009, and 0.008 respectively for T-scores). CONCLUSIONS: We found that high protein intake led to a lower BMD of lumbar vertebrae in patients with SCI after controlling for confounders including demographic and injury-related characteristics and calcium intake. No relationship between higher amino acids intake and BMD of the femur and hip was detected. Intake of alanine, arginine, and aspartic acid were not related to BMD.

Peripapillary retinal nerve fiber layer thickness in bipolar disorder.

BACKGROUND: To compare peripapillary retinal nerve fiber layer thickness (RNFLT) between patients with bipolar disorder and a control group by optical coherence tomography (OCT). METHODS: This prospective comparative case series included 60 eyes of 30 patients with bipolar disorder and 60 eyes of 30 age-matched healthy control subjects. Using OCT, peripapillary RNFLT of the 4 quadrants and the mean of them was compared between the two groups. Variables such as age of onset, duration, smoking, psychosis, mania and depression episodes in the case group and their relationships with RNFLT were evaluated by OCT. RESULTS: Mean RNFLT was 99 ± 8 in the case group, significantly less than the 106 ± 8 mµ in the control group (p = 0.001). The inferior, superior, and nasal quadrants in the case and control groups showed significant difference in RNFLT (p < 0.001) (p = 0.040) (p = 0.005); however, the temporal quadrant was not reduced significantly, compared to the control value (p = 0.907). Moreover, the only variable showing significant relation with RNFLT was duration of bipolar disorder (p = 0.040). CONCLUSION: Reduction of peripapilary RNFLT occurs in patients with bipolar disorder, and is related to the duration of disease. RNFLT can be a beneficial value for studying neurodegenerative changes over time towards detecting the severity and duration of disorder.

Risk factors for increased multiple sclerosis susceptibility in the Iranian population.

Multiple sclerosis (MS) is a complex autoimmune disease with increasing prevalence. Many factors have been assessed in relation to its development and its worldwide geographical and racial distribution. Therefore, we decided to conduct a nationwide case-control matched study to estimate the possible influence of putative risk factors on MS status in an Iranian MS population. Between January 2008 and September 2013, 1403 patients diagnosed with MS according to the Poser or McDonald criteria and 883 controls were studied. Of all patients, there were 921 women and 296 men (ratio 3.1:1) with a mean age of 32.6 ± 8.7 years. In the multivariate model adjusted for sex and age (±2years), we found associated risk factors of MS to be: history of any allergic condition (Odds ratio (OR): 1.92, 95% Confidence interval (CI): 1.55-2.47, p<0.001), and smoking (OR: 1.93, 95% CI: 1.31-2.73, p<0.001). Sunlight exposure ⩾ 3 hours was found to be associated with a reduced risk of MS (OR: 0.23, 95% CI: 0.15-0.31, p<0.001). As expected, cases were more likely to have a positive family history of MS than controls (OR: 1.91, 95% CI: 1.33-2.75, p<0.001). A significant association was found between family history of other autoimmune diseases and MS risk (OR: 1.57, 95% CI: 1.18-2.09, p=0.002). These results support the hypothesis that sun exposure is associated with a decreased risk of MS while smoking, autoimmune family history, MS family history, and personal allergy history are risk factors for MS susceptibility.

Mortality and functional disability after spontaneous intracranial hemorrhage: the predictive impact of overall admission factors.

To determine the effects of different prognostic factors, including previous antiplatelet therapy, admission data, and radiographic findings on discharge and 3-month neurological condition using modified Rankin scale (mRS) and mortality at 30 days and 3-month follow-up in patients presenting to the emergency department with spontaneous intracranial hemorrhage (sICH). Between January and July 2012, 120 consecutive patients (males 62%, females 38%), who were admitted within 48 h of symptoms onset, were included. We recorded the following data on admission: demographics; functional scores of ICH, Glasgow Coma Scale, and National Institutes of Health Stroke Scale; vital signs; smoking status; use of illicit drug; preadmission antiplatelet treatment; results of laboratory tests (platelet count, serum glucose, sodium and creatinine levels, and prothrombin time); and primary neuroimaging findings [intraventricular hemorrhage (IVH), midline shift, and hydrocephalus]. In multivariate analysis using adjusted model for demographics and prior antiplatelet therapy; functional scores, laboratory results, and diabetes history correlated with mortality during 30 days after the event. Moreover, the parameters on the initial computed tomography scan significantly increased 30-day fatality rate and was correlated with increase in the discharge mRS score of survivors. The odds ratio (OR) and 95% confidence interval (CI) of early mortality associated with IVH presentation was 2.34 (CI 1.76-3.02, p = 0.003). The corresponding ORs in those with midline shift displacement and hydrocephalus were 2.18 (95% CI 2.08-3.80, p = 0.01) and 1.62 (95% CI 1.01-2.63, p = 0.02), respectively. In patients with ICH, prognostic factors, include various clinical parameters and paraclinical findings of admission time.

The citrus flavonoid hesperidin induces p53 and inhibits NF-κB activation in order to trigger apoptosis in NALM-6 cells: involvement of PPARγ-dependent mechanism.

BACKGROUND: Hesperidin, a flavanone present in citrus fruits, has been identified as a potent anticancer agent because of its proapoptotic and antiproliferative characteristics in some tumor cells. However, the precise mechanisms of action are not entirely understood. AIM: The main purpose of this study is to investigate the involvement of peroxisome proliferator-activated receptor-gamma (PPARγ) in hesperidin's anticancer actions in human pre-B NALM-6 cells, which expresses wild-type p53. METHODS: The effects of hesperidin on cell-cycle distribution, proliferation, and caspase-mediated apoptosis were examined in NALM-6 cells in the presence or absence of GW9662. The expression of peroxisome proliferator-activated receptor-gamma (PPARγ), p53, phospho-IκB, Bcl-2, Bax, and XIAP proteins were focused on using the immunoblotting assay. The transcriptional activities of PPARγ and nuclear factor-kappaB (NF-κB) were analyzed by the transcription factor assay kits. The expression of PPARγ and p53 was analyzed using the RT-PCR method. RESULTS: Hesperidin induced the expression and transcriptional activity of PPARγ and promoted p53 accumulation and downregulated constitutive NF-κB activity in a PPARγ-dependent and PPARγ-independent manner. The growth-inhibitory effect of hesperidin was partially reduced when the cells preincubated with PPARγ antagonist prior to the exposure to hesperidin. CONCLUSIONS: The findings of this study clearly demonstrate that hesperidin-mediated proapoptotic and antiproliferative actions are regulated via both PPARγ-dependent and PPARγ-independent pathways in NALM-6 cells. These data provide the first evidence that hesperidin could be developed as an agent against hematopoietic malignancies.

Inactivation of nuclear factor-κB by citrus flavanone hesperidin contributes to apoptosis and chemo-sensitizing effect in Ramos cells.

Hesperidin, a flavonoid present in fruits and vegetables, possesses anti-inflammatory and chemopreventive effects. Some evidence implies that hesperidin may recruit Peroxisome Proliferator-Activated Receptor-gamma (PPARγ) to exert biological action. It has been shown also that inactivation of Nuclear Factor-kappaB is another mechanism of flavonoids' action. Therefore, we wished to investigate the role of these transcription factors in apoptosis induced by hesperidin in Ramos Burkitt's lymphoma cells. We found that incubation of Ramos cells with hesperidin abrogates constitutive and doxorubicin-induced NF-κB activation through inhibition of phosphorylation of its inhibitory subunits (IκB). Moreover, our results showed that incubation of Ramos cells with hesperidin resulted in inhibition of proliferation and apoptosis in a PPARγ-independent way. Our results demonstrated that hesperidin inhibits proliferation of Ramos cells and sensitizes them to doxorubicin-induced apoptosis through inhibition of both constitutive and doxorubicin-mediated NF-κB activation in a PPARγ-independent manner.