Effect of quercetin and role of nitric oxide pathway in chloroquine-induced scratching

Nitric oxide (NO) is an abundant mediator which is demonstrated to be involved in pruritus. Assuming that the increased NO also mediates chloroquine-induced pruritus, which is a frequent complication seen in the chronic chloroquine treatment, the current study aimed to investigate the effect of quercetin and the role of NO in chloroquine-induced pruritus in C57BL/6 mice. Model was created with subcutaneous chloroquine (400µg/site) injection to the nape of the mice. Effect of quercetin and role of NO were investigated with administration of quercetin, and co-administration with L-NAME, 7-NI and L-arginine before chloroquine injection. Locomotor activity was assessed by activity cage and number of the scratching bouts after chloroquine injection was recorded for 30 minutes. Our results show that quercetin significantly reduced scratching bouts at the doses of 10, 20, 40 and 80 mg/kg. Locomotor activity was decreased at the 40 and 80 mg/kg doses of quercetin. Additionally, decrease of the number of scratching bouts by quercetin prevented by L-arginine treatment, while L-NAME and 7-NI enhanced the anti-pruritic effect of sub-effective doses of quercetin. Therefore, our study demonstrated that acute injection of quercetin significantly diminished chloroquine-induced scratching behavior, and this effect is partly mediated by inhibition of neuronal nitric oxide synthase enzyme

The neuroprotective action of lenalidomide on rotenone model of Parkinson's Disease:Neurotrophic and supportive actions in the substantia nigra pars compacta

Lenalidomide is a centrally active thalidomide analog that has potent anti-inflammatory and antiangiogenic activities. Currently, it is primarily used in the treatment of multiple myeloma and myelodysplastic syndromes. However, recent studies have revealed in addition to neuroprotection and neuromodulation of lenalidomide. Because of this combination of inflammation and neuro-immunogenic properties, lenalidomide is considered as a high potential compound for the treatment of neurodegenerative diseases. Despite intensive research during the last decade, the role of neurotrophic elements in the effect of lenalidomide is still not well understood. Therefore, in the current study, the effects of lenalidomide on neurodegeneration were investigated in a rotenone model of Parkinson's disease (PD) rat model. The PD rat model was generated by rotenone injection into the substantia nigra pars compacta (SNpc). After validation of the PD model, the rats were treated with lenalidomide (100 mg/kg) for 28 days. Our data shows that lenalidomide alleviated rotenone-induced motor impairments and deficits in dopamine-related behaviors and resulted in increased levels of tumor necrosis factor-α and calcium-binding protein B in the SNpc. Moreover, chronic lenalidomide treatment resulted increase in transforming growth factor immunoreactivity and brain derived neurotrophic factor expression in the SNPc. In addition, chronic treatment mitigated tyrosine hydroxylase expression prevented the rotenone-induced decrease in dopamine levels, and consequently a decrease in caspase-3/9 immunoreactivity. This thus shows that chronic lenalidomide treatment improves neuronal survival. Together with our data demonstrate that lenalidomide, in addition to its anti-inflammatory and immunomodulatory actions, is also capable of increasing neurotrophic factors in the SNpc, thereby preventing rotenone-induced motor impairments

LİDER İLE ÖRGÜT DÜZEYİNDEKİ GÜVEN DUYGUSUNUN YENİLİKÇİ İŞ DAVRANIŞI ÜZERİNDEKİ ETKİSİ: DEĞİŞİME DİRENCİN ROLÜ

Bu çalışma ile örgüte güvenin ve lidere güvenin yenilikçi iş davranışlarının önemli öncülleri arasında olabileceği iddia edilmektedir. Yenilikçi iş davranışı, yeni fikirlerin veya davranışların üretilmesini, geliştirilmesini ve uygulanmasını içeren bir süreçtir. Ancak çalışanlar örgütlerde yeniliğe karşı direnebilirler. Bu nedenle bu çalışmada örgüte / lidere güven ile yenilikçi iş davranışı arasındaki ilişkide değişime karşı direncin aracı rolü incelenmiştir.Bu amaç doğrultusunda, İstanbul/Türkiye’de hizmet sektöründeki çeşitli firmalardan 229 çalışanın katılımıyla kesitsel bir araştırma yapılmıştır. Araştırmanın bulguları, örgüte güven ve lidere güvenin yenilikçi iş davranışı üzerinde önemli olumlu etkileri olduğunu göstermektedir (β = 0,465; t = 7,914; p =, 000 ve β = 0,503; t = 8,779; p =, 000). Böylece araştırmada önerildiği gibi hipotez 1 ve hipotez 2 desteklenmiştir. Ek olarak, değişime karşı direncin örgüte / lidere güven ile yenilikçi iş davranışı arasındaki ilişkide aracı rolü tespit edilmiştir (β = .056; LLCI = .0221; ULCI = .0990 ve β = .050; LLCI = .0190; ULCI = .0892; sırasıyla). Bu nedenle çalışmada önerilen hipotez 1a ve hipotez 2a desteklenmiştir

Material and design toolkit for drug delivery: state of the art, trends, and challenges

The nanomaterial and related toolkit have promising applications for improving human health and well-being. Nanobased drug delivery systems use nanoscale materials as carriers to deliver therapeutic agents in a targeted and controlled manner, and they have shown potential to address issues associated with conventional drug delivery systems. They offer benefits for treating various illnesses by encapsulating or conjugating biological agents, chemotherapeutic drugs, and immunotherapeutic agents. The potential applications of this technology are vast; however, significant challenges exist to overcome such as safety issues, toxicity, efficacy, and insufficient capacity. This article discusses the latest developments in drug delivery systems, including drug release mechanisms, material toolkits, related design molecules, and parameters. The concluding section examines the limitations and provides insights into future possibilities

Neuroprotective effects of sinapic acid involve the iron regulatory role on the rotenone-induced Parkinson’s disease model

In the last decades, ferroptosis and its relationship with Parkinson’s disease have gained significant attention. Compounds that affect ferroptosis and iron-dependent pathways in particular, have possible candidates for study in this context.Sinapic acid is an iron-chelator and high antioxidant bioactive phenolic acid. Its neuroprotective action, due to the antioxidant capacity, has been shown in several experimental models.However, the relationship between iron and antioxidant actions is still misunderstood and therefore, in the current study, we tried to investigate the effects of sinapic acid in rotenone-induced Parkinson’s disease with the aspect of ferroptosis and iron-dependent alterations.The Parkinson’s disease model was induced by a single dose intrastriatal and intrategmental rotenone (5µg/µl) injection.Sinapic acid (30mg/ kg) was orally administered during a 28-day period after the Parkinson’s disease model was validated.Our results demonstrated that sinapic acid treatment attenuated rotenone-induced increase of serum transferrin and iron levels.Furthermore, sinapic acid inhibited rotenone-induced heme oxygenase-1(HO-1) increase and decrease of glutathione peroxidase-4 (GPx-4) levels in brain tissue. Also, sinapic acid treatment decreased motor impairment, likely as a result of the ameliorative effects on the tyrosine hydroxylase immunoreactivity loss after the rotenone insult.Our study suggests that the iron regulatory role of sinapic acid possibly plays a role in the protective effect on rotenone-induced neuronal damage

Angina Pektoris Nedeniyle Acile Başvuran Hastaların Tanısında Scube1’in Değeri

Objective: The purpose of this study was to investigate the value of signal peptide-CUB-EGF domain-containing protein 1 (SCUBE1) in the diagnosis of angina pectoris in patients presenting to the emergency department. Material and Methods: This prospective research was planned as a cross-sectional, single-center clinical study. Patients presenting to the emergency department with angina pectoris symptoms over a period of five months from receipt of ethical committee approval were included. Patients presenting with ischemic chest pain were divided on the basis of etiology into stable angina pectoris (SAP), unstable angina pectoris (UAP), non-ST elevation myocardial infarction (NSTEMI), and ST segment elevation myocardial infarction (STEMI) groups. Clinical, laboratory and demographic characteristics were recorded. SCUBE1 levels from each group were compared with a healthy control group. Results: A total of 118 individuals were enrolled in the study, 78 patients meeting the inclusion criteria and 40 healthy controls. Patients’ mean age was 54.36 14.03 years, and 88.5% (n69) were male. Hypertension (59%) and smoking (62%) predominated over other risk factors. NSTEMI was the most common factor (46.1%) in patients enrolled due to ischemic chest pain. No statistically significant difference was determined between patients’ serum SCUBE1 levels at time of presentation and at 6 h and 12 h and the control group (p0.05). Conclusion: On the basis of our study findings, SCUBE1 is of no value in the diagnosis of ischemic chest pain etiologies.Amaç: Bu çalışmanın amacı göğüs ağrısı nedeniyle acil servise başvuran hastalarda Signal peptide-CUB-EGF Domain-containing Protein 1 (SCUBE 1)’in angina pektoris tanısındaki değerini araştırmaktır. Gereç ve Yöntemler: Bu çalışma prospektif, kesitsel, tek merkezli bir klinik çalışma olarak planlandı. Etik kurul onayının alınmasından itibaren toplam 5 ay süreyle acil servise iskemik göğüs ağrısı şikayetiyle başvuran hastalar dahil edildi. İskemik göğüs ağrısı ile başvuran hastalar etyolojilerine göre stabil angina pektoris (SAP), unstabil angina pektoris (UAP), ST elevasyonu olmayan myokard infarktüsü (NSTEMI), ST elevasyonlu myokard infarktüsü (STEMI) olmak üzere gruplara ayrıldı. Klinik, laboratuar ve demografik özellikleri kayıt altına alındı. Her bir gruptan ölçülen serum SCUBE 1 düzeyleri istatistiksel olarak analiz edilerek sağlıklı kontrol grubuyla karşılaştırılarak analiz edildi. Bulgular: Çalışmanın dahil etme kriterlerine uygunluk gösteren 78 hasta ile 40 sağlıklı kontrol olmak üzere toplam 118 kişi çalışmaya alındı. Hastaların yaş ortalaması 54.3614.03 olup %88.5’i (n69) tanesi erkekti. Hastaların risk faktörleri incelendiğinde HT(%59) ve sigara (%62) diğer risk faktörlerine göre daha ağırlıktaydı. İskemik göğüs ağrısı şikayetiyle çalışmaya dahil ettiğimiz hastalarda en sık etken NSTEMI olarak tespit edildi (%46.1). Hastaların başvuru anında, 6.saat ve 12. saat serum SCUBE-1 değerleri kontrol grubu ile karşılaştırıldığında istatiksel olarak anlamlı fark bulunmadı (p0.05). Sonuç: Çalışmamızın bulgularına göre SCUBE 1, iskemik göğüs ağrısı etiyolojilerinin tanısında değeri bulunmamaktadır

The effects of agomelatine in cisplatin-induced toxicity on the kidney and liver tissues: In vivo study

Nephrotoxicity and hepatotoxicity are frequently seen adverse effects during cisplatin chemotherapy. In this study, we investigated the effects of agomelatine on cisplatin-induced toxicity in the kidney and liver. Animals were administered with a single dose of cisplatin (7 mg/kg, i.p.) and treated with agomelatine (20 and 40 mg/kg, p.o) for seven days. Renal and hepatic functions were evaluated by measuring concentrations of creatinine, BUN, AST and ALT in the serum. Oxidative stress and protein peroxidation were assessed by measuring SOD, CAT, GSH and AOPP levels in both tissues. Serum PON-1 levels were also evaluated. Histopathological analysis was performed to determined structural changes in the kidney and liver. Agomelatine (20 mg/kg) treatment approximately halved cisplatin-related increase in serum creatinine, BUN, AST and ALT levels. Agomelatine (20 mg/kg) significantly prevented the cisplatin-induced excessive decrease in SOD, CAT, GSH in both tissues and serum PON-1 levels. Agomelatine (20 and 40 mg/kg) protected the structural integrity of the kidney against cisplatin-insult. Although agomelatine (40 mg/kg) protected the kidney and showed parallel results with 20 mg/kg biochemically, it failed to show the same liver tissue effects in both analyses. Although agomelatine protected against cisplatin-induced toxicity in the kidney and liver, care should be taken with higher doses for possible hepatotoxicity

The beneficial effect of salubrinal on neuroinflammation and neuronal loss in intranigral LPS-induced hemi-Parkinson disease model in rats

OBJECTIVE: Endoplasmic reticulum stress (ERS) and neuroinflammation are triggers for neurodegenerative disorders. Salubrinal is a selective inhibitor of protein phosphatase 1 (PP1) complex involving dephosphorylation of phosphorylated eukaryotic initiation factor-2α (eIF2α), the key crucial pathway in the ERS. Therefore, this study assessed the effects of inhibition of the ERS with salubrinal in the intranigral hemi-Parkinson disease (PD) model. MATERIALS AND METHODS: Animals were treated with salubrinal for one week after the PD model was created by intranigral lipopolysaccharide (LPS) administration. Apomorphine-induced rotation, rotarod, cylinder, and pole tests were performed to evaluate behavioral changes. Proinflammatory cytokines and the expression level of the dual specificity protein phosphatase 2 (DUSP2), PP1, and p-eIF2α were evaluated. Nigral expression of inducible nitric oxide synthase (iNOS), nuclear factor kappaB (Nf-κB), and cyclooxygenase (COX)-2 was determined. Finally, tyrosine hydroxylase and caspase-3/ caspase-9 expressions were assessed by immunohistochemistry. RESULTS: Salubrinal reduced the motor impairments and dopamine-related behavioral deficiencies caused by the LPS. Salubrinal attenuated the LPS-induced increased levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and salubrinal rescued the loss of TH expression and dopamine levels and prevented the caspase-3/9 increase in the substantial nigra (SN). LPS potently increased iNOS, Nf-κB, and COX-2 expression, but this effect was reduced after salubrinal treatment. Additionally, salubrinal attenuated the LPS-induced PP1 and DUSP2 increase. CONCLUSION: Our results reveal that salubrinal is attenuating several inflammatory mediators and thereby decreased the inflammatory effects of LPS in the neurons of the SN. Together this results in increased cellular survival and maintained integrity of SN. Taken together our data show the beneficial effects of inhibition of ERS to restrict neuroinflammatory progression and neuronal loss in a PD model