Investigation of the Ameliorating Effect of Copper Albumin Complex on Lysyl oxidase in monosodium iodoacetate -Induced Knee Osteoarthritis in Rats

Knee osteoarthritis (KOA) is a common type of joint degeneration which causes progressive damage of the joint structure and has less therapeutic options. It has been found that oral consumption of Copper Albumin Complex as anti-inflammatory drug has a positive effect on the treatment of joint deterioration. The present study aimed to investigate the effect of oral administration of Copper Albumin Complex (cu-albumin complex) on Lysyl oxidase (LOX) which acts as a protective factor in KOA. Fifty adult albino rats were divided into 3 groups: negative control (10 normal rats); positive control (20 rats with KOA which left without induction treatment); and treated group (20 rats with KOA which treated with administration of copper albumin complex). Treated and untreated arthritic groups were subdivided equally into mild and severe groups (10 rats for each) according to the severity of clinical signs. KOA was induced by intra-articular injection of monosodium iodoacetate (MIA). At the experimental end, the joints were examined histopathologically and immunohistochemically after cervical dislocation of rats. It was observed that the treatment with CU- was effective in reducing disease severity and in improvement of Lysyl oxidase KOA. It was concluded that Copper albumin complex has a positive effect in the improvement of LOX of Knee joint cartilages of rats affected by osteoarthritis (OA)

In Vivo Investigation of the Ameliorating Effect of Copper Albumin Complex on chondroitin sulfate in Monosodium iodoacetate -Induced Knee Osteoarthritis

Osteoarthritis (OA) is a condition that manifests as cartilage deterioration and subchondral bone sclerosis in the joint tissues. The weight-bearing joint is most severely impacted by OA. According to some research, consuming foods high in copper albumin complex (cu-albumin complex) can help with OA-related joint degeneration and pain relief. The current study's objective to determine how oral administration of the cu-albumin complex as an anti-inflammatory medication affected the development of rat knee osteoarthritis (KOA). Fifty adult albino rats were divided into three groups: negative control untreated (n= 10, no KOA induction); positive untreated control (n= 20, KOA induction); and treated group (n= 20, KOA induction with administration of cu-albumin complex). According to the severity of the clinical symptoms, treated and untreated arthritic groups were equally divided into mild and severe groups (n=10). Monosodium iodoacetate (MIA) was used as intra-articular injection for osteoarthritis induction. Rats were euthanized after a month of the beginning of the experiment, and the joints were examined histopathologically and immunohistochemically. It was indicated that the treatment was effective in reducing KOA severity and in improvement of chondroitin sulfate of the affected cartilages. In conclusion, the structure of the chondroitin sulphate in the knee joint cartilages of KOA-affected rats was modified by the cu-albumin complex

The relation between Parkinson’s disease and non-steroidal anti-inflammatories; a systematic review and meta-analysis

Background: Parkinson’s disease (PD) is a neurological condition that typically shows up with aging. It is characterized by generalized slowness of movement, resting tremor or stiffness, and bradykinesia. PD patients’ brains mostly exhibit an increase in inflammatory mediators and microglial response. Nevertheless, a variety of non-steroidal anti-inflammatory medications (NSAIDS) offered neuroprotection in animal models and preclinical trials.Aim: The current systematic review and meta-analysis were designed to try to resolve the debate over the association of NSAID use with the development of PD because the results of several studies were somehow contradictory.Methods: An intense search was performed on Scopus, PubMed, and Web of Science databases for articles relating the incidence of PD to the use of NSAIDs. Statistical analysis of the included studies was carried out using Review Manager version 5.4.1 by random effect model. The outcome was identified as the development of PD in patients who were on NSAIDs, ibuprofen only, aspirin only, and non-aspirin NSAIDs. This was analyzed using pooled analysis of odds ratio (OR) at a significance level of ≤0.05 and a confidence level of 95%. A statistically significant decreased risk of PD was observed in patients taking NSAIDs, Ibuprofen, and non-aspirin NSAIDs.Results: The ORs of PD occurrence in patients who took NSAIDs, Ibuprofen, and non-aspirin NSAIDs were 0.88 [95% CI (0.8–0.97), p = 0.01], 0.73 [95% CI (0.53–1), p = 0.05] and 0.85 [95% CI (0.75–0.97), p = 0.01]. Meanwhile, the risk of PD in patients who took aspirin was not statistically significant.Conclusion: In conclusion, Ibuprofen, non-aspirin NSAIDs, and other types of NSAIDs could be associated with a reduction in PD risk. However, there was no association between aspirin intake and the development of PD

Chlamydia species in free-living Cattle Egret (Bubulcus ibis) and Hoopoe (Upupa epops) in Egypt

Little information is available on the presence of chlamydia infection in wildlife. This study was conducted to assess the occurrence of chlamydiae in asymptomatic birds from two species of wild birds (Cattle Egret and Hoopoe) in Egypt. In the present study Chlamydiaceae was analyzed using Giemsa stain, Giménez stain, fluorescent antibody test (FAT) and PCR. The results of these techniques were compared with CFT for detecting Chlamydia psittaci antibodies among the examined birds. The results reveal that 96.4%, 81.8%, 89.1%, 80.0% and 58.2% of the examined samples were positive for chlamydiosis using PCR, Giemsa stain, Giménez stain, FA, and CFT respectively among Hoopoe. The percentages were 90.6%, 77.4%, 83.0%, 75.5% and 66.0% respectively for the previous tests among Cattle Egret birds. The results suggest that Cattle Egret and Hoopoe may be reservoir of Chlamydiaceae species and thus shed the organisms in their excreta. The shedding of chlamydiae by free living birds in Egypt may expose humans that come in contact with these birds to zoonotic risks

Novel VEGFR2 inhibitors with thiazoloquinoxaline scaffold targeting hepatocellular carcinoma with lower cardiotoxic impact

Abstract Hepatocellular carcinoma (HCC) is a fatal tumor which is usually diagnosed at advanced stage. Molecular targeted drugs were used recently to treat HCC, however, due to serious side effects, mainly cardiotoxicity and emergence of resistance, there is demanding to explore new chemotherapeutics. 10 novel thiazoloquinoxaline derivatives coupled with different sulfonamide moieties 4(a–j) were designed and synthesized fulfilling pharmacophoric features of VEGFR-2 inhibition. Structures of all new compounds were verified via spectral and microanalytical data. After carrying in-vitro VEGFR-2 assay for compounds 4(a–j); sulfapyridine and sulfamethoxazole derivatives 4d and 4f showed potential inhibitory effect [61.04 and 83.35 nM], respectively, comparable to standard sorafenib [51.41 nM]. Both were then further evaluated for their cytocidal activity against HepG2 cell-line and against myocardium cells using H9C2 cell-line. As a result, only sulfapyridine derivative 4d exhibited a significant inhibition of HepG2 cells viability [IC50 = 4.31 μM]. Furthermore, it showed relatively lower cytotoxic impact against normal H9C2 myocardium cells [IC50, 33.47 μM] compared to that of sorafenib [IC50, 98.07 μM]. In-vivo study was carried out to determine myocardium safety of compound 4d on irradiated mice (8 Gy). In-vivo results of sulfapyridine derivative 4d showed normal cardiac enzyme function (CK) and serum catalase activity with significant reductions in LDH, cardiac TNF-α and caspase-9 levels, alongside with its efficacy in suppressing the expression of hepatic VEGF. In conclusion, sulfapyridine derivative 4d could be considered a promising candidate as VEGFR-2 inhibitor with less myocardium side effect

Comparative Protective Effects of N-Acetylcysteine, N-Acetyl Methionine, and N-Acetyl Glucosamine against Paracetamol and Phenacetin Therapeutic Doses–Induced Hepatotoxicity in Rats

Background and Aims. Both paracetamol (PA) and phenacetin (PH) are analgesic and antipyretic agents. Part of phenacetin therapeutic activity is attributed to its metabolism into paracetamol. Paracetamol causes direct hepatic oxidative stress damage. The present study aimed to investigate the possible damaging effects of both PA and PH, when used in therapeutic doses, on rat liver and to compare the antioxidant and hepatoprotective effects of N-acetylcysteine (NAC), N-acetyl-methionine (NAM), and N-acetylglucosamine (NAG) against PA- or PH-induced hepatic damage. Methods. 90 male Wistar albino rats (120-140 gm) were undertaken, categorized randomly into 9 groups of 10 rats each, and administered by gavage for 2 weeks with DMSO 1% (controls), PA, PA+NAC, PA+NAM, PA+NAG, PH, PH+NAC, PH+NAM, and PH+NAG. Biochemical assays of malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), total thiols, and alpha-fetoprotein (AFP) in liver homogenates and serum assays of ALT, AST, 8-hydroxy guanine (8-OH-Gua), and AFP were done. Also histopathological examinations of liver tissues in various groups were done. Results. PA and PH cause significant increase in hepatic levels of MDA, NO, and AFP and serum ALT, AST, and 8-OH-Gua levels, with significant decrease in hepatic GSH and total thiols. NAG and NAC significantly improve the PA- and PH-induced hepatic and blood, biochemical, and histopathological disturbances, respectively. Conclusions. Both PA and PH induce oxidative stress in rat liver within their therapeutic doses. NAG and NAC in pharmacological doses can antagonize the oxidative damaging effect of both PA and PH

Vitamin D receptor gene polymorphism and polycystic ovary syndrome susceptibility

Abstract Background Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women. This study was designed to investigate the associations of vitamin D receptor (VDR) gene variants with PCOS risk and the severity of the disease phenotype among Egyptian women. Methods In this study, 185 women with PCOS and 207 fertile women as controls were recruited. Cases were divided into phenotype groups based on their clinical and paraclinical features. Clinical and laboratory data were measured in the patient and control groups. All individuals were genotyped for nine single-nucleotide polymorphisms (SNPs) located across the VDR gene using TaqMan allelic discrimination real-time polymerase chain reaction. Results Women with PCOS were significantly (P ≤ 0.001) higher body mass index (BMI) (22.77 ± 2.5) than controls (21.68 ± 1.85 kg/m2). Women with PCOS had significantly higher anti-Mullerian hormone, prolactin, luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH), free testosterone, total testosterone, and dehydroepiandrosterone sulfate levels than the control group (P ≤ 0.001). The level of FSH was significantly lower in women with PCOS than in the control group (P ≤ 0.001). Analysis of the VDR rs4516035, rs2107301, rs1544410 (BsmI), and rs731236 (TaqI) SNPs showed a significant association with PCOS phenotype A. Furthermore, rs2228570 (FokI), rs3782905, rs7975232 (ApaI), and rs739837 SNPs showed a significant association with PCOS phenotype C. Furthermore, rs11568820 SNP showed a significant association with PCOS phenotype D (P < 0.05). Conclusions The findings of this study indicate that variations in the VDR gene were associated with an increased risk of PCOS in Egyptian women

Design, Molecular Docking, Synthesis, Anticancer and Anti-Hyperglycemic Assessments of Thiazolidine-2,4-diones Bearing Sulfonylthiourea Moieties as Potent VEGFR-2 Inhibitors and PPARγ Agonists

Newly designed thiazolidine-2,4-diones 3–7a–c were synthesized, and their anticancer activities were screened against three cancer lines. They showed potent activities against HepG2 compared to the other HCT116 and MCF-7 tumor cell lines. Compounds 7c and 6c were detected as highly effective derivatives against MCF-7 (IC50 = 7.78 and 8.15 µM), HCT116 (IC50 = 5.77 and 7.11 µM) and HepG2 (IC50 = 8.82 and 8.99 µM). The highly effective derivatives 6a–c and 7a–c were tested against VERO normal cell lines. All derivatives were evaluated for their VEGFR-2 inhibitory actions and demonstrated high to low activities, with IC50 values varying from 0.08 to 0.93 µM. Moreover, derivatives 5a–c, 6a–c and 7a–c were assessed to verify their in vitro binding affinities to PPARγ and insulin-secreting activities. Finally, docking studies were performed to explore their affinities and binding modes toward both VEGFR-2 and PPARγ receptors