Trichinella spiralis Larval Extract as a Biological Anti-Tumor Therapy in a Murine Model of Ehrlich Solid Carcinoma.

Trichinella spiralis (T. spiralis) is an immunomodulating parasite that can adversely affect tumor growth and extend host lifespan. The aim of this study was to elucidate the mechanisms by which T. spiralis larval antigens achieve this effect using Ehrlich solid carcinoma (ESC) murine model. Assessment was done by histopathological and immunohistochemical analysis of caspase-3, TNF-α, Ki-67 and CD31. Additionally, Bcl2 and Bcl2-associated protein X (Bax) relative gene expression was assessed by molecular analysis for studying the effect of T. spiralis crude larval extract (CLE) antigen on tumor necrosis, apoptosis, cell proliferation and angiogenesis. We found that both T. spiralis infection and CLE caused a decrease in the areas of necrosis in ESC. Moreover, they led to increased apoptosis through activation of caspase-3, up-regulation of pro-apoptotic gene, Bax and down-regulation of anti-apoptotic gene, Bcl2. Also, T. spiralis infection and CLE diminished ESC proliferation, as evidenced by decreasing Ki-67. T. spiralis infection and CLE were able to suppress the development of ESC by inhibiting tumor proliferation, inducing apoptosis and decreasing tumor necrosis, with subsequent decrease in tumor metastasis. T. spiralis CLE antigen may be considered as a promising complementary immunotherapeutic agent in the treatment of cancer.

Worsening effect of testosterone deficiency on males with heart failure with preserved ejection fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF)is challenging. Patients usually have normal LV size and ejection fraction. This clinical syndrome develops from a complex interaction of several risk factors that cause organ dysfunction and clinical symptoms. There's evidence that testosterone deficiency is associated with a worse cardiometabolic profile and increased inflammatory markers. We thought that these changes might have an impact on heart failure pathogenesis. We aimed to study the relationship between testosterone level and symptoms in HFpEF. METHODS: We studied 120 male patients with HFpEF. According to New York Heart Association (NYHA), patients were classified into I, II and III classes; class IV patients were excluded. All patients were subjected to clinical and echocardiographic examinations. In addition, we measured serum testosterone, cardio-metabolic profile, intracellular adhesive molecule-1(ICAM-1), P-selectin and nitric oxide (NO) levels. RESULTS: Patients with testosterone deficiency had worse NYHA class and higher BNP P = (0.001). Additionally, they had a significantly worse metabolic profile; higher total cholesterol, triglycerides, LDL cholesterol, fasting insulin and HOMA-IR P = (0.005, 0.001, 0.001, 0.001), respectively. Also, they had higher inflammatory markers and worse endothelial functional parameters; (ICAM-1, NO and P- selectin) P = (0.001). Age, BNP and testosterone deficiency can be used as independent predictors of NYHA class III symptoms with a Testosterone cutoff value of 2.7 ng/ml. CONCLUSION: Testosterone deficiency could be used as an independent predictor of symptom severity in HFpEF, and it aggravates systemic inflammation and endothelial dysfunction in these patients.

Novel insights into the synergistic effects of selenium nanoparticles and metformin treatment of letrozole - induced polycystic ovarian syndrome: targeting PI3K/Akt signalling pathway, redox status and mitochondrial dysfunction in ovarian tissue.

PURPOSE: Polycystic ovary syndrome (PCOS) has a series of reproductive and metabolic consequences. Although the link between PCOS, IR, and obesity, their impact on the pathogenesis of PCOS has yet to be determined. Dysfunction of PI3K/AKT pathway has been reported as the main cause of IR in PCOS. This study purposed to explore the effects of selenium nanoparticles (SeNPs) alone and combined with metformin (MET) in a PCOS-IR rat model. METHODS: After 3 weeks of treatment with SeNPs and/or MET, biochemical analysis of glycemic & lipid profiles, and serum reproductive hormones was performed. Inflammatory, oxidative stress, and mitochondrial dysfunction markers were determined colormetrically. The expression of PI3K and Akt genes were evaluated by Real-time PCR. Histopathological examination and Immunohistochemical analysis of Ki-67 expression were performed. RESULTS: The results showed that treatment with SeNPs and/or MET significantly attenuated insulin sensitivity, lipid profile, sex hormones levels, inflammatory, oxidative stress and mitochondrial functions markers. Additionally, PI3K and Akt genes expression were significantly upregulated with improved ovarian histopathological changes. CONCLUSION: Combined SeNPs and MET therapy could be potential therapeutic agent for PCOS-IR model via modulation of the PI3K/Akt pathway, enhancing anti-inflammatory and anti-oxidant properties and altered mitochondrial functions.HighlightsThe strong relationship between obesity, insulin resistance, and polycystic ovarian syndrome.Disturbance of the PI3K/Akt signaling pathway is involved in the progression of polycystic ovary syndrome-insulin resistance (PCOS-IR).In PCOS-IR rats, combined SeNPs and metformin therapy considerably alleviated IR by acting on the PI3K/Akt signaling pathway.The combination of SeNPs and metformin clearly repaired ovarian polycystic pathogenesis and improved hormonal imbalance in PCOS-IR rats.

The Prospective Ameliorative Role of Zinc Oxide Nanoparticles in STZ-Induced Diabetic Nephropathy in Rats: Mechanistic Targeting of Autophagy and Regulating Nrf2/TXNIP/NLRP3 Inflammasome Signaling.

Diabetic nephropathy (DN) as one of the common microvascular complications of diabetes mellitus, is the main cause of end-stage renal disease. Zinc oxide nanoparticles (ZnO NPs) have been employed in several biomedical aspects. This study purposed to explore the mechanistic renoprotective effects of ZnO NPs in STZ-induced DN. Sixty male Wistar rats were allocated into four equal groups: control, ZnO NPs control, STZ, and STZ + ZnO NPs groups. At the end of the experiment, blood and urine biochemical parameters were assayed. Renal tissue level of advanced glycation end products (AGEs) was assayed spectrofluorometrically, moreover, nuclear factor erythroid 2-related factor 2 (Nrf2) DNA-binding activity and IL-1ß levels were detected by ELISA. The gene expression levels of thioredoxin-interacting protein (TXNIP) and NOD-like receptor family pyrin domain containing 3 (NLRP3) were detected by quantitative real-time PCR. Oxidative stress markers were determined spectrophotometrically. Also, renal tissue histopathological and immunohistochemical analyses were determined. After 6 weeks of treatment, ZnO NPs markedly improved the biochemical, renal functions, and histopathological findings. Furthermore, ZnO NPs significantly increased Nrf2-DNA-binding activity and downregulated TXNIP gene expression leading to restoration of the redox status. Additionally, ZnO NPs ameliorated AGEs levels, enhanced autophagy activity, and attenuated inflammasome activation via downregulation of NLRP3 expression and reducing IL-1ß levels. Based on our results, we concluded that ZnO NPs can be considered as a promising agent for slowing the progression of DN via interplay between autophagy and Nrf2/TXNIP/NLRP3 inflammasome signaling.

The impact of cichorium intybus L. On GDF-15 level in obese diabetic albino mice as compared with metformin effect.

BACKGROUND: Diabetes mellitus (DM) and obesity comorbidity signify a frequent metabolic disorder, representing a huge public health burden. Metformin, the most used anti-diabetic medication, is found to reduce body weight via growth differentiation factor 15 (GDF-15) signalling pathways. The medicinal herb Cichorium intybus L. (chicory or cichorium) has a promising pharmacological impact on energy homeostasis. On the other hands, little data is available on its role in DM and obesity. Despite its irrefutable effect, its exact mechanism of action has not completely elucidated; the present study evaluated the effect of chicory on DM, antioxidant status, inflammation, and GDF-15 level in comparison with the metformin effect. MATERIAL AND METHODS: Eighty albino mice were grouped as (control, obese diabetic group, metformin-treated, and Cichorium intybus L. -treated group). The study assessed blood glucose, lipid profile, inflammatory markers (IL-6, TNF-α), total antioxidant capacity (TAC) and caspase-3. Quantitative RT-PCR assessed GDF-15 and leptin relative mRNA expression. RESULTS: Cichorium intybus L. has significantly lowered inflammatory, apoptotic markers, and leptin levels compared with the diseased group. Likewise, the plant upregulated GDF-15 and TAC's levels. The study documented a non-significant difference between the Cichorium intybus L. -treated and the metformin-treated groups in all estimated markers. CONCLUSION: The Cichorium intybus L. is a promising herbal supplement with anti-inflammatory, antioxidant, anti-diabetic, and weight reduction effects via affecting GDF-15 signalling pathways. GRAPHICAL ABSTRACT: GDF-15 has anti-inflammatory, anti-oxidative stress and anti-apoptotic effect in DM and obesity via targeting NF-κB mechanisms.

Enhanced adsorption of Levofloxacin and Ceftriaxone antibiotics from water by assembled composite of nanotitanium oxide/chitosan/nano-bentonite.

A novel NBent-NTiO2-Chit nanocomposite has been synthesized from the crosslinking combination of nanotitanium oxide-chitosan (NTiO2-Chit) and nanotitanium oxide-bentonite (NTiO2-Bent) via formaldehyde. The characterization of NBent-NTiO2-Chit was confirmed by different instrumentations. The particle size (34-97 nm) and surface area (16.385 m2 g-1) were confirmed from the scanning electron microscopy and BET measurement, respectively. The FT-IR of NBent-NTiO2-Chit confirmed the presence of OH, N-H, Si-O-Al and Si-O-Si functional groups. Four thermal degradation steps were characterized from the TGA of NBent-NTiO2-Chit with a total loss = 23.514% in the temperature range 30-600 °C. The assembled nanocomposite enhanced the removal of two important classes of antibiotics including Levofloxacin (LEVO) Ceftriaxone (CFT) in the forms of Fluoroquinolone and Cephalosporin, respectively. The various factors that affected the percentage of extraction were applied and optimized such as pH, dosage, initial concentration of LEVO and CFT, contact time and interfering ions. Maximum percentage values of 90.2% (pH 4) and 93.5% (pH 5) for LEVO and CFT, respectively, were achieved at 10 min. The enhancement in removal percentage of LEVO to 92.4% was mainly established by increasing the dose of NBent-NTiO2-Chit to 60.0 mg. The extraction mechanisms of LEVO and CFT were positively explained by three models of adsorption isotherm including Langmuir, Freundlich and Temkin. The obtained correlation coefficients (R2) by Langmuir model were 0.952 and 0.987 for LEVO and CFT, respectively to offer excellent fit to the adsorption processes. The thermodynamics parameters of NBent-NTiO2-Chit were evaluated and referred that the reaction is spontaneous and endothermic. The kinetic studies of NBent-NTiO2-Chit with LEVO and CFT antibiotics were better fitted by the pseudo-second-order based on the acquired R2 values as 0.999 and 0.997 for LEVO and CFT, respectively. The results proved that the designed NBent-NTiO2-Chit was successively implemented for extraction of LEVO and CFT from industrial wastewater providing percentage values 83.2 and 79.0% using 10.0 and 150.0 ±â€¯1.0 mg NBent-NTiO2-Chit, respectively.

Impact of CD40 gene polymorphisms on the risk of immune thrombocytopenic purpura.

OBJECTIVES: To evaluate the relationship between two common single nucleotide polymorphisms (SNPs) of CD40 gene (rs1883832 C/T and rs4810485 G/T) and the risk of immune thrombocytopenia (ITP) in the Egyptian population. METHODS: A case-control study was conducted retrospectively on 101 cases with ITP and 97 healthy subjects. Two SNPs of CD40 gene (rs1883832 C/T and rs4810485 G/T) were genotyped via Taqman allele discrimination real-time PCR. The frequencies of different genetic models of both SNPs were calculated and compared between ITP cases and controls. Linkage analysis was performed between the studied SNPs. Odds ratio (OR) and 95% confidence interval (CI) were assessed using multinomial logistic regression analysis to determine the association of CD40 gene SNPs genotypes, alleles, and haplotypes with the risk of ITP. The odds ratio was further adjusted to the confounders for risk stratification. RESULTS: CD40 (rs1883832) TT genotype carriers have a significantly higher risk of ITP when compared to CC genotype carriers (adjusted OR: 3.792, 95%CI: 1.252-11.49, P = 0.018). T allele also represents 1.711-fold increased risk of ITP which is more evident in males (P = 0.016). No significant difference was observed in the frequency of CD40 (rs4810485 G/T) genetic models between cases and controls. Linkage disequilibrium was found between the two SNPs and revealed four main haplotypes (C-G; C-T; T-G; T-T) with a significantly higher frequency of T-G haplotype in ITP cases than in healthy controls which confers an increased risk of ITP development (OR: 2.349, 95%CI: 1.271-4.339, P = 0.006). CONCLUSIONS: CD40 gene SNP rs1883832 is associated with an increased risk of ITP development in the Egyptian population, while the SNP rs4810485 has no association. Moreover, T-G haplotype is a risk genetic model for ITP.

Synthesis, characterization and optical properties of nanosized lanthanum (III) complexes thin film with aryl-azo-pyrogallol derivatives.

The present study is focused on the assembly of two new thin films based on the direct layer deposition of lanthanum ion from solution with two aryl-azo-pyrogallol ligands onto the surface of a glass substrate. Assembled lanthanum (III) complexes were characterized by different techniques including thermal gravimetric analysis, metal analysis by acid digestion and complexometric titration, Fourier transforms infrared, transmission electron microscopy, and X-ray diffraction. Two complexes were highly similar in their patterns and crystallinities with the characterized particle size range 23.16-23.31 nm. Energy gaps of the two complexes NS Na3La(III)-(L1)2 and NS Na3La(III)-(L2)2 were found to be 2.09 and 2.33 eV, respectively. Linear and calculated nonlinear optical properties have been studied for the two complexes. The nonlinear refractive index has been calculated and NS Na3La(III)-(L2)2 showed a high nonlinear behavior (n2 = 8 × 10-7 esu) and it could be a promising low-cost material in the optical nonlinear application.