Evidence of intra-hepatic vascular proliferation remodeling early after cure in experimental schistosomiasis mansoni: an immunohistochemical descriptive study

Experimental studies have demonstrated the occurrence of angiogenesis, blood vessels formation from pre-existing vessels, in the initial phase of bilharzial granuloma formation and during fibrosis progression in chronic hepatic schistosomiasis. Paradoxically, a recent work demonstrated an occurrence of angiogenesis during fibrosis regression months after curative treatment. Studies regarding the in situ kinetics of blood vessels in the phase of granuloma resolution and liver tissue healing early after treatment are lacking. The current work compared the kinetics of blood vessels by immunohistochemical staining using CD34, vascular endothelial growth factor (VEGF) and actin in the livers of normal control mice, Schistosoma mansoni infected mice and mice 2 weeks after curative treatment. The present study demonstrated a process of angiogenesis remodeling in the liver in the curative phase of hepatic schistosomiasis during the stage of granuloma resolution. Such finding raises the evidence of the importance and potential beneficial effect of vascular proliferation in the process of healing and restoration of liver tissue functions. Thus, blocking of angiogenesis may not represent the appropriate therapeutic target for the early treatment of schistosomal liver fibrosis.     

Serum miR‐122 and miR‐192 as biomarkers of intrinsic and idiosyncratic acute hepatotoxicity: A quantitative real‐time polymerase chain reaction study in adult albino rats

miR‐122 and miR‐192 were investigated as indicators of toxic liver injury caused by acetaminophen, but their role in idiosyncratic toxic liver injury remains controversial. So, this work aimed to assess and compare the expressions of miR‐122 and miR‐192 in two different types of toxic liver injury (intrinsic [acetaminophen] and idiosyncratic [diclofenac]). Forty male adult Wistar albino rats were divided into equal five groups, in which serum liver enzymes; microRNAs (miRNAs) expressions (miR‐122 and miR‐192) and histopathological findings were studied. The present study showed that (1) miR‐122 and miR‐192 are good serum biomarkers of toxic liver injury whatever its etiology, as their serum levels exhibited a significantly earlier increase and earlier return to normal baseline levels as compared to serum aminotransferase levels; (2) miR‐122 is more specific than miR‐192; and (3) both serum levels of miR‐122 and miR‐192 showed non‐significant differences in relation to the type of toxic liver injury.     

Down regulation of miR-30a-5p and miR-182–5p in gastric cancer: Clinical impact and survival analysis

Background and aimGastric Cancer (GC) is a leading cause of morbidity and mortality worldwide, particularly in developing nations, only a few suitable gastric cancer serum biomarkers with acceptable sensitivity and specificity exist. This work aims to highlight and uncover miR-30a-5p and miR-182–5p′s diagnostic roles regarding gastric cancer and their roles in predicting prognosis.Methods148 patients participated in this study. Groups I, II, and III had 47 patients with GC, 54 patients with benign gastric lesions, and 47 apparently healthy subjects of coincided age and gender as controls, respectively. All participants were clinically evaluated and subjected to CBC, serum CEA, and CA19-9 by ELISA, and real-time PCR tests of miR-30a-5p and miR-182–5p.ResultsMiR30a-5p and miR-182–5p were down regulated in gastric cancer patients in Group I more than Groups II and III (P < 0.001). ROC curve analysis revealed that miR30a-5p had better AUC, sensitivity, and specificity (0.961%, 93.62%, and 90.74%respectively). When miR-182–5p was gathered with CEA and CA19-9, specificity raised to 98.15% and PPV to 97.6%. Lower miR-30a-5p levels are linked with the presence of distant metastases, advanced TNM stage, and degree of pathological differentiation of tumors in GC patients (p = 0.034, 0.019, 0.049) respectively. According to the multivariate analysis, miR30a-5p expression level could be an independent predictor of GC.ConclusionOur results exhibited that miRNAs, miR-30a-5p and miR182–5p, gene expression have a diagnostic power and can identify patients with GC. MiR-30a-5p displayed the highest diagnostic specificity and sensitivity. Besides other known tumor markers, they could offer simple noninvasive biomarkers that predict gastric cancer.     

Protective effect of hesperidin against lung injury induced by intestinal ischemia/reperfusion in adult albino rats: Histological,immunohistochemical and biochemical study

Hesperidin is a naturally common flavonoid. It is an abundant and cheap by-product of citrus cultivation. It is reported to have antioxidative, anti-inflammatory and anticarcinogenic effects. This work was performed to investigate the possible protective role of hesperidin in ameliorating the effect of experimentally induced intestinal ischemia/reperfusion injury (I/R) on lung tissue, histologically, immunohistochemically and biochemically. Thirty male Wistar adult albino rats were randomized into three groups named: group I (control group); group II (I/R); and group III (I/R with hesperidin). Intestinal I/R was induced by occluding the superior mesenteric artery for 60 min, followed by 120 min of reperfusion period. Animals were given hesperidin orally 1 h before the onset of ischemia. At the end of the reperfusion period the lung tissues were extracted for histopathological examination and immunohistochemical detection of the distribution of inducible nitric oxide synthase (iNOS). Pulmonary edema was evaluated by lung tissue wet/dry weight ratios. The levels of malondialdehyde (MDA, a biomarker of oxidative damage), myeloperoxidase (MPO, an index of the degree of neutrophil accumulation) and glutathione (GSH, a biomarker of protective oxidative injury) were also determined in all dissected tissues. Pretreatment with hesperidin (in group III) alleviated lung morphological changes noticed in I/R group and the levels of MDA and MPO were significantly decreased whereas those of GSH were significantly increased. Immunohistochemical study revealed a significant decrease in the iNOS. Hesperidin also significantly alleviated the formation of pulmonary edema as evidenced by the decreased organ wet/dry weight ratios. Hesperidin exerts a protective effect against lung damage induced by intestinal I/R injury in rats by reducing oxidative stress.     

Dietary Intake of Pesticides Based on Vegetable Consumption in Ismailia,Egypt: A Case Study

The objective of this study was to assess pesticide residues in tomatoes, cucumbers, peppers, strawberries, and potatoes collected from local markets in Ismailia, Egypt, and to assess dietary intake and health risk implications of pesticide residues through food consumption. Vegetable selection was based on their popularity and consumption. Selection of pesticides was based on their impact on humans, and on their heavy use. The majority of the analyzed samples contained detectable levels of pesticides. Residues of some organophosphorus pesticides, including malathion, ethion, and profenofos and some pyrethroid pesticides such as fenpropathrin and cypermethrin were found in some samples at concentration equal to or exceeding their European Union's maximum residue limits (EU-MRLs). The fungicide bupirimate detected in potato samples exceeded the EU-MRL by 1500%. Phentohate and profenofos were the most frequently detected pesticides in 30 and 27% of analyzed samples, respectively. Data were used to estimate the potential health risks associated with exposure to these pesticides by ingestion of food. Estimated daily intakes (EDIs) of pesticides ranged from 0.03% to 40% of the acceptable daily intakes (ADIs), depending on pesticide concentration and vegetable consumption. Overall, the EDIs of the different pesticides from vegetable consumption are not considered a public health problem.     

CD127 Expression,Exhaustion Status and Antigen Specific Proliferation Predict Sustained Virologic Response to IFN in HCV/HIV Co-Infected Individuals

Hepatitis C virus (HCV) infection is a major cause of morbidity and mortality in the HIV co-infected population. Interferon-alpha (IFN-α) remains a major component of anti-HCV therapy despite its deleterious effects on the immune system. Furthermore, IFN-α was recently shown to diminish the size of the latent HIV reservoir. The objectives of this study were to monitor the impact of IFN-α on T cell phenotype and proliferation of HIV and HCV-specific T cells during IFN therapy, and to identify immune markers that can predict the response to IFN in HICV/HIV co-infected patients. We performed longitudinal analyses of T cell numbers, phenotype and function in co-infected patients undergoing IFN-α therapy with different outcomes including IFN-α non-responders (NR) (n = 9) and patients who achieved sustained virologic response (SVR) (n = 19). We examined the expression of activation (CD38, HLA-DR), functional (CD127) and exhaustion markers (PD1, Tim-3, CD160 and CD244) on total CD4 and CD8 T cells before, during and after therapy. In addition, we examined the HIV- and HCV-specific proliferative responses against HIV-p24 and HCV-NS3 proteins. Frequencies of CD127⁺ CD4 T cells were higher in SVR than in NR patients at baseline. An increase in CD127 expression on CD8 T cells was observed after IFN-α therapy in all patients. In addition, CD8 T cells from NR patients expressed a higher exhaustion status at baseline. Finally, SVR patients exhibited higher proliferative response against both HIV and HCV antigens at baseline. Altogether, SVR correlated with higher expression of CD127, lower T cell exhaustion status and better HIV and HCV proliferative responses at baseline. Such factors might be used as non-invasive methods to predict the success of IFN–based therapies in co-infected individuals.     

Renoprotective effect of a combination of garlic and telmisartan against ischemia/reperfusion-induced kidney injury in obese rats

Obesity enhances the frequency and severity of acute kidney injury (AKI). Telmisartan pre-treatment was used experimentally in the amelioration of ischemia/reperfusion (IR)-induced AKI. However, there is a lack of evidence regarding its beneficial effects on AKI in obese animals. The present study, therefore, aimed to explore the protective effects of garlic and/or telmisartan against renal damage induced by unilateral IR in obese rats. Meloxicam was used as a standard anti-inflammatory agent. Prophylactic oral administration of meloxicam (3?mg kg^?1), garlic (500?mg kg^?1) and/or telmisartan (5 and 10?mg kg^?1) for 4 wk protected against renal function deterioration induced by IR in obese rats. Both doses of telmisartan significantly reduced serum total cholesterol and triacyglycerol levels as well as peri-renal adipocytes size and renal fibrosis. Renal nuclear factor-kappa B immunoreactivity, tumor necrosis factor-alpha content as well as interleukin-10, adiponectin receptor 1 and macrophages (M1, M2) polarization markers (CD11c, CD206) mRNA expressions were down-regulated in ischemic kidney tissues and white adipose tissues around them by all treatments. Moreover, garlic, telmisartan and their combinations significantly suppressed oxidative stress in renal ischemic tissues. Histological picture was also improved by these treatments. Interestingly, the combinations provided a greater protection than their monotherapy in a dose-dependent manner. We suppose that this combination may be a promising prophylactic regimen for managing AKI in case of obesity. Thus, future experimental and clinical large-scale studies are necessary.     

Noninvasive in vivo monitoring of methemoglobin formation and reduction with broadband diffuse optical spectroscopy.

We present noninvasive, quantitative in vivo measurements of methemoglobin formation and reduction in a rabbit model using broadband diffuse optical spectroscopy (DOS). Broadband DOS combines multifrequency frequency-domain photon migration (FDPM) with time-independent near infrared (NIR) spectroscopy to quantitatively measure bulk tissue absorption and scattering spectra between 600 nm and 1,000 nm. Tissue concentrations (denoted by brackets) of methemoglobin ([MetHb]), deoxyhemoglobin ([Hb-R]), and oxyhemoglobin ([HbO2]) were determined from absorption spectra acquired in "real time" during nitrite infusions in nine pathogen-free New Zealand White rabbits. As little as 30 nM [MetHb] changes were detected for levels of [MetHb] that ranged from 0.80 to 5.72 microM, representing 2.2 to 14.9% of the total hemoglobin content (%MetHb). These values agreed well with on-site ex vivo cooximetry data (r2= 0.902, P < 0.0001, n = 4). The reduction of MetHb to functional hemoglobins was also carried out with intravenous injections of methylene blue (MB). As little as 10 nM changes in [MB] were detectable at levels of up to 150 nM in tissue. Our results demonstrate, for the first time, the ability of broadband DOS to noninvasively quantify real-time changes in [MetHb] and four additional chromophore concentrations ([Hb-R], [HbO2], [H2O], and [MB]) despite significant overlapping spectral features. These techniques are expected to be useful in evaluating dynamics of drug delivery and therapeutic efficacy in blood chemistry, human, and preclinical animal models.     

Evidence for a dominant major gene conferring predisposition to hepatitis C virus infection in endemic conditions

Hepatitis C virus (HCV), infecting 170 million people worldwide, is a major public health problem. In developing countries, unsafe injections and blood transfusions are thought to be the major routes of transmission. However, our previous work in a population from Egypt, endemic for HCV, revealed highly significant familial correlations, strongly suggesting the existence of both familial transmission of the virus and genetic predisposition to HCV infection. We investigated the hypothesis of genetic predisposition by carrying out a segregation analysis of HCV infection in the same population. We used a logistic regression model simultaneously taking into account a major gene effect, familial correlations and relevant risk factors. We analyzed 312 pedigrees (3,703 subjects). Overall HCV seroprevalence was 11.8% and increased with age. The main associated risk factors were previous parenteral treatment for schistosomiasis and blood transfusions. We found strong evidence for a dominant major gene conferring a predisposition to HCV infection. The frequency of the predisposing allele was 0.013, reflecting a strong predisposition to HCV infection in 2.6% of the subjects, particularly those under the age of 20. This study provides evidence for the involvement of host genetic factors in susceptibility/resistance to HCV infection in endemic conditions.