Assessing the toxicity of pesticides exposure on hepatic miRNA-target gene alterations in rat liver tissues via molecular and integrated network bioinformatics analysis.

The prevalent use of pesticides, including pirimiphos-methyl (PPM) and bifenthrin (BF), poses a serious health risk, particularly to workers who encounter these chemicals daily. Despite the recognized hepatotoxic effects, the specific molecular mechanisms, especially those involving miRNAs in liver damage caused by PPM and BF, are not fully elucidated. Prior studies have not exhaustively analyzed the hepatic miRNA-target gene dynamics following exposure to these pesticides; thus, this research aims to fill that gap through an extensive miRNA analysis to discern their regulation in PPM or BF-induced hepatic toxicity. In this study, male Sprague-Dawley rats were exposed to BF or PPM for 28 days through oral gavage, simulating the chronic exposure faced by humans. We conducted a thorough assessment of the hepatotoxicity induced by PPM and BF, employing multiple evaluation levels, including histological analysis, liver enzyme measurements, and real-time PCR to detect changes in hepatic miRNA-target gene expressions. Additionally, we utilized DIANA-miRPath prediction tools to delineate the functional implications of these hepatic miRNA target genes. Our findings reveal a significant modulation in the expression of rno-miR-155-5p and rno-miR-122-5p, along with their target genes, following PPM and BF treatment. In contrast, rno-miR-21-5p levels remained unaltered. These observations suggest potential utility of these specific hepatic miRNAs as biomarkers for liver injury resulting from pesticide exposure. Subsequent GO enrichment analysis linked target genes to functions like molecular activity, protein binding, and cellular processes. Additionally, KEGG pathway analysis showed these genes, influenced by varied miRNA expressions, play significant roles in metabolic and signaling pathways In conclusion, this study enhances our comprehension of the biological roles of miRNAs in hepatic toxicity induced by PPM and BF. The insights gained here not only shed light on molecular mechanisms but also open avenues for considering these miRNAs as potential diagnostic biomarkers in conditions of pesticide-induced hepatotoxicity, thereby guiding future therapeutic strategies.

IL-6 at the center of cytokine storm: Circulating inflammation mediators as biomarkers in hospitalized COVID-19 patients.

INTRODUCTION: The management of hospitalized COVID-19 patients depends largely on controlling the intensified inflammatory response known as the cytokine storm. Candidate inflammatory cytokines can serve as new biomarkers for the management of hospitalized COVID-19 patients. METHODS: Patients (80) were recruited into three groups: room air (RA), oxygen (OX) and mechanical ventilator (MV). Blood analysis was performed for RBC, WBC, Hb, Platelets, serum albumin and creatinine, INR, PTT, and hematocrit. ELISA was used to quantify a panel of inflammatory mediators including GM-SCF, IFN-α, IFNγ, IL-1ß, IL-1R, IL-2, IL-2Ra, IL-6, IL-8, IL-10, IL-12p70, IL-13, MCP-1, MIP-1a, and TNF-α. Correlations between laboratory results and the levels of circulating inflammation mediators were investigated. RESULTS: Patients on MV had low RBC, Hb, albumin, and HCT and high WBC count, PTT, and INR when compared to RA and OX groups. A statistical positive correlation was found between WBC and the levels of IL-6 and MCP-1. RBCs correlated negatively with IL-6 and IL-10 and positively with IL-8. Higher TNF-α correlated with lower platelet counts while higher levels of IL-1Rα and IL-10 were associated with lower Hb levels. Increases in IFN-γ and TNF-α were indicative of compromised kidney functions as creatinine levels increased significantly. Most significant correlations were found between IL-6 and lab results, showing positive correlation with WBC and INR, and negative correlation with RBC, albumin, and HCT. CONCLUSIONS: Having the most significant correlations, IL-6 high levels in mechanically ventilated patients were shown to affect laboratory results, and, therefore, is suggested as a severity biomarker of COVID-19.

Identification of Chemo and Radio-Resistant Sub-Population of Stem Cells in Human Cervical Cancer HeLa Cells.

BACKGROUND: Cervical cancer ranks the second female malignancy after breast cancer. Cancer stem cells (CSCs) are hard to be eradicated, so can recur. We aim to isolate and characterize CSCs from HeLa cells. METHODS: These cells express clusters of differentiation (CDs), 44 and 24, to be sorted by fluorescence-activated cell sorting (FACS). RESULTS: CD44+CD24+ cells showed potential to form spheres, tumorigenicity, stemness genes and higher resistance to cisplatin, X-ray. CONCLUSION: CD44+CD24+ HeLa cells hold characteristics of CSCs, in vitro, in vivo studies, suggesting that targeting may lead to screening of new anti-cancer therapies.

A study of the hepatoprotective effect of Plantago psyllium L. seed extract against Carbon tetrachloride induced hepatic injury in rats.

BACKGROUND: The liver is the main metabolic organ involved in disposal and detoxification of various molecules. Plantago psyllium L. seed has been reported to exert positive effects in some pathological conditions. The current study aims to assess the hepatoprotective effect of Plantago psyllium L. seed extract against carbon tetrachloride-induced hepatotoxicity. METHODS: Male albino Wistar rats were randomly divided into five groups of 10 rats each. Hepatotoxicity was induced by orally administered carbon tetrachloride (CCl4) for nine weeks with or without the different treatments which were utilized daily for the whole nine weeks. Serum and tissue samples were then withdrawn and different liver biomarkers were investigated. RESULTS: Treatment of rats with Psyllium seed ethanolic extract significantly alleviated the toxic effects of CCl4. This was evidenced by its ability to restore liver biomarkers levels. Moreover, treatment with Psyllium seed extract normalized levels of oxidative biomarkers such as lipid peroxidation, hepatic content of reduced glutathione and catalase activity, as well as the expression level of the inflammatory marker TNF-α. Histopathological examination reflected the protective effect of the extract on liver architecture and confirmed the observed biochemical data. CONCLUSIONS: The presented data demonstrates a potential hepatoprotective effect of Psyllium seed extract compared to the standard hepatoprotective drug silymarin. This effect can be attributed to the antioxidant and anti-inflammatory effects of Psyllium extract.

Experimental evidence for the therapeutic potential of tempol in the treatment of acute liver injury.

Oxidative stress is one of the mechanisms involved in the acute carbon tetrachloride (CCl4)-induced hepatotoxicity. Since 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl, known as tempol, has powerful antioxidant properties, we investigated its potential hepatoprotective effects and the underlying mechanisms that may add further benefits for its clinical usefulness using an acute model of CCl4-induced hepatotoxicity. One hour after CCl4 induction of acute hepatotoxicity, mice were treated with a daily dose of 20 mg/kg/day tempol for 3 days. It was found that treatment of animals with tempol significantly negated the pathological changes in liver function parameters as well as histology induced by CCl4. In addition, tempol significantly ameliorated CCl4-induced lipid peroxidation and GSH depletion, and improved catalase activity. Furthermore, tempol alleviated the inflammation induced by CCl4 as indicated by reducing the liver expression level of nuclear factor-kappa B (NF-κB) and tumor necrosis factor-α (TNF-α). Finally, tempol significantly reduced expression level of the B-cell lymphoma-2 protein (Bcl-2) and active caspase-3 which are known markers of apoptosis. In conclusion, the present study provides important evidences for the promising hepatoprotective effects of tempol that can be explained by amelioration of oxidative stress mainly through replenishment of GSH, restoration of antioxidant enzyme activities, and reduction of lipid peroxides alongside its anti-inflammatory properties.

Hepatoprotective activity of ethanolic extract of Salix subserrata against CCl4-induced chronic hepatotoxicity in rats.

BACKGROUND: The liver performs diverse functions that are essential for life. In the absence of reliable liver protective drugs, a large number of natural medicinal preparations are used for the treatment of liver diseases. Therefore the present study aims to investigate the hepatoprotective effects of Salix subserrata Willd flower ethanolic extract (SFEE) against carbon tetrachloride (CCl4)-induced liver damage. METHODS: Rats were divided into 4 groups of 10 animals each. Group I served as the normal healthy control, groups II rats were intoxicated with CCl4 i.p. (0.8 ml/kg body weight CCl4/olive oil, twice weekly for 9 weeks), group III rats received CCl4 i.p. and SFEE orally (150 mg/kg daily) and group IV rats received CCl4 i.p. and Silymarin orally (100 mg/kg, daily). The hepatoprotective potential of SFEE in rats was evaluated by measuring the protein levels of two inflammatory biomarkers; tumor necrosis factor-alpha (TNF-α) and nuclear factor kappa-B (NF-kB) in addition to other liver biomarkers. Histopathological changes in the liver were assessed using hematoxylin and eosin staining (HE). RESULTS: The administration of SFEE showed hepatic protection at an oral dose of 150 mg/kg. SFEE significantly reduced the elevated serum levels of intracellular liver enzymes as well as liver biomarkers in comparison to CCl4- intoxicated group. Notably, SFEE significantly reduced the expression levels of TNF-α and NFkB proteins compared to their levels in CCl4 intoxicated group. These findings were confirmed with the histopathological observations, where SFEE was capable of reversing the toxic effects of CCl4 on liver cells compared to that observed in CCl4-intoxicated animals. CONCLUSION: Our results show that SFEE has potential hepatoprotective effects at 150 mg/kg. These effects can be regarded to the antioxidant and anti-inflammatory properties of the extract.

Curcumin ameliorate DENA-induced HCC via modulating TGF-ß, AKT, and caspase-3 expression in experimental rat model.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. In laboratory animal models, diethylnitrosamine (DENA) is a well-known agent that has a potent hepatocarcinogenic effect that is used to induce HCC. As curcumin has a potent anti-inflammatory effect with strong therapeutic potential against a variety of cancers, our present study aims to investigate its curative effects and the possible mechanisms of action against DENA-induced HCC in male rats. Investigation of biochemical and molecular parameters of HCC animal model liver showed an overexpression of TGF-ß and Akt proteins accompanied with a significant reduction of the proapoptotic marker caspase-3. DENA-induced hepatic cellular injury resulted also in a significant increase in liver function marker enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lipid peroxides in this group. Curcumin treatment partially reversed DENA-induced damage as it reduced the overexpression of the angiogenic and anti-apoptotic factors TGF-ß and Akt and improved caspase-3 expression. Also, it could partially normalize the serum values of liver marker enzymes and lipid peroxidation and improve liver architecture. Curcumin shows a unique chemotherapeutic effect in reversing DENA-induced HCC in rat model. This effect is possibly mediated through its proapoptotic, antioxidant, anti-angiogenic, as well as antimitotic effects. It interferes and modulates cell signaling pathways and hence turns death signals and apoptosis on within tumor cells.

The Association between Maternal Endocrine-Disrupting Chemical Exposure during Pregnancy and the Incidence of Male Urogenital Defects: A Systematic Review and Meta-Analysis.

The increasing incidence of hypospadias and cryptorchidism, coupled with the widespread presence of endocrine-disrupting chemicals (EDCs), has raised concerns about the potential impact of these environmental factors on male urogenital development. This systematic review and meta-analysis aims to evaluate the association between maternal exposure to various EDCs and the risk of hypospadias and cryptorchidism. We conducted a comprehensive search of PubMed, Scopus, Web of Science, and Cochrane databases from inception until May 2024. We included case-control and cohort studies that examined the association between maternal EDC exposure and hypospadias or cryptorchidism, reporting adjusted odds ratios (aOR) or crude odds ratios (cOR). Data were extracted and pooled using a random effects model, and heterogeneity was assessed using the Q test and I-square statistics. The risk of bias was evaluated using the Newcastle-Ottawa Scale (NOS). A total of 48 studies were included in the systematic review, with 46 studies included in the meta-analysis. The pooled analysis revealed a significant association between maternal EDC exposure and an increased risk of hypospadias (aOR = 1.26, 95% CI: 1.18-1.35, p < 0.0001) and cryptorchidism (aOR = 1.37, 95% CI: 1.19-1.57, p < 0.001). Subgroup analyses showed that exposure to pesticides, phthalates, alkyl phenolic compounds (ALKs), and heavy metals significantly increased the risk of hypospadias. In contrast, polychlorinated biphenyls (PCBs) did not show a significant association. Significant associations were found with pesticide and PCB exposure for cryptorchidism, but not with phthalate, ALK, or heavy metal exposure. Maternal exposure to certain EDCs is associated with an increased risk of hypospadias and cryptorchidism in male children. These findings underscore the importance of addressing environmental and occupational exposures during pregnancy to mitigate potential risks. Further research is needed to elucidate the mechanisms by which EDCs affect urogenital development and to develop effective interventions to reduce exposure among vulnerable populations.

Improvement of solubility, dissolution, and bioavailability of phenytoin intercalated in Mg-Al layered double hydroxide.

Layered double hydroxides (LDHs) are highly effective drug delivery systems, owing to their capacity to intercalate or adsorb biomaterials, flexible structure, swelling property, high stability, good biocompatibility, and ease of synthesis. Phenytoin (PHT) is an antiseizure BCS (Biopharmaceutics Classification System) class II drug, presenting low aqueous solubility. Therefore, the current study aimed at increasing its solubility, dissolution, and bioavailability. PHT was intercalated to the MgAl-LDH formed in situ and successful intercalation to form MgAl-PHT-LDH was confirmed by FTIR, PXRD, DSC, and TGA. Examination of particle size and morphology (by photon correlation spectroscopy and electron microscopy, respectively) confirmed the formation and intercalation of nanostructured LDH. Intercalation enhanced the saturation solubility of PHT at 25°C in 0.1N HCl and phosphate buffer (pH 6.8) by 6.57 and 10.5 times respectively. The selected drug excipient powder blend for the formulation of MgAl-PHT-LDH tablets exhibited satisfactory properties in both pre-compression parameters (angle of repose, bulk density, tapped density, Carr's index, and Hausner ratio) and tablet characteristics (weight variation, thickness, hardness, friability, content uniformity, and disintegration time). MgAl-PHT-LDH tablets showed better dissolution of PHT compared to unprocessed PHT tablets at all time points. Oral bioavailability of MgAl-PHT-LDH tablets and unprocessed PHT tablets was tested in two groups of Sprague Dawley rats based on analysis of serum levels of both forms of PHT by UPLC-ESI-MS/MS serum. MgAl-PHT-LDH tablets demonstrated a relative bioavailability of 130.15% compared to unprocessed PHT tablets, confirming a significantly higher oral bioavailability of MgAl-PHT-LDH. In conclusion, MgAl-PHT-LDH could provide a strategy for enhancing solubility, dissolution, and thereby bioavailability of PHT, enabling the evaluation of theclinical efficacy of MgAl-PHT-LDH tablets for the treatment of seizures at lower PHT doses.

Comparative Analysis of Intralesional Immunotherapy and Conventional Treatments for Non-Genital Warts: A Systematic Review and Network Meta-Analysis.

INTRODUCTION: Warts, benign skin growths caused by various human papillomavirus strains, are categorized as genital and non-genital. Non-genital warts often lack noticeable symptoms but can lead to psychological distress due to factors like embarrassment. Traditional treatments, including physical and chemical methods, show limitations, prompting the exploration of novel approaches like intralesional immunotherapy. The clinical challenge lies in selecting the most effective modality. OBJECTIVE: In our study, we used the network meta-analysis (NMA) as a statistical tool to explore the most effective intralesional immunotherapy interventions. METHODS: Comprehensive searches of Web of Science, PubMed, Cochrane, and Scopus databases were conducted until December 2023. Eligible studies were analyzed for outcomes presented as risk ratios (RRs) with 95% confidence intervals (CI). Treatments were ranked using the P-score in an NMA performed with R software. RESULTS: We included 68 RCTs in our study. For complete response, needling showed a significant difference compared to Candida albicans antigen (RR= 0.13, 95% CI [0.02; 0.99]) and Mw (RR= 0.12, 95% CI [0.02; 0.94]). In overall response, both bleomycin and furosemide with digoxin were significant compared to autoimplantation (RR= 0.46, 95% CI [0.24; 0.88]) and (RR= 0.40, 95% CI [0.18; 0.91]) respectively. Similarly, both were significant compared to cryotherapy (RR= 0.45, 95% CI [0.27; 0.76]) and (RR= 0.40, 95% CI [0.19; 0.82]) respectively. CONCLUSION: This NMA indicates needling, furosemide with digoxin, and PBP antigen stimulants as effective for non-genital warts, surpassing traditional treatments in complete and overall response. Direct comparisons in future research are warranted to confirm their superiority.

Sitagliptin ameliorates L-arginine-induced acute pancreatitis via modulating inflammatory cytokines expression and combating oxidative stress.

Background: Acute pancreatitis (AP) is an inflammatory condition that resolves spontaneously, but occasionally, develops into systemic inflammation, organ failure and mortality. Oxidative stress and activation of inflammatory pathways represent major players in AP pathogenesis. Current management of AP relies on attenuating injuries to the pancreas and putting the inflammatory process under control. In this study, we investigated the role of sitagliptin in modulating L-arginine-induced AP in rats. Methods: Swiss rats were subdivided into a healthy control group, AP group (a single dose of L-arginine 250 mg/100 g, intraperitoneal), and sitagliptin + L-arginine-treated group (10 mg sitagliptin/kg body weight/day, orally). Sitagliptin treatment started 1 hour after L-arginine injection and continued for 3days. Biochemical and histopathological investigations were performed on serum and tissue samples collected from test animals. Results: L-arginine increased pancreatic meyloperoxidase and serum amylase- and lipase activities and serum levels of TNF-α, LT-α, IFN-γ, IL-1α/ß, IL-6, IL-10, IL-12, and IL-15. AP animals showed elevated MDA and NO and decreased GSH and serum calcium levels. Histopathological changes were observed by H&E staining. Sitagliptin treatment significantly ameliorated these biochemical and histological changes diminishing the signs of AP. Conclusion: Sitagliptin treatment was effective in ameliorating L-arginine-induced AP which can be regarded to its anti-inflammatory and antioxidant effect.

Hepatoma-derived growth factor and nucleolin exist in the same ribonucleoprotein complex.

BACKGROUND: Hepatoma-derived growth factor (HDGF) is a protein which is highly expressed in a variety of tumours. HDGF has mitogenic, angiogenic, neurotrophic and antiapoptotic activity but the molecular mechanisms by which it exerts these activities are largely unknown nor has its biological function in tumours been elucidated. Mass spectrometry was performed to analyse the HDGFStrep-tag interactome. By Pull-down-experiments using different protein and nucleic acid constructs the interaction of HDGF and nucleolin was investigated further. RESULTS: A number of HDGFStrep-tag copurifying proteins were identified which interact with RNA or are involved in the cellular DNA repair machinery. The most abundant protein, however, copurifying with HDGF in this approach was nucleolin. Therefore we focus on the characterization of the interaction of HDGF and nucleolin in this study. We show that expression of a cytosolic variant of HDGF causes a redistribution of nucleolin into the cytoplasm. Furthermore, formation of HDGF/nucleolin complexes depends on bcl-2 mRNA. Overexpression of full length bcl-2 mRNA increases the number of HDGF/nucleolin complexes whereas expression of only the bcl-2 coding sequence abolishes interaction completely. Further examination reveals that the coding sequence of bcl-2 mRNA together with either the 5' or 3' UTR is sufficient for formation of HDGF/nucleolin complexes. When bcl-2 coding sequence within the full length cDNA is replaced by a sequence coding for secretory alkaline phosphatase complex formation is not enhanced. CONCLUSION: The results provide evidence for the existence of HDGF and nucleolin containing nucleoprotein complexes which formation depends on the presence of specific mRNAs. The nature of these RNAs and other components of the complexes should be investigated in future.

Alpha-Mangostin ameliorates acute kidney injury via modifying levels of circulating TNF-α and IL-6 in glycerol-induced rhabdomyolysis animal model.

Alpha mangostin (AM), isolated from G. mangostana, showed beneficial effects in several disorders due to its antioxidant and anti-inflammatory properties. Acute kidney injury (AKI) due to different etiologies can develop into severe complications, resulting in high mortality rates. In this work, AM is tested for its ability to alleviate AKI in glycerol-induced AKI rat model, where 30 Male Sprague-Dawley rats were assigned to a healthy group, glycerol-treated group and AM-treated group. Glycerol- and AM groups received a single dose of glycerol (per IM, 50% glycerol in saline, 8 ml/kg), whereas control group was injected with saline. AM treatment (a single daily dose, per IP, 175mg/kg) was accomplished for three days. Animals were executed to collect blood samples and kidney tissue for biochemical and histological examination. It was found that glycerol induced increase in serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, serum magnesium, TNF-α and IL-6. It also induced renal edema and hypocalcemia along with histopathological renal damage. AM treatment improved renal histological features and alleviated increase in serum creatinine, BUN, serum magnesium, TNF-α and IL-6 levels, as well as renal edema and lipid peroxidation but did not affect serum calcium levels. This suggests AM as a potential therapeutic agent for treating AKI mainly via its antioxidant and anti-inflammatory properties.

Overexpression of hepatoma-derived growth factor in melanocytes does not lead to oncogenic transformation.

BACKGROUND: HDGF is a growth factor which is overexpressed in a wide range of tumors. Importantly, expression levels were identified as a prognostic marker in some types of cancer such as melanoma. METHODS: To investigate the presumed oncogenic/transforming capacity of HDGF, we generated transgenic mice overexpressing HDGF in melanocytes. These mice were bred with mice heterozygous for a defective copy of the Ink4a tumor suppressor gene and were exposed to UV light to increase the risk for tumor development both genetically and physiochemically. Mice were analyzed by immunohistochemistry and Western blotting. Furthermore, primary melanocytes were isolated from different strains created. RESULTS: Transgenic animals overexpressed HDGF in hair follicle melanocytes. Interestingly, primary melanocytes isolated from transgenic animals were not able to differentiate in vitro whereas cells isolated from wild type and HDGF-deficient animals were. Although, HDGF-/-/Ink4a+/- mice displayed an increased number of epidermoid cysts after exposure to UV light, no melanomas or premelanocytic alterations could be detected in this mouse model. CONCLUSIONS: The results therefore provide no evidence that HDGF has a transforming capacity in tumor development. Our results in combination with previous findings point to a possible role in cell differentiation and suggest that HDGF promotes tumor progression after secondary upregulation and may represent another protein fitting into the concept of non-oncogene addiction of tumor tissue.

Hepatoma-derived growth factor-related protein-3: a new neurotrophic and neurite outgrowth-promoting factor for cortical neurons.

Hepatoma-derived growth factor-related proteins (HRPs) make up a family of six members. Hepatoma-derived growth factor-related protein-3 (HRP-3) is the only family member whose expression is almost restricted to nervous tissue. Here we show that soluble HRP-3 acts as a novel neurotrophic factor for cultured primary cortical neurons. Antibody-mediated neutralization of HRP-3 function results in neuronal degeneration. In contrast, HRP-3 as the only addition to a culture medium not supporting neuronal survival rescues neurons to an extent comparable to the addition of FCS. Besides this neuroprotective capability, the protein exerts a neurite outgrowth-promoting effect when it is presented as a coated substrate but not as a soluble factor. This study points to an important role of HRP-3 during the development of the nervous system.

Antioxidant, anti-inflammatory and anti-fibrotic effects of Boswellia serrate gum resin in CCl4-induced hepatotoxicity.

The present study aims to investigate the potential antioxidant, anti-inflammatory and anti-fibrotic effects of Boswellia serrate (BS) gum resin against carbon tetrachloride (CCl4)-induced liver damage. Four groups consisting of eight rats each were designated: Group I, normal healthy control; group II, CCl4-induced liver fibrosis; group III, CCl4-induced liver fibrosis followed by BS treatment daily for two weeks; and group IV, CCl4-induced liver fibrosis followed by silymarin treatment daily for two weeks. Expression of tumor necrosis factor-α (TNF-α) and nuclear factor κB (NF-κB), interleukin-6 (IL-6), transforming growth factor-ß (TGF-ß) and cyclooxygenase-2 (COX-2) were assessed, in addition to histopathological and fibrotic changes in liver tissues isolated from the rats. BS significantly ameliorated CCl4-induced increases in serum aspartate (AST) and alanine transaminase (ALT) levels, reduced lactate dehydrogenase (LDH) activities in addition to restoring total bilirubin, triglyceride and albumin levels. BS treatment also alleviated oxidative stress and improved total antioxidant capacity in the liver, and reduced the expression of TNF-α, NF-κB, TGF-ß, IL-6 and COX-2. On a histopathological level, BS treatment also exhibited antifibrotic activity. In conclusion, these findings suggest that BS contains potentially hepatoprotective effects against CCl4-induced liver injury via its antioxidant, anti-inflammatory and antifibrotic characteristics.

The metabolic disorders associated with chronic consumption of soft and energy drinks in rats.

BACKGROUND: Energy Drinks (EDs) and Soft Drinks (SDs) are widely consumed among adolescents and young adults. These drinks contain variable amounts of caffeine which is a central nervous system stimulator; in addition to sugar, taurine, vitamins and herbal extracts. Several adverse effects have been reported for the excessive consumption of caffeine and sugar. AIM: This work aimed at providing a comparison between the effect of chronic consumption of both drinks on metabolism biochemically as well as at the histopathological level. METHODS: Adult albino rats were randomly divided into three groups and treated for 4 weeks. Animals received water (control, group 1), 12.5 ml/kg/day of either Pepsi® (SD, group 2) or Power Horse® (ED, group 3). All animals had free access to water and standard animal chow. RESULTS: ED and SD groups showed a significant weight gain compared to control. ED animals showed a significant increase in serum urea, hyperlipidemia and hyperglycemia in comparison to control and SD groups. Serum uric acid significantly increased in ED and SD groups. ED group showed congestion and inflammation in their renal tissues in addition to splenomegaly and increased phagocyte infiltration. CONCLUSION: The high caffeine-sugar content in ED exerts a more significant influence on the metabolic pathways than SDs. Both increase the incidence of cardiovascular diseases and tissue inflammation due to their effect on lipid profile and blood glucose. The other ingredients in EDs may play a role in the observed metabolic disturbances. Chronic use of EDs should be especially discouraged to avoid these negative effects.

Generation of Combinatorial Lentiviral Vectors Expressing Multiple Anti-Hepatitis C Virus shRNAs and Their Validation on a Novel HCV Replicon Double Reporter Cell Line.

Despite the introduction of directly acting antivirals (DAAs), for the treatment of hepatitis C virus (HCV) infection, their cost, patient compliance, and viral resistance are still important issues to be considered. Here, we describe the generation of a novel JFH1-based HCV subgenomic replicon double reporter cell line suitable for testing different antiviral drugs and therapeutic interventions. This cells line allowed a rapid and accurate quantification of cell growth/viability and HCV RNA replication, thus discriminating specific from unspecific antiviral effects caused by DAAs or cytotoxic compounds, respectively. By correlating cell number and virus replication, we could confirm the inhibitory effect on the latter of cell over confluency and characterize an array of lentiviral vectors expressing single, double, or triple cassettes containing different combinations of short hairpin (sh)RNAs, targeting both highly conserved viral genome sequences and cellular factors crucial for HCV replication. While all vectors were effective in reducing HCV replication, the ones targeting viral sequences displayed a stronger antiviral effect, without significant cytopathic effects. Such combinatorial platforms as well as the developed double reporter cell line might find application both in setting-up anti-HCV gene therapy approaches and in studies aimed at further dissecting the viral biology/pathogenesis of infection.

Expression of hepatoma-derived growth factor family members in the adult central nervous system.

BACKGROUND: Hepatoma-derived growth factor (HDGF) belongs to a polypeptide family containing five additional members called HDGF related proteins 1-4 (HRP-1 to -4) and Lens epithelial derived growth factor. Whereas some family members such as HDGF and HRP-2 are expressed in a wide range of tissues, the expression of others is very restricted. HRP-1 and -4 are only expressed in testis, HRP-3 only in the nervous system. Here we investigated the expression of HDGF, HRP-2 and HRP-3 in the central nervous system of adult rats on the cellular level by immunohistochemistry. In addition we performed Western blot analysis of various brain regions as well as neuronal and glial cell cultures. RESULTS: HDGF was rather evenly expressed throughout all brain regions tested with the lowest expression in the substantia nigra. HRP-2 was strongly expressed in the thalamus, prefrontal and parietal cortex, neurohypophysis, and the cerebellum, HRP-3 in the bulbus olfactorius, piriform cortex and amygdala complex. HDGF and HRP-2 were found to be expressed by neurons, astrocytes and oligodendrocytes. In contrast, strong expression of HRP-3 in the adult nervous system is restricted to neurons, except for very weak expression in oligodendrocytes in the brain stem. Although the majority of neurons are HRP-3 positive, some like cerebellar granule cells are negative. CONCLUSION: The coexpression of HDGF and HRP-2 in glia and neurons as well as the coexpression of all three proteins in many neurons suggests different functions of members of the HDGF protein family in cells of the central nervous system that might include proliferation as well as cell survival. In addition the restricted expression of HRP-3 point to a special function of this family member for neuronal cells.