Competitive endogenous RNA networks: Decoding the role of long non-coding RNAs and circular RNAs in colorectal cancer chemoresistance.

Colorectal cancer (CRC) is recognized as one of the most common gastrointestinal malignancies across the globe. Despite significant progress in designing novel treatments for CRC, there is a pressing need for more effective therapeutic approaches. Unfortunately, many patients undergoing chemotherapy develop drug resistance, posing a significant challenge for cancer treatment. Non-coding RNAs (ncRNAs) have been found to play crucial roles in CRC development and its response to chemotherapy. However, there are still gaps in our understanding of interactions among various ncRNAs, such as long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs). These ncRNAs can act as either oncogenes or tumour suppressors, affecting numerous biological functions in different cancers including CRC. A class of ncRNA molecules known as competitive endogenous RNAs (ceRNAs) has emerged as a key player in various cellular processes. These molecules form networks through lncRNA/miRNA/mRNA and circRNA/miRNA/mRNA interactions. In CRC, dysregulation of ceRNA networks has been observed across various cellular processes, including proliferation, apoptosis and angiogenesis. These dysregulations are believed to play a significant role in the progression of CRC and, in certain instances, may contribute to the development of chemoresistance. Enriching our knowledge of these dysregulations holds promise for advancing the field of diagnostic and therapeutic modalities for CRC. In this review, we discuss lncRNA- and circRNA-associated ceRNA networks implicated in the emergence and advancement of drug resistance in colorectal carcinogenesis.

Evaluation of epigenetic (HDAC, DNMT) and pain (Gad65, TGF) factors following photobiomodulation therapy in a neuropathic pain model.

Photobiomodulation therapy (PBMT) is converted to the most common analgesic treatment before the whole mechanism is yet to be discovered. This study for the first time was designed to investigate alternations of epigenetic factors after pain and PBMT. The CCI model was chosen to induce pain. Pain evaluation tests including plantar, acetone, von Frey, and pinch were done weekly. Then spinal cord tissue was isolated for evaluating mRNA expression of DNMT3a, HDAC1, and NRSF using RT-qPCR method, and protein expression factors of HDAC2 and DNMT3a using western blotting. GAD65 and TGF-ß proteins were assessed by the IHC method. PBMT increased the pain threshold up to the point where it roughly met the pain threshold of the control group. After three weeks of treatment, both PBMT protocols demonstrated a reduction in allodynia and hyperalgesia. While some molecules, such as TGF-ß and Gad65, increased following PBMT, we observed no inhibition of NRSF, HDAC1, and DNMT3a expression despite implementing two different protocols.

Whole exome sequencing identifies novel pathogenic variants in TGM1 and ALOX12B in patients with hereditary ichthyosis.

BACKGROUND: Hereditary ichthyosis is a clinically and genetically heterogeneous disorder associated with more than 50 genes with TGM1, ALOX12B, and ALOXE3 being the most prevalent. Establishing an accurate diagnosis is important for effective genetic counseling and optimal patient management. OBJECTIVE: We studied the diagnostic value of whole exome sequencing (WES) in a small case series with hereditary ichthyosis. METHODS: During a 1-year period, index cases of 5 unrelated families clinically diagnosed with hereditary ichthyosis went through WES, followed by extensive segregation analysis. Prenatal diagnosis (PND) was conducted where indicated. RESULTS: We identified 4 homozygous variants-2 in TGM1 (c.655A > G and c.797A > G) and 2 in ALOX12B (c.527 + 2 T > G and c.1654G > T)-alongside a heterozygous variant in TGM1 (c.428G > A) in 5 families. The variants were all pathogenic/likely pathogenic according to the ACMG classification and segregation analysis, except for c.797A > G in TGM1 which remained a variant of unknown clinical significance. Four variants were novel. All families were referred either during pregnancy or before reproductive planning; 4 benefited from WES as it identified the mutation in the probands and enabled carrier detection in at-risk relatives; PND was conducted in 2 families. CONCLUSION: Our findings further support WES is a powerful tool for the comprehensive, accurate, and rapid molecular diagnosis of hereditary ichthyosis and can offer opportunities for reproductive planning, carrier screening and prenatal diagnosis to at-risk families.

The prevalence of restless legs syndrome (RLS) in patients with multiple sclerosis (MS): a systematic review and meta-analysis-an update.

INTRODUCTION: The prevalence of restless legs syndrome (RLS) is reported to vary in patients with multiple sclerosis (MS) in studies which are conducted in different populations. The goal of this systematic review and meta-analysis is to update the prevalence of RLS in MS cases. METHODS: We searched PubMed, Scopus, EMBASE, CINAHL, Web of Science, Google Scholar, and gray literature including references from identified studies and conference abstracts which were published up to June 2021. Data on the total number of participants, first author, country, disease duration, number of controls, mean patient age, male and female numbers, mean EDSS, and number of cases and/or controls with RLS were extracted from the included studies. RESULTS: The literature search revealed 855 articles; after deleting duplicates, 530 remained. For the meta-analysis, 75 studies were included (Fig. 1). In six articles, the authors did not differentiate between CIS and MS cases when reporting RLS cases. In total, 15,411 MS/CIS patients were evaluated and 4309 had RLS. The pooled prevalence of RLS was 28% (95% CI: 24-33%). The pooled prevalence of RLS in men was 22% (95% CI: 17-26%), and the pooled prevalence of RLS in women was 30% (95% CI: 25-35%). The pooled prevalence of RLS in controls was 8% (95% CI: 6-10%). CONCLUSION: The results of this systematic review and meta-analysis show that the pooled prevalence of RLS is 28% in MS cases and 8%. The pooled prevalence is higher in women than men (30% vs 22%).

Circulating serum miR-1246 and miR-1229 as diagnostic biomarkers in colorectal carcinoma.

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide. Although colonoscopy is considered as the "Gold Standard" technique to detect CRC, its application is invasive and cost incurred. Thus, noninvasive or minimally invasive approaches are of utmost importance. The aberrant expression of some microRNAs (miRNAs, miRs) has been suggested in association with CRC pathogenesis. This study aimed to validate if circulating serum miR-1229 and miR-1246 are diagnostic biomarkers for CRC. Materials and Methods: Serum samples were isolated from 45 CRC patients and also 45 healthy controls (HC). The expression levels of circulating serum-derived miR-1229 and miR-1246 were evaluated by quantitative real-time polymerase chain reaction. Receiver operating characteristic (ROC) curves were constructed to evaluate the CRC diagnostic accuracy of selected miRNAs. Furthermore, the association of candidate miRNAs and clinicopathological characteristics were evaluated. Functional enrichment of the candidate miRNAs was applied using in silico tools. Results: The expression of miR-1229 and miR-1246 was significantly higher in CRC patients than HC (P < 0.0001) and also was found in association with lymph node metastasis (P < 0.05). We demonstrated a significant up-regulation of serum-derived miR-1246 in advanced tumor-node-metastasis stage III of CRC patients (P < 0.05). Areas under the ROC curve of miR-1229 and miR-1246 were 0.81 and 0.84, respectively (P < 0.0001). Conclusion: We confirmed the capability of circulating serum miR-1229 and miR-1246 as novel diagnostic biomarkers for CRC.

Structural Analysis and Conformational Dynamics of Short Helical Hyperphosphorylated Segments of Tau Protein (Sequence 254-290) in Alzheimer's Disease: A Molecular Dynamics Simulation Study.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder whose early diagnosis leads to a chance for successful treatment and decreases the side effects. Hyperphosphorylation of tau proteins is a pathological hallmark of AD that causes it to lose its attachment ability to the microtubules. Alteration of tau structure due to its hyperphosphorylation is an exciting challenge regarding AD treatments. Here, we aimed to examine the structural alterations of short helical segments of tau protein with one to three phosphorylated sites by molecular dynamics simulation. Results indicated that the interaction of two similar segments with three phosphorylated sites (P-Ser262, 285, and 289) formed a compact and more stable structure than the one phosphorylated site complex (P-Ser262). Moreover, due to the high dynamics of the P-Ser262 complex, several structures were made with different conformational dynamics, but there was only one stable cluster of the P-Ser262, 285, and 289 complex during simulation. It seems that the P-Ser262, 285, and 289 complex plays an important role in the formation of paired helical filaments (PHFs) by forming a stable dimer. Generally, it is important to identify how structural features of segments in tau protein change when the phosphorylated sites increase from one to three sites and their effects on the formation of PHFs for drug design and diagnostic biomarkers.

Oligodendrocyte Development and Implication in Perinatal White Matter Injury.

Perinatal white matter injury (WMI) is the most common brain injury in premature infants and can lead to life-long neurological deficits such as cerebral palsy. Preterm birth is typically accompanied by inflammation and hypoxic-ischemic events. Such perinatal insults negatively impact maturation of oligodendrocytes (OLs) and cause myelination failure. At present, no treatment options are clinically available to prevent or cure WMI. Given that arrested OL maturation plays a central role in the etiology of perinatal WMI, an increased interest has emerged regarding the functional restoration of these cells as potential therapeutic strategy. Cell transplantation and promoting endogenous oligodendrocyte function are two potential options to address this major unmet need. In this review, we highlight the underlying pathophysiology of WMI with a specific focus on OL biology and their implication for the development of new therapeutic targets.

Deep brain stimulation for multiple sclerosis tremor: A systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aims to evaluate efficacy of deep brain stimulation (DBS) in treating MS-related tremor. METHODS: We systematically searched PubMed, Web of Science, Embase, Scopus, Google Scholar, and gray literature using a search strategy including the MeSH and text words as (((Brain Stimulations) OR (Deep Brain Stimulations) OR (Deep Brain Stimulations) OR (Deep Brain Brain Stimulation) OR (Deep Electrical Stimulation of the Brain)) AND (Multiple Sclerosis OR Sclerosis, Multiple) OR Sclerosis, Disseminated) OR Disseminated Sclerosis) OR MS (Multiple Sclerosis)) OR Multiple Sclerosis, Acute Fulminating). RESULTS: The literature search revealed 1663 articles, 1027 of which remained after removing duplicates. Seventeen articles, published between 1999-2018, were included for the meta-analysis, including overall 168 patients. Follow-up time ranged between 6-62 months. The pooled frequency of tremor improvement among the enrolled patients was 73%, (95% CI:64-83%) (I2=84.1%, p<0.001). The pooled standardized mean difference (SMD) (after -before) was -2.9, (95% CI:-4.8, -0.98) (I2=89.8%, p<0.001). CONCLUSION: The results of this systematic review and meta-analysis demonstrate MS-related tremor improvement after DBS.

Dendrosomal nanocurcumin promotes remyelination through induction of oligodendrogenesis in experimental demyelination animal model.

Multiple sclerosis (MS) is an autoimmune disease, associated with central nervous system (CNS) inflammation, demyelination, and axonal loss. Myelin, a multilayer membranous that covers nerve fibers, is essential for rapid impulse conduction. Oligodendrocytes that are generated either from CNS-resident oligodendrocyte progenitor cells (OPCs) or subventricular zone-derived neural stem cells (NSCs) are the myelinating cells of the CNS. The adult CNS maintains a certain endogenous potential to repair myelin damage. However, this process often fails as MS progresses. The origin of this failure is not fully understood, but it is likely to relate to progenitors/stem cells' arrestment in a quiescent state, incapable of generating new oligodendrocyte. Current treatments for MS are immunomodulatory or immunosuppressive medications, with little to no effect on myelin restoration. Recent studies have provided proof-of-principle that CNS remyelination can be promoted either via enhancing endogenous remyelination or by transplanting myelinating cells. Curcumin, a natural polyphenolic compound, has been shown to have therapeutic properties in several neurodegenerative diseases. Here, we investigated the effect of a curcumin nanoformulation, dendrosomal nanoparticles (DNC) on oligodendrogenesis and remyelination, both in vitro and in animal model of demyelination. We indicated that DNC enhanced oligodendrogenesis from NSCs and OPCs, in vitro in dose dependent manner. DNC also induced in vivo remyelination via promotion of oligodendrogenesis. Furthermore, DNC enhanced remyelination capacity of transplanted NSCs through promoting their survival and oligodendrogenesis capacity. Our findings suggest that DNC has significant beneficial effects in demyelinating conditions, either as mono-therapy or as being paired with transplantation approaches.

Protective Effects of a Nano-Formulation of Curcumin against Cuprizone-Induced Demyelination in the Mouse Corpus Callosum.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS), characterized by neuroinflammation, oligodendrocytes (OLs) loss, and demyelination Curcumin, a natural phenolic substance, has been shown to have significant therapeutic properties in various neurodegenerative diseases, including MS. In our laboratory by loading curcumin in dendrosome nanoparticles we improved its solubility and bioavailability. Our previous study showed anti-inflammatory and anti-oxidative effects of dendrosomal nano-curcumin (DNC) in experimental autoimmune encephalomyelitis (EAE) model of MS. Here, by using a toxic demyelination model, induced by cuprizone (CPZ), we investigated the protective effect of DNC on oligodendroglial lineage cells (OLLC) and myelin preservation in context of acute demyelination. CPZ is a copper chelator, thus its intake reduces the mitochondrial activity, activates oxidative stress response, leading to specific OLs death, due to their high-energy consumption. We also evaluated DNC effect on activation of astrocytes and microglia, which are enriched in both MS and CPZ demyelinated lesions. Our results demonstrated that DNC treatment protected Oligodendrocyte lineage cells (OLLCs) against CPZ toxin. Besides DNC treatment suppressed accumulation of astrocytes and microglia in CC of CPZ-fed mice, compared to PBS treated onse. Moreover, DNC treatment lead to higher index of luxol fast bluefast blue (LFB) and myelin-specific proteins, myelin basic protein (MBP) intensity in the corpus callosum (CC), as indicators of myelin content. These results suggest a potent pleiotropic therapeutic efficiency for DNC for protection of myelinating cells, possibly via suppression of astrocytes and microglia.

Autophagy Modulators: Mechanistic Aspects and Drug Delivery Systems.

Autophagy modulation is considered to be a promising programmed cell death mechanism to prevent and cure a great number of disorders and diseases. The crucial step in designing an effective therapeutic approach is to understand the correct and accurate causes of diseases and to understand whether autophagy plays a cytoprotective or cytotoxic/cytostatic role in the progression and prevention of disease. This knowledge will help scientists find approaches to manipulate tumor and pathologic cells in order to enhance cellular sensitivity to therapeutics and treat them. Although some conventional therapeutics suffer from poor solubility, bioavailability and controlled release mechanisms, it appears that novel nanoplatforms overcome these obstacles and have led to the design of a theranostic-controlled drug release system with high solubility and active targeting and stimuli-responsive potentials. In this review, we discuss autophagy modulators-related signaling pathways and some of the drug delivery strategies that have been applied to the field of therapeutic application of autophagy modulators. Moreover, we describe how therapeutics will target various steps of the autophagic machinery. Furthermore, nano drug delivery platforms for autophagy targeting and co-delivery of autophagy modulators with chemotherapeutics/siRNA, are also discussed.

Genotypic effect of a mutation of the MYBPC3 gene and two phenotypes with different patterns of inheritance.

BACKGROUND: MYBPC3 mutations have been described in dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). A mutation, c.3373G>A, has been reported to cause autosomal recessive form of HCM. Here, we report that this mutation can cause autosomal dominant form of DCM. METHODS: Next-generation sequencing using targeted panel of a total of 23 candidate genes and following Sanger sequencing was applied to detect causal mutations of DCM. Computational analyses were also performed using available software tools. In silico structural and functional analyses including protein modeling and prediction were done for the mutated MYBPC3 protein. RESULTS AND CONCLUSION: Targeted sequencing showed one variant c.3373G>A (p.Val1125Met) in the studied family following autosomal dominant inheritance. Computational programs predicted a high score of pathogenicity. Secondary structure of the region surrounding p.Val1125 was changed to a shortened beta-strand based on prediction of I-TASSER and Phyre2 servers with high confidence value for the mutation. cMyBP-C protein was modeled to 3dmkA. Our findings suggest that one single mutation of MYBPC3 may have different effects on the cellular mechanisms based of its zygosity. Various factors might be considered for explaining this phenomenon. This gene may have an important role in Iranian DCM and HCM patients.

MYO15A splicing mutations in hearing loss: A review literature and report of a novel mutation.

Sensorineural hearing loss (SNHL) is the most prevalent genetic sensory defect in humans, affecting about 1 in 1000 newborns around the world. Non-syndromic SNHL accounts for nearly 70% of hereditary hearing loss and 80% of SNHL cases show an autosomal recessive mode of inheritance (ARNSHL). In the present study, we applied targeted-exome sequencing to a family with a single proband affected by congenital sensorineural hearing loss. 127 known genes were sequenced to find the causative mutation. One novel homozygous donor splice site mutation, c.4596 + 1G > A (IVS12 + 1G > A) was found in MYO15A gene. Analysis of this mutation within the family showed that the mutation segregates with hearing loss. New DNA sequencing technologies could lead to identification of the disease causing variants especially in highly heterogeneous disorders such as hearing loss.

Attempts to Overcome Remyelination Failure: Toward Opening New Therapeutic Avenues for Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system that results in destruction of the myelin sheath wrapped around the axons and eventual axon degeneration. The disease is pathologically heterogeneous; however, perhaps its most frustrating aspect is the lack of efficient regenerative response for remyelination. Current treatment strategies are based on anti-inflammatory or immunomodulatory medications that have the potential to reduce the numbers of newly evolving lesions. However, therapies are still required that can repair already damaged myelin for which current treatments are not effective. A prerequisite for the development of such new treatments is understanding the reasons for insufficient endogenous repair. This review briefly summarizes the currently suggested causes of remyelination failure in MS and possible solutions.

Evaluation of Iron Oxide Nanoparticles Toxicity on Liver Cells of BALB/c Rats.

BACKGROUND: Because of their unique magnetic properties, Fe3O4 nanoparticles (Fe3O4-NPs) have extensive applications in various biomedical aspects. Investigation of the possible adverse aspects of these particles has lagged far behind their fast growing application. OBJECTIVES: The current study aimed to evaluate the toxicity of Fe3O4-NPs in the liver of mice. MATERIALS AND METHODS: In the present clinical trial, 90 BALB/c mice were randomly divided in 15 groups. Five control groups were fed by usual water and food. Five placebo groups were gavaged with physiological serum in doses of 25, 50, 75, 150, and 300 micrograms per gram of body weight (µg/gr). Five experimental groups were gavaged with Fe3O4-NPs, in doses of 25, 50, 75, 150, and 300 µg/gr. This pattern was repeated every other day, for 3 days. Then, the levels of liver enzymes [alanine transaminase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP)] were compared between these groups. The histological alterations of livers were examined, as well. For statistical analysis, Kruskal-Wallis and Mann-Whitney, with type I Bonferroni correction, as post-hoc, have been used. RESULTS: The administration of 150 and 300 µg/gr doses of Fe3O4-NPs were associated with significant elevation in liver enzymes, compared to controls (P < 0.0001). Furthermore, the histopathological effects were observed in the liver tissue of these groups. However, in groups treated with lower doses of Fe3O4-NPs, no significant adverse effect was observed. CONCLUSIONS: Based on our results, the administration of Fe3O4-NPs causes dose dependent adverse effects on liver.

The therapeutic use of analgesics in patients with liver cirrhosis: a literature review and evidence-based recommendations.

CONTEXT: Pain management in cirrhotic patients is a major clinical challenge for medical professionals. Unfortunately there are no concrete guidelines available regarding the administration of analgesics in patients with liver cirrhosis. In this review we aimed to summarize the available literature and suggest appropriate evidence-based recommendations regarding to administration of these drugs. EVIDENCE ACQUISITION: An indexed MEDLINE search was conducted in July 2014, using keywords "analgesics", "hepatic impairment", "cirrhosis", "acetaminophen or paracetamol", "NSAIDs or nonsteroidal anti-inflammatory drugs", "opioid" for the period of 2004 to 2014. All randomized clinical trials, case series, case report and meta-analysis studies with the above mentioned contents were included in review process. In addition, unpublished information from the Food and Drug Administration are included as well. RESULTS: Paracetamol is safe in patients with chronic liver disease but a reduced dose of 2-3 g/d is recommended for long-term use. Non-steroidal anti-inflammatory drugs (NSAIDs) are best avoided because of risk of renal impairment, hepatorenal syndrome, and gastrointestinal hemorrhage. Most opioids can have deleterious effects in patients with cirrhosis. They have an increased risk of toxicity and hepatic encephalopathy. They should be administrated with lower and less frequent dosing in these patients and be avoided in patients with a history of encephalopathy or addiction to any substance. CONCLUSIONS: No evidence-based guidelines exist on the use of analgesics in patients with liver disease and cirrhosis. As a result pain management in these patients generates considerable misconception among health care professionals, leading under-treatment of pain in this population. Providing concrete guidelines toward the administration of these agents will lead to more efficient and safer pain management in this setting.

Interleukin 18 gene promoter polymorphisms and susceptibility to chronic hepatitis B infection: a review study.

CONTEXT: The variation in clinical outcome of hepatitis B virus (HBV) infection is determined by virological, immunological and host genetic factors. Genes encoding cytokines are one of the candidates among host genetic factors. Polymorphisms in gene promoter can lead to different levels of cytokine expression and unique immune response. Being involved in the inflammatory cytokine network, interleukin-18 (IL-18) plays an important role in pathogenesis of HBV infection. The aim of this review is considering available literature on the association between IL-18 gene promoter single nucleotide polymorphisms (-137 C/G and -607 A/C) and susceptibility to chronic HBV infection. EVIDENCE ACQUISITION: Published literature from PubMed, EMBASE, and other databases were retrieved. All studies investigating the association of IL-18 gene promoter SNPs, -137 C/G and -607 A/C, with susceptibility to chronic HBV infection were included. RESULTS: Findings showed that the genotype -607A/A is associated with the susceptibility to chronic hepatitis B. Furthermore, allele C at position -137 is suggested to play a protective role against development of chronic HBV infection. CONCLUSIONS: Host genetic factors play an important role in determining the outcome of HBV infection. It is suggested that IL-18 genotype -607 A/A is associated with susceptibility to chronic hepatitis B. Furthermore, the carriage of allele C at position -137 may play a protective role in the development of chronic HBV infection.

Anesthesia Personnel's Knowledge of, Attitudes Toward, and Practice to Prevent Needlestick Injuries.

Anesthesia personnel are at risk for needlestick injuries (NSIs). This study evaluated the knowledge of, attitudes toward, and practice of preventing NSIs among anesthesia personnel in four Iranian university hospitals. A self-administered anonymous questionnaire was distributed to 104 anesthesia personnel. In addition, hospital infection control center records were reviewed. The prevalence of NSI among anesthesia personnel was 56.8%. Only 32.2% reported their NSI. Men were more knowledgeable about the risks associated with NSI and the application of standard precautions than women, but were also more likely to experience NSI. Standard precautions were often not followed. In contrast with other hospital staff, most reported NSIs among anesthesia personnel produced high-risk exposures. The knowledge and prevention practices of anesthesia personnel related to needles and other sharps were not satisfactory. These health care providers need appropriate training on standard precautions and administrative oversight to improve their practices. Anesthesia personnel's gender and position should also be considered to improve compliance.

Distinct Toll-like Receptor 3 and 7 Expression in Peripheral Blood Mononuclear Cells From Patients with Chronic Hepatitis C Infection.

BACKGROUND: Hepatitis C virus (HCV) is a major cause of chronic liver disease, with around 130 million infected people worldwide. HCV is recognized by Toll-like receptors (TLRs), which are key mediators of innate immune response. Up on activation of TLRs, anti-viral cytokines and pre-inflammatory are produced. OBJECTIVES: In this study, we compared the expression levels of two members of the TLR family (TLR3 and TLR7) that recognize viral RNA in peripheral blood mononuclear cell (PBMC) of patients with chronic HCV infection and healthy controls. PATIENTS AND METHODS: In this case-control study, blood samples were collected from patients admitted to Blood Transfusion Research Center, Tehran, Iran. PBMC was isolated from blood of chronic HCV patients (n = 25) and age and sex-matched healthy controls (n = 25). RNA was extracted from PBMC and cDNA was synthesized from total RNA templates using reverse transcriptase. The relative level of expression was quantified by real-time PCR using Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as reference gene and the results were compared by Pfaffl method. Data were analyzed using non-parametric Wilcoxon test. P < 0.05 was considered significant. RESULTS: In both groups, we had 13 males and 12 females with a mean age of 48.7 ± 16. TLR3 (6.23 ± 0.91 vs. 3.89 ± 0.85, P < 0.001) and TLR7 (1.48 ± 0.82 vs-1.33 ± 1.18, P < 0.001) expressions were significantly lower in patients with chronic HCV infection when compared with healthy controls. CONCLUSIONS: This study suggests that decrease in levels of TLR3 and TLR7 expression is a mechanism that may enable HCV to evade the host innate immune response.

Hepatotoxicity of halogenated inhalational anesthetics.

CONTEXT: Halogenated inhalational anesthetics are currently the most common drugs used for the induction and maintenance of general anesthesia. Postoperative hepatic injury has been reported after exposure to these agents. Based on much evidence, mechanism of liver toxicity is more likely to be immunoallergic. The objective of this review study was to assess available studies on hepatotoxicity of these anesthetics. EVIDENCE ACQUISITION: We searched PubMed, Google Scholar, Scopus, Index Copernicus, EBSCO and the Cochrane Database using the following keywords: "inhalational Anesthetics" and "liver injury"; "inhalational anesthetics" and "hepatotoxicity"; "volatile anesthetics" and "liver injury"; "volatile anesthetics" and hepatotoxicity for the period of 1966 to 2013. Fifty two studies were included in this work. RESULTS: All halogenated inhalational anesthetics are associated with liver injury. Halothane, enflurane, isoflurane and desflurane are metabolized through the metabolic pathway involving cytochrome P-450 2E1 (CYP2E1) and produce trifluoroacetylated components; some of which may be immunogenic. The severity of hepatotoxicity is associated with the degree by which they undergo hepatic metabolism by this cytochrome. However, liver toxicity is highly unlikely from sevoflurane as is not metabolized to trifluoroacetyl compounds. CONCLUSIONS: Hepatotoxicity of halogenated inhalational anesthetics has been well documented in available literature. Halothane-induced liver injury was extensively acknowledged; however, the next generation halogenated anesthetics have different molecular structures and associated with less hepatotoxicity. Although anesthesia-induced hepatitis is not a common occurrence, we must consider the association between this disorder and the use of halogenated anesthetics.