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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.

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.

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. 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. 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. 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.

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.

Abstract IntroductionThe 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.MethodsWe 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.ResultsThe 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%).ConclusionThe 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%).

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. 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. 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. 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.

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.

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.

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

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.