role of microRNAs in the main molecular pathways of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is the most common primary liver malignant neoplasia. HCC is characterized by a poor prognosis. The need to find new molecular markers for its diagnosis and prognosis has led to a progressive increase in the number of scientific studies on this topic. MicroRNAs(miRNAs) are small noncoding RNA that play a role in almost all main cellular pathways. miRNAs are involved in the regulation of expression of the major tumor-related genes in carcinogenesis, acting as oncogenes or tumor suppressor genes. The aim of this review was to identify papers published in 2017 investigating the role of miRNAs in HCC tumorigenesis. miRNAs were classified according to their role in the main molecular pathways involved in HCC tumorigenesis:(1) m TOR;(2) Wnt;(3) JAK/STAT;(4) apoptosis; and(5) MAPK. The role of miRNAs in prognosis/response prediction was taken into consideration. Bearing in mind that the analysis of miRNAs in serum and other body fluids would be crucial for clinical management, the role of circulating miRNAs in HCC patients was also investigated. The most represented mi RNA-regulated pathway in HCC is m TOR, but apoptosis, Wnt, JAK/STAT or MAPK pathways are also influenced by mi RNA expression levels. These miRNAs could thus be used in clinical practice as diagnostic, prognostic or therapeutic targets for HCC treatment.

Molecular alterations in pancreatic tumors

Genetic alterations in pancreatic tumors can usually be classified in:(1)Mutational activation of oncogenes;(2)Inactivation of tumor suppressor genes;and(3)Inactivation of genome maintenance genes controlling the repair of DNA damage.Endoscopic ultrasound-guided fine-needle aspiration has improved preoperative diagnosis,but the management of patients with a pancreatic lesion is still challenging.Molecular testing could help mainly in solving these“inconclusive”specimens.The introduction of multi-gene analysis approaches,such as next-generation sequencing,has provided a lot of useful information on the molecular characterization of pancreatic tumors.Different types of pancreatic tumors(e.g.,pancreatic ductal adenocarcinomas,intraductal papillary mucinous neoplasms,solid pseudopapillary tumors)are characterized by specific molecular alterations.The aim of this review is to summarize the main molecular alterations found in pancreatic tumors.

Peptides-based vaccine against SARS-nCoV-2 antigenic fragmented synthetic epitopes recognized by T cell and β-cell initiation of specific antibodies tofightthe infection

The World Health Organization has declared the rapidly spreading coronavirus to be a global pandemic.The FDA is yet to approve a vaccine for human novel coronavirus.Here,we developed a peptide-based vaccine and used high-throughput screening by molecular dynamics simulation to identify T-cell-and p-cell-recognized epitopes for producing specific antibod-ies against SARS-nCoV-2.We construct~12 P'antigenic epitope peptides to develop a more effective vaccine and identify specific antibodies.These epitope peptides selectively presented the best antigen presentation scores for both human pMHC class I and II alleles to develop a strong binding affinity.All antigens identified of SARS-nCoV-2 different proteins by each attached specific~1-7 L linker adaptor were used to construct a broad single peripheral peptide vaccine.It is expected to be highly antigenic with a minimum allergic effect.As a result of these exciting outcomes,expressing a vaccine using the intimated peptide was highly promising and positive to be highly proposed as epitope-based peptide vaccine of specific antibody against SARS-nCoV-2 by initiating T cells and β-cells.An in vitro study for the proposed peptide-based vaccine is.mostly recommended.Further clinical trials are required to check the efficacy of this vaccine.

Interpreting Results of Ethanol, Carbamazepine and Topiramate in Putrefied Postmortem Specimens： A Case Report

CBZ （carbamazepine）, CBZ-epox （carbamazepine-10,11-epoxide）, TPR （topiramate） and ethanol were detected in 37-year-old woman buried in the wall founded eighteen months after death. The woman was in treatment with anticonvulsants. The cause of death was strangulation investigated by immunohistochemical with GPA （glycophorin A）. Routine analyses for drugs of abuse, therapeutic drugs and volatiles were conducted. Carbamazepine, Topiramate and Alcohol were quantified in abdominal effusion, gastric wall, spleen, douglas fluid, skeletal muscles, endothoracic fluid, kidney, liver, heart and bone marrow. CBZ, CBZ-epox and TPR were recovered in samples deproteinized by acetonitrile spiked with DNSnVal as Internal Standard. Compounds were detected by HPLC-MS/MS. Alcohol was detected in any specimens by HS-GC/FID. CBZ concentrations were ranged from 0.49 in liver to 13.6 ~tg/g in endothoracic fluid; CBZ-Epox 0.46 in skeletal muscle, and 1.13 pg/g in Douglas fluid; TPR 0.11 in gastric wall and 1.23 Ixg/g in endothoracic fluid; alcohol from 0.17 in bone marrow to 0,75 mg/g in Douglas fluid. To our knowledge this is the first report of the presence of carbamazepine, topiramate, and alcohol in post mortem putrefied specimens.

Mitochondrial cytochrome oxidase 1 reveals genetic diversity of the African Snakehead fish Parachanna obscura,Gunther,1861 from Nigeria’s freshwater environment

The study investigated the genetic variation of Parachanna obscura from five rivers(Anambra,Ibbi,Imo,Katsina-Ala and Ogun)in Nigeria using the mitochondrial cytochrome oxidase 1 gene.DNA was extracted from 19,22,16,18 and 21 fin clips per river population,respectively and subjected to polymerase chain reaction.A total of 96 sequences,each with 671 bp were obtained with 38(5.6%)polymorphic,27(3.8%)parsimoniously informative and 659(98.2%)conserved sites.Mean nucleotide composition was C=28.07%,T=29.43%,A=22.18%,G=20.32%.A total of 40 haplotypes with 38 unique sequences as well as 24 substitutions with 22 transversions and two transitions were obtained.Nucleotide diversity among populations ranged from 0.00184 to 0.00888 representing Ibbi and Imo,respectively while haplotype diversity ranged from 0.77056 to 0.95000 also,from Ibbi and Imo,respectively.Analyses of molecular variance showed that the intra-population variation accounted for 50.05%.Topology from phylogenetic analyses revealed that P.obscura from Imo River was distinctly different from the rest.

Retrospective cytological evaluation of indeterminate thyroid nodules according to the British Thyroid Association 2014 classification and comparison of clinical evaluation and outcomes

The cytology of 130 indeterminate nodules （Thy 3） was retrospectively reviewed according to the British Thyroid Association 2014 classification. Nodules were divided into Thy 3a （atypical features） and Thy 3f （follicular lesion） categories. Histology was available as a reference for 97 nodules. Pre-surgical evaluations comprised biochemical tests, color-Doppler ultrasonogrephy （US）, semi-quantitative elastography-US （USE）, contrast-enhanced US （CEUS）, and mutation analysis from cytological slides. Thyroid malignancy was the final diagnosis for 19% of surgically- treated nodules. No statistically significant difference in the risk of malignancy was found between Thy 3a （26%） and Thy 3f （14%） nodules. Histology of the Thy 3a and Thy 3f nodules showed a higher incidence of Hurtle cell adenomas in Thy 3f （29%） than in Thy 3a （3%） nodules （P=0.01）. The only pre-surgical difference concerned the BRAF V600E mutation, which was positive in some Thy 3a but not in any Thy 3f nodules （P=0.04）. Receiver-operating characteristic （ROC） analysis was used to obtain cut-off values from US （score）, USE （ELX 2/1 strain index）, and CEUS （time-to- peak index and peak index） data. The cut-off values were similar for Thy 3a and Thy 3f nodules. Data showed that malignancy can be suspected if the US score is 〉2, ELX 1/2 strain index 〉1, time-to-peakindex 〉1, and peak index 〈1. In a sub-group of 24 revised nodules （12 Thy 3a and 12 Thy 3f） with histology as a reference, the diagnostic power of cumulative pre-surgical analysis by means of US, USE, and CEUS showed high positive and negative predictive values （83% and 100%, respectively） for the presence of malignancy in Thy 3a and Thy 3f nodules. In conclusion, in our series of revised Thy 3 nodules, malignancy was low and displayed no significant differences between Thy 3a and Thy 3f categories. The use of cut-offs based on histology as a reference could reduce surgery. Our data support the conviction that, in mutation-negative Thy 3a and Thy 3f nodules, observation should be the first choice when not all instrumental results are suspect.