A novel HCV electrochemical biosensor based on a polyaniline@Ni-MOF nanocomposite.

Hepatitis-C virus ribonucleic acid (HCV-RNA) recognition and quantification based on real-time polymerase chain reaction (RT-PCR) is key to infection control, management, and response to treatment due to its specificity, sensitivity, and quantification capabilities. However, the high cost, time requirements, and need for sophisticated laboratory infrastructure have limited the use of this method in rapid screening, blood banks, and point-of-care testing (POCT). In this work, a novel label-free electrochemical biosensor constructed using a polyaniline@nickel metal-organic framework (Ni-MOF) nanocomposite was developed for direct detection of unamplified HCV nucleic acid. A robust biosensor was fabricated using smooth layer-by-layer deposition of the polyaniline@Ni-MOF nanocomposite, deoxyribonucleic acid (DNA) probe, and bovine serum albumin (BSA) onto a glassy carbon electrode (GCE) and was subsequently monitored real-time via cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The sensitivity and specificity of the newly developed biosensor were specifically examined using the EIS approach. The results revealed that the novel biosensor is highly efficient in quantitative sensing of the HCV target in the presence of nonspecific nucleic acids over the range of 1 fM-100 nM with a detection limit of 0.75 fM (at a S/N ratio of 3). To the best of the authors' knowledge, the proposed biosensor is superior to other MOF platforms. These research findings are expected to have a positive influence on the quantitative detection of HCV RNA and other nucleic acids by offering exceptional accuracy and cost effectiveness, especially in low resource countries. Moreover, this biosensor could be simply adopted for full automation and used in point-of-care testing.

Nucleic acids biosensors based on metal-organic framework (MOF): Paving the way to clinical laboratory diagnosis.

Development of ultra-sensitive, high specific and cost-effective nucleic acids (NAs) biosensors is critical for early diagnosis of cancer, genetic diseases and follows up response to treatment. Metal-organic frameworks (MOFs) as sensing materials underwent significant development in recent years due to their unique merits, such as structural diversity, tunable pore scale, large surface area, remarkable adsorption affinities, and good thermal stability. MOFs have shown potential contribution in nucleic acids biosensors research. Herein, a comprehensive overview on NAs biosensors state of the art based on MOFs has been discussed extensively, including different MOFs platforms sensing strategies (fluorescence, electrochemistry, electrochemiluminescence, and colorimetric techniques), their analytical performance and figures of merit in clinical diagnostics, with the future perspective in introducing MOFs in clinical laboratory diagnostics. Moreover, the different MOFs synthesis methods have been highlighted to serve as a guide for the researchers in selecting the appropriate platform that suits their research needs, and applications.

Chromatographic determination of some biomarkers of liver cirrhosis and hepatocellular carcinoma in Egyptian patients.

Metabolomics has been shown to be an effective tool for disease diagnosis, biomarker screening and characterization of biological pathways. A total of 140 subjects were included in this study; urine metabolomes of patients with liver cirrhosis (LC, n = 40), patients with hepatocellular carcinoma (HCC; n = 55) and healthy male subjects (n = 45) as a control group were studied. Gas chromatography/mass spectrometry-based urine metabolomics profiles were investigated for all participants. Diagnostic models were constructed with a combination of marker metabolites, using principal components analysis and receiver operator characteristic curves. A total of 57 peaks could be auto-identified of which 13 marker metabolites (glycine, serine, threonine, proline, urea, phosphate, pyrimidine, arabinose, xylitol, hippuric acid, citric acid, xylonic acid and glycerol) were responsible for the separation of HCC group from healthy subjects. Also, eight markers metabolites (glycine, serine, threonine, proline, citric acid, urea, xylitol and arabinose) showed significant differences between the LC group and healthy subjects. No significant difference was detected between HCC and LC groups regarding all these metabolites. Metabolomic profile using GC-MS established an optimized diagnostic model to discriminate between HCC patients and healthy subjects; also it could be useful for diagnosis of LC patients. However, it failed to differentiate between HCC and LC patients.

Recent Advances in Immunotherapy in Metastatic NSCLC.

Non-small cell lung cancer (NSCLC) is one of most common malignancies and the leading cause of cancer deaths worldwide. Despite advances in targeted therapies, majority of NSCLC patients do not have targetable genomic alterations. Nevertheless, recent discovery that NSCLC is an immunogenic tumor type, and several breakthroughs in immunotherapies have led to rapid expansion of this new treatment modality in NSCLC with recent FDA approvals of programed death receptor-1 inhibitors, such as nivolumab and pembrolizumab. Here, we review promising immunotherapeutic approaches in metastatic NSCLC, including checkpoint inhibitors, agents with other mechanisms of action, and immunotherapy combinations with other drugs. With advent of immunotherapy, therapeutic options in metastatic NSCLC are rapidly expanding with the hope to further expand life expectancy in metastatic lung cancer.

Recent Advances in Targetable Therapeutics in Metastatic Non-Squamous NSCLC.

Lung adenocarcinoma is the most common subtype of non-small cell lung cancer (NSCLC). With the discovery of epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) rearrangements, and effective targeted therapies, therapeutic options are expanding for patients with lung adenocarcinoma. Here, we review novel therapies in non-squamous NSCLC, which are directed against oncogenic targets, including EGFR, ALK, ROS1, BRAF, MET, human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor receptor 2 (VEGFR2), RET, and NTRK. With the rapidly evolving molecular testing and development of new targeted agents, our ability to further personalize therapy in non-squamous NSCLC is rapidly expanding.

Everolimus in the Treatment of Metastatic Breast Cancer.

The discovery of the mammalian target of rapamycin (mTOR) molecular pathway has brought insight into its vital role in breast cancer pathogenesis. Several clinical trials have shown that the mTOR inhibitor everolimus could improve patient outcomes in several subtypes of breast cancer, including hormone receptor-positive, human epidermal growth factor receptor-negative metastatic disease that has progressed after prior endocrine therapy. This review summarizes findings from clinical trials that have demonstrated the benefit of everolimus in metastatic breast cancer and highlights some new research directions utilizing everolimus.

Hyperhemolysis Syndrome without Underlying Hematologic Disease.

Introduction. Hyperhemolysis is characterized by a life-threatening hemolytic transfusion reaction, with hemoglobin (Hb) and hematocrit (Hct) dropping markedly lower than before transfusion. This phenomenon, commonly described in sickle cell disease, is a rare occurrence in patients without hemoglobinopathies. Case Report. A 55-year-old male presented to the hospital after a motorcycle crash and received 10 units of cross-matched blood for active bleeding. The patient was blood group O, with a negative antibody screen. Ten days later, he represented complaining of dyspnea and was found to have a hematocrit of 12%. The direct antiglobulin test was positive for anti-immunoglobin G and complement. Indirect antiglobulin test was positive for anti-Jka alloantibodies. The presence of Jka antigen was revealed in one unit of previously transfused blood; patient's RBCs were negative for the Jka antigen. Laboratory data demonstrated findings consistent with DHTR, as well as reticulopenia and elevated ferritin levels. He continued to show signs of active hemolysis, requiring a total of 4 subsequent units of pRBCs. Each transfusion precipitated a drop in Hb and Hct to levels lower than before transfusion; once transfusions were held, the patient slowly recovered. Discussion. Hyperhemolysis in the setting of a DHTR can occur in patients without hematologic disease.