A Review on Serum, Genetic and Mirna Associated Biomarkers for The Early Diagnosis of Hepatocellular Carcinoma (HCC))

Hepatocellular carcinoma is the most devastating complication of liver cirrhosis and diagnosis in earlier stages could be useful in curative interventions. The main aim of this review was to analyze current diagnostic biomarkers which are available for the early diagnosis of hepatocellular carcinoma (HCC). For this purpose, we searched different web databases including Medline/Pubmed. We found multiple significant serum biomarkers for imperative diagnosis including α- Fetoprotein, Des- γ -carboxyprothrombin (DCP), Osteopontin (OPN), Glypican-3 (GPC3), Golgi protein-73 (GP73), Squamous cell carcinoma antigen (SCCA), Annexin A2 (ANXA2) and Heat shock protein 70 (HSP70) but all of these represent low sensitivity and low specificity. Hepatocellular carcinoma diagnosis have also been reported at the genetic level with the help of associated genes such as p53, RAS, MERTK (MER-Tyrosine Kinase), EGF, TGF-β/IGF, ALDH2, CAT, Glutathione S-transferase (GSTM1), X-ray repair cross-complementing group1 (XRCC1), Receptor tyrosine kinase (ROR1), RASSF1A, SOCS1, NUF2, CXCL2 and Interleukin-1 Gene (IK-1). Inhibition of these cancerous genes is under research and could be a novel therapeutic approach in future. Recently, differential diagnosis with miRNA has been found important for hepatocellular carcinoma. Anti-miR-122 could revolutionize the early diagnosis of HCC and has the potential to be marketed for therapy. However, most of the drugs are under clinical trial phase. It is recommended to use them in conjunction with each other so these could be employed as a way to decrease mortality and stigma associated with hepatocellular carcinoma

Hepcidin Antimicrobial Peptide (HAMP) Screening for P.CYS70ARG Variant and Iron Overload in β -Thalassemia Major Patients

Hereditary Hemochromatosis is a rare genetic iron overload disorder characterized by iron accumulation in vital body organs such as the lungs, liver, and pancreas. HAMP mutations are reported as one of the principal sources for the disturbance of iron homeostasis. This study was designed to screen the involvement of p.Cys70Arg HAMP variant in iron overload in the β-thalassemia patients. For the purpose, bioinformatics tools were used for the structural and functional manifestation of mutated protein which revealed 1.93 kcal/mol energy differences between the wild-type and mutated proteins, causing the stability decline. Following that, clinical data was collected for 106 β-thalassemia major (β-TM) patients which showed a higher prevalence of splenectomy, hepatomegaly and ascites. The PCR-RFLPs were performed to screen the HAMP p.Cys70Arg in 27 controls and 106 β-TM patients. Sac ӀӀ restriction enzyme was used to screen genetically affected and ethnically matched control samples but no control was found with HAMP p.Cys70Arg variant. Out of these 106 β-thalassemia patients, eight patients were HCV+ with higher levels of ferritin in blood. HAMP exon 3 Sanger sequencing did not reveal any mutation in these patients conferring iatrogenic hemochromatosis. Future recommendations include sequencing of complete HAMP gene with its three exons in a large sample size

Identification and Characterization of Active Ingredient Eugenol from Syzygium Aromaticum (Clove Oil) through HPLC and its Phytochemical Analysis

Clove, Syzygium aromaticum, is one of the most valuable, ancient and premium essential oil which has been used as source of spice in agro-food industry and therapeutics for centuries. The aim of the present study was to analyze biological activities of clove oil as well as characterization of its active component Eugenol to make it worthwhile for different food and pharmaceutical formulations. Clove oil extraction was performed by Soxhlet method. Its phytochemical analysis showed the presence of carbohydrates, flavonoids, coumarins, steroids, saponnins, and tannins while proteins and leucoanthocyanins were absent in it. DPPH (2, 2-diphenyl-1-picrylhydrazyl) scavenging assay was performed which showed an increase in percentage inhibition with an increase in concentration of clove oil which confirmed its antioxidant property. Antimicrobial activity of clove oil was tested against three gram positive strains Bacillus subtilis, Staphylococcus aureus and Bacillus thuringiensis and one gram negative strain Escherichia coli by well diffusion and disc diffusion methods. E.coli presented largest zone of inhibition. T-test was applied for statistical analysis of antimicrobial activity. P-value obtained was 0.0215 which is ˂0.05. Aqueous clove nanoparticles were made and were found to have antimicrobial activity against E.coli and B.subtilis. Correlation coefficient (R2) through HPLC was found to be 0.973531. Quantitative estimation showed the presence of 740 ppm eugenol. These properties of clove proved it as a valuable spice in pharmaceutical and agro-food sector

Comparison of the WHO Retreatment Regimen with the Six Drugs Regimen in Patients of Pulmonary Tuberculosis

Objective: To compare the frequency of early response of WHO retreatment regimen with the six drugs regimen in pulmonary tuberculosis retreatment Category patients.Study design: Randomized control trial (RCT)Place and Duration: Chest Department, Fauji Foundation Hospital Rawalpindi from 22nd May 2016 to 22nd November 2016.Methodology: Patients who had previously been treated for pulmonary tuberculosis for at least 1 month duration and is a failure, relapse or defaulter case presenting in Fauji Foundation Hospital Rawalpindi, both indoor and outdoor were enrolled in the study. Patients were randomized by lottery method to either of the two treatment arms; WHO retreatment regimen or six drug formulations. Clinical features were documented, baseline investigations, AFB smear, Gene Xpert and AFB Culture were sent. Drugs were given on once daily dosage. AFB smear and AFB culture were repeated at 3rd month of treatment. They had a regular follow up in Chest OPD and had monthly visits to the ophthalmology department for visual acuity, fundoscopy and to ENT department for audiometry. Their chest X-ray was done baseline then 3 months. Blood complete picture and liver function tests, serum uric acid, renal function tests were performed baseline, at 2 weeks then 3 months. After their treatment was completed they were followed to look for relapse.Results: Total 490 patients were included according to the inclusion criteria of the study. Patients were divided into two equal groups. Mean age (years) in the study was 40.00+21.10. There were 33 (6.7) male and 457 (93.3) female patients whereas the frequency of early response of WHO retreatment regimen with the six drugs regimen in pulmonary tuberculosis retreatment category patients was 187 (76.3) and 211 (86.1) respectively which was statistically significant (p-value 0.000).Conclusion: The study concludes that six drug regimen was superior to WHO standard regimen in the success rate of pulmonary tuberculosis retreatment category patients which useful in bringing new facts regarding management of retreatment category patient in our country as well as worldwide because of the limited research was done on this category of tuberculosis

Comparison of High Intensity Non-Invasive Ventilation With Low Intensity Non-Invasive Ventilation In Patients With Acute Copd Exacerbation

Objective: To determine the outcome of high intensity non-invasive positive pressure ventilation (HI-NPPV) as compared to low intensity non-invasive positive pressure ventilation (LI-NPPV) in patients with acute COPD exacerbations. Methodology: This Randomized controlled trial Department of PulmonologyFauji Foundation Hospital Rawalpindi from  31st December 2016 to 30thJune 2017. Arterial blood gases will be taken at admission. If values of pH and paCO2 meet the criteria for non-invasive ventilation then patients will be enrolled in the study. Patients will be randomly divided into two groups by lottery method. GROUP A and GROUP B. GROUP A will receive high intensity NIV (HI-NPPV) and GROUP B will receive low intensity NIV (LI-NPPV) by TRIOLOGY machine. Expiratory positive airway pressure (EPAP) will remain between 4 to 6 cmH2O.  Arterial blood gases (ABGs) will be done at baseline and then 72 hours after admission. Improvement in PaCO2, HCO3, and FEV1 will be recorded 72 hours from baseline and collected on proforma (attached). Results: Mean age (years) in the study was 55.54+3.81. There were 08 male patients included the study meeting the inclusion criteria. Of these, 05 and 03 male patients among both the groups respectively. Similarly, there were 92 female patients included the study meeting the inclusion criteria, of these, 45 and 47 female patients among both the groups respectively. Outcome of the study was assessed in terms of mean PaCO2 (mmHg), HCO3 (mmol/L) and FEV1 at baseline and after 72 hours. Mean PaCO2, HCO3 and FEV1 at baseline was 64.87+5.22, 33.75+4.17 and 0.66+0.04 respectively. After 72 hours, mean PaCO2 (mmHg) , HCO3(mmol/L), and FEV1 among both the groups was 63.98+6.58 vs 41.46+2.40, 33.10+4.81 vs 23.12+2.01, 0.66+0.05 vs 0.72+0.04 with following P value of (0,000, 0.000, 0.000) respectively. Conclusion: High intensity non-invasive positive pressure ventilation (HI-NPPV) has no different outcome as compared to low intensity non-invasive positive pressure ventilation (LI-NPPV) in patients with acute COPD exacerbations

A Review on Empirical Approach to Therapeutic Recombinant Protein Production Factories: Applications, Pharmacokinetics and Challenges

Major portion of the proteins in a cell refers to their critical roles in metabolism of the living body. Proteins dysfunction results in the severe disorders which need to be treated in time. For this, respective proteins can be extracted by the external sources and be supplied to the human beings. Such medicinal proteins are known as therapeutic proteins (TPs). This review summarizes some of the key areas about these miracle proteins like their types, classification, production factories, routes of administration, pharmacokinetics, and potential applications. Furthermore, challenges and hurdles faced in getting a potential protein drug, its FDA approval and commercial availability are also highlighted for further research

Comparison of the WHO Retreatment Regimen with the Six Drugs Regimen in Patients of Pulmonary Tuberculosis

Objective: To compare the frequency of early response of WHO retreatment regimen with the six drugs regimen in pulmonary tuberculosis retreatment Category patients.Study design: Randomized control trial (RCT)Place and Duration: Chest Department, Fauji Foundation Hospital Rawalpindi from 22nd May 2016 to 22nd November 2016.Methodology: Patients who had previously been treated for pulmonary tuberculosis for at least 1 month duration and is a failure, relapse or defaulter case presenting in Fauji Foundation Hospital Rawalpindi, both indoor and outdoor were enrolled in the study. Patients were randomized by lottery method to either of the two treatment arms; WHO retreatment regimen or six drug formulations. Clinical features were documented, baseline investigations, AFB smear, Gene Xpert and AFB Culture were sent. Drugs were given on once daily dosage. AFB smear and AFB culture were repeated at 3rd month of treatment. They had a regular follow up in Chest OPD and had monthly visits to the ophthalmology department for visual acuity, fundoscopy and to ENT department for audiometry. Their chest X-ray was done baseline then 3 months. Blood complete picture and liver function tests, serum uric acid, renal function tests were performed baseline, at 2 weeks then 3 months. After their treatment was completed they were followed to look for relapse.Results: Total 490 patients were included according to the inclusion criteria of the study. Patients were divided into two equal groups. Mean age (years) in the study was 40.00+21.10. There were 33 (6.7) male and 457 (93.3) female patients whereas the frequency of early response of WHO retreatment regimen with the six drugs regimen in pulmonary tuberculosis retreatment category patients was 187 (76.3) and 211 (86.1) respectively which was statistically significant (p-value 0.000).Conclusion: The study concludes that six drug regimen was superior to WHO standard regimen in the success rate of pulmonary tuberculosis retreatment category patients which useful in bringing new facts regarding management of retreatment category patient in our country as well as worldwide because of the limited research was done on this category of tuberculosis

Comprehensive Investigation of Pyrimidine Synthesis, Reactions, and Biological Activity

<p>Researchers have devoted much attention to the study of the chemistry of pyrimidines due to their broad range of pharmaceutical activities. The important role of pyrimidines in the field of drugs is derived from the fact that they are present in genetic material of cells. In this review, we discuss various synthetic methods for pyrimidine derivatives, as well as their various categories of reactions and biological activities as illustrated by research conducted in recent years.</p><p>Keywords:- Pyrimidine; Pharmaceutical Activities; Drugs.</p&gt

Genome Sequencing of Consanguineous Family Implicates Ubiquitin-Specific Protease 53 (<i>USP53</i>) Variant in Psychosis/Schizophrenia: Wild-Type Expression in Murine Hippocampal CA 1–3 and Granular Dentate with AMPA Synapse Interactions

Psychosis is a severe mental disorder characterized by abnormal thoughts and perceptions (e.g., hallucinations) occurring quintessentially in schizophrenia and in several other neuropsychiatric disorders. Schizophrenia is widely considered as a neurodevelopmental disorder that onsets during teenage/early adulthood. A multiplex consanguineous Pakistani family was afflicted with severe psychosis and apparent autosomal recessive transmission. The first-cousin parents and five children were healthy, whereas two teenage daughters were severely affected. Structured interviews confirmed the diagnosis of DSM-V schizophrenia. Probands and father underwent next-generation sequencing. All available relatives were subjected to confirmatory Sanger sequencing. Homozygosity mapping and directed a priori filtering identified only one rare variant [MAF −5] at a residue conserved across vertebrates. The variant was a non-catalytic deubiquitinase, USP53 (p.Cys228Arg), predicted in silico as damaging. Genome sequencing did not identify any other potentially pathogenic single nucleotide variant or structural variant. Since the literature on USP53 lacked relevance to mental illness or CNS expression, studies were conducted which revealed USP53 localization in regions of the hippocampus (CA 1–3) and granular dentate. The staining pattern was like that seen with GRIA2/GluA2 and GRIP2 antibodies. All three proteins coimmunoprecipitated. These findings support the glutamate hypothesis of schizophrenia as part of the AMPA-R interactome. If confirmed, USP53 appears to be one of the few Mendelian variants potentially causal to a common-appearing mental disorder that is a rare genetic form of schizophrenia