Phage Therapy in the Treatment of Infectious Diseases: An Overview

Today, we are facing the spread of antibiotic resistance in various microbial communities. Also, researchers are using new methods to replace conventional treatments to prevent chronic bacterial infections. Hence, the used of phages or bacterial contaminant particles are now used as an effective method in the treatment of many infectious diseases. Several studies have suggested that the use of bacteriophages is effective in treating some bacterial diseases. Therefore, the present study was performed to evaluate phage therapy studies against infections caused by bacterial infections. The use of bacteriophages as new targets in the treatment of bacterial diseases restricts the development of infectious diseases. Bacteriophages can provide a new perspective in the development of new drugs to reduce the rate of bacterial infections. Also, it seems more research should be done in this field and more developed techniques should be used to evaluation of new phages.

COL1A1 Gene Expression in Hepatitis B Virus (HBV) Related Hepatocellular Carcinoma (HCC) Egyptian's Patients

Introduction: Collagens are the most abundant proteins in the human body, accounting for one-third of total proteins. Over the last few years, accumulated evidence have indicated that some collagens are differentially expressed in cancer. The aim of the study was to assess COL1A1 gene expression as a novel marker for the progression of hepatitis B cirrhosis into hepatocellular carcinoma. Methods: This cohort study included 348 subjects and was conducted between May 2018 and June 2019. Subjects were divided into 4 groups: group1 included HBV positive hepatocellular carcinoma patients “HCC” (n= 87), group II included HBV positive patients with liver cirrhosis “LC” (n = 87), group III included chronic hepatitis B patients with neither HCC nor cirrhosis “ C-HBV” (n = 87) and group IV consisted of healthy volunteers as controls (n = 87). Fasting venous blood samples (10 ml) were collected from each participant in this study and were used for assessment of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, albumin and alfa-fetoprotein (AFP). Another portion of blood was collected in 2 vacutainer tubes containing EDTA, one for Complete blood count and the other for gene expression of COL1A1. Results: The gene expression of collagen was 6.9 ± 8.8 in group 1 (HBV positive hepatocellular carcinoma patients) and this was a significant increase in comparison with the other groups. In group 2 (HBV positive patients with liver cirrhosis), the gene expression (collagen) was 3.7±1.5 and it was significantly increased when compared with group 4 (healthy volunteers). Conclusion: COL1A1 gene expression can be used as an indicator of the progression of hepatitis B cirrhosis into hepatocellular carcinoma.

Prognostic Value of Long Non-coding RNAs in Urological Malignancies: A Systematic Review, and Meta-Analysis

Background: Many studies have explored the potential roles of long non-coding RNAs (lncRNAs) in urological cancer (UC) progression. The clinical outcome and prognosis of UCs remain weak. Therefore, finding clinical prognostic markers is needed to improve therapeutic potential. The aim of this study was to consider the possible association between the lncRNAs expression with the survival time and clinical outcomes in patients with UC. Methods: A literature search was performed in several related databases to find eligible English papers published before 9 February 2021. Hazard ratios (HRs) with 95% CI were calculated to investigate the association between lncRNAs expression and overall survival in patients with UC. Results: A total of 46 studies, including 39 lncRNAs were identified. Results indicated that lncRNAs expression was significantly correlated with poor overall survival (OS) outcome in patients with UCs (HR: 1.923, 95% CI: 1.448-2.554, P<0.001). Also, we divided included studies into up-regulated and down-regulated subgroups according to lncRNAs expression. The results indicated a significant association with poor OS outcomes in both up-regulated (HR=2.546, 95% CI: 1.896-3.41, P<0.001) and down-regulated (HR=0.33, 95% CI: 0.22-0.49, P<0.001). Moreover, expression of lncRNAs was significantly associated with lymph node metastasis (LNM) (OR=0.25, 95% CI: 0.13-0.47, P<0.001) Conclusion: Abnormal expression of various lncRNAs is a potential novel marker for predicting the clinical outcomes of urological tumors.

Rapid Serological Testing for Managing the COVID-19 Pandemic: A Review

With the onset of the novel coronavirus disease pandemic (COVID-19) that emerged from Wuhan in China, the need of the hour can be summarized into two groups. The first one is a potent vaccine as a prophylactic measure to prevent the virus from infecting people, and the second is a rapid diagnosis of the disease to help healthcare professionals and government authorities to plan and control the spread and provide effective care and treatment. This review delves into the latter, describing the COVID-19 and its treatment, including the race for an effective vaccine, and highlighting the role of serological testing in managing the pandemic since a well-designed study to understand mechanisms and serological correlations of protective immunity is crucial for rational clinical and public health policies. In conclusion, swift vaccination and response tactics, such as social distancing, hand hygiene, wearing of masks, and, if required, lockdown practices continue to be important in managing the pandemic while carefully monitoring any possible outbreak due to the variants.

Lipid Profiles as Markers for the Severity of Liver Diseases in Cirrhotic Patients

Background Liver cirrhosis is a diffuse process in which the anatomical structure and function of the liver are disturbed. Lipid metabolism occurs mainly in the hepatocytes. In liver cirrhosis, it is expected to detect abnormal lipid profile and abnormal neutrophil to lymphocyte ratio due to necro-inflammation and hepatocyte dysfunction. This study aimed to estimate the lipid profile in patients with liver cirrhosis and to assess its relation to the severity of the liver disease based on Child-Pugh Turcotte score and Neutrophil to Lymphocyte Ratio (NLR). Methods: This study included 500 cirrhotic patients. All patients are subjected to history taking, clinical examination, liver and renal function tests, lipid profile, and also abdomino-pelvic ultrasound. Child -Pugh score, fibrosis-4 score (FIB4), and neutrophil and platelet lymphocyte ratio were calculated. Results: A total of 500 patients were enrolled in this study; 12 patients were excluded (two patients were on the immunosuppressive drug, three patients had body mass index (BMI) >30, and seven patients took lipid-lowering drugs). Cholesterol level was significantly higher in patients with Child- Score A than B and C. Cholesterol, Low-Density Lipoprotein (LDL), and very-low-density lipoprotein (VLDL) cholesterol were significantly higher in Child B than C. A significant negative correlation was found between cholesterol level and each of FIB4 and NLR ratios. Conclusion: There was a significant negative correlation between the severity of liver cirrhosis and lipid profiles (except triglyceride), FIB4 and NLR ratio.

Vitamin D Receptor Gene Polymorphisms and the Risk of Chronic Hepatitis C Related Hepatocellular Carcinoma in Egyptian Population

Background: Small percentage of hepatitis C (HCV) patients develop hepatocellular carcinoma (HCC) during their lifetime, suggesting that genetic factors might modulate HCC development. Numerous variations on the vitamin D receptor gene (VDR) have been recognized in human cancers. The majority of them cause VDR to be unable to bind to 1, 25-OH-D. The aim of the present work was to investigate the relation of VDR FokI (rs2228570), BsmI (rs3782905) and ApaI (rs7975232) gene polymorphisms and the risk of HCC development in chronic HCV Egyptian patients. Methods: A total of 311 Egyptian patients were enrolled for this study. They were divided into 3 groups: 103 patients with liver Cirrhosis, 107 patients with HCC and 101 normal healthy subjects as the control group. Human genomic DNA Extraction was carried out using QIAamp® DNA Blood Mini Kit (QIAGEN) Genotyping of VDR ApaI (rs7975232) single nucleotide polymorphism (SNP) was carried out using real-time PCR TaqMan allelic discrimination assay with allele-specific designed fluorescent MGB probes. Results: Patients with HCC had a higher frequency of ApaI CC genotype (P=0.035) CI (0.031-0.038). Patients with HCC carried a higher ratio of ApaI CC genotype compared to those with liver cirrhosis (x2=5.4 and P = 0.03) or controls (x2=6.8 and P = 0.01). Univariate analysis revealed that age, lower platelet count (<150×103/μL), higher AFP (>100 ng/ml), and ApaI CC genotype were the factors significantly associated with the development of HCC. Stepwise logistic regression analysis showed that all were independent predictors. Conclusion: ApaI CC VDR gene mutation is an independent risk factor for HCC development in Egyptian Cirrhotic HCV patients.

Prognostic Genomic Predictive Biomarkers for Early-Stage Lung Cancer Patients

Aims: Our goal is to find predictive genomic biomarkers in order to identify subgroups of early-stage lung cancer patients that are most likely to benefit from adjuvant chemotherapy with surgery (ACT). Background: Receiving ACT appears to have a better prognosis for more severe early-stage non-small cell lung cancer patients than surgical resection only. However, not all patients benefit from chemotherapy. Objective: Preliminary studies suggest that the application of ACT is associated with a better prognosis for more severe NSCLC patients compared to those who only underwent surgical resection. Given the immense personal and financial costs associated with ACT, finding the patients who are most likely to benefit from ACT is paramount. Thus, the purpose of this research is to utilize gene expression and clinical data from lung cancer patients to find treatment-associated genomic biomarkers. Methods: To investigate the treatment effect, a modified-covariate regularized Cox regression model with lasso penalty is implemented using National Cancer Institute gene expression data to find genomic biomarkers. Results: This research utilized an independent validation dataset involving 318 lung cancer patients to validate the models. In the validation set with 318 patients, the modified covariate Cox model with lasso penalty were able to show patients who followed their predicted recommendation (either ACT for low-risk group or OBS for the high-risk group, n = 171) have higher survival benefits than 147 patients who did not follow the recommendations (p < .0001). Conclusion: Based on validation data, patients who follow our predicted recommendation by genomic biomarkers selected from the proposed model will likely benefit from ACT.

Epidermal Growth Factor rs4444903 A>G Gene Polymorphism Association with Chronic Hepatitis B Liver Disease Progression among Egyptian Children: A Multicenter Study

Background: Polymorphisms of genes encoding the pro-inflammatory and anti-inflammatory cytokines can affect the clinical presentation of the infection. We aimed to assess the role of EGF gene single-nucleotide polymorphism in the outcome of chronic hepatitis B virus (HBV) infection in children. Methods: One hundred HBV-infected children and 75 healthy matched controls were enrolled in this prospective study. Patients included 18 chronic inactive and 82 chronic active carriers. EGF rs4444903 A>G genotypes were determined using allele-specific amplification. Results: Significant differences regarding EGF genotypic frequency (p=0.001) in patients compared to controls (p=0.001). Eighteen percent were inactive, and 82% were active carriers. AA, AG and GG genotypic frequency were 66.7%, 33.3%, 0% and were 3.7%, 37.8% and 58.5% in the inactive and active carriers, respectively, with significant differences regarding AA, AG, GG genotypic frequency (p=0.001 for all). EGF AA, AG, GG genotypes frequency were 1.9%, 33.3%, and 64.8%, respectively, with significant differences between cirrhotic and non-cirrhotic patients regarding AA, AG, GG genotypic frequency (p=0.001 for all). Conclusion: Increased G allele frequency in EGF rs4444903 A > G polymorphism in HBV- Egyptian children is associated with worse outcomes.

The Hidden Danger of Environmental Chemicals during the “Windows of Susceptibility” in a Woman’s Life – How can we use Intermediate Biomarkers to Improve Breast Cancer Prevention?

Introduction: It has been observed that many toxic environmental agents increase risk, accelerate development, or deteriorate the course of breast cancer (BC). In particular, endocrine-disrupting chemicals (EDC) are harmful to endocrine receptor actions and signaling in the breast tissue. Usually, there is a long interval of time between the exposure to EDC and BC incidence, and this often represents a serious obstacle for effective BC prophylaxis. Notably, during certain periods of a woman’s life cycle, the BC risk is particularly elevated due to increased susceptibility to some EDC. These windows of susceptibility (WOS) include prenatal, puberty, pregnancy, and menopausal transition stages of a female’s life course. Four WOS have been considered as the most vulnerable periods for BC since the mammary gland undergoes the main anatomical and physiological transformations at those intervals. This means that during specific WOS, the EDC from the environment can have the most dangerous impact on BC risk and possible BC development later in a woman’s life. However, most clinical BC studies related to toxic environmental exposures have not been connected to the specific WOS. Therefore, the goal of this article is to briefly describe some important research results, focused on the links between EDC and BC, within four critical WOS. In addition, this mini-review outlines some useful biomarkers for further research and prophylaxis of BC and also for both the research community and the medical professionals. Conclusion: To bridge the gap in BC prevention, it is essential to recognize the links between EDC and BC within the critical WOS. Moreover, an integrative model of BC research, applying intermediate biomarkers, is necessary to determine the mechanisms of action of various EDC during critical periods in a woman’s lifespan. Hopefully, this will lead to progress in BC prevention.

Plasma Fibrinogen as a Biomarker of Stable and Exacerbated Chronic Obstructive Pulmonary Disease

Study Design: An experimental, comparative, cross-sectional study Place and Duration of Study: Department of Physiology, Federal Post Graduate Medical Institute (FPGMI), Sheikh Zayed Medical Complex Lahore, Pakistan from August 2013 to 2014 Background: Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable disease, but is a partially reversible chronic inflammatory condition characterized by airway obstruction. COPD remains under-diagnosed and under-treated because the only available diagnostic method at present is testing lung functions by spirometry which is not helpful to determine the severity and clinical outcomes of the disease. Circulating biomarkers are under consideration for various diseases worldwide. Plasma fibrinogen is emerging as one of the most promising biomarkers of COPD in smokers. Objective: The objective of this study is to investigate if plasma fibrinogen can serve as a diagnostic biomarker of COPD in smokers, and if its further higher levels are seen in the exacerbated state of the disease in comparison to the stable disease. Materials and Methods: 75 middle-aged to old-age smokers of either gender were selected. Lung functions of every participant were measured to determine Forced Expiratory Volume in the first second (FEV1), Forced Vital Capacity (FVC), and the ratio of FEV1/FVC by spirometry. On the basis of the results of the tests, subjects were divided into three groups; firstly, the control group of chronic smokers without COPD, secondly, smokers with COPD in a stable state, and thirdly, patients in an exacerbated state of COPD. Plasma fibrinogen was quantitatively estimated in every individual of all three groups by the Clauss method using the Hemostat Fibrinogen kit. Results: The average Plasma fibrinogen level was found to be 235.008 mg/dl in healthy smokers (control group), while an average of 440.12mg/dl was measured in patients with stable COPD. The difference in plasma fibrinogen levels was found to be significant, having a p-value of (0.000). In the third group with declined lung function predicting acute exacerbated COPD, fibrinogen was found to be > 453.2 mg/dl, which was significantly higher than in the stable disease group (p-value > 0.0017) Conclusion: Plasma fibrinogen level measurement is a reliable and accessible test in terms of a diagnostic marker of COPD, as compared to conventional lung function testing done in the past.