Lupus nephritis (LN) represents a major complication in systemic lupus erythematosus (SLE). The objective of this study was to evaluate the TRIM8 gene and its associated non-coding RNAs (lnc-SSBP2-1:1 and hsa-miR-126-5p) as potential non-invasive biomarkers for LN activity. Bioinformatics analyses were initially employed to identify candidate mRNA and associated non-coding RNAs (ncRNAs) implicated in LN. Expression profiles of TRIM8lnc-SSBP2-1:1and hsa-miR-126-5p were validated in blood samples from 40 active LN, 30 inactive LN patients, and 20 healthy individuals via real-time PCR. TRIM8 mRNA and lnc-SSBP2-1:1 lncRNA levels were notably upregulated in active LN (p < 0.001), while hsa-miR-126-5p was reduced (p < 0.001). SLEDAI-2K scores correlated positively with TRIM8 mRNA and lnc-SSBP2-1:1, and negatively with hsa-miR-126-5p. This study highlights TRIM8-associated ncRNA regulatory network as promising biomarkers in LN activωity, with potential clinical impact.

Colorectal cancer (CRC) is ranked as the third most commonly diagnosed cancer and the third cause of cancer related deaths. CRC is greatly attributed to genetic and epigenetic mutations and immune dysregulation. Tumor aberrant expression of Toll-like Receptors (TLRs) can contribute to tumorigenesis. Recent studies suggested that microRNAs act as direct ligands of TLRs altering their expression and signaling pathways. To prove our concept that specific miRNA mimics may act as antagonists of their specific toll like receptors inhibiting their expression that could limit the release of pro-inflammatory and pro-tumorigenic cytokines leading to apoptosis of tumor cells. From public microarray databases, we retrieved TLRs and miRNAs related to CRC followed by in silico docking of the selected miRNA ligands into the TLRs. Clinical validation after co-immunoprecipitation of TLRs and their interacting miRNA ligands was done. Expression of TLRs 1, 7,8 was determined by ELISA while miRNAs was measured by RT-qPCR. In addition, microRNA mimics of the down regulated miRNAs were transfected into human CRC cell lines. Our data demonstrate that TLRs 1, 7, 8 are up regulated in CRC compared to controls. Further, three miRNAs (-122, -29b and -15b) are relatively downregulated, while 4 miRNAs (-202, miRNA-98, -21 and -let7i) are upregulated in CRC patients compared to those with benign tumor and healthy controls. Transfection of down regulated miRNA mimics into CRC cell lines resulted in a significant reduction of the number and viability of cells as well as down regulating the expression of TLRs 1, 7 and 8 with ultimate reduction of downstream effector IL6 protein, suggesting that these miRNAs are negative regulators of carcinogenesis. MicroRNAs could act as antagonistic ligands of TLRs limiting the inflammatory tumor microenvironment. • Specific miRNAs were identified by in silico docking as signaling antagonists of 3 TLRs and were validated in clinical samples. • TLRs 1, 7, 8 were upregulated while their miRNAs (-122, -29b and -15b)were down regulated in CRC. • Transfection of downregulated miRNA mimics into CRC cell lines resulted in downregulation of TLRs that was associated with reduction in IL6 protein and tumor growth. • The present study proposed a novel approach that enables a reliable integration of Toll like receptors and miRNAs in CRC pathogenesis.

Non-alcoholic steatohepatitis (NASH) is the clinically aggressive variant of non-alcoholic fatty liver disease. Hippo pathway dysregulation can contribute to NASH development and progression. The use of probiotics is effective in NASH management. Our aim is to investigate the efficacy of kefir Milk in NASH management via modulation of hepatic mRNA-miRNA based panel linked to NAFLD/NASH Hippo signaling and gut microbita regulated genes which was identified using bioinformatics tools. Firstly, we analyzed mRNAs (SOX11, SMAD4 and AMOTL2), and their epigenetic regulator (miR-6807) followed by validation of target effector proteins (TGFB1, IL6 and HepPar1). Molecular, biochemical, and histopathological, analyses were used to evaluate the effects of kefir on high sucrose high fat (HSHF) diet -induced NASH in rats. We found that administration of Kefir proved to prevent steatosis and development of the inflammatory component of NASH. Moreover, Kefir improved liver function and lipid panel. At the molecular level, kefir down-regulated the expression of miR 6807-5p with subsequent increase in the expression of SOX 11, AMOTL2 associated with downregulated SMAD4, resulting in reduction in the expression of the inflammatory and fibrotic markers, IL6 and TGF-β1 in the treated and prophylactic groups compared to the untreated rats. In conclusion, Kefir suppressed NASH progression and improved both fibrosis and hepatic inflammation. The produced effect was correlated with modulation of SOX11, SMAD4 and AMOTL2 mRNAs) – (miR-6807-5p) – (TGFB, IL6 and, HepPar1) expression.

Non-alcoholic steatohepatitis (NASH) is the clinically aggressive variant of non-alcoholic fatty liver disease. Hippo pathway dysregulation can contribute to NASH development and progression. The use of probiotics is effective in NASH management. Our aim is to investigate the efficacy of kefir Milk in NASH management via modulation of hepatic mRNA-miRNA based panel linked to NAFLD/NASH Hippo signaling and gut microbita regulated genes which was identified using bioinformatics tools. Firstly, we analyzed mRNAs (SOX11, SMAD4 and AMOTL2), and their epigenetic regulator (miR-6807) followed by validation of target effector proteins (TGFB1, IL6 and HepPar1). Molecular, biochemical, and histopathological, analyses were used to evaluate the effects of kefir on high sucrose high fat (HSHF) diet -induced NASH in rats. We found that administration of Kefir proved to prevent steatosis and development of the inflammatory component of NASH. Moreover, Kefir improved liver function and lipid panel. At the molecular level, kefir down-regulated the expression of miR 6807-5p with subsequent increase in the expression of SOX 11, AMOTL2 associated with downregulated SMAD4, resulting in reduction in the expression of the inflammatory and fibrotic markers, IL6 and TGF-β1 in the treated and prophylactic groups compared to the untreated rats. In conclusion, Kefir suppressed NASH progression and improved both fibrosis and hepatic inflammation. The produced effect was correlated with modulation of SOX11, SMAD4 and AMOTL2 mRNAs) – (miR-6807-5p) – (TGFB, IL6 and, HepPar1) expression.

Background Problem-based learning (PBL) remains a valid and effective tool for small-group medical education. Using Virtual patients (VP) case simulation in PBL is a recognizable educational method that has successfully prepared students to focus learning on core information that uses realistic patient-based cases relating to everyday clinical scenarios. Using other modalities as the virtual patient in PBL instead of the paper-based methods remains debatable. This study aimed to evaluate the effectiveness of using VP case simulation mannequin in PBL versus the PBL in paper-based cases in improving the cognitive skills by comparing the grades of a multiple-choice question test and assess its ability to reach students' satisfaction using questionnaire with Likert survey instrument. Methods The study was conducted on 459 fourth-year medical students studying in the pulmonology module of the internal medicine course, Faculty of Medicine, October 6 University. All students were divided into 16 PBL classes and randomly divided into groups A and B by simple manual randomization. The groups were parallel with a controlled cross-over study between paper-based and virtual patient PBL. Results The pre-test showed no significant difference between both, while post-test scores were significantly higher in both VP PBL cases 1 discussing COPD (6.25 ± 0.875) and case 2 discussing pneumonia (6.56 ± 1.396) compared to paper-based PBL (5.29 ± 1.166, 5.57 ± SD1.388, respectively) at p < 0.1 When students in Group A experienced PBL using VP in case 2 after paper-based PBL in case 1, their post-test score improved significantly. (from 5.26 to 6.56, p < .01). Meanwhile, there was a significant regression in the post-test score of the students in Group B when they experienced the paper-based PBL session in case 2 after using PBL using VP in case 1, (from 6.26 to 5.57, p < .01). Most of the students recommended using VP in PBL as they found VP was more engaging and inducing concentration in gathering the information needed to characterize the patient’s problem than in a classroom- paper-based cases session. They also enjoyed the teaching of the instructor and found it a suitable learning style for them. Conclusion Implementing virtual patients in PBL increased knowledge acquisition and understanding in medical students and was more motivating for students than paper based PBL to gather the needed information.

Background NAFLD and NASH are emerging as primary causes of chronic liver disease, indicating a need for an effective treatment. Mutaflor® probiotic, a microbial treatment of interest, was effective in sustaining remission in ulcerative colitis patients. Objective To construct a genetic-epigenetic network linked to HSC signaling as a modulator of NAFLD/NASH pathogenesis, then assess the effects of Mutaflor ® on this network. Methods First, in silico analysis was used to construct a genetic-epigenetic network linked to HSC signaling. Second, an investigation using rats, including HFHSD induced NASH and Mutaflor ® treated animals, was designed. Experimental procedures included biochemical and histopathologic analysis of rat blood and liver samples. At the molecular level, the expression of genetic (FOXA2, TEAD2, and LATS2 mRNAs) and epigenetic (miR-650, RPARP AS-1 LncRNA) network was measured by real-time PCR. PCR results were validated with immunohistochemistry (α-SMA and LATS2). Target effector proteins, IL-6 and TGF-β, were estimated by ELISA. Results Mutaflor ® administration minimized biochemical and histopathologic alterations caused by NAFLD/NASH. HSC activation and expression of profibrogenic IL-6 and TGF-β effector proteins were reduced via inhibition of hedgehog and hippo pathways. Pathways may have been inhibited through upregulation of RPARP AS-1 LncRNA which in turn downregulated the expression of miR-650, FOXA2 mRNA and TEAD2 mRNA and upregulated LATS2 mRNA expression. Conclusion Mutaflor ® may slow the progression of NAFLD/NASH by modulating a genetic-epigenetic network linked to HSC signaling. The probiotic may be a useful modality for the prevention and treatment of NAFLD/NASH.

Aim: we aimed to construct a bioinformatics-based co-regulatory network of mRNAs and non coding RNAs (ncRNAs), which is implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), followed by its validation in a NAFLD animal model. Materials and Methods: The mRNAs–miRNAs–lncRNAs regulatory network involved in NAFLD was retrieved and constructed utilizing bioinformatics tools. Then, we validated this network using an NAFLD animal model, high sucrose and high fat diet (HSHF)-fed rats. Finally, the expression level of the network players was assessed in the liver tissues using reverse transcriptase real-time polymerase chain reaction. Results: in-silico constructed network revealed six mRNAs (YAP1, FOXA2, AMOTL2, TEAD2, SMAD4 and NF2), two miRNAs (miR-650 and miR-1205), and two lncRNAs (RPARP-AS1 and SRD5A3-AS1) that play important roles as a co-regulatory network in NAFLD pathogenesis. Moreover, the expression level of these constructed network–players was significantly different between NAFLD and normal control. Conclusion and future perspectives: this study provides new insight into the molecular mechanism of NAFLD pathogenesis and valuable clues for the potential use of the constructed RNA network in effective diagnostic or management strategies of NAFLD.

We intended to examine the molecular mechanism of action of isorhamnetin (IHN) to regulate the pathway of insulin signaling. Molecular analysis, immunofluorescence, and histopathological examination were used to assess the anti-hyperglycemic and insulin resistance lowering effects of IHN in streptozotocin /high fat diet induced type 2 diabetes using Wistar rats. At the microscopic level, treatment with IHN resulted in the restoration of myofibrils uniform arrangement and adipose tissue normal architecture. At the molecular level, treatment with IHN at three different doses showed a significant decrease in m-TOR, IGF1-R & LncRNA-RP11773H22.4. expression and it up-regulated the expression of AKT2 mRNA, miR-1, and miR-3163 in both skeletal muscle and adipose tissue. At the protein level, IHN treated group showed a discrete spread with a moderate faint expression of m-TOR in skeletal muscles as well as adipose tissues. We concluded that IHN could be used in the in ameliorating insulin resistance associated with type 2 diabetes mellitus.

Background : In this study, we aimed to construct Insilco, a competing endogenous RNAs (ceRNAs) network linked to the pathogenesis of insulin resistance followed by its experimental validation in patients’, matched control and cell line samples. And also, to evaluate the efficacy of CRISPR/Cas9 as a potential therapeutic strategy to modulate the expression of this deregulated network. By applying bioinformatic tools, we identified and verified a ceRNA network panel of lncRNA, miRNAs and mRNAs related to insulin resistance and then we validated its expression in 123 patients’ and 106 matched controls and cell line samples using real time PCR. Results : LncRNA-RP11‐773H22.4, together with RET , IGF1-R and m-TOR mRNAs showed significant upregulation in T2DM compared with matched controls while miRNAs: miR-3163, miR-1 and mRNAs: GLUT-4 and AKT2 expression displayed marked downregulation in diabetic samples.Two guide RNAs were designed to target the sequence flanking LncRNA/miRNAs interaction by CRISPER/Cas9 in cell culture. Gene editing tool efficacy was assessed by measurement of the network downstream proteins, GLUT4 and mTOR by immunofluorescence. CRISPR/Cas9 successfully knockout LncRNA-RP11-773H22.4 as evidenced by the reversal of the gene expression of the identified network at RNA and protein levels to the normal expression pattern after gene editing. Conclusion : The presented study provides the significance of this ceRNA based network and its related target genes panel both in the pathogenesis of insulin resistance and as a therapeutic target for gene editing in T2DM.

Background: Type 2 diabetes mellitus is one of the leading causes of morbidity and mortality worldwide and is derived from an accumulation of genetic and epigenetic changes. In this study, we aimed to construct Insilco, a competing endogenous RNA (ceRNA) network linked to the pathogenesis of insulin resistance followed by its experimental validation in patients’, matched control and cell line samples, as well as to evaluate the efficacy of CRISPR/Cas9 as a potential therapeutic strategy to modulate the expression of this deregulated network. By applying bioinformatics tools through a two-step process, we identified and verified a ceRNA network panel of mRNAs, miRNAs and lncRNA related to insulin resistance, Then validated the expression in clinical samples (123 patients and 106 controls) and some of matched cell line samples using real time PCR. Next, two guide RNAs were designed to target the sequence flanking LncRNA/miRNAs interaction by CRISPER/Cas9 in cell culture. Gene editing tool efficacy was assessed by measuring the network downstream proteins GLUT4 and mTOR via immunofluorescence. Results: LncRNA-RP11-773H22.4, together with RET, IGF1R and mTOR mRNAs, showed significant upregulation in T2DM compared with matched controls, while miRNA (i.e., miR-3163 and miR-1) and mRNA (i.e., GLUT4 and AKT2) expression displayed marked downregulation in diabetic samples. CRISPR/Cas9 successfully knocked out LncRNA-RP11-773H22.4, as evidenced by the reversal of the gene expression of the identified network at RNA and protein levels to the normal expression pattern after gene editing. Conclusions: The present study provides the significance of this ceRNA based network and its related target genes panel both in the pathogenesis of insulin resistance and as a therapeutic target for gene editing in T2DM.

Aim: To investigate the prophylactic efficacy of gut microbiota-based treatments on nonalcoholic steatohepatitis (NASH) management via modulation of Hippo signaling pathway-related genes (YAP1, LATS1 and NF2), and their epigenetic regulators (miR-1205 and lncRNA SRD5A3-AS1) retrieved from in-silico data analysis. Materials & methods: Histopathological, biochemical, molecular and immunohistochemistry analyses were used to assess the effects of multistrain probiotic mixture and prebiotic inulin fiber on high sucrose high fat (HSHF) diet-induced NASH in rats. These treatments were administered orally either alone or in combination, along with HSHF diet. Results: Both probiotic mixture and prebiotic inulin fiber attenuated steatosis, inflammation and fibrosis grades in HSHF diet-induced NASH rats. Moreover, the applied treatments significantly prevented the elevation of serum liver enzymes and improved lipid panel. At the molecular level, both treatments down-regulated hepatic YAP1 mRNA and miR-1205 expressions, and concomitantly up-regulated the expression of hepatic LATS1& NF2 mRNAs and the lncRNA SRD5A3-AS1. At the protein level, both treatments decreased the hepatic content of the inflammatory marker IL6 and the fibrotic marker TGF beta 1. Moreover, an observable reduction in alpha-SMA together with noticeable elevation in LATS1/2 protein expression levels were detected in liver sections compared to the untreated rats. Conclusion: Probiotic mixture and prebiotic inulin fiber, either alone or in combination, attenuated NASH progression and ameliorated both fibrosis and hepatic inflammation in the applied animal model. The produced effect was correlated with modulation of the retrieved (YAP1, LATS1 and NF2) - (miR-1205) - (lncRNA SRD5A3AS1) RNA panel.

Aim: To assess isorhamnetin efficacy for diabetic kidney disease in a Type 2 diabetes mellitus rat model, through investigating its effect at the epigenetic, mRNA and protein levels. Materials & methods: Type 2 diabetes mellitus was induced in rats by streptozotocin and high-fat diet. Rats were treated with isorhamnetin (50 mg/kg/d) for 4 or 8 weeks. Fasting blood glucose, renal and lipid profiles were evaluated. Renal tissues were examined by light and electron microscopy. Autophagy genes ( FYCO1, ULK, TECPR1 and WIPI2) and miR-15b, miR-34a and miR-633 were assessed by qRT-PCR, and LC3A/B by immunoblotting. Results: Isorhamnetin improved fasting blood glucose, renal and lipid profiles with increased autophagosomes in renal tissues. It suppressed miRNA regulation of autophagy genes. Conclusion: We propose a molecular mechanism for the isorhamnetin renoprotective effect by modulation of autophagy epigenetic regulators.

Non-alcoholic steatohepatitis (NASH) is the clinically aggressive variant of non-alcoholic fatty liver disease. Hippo pathway dysregulation can contribute to NASH development and progression. The use of probiotics is effective in NASH management. Our aim is to investigate the efficacy of kefir Milk in NASH management via modulation of hepatic mRNA-miRNA based panel linked to NAFLD/NASH Hippo signaling and gut microbita regulated genes which was identified using bioinformatics tools. Firstly, we analyzed mRNAs (SOX11, SMAD4 and AMOTL2), and their epigenetic regulator (miR-6807) followed by validation of target effector proteins (TGFB1, IL6 and HepPar1). Molecular, biochemical, and histopathological, analyses were used to evaluate the effects of kefir on high sucrose high fat (HSHF) diet -induced NASH in rats. We found that administration of Kefir proved to prevent steatosis and development of the inflammatory component of NASH. Moreover, Kefir improved liver function and lipid panel. At the molecular level, kefir down-regulated the expression of miR 6807-5p with subsequent increase in the expression of SOX 11, AMOTL2 associated with downregulated SMAD4, resulting in reduction in the expression of the inflammatory and fibrotic markers, IL6 and TGF-β1 in the treated and prophylactic groups compared to the untreated rats. In conclusion, Kefir suppressed NASH progression and improved both fibrosis and hepatic inflammation. The produced effect was correlated with modulation of SOX11, SMAD4 and AMOTL2 mRNAs) – (miR-6807-5p) – (TGFB, IL6 and, HepPar1) expression.

Colorectal cancer (CRC) is characterized by high heterogeneity and a complex microenvironment that leads to high inter-patient variability. Personalized management of CRC could address this. Accumulating data highlights the interaction between the CRC microenvironment and the immune system through different cells and receptors with a focus on the toll-like receptors (TLRs). Multiple studies identified a bidirectional role played by TLRs in CRC with involvement in both carcinogenesis and therapy. Areas covered A study to highlight the interaction between TLRs and CRC microenvironment on different molecular levels was undertaken, addressing TLR gene polymorphism, TLR genetic and epigenetic deregulation and TLR ligand binders. In addition, the use of these TLRs and their interaction with CRC microenvironment were evaluated to identify novel CRC therapeutics. Expert commentary Previous literature has shown that TLRs are incriminated in CRC pathogenesis and thus research effort was directed to make use of these TLRs in drawing new therapeutic patterns for CRC. However, to date, these immune-therapeutic patterns of CRC have shown limited success in reducing tumor burden. This highlights the need for more studies that would better illustrate the interaction between TLRs and CRC microenvironment and the impact of TLR modifications to yield more efficient and precise CRC therapeutics.

With the introduction of integrated approach in the medical curriculum, there is a need to teach basic sciences in a way relevant to real clinical scenarios. The aim of this study is to investigate the feasibility of case-based learning (CBL) for teaching of medical biochemistry to a large number of medical students. It also evaluates both the students’ and faculty members’ perception of this approach. CBL was introduced in teaching medical biochemistry in the Neuroscience block for the second-year medical students. This study’s students were from two consecutive academic years ( n = 721 and 769). Four clinical cases were prepared. Students were divided into subgroups, each having one CBL session every 2 weeks. Students were encouraged to work together to understand the given clinical scenario by building on past knowledge obtained through other teaching modalities and new knowledge acquired during the session. A pretest was administered at the beginning of the session, and an identical posttest administered at the end of the session. Perception of both the students and facilitators of the CBL-teaching approach was evaluated using end-of-block questionnaires. In both studied academic years, students got higher scores in posttest compared to pretest scores with a statistically significant difference of the paired scores ( P < 0.001). Analysis of the students’ questionnaire demonstrated that most students positively perceived the CBL approach, with a feeling that CBL has helped them learning the biochemistry concepts. Likewise, analyzing staff questionnaire revealed staff’s positive attitude toward the impact of CBL in teaching biochemistry on the students and on themselves. The current work suggests that CBL is both feasible and efficient to be applied for teaching medical biochemistry on a large scale. It is positively perceived by both students and teaching staff. Future work is still needed to solve certain challenges such as increasing work load on the faculty members and to test the impact of this teaching modality on long-term retention of knowledge.

Introduction Bladder cancer is a common global cause of morbidity and mortality, with many patients not responding to -or not tolerating- traditional chemotherapeutic regimens. Recent studies have allowed us to utilize the genetic profile of tumors to better target therapy as is required, as well as innovate novel therapeutic interventions usable when more traditional options prove futile. Areas covered The development of novel interventions in bladder cancer, particularly immune checkpoint inhibitors, as well as using genetic markers to guide both traditional and novel therapeutic interventions. We also discuss the utility of these markers in diagnosing and prognosticating bladder cancer patients. Expert opinion Biomarker-guided therapy could revolutionize bladder cancer care in several ways: not only do novel therapeutic agents provide alternate treatment options for more difficult cases, but it can also increase the efficacy of more traditional treatment options. In addition, it may have a role in the early diagnosis and detection of bladder cancer, as well as predicting the course and prognosis of these patients. Unresolved challenges include how to best optimize therapy with novel agents as regarding duration and patient selection, as well as investigations as to whether using gene-guidance results in clinically improved patient outcomes.

Diabetic nephropathy (DN) is a major leading cause of kidney failure. So, early detection of DN by assessing urinary microRNAs (miRNAs) expression may be of clinical value. In this study, the diagnostic value of two urinary miRNAs (miR-210 & miR-34a) as biomarkers for diagnosis of DN was assessed using a simple colorimetric gold nanoparticle (AuNP) assay and real-time PCR. MiR-(210 & 34a) were markedly up-regulated in DN groups (micro-albuminuric and macro-albuminuric groups) compared to the non-albuminuric group and healthy controls. The sensitivity and specificity for the qualitative detection of urinary miR-(210 & 34a) using the AuNP assay were (78% and 72%) & (81% and 69%), respectively, which were consistent with the results of real-time PCR. There was a highly significant correlation between urinary miR-(210 & 34a) detected by either qRT-PCR or qualitative AuNP assay. Accordingly, this simple AuNP assay may be considered a valid test for the detection of these two urinary miRNAs as potential biomarkers that can aid in the noninvasive diagnosis of DN.

Bacteremia is one of the major causes of life-threatening complications in patients with cancer. Significant changes in the spectrum of microorganisms isolated from blood culture BC have been reported in cancer patients over the past years. This study aimed to determine the predominant bacterial species causing bacteremia among febrile neutropenic FN cancer patients at the National Cancer Institute in Egypt (NCI). A total of 300 BC collected from 300 FN cancer patients at NCI, Cairo. All cases were in patients with a mean age of 51 years, 158 patients were male (53%) while 142 patients were females (47%). BC was collected for microbiological investigations. Identification of the isolated organisms by the cultural characters (Morphological of bacterial isolates, Gram stain reaction, motility test, and biochemical tests) for each organism using standard semi- automated techniques. 68 (22.6%) BC were positive while 232 (77.4%) BC were negative. Gram-negative bacteria isolated and identified in 11 blood cultures (16.17%), while gram-positive isolates identified in 57 BC (83.8%). Among the Gram- negative organisms, 4 (5.8%) were Pseudomonas aeruginosa, 4 (5.8%) were E. coli, 1 (1.5%) was Klebssila pneumoni, 1 (1.5%) was Acintobacter and 1 (1.5%) was Citrobacter frenudiri. Among the Gram-positive organisms, Coagulase-negative Staphylococci CNS were most predominant in most cases 35 (61.4%). 7 (12%) were S. aureus, 5 (8%) were S. epidermises, 5 (8%) were Streptococcus spp., 1 (1.5%) were Listeria spp., 4 (5.88%) Achromobacter spp., 4 (5.88%) were Gram-Positive Cocci and 1(1.5%) Micrococcus spp. The study of R-factor in all positive BC showed the resistant bacterial isolates to the commonly used antimicrobial agents, especially to ampicillin and penicillin. This study showed that patients with febrile neutropenia are vulnerable to developing bacteremia. the prevalence rate of bacteremia in post-chemotherapy FN in our center is relatively high compared to the national rate. Multidrug-resistant are the main cause of bacteremia in febrile cancer patients in Egypt. There is a need for ongoing antimicrobial surveillance to guide antimicrobial therapy and support the development of infection control programs in Egypt

Background: Autophagy and Insulin resistance play a crucial role in pathogenesis of T2DM. Novel accurate strategies for detection of molecular pathogenesis of insulin resistance are distinctly needed. Aim of the work: To retrieve potential mRNA associated with insulin resistance related autophagy from databases followed by validation of this network in patients’ clinical samples. Material and Methods: Bioinformatics’ Analysis was done to retrieve a gene related to autophagy and IR in T2DM, then biomarker' verification was done through Gene Cards Database. Extraction of total RNA from PMNCs followed by reverse transcription PCR, then quantitative real time PCR for mRNA m-TOR in PMNCs of 123 patients with T2DM and 106 healthy normal volunteers. Results: The mRNA m-TOR had high sensitivity and specificity for discriminating T2DM patients from healthy controls. Conclusion: The mRNA m-TOR can serve as a potential biomarker for T2DM diagnosis and prognosis.

Objective: To assist in the diagnosis, treatment, and prognostic prediction of bladder cancer, the molecular patterns associated with it should be elucidated. Competing endogenous RNA network: MicroRNA (miRNA), long noncoding RNA (lncRNA), and their target autophagy genes have been strongly implicated in tumor development and metastasis. Patients and methods: Bioinformatics analysis was performed to retrieve a ceRNA: lncRNA-miRNA-mRNA network linked to autophagy and relevant to bladder cancer. Expression of selected noncoding human RNAs (miR-324-5p, miR-4738-3p, and lncRNA miR-497-HG) and their target genes (RCAN1 mRNA and FOSB mRNA) was examined by qPCR in bladder tissues and urine samples obtained from 196 individuals (98 patients with bladder cancer, 48 patients with benign lesions, and 50 healthy controls). Results: Expression levels of the selected genes in urine samples in the bladder cancer group were significantly different from those in the control group (P < 0.001). Expression in bladder cancer tissue samples correlated with that in urine samples. Urinary expression levels of all biomarkers had high accuracy to distinguish patients with and without bladder cancer, with FOSB mRNA and RCAN1 mRNA having the highest accuracy (99% for RCAN1 mRNA or FOSB mRNA, 87.8% for miR-324-5p, 84.7% for miR-4738-3p, and 90.5% for lncRNA miR-497-HG). FOSB mRNA and RCAN1 mRNA expression showed also a higher accuracy than cytology (77.6%). Conclusion: The significant differential expression of the ceRNA network: lncRNA-miRNA-mRNA network in bladder cancer as compared to noncancerous controls has revealed the superior accuracy of the chosen biomarkers to cytology, especially FOSB mRNA and RCAN1 mRNA, suggesting their involvement in bladder cancer pathogenesis and promising role for future diagnosis, and targeted therapy. (C) 2019 Elsevier Inc. All rights reserved.