Presence of Human Herpes Virus 6 (HHV6) in pediatric lymphomas: impact on clinical course and association with cytomegalovirus infection

<p>Abstract</p> <p>Background</p> <p>Activation of herpes virus 6 (HHV6) has seen in Hodgkin's and non-Hodgkin's Lymphoma (HL&NHL) as a result of lymphoma associated immunosuppression. Multiple studies have suggested an association between both HHV6 and cytomegalovirus CMV for development of CMV disease affecting the pathogenesis of lymphoma. Therefore, this study investigated the frequency of HHV6, its impact on clinical manifestations of lymphoma and its possible association with risk for development of CMV infection in pediatric lymphoma patients.</p> <p>Methods</p> <p>Presence of HHV6 DNA and CMV DNA was investigated by PCR assay in both WBC's and plasma samples from 50 patients diagnosed with HL or NHL. CMV antibody titer was also determined in sera obtained from each patient. Twenty apparently healthy siblings were used as a control group.</p> <p>Results</p> <p>In a study group of 50 patients diagnosed with HL or NHL, 23/50 (46%) were found to be positive for herpes virus DNA (HHV6 or CMV) in WBC's or plasma by PCR assay and this was significantly higher than its presence in the pediatric control group 2/20 (10%) (p = 0.005). Ten out of these 23 (43%) were found to have active CMV infection. Fifty six percent of patients with CMV infection were found among NHL cases with B- subtype. The presence of both herpes viruses DNA was significantly associated with more frequent episodes of febrile neutropenia (median 3 episodes), absolute neutrophil count (< 0.8), lymphocytes (< 0.5), and low hemoglobin level (< 9.1), (p < 0.05).</p> <p>Conclusion</p> <p>The presence of HHV6 can be considered as a predicting indicator of cellular immunosuppression preceding the onset of CMV infection which may result in a severe outcome among pediatric lymphoma patients.</p

Development of polyvinyl alcohol nanofiber scaffolds loaded with flaxseed extract for bone regeneration: phytochemicals, cell proliferation, adhesion, and osteogenic gene expression

Introduction: Bone tissue engineering seeks innovative materials that support cell growth and regeneration. Electrospun nanofibers, with their high surface area and tunable properties, serve as promising scaffolds. This study explores the incorporation of flaxseed extract, rich in polyphenolic compounds, into polyvinyl alcohol (PVA) nanofibers to improve their application in bone tissue engineering.Methods: High-performance liquid chromatography (HPLC) identified ten key compounds in flaxseed extract, including polyphenolic acids and flavonoids. PVA nanofibers were fabricated with 30 wt.% flaxseed extract (P70/E30) via electrospinning. We optimized characteristics like diameter, hydrophilicity, swelling behavior, and hydrolytic degradation. MG-63 osteoblast cultures were used to assess scaffold efficacy through cell adhesion, proliferation, viability (MTT assay), and differentiation. RT-qPCR measured expression of osteogenic genes RUNX2, COL1A1, and OCN.Results: Flaxseed extract increased nanofiber diameter from 252 nm (pure PVA) to 435 nm (P70/E30). P70/E30 nanofibers showed higher cell viability (102.6% vs. 74.5% for pure PVA), although adhesion decreased (151 vs. 206 cells/section). Notably, P70/E30 enhanced osteoblast differentiation, significantly upregulating RUNX2, COL1A1, and OCN genes.Discussion: Flaxseed extract incorporation into PVA nanofibers enhances bone tissue engineering by boosting osteoblast proliferation and differentiation, despite reduced adhesion. These properties suggest P70/E30’s potential for regenerative medicine, emphasizing scaffold optimization for biomedical applications

Chronic hepatitis c genotype-4 infection: role of insulin resistance in hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatocellular carcinoma (HCC) and different HCV genotypes show characteristic variations in their pathological properties. Insulin resistance (IR) occurs early in HCV infection and may synergize with viral hepatitis in HCC development. Egypt has the highest reported rates of HCV infection (predominantly genotype 4) in the world; this study investigated effects of HCV genotype-4 (HCV-4) on prevalence of insulin resistance in chronic hepatitis C (CHC) and HCC in Egyptian patients.</p> <p>Methods</p> <p>Fifty CHC patients, 50 HCC patients and 20 normal subjects were studied. IR was estimated using HOMA-IR index and HCV-4 load determined using real-time polymerase chain reaction. Hepatitis B virus was excluded by enzyme-linked immunosorbent assay. Standard laboratory and histopathological investigations were undertaken to characterize liver function and for grading and staging of CHC; HCC staging was undertaken using intraoperative samples.</p> <p>Results</p> <p>HCC patients showed higher IR frequency but without significant difference from CHC (52% vs 40%, p = 0.23). Multivariate logistic regression analysis showed HOMA-IR index and International Normalization Ratio independently associated with fibrosis in CHC; in HCC, HbA1c, cholesterol and bilirubin were independently associated with fibrosis. Fasting insulin and cholesterol levels were independently associated with obesity in both CHC and HCC groups. Moderate and high viral load was associated with high HOMA-IR in CHC and HCC (p < 0.001).</p> <p>Conclusions</p> <p>IR is induced by HCV-4 irrespective of severity of liver disease. IR starts early in infection and facilitates progression of hepatic fibrosis and HCC development.</p

HPLC-ESI/MS-MS characterization of compounds in Dolomiaea costus extract and evaluation of cytotoxic and antiviral properties: molecular mechanisms underlying apoptosis-inducing effect on breast cancer

Abstract Background Dolomiaea costus (syn: Saussurea costus; Family Asteraceae) occupies an important place in the traditional Chinese medicinal plants and is prescribed for a wide range of disorders. The current study aimed to tentatively identify the phytoconstituents of D. costus extract and to explore antiproliferative activity against human breast cancer cells and its possible apoptotic mechanism along with antiviral activity against human adenovirus 5 (Adv-5). Methods The phytoconstituents of 70% ethanol extract of D. costus were assessed using HPLC/ESI-MS/MS technique. The cell viability was investigated against breast cancer cell line (MCF-7) via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Mechanistically, the apoptotic effects on the Bax, Bcl2 and Caspase 3 were determined via quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR). Further, the antiviral activity was assessed against Adv-5 based on virucidal and adsorption mechanisms. Results The HPLC/MS analysis of the extract revealed tentative identification of twenty compounds of polyphenolic nature, mainly flavonoids, lignans, coumarins, and anthocyanidins. The plant extract showed a cytotoxic effect against MCF-7 and Vero cells with IC50 values of 15.50 and 44 µg/ml, respectively, indicating its aggressiveness against the proliferation of breast cancer cells as confirmed by apoptotic genes expression which revealed upregulation of Bax and Caspase 3 but further insight analysis is needed to explore exact mechanistic pathway. Antiviral activity against Adv-5 was observed at a non-toxic concentration of the tested extract. Conclusions Such observations against human breast cancer and viral replication supported further studies for nanoformulations in drug delivery systems as targeting therapy and in vivo studies before biomedical applications

Facile synthesis of Fe2O3, Fe2O3@CuO and WO3 nanoparticles: characterization, structure determination and evaluation of their biological activity

Abstract Due to their high specific surface area and its characteristic’s functionalized nanomaterials have great potential in medical applications specialty, as an anticancer. Herein, functional nanoparticles (NPs) based on iron oxide Fe2O3, iron oxide modified with copper oxide Fe2O3@CuO, and tungsten oxide WO3 were facile synthesized for biomedical applications. The obtained nanomaterials have nanocrystal sizes of 35.5 nm for Fe2O3, 7 nm for Fe2O3@CuO, and 25.5 nm for WO3. In addition to octahedral and square nanoplates for Fe2O3, and WO3; respectively. Results revealed that Fe2O3, Fe2O3@CuO, and WO3 NPs showed remarked anticancer effects versus a safe effect on normal cells through cytotoxicity test using MTT-assay. Notably, synthesized NPs e.g. our result demonstrated that Fe2O3@CuO exhibited the lowest IC50 value on the MCF-7 cancer cell line at about 8.876 µg/ml, compared to Fe2O3 was 12.87 µg/ml and WO3 was 9.211 µg/ml which indicate that the modification NPs Fe2O3@CuO gave the highest antiproliferative effect against breast cancer. However, these NPs showed a safe mode toward the Vero normal cell line, where IC50 were monitored as 40.24 µg/ml for Fe2O3, 21.13 µg/ml for Fe2O3@CuO, and 25.41 µg/ml for WO3 NPs. For further evidence. The antiviral activity using virucidal and viral adsorption mechanisms gave practiced effect by viral adsorption mechanism and prevented the virus from replicating inside the cells. Fe2O3@CuO and WO3 NPs showed a complete reduction in the viral load synergistic effect of combinations between the tested two materials copper oxide instead of iron oxide alone. Interestingly, the antimicrobial efficiency of Fe2O3@CuO NPs, Fe2O3NPs, and WO3NPs was evaluated using E. coli, S. aureus, and C. albicans pathogens. The widest microbial inhibition zone (ca. 38.45 mm) was observed with 250 mg/ml of WO3 NPs against E. coli, whereas using 40 mg/ml of Fe2O3@CuO NPS could form microbial inhibition zone ca. 32.86 mm against S. aureus. Nevertheless, C. albicans was relatively resistant to all examined NPs. The superior biomedical activities of these nanostructures might be due to their unique features and accepted evaluations