Molecular basis of the potential interaction of SARS-CoV-2 spike protein to CD147 in COVID-19 associated-lymphopenia.

Lymphopenia is considered one of the most characteristic clinical features of the coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects host cells via the interaction of its spike protein with the human angiotensin-converting enzyme 2 (hACE2) receptor. Since T lymphocytes display a very low expression level of hACE2, a novel receptor might be involved in the entry of SARS-CoV-2 into T cells. The transmembrane glycoprotein CD147 is highly expressed by activated T lymphocytes, and was recently proposed as a probable route for SARS-CoV-2 invasion. To understand the molecular basis of the potential interaction of SARS-CoV-2 to CD147, we have investigated the binding of the viral spike protein to this receptor in-silico. The results showed that this binding is dominated by electrostatic interactions involving residues Arg403, Asn481, and the backbone of Gly502. The overall binding arrangement shows the CD147 C-terminal domain interacting with the spike external subdomain in the grove between the short antiparallel ß strands, ß1' and ß2', and the small helix α1'. This proposed interaction was further confirmed using MD simulation and binding free energy calculation. These data contribute to a better understanding of the mechanism of infection of SARS-CoV-2 to T lymphocytes and could provide valuable insights for the rational design of adjuvant treatment for COVID-19. Communicated by Ramaswamy H. Sarma.

Efficient tailoring of platinum nanoparticles supported on multiwalled carbon nanotubes for cancer therapy.

Aim: Therapeutically targeting cancer stem cells (CSCs), which play a role in tumor initiation and relapse, remains challenging. Materials & methods: Novel-formulated platinum nanoparticles (Pt-NPs) supported on polybenzimidazole (PBI)-functionalized polymers and multiwalled carbon nanotubes (MWCNT) were prepared and their effect on CSCs was evaluated. Results: Pt-NPs showed homogenous distribution on the surface of MWCNT/PBI composites, with very narrow particle size. MWCNT/PBI/Pt-NPs resulted in a dramatic decrease in the proliferation rate of CSCs but not bone marrow mesenchymal stem cells (BM-MSCs). Quantitative gene expression analysis revealed that MWCNT/PBI/Pt had a significant inhibitory effect on the epithelial-mesenchymal transition and cell cycle markers of CSCs. Conclusion: MWCNT/PBI/Pt exhibited a specific cytotoxic effect on breast CSCs but not on adult stem cells.

Nitric oxide levels and sustained virological response to pegylated-interferon alpha2a plus ribavirin in chronic HCV genotype 4 hepatitis: A prospective study.

BACKGROUND: The role of nitric oxide (NO) in infectious diseases is gaining attention because of its antiviral effects. AIM: To evaluate whether serum and hepatic NO levels are predictors of the outcome of treatment in patients with chronic hepatitis C genotype 4. METHODS: Fifty six patients with chronic HCV genotype 4 treated with pegylated interferon (IFN) alpha-2a plus ribavirin underwent blood tests, assessment of serum level of NO and hepatic tissue expression of NO synthase (iNOS) before and during treatment. RESULTS: The pre-treatment serum NO level was significantly higher in sustained responders (SR) [39.583 (35-43.8)] compared to relapsers [36.25 (26-43.8)], and non responders (NR) [35.417 (25.0-43.8)]. During treatment, the serum NO level was significantly higher in SR [58.125 (47.9-60.6)] compared to relapsers [53.854 (47.9-59.4)] and NR [50 (42.9-59.4)]. The pre-treatment iNOS expression was significantly higher in SR [37.5 (15-75)] compared with either relapsers [25 (15-45)] and or NR [20 (2-45)]. In multivariate logistic regression analysis, the serum NO was correlated with the virological response to pegylated interferon alpha-2a plus ribavirin therapy. CONCLUSION: In patients with chronic hepatitis C, nitric oxide levels may be associated with the outcome of pegylated-IFN-α 2a plus ribavirin treatment.

Successful pregnancies post renal transplantation.

To evaluate the maternal and fetal outcomes in renal transplant female recipients who became pregnant from 1989 to 2005 in our center, we retrospectively studied 20 incident pregnancies in 12 renal transplant recipients; 5 (41.7 %) of them from living related, 4 (33.3%) from deceased, and 3 (25%) from living unrelated donors. The mean age at pregnancy was 30.5 +/- 4.5 years and mean interval from transplantation to pregnancy was 21 +/- 5.7 months with the interval was 132 micromol/L, and another with short interval from transplantation to pregnancy UTI (25%), preterm delivery respectively. Gestational age at delivery was 36.3 +/- 3.9 weeks, and mean fetal birth weight was 2349 +/- 574 gm. Apgar score was 9-10 in all of the 20 babies, and none revealed intrauterine growth retardation or congenital anomalies. We conclude that consecutive pregnancies demonstrate long-term maternal and fetal survival and function. The major risk factors are elevated starting serum creatinine, hypertension, and short time interval from transplantation to pregnancy.

The effect of portal vein branch plus heterochronous hepatic artery branch ligation on liver regeneration (experimental study).

The proliferative capacity of non-ligated liver lobes was designned experimental study on dogs in which portal vein and hepatic artery ligation was done either simultaneously or heterochronously. Dogs were divided into four groups: G I (control G); laparotomy was performed without vascular ligation, G II; dogs were subjected to ligation of the right lateral and median branches of portal vein alone, G III, dogs were subjected to hepatic artery branches ligation 48h after portal vein branches ligation. G IV, dogs were subjected to ligation of the same branches of the portal vein and hepatic artery simultaneously. Dogs from each group were subjected to a liver biopsy before and 24, 48, 72, & 168h (one week) after surgery. Standard serum liver functions were tested before ligation, 72 hs and one week after ligation. Hepatic regeneration in the non-ligated lobe was assessed through histo-pathological study, DNA quantitation of the hepatic nuclei by the computerized image analysis system and estimation of proliferation marker in hepatic tissue. In this study, the labeling index of the nuclear factor NF Kappa B (P105), a novel monoclonal antibody specific for P105 protein, was determined immunohistochemically. Results showed induction of the NK kappa B (P105) labeling index showed maximum levels G III. Quantitative determination of serum glutamic-oxalacetate transaminase (GOT) showed peak levels in G IV at 24h after surgery. Our finding for this index that heterochronous partial portal vein and hepatic artery ligation (i.e., G III) is effective, because this procedure leads to an increase in the compensatory hypertrophy of the non-ligated liver lobes that depends on the regenerative capacity of the lobes themselves. In contrast, in G IV (i.e., synchronous ligation of portal vein and hepatic artery branches) liver regeneration did not occur due to the severe systemic damage induced by infectious necrosis in the ligated lobe. The serial changes in liver function in G III indicate that the use of this technique may minimize dysfunction in the remaining hypertrophied liver lobes, similar to findings in G II. So, the PVBL plus heterochronous HABL procedure is safer and more effective than PVBL alone, or PVBL plus simultaneous HABL. A better knowledge of the events following such heterochronous ligation should improve the clinical outcome of hepatic resection for liver diseases.

Clinical significance of T.T. virus infection in maintenance hemodialysis patients of an endemic area for hepatitis C infection.

Clinical significance of TTV infection was analyzed in Egyptian hemodialysis (HD) patients. Forty-seven Egyptian patients on maintenance HD and 50 age-matched volunteer blood donors were investigated. TT virus (TTV) DNA detection and genotyping were performed using a semi-nested polymerase chain reaction with specific primers. The prevalence of TTV DNA in patients on HD (66%) was significantly (P<0.001) higher than in blood donors (24%) with genotype 1b predominance (89%) in both. Clinical background including mean age, sex, history of blood transfusion, and positive markers for either hepatitis B virus (HBV) or hepatitis C virus (HCV) did not differ between TTV DNA positive and negative HD patients. However, the mean duration of HD was significantly (P=0.032) shorter in the TTV positive patients (28+/-19 months) than in the negative ones (45+/-34 months). Mean alanine aminotransferase level in patients with HCV infection alone (41+/-24 IU/l) did not differ from that in patients with both co-infection (33+/-28 IU/l), but was significantly higher than that in patients with TTV infection alone (26+/-10 IU/l). Occurrence of chronic hepatic changes in patients with TTV infection alone (7%) was significantly less common than those with HCV infection alone (100%, P<0.001) or those with both co-infection (100%, P<0.001). Serum level of HCV core protein was similar between patients with HCV infection alone and those with co-infection with TTV. In conclusion, the prevalence of TTV infection is high in Egyptian patients on regular HD, especially with shorter duration on HD. No clinical significance of TTV virus could be elicited in HD Egyptian patients; neither it showed any clinical impact as a co-infection with HCV.