Effect of aged garlic extract and s-allyl cysteine and their interaction with atenolol during isoproterenol induced myocardial toxicity in rats

Objectives:

The study evaluates the cardioprotective effect of aged garlic extract (AGE) and its constituent; S-allylcysteine (SAC) and their interaction with atenolol during isoproterenol induced cardiac toxicity in rats.

Materials and Methods:

Rats were administered AGE at two different doses of 2 ml/kg or 5 ml/kg orally whereas SAC was administered either at a dose 13.1 mg/kg or 32.76 mg/kg. The AGE or SAC was given alone or in combination with atenolol (6 mg/kg, p.o), every alternate day for three weeks. At the end of treatment, two doses of isoproterenol (150 mg/kg, s.c) were administered to rats. The electrocardiogram (ECG) was recorded followed by withdrawal of blood to estimate serum lactate dehydrogenase (LDH) and creatinine kinase-MB (CK-MB) activities. The activities of LDH, CK-MB as well as superoxide dismutase (SOD), catalase and thiobarbituric acid reactive substances (TBARS) were also determined in the heart tissue homogenate (HTH).

Results:

The isoproterenol induced ECG changes were restored to normal in all treated groups. The AGE and SAC administration caused a decrease in serum LDH and CK-MB activities and an elevation of LDH and CK-MB activities in HTH. Atenolol alone or in combination with AGE and S-allylcsyteine demonstrated similar changes in biomarker activities.

Conclusion:

AGE showed dose-dependent cardioprotection. However, concurrent administration of SAC with atenolol (6 mg/kg, p.o) combated more effectively the myocardial dysfunction during isoproterenol induced cardiotoxicity in rats.KEY WORDS: Acute myocardial injury, aged garlic extract, atenolol, isoproterenol s-allyl cysteine     

Structure-Function Analyses of New SARS-CoV-2 Variants B.1.1.7, B.1.351 and B.1.1.28.1: Clinical,Diagnostic, Therapeutic and Public Health Implications

SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus 2) has accumulated multiple mutations during its global circulation. Recently, three SARS-CoV-2 lineages, B.1.1.7 (501Y.V1), B.1.351 (501Y.V2) and B.1.1.28.1 (P.1), have emerged in the United Kingdom, South Africa and Brazil, respectively. Here, we have presented global viewpoint on implications of emerging SARS-CoV-2 variants based on structural–function impact of crucial mutations occurring in its spike (S), ORF8 and nucleocapsid (N) proteins. While the N501Y mutation was observed in all three lineages, the 501Y.V1 and P.1 accumulated a different set of mutations in the S protein. The missense mutational effects were predicted through a COVID-19 dedicated resource followed by atomistic molecular dynamics simulations. Current findings indicate that some mutations in the S protein might lead to higher affinity with host receptors and resistance against antibodies, but not all are due to different antibody binding (epitope) regions. Mutations may, however, result in diagnostic tests failures and possible interference with binding of newly identified anti-viral candidates against SARS-CoV-2, likely necessitating roll out of recurring “flu-like shots” annually for tackling COVID-19. The functional relevance of these mutations has been described in terms of modulation of host tropism, antibody resistance, diagnostic sensitivity and therapeutic candidates. Besides global economic losses, post-vaccine reinfections with emerging variants can have significant clinical, therapeutic and public health impacts.     

Efficacy of mesenchymal stem cell therapy on glucose levels in type 2 diabetes mellitus: A systematic review and meta-analysis

Aims/IntroductionIn recent years, mesenchymal cellular therapies have received much attention in the treatment of diabetes. In this meta‐analysis, we aimed to evaluate the efficacy of mesenchymal stem cell therapy in type 2 diabetes mellitus patients.Materials and MethodsA comprehensive literature search was carried out using PubMed, Scopus, Web of Science and Central databases. A total of 1,721 articles were identified, from which nine full‐text clinical trials were qualified to enter the current meta‐analysis. The assessment groups included patients with type 2 diabetes, and levels of C‐peptide, glycosylated hemoglobin and insulin dose were analyzed before and after mesenchymal stem cell infusion. Data analysis was carried out in Stata version 11, and the Jadad Score Scale was applied for quality assessment.ResultsChanges in levels of C‐peptide after mesenchymal stem cell therapy were: standardized mean difference 0.20, 95% confidence interval −0.61 to 1.00, glycosylated hemoglobin levels were: standardized mean difference −1.45, 95% confidence interval −2.10 to −0.79 and insulin dose were: standardized mean difference −1.40, 95% confidence interval −2.88 to 0.09.ConclusionsThis meta‐analysis of prospective studies showed associations between mesenchymal stem cell therapy and control of glucose level in patients with type 2 diabetes.     

Outcomes of planned pregnancy in patients with systemic lupus erythematosus and their neonates

Aim of the workTo assess the outcome of planned pregnancies in patients with systemic lupus erythematosus (SLE). Patients and methods: The study was conducted on 32 patients. The medical management included pre-pregnancy planning at the quiescent phase of the disease and after at least six months of clinical remission. The patients had a monthly visit during pregnancy and three months post-delivery. Disease flare was characterized by the recurrence of symptoms and signs in different organs, as well as the need for an increase in medication dose. Results: There were 36 planned pregnancies in 32 patients, of which 15 and 17 cases were primiparous and multiparous, respectively. The SLE flares were observed in 36.1% of the cases, 8.3% of which developed postpartum; moreover, they were moderate in severity and mostly involved the kidneys and joints. Pregnancy outcomes included18 (50%) cases ended in term labor; 13 (36.1%) pregnancies had preterm labor, and 5 (13.8%) pregnancies terminated with abortions. Furthermore, obstetric complications included 2(6.5%) patients with premature rupture of membranes, 5(15.6%) fetuses with intrauterine growth retardation, and 2(6.4%) mothers with preeclampsia. 10(27.7%) pregnancies occurred in patients with lupus nephritis. Cesarean section was performed on 24(77.4%) patients, and low birth weight was observed in 7(21.8%) infants. None of the infants had neonatal lupus, congenital deformities or infection. Conclusion: Pre-pregnancy planning in patients with SLE can considerably improve pregnancy outcomes. Neonatal lupus, congenital anomalies or infection were not present. SLE patients intending to become pregnant should be provided with close medical supervision for a safe maternal and fetal outcome.     

The Use of Cellulose Nanocrystals for Potential Application in Topical Delivery of Hydroquinone

Nanotechnology‐based drug delivery systems can enhance drug permeation through the skin and improve the drug stability. The biodegradability and biocompatibility of cellulose nanocrystals have made these nanoparticles good candidates to use in biomedical applications. The hyperpigmentation is a common skin disorder that could be caused by number of reasons such as sun exposure and pregnancy. Hydroquinone could inhibit the production of melanin and eliminate the discolorations of skin. This study is aimed at introducing cellulose nanocrystals as suitable carriers for drug delivery to skin. Prepared cellulose nanocrystals were characterized by dynamic light scattering and atomic force microscopy. The size of cellulose nanocrystals determined using dynamic light scattering was 301 ± 10 nm. Hydroquinone–cellulose nanocrystal complex was prepared by incubating of hydroquinone solution in cellulose nanocrystals suspension. The size of hydroquinone–cellulose nanocrystal complex determined using dynamic light scattering was 310 ± 10 nm. The hydroquinone content of the hydroquinone–cellulose complex was determined using UV/vis spectroscopy. Hydroquinone was bound to cellulose nanocrystals representing 79.3 ± 2% maximum binding efficiency when 1.1 mg hydroquinone was added to 1 mL of cellulose nanocrystals suspension (2 mg cellulose nanocrystal). The hydroquinone–cellulose nanocrystal complex showed an approximately sustained release profile of hydroquinone. Approximately, 80% of bound hydroquinone released in 4 h.     

Adenovirus transduction to effect CD40 signalling improves the immune stimulatory activity of myeloma cells

Neoplastic plasma cells from patients with myeloma fail to stimulate an effective anti-myeloma immune response, which may be in part due to their deficient expression of immune accessory molecules. Attempting to alter this, we infected myeloma cell lines and patient-derived primary myeloma cells with an adenovirus encoding CD154 (Ad-CD154). Myeloma cells were made to express the CD154 transgene at multiplicity of infection (MOI) between 10 and 1000. Furthermore, infection of CD40(positive) myeloma cells with Ad-CD154, but not an adenovirus encoding an irrelevant transgene, beta-galactosidase (Ad-LacZ), induced enhanced expression of immune accessory molecules, such as CD54, HLA-DR and CD70. In addition, Ad-CD154-infected myeloma cells could activate bystander CD40(positive) antigen-presenting cells to express immune accessory molecules. Consequently, Ad-CD154 infected myeloma cells stimulated proliferation in allogeneic mixed lymphocyte reactions (MLR). Finally, co-infection of CD40(negative) myeloma cells with Ad-CD154 and an adenovirus encoding CD40 (Ad-CD40) induced expression of immune accessory molecules and enhanced the MLR stimulatory capacity of transduced myeloma cells. Collectively, these results indicate that infection of myeloma cells with Ad-CD154 or Ad-CD154/Ad-CD40 can induce changes in myeloma cells that enhance their ability to induce cellular immune activation. As such, this approach may have potential application for immune therapy of patients with this disease.