Comparing the effect of Toll-like receptor agonist adjuvants on the efficiency of a DNA vaccine

We have investigated whether poly(I:C) Toll-like receptor 3 (TLR3) and resiquimod Toll-like receptor 7 (TLR7) agonists can serve as vaccine adjuvants and promote the efficiency of therapeutic DNA vaccination against tumors expressing the human papilloma virus 16 (HPV-16) E7 protein. For this purpose, C57BL/6 mice were inoculated with 2 × 10⁵ TC-1 cells, and they were then immunized with HPV-16 E7 DNA vaccine alone or with 50 μg of resiquimod or poly(I:C) individually. We found that poly(I:C) and resiquimod could induce more antigen-specific lymphocyte proliferation and cytolytic activity compared to vaccination with E7 DNA alone. While E7 DNA had no significant inhibitory effect on tumor growth, co-administration of poly(I:C) and resiquimod with E7 DNA induced significant tumor regression. Peripheral and local cytokine assays demonstrated that co-administration of poly(I:C) and resiquimod with E7 DNA induced circulating antigen-specific IFN-γ and nonspecific intratumoral IL-12. TLR3 and TLR7 agonists can be used to enhance the immune response to DNA vaccine immunogens. Taken together, these data indicate that combined vaccination with DNA encoding HPV-16 E7 plus TLR agonists provides a strategy for improving the efficacy of a vaccine as a possible immunotherapeutic strategy for cervical cancer.     

Vitamin B6 dose-dependently ameliorates renal hemodynamic toxicity of cisplatin in rat model of nephrotoxicity: the histopathologic and biochemical findings

Despite its significant anticancer activity, the clinical use of cisplatin is often limited by its undesirable side effects in the kidney known as nephrotoxicity. It is a common and often overlooked clinical entity that presents itself in the setting of oxidative stress-associated diseases in older individuals with renal failure. In this study, we investigated the antioxidant-protecting effects of vitamin B₆ in the kidney, with a view on the vasoregulatory role of renal pyridoxal 5′-phosphate at reducing the hemodynamic toxicity of cisplatin. Hence, 50 male Sprague–Dawley rats were randomly assigned in one of five groups of the study to receive a corresponding dose of either normal saline, vitamin B₆ (200 mg/kg/bw; i.m.) or cisplatin alone (7 mg/kg/bw; i.m.), or in combination with vitamin B₆ at low (100 mg/kg/bw; i.m.) and high dose (200 mg/kg/bw; i.m.) for 10 days as animal model of renal failure. Daily administration of cisplatin at a dose of 7 mg/kg/bw resulted in a significant increase in local and systemic oxidative stress of the kidney and a decrease in glomerular function as a result of early hemodynamic toxicity. Histopathological examinations of renal tissues revealed acute tubular necrosis with hyaline cast formation triggered by cisplatin over 9 days of the study, in addition to interstitial nephritis and tubular epithelial loss. Further biochemical studies in HVB group showed the protecting effects of supplemented vitamin B₆ at a high dose, including a slowdown in urinary enzyme activity, a significant decrease in plasma lipid peroxidation, and an increased tissue superoxide dismutase activity with recovery in the glomerular hemodynamicity and ATPase activity up to 50 % when compared to the low-dose rats and controls. In high-dose animals, the normal glomerular and tubular function on recovery from toxic renal failure led us to conclude that the antioxidant property of vitamin B₆ consistently increases with the dose intensity. The present study also provided evidence that high dose of vitamin B₆ prevented both functional and histological renal changes induced by cisplatin in rats, more efficient than low dose of the vitamin.     

Identification of novel variants in Iranian consanguineous pedigrees with nonsyndromic hearing loss by next-generation sequencing

BackgroundThe extremely high genetic heterogeneity of hearing loss due to diverse group of genes encoding proteins required for development, function, and maintenance of the complex auditory system makes the genetic diagnosis of this disease challenging. Up to now, 121 different genes have been identified for nonsyndromic hearing loss (NSHL), of which 76 genes are responsible for the most common forms of NSHL, autosomal recessive nonsyndromic hearing loss (ARNSHL).MethodsAfter excluding mutations in the most common ARNSHL gene, GJB2, by Sanger sequencing, genetic screening for a panel of genes responsible for hereditary hearing impairment performed in 9 individuals with ARNSHL from unrelated Iranian consanguineous pedigrees.ResultsOne compound heterozygote and eight homozygote variants, of which five are novel, were identified: CDH23:p.(Glu1970Lys), and p.(Ala1072Asp), GIPC3:p.(Asn82Ser), and (p.Thr41Lys), MYO7A:p.[Phe456Phe]; p.[Met708Val], and p.(Gly163Arg), TECTA:p.(Leu17Leufs*19), OTOF:c.1392+1G>A, and TRIOBP:p.(Arg1068*). Sanger sequencing confirmed the segregation of the variants with the disease in each family.ConclusionFinding more variants and expanding the spectrum of hearing impairment mutations can increase the diagnostic value of molecular testing in the screening of patients and can improve counseling to minimize the risk of having affected children for at risk couples.     

A giant early second‐trimester placental chorioangioma associated with isolated proteinuria and histopathologically confirmed placental insufficiency,a novel association: A case report

We present a case of giant chorioangioma at 18 weeks of gestation leading to fetal hypertrophic cardiomyopathy without other evidences of fetal volume overload and late‐onset isolated proteinuria. Oligohydramnios developed at term and placental insufficiency was confirmed on histopathological examination and a nonanemic nonthrombocytopenic normal weight healthy baby was delivered.     

Mean drop behavior in the standard liquid–liquid extraction systems on an L-shaped pulsed sieve-plate column: experiment and modeling

In this study, the effect of operating parameters on drop behavior was investigated experimentally in an L-shaped pulsed sieve-plate column (LPSPC). LPSPC offers enhanced efficiency due to a high mixing rate provided by pneumatic or hydraulic pulsation of the liquids, which makes the dispersed phase drops coalesce and break. The response surface methodology (RSM) based on the central composite design (CCD) approach was applied for experimental modeling of three standard systems including toluene–water, butyl acetate–water, and butanol–water. Four parameters including pulsation intensity, interfacial tension, dispersion, and continuous phase velocities were examined in the experiments. Experimental results indicated that an increase in the pulsation intensity led to a decrease in Sauter mean diameter (SMD), and an increase in the flow rates of the phase cause an increase in SMD, although the effect of the flow rates on SMD was much lower than the pulsation intensity. Based on the obtained experimental data, new correlations have been proposed to predict SMD in two sections of the column tested by the goodness-of-fit statistics through analysis of variance. The coefficient of determination was achieved at 0.998 and 0.978 for horizontal and vertical sections, respectively, which demonstrated that the presented models estimated the experimental values very well. The optimum SMDs were obtained at 0.789 mm and 0.639 mm for the horizontal and vertical sections, respectively.

The effect of operating parameters on drop behavior was investigated experimentally in a L-shaped pulsed sieve-plate column (LPSPC).     

Ionized and total magnesium concentration in patients with severe preeclampsia-eclampsia undergoing magnesium sulfate therapy

AIM: As ionized magnesium is the active form of magnesium and exerts a therapeutic effect, the present study was performed to determine the levels and correlations between ionized and total magnesium under baseline and therapeutic conditions in patients with severe preeclampsia and eclampsia receiving magnesium sulfate. METHODS: Fifty singleton patients with severe preeclampsia received a loading dose of 4 g of magnesium sulfate, followed by 2 g per hour as maintenance dose until 24 h after delivery, or 24 h after the last seizure in case of postpartum convulsions. Serial blood samples were taken before magnesium sulfate infusion, 30 min and 240 min after the initiation of the infusion and 4 h after the discontinuation of the drug. Data were analyzed by repeated measure ANOVA and paired t-test. RESULTS: Baseline levels of total and ionized magnesium were 2.4+/-0.6 mEq/L and 1.3+/-0.5 mEq/L (mean+/-SD), respectively. Putative level of 4 mEq/L of total magnesium was not obtained in up to 42% of patients during the treatment. There was not any significant correlation between the two forms of magnesium under baseline and therapeutic conditions. CONCLUSION: Despite the effectiveness of the standard regimen of magnesium sulfate in the treatment and prevention of eclamptic seizures, it can not provide the proposed therapeutic level of magnesium in all patients. With respect to the lack of correlation between ionized and total magnesium, further studies are necessary to investigate the superiority of measurement of ionized, rather than total magnesium, for titration of therapeutic magnesium sulfate infusion.     

Preparation of NiFe2O4@MIL-101(Fe)/GO as a novel nanocarrier and investigation of its antimicrobial properties

In this research, we have investigated a novel magnetic nanocomposite including NiFe₂O₄@MIL-101(Fe)/GO for the delivery of the antibiotic tetracycline (TC). Moreover, the antibacterial activity of NiFe₂O₄@MIL-101(Fe)/GO, NiFe₂O₄@MIL-101(Fe)/GO/TC and pure TC was evaluated by agar well diffusion and minimum inhibitory concentration (MIC) methods on both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. In addition, the cytotoxicity of NiFe₂O₄@MIL-101(Fe)/GO/TC on HeLa cells was determined by an MTT assay which showed good results. The structure of the prepared nanocarrier was investigated by various spectroscopic techniques such as Fourier-transform infrared spectroscopy (FT-IR), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), Brunauer–Emmett–Teller (BET), and thermal gravimetric analysis (TGA). The results of this study showed that 98% of the TC was loaded on the synthesized nanocomposite. Drug release occurred at pH: 7.4 (phosphate buffer saline) and pH: 5.0 (acetate buffer) within 3 days, resulting in 77% and 85% release of the drug, respectively.

A schematic exhibition of the synthetic procedure of NiFe₂O₄@MIL-101(Fe)/GO as TC carrier and antibacterial activities.     

Worldwide prevalence of microbial agents’ coinfection among COVID‐19 patients: A comprehensive updated systematic review and meta‐analysis

BackgroundTo provide information about pathogens’ coinfection prevalence with SARS‐CoV‐2 could be a real help to save patients’ lives. This study aims to evaluate the pathogens’ coinfection prevalence among COVID‐19 patients.MethodIn order to find all of the relevant articles, we used systematic search approach. Research‐based databases including PubMed, Web of Science, Embase, and Scopus, without language restrictions, were searched to identify the relevant bacterial, fungal, and viral coinfections among COVID‐19 cases from December 1, 2019, to August 23, 2021. In order to dig deeper, other scientific repositories such as Medrxiv were probed.ResultsA total of 13,023 studies were found through systematic search. After thorough analysis, only 64 studies with 61,547 patients were included in the study. The most common causative agents of coinfection among COVID‐19 patients were bacteria (pooled prevalence: 20.97%; 95% CI: 15.95–26.46; I ²: 99.9%) and less frequent were virus coinfections (pooled prevalence: 12.58%; 95% CI: 7.31–18.96; I ²: 98.7%). The pooled prevalence of fungal coinfections was also 12.60% (95% CI: 7.84–17.36; I ²: 98.3%). Meta‐regression analysis showed that the age sample size and WHO geographic region did not influenced heterogeneity.ConclusionWe identified a high prevalence of pathogenic microorganism coinfection among COVID‐19 patients. Because of this rate of coinfection empirical use of antibacterial, antifungal, and antiviral treatment are advisable specifically at the early stage of COVID‐19 infection. We also suggest running simultaneously diagnostic tests to identify other microbiological agents’ coinfection with SARS‐CoV‐2.     

1,2,3-Triazole framework: a strategic structure for C–H⋯X hydrogen bonding and practical design of an effective Pd-catalyst for carbonylation and carbon–carbon bond formation

1,2,3-Triazole is an interesting N-heterocyclic framework which can act as both a hydrogen bond donor and metal chelator. In the present study, C–H hydrogen bonding of the 1,2,3-triazole ring was surveyed theoretically and the results showed a good agreement with the experimental observations. The click-modified magnetic nanocatalyst Pd@click-Fe₃O₄/chitosan was successfully prepared, in which the triazole moiety plays a dual role as both a strong linker and an excellent ligand and immobilizes the palladium species in the catalyst matrix. This nanostructure was well characterized and found to be an efficient catalyst for the CO gas-free formylation of aryl halides using formic acid (HCOOH) as the most convenient, inexpensive and environmentally friendly CO source. Here, the aryl halides are selectively converted to the corresponding aromatic aldehydes under mild reaction conditions and low Pd loading. The activity of this catalyst was also excellent in the Suzuki cross-coupling reaction of various aryl halides with phenylboronic acids in EtOH/H₂O (1 : 1) at room temperature. In addition, this catalyst was stable in the reaction media and could be magnetically separated and recovered several times.

The C–H hydrogen bonding of a 1,2,3-triazole framework was studied. An Fe₃O₄–chitosan core–shell incorporating a triazole/Pd complex was investigated as a nanocatalyst in carbonylation and C–C coupling.