Industrial and Engineering Chemistry最新文献

Objective: Cytokine storm in coronavirus disease 2019 (COVID-19) patients causes lung damage and acute respiratory distress syndrome (ARDS). Immunomodulators such as steroids are widely used to control this situation. This study investigates the effectiveness of steroids used in COVID-19 patients, and their effects on secondary infections, morbidity, and mortality.

Methods: Data were obtained by retrospectively scanning the files of patients in our hospital's intensive care unit clinic during the three peak periods.

Results: Between the steroid and non-steroid groups, there was no statistically significant difference in reproductive rates. These rates were 49.7% and 43.2%, respectively. Reproductive rates among steroid types were determined as 25 (56.8%) in the Methylprednisolone group, 18 (69.2%) (Highest) in the Dexamethasone + Methylprednisolone group, and 54 (43.2%) (Lowest) in the Dexamethasone group. Steroid treatment duration was effective on reproduction. Steroids cause more infections, especially after invasive procedures (Tracheal intubation, central venous catheter, etc.). In the groups with and without tracheal aspirate steroids, the growth rates were 71 (76.3%) and 32 (54.2%) respectively. There was no difference in mortality between the groups.

Conclusion: Cytokine storm causes lung damage and ARDS. Steroids can be useful in controlling this hyper-inflammatory situation. However, increased secondary infections, an important side effect of steroids, increase mortality. Steroids more often cause these infections, especially in patients undergoing invasive Strict adherence to infection control measures during steroid treatment will reduce this risk. In conclusion, while steroids reduce mortality by controlling the hyper-inflammatory picture, they also increase mortality with increased secondary infections. Preventing infections enables success with steroids.

Small interfering RNA (siRNA) application in therapy still faces a major challenge with the lack of an efficient and specific delivery system. Current vehicles are often responsible for poor efficacy, safety concerns, and burden costs of siRNA-based therapeutics. Here, we describe a novel strategy for targeted delivery of siRNA molecules to inhibit human immunodeficiency virus (HIV) infection. Specific membrane translocation of siRNA inhibitor was addressed by an engineered nanobody targeting the HIV co-receptor CXCR4 (NbCXCR4) in fusion with a single-chain variable fragment (4M5.3) that carried the FITC-conjugated siRNA. 4M5.3-NbCXCR4 conjugate (4M5.3X4) efficiently targeted CXCR4⁺ T lymphocytes, specifically translocating siRNA by receptor-mediated endocytosis. Targeted delivery of siRNA directed to the mRNA of HIV transactivator tat silenced Tat-driven viral transcription and inhibited the replication of distinct virus clades. In summary, we have shown that the engineered nanobody chimera developed in this study constitutes an efficient and specific delivery method of siRNAs through CXCR4 receptor.

Increased Connexin43 hemichannel opening is associated with inflammasome pathway activation and inflammation in a range of pathologies including ocular disorders, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). In this study, the effect on retinal function and morphology of clinically safe doses of orally delivered tonabersat, a small molecule connexin hemichannel blocker, was investigated in the light-damaged retina animal model of dry AMD and in a spontaneous rat model of DR. Clinical parameters (fundus imaging, optical coherence tomography (OCT), and electroretinography) and inflammatory markers (immunohistochemistry for Iba-1 microglial marker, astrocyte marker glial fibrillary acidic protein, and Connexin43 protein expression) were assessed. Tonabersat treatment reduced inflammation in the retina in parallel with preservation of retinal photoreceptor function when assessed up to 3 months post light damage in the dry AMD model. In the DR model, clinical signs, including the presence of aneurysms confirmed using Evans blue dye perfusion, were reduced after daily tonabersat treatment for 2 weeks. Inflammation was also reduced and retinal electrical function restored. Tonabersat regulates assembly of the inflammasome (NLRP3) through Connexin43 hemichannel block, with the potential to reduce inflammation, restore vascular integrity and improve anatomical along with some functional outcomes in retinal disease.

A high-affinity anti-cocaine monoclonal antibody, designated h2E2, is entering phase 1 clinical trials for cocaine abuse therapy. To gain insight into the molecular details of its structure that are important for binding cocaine and cocaine metabolites, the Fab fragment was generated and crystallized with and without ligand. Structures of the unliganded Fab and the Fab fragment bound to benzoylecgonine were determined, and were compared with each other and with other crystallized anti-cocaine antibodies. The affinity of the h2E2 antibody for cocaine is 4 nM, while that of the cocaine metabolite benzoylecgonine is 20 nM. Both are higher than the reported affinity for cocaine of the two previously crystallized anti-cocaine antibodies. Consistent with cocaine fluorescent quenching binding studies for the h2E2 mAb, four aromatic residues in the CDR regions of the Fab (TyrL32, TyrL96, TrpL91 and TrpH33) were found to be involved in ligand binding. The aromatic side chains surround and trap the tropane moiety of the ligand in the complex structure, forming significant van der Waals interactions which may account for the higher affinity observed for the h2E2 antibody. A water molecule mediates hydrogen bonding between the antibody and the carbonyl group of the benzoyl ester. The affinity of binding to h2E2 of benzoylecgonine differs only by a factor of five compared with that of cocaine; therefore, it is suggested that h2E2 would bind cocaine in the same way as observed in the Fab-benzoylecgonine complex, with minor rearrangements of some hypervariable segments of the antibody.

Background: Few accurate up-to-date studies provide liver cancer mortality and survival information in Zhejiang province. This research aimed to depict the mortality and survival of liver cancer in Zhejiang province in China during 2005-2010.

Methods: The data were collected from the Zhejiang Chronic Disease Surveillance Information and Management System, and the mortality rates of liver cancer were calculated by gender, age, and areas. Chinese population census in 2000 and Segi's world population were used for age-standardized mortality rate. The observed and relative survival rates of liver cancer patients were analyzed.

Results: The crude mortality rate of liver cancer was 32.11/10⁵. The age-standardized mortality rate was 17.39/10⁵ and 23.07/10⁵ by Chinese population (ASIRC) and Segi's world population (ASIRW), respectively. The crude liver cancer mortality rate and age-standardized rate in urban areas were lower than those of rural areas. The overall 1-, 3-, and 5-year observed survival (OS) rates of liver cancer patients were 38.61%, 21.65%, and 16.83%, respectively. The 1-, 3-, and 5-year relative survival (RS) rates of liver cancer patients were 39.49%, 23.27%, and 19.09%, respectively. Survival rate decreased obviously within 1 to 5 years and then leveled off. It was shown that the male overall survival rate was higher than the female one and the difference was statistically significant (P<0.05).

Conclusions: Both lower mortality and better survival rates were observed in urban areas, compared to rural areas. Relevant parties including government, public resource, and propaganda department should devote enough attention to rural areas.