Investigating the antimicrobial activity, cytotoxicity, and action mechanism of acylated and amidated derivatives of AurH1 antifungal peptide.

BACKGROUND: The increasing growth of microbial resistance threatens the health of human societies. Therefore, the discovery and design of new antibiotics seem necessary. Today, antimicrobial peptides (AMPs) are receiving attention due to their unique properties. In our previous studies, exclusive antifungal effects of AurH1, which is a truncated and modified form of Aurein1.2, were synthesized. In this study, AurH1 antifungal peptide was synthesized into acylated (Ac-AurH1) and amidated (AurH1-NH2) derivatives, and their antifungal activity, cytotoxicity, anticancer activity, hemolytic effects were investigated. Finally, the time- of killing, the action mechanism of amidated and acylated peptides, and the effects of salts and human serum on their antimicrobial potency were determined. All the results obtained about these peptides were compared with the AurH1 without chemical modifications. RESULTS: The results showed that amidation at the C-terminal of AurH1 compared to acylation at the N-terminal of it can improve the antifungal properties and cytotoxicity of AurH1. The results showed that AurH1 amidation can maintain the antifungal activity of this peptide in the culture medium containing specific dilutions of human serum compared to the intact AurH1. Also, the amidation of the C-terminal of AurH1 could not affect the mechanism of action and its time -of killing. CONCLUSION: As a result, the amidation of the C-terminal of the AurH1 is a suitable strategy to improve its antifungal properties and cytotoxicity. This modification can enhance its properties for animal studies.

Evaluation of quality of life and depression in family caregivers of patients with type 1 diabetes in Iran: A case-control study.

Objective: Diabetes as a silent epidemic and one of the top four causes of death in the world. This study was designed to evaluate the quality of life and depression in family caregivers of patients with type 1 diabetes in Iran. Methods: The study was case-control study (cases, n = 50; controls, n = 50). The cases consisted of family caregivers of patients with type 1 diabetes who referred to the endocrinology clinic of Kosar Hospital in Semnan in 2020. The controls were a random sample from among family caregivers of non-diabetic patients who had referred to the same center in the same year. Demographic and family variables, the 36-Item Short Form Survey questionnaire, and Beck's Depression Inventory were used to collect data. Univariate and multivariable logistic regression models with receiver operator characteristic (ROC) curve were used to data analysis in STATA 14. Results: The multivariable logistic regression model showed a significant association between existence of a patient with type 1 diabetes with number of caregivers' children (odds ratio (OR) = 1.77; 95% confidence interval (CI): 1.06-2.94), quality of life (OR = 0.82; 95% CI: 0.74-0.90), sex (OR = 10.04; 95% CI: 2.29-43.99), and income level of caregivers (OR = 6.49; 95% CI: 1.35-31.08); however, it did not show a significant relationship with depression (OR = 1.02; 95% CI: 0.94-1.10). Conclusion: The quality of life in family caregivers of type 1 diabetics is low and gender, income level, and number of caregivers' children were the most important factors predicting it. Therefore, psychological interventions to manage stress and improve the quality of life of family caregivers are recommended.

Determination of antifungal activity and action mechanism of the modified Aurein 1.2 peptide derivatives.

BACKGROUND: With the emergence of drug-resistant fungi and the increased population prone to fungal infections, more effective antifungal drugs are needed. Aurein 1.2 is a potent antimicrobial peptide. Here, we designed a novel derivative of Aurein 1.2, called Aurein N3, which is a modified form of Aurein N2 (another Aurein 1.2 derivative), in which Lys 8 residue was replaced with Leu 13, and was also modified by creating two other mutations. METHODS: Aurein N3 was designed using several algorithms and docking studies. All peptides were synthesized and some of their bio-activity indices such as antifungal properties on 11 fungi, cytotoxicity, hemolysis, and time of the killing were investigated. Electron microscopy, lived/dead staining, and ergosterol binding assay were performed to study their mechanism of action. RESULTS: In comparison to Aurein 1.2 and N2, the docking studies showed that Aurein N3 has reduced binding energy toward ergosterol. The antifungal assessments showed that both Aurein N2 and N3 had strong activity against many fungi. Aurein N3 had lower cytotoxicity and higher binding capability to ergosterol. The hemolytic activity of Aurein N2 and N3 was less than parental Aurein 1.2. All peptides were able to attack the cell wall/membrane and enter the fungi cells. CONCLUSION: Here we introduced a novel derivative of Aurein 1.2 which has lower cytotoxicity, higher ergosterol-binding capability, and comparable antifungal activity compared to the original peptides. It can bind to ergosterol and can also attack the cell wall/membrane of fungi, although more studies are required to find its accurate mechanism of action.

The Relationship Between Sleep Quality and Quality of Life Among Patients With Asthma.

Background and objective Asthma is a chronic recurring respiratory disease, and its prevalence is on the rise. A drop in the quality of life (QoL), as well as sleep problems, has been reported in asthmatic patients in the literature. This study was conducted to determine the relationship between QoL and sleep quality in asthmatic patients. Methods This cross-sectional study recruited 76 diagnosed asthmatic outpatients from our university clinic. The subjects completed the self-administered 36-Item Short-Form Health Survey QoL questionnaire (SF-36) and the Pittsburgh Sleep Quality Index (PSQI) assessment. Results The study results revealed poor sleep quality in 55 (72.4%) of the subjects. The total sleep quality scores significantly and negatively correlated with the physical and mental components of QoL (moderate, p=0.00). All QoL subscales were significantly higher in patients with good sleep quality (PSQI: <5, p<0.00). Logistic regression analysis showed that good sleep quality (modified) could predict a mental component score (MCS) of more than 64. Conclusion Poor sleep quality can bring down the scores of all QoL components in asthma patients and is the best predictor of their QoL. Therefore, sleep quality and QoL indicators could be applied as part of a better approach to classification, management, and control of asthma.

Novel ABCD1 gene mutations in Iranian pedigrees with X-linked adrenoleukodystrophy.

Background X-linked adrenoleukodystrophy (X-ALD), the most common peroxisomal disorder, is caused by mutations in the ABCD1 gene located on Xq28. X-ALD is characterized by a spectrum of different manifestations varying in patients and families. Methods Four pedigrees with X-ALD consisting of patients and healthy members were selected for investigation of ABCD1 gene mutations. The mutation analysis was performed by polymerase chain reaction (PCR) followed by direct sequencing of all exons. The identified mutations were investigated using bioinformatics tools to predict their effects on the protein product and also to compare the mutated sequence with close species. Results One previously known missense mutation (c.1978 C > T) and three novel mutations (c.1797dupT, c.879delC, c.1218 C > G) were identified in the ABCD1 gene, each in one family. Predicting the effects of the mutations on protein structure and function indicated the probable damaging effect for them with significant alterations in the protein structure. We found three novel mutations in the ABCD1 gene with damaging effects on its protein product and responsible for X-ALD.

Study on KAL1 Gene Mutations in Idiopathic Hypogonadotropic Hypogonadism Patients with X-Linked Recessive Inheritance.

Idiopathic hypogonadotropic hypogonadism (IHH) is a condition caused by low doses of hypothalamic gonadotropin-releasing hormone (GnRH) leading to absence or incomplete sexual maturation. One of the disorders leading to IHH is Kallmann syndrome which is characterized by GnRH deficiency with anosmia or hyposmia. This disorder generally occurs as a hereditary syndrome with X-linked recessive inheritance pattern. However, autosomal dominant or recessive and sporadic cases have also been reported. KAL1 is the most common mutated gene among these patients. The aim of this study was to determine the mutation spectrum of KAL1 gene in twenty patients. KAL1 exons were amplified by PCR method and the products were assessed by high resolution melting (HRM) technique. In addition, for one of the patients, all coding exons of the KAL1 gene were sequenced. Deletion of exons 4, 5 and 6 were evident in 5%, 10%, and 10% of patients, respectively. Furthermore, HRM results showed hemizygous mutation of exon 12 with more than 95% probability in 25% of patients. Finding these mutations could be helpful in the early diagnosis and presymptomic treatment of Kallman syndrome.