Investigation of gyrA and parC mutations and the prevalence of plasmid-mediated quinolone resistance genes in Klebsiella pneumoniae clinical isolates.

BACKGROUND: The emergence of fluoroquinolone resistance in clinical isolates of Klebsiella pneumoniae is a growing concern. To investigate the mechanisms behind this resistance, we studied a total of 215 K. pneumoniae isolates from hospitals in Bushehr province, Iran, collected between 2017 and 2019. Antimicrobial susceptibility test for fluoroquinolones was determined. The presence of plasmid mediated quinolone resistance (PMQR) and mutations in quinolone resistance-determining region (QRDR) of gyrA and parC genes in ciprofloxacin-resistant K. pneumoniae isolates were identified by PCR and sequencing. RESULTS: Out of 215 K. pneumoniae isolates, 40 were resistant to ciprofloxacin as determined by E-test method. PCR analysis revealed that among these ciprofloxacin-resistant isolates, 13 (32.5%), 7 (17.5%), 40 (100%), and 25 (62.5%) isolates harbored qnrB, qnrS, oqxA and aac(6')-Ib-cr genes, respectively. Mutation analysis of gyrA and parC genes showed that 35 (87.5%) and 34 (85%) of the ciprofloxacin-resistant isolates had mutations in these genes, respectively. The most frequent mutations were observed in codon 83 of gyrA and codon 80 of parC gene. Single gyrA substitution, Ser83→ Ile and Asp87→Gly, and double substitutions, Ser83→Phe plus Asp87→Ala, Ser83→Tyr plus Asp87→Ala, Ser83→Ile plus Asp87→Tyr, Ser83→Phe plus Asp87→Asn and Ser83→Ile plus Asp87→Gly were detected. In addition, Ser80→Ile and Glu84→Lys single substitution were found in parC gene. CONCLUSIONS: Our results indicated that 90% of isolates have at least one mutation in QRDR of gyrA orparC genes, thus the frequency of mutations was very significant and alarming in our region.

Apigenin in cancer therapy: Prevention of genomic instability and anticancer mechanisms.

The incidence of cancer has been growing worldwide. Better survival rates following the administration of novel drugs and new combination therapies may concomitantly cause concern regarding the long-term adverse effects of cancer therapy, for example, second primary malignancies. Moreover, overcoming tumour resistance to anticancer agents has been long considered as a critical challenge in cancer research. Some low toxic adjuvants such as herb-derived molecules may be of interest for chemoprevention and overcoming the resistance of malignancies to cancer therapy. Apigenin is a plant-derived molecule with attractive properties for chemoprevention, for instance, promising anti-tumour effects, which may make it a desirable adjuvant to reduce genomic instability and the risks of second malignancies among normal tissues. Moreover, it may improve the efficiency of anticancer modalities. This paper aims to review various effects of apigenin in both normal tissues and malignancies. In addition, we explain how apigenin may have the ability to protect usual cells against the genotoxic repercussions following radiotherapy and chemotherapy. Furthermore, the inhibitory effects of apigenin on tumours will be discussed.

The worldwide prevalence of anxiety in acquired immune deficiency syndrome patients: A systematic review and meta-analysis.

Background: Anxiety affects social, economic, and physical aspects of daily life in patients with AIDS. Therefore, it is necessary to take preventive measures and design plans to maintain their general health. The present study was the first comprehensive systematic literature review research that examined the worldwide prevalence rate of anxiety in patients with AIDS. Methods: We searched for papers published in the English language in the major databases including Embase, PubMed, Web of Science, Scopus, Cochrane, and Google Scholar from 2000 to October 2018. There were 40 studies which found to be eligible. These studies were independently evaluated and the collected data were entered in a data extraction form, which was then analyzed by two authors and a third author if necessary. Der Simonian-Laird model was used to estimate the prevalence rate on a Forest plot at the interval confidence of 95%. Results: The total sample size was 24111, and the total number of people with anxiety was 5546. The results based on the random-effects model showed that the rate of anxiety prevalence in the patients was 25% (CI: 95%, 21% -30%) with heterogeneity of 97.9% and a significance level of p<0.001. The South America continent with a prevalence of 38% (95% CI, 34%-42%) had the highest anxiety prevalence rates and Africa with 19% (95% CI, 12% -29%) had the lowest anxiety prevalence rates. Conclusion: Based on findings, the prevalence of anxiety in developed countries was partially higher than in underdeveloped countries and the obtained mean in the present study. It can be a significant point for policymakers. Therefore, WHO and the world community should have special plans for these countries.

A new series of Schiff base derivatives bearing 1,2,3-triazole: Design, synthesis, molecular docking, and α-glucosidase inhibition.

A series of new Schiff bases bearing 1,2,3-triazole 12a-o was designed, synthesized, and evaluated as α-glucosidase inhibitors. All the synthesized compounds showed promising inhibition against α-glucosidase and were more potent than the standard drug acarbose. The kinetic study on the most potent compound 12n showed that this compound acted as a competitive α-glucosidase inhibitor. The docking study revealed that the synthesized compounds interacted with the important residues in the active site of α-glucosidase.

Design, synthesis, docking study, α-glucosidase inhibition, and cytotoxic activities of acridine linked to thioacetamides as novel agents in treatment of type 2 diabetes.

A novel series of acridine linked to thioacetamides 9a-o were synthesized and evaluated for their α-glucosidase inhibitory and cytotoxic activities. All the synthesized compounds exhibited excellent α-glucosidase inhibitory activity in the range of IC50 = 80.0 ±â€¯2.0-383.1 ±â€¯2.0 µM against yeast α-glucosidase, when compared to the standard drug acarbose (IC50 = 750.0 ±â€¯1.5 µM). Among the synthesized compounds, 2-((6-chloro-2-methoxyacridin-9-yl)thio)-N-(p-tolyl) acetamide 9b displayed the highest α-glucosidase inhibitory activity (IC50 = 80.0 ±â€¯2.0 µM). The in vitro cytotoxic assay of compounds 9a-o against MCF-7 cell line revealed that only the compounds 9d, 9c, and 9n exhibited cytotoxic activity. Cytotoxic compounds 9d, 9c, and 9n did not show cytotoxic activity against the normal human cell lines HDF. Kinetic study revealed that the most potent compound 9b is a competitive inhibitor with a Ki of 85 µM. Furthermore, the interaction modes of the most potent compounds 9b and 9f with α-glucosidase were evaluated through the molecular docking studies.

Nobiletin in Cancer Therapy; Mechanisms and Therapy Perspectives.

Cancer has remained to be one of the major challenges in medicine and regarded as the second leading cause of death worldwide. Different types of cancer may resist anti-cancer drugs following certain mutations such as those in tumor suppressor genes, exhaustion of the immune system, and overexpression of drug resistance mediators, which increase the required concentration of anticancer drugs so as to overcome drug resistance. Moreover, treatment with a high dose of such drugs is highly associated with severe normal tissue toxicity. Administration of low-toxic agents has long been an intriguing idea to enhance tumor suppression. Naturally occurring agents e.g., herb-derived molecules have shown a dual effect on normal and malignant cells. On the one hand, these agents may induce cell death in malignant cells, while on the other hand reduce normal cell toxicity. Nobiletin, one of the well-known polymethoxyflavones (PMFs), has reportedly shown various beneficial effects on the suppression of cancer and the protection of normal cells against different toxic agents. Our review aims to explain the main mechanisms underlying nobiletin as an inhibitor of cancer. We have reviewed the mechanisms of cancer cell death caused by nobiletin, such as stimulation of reactive oxygen species (ROS), modulation of immune evasion mechanisms, targeting tumor suppressor genes, and modulation of epigenetic modulators, among others; the inhibitory mechanisms of nobiletin affecting tumor resistance properties such as modulation of hypoxia, multidrug resistance, angiogenesis, epithelial-mesenchymal transition (EMT) have been fully investigated. Also, the inhibition of anti-apoptotic and invasive mechanisms induced by nobiletin will later be discussed. In the end, protective mechanisms of nobiletin on normal cells/tissue, clinical trial results, and future perspectives are reviewed.

Modulation of the immune system by melatonin; implications for cancer therapy.

Immune system interactions within the tumour have a key role in the resistance or sensitization of cancer cells to anti-cancer agents. On the other hand, activation of the immune system in normal tissues following chemotherapy or radiotherapy is associated with acute and late effects such as inflammation and fibrosis. Some immune responses can reduce the efficiency of anti-cancer therapy and also promote normal tissue toxicity. Modulation of immune responses can boost the efficiency of anti-tumour therapy and alleviate normal tissue toxicity. Melatonin is a natural body agent that has shown promising results for modulating tumour response to therapy and also alleviating normal tissue toxicity. This review tries to focus on the immunomodulatory actions of melatonin in both tumour and normal tissues. We will explain how anti-cancer drugs may cause toxicity for normal tissues and how tumours can adapt themselves to ionizing radiation and anti-cancer drugs. Then, cellular and molecular mechanisms of immunoregulatory effects of melatonin alone or combined with other anti-cancer agents will be discussed.

Global health-related quality of life in schizophrenia: systematic review and meta-analysis.

BACKGROUND AND AIM: Signs and symptoms of schizophrenia may have serious impacts on patients' quality of life leading to concern about different aspects of their lives. This study presents a systematic review and meta-analysis of the studies examining the quality of life among patients with schizophrenia and its relationship with patients' characteristics. MATERIALS AND METHODS: A total of 40 studies were extracted from searching of relevant databases published between 2000 and 2020. Descriptive data and correlation coefficients between patient's characteristics and quality of life were extracted and the results were reported according to Preferred Reporting Items for Systematic Reviews and Meta-analyses standards and meta-analysis of pooled studies. RESULTS: In total, 8363 patients with schizophrenia participated in 40 studies which used Schizophrenia Quality of Life Scale revision 4. The total score of quality of life (QOL) in the study subjects was reported to be 40.66. Weighted effect size analyses revealed a significant relationship between QOL and variables including patients' age and duration of the disease. Furthermore, the highest (the worst) score of QOL in schizophrenia patients was observed in Europe 47.04 (95% CI 41.26 to 52.82) and the Euro region 47.05 (95% CI 41.18 to 52.92). CONCLUSION: Overall, the QOL among patients with schizophrenia was in a good status, which could be improved through considering different life aspects of people living in various contexts. In fact, clarifying the determinants of QOL would be a key step in the provision of future treatment efforts.

Global systematic review and meta-analysis of health-related quality of life in Behcet's patients.

Background: Behcet's disease (BD) is a chronic fatal illness with a relapsing remitting nature and significant organ-threatening morbidity and mortality. The aim of this research was to examine studies which were conducted on investigation of prevalence of quality of life among patients with Behcet's disease. Methods: A total of 13 articles were extracted from four main databases including PubMed, EMBASE, Scopus, and Web of Science from the onset of 2000 to January 2021. All studies published in English with the purpose of examining quality of life (QOL) among patients with BD or investigating its main determinants were included. Results: Totally, 1137 BD patients participated in 13 studies. Based on random effect analysis, the total score of physical health-related QOL was 46.7 (95% CI=41.26 to 52.13) and the total score of mental health-related QOL was 49.01 (95% CI=43.83 to 54.18) representing a moderate level of QOL among BD patients. Furthermore, weighted effect size analyses showed a significant correlation between QOL and variables such as patients' age, gender, disease duration and depression (pvalue: 0.00). Conclusion: As the symptoms of BD worsen over time, patients confront with more severe body pain, mobility restrictions, and difficulties in chewing, eating, speaking and swallowing which negatively affect social interactions of patients and reduce their QOL. Furthermore, depression was proved to act as a deteriorating factor for Health-Related Quality of Life (HRQOL) among BD patients. Thus, patients need to be psychologically supported by a specialized team and be informed during the course of treatment to gain useful information about the disease, treatment approaches and coping strategies.