scholarly journals Candida auris ve Antifungal İlaçlara Direnç Mekanizmaları

2021 ◽  
Vol 55 (1) ◽  
pp. 99-112
Author(s):  
Şehnaz Alp ◽  
Sevtap Arıkan Akdağlı
Keyword(s):  
Molecular Mechanisms ◽  
Antifungal Agents ◽  
Health Concern ◽  
Clinical Samples ◽  
High Survival ◽  
Candida Auris ◽  
Related Factors ◽  
Ongoing Research ◽  
Survival Potential ◽  
High Minimum Inhibitory Concentration

Candida auris has been isolated from clinical samples in different regions and countries since it was first described in 2009. Due to the difficulties in identification; decreased susceptibility or resistance to antifungal agents; exceptional capacity to colonize and persist on surfaces; ability to survive despite standard disinfection procedures; and significant increase in the number of regions and countries with reported cases, C.auris has become a global health concern and placed among the World’s ten most concerned fungi list in 2018. It is stated that 60-90% of C.auris strains are resistant to fluconazole, 10-30% exhibit high minimum inhibitory concentration values for amphotericin B, and up to 5% can be considered as resistant to echinocandins. Existing data obtained from ongoing research on molecular mechanisms of antifungal resistance in C.auris revealed some common features with other Candida species. However, diverging aspects are also reported. In this review article, current information on molecular mechanisms and biofilm-related factors responsible for decreased susceptibility or resistance to antifungal agents and unexpectedly high survival potential of C.auris have been discussed.

scholarly journals Detection of Candida auris and its antifungal susceptibility: first report from Bangladesh

2020 ◽  
Vol 13 (2) ◽  
pp. 18-22
Author(s):  
Subarna Dutta ◽  
Md Hasibur Rahman ◽  
Kazi Shakhawath Hossain ◽  
Jalaluddin Ashraful Haq
Keyword(s):  
Antifungal Agents ◽  
Antifungal Susceptibility ◽  
Disk Diffusion ◽  
Diffusion Method ◽  
Clinical Samples ◽  
Dhaka City ◽  
Candida Auris ◽  
Large Hospital ◽  
Disk Diffusion Method ◽  
First Report

Background and objectives: Candida auris is an emerging multidrug-resistant fungal pathogen that has been associated with nosocomial infections with a high mortality. The organism has been reported from several countries of the world except Bangladesh. The present study describes the presence of C. auris in clinical samples obtained from a large hospital of Dhaka city, Bangladesh. Materials and methods: The A total of 100 Candida species isolated from different clinical samples were purposively included in the present study. Samples were obtained from patients attending a 750 bed hospital of Dhaka city. C. auris was identified by growth characteristics, biochemical and carbohydrate assimilation test and further confirmed by polymerase chain reaction and sequencing using ITS1 and ITS2 targeting the conserved regions of 5.8S rRNA. Antifungal susceptibility of identified C. auris was performed by disk diffusion and minimum inhibitory concentration (MIC) methods. Results: Out of 100 Candida sp. tested, 21 isolates were identified as C. auris. Of the 21 C. auris, 14 (66.7%) were isolated from blood samples and the remaining 7 (33.4%) were from urine. Most of the C. auris isolated were from patients admitted in intensive care units. Out of 21 C. auris, 17 (81.0%), 7 (33.3%) and 3 (14.3%) were sensitive to amphotericin B, fluconazole and voriconazole respectively by disk diffusion method. Out of 14 fluconazole resistant isolates, 5 were susceptible dose-dependent (SS-D) by MIC method. Conclusion: The present study is the first report demonstrating the presence of C. auris in clinical samples obtained from a large hospital of Bangladesh. Majority of isolates showed resistance to fluconazole and variable susceptibility to other antifungal agents. Further study is suggested to find its true magnitude and its susceptibility pattern to a range of antifungal agents. Ibrahim Med. Coll. J. 2019; 13(2): 18-22

Chemopreventive Role of Phytoconstituents in Breast Cancer: An Integration Therapy

2021 ◽  
Vol 18 ◽  
Author(s):  
Priya Bhatt ◽  
Mehul Patel ◽  
Aashka Thakkar ◽  
Umang Shah ◽  
Ashish Patel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Modern Medicine ◽  
Chemotherapeutic Agents ◽  
Primary Objective ◽  
Health Concern ◽  
Ongoing Research ◽  
Significant Public Health

As we enter into the era of modern medicine, breast cancer remains a significant public health concern that has a noteworthy global impact in developed and developing countries. The modern era has seen an increase in the knowledge of the molecular mechanisms underlying cancer progression, leading to many anticancer drugs. The practice of curing certain diseases with the help of plant-derived compounds was one of the traditional methods. Phytochemicals and derivatives present in plants have shown a promising effect for improving efficiency in the treatment of cancer patients and reducing adverse reactions such as integration therapy with chemotherapeutic agents. The primary objective of this review is to compile ongoing research, preclinical studies, and clinical trials of some of the important phytochemicals. In recent years, increasing evidence from preclinical and clinical studies suggests that phytochemicals can favorably modulate several signaling pathways involved in cancer development and progression. Furthermore, phytoconstituents or plant-derived compounds show synergistic action against breast cancer when integrated with chemotherapy. Thus, the therapeutic potential of naturally occurring phytochemicals is of great interest as a part of integration therapy in cancer care. This review focuses on phytochemicals from quinones, terpenoids, alkaloids, polyphenols, steroidal lactones, and glycosides classes that help treat breast cancer. In addition, the phytochemicals act by various pharmacological mechanisms like carcinogen inactivation, inhibiting proliferation, cell cycle arrest, and apoptosis. Collectively, detailed information about specific classes of phytoconstituents along with their mechanism of action is mentioned in this review.

Galectin-3: A factotum in carcinogenesis bestowing an archery for prevention

Tumor Biology ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 77-96
Author(s):  
T. Jeethy Ram ◽  
Asha Lekshmi ◽  
Thara Somanathan ◽  
K. Sujathan
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Therapy Resistance ◽  
Cellular Level ◽  
Clinical Samples ◽  
Innovative Strategy ◽  
Mesenchymal Transition ◽  
Galectin 3

Cancer metastasis and therapy resistance are the foremost hurdles in oncology at the moment. This review aims to pinpoint the functional aspects of a unique multifaceted glycosylated molecule in both intracellular and extracellular compartments of a cell namely galectin-3 along with its metastatic potential in different types of cancer. All materials reviewed here were collected through the search engines PubMed, Scopus, and Google scholar. Among the 15 galectins identified, the chimeric gal-3 plays an indispensable role in the differentiation, transformation, and multi-step process of tumor metastasis. It has been implicated in the molecular mechanisms that allow the cancer cells to survive in the intravascular milieu and promote tumor cell extravasation, ultimately leading to metastasis. Gal-3 has also been found to have a pivotal role in immune surveillance and pro-angiogenesis and several studies have pointed out the importance of gal-3 in establishing a resistant phenotype, particularly through the epithelial-mesenchymal transition process. Additionally, some recent findings suggest the use of gal-3 inhibitors in overcoming therapeutic resistance. All these reports suggest that the deregulation of these specific lectins at the cellular level could inhibit cancer progression and metastasis. A more systematic study of glycosylation in clinical samples along with the development of selective gal-3 antagonists inhibiting the activity of these molecules at the cellular level offers an innovative strategy for primary cancer prevention.

scholarly journals Molecular Identification of Mushroom Species in Italy: An Ongoing Project Aimed at Reinforcing the Control Measures of an Increasingly Appreciated Sustainable Food

2020 ◽  
Vol 13 (1) ◽  
pp. 238
Author(s):  
Alice Giusti ◽  
Enrica Ricci ◽  
Laura Gasperetti ◽  
Marta Galgani ◽  
Luca Polidori ◽  
...  
Keyword(s):  
Selection Process ◽  
Winning Strategy ◽  
Control Measures ◽  
Effective Control ◽  
Mushroom Poisoning ◽  
Clinical Samples ◽  
Similar Species ◽  
Mushroom Species ◽  
Ongoing Research ◽  
Genotypic Analysis

Proper investment in mushroom production (farming and wild mushroom picking activities) may represent a winning strategy for many countries, including Italy, to better face the problems of food security and environmental impact, and to break away from imports, enhancing the local products. However, the risk related to the consumption of poisoning species requires governments to implement or reinforce effective control measures to protect consumers. Mushroom identification by phenotype observation is hardly applicable if morphologically-similar species, non-whole specimens, or clinical samples are involved. Genotypic analysis is a valid alternative. An ongoing research project involving the Experimental Zooprophylactic Institute of Lazio and Tuscany, the regional Mycological Inspectorate, the Tuscany Mycological Groups Association, and the Department of Veterinary Sciences of the University of Pisa aims to reinforce the collaboration among institutions for the management of mushroom poisoning. The core’s project aims to develop an internal genetic database to support the identification of wild and cultivated mushroom species in the Italian territory. The database will include Internal Transcribed Spacer (ITS) sequences retrieved from official databases (the NCBI GenBank and the BOLD system) which are considered to be reliable, after a proper selection process, and sequences from specimens collected directly and identified by expert mycologists. Once it is validated, the database will be available and further implementable by the official network of national laboratories.

scholarly journals Experimental Models of Hepatocellular Carcinoma—A Preclinical Perspective

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3651
Author(s):  
Alexandru Blidisel ◽  
Iasmina Marcovici ◽  
Dorina Coricovac ◽  
Florin Hut ◽  
Cristina Adriana Dehelean ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Prediction Models ◽  
3D Models ◽  
Experimental Models ◽  
Health Concern ◽  
Liver Carcinoma ◽  
Tumor Type

Hepatocellular carcinoma (HCC), the most frequent form of primary liver carcinoma, is a heterogenous and complex tumor type with increased incidence, poor prognosis, and high mortality. The actual therapeutic arsenal is narrow and poorly effective, rendering this disease a global health concern. Although considerable progress has been made in terms of understanding the pathogenesis, molecular mechanisms, genetics, and therapeutical approaches, several facets of human HCC remain undiscovered. A valuable and prompt approach to acquire further knowledge about the unrevealed aspects of HCC and novel therapeutic candidates is represented by the application of experimental models. Experimental models (in vivo and in vitro 2D and 3D models) are considered reliable tools to gather data for clinical usability. This review offers an overview of the currently available preclinical models frequently applied for the study of hepatocellular carcinoma in terms of initiation, development, and progression, as well as for the discovery of efficient treatments, highlighting the advantages and the limitations of each model. Furthermore, we also focus on the role played by computational studies (in silico models and artificial intelligence-based prediction models) as promising novel tools in liver cancer research.

scholarly journals In Vitro Synergistic Interactions of Isavuconazole and Echinocandins against Candida auris

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 355
Author(s):  
Unai Caballero ◽  
Sarah Kim ◽  
Elena Eraso ◽  
Guillermo Quindós ◽  
Valvanera Vozmediano ◽  
...  
Keyword(s):  
Interaction Model ◽  
Antifungal Drugs ◽  
Health Concern ◽  
Candida Auris ◽  
Fungistatic Activity ◽  
Drug Concentrations ◽  
Low Concentrations ◽  
Wide Range ◽  
Time Kill

Candida auris is an emergent fungal pathogen that causes severe infectious outbreaks globally. The public health concern when dealing with this pathogen is mainly due to reduced susceptibility to current antifungal drugs. A valuable alternative to overcome this problem is to investigate the efficacy of combination therapy. The aim of this study was to determine the in vitro interactions of isavuconazole with echinocandins against C. auris. Interactions were determined using a checkerboard method, and absorbance data were analyzed with different approaches: the fractional inhibitory concentration index (FICI), Greco universal response surface approach, and Bliss interaction model. All models were in accordance and showed that combinations of isavuconazole with echinocandins resulted in an overall synergistic interaction. A wide range of concentrations within the therapeutic range were selected to perform time-kill curves. These confirmed that isavuconazole–echinocandin combinations were more effective than monotherapy regimens. Synergism and fungistatic activity were achieved with combinations that included isavuconazole in low concentrations (≥0.125 mg/L) and ≥1 mg/L of echinocandin. Time-kill curves revealed that once synergy was achieved, combinations of higher drug concentrations did not improve the antifungal activity. This work launches promising results regarding the combination of isavuconazole with echinocandins for the treatment of C. auris infections.

scholarly journals Kinetic characterisation and inhibitor sensitivity of Candida albicans and Candida auris recombinant AOX expressed in a self-assembled proteoliposome system

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alice C. Copsey ◽  
Mario R. O. Barsottini ◽  
Benjamin May ◽  
Fei Xu ◽  
Mary S. Albury ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Future Development ◽  
Therapeutic Target ◽  
Fungicide Resistance ◽  
Alternative Oxidase ◽  
Antifungal Agents ◽  
Candida Auris ◽  
Novel Treatments ◽  
Membrane Bound ◽  
Self Assembled

AbstractCandidemia caused by Candida spp. is a serious threat in hospital settings being a major cause of acquired infection and death and a possible contributor to Covid-19 mortality. Candidemia incidence has been rising worldwide following increases in fungicide-resistant pathogens highlighting the need for more effective antifungal agents with novel modes of action. The membrane-bound enzyme alternative oxidase (AOX) promotes fungicide resistance and is absent in humans making it a desirable therapeutic target. However, the lipophilic nature of the AOX substrate (ubiquinol-10) has hindered its kinetic characterisation in physiologically-relevant conditions. Here, we present the purification and expression of recombinant AOXs from C. albicans and C. auris in a self-assembled proteoliposome (PL) system. Kinetic parameters (Km and Vmax) with respect to ubiquinol-10 have been determined. The PL system has also been employed in dose–response assays with novel AOX inhibitors. Such information is critical for the future development of novel treatments for Candidemia.

scholarly journals MAPK/ERK Signaling Pathway in Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3026
Author(s):  
Hyuk Moon ◽  
Simon-Weonsang Ro
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Erk Signaling ◽  
Health Concern ◽  
Alternative Mechanism ◽  
Major Health ◽  
Activating Mutations ◽  
Genetic Events

Hepatocellular carcinoma (HCC) is a major health concern worldwide, and its incidence is increasing steadily. Recently, the MAPK/ERK signaling pathway in HCC has gained renewed attention from basic and clinical researchers. The MAPK/ERK signaling pathway is activated in more than 50% of human HCC cases; however, activating mutations in RAS and RAF genes are rarely found in HCC, which are major genetic events leading to the activation of the MAPK/ERK signaling pathway in other cancers. This suggests that there is an alternative mechanism behind the activation of the signaling pathway in HCC. Here, we will review recent advances in understanding the cellular and molecular mechanisms involved in the activation of the MAPK/ERK signaling pathway and discuss potential therapeutic strategies targeting the signaling pathway in the context of HCC.

scholarly journals SCA Medium: A New Culture Medium for the Isolation of All Candida auris Clades

2021 ◽  
Vol 7 (6) ◽  
pp. 433
Author(s):  
Ahmad Ibrahim ◽  
Lucie Peyclit ◽  
Rim Abdallah ◽  
Saber Khelaifia ◽  
Amanda Chamieh ◽  
...  
Keyword(s):  
Culture Medium ◽  
Limit Of Detection ◽  
Bacterial Species ◽  
Multidrug Resistant ◽  
Rapid Identification ◽  
Clinical Samples ◽  
Candida Auris ◽  
Phenotypic Profile ◽  
Stool Samples ◽  
Selective Culture Medium

Candida auris is an emerging multidrug-resistant yeast causing nosocomial infections and associated with high mortality in immunocompromised patients. Rapid identification and characterisation are necessary for diagnosis and containing its spread. In this study, we present a selective culture medium for all C. auris clades. This medium is sensitive with a limit of detection ranging between 101 and 102 CFU/mL. The 100% specificity of SCA (specific C. auris) medium is confirmed on a set of 135 Candida strains, 50 bacterial species and 200 human stool samples. Thus, this medium specifically selects for C. auris isolation from clinical samples, allowing the latter to study its phenotypic profile.

GCSF As a Potential Molecular Target for Overall Survival of Hepatocellular Carcinoma

2021 ◽  
Vol 24 ◽  
Author(s):  
Heng Cao ◽  
Peng Guo ◽  
Xiaohui Wu ◽  
Jiankun Li ◽  
Chenlong Ge ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Survival Analysis ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Basic Research ◽  
Clinical Samples ◽  
Tumor Diameter ◽  
Overall Survival Analysis

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of digestive tract in the world. Therefore, it is important to carry out studies on the molecular mechanisms of early diagnosis and treatment of HCC to reduce mortality. Methods: Bioinformatic analysis was performed to explore the significant role of GCSF on the occurrence and development of neoplasm. Differently expressed genes (DEGs) were screened, and the significant hub genes related with GCSF were identified by the multiple algorithms of Cytoscape. Functional annotation for DEGs, pathological stage and overall survival analysis were implemented. In addition, the verification for the role of GCSF on HCC was made via the clinical samples. A total of 70 participates diagnosed as HCC were recruited from November 2014 to November 2019. The immunohistochemistry assay, qRT-PCR, receiver operating characteristic (ROC) curves, and overall survival analysis were carried out. Results: GCSF was related with the tumor size, and the expression of GCSF was up-regulated in hepatocellular carcinoma tissues. The enrichment results of GO and KEGG analysis were mainly enriched in “Inflammatory response”, “Protein binding”, “Metabolic pathways”, and “Proteasome”. The tumor diameter (P < 0.001), and survival time (P < 0.001) were significantly associated with expression of GCSF via the verification of clinical data. The univariate and multivariate Cox proportional regression analysis manifested that high expression of GCSF in patients with HCC was related to poor OS. Conclusion: The expression level of GCSF is significantly associated with the prognostic survival of HCC, and it is expected to become a new prognostic marker of HCC, providing a novel idea for future basic research as well as targeted therapy.

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