Antifungal Activity of Thai Cajuput Oil and Its Effect on Efflux-Pump Gene Expression in Fluconazole-Resistant Candida albicans Clinical Isolates

Alexandros G.Sfakianakis shared this article with you from Inoreader Antifungal Activity of Thai Cajuput Oil and Its Effect on Efflux-Pump Gene Expression in Fluconazole-Resistant Candida albicans Clinical Isolates Μέσω Hindawi Publishing Corporation Candidiasis caused by the fluconazole-resistant opportunistic pathogen Candida albicans is an intractable clinical problem that threatens immunocompromised or normal individuals. The most common mechanism of fluconazole resistance in C. albicans is the failure of cells to accumulate the drug due to increased expression of the efflux proteins encoded by the CDR1, CDR2, and MDR1 genes. Because the number of current antifungal drugs is limited, it is necessary to develop new therapeutic strategies. This study aimed to evaluate the antifungal activity of Thai Cajuput oil, its synergism with fluconazole, and its effect on efflux-pump gene expression in fluconazole-resistant C. albicans clinical isolates. Thus, we first detected the efflux-pump genes in fourteen resistant strains by PCR. The frequencies of the CDR1, CDR2, and MDR1 genes were 68.75%, 62.5%, and 87.5%, respectively, and these efflux-pump genes were distributed in three distinct patterns. Subsequently, the antifungal activity of Thai Cajuput oil was assessed by broth macrodilution and its synergism with fluconazole was evaluated by the checkerboard assay. The changes in the expression levels of CDR1, CDR2, and MDR1 after treatment with Thai Cajuput oil were analyzed by qRT-PCR. The MICs and MFCs of Thai Cajuput oil ranged from 0.31 to 1.25 μl/ml and 0.63 to 1.25 μl/ml, respectively, and its activity was defined as fungicidal activity. The MICs of the combination of Thai Cajuput oil and fluconazole were much lower than the MICs of the individual drugs. Interestingly, sub-MICs of Thai Cajuput oil significantly reduced the MDR1 expression level in resistant strains . Our study suggests that Thai Cajuput oil can be used to create new potential combination therapies to combat the antifungal resistance of C. albicans . View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Electroacupuncture Improves Cognitive Function in Senescence-Accelerated P8 (SAMP8) Mice via the NLRP3/Caspase-1 Pathway

Alexandros G.Sfakianakis shared this article with you from Inoreader Electroacupuncture Improves Cognitive Function in Senescence-Accelerated P8 (SAMP8) Mice via the NLRP3/Caspase-1 Pathway Μέσω Hindawi Publishing Corporation Background. Clinically, electroacupuncture (EA) is the most common therapy for aging-related cognitive impairment (CI). However, the underlying pathomechanism remains unidentified. The aims of this study were to observe the effect of EA on cognitive function and explore the potential mechanism by which EA acts on the NLRP3/caspase-1 signaling pathway. Main Methods. Thirty male SAMP8 mice were randomly divided into the model, the 2 Hz EA and 10 Hz EA groups. Ten male SAMR1 mice were assigned to the control group. Cognitive function was assessed through the Morris water maze test. Hippocampal morphology and cell death were observed by HE and TUNEL staining, respectively. The serum IL-1β, IL-6, IL-18, and TNF-α levels were measured by ELISA. Hippocampal NLRP3, ASC, caspase-1, GSDM-D, IL-1β, IL-18, Aβ, and t au proteins were detected by Western blotting. Key Findings. Cognitive function, hippocampal morphology, and TUNEL-positive cell counts were improved by both EA frequencies. The serum IL-1β, IL-6, IL-18, and TNF-α levels were decreased by EA treatment. However, 10 Hz EA reduced the number of TUNEL-positive cells in the CA1 region and serum IL-1β and IL-6 levels more effectively than 2 Hz EA. NLRP3/caspase-1 pathway-related proteins were significantly downregulated by EA, but 2 Hz EA did not effectively reduce ASC protein expression. Interestingly, both EA frequencies failed to reduce the expression of Aβ and tau proteins. Significance. The effects of 10 Hz EA at the GV20 and ST36 acupoints on the NLRP3/caspase-1 signaling pathway may be a mechanism by which this treatment relieves aging-related CI in mice. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Central Venous Catheter Insertion: A Scoring System for Evaluation of Both the Procedure and the Operator (CVCI Score/Gaber Score)

Alexandros G.Sfakianakis shared this article with you from Inoreader Central Venous Catheter Insertion: A Scoring System for Evaluation of Both the Procedure and the Operator (CVCI Score/Gaber Score) Μέσω Hindawi Publishing Corporation Introduction. Currently, there is no method to assess the performance while inserting a central venous catheter. We suggest a new scoring system for evaluation of both the technique as well as the operator, and then we applied it for the comparison between the landmark and ultrasound techniques to assess its validity. Methods. Four hundred patients were divided into two equal groups: group (A): internal jugular vein (IJV) and group (B): subclavian vein (SV). The landmark technique and the ultrasound guidance were used equally (100 patients for each) in both groups. Results. In group (A), 20% of patients in the landmark group achieved score 4, while 82% of patients in the ultrasound group achieved the same score. This suggests that the ultrasound technique for catheterization of IJV decreased overall compli cations and improved the success rate. In group (B), there were 70% of patients in the landmark group who achieved score 5, while 49% of patients in the ultrasound group achieved the same score which proposes that the landmark technique might be deceptively better than the ultrasound technique for catheterization of SV. This could be because the time required for catheterization of SV by the ultrasound technique was longer than that in the landmark technique. Overall complications of 15% with the landmark technique vs. 2% with ultrasound guidance in this group of patients are not only statistically significant but also increase morbidity and mortality with a highly invasive procedure. Complications and their incidences are by far more significant than seconds of time. Our results suggest that the ultrasound technique could decrease the incidence of overall complications, but it is time-consuming in group (B). These results support the validity of our new scoring system. Conclusion. We suggest a new scoring system for CVC insertion that can be used for evaluation of both the technique and the operator. It can evaluate the performance of junior staff and follow their progress. It can be applied in the medical and critical care practice as well as the quality management privileges and protocols. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Antimicrobial Activity of Pomegranate Peel and Its Applications on Food Preservation

Alexandros G.Sfakianakis shared this article with you from Inoreader Antimicrobial Activity of Pomegranate Peel and Its Applications on Food Preservation Μέσω Hindawi Publishing Corporation Pomegranate (Punica granatum L.) fruit is being cultivated since the civilization is known, and its production and consumption have been increased since the last century due to the scientific confirmation of its health benefits. Pomegranate fruits, fruit juice, its seeds, and peels are known to have higher contents of bioactive compounds, viz., phenolic acids, flavonoids, and hydrolysable tannins. The peels of pomegranate fruits are the major by-products produced during food processing of pomegranate enriched in antioxidants and broad-spectrum antimicrobial agents and can prevent food deterioration even. This health potential of pomegranate is known to vary significantly upon the varieties, growing conditions, cultivation practices, stages of the development, and the extraction methods. Herein, the biochemica l composition of the pomegranate peel extract (PPE), its efficacy in food preservation, and antimicrobial activities are discussed to provide a comprehensive guide for farmers, food processing, and storage sectors and academia. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Five Years Pathological Evaluation of Corneal Regrafts: A Study from Southern Iran

Alexandros G.Sfakianakis shared this article with you from Inoreader Five Years Pathological Evaluation of Corneal Regrafts: A Study from Southern Iran Μέσω Hindawi Publishing Corporation Purpose. Corneal regrafts sometimes needed to restore the transparency after graft failure. The aim of the study is five years epidemiologic and histopathological evaluation of corneal regrafts. Methods. In this cross-sectional study, all corneal regrafts during 5 years (2012–2016) were assessed in the Khalili Ophthalmology Center at Shiraz city. Demographic data including age, area of residence, primary disease, type of graft, cause of regraft, interval between primary and subsequent grafts (IPSG), associated eye diseases or surgeries, and systemic diseases were recorded. Also, microscopic findings of corneas were reviewed. Results. Among a total of 1190 corneal grafts, 76 of them (6.38%) were regrafts. The most common type of grafting was penetrating keratoplasty (PK). The shortest IPSG was observed in fungal keratitis. Main causes of graft failure were endothelial dysfunction, infection, immunologic rejection, technical problems, and recurrence of primary disease, respectively. The most common histopathological finding in failed grafts was severe endothelial cell loss (89.8%). Also, more than half and one-third of cases had Descemet membrane changes and stromal ingrowth, respectively. Conclusion. Endothelial cell loss was the major cause of failure in our study. Also, recurrence rate in infective cases, especially fungal keratitis, was very high. Considerable presence of histopathological changes such as doubling of Descemet membrane and retrocorneal fibrous ingrowth need further investigations. Perhaps, modification in techniques of corneal grafting and assessment of donor tissue and recipient bed along with any need for longer medical treatment are the basis for future studies in order to increase graft survival. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Unilateral Toxic Anterior Segment Syndrome Resulting in Cataract and Urrets-Zavalia Syndrome after Sequential Uneventful Implantation of a Posterior Chamber Phakic Toric Intraocular Lens at Two Different Surgical Facilities: A Series of Unfortunate Events

Alexandros G.Sfakianakis shared this article with you from Inoreader Unilateral Toxic Anterior Segment Syndrome Resulting in Cataract and Urrets-Zavalia Syndrome after Sequential Uneventful Implantation of a Posterior Chamber Phakic Toric Intraocular Lens at Two Different Surgical Facilities: A Series of Unfortunate Events Μέσω Hindawi Publishing Corporation Background. Phakic Intraocular Lens (P-IOL) implantation is a safe, easy, predictable intervention designed to manage moderate to high refractive errors. Complications are relatively uncommon and include mainly cataract and intraocular pressure spikes. Toxic Anterior Segment Syndrome (TASS) is a rather unusual sterile anterior segment inflammation after uneventful intraocular surgery, extremely rarely reported after P-IOL implantation. Urrets-Zavalia Syndrome (UZS) is also very rarely described after P-IOL. To date, to the best of the authors' knowledge, no article has ever described the simultaneous occurrence of TASS and UZS in a patient after P-IOL implantation. Objective. In this article, the authors present the case of a female patient with moderate myopic astigmatism, who underwent sequential P-IOL implantation at two different facilities. The postoperative course of the first eye was uneventful, but she developed complications associated to the intervention in the second eye. Materials. The article describes the case of a young patient who underwent a sequential Phakic Intraocular Lens (P-IOL) implantation at two different institutions. The postoperative course of the first eye (left eye) was uneventful; however, the second eye (right eye) initially developed Toxic Anterior Segment Syndrome (TASS). Although timely and correct management was instituted, upon resolution of TASS, the patient developed Urrets-Zavalia Syndrome, anterior subcapsular cataract, and significant endothelial damage in the same eye. Results. The patient was followed closely and managed accordingly; corneal edema and anterior segment inflammation of the right eye eventually resolved. Nevertheless, an anterior subcapsular cataract and a fixed dilated pupil remained; with normal intraocular pressure (IOP). Specular microscopy confirmed an endothelial cell loss in the TASS eye (right eye). Pupil size showed no reaction to repeated doses of Pilocarpine 2%. A month after surgery, refraction on her right eye was , which resulted in a 20/50 vision. Conclusions. TASS and UZS are both extremely rare complications after uneventful P-IOL implantation, with only a handful of cases having been reported of each of them. To date, this is the very first case where UZS ensued after and potentially as a consequence of TASS in a patient who had undergone P-IOL implantation. Although a direct causative element could not be pinpointed, the fact that the complication ensued after being operated in one surgical institution and not the other, could suggest some role of different sterilization and handling procedures, but no direct conclusion can be made on this case. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Upregulated Long Noncoding RNA UCA1 Enhances Warburg Effect via miR-203/HK2 Axis in Esophagal Cancer

Alexandros G.Sfakianakis shared this article with you from Inoreader Upregulated Long Noncoding RNA UCA1 Enhances Warburg Effect via miR-203/HK2 Axis in Esophagal Cancer Μέσω Hindawi Publishing Corporation Reprogrammed glucose metabolism of enhanced aerobic glycolysis, also known as Warburg effect, which exerts a significant contributor to cancer progression, is regarded as a hallmark of cancer. The roles of long noncoding RNAs (lncRNA) in regulating cancer via metabolic reprogramming are mostly unknown, including esophagal cancer (EC). Here, we showed that how the lncRNA urothelial carcinoma associated 1 (UCA1) exerts pro-oncogene in regulating EC glucose metabolism. Firstly, we found that upregulated UCA1 expression enhances the malignant phenotypes of EC, including poor outcome, larger tumor size, positive lymphatic invasion, and advanced pathological stages. UCA1 silencing could suppress EC cell proliferation and metastasis. Following, bioinformatics analyses revealed that UCA1 regulated the HK2 expression thr ough functioning as a competing endogenous RNA (ceRNA). Mechanistically, UCA1 overexpression could elevate the activation of HK2 oncogenes via inhibition of miR-203 activity, as evidenced by the positive correlation of UCA1 with HK2 and inverse correlation with miR-203 expression. Luciferase activity assay further verified the targeting relationship between UCA1, miR-203, and HK2. Upregulated UCA1 in EC cells significantly suppressed the degradation of HK2 by miR-203. Further research showed that upregulated UCA1 effectively increased the rate of glucose uptake, lactate output, and ECAR value, all of which can be attenuate by HK2 interference and 2-DG, whereas knockdown of UCA1 had the opposite effect. In sum, our findings suggest that the UCA1/miR-203/HK2 axis contributes to EC development by reprogramming tumor glucose metabolism, providing new insight into the management of EC patients. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Germline RET Analysis in a Series of Patients with Medullary Thyroid Carcinoma: The Challenge of the Variants of Uncertain Significance

Alexandros G.Sfakianakis shared this article with you from Inoreader Cancers, Vol. 12, Pages 3268: Results and Clinical Interpretation of Germline RET Analysis in a Series of Patients with Medullary Thyroid Carcinoma: The Challenge of the Variants of Uncertain Significance Μέσω Cancers Cancers, Vol. 12, Pages 3268: Results and Clinical Interpretation of Germline RET Analysis in a Series of Patients with Medullary Thyroid Carcinoma: The Challenge of the Variants of Uncertain Significance Cancers doi: 10.3390/cancers12113268 Authors: Giovanni Innella Cesare Rossi Maria Romagnoli Andrea Repaci Davide Bianchi Maria Elena Cantarini Davide Martorana Lea Godino Andrea Pession Antonio Percesepe Uberto Pagotto Daniela Turchetti Germline RET variants are responsible for approximately 25% of medullary thyroid carcinoma (MTC) cases. Identification of RET variant carriers allows for the adoption of preventative measures which are dependent on the risk associated with the specific alteration. From 2002 to 2020, at our cancer genetics clinic, RET genetic testing was performed in 163 subjects (102 complete gene analyses and 61 targeted analyses), 72 of whom presented with MTC. A germline RET variant was identified in 31.9% of patients affected by MTC (93.8% of those having positive family history and 14.3% of clinically sporadic cases). Subsequent target testing in relatives allowed us to identify 22 asymptomatic carriers, who could undertake appropriate screening. Overall, patients with germline RET variants differed significantly from those who tested negative by family history (p < 0.001) and mean age at MTC diagnosis (44.45 vs. 56.42 years; p = 0.010), but the difference was not significant when onl y carriers of moderate risk variants were considered (51.78 vs. 56.42 years; p = 0.281). Out of 12 different variants detected in 49 patients, five (41.7%) were of uncertain significance (VUS). For two of these, p.Ser904Phe and p.Asp631_Leu633delinsGlu, co-segregation and genotype/phenotype analysis, matched with data from the literature, provided evidence supporting their classification in the moderate and the highest/high risk class (with a MEN2B phenotype), respectively. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Myeloma Cells Deplete Bone Marrow Glutamine and Inhibit Osteoblast Differentiation Limiting Asparagine Availability

Alexandros G.Sfakianakis shared this article with you from Inoreader Cancers, Vol. 12, Pages 3267: Myeloma Cells Deplete Bone Marrow Glutamine and Inhibit Osteoblast Differentiation Limiting Asparagine Availability Μέσω Cancers Cancers, Vol. 12, Pages 3267: Myeloma Cells Deplete Bone Marrow Glutamine and Inhibit Osteoblast Differentiation Limiting Asparagine Availability Cancers doi: 10.3390/cancers12113267 Authors: Martina Chiu Denise Toscani Valentina Marchica Giuseppe Taurino Federica Costa Massimiliano G. Bianchi Roberta Andreoli Valentina Franceschi Paola Storti Jessica Burroughs-Garcia Rosa Alba Eufemiese Benedetta Dalla Palma Nicoletta Campanini Eugenia Martella Cristina Mancini Jixiu Shan Michael S. Kilberg Giovanna D'Amico Erica Dander Luca Agnelli Giancarlo Pruneri Gaetano Donofrio Ovidio Bussolati Nicola Giuliani Multiple myeloma (MM) cells consume huge amounts of glutamine and, as a consequence, the amino acid concentration is lower-than-normal in the bone marrow (BM) of MM patients. Here we show that MM-dependent glutamine depletion induces glutamine synthetase in stromal cells, as demonstrated in BM biopsies of MM patients, and reproduced in vitro by co-culturing human mesenchymal stromal cells (MSCs) with MM cells. Moreover, glutamine depletion hinders osteoblast differentiation of MSCs, which is also severely blunted by the spent, low-glutamine medium of MM cells, and rescued by glutamine restitution. Glutaminase and the concentrative glutamine transporter SNAT2 are induced during osteoblastogenesis in vivo and in vitro, and both needed for MSCs differentiation, pointing to enhanced the requirement for the amino acid. Osteoblastogenesis also triggers the induction of glutamine-dependent asparagine synthetase (ASNS), and, among non-essential amino acids, asparagine rescues differentia tion of glutamine-starved MSCs, by restoring the transcriptional profiles of differentiating MSCs altered by glutamine starvation. Thus, reduced asparagine availability provides a mechanistic link between MM-dependent Gln depletion in BM and impairment of osteoblast differentiation. Inhibition of Gln metabolism in MM cells and supplementation of asparagine to stromal cells may, therefore, constitute novel approaches to prevent osteolytic lesions in MM. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Buccolingual Inclination of Canine and First and Second Molar Teeth and the Curve of Wilson in Different Sagittal Skeletal Patterns of Adults Using Cone-Beam Computed Tomography

Alexandros G.Sfakianakis shared this article with you from Inoreader Buccolingual Inclination of Canine and First and Second Molar Teeth and the Curve of Wilson in Different Sagittal Skeletal Patterns of Adults Using Cone-Beam Computed Tomography Μέσω Hindawi Publishing Corporation Objectives. This study aimed to assess the buccolingual inclination of canine and first and second molar teeth and the curve of Wilson in different sagittal skeletal patterns in untreated adults using cone-beam computed tomography (CBCT). Materials and Methods. Sixty-six CBCT scans of adults (mean age: 28.74 ± 5.25 years) were evaluated in this cross-sectional study. The images were standardized using the Frankfurt horizontal plane and the interorbital line. The sagittal skeletal pattern was determined using the ANB angle and Wits appraisal. Inclination angles were measured by NNT Viewer and Mimics software. The curve of Wilson was measured by connecting the tips of mesiobuccal and mesiolingual cusps of maxillary first and second molars along the buccal groove and measuring the formed angle. Data were an alyzed using ANOVA. Results. The intraobserver agreement was 0.969. The mean inclination of maxillary first and second molars in class I and III patients was significantly higher than that in class II patients . The mean inclination of mandibular first and second molars in class II patients was significantly higher than that in class I and III patients . The difference in inclination of maxillary and mandibular canine teeth was not significant . The mean curve of Wilson in second molars of class II patients was significantly higher than that in class I patients .Conclusion. In different sagittal skeletal patterns, a compensatory relationship exists between the opposing teeth, which, along with the standards of crowns, can be used to determine the appropriate position of teeth in dental arch. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Identification of Prognosis-Related Genes in Bladder Cancer Microenvironment across TCGA Database

Alexandros G.Sfakianakis shared this article with you from Inoreader Identification of Prognosis-Related Genes in Bladder Cancer Microenvironment across TCGA Database Μέσω Hindawi Publishing Corporation Background. Bladder cancer (BCa) is a common urothelial malignancy. The Cancer Genome Atlas (TCGA) database allows for an opportunity to analyze the relationship between gene expression and clinical outcomes in bladder cancer patients. This study is aimed at identifying prognosis-related genes in the bladder cancer microenvironment. Methods. Immune scores and stromal scores were calculated by applying the ESTIMATE algorithm. We divided bladder cancer patients into high and low groups based on their immune/stromal scores. Then, differentially expressed genes (DEGs) were identified in bladder cancer patients based on the TCGA database. We evaluated the correlation between immune/stromal scores and clinical characteristics as well as prognosis. Finally, we validated identified genes associated with bladder ca ncer prognosis through a cohort study in the Gene Expression Omnibus (GEO) database. Results. A higher stromal score was associated with female (vs. male), (vs.), T3/4 (vs. T1/2,), N status, and pathological high grade (vs. low grade). By analyzing DEGs, there were 1125 genes commonly upregulated, and 209 genes were commonly downregulated. Protein-protein interaction networks further showed the important protein that may be involved in the biological behavior and prognosis of BCa, such as FN1, CXCL12, CD3E, LCK, and ZAP70. A total of 14 DEGs were found to be associated with overall survival of bladder cancer. After validation by a cohort of 165 BCa cases with detailed follow-up information from GSE13507, 10 immune-associated DEGs were demonstrated to be predictive of prognosis in BCa. Among them, 5 genes have not been reported previously associated with the prognosis of BCa, including BTBD16, OLFML2B, PRRX1, SPINK4, and SPON2. Conclusions. Our study elucidated tight associations bet ween stromal score and clinical characteristics as well as prognosis in BCa. Moreover, we obtained a group of genes closely related to the prognosis of BCa in the tumor microenvironment. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.