Αναζήτηση αυτού του ιστολογίου

Τετάρτη 14 Ιουλίου 2021

Ototoxicity in Patients of Advanced Head and Neck Malignancies Receiving Chemoradiation Versus Radiation Alone: Comparative Study

xlomafota13 shared this article with you from Inoreader

12070.jpg

Abstract

To evaluate ototoxicity in patients receiving combined cisplatin and radiotherapy in comparison to patients receiving radiotherapy alone. A prospective study was conducted in sixty (60) cases of advanced Head and Neck malignancy (stage III and IV). Patient were divided in two randomized groups (30 each), group I received chemoradiation and group II received radiation alone. Inclusion criteria were histopathologically confirmed head & neck malignancy, normal baseline audiograms. Exclusion criteria were defined as: previously treated cases with chemotherapy/radiotherapy, patients who didn't complete treatment or lost to follow up. Ototoxicity was evaluated as per criterion established by the American speech-language-hearing association. Study participants were evaluated for ototoxicity at intervals defined as per study design. Sensorineural hearing loss (SNHL) was noticed in 56.6% and 36.6% of subjects in Group I & II respectively at 6 months follow up post completion of treatment. Incidence of sensorineural hearing loss increased significantly with cumulative dosages of chemoradiotherapy in group I and radiotherapy in group II. Incidence of SNHL in both study groups was found to be higher in patients older than 50 years. Incidence of ototoxicity in chemoradiated patients was found to be higher in comparison to patients receiving radiation alone. Ototoxicity occurred more with cumulative doses, with higher speech frequencies affected earlier in comparison to middle range frequencies. Lower frequencies were spared.

View on the web

“Association of High Risk Factors and Hearing Impairment in Infants—A Hospital Based Study”

xlomafota13 shared this article with you from Inoreader

12070.jpg

Abstract

The aim of the study was to find the association of various risk factors with permanent hearing impairment in infants. A case–control study was designed on 420 infants with permanent hearing impairment and normal hearing. The case control ratio was 1:1. Alternate sampling method was used for selecting the control group. Review of medical records and parent interview was done to collect the information of risk factors. Family history(adj. OR 7.5; 95% CI 3, 14; P = 0.000), Consanguinity (adj. OR: 4; 95% CI 2,4; P = 0.000), intra uterine infection (adj. OR 18, 95% CI: 2.3–126.5, P = 0.000), post natal infection (adj. OR 3, 95% CI: 1.3–5, P = 0.004), low Apgar score (adj.OR: 4.6, 95% CI: 1.3–15), craniofacial anomaly (OR-4.6, 95% CI: 1.4–9.5, P = 0.005) and low birth weight (adj. OR: 2.3, 95% CI: 1.2–3.8) were significantly associated with hearing impairment. Among the risk factors, int ra uterine infection was having highest significant association with permanent hearing impairment. This is followed by family history, low Apgar score, craniofacial anomaly, consanguinity, post natal infection and low birth weight.

View on the web

At elevated temperatures, heat shock protein genes show altered ratios of different RNAs and expression of new RNAs, including several novel HSPB1 mRNAs encoding HSP27 protein isoforms

xlomafota13 shared this article with you from Inoreader

Exp Ther Med. 2021 Aug;22(2):900. doi: 10.3892/etm.2021.10332. Epub 2021 Jun 24.

ABSTRACT

Heat shock proteins (HSP) serve as chaperones to maintain the physiological conformation and function of numerous cellular proteins when the ambient temperature is increased. To determine how accurate the general assumption that HSP gene expression is increased in febrile situations is, the RNA levels of the HSF1 (heat shock transcription factor 1) gene and certain HSP genes were determined in three cell lines cultured at 37˚C or 39˚C for three days. At 39˚C, the expression of HSF1, HSPB1, HSP90AA1 and HSP70A1L genes demonstrated complex changes in the ratios of expression levels between different RNA variants of the same gene. Several older versions of the RNAs of certain HSP genes that have been replaced by a newer version in the National Center for Biotechnology Information database were also detected, indicating that the older versions are actually RNA variants of these genes. The present study cloned four new RNA variants of the HSP27-encoding HSPB1 gene, which together encode three short HSP27 peptides. Reanalysis of the proteomics data from our previous studies also demonstrated that proteins from certain HSP genes could be detected simultaneously at multiple positions using SDS-PAGE, suggesting that these genes may engender multiple protein isoforms. These results collectively suggested that, besides increasing their expression, certain HSP and associated genes also use alternative transcription start sites to produce multiple RNA transcripts and use alternative splicing of a transcript to produce multiple mature RNAs, as important mechanisms for responding to an increased ambient temperature in vitro.

PMID:34257713 | PMC:PMC8243336 | DOI:10.3892/etm.2021.10332

View on the web

Sevoflurane exerts improved protective effects than propofol on hypoxia-reoxygenation injury by regulating the microRNA-221-5p/ADAM8 axis in cardiomyocytes

xlomafota13 shared this article with you from Inoreader

Exp Ther Med. 2021 Aug;22(2):893. doi: 10.3892/etm.2021.10325. Epub 2021 Jun 18.

ABSTRACT

Myocardial ischemia-reperfusion (I/R) injury is a leading cause of heart disease and death. Decreasing the detrimental effect of I/R remains an urgent issue in clinical practice. The present study examined the interaction of the anesthetics (sevoflurane and propofol), ADAM8, and microRNA (miR)-221-5p in myocardial tissue protection in the hypoxia-reoxygenation (H/R) model. H9C2 cells were cultured and subjected to H/R stimulation for further verifications in vitro. Reverse transcription-quantitative PCR or western blotting was performed to evaluate mRNA or protein expression levels. Cell Counting Kit-8, BrdU, and caspase-3 activity assays were performed to investigate cell viability, proliferation and apoptosis. A dual-luciferase reporter assay was performed to verify the association between miR-221-5p and ADAM8. Sevoflurane had greater pro tective effects on the life of cardiomyocytes with H/R injury compared with propofol by promoting cell viability, proliferation and inhibiting apoptosis. Concurrently, compared with propofol-treated H/R injured cardiomyocytes, the expression level of ADAM8 in sevoflurane-treated H/R injured cardiomyocytes was higher. In addition, overexpression of ADAM8 promoted the cell viability and proliferation of sevoflurane-treated cardiomyocytes with H/R injury but inhibited cell apoptosis, while the downregulation of miR-221-5p showed an opposite trend to that of ADAM8 overexpression. The present data provide evidence that sevoflurane can mediate the miR-221-5p/ADAM8 axis, playing a better protective role compared with propofol in cardiomyocytes with H/R injury.

PMID:34257708 | PMC:PMC8243314 | DOI:10.3892/etm.2021.10325

View on the web

Clinical impact of copy number variation changes in bladder cancer samples

xlomafota13 shared this article with you from Inoreader

Exp Ther Med. 2021 Aug;22(2):901. doi: 10.3892/etm.2021.10333. Epub 2021 Jun 24.

ABSTRACT

The aim of the present study was to detect copy number variations (CNVs) related to tumour progression and metastasis of urothelial carcinoma through whole-genome scanning. A total of 30 bladder cancer samples staged from pTa to pT4 were included in the study. DNA was extracted from freshly frozen tissue via standard phenol-chloroform extraction and CNV analysis was performed on two alternative platforms (CytoChip Oligo aCGH, 4x44K and Infinium OncoArray-500K BeadChip; Illumina, Inc.). Data were analysed with BlueFuse Multi software and Karyostudio, respectively. The results highlight the role of genomic imbalances in regions containing genes with metastatic and proliferative potential for tumour invasion. A high level of genomic instability in uroepithelial tumours was observed and a total of 524 aberrations, including 175 losses and 349 gains, w ere identified. The most prevalent genetic imbalances affected the following regions: 1p, 1q, 2q, 4p, 4q, 5p, 5q, 6p, 6q, 7q, 8q, 9p, 9q, 10p, 10q, 11q, 13q and 17q. High-grade tumours more frequently harboured genomic imbalances (n=227) than low-grade tumours (n=103). A total of 36 CNVs in high-grade bladder tumours were detected in chromosomes 1-5, 8-11, 14, 17, 19 and 20. Furthermore, five loss of heterozygosity variants containing 176 genes were observed in high-grade bladder cancer and may be used as potential targets for precision therapy. Revealing specific chromosomal regions related to the metastatic potential of uroepithelial tumours may lay a foundation for implementing molecular CNV profiling of bladder tumours as part of a routine progression risk estimation strategy, thus expanding the personalized therapeutic approach.

PMID:34257714 | PMC:PMC8243332 | DOI:10.3892/etm.2021.10333

View on the web

BMP-2 alleviates heart failure with type 2 diabetes mellitus and doxorubicin-induced AC16 cell injury by inhibiting NLRP3 inflammasome-mediated pyroptosis

xlomafota13 shared this article with you from Inoreader

Exp Ther Med. 2021 Aug;22(2):897. doi: 10.3892/etm.2021.10329. Epub 2021 Jun 23.

ABSTRACT

Chronic heart failure (CHF) and diabetes mellitus are associated with morbidity and mortality. CHF and diabetes generally simultaneously occur, resulting in adverse outcomes. Diabetes complicates cardiomyopathy and exacerbates heart failure conditions. An increase in natriuretic peptides, including atrial natriuretic peptide (ANP), and another endsogenously generated peptide, brain natriuretic peptide (BNP), serves an essential role in CHF. The aim of this study was to explore the molecular regulation between bone morphogenetic protein-2 (BMP-2) and ANP or BNP in diabetes-associated cardiomyopathy. In total, 25 serum samples were collected from patients with CHF with or without type 2 diabetes mellitus to compare with 25 controls. Cardiomyopathy and hyperglycemia were induced in rats by doxorubicin and streptozotocin, respectively. AC16 cells were used to study molecular mechanisms. BMP, ANP and BNP concentration in patients and rats were measured by ELISA. Flow cytometry was performed to analyze cell pyroptosis and ROS production. Reverse transcription-quantitative PCR and western blotting were used to examine mRNA and protein expression of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), pro-caspase-1, caspase-1 (p20) and gasdermin D. BMP-2 was negatively correlated with ANP and BNP in CHF patients with type 2 diabetes mellitus. Similar results were obtained in rats and AC16 cells. BMP-2 decreased the NLRP3 inflammasome activation and cell pyroptosis. The present study found evidence that the cardioprotective effects of BMP-2 act through ANP and BNP both in vivo and in vitro. BMP-2 inhibits inflammasome formation. The results suggested that BMP-2 may serve as a novel therapeutic target for the treatment of diabetic heart conditions.

PMID:34257710 | PMC:PMC8243329 | DOI:10.3892/etm.2021.10329

View on the web

RUNX1 gene expression changes in the placentas of women smokers

xlomafota13 shared this article with you from Inoreader

Exp Ther Med. 2021 Aug;22(2):902. doi: 10.3892/etm.2021.10334. Epub 2021 Jun 24.

ABSTRACT

The placenta can be affected by environmental factors, such as exposure to cigarette smoke. This exposure in the fetal context is considered a risk factor for the development of short-term postnatal diseases, such as asthma. Asthma is an inflammatory disease characterized by predominant acquisition of CD4 T lymphocytes (TLs) of the Th2 type. Transcription factors such as GATA binding protein 3 (GATA3) and STAT6 actively participate in the differentiation of virgin TLs towards the Th2 profile, while transcription factors such as STAT1, T-Box transcription factor 21 (T-BET), RUNX1 and RUNX3 participate in their differentiation towards the Th1 profile. The objective of the current study was to evaluate the impact of exposure to cigarette smoke on the gene expression of STAT1, T-BET, GATA3, IL-4, RUNX1 and RUNX3 during the gestation peri od, and to determine whether the expression levels of these genes are associated with changes in global methylation. STAT1, GATA3, RUNX1 and RUNX3 protein and mRNA expression levels in the placental tissue of women smokers and non-smoking women were determined via immunohistochemistry and quantitative PCR (qPCR) respectively. Additionally, T-BET and IL-4 mRNA expression levels were determined by qPCR. On the other hand, global methylation was determined via ELISA. In the present study, significant increases were observed in RUNX1 transcription factor expression in placentas from women smokers when compared with placentas of non-smoking women. Similarly, significant increases in the expression of GATA3, IL-4 and RUNX3 mRNA were observed. The changes in gene expression were not associated with changes in the global methylation levels. Finally, a higher frequency of low-birth-weight infants were identified in cases of exposure to cigarette smoke durin g pregnancy when compared with infants not exposed to cigarette smoke during pregnancy. Thus, the data of the present study contributed to the understanding of the genetic and clinical impacts of exposure to cigarette smoke during pregnancy and its importance in maternal and fetal health.

PMID:34257715 | PMC:PMC8243315 | DOI:10.3892/etm.2021.10334

View on the web

Zhike pingchuan granules improve bronchial asthma by regulating the IL-6/JAK2/STAT3 pathway

xlomafota13 shared this article with you from Inoreader

Exp Ther Med. 2021 Aug;22(2):899. doi: 10.3892/etm.2021.10331. Epub 2021 Jun 23.

ABSTRACT

The present study aimed to investigate the effects of zhike pingchuan granules (ZKPC) on bronchial asthma and the underlying mechanism. A bronchial asthma mouse model was established by aerosol inhalation of ovalbumin. The changes in lung pathomorphology were observed by hematoxylin and eosin staining. The levels of IL-1β, TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF) and serum were detected by corresponding ELISA kits. Levels of reactive oxygen species, malondialdehyde and superoxide dismutase in lung tissues were analyzed using corresponding kits. The expression of proteins related to apoptosis and the IL-6/janus kinase 2 (JAK2)/STAT3 pathway was detected by western blot analysis. The results showed that ZKPC significantly restored the dry/wet ratio and alleviated lung pathomorphology of bronchial asthmatic mice. In addition, ZKPC inhi bits inflammation, oxidative stress levels and cell apoptosis in bronchial asthmatic mice and also suppressed the IL-6/JAK2/STAT3 pathway. Fedratinib (a JAK2 inhibitor) further strengthened the alleviative effects of ZKPC on bronchial asthma. In conclusion, ZKPC improved bronchial asthma by suppressing the IL-6/JAK2/STAT3 pathway.

PMID:34257712 | PMC:PMC8243345 | DOI:10.3892/etm.2021.10331

View on the web

Lipoblastoma: Diagnosis and surgical considerations

xlomafota13 shared this article with you from Inoreader

Exp Ther Med. 2021 Aug;22(2):903. doi: 10.3892/etm.2021.10335. Epub 2021 Jun 24.

ABSTRACT

Lipoblastoma (LB) and lipoblastomatosis (LBS) are uncommon benign mesenchymal tumors of embryonal fat, occurring almost exclusively in infancy and early childhood. These fast-growing tumors have an excellent prognosis if properly treated. Eight consecutive children having pathologically demonstrated LB treated by the same surgical team were retrospectively reviewed. There were 5 boys and 3 girls between 7 to 36 months (median age 22 months). The localization of the tumors was on the thigh (1 case), abdomen (2 cases), axillary and pectoral region (1 case) paragluteal region (1 case), lumbar area (1 case), inguinal-scrotal (1 case), and in one case, presacral, gluteal and perirectal region (1 case). Five were focal and in 3 cases an infiltrative growth pattern was observed. One case exhibited a gross appearance resembling sacrococcygeal teratoma, wi th associated Dravet syndrome. No recurrence was noted in our series, after a mean follow-up of 28 months post operatory. Despite its rareness, LB must be kept in mind when diagnosing a rapidly growing fatty mass in children. Even when dealing with very large abdominal LB, complete surgical excision is possible, with an excellent prognosis. Due to the relatively high recurrence rate noted in the literature, particularly in LBS, follow-up is extremely important.

PMID:34257716 | PMC:PMC8243331 | DOI:10.3892/etm.2021.10335

View on the web

LncRNA SNHG11 aggravates cell proliferation and migration in triple-negative breast cancer via sponging miR-2355-5p and targeting CBX5

xlomafota13 shared this article with you from Inoreader

Exp Ther Med. 2021 Aug;22(2):892. doi: 10.3892/etm.2021.10324. Epub 2021 Jun 18.

ABSTRACT

Triple-negative breast cancer (TNBC) is one of the most common malignances worldwide. Concurrently, the incidence of TNBC has continued to rise in recent years. It is reported that long non-coding RNAs (lncRNAs) are involved in biological processes in numerous cancers including TNBC. Small nucleolar RNA host gene 11 (SNHG11) has already been studied and reported in some cancers. However, the role of SNHG11 in TNBC remains unknown. RT-qPCR was used to measure gene expression in the current study. CCK-8, colony formation, flow cytometry, Transwell and western blotting experiments were also performed to determine the biological function of SNHG11 in TNBC cells. Luciferase reporter and RIP assays were performed to measure relationship between genes. In the present study, the results indicated SNHG11 was highly expressed in TNBC tissues and cell lines. Moreover, SNHG11 aggravated cell proliferation and migration, and whereas it attenuated cell apoptosis in TNBC. Furthermore, SNHG11 sponged microRNA 2355-5p (miR-2355-5p) in TNBC. Silencing SNHG11 increased miR-2355-5p expression. In addition, chromobox 5 (CBX5) was identified to be targeted by miR-2355-5p in TNBC. It was also suggested that CBX5 silencing suppressed cell proliferation and migration. Furthermore, overexpressed CBX5 recovered the inhibitive influence of SNHG11 silencing on proliferative and migrative abilities of TNBC cells. Overall, SNHG11 acted as a tumor promoter in TNBC and regulated TNBC cell growth by modulating the miR-2355-5p/CBX5 axis, which indicated that it may be used as a biomarker for TNBC treatment.

PMID:34257707 | PMC:PMC8243335 | DOI:10.3892/etm.2021.10324

View on the web

Macrophage activation syndrome: A diagnostic challenge (Review)

xlomafota13 shared this article with you from Inoreader

Exp Ther Med. 2021 Aug;22(2):904. doi: 10.3892/etm.2021.10336. Epub 2021 Jun 24.

ABSTRACT

Macrophage activation syndrome (MAS) represents an acute and severe inflammatory syndrome, idiopathic (primary) or secondary to infections, rheumatic diseases, malignancies, or drugs. MAS is underdiagnosed, being confused with sepsis, adverse effects of anti-arthritic drugs or exacerbated symptoms of evolving rheumatologic or infectious diseases. Because of the late diagnosis, most patients do not benefit from effective therapy, leading to death. Elucidation of valid early diagnostic criteria of MAS would be a particularly important step in reducing the mortality due to this pathology. Thus, the purpose of this review based on 40 studies centered on the diagnostic criteria of MAS. We detailed the main diagnostic criteria and the few diagnostic scores or sets of criteria that have been recently published. The criteria most frequently encountered in the literature include: Fever, hepatosplenomegaly, hyperferritinemia, hepatopathy, coagulopathy, thrombocytopenia, hypertriglyceridemia, decrease in erythrocyte sedimentation rate and bone marrow hemophagocytosis. The most elaborate diagnostic score will result following an ongoing international project and consensus, the Delphi International Survey.

PMID:34257717 | PMC:PMC8243343 | DOI:10.3892/etm.2021.10336

View on the web