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1.
Exp Ther Med ; 28(1): 286, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38827470

RESUMEN

Models of inflammation, oxidative stress, hyperoxia and hypoxia have demonstrated that magnesium sulfate (MgSO4), a commonly used drug in obstetrics, has neuroprotective potential. In the present study, the effects of MgSO4 treatment on inflammation, oxidative stress and fetal brain histopathology were evaluated in an experimental rat model following sevoflurane (Sv) exposure during the mid-gestational period. Rats were randomly divided into groups: C (control; no injections or anesthesia), Sv (exposure to 2.5% Sv for 2 h), MgSO4 (administered 270 mg/kg MgSO4 intraperitoneally) and Sv + MgSO4 (Sv administered 30 min after MgSO4 injection). Inflammatory and oxidative stress markers were measured in the serum and neurotoxicity was investigated histopathologically in fetal brain tissue. Short-term mid-gestational exposure to a 1.1 minimum alveolar concentration of Sv did not significantly increase the levels of any of the measured biochemical markers, except for TNF-α. Histopathological evaluations demonstrated no findings suggestive of pathological apoptosis, neuroinflammation or oxidative stress-induced cell damage. MgSO4 injection prior to anesthesia caused no significant differences in biochemical or histopathological marker levels compared to the C and Sv groups. The present study indicated that short-term exposure to Sv could potentially be considered a harmless external stimulus to the fetal brain.

2.
Exp Ther Med ; 28(2): 313, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38911048

RESUMEN

Acute kidney injury (AKI) caused by ischemia and, exogenous or endogenous nephrotoxic agents poses a serious health issue. AKI is seen in 1% of all hospital admissions, 2-5% of hospitalizations and 67% of intensive care unit (ICU) patients. The in-hospital mortality rates for AKI is 40-50, and >50% for ICU patients. Ischemia-reperfusion (I/R) injury in the kidney can activate inflammatory responses and oxidative stress, resulting in AKI. The common endpoint in acute tubular necrosis is a cellular insult secondary to ischemia or direct toxins, which results in effacement of brush border, cell death and decreased function of tubular cells. The aim of the present study was to assess if the reported antioxidant and anti-inflammatory agent lupeol can exert any effects against renal I/R damage. In total, 24 Wistar Albino rats were randomly assigned into four groups of 6, namely Sham, lupeol, ischemia and therapy groups. In the lupeol group, intraperitoneal administration of 100 mg/kg lupeol was given 1 h before laparotomy, whilst only laparotomy was conducted in the sham group. The renal arteries of both kidneys were clamped for 45 min, 1 h after either intraperitoneal saline injection (in the ischemia group) or 100 mg/kg lupeol application (in the therapy group). The blood samples and renal tissues of all rats were collected after 24 h. In blood samples, blood urea nitrogen (BUN) was measured by the urease enzymatic method, and creatinine was measured by the kinetic Jaffe method. Using ELISA method, TNF-α and IL-6 levels were measured in the blood samples, whereas malondialdehyde (MDA), glutathione (GSH), caspase-3 levels were measured in kidney tissues. In addition, kidney histopathological analysis was performed by evaluating the degree of degeneration, tubular dilatation, interstitial lymphocyte infiltration, protein cylinders, necrosis and loss of brush borders. It was determined that renal damage occurred due to higher BUN, creatinine, MDA, TNF-α and caspase-3 values observed in the kidney tissues and blood samples of rats in ischemia group compared with the Sham group. Compared with those in the ischemia group, rats in the therapy group exhibited increased levels of GSH and reduced levels of BUN, TNF-α, MDA. Furthermore, the ischemia group also had reduced histopathological damage scores. Although differences in creatinine, IL-6 and caspase-3 levels were not statistically significant, they were markedly reduced in the treatment group. Taken together, these findings suggest that lupeol can prevent kidney damage as mainly evidenced by the reduced histopathological damage scores, decreased levels of oxidative stress and reduced levels of inflammatory markers. These properties may allow lupeol to be used in the treatment of AKI.

3.
Int J Gynecol Pathol ; 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38914021

RESUMEN

The aim of this study is to evaluate the expressions of programmed death-ligand 1 (PD-L1), V-domain Ig suppressor of T-cell activation (VISTA), lymphocyte activation gene-3 (LAG-3), and galectin-3 (GAL-3), in mismatch repair-deficient (MMRd)/MMR-proficient and abnormal p53 expressing endometrial carcinomas and their relationship with clinical-histopathological features. Patients who underwent surgery for endometrial carcinoma between January 2008 and December 2018 were included in the study. Immunohistochemical analysis of MLH1, PMS2, MSH2, MSH6, p53, PD-L1, VISTA, LAG-3, and GAL-3 was performed on the tissue samples of microarray. A total of 529 patients were included. MMRd and p53-mutant tumors accounted for 31.5% and 11.5% of cases, respectively. PD-L1 and LAG-3 expressions in the MMRd and p53-mutant groups were higher than in the MMR-proficient group (P < 0.001). GAL-3 expression in the MMR-proficient group was statistically higher than in the MMRd and p53-mutant groups (P < 0.001). Mean age, grade, International Federation of Gynecology and Obstetrics stage, lymphovascular invasion, and lymph node metastasis were significantly higher in the p53-mutant group (P < 0.001). In the group with PD-L1 expression, nonendometrioid histologic type, tumor grade, and lymphovascular invasion were significantly higher (P < 0.001). Tumor grade, lymphovascular invasion, lymph node metastasis, and microcystic, elongated and fragmented pattern of invasion were significantly higher in the group with high VISTA expression (P < 0.05). Tumor grade was significantly higher in the group with LAG-3 expression (P < 0.001). Immunohistochemically determined subgroups and PD-L1, VISTA, LAG-3, and GAL-3 expression levels may be useful indicators of molecular features, and clinical outcomes also may have important implications for the development of targeted therapies in endometrial carcinoma.

4.
Artículo en Inglés | MEDLINE | ID: mdl-38727512

RESUMEN

AIMS: Colorectal cancer (CRC), the most common type of gastrointestinal cancer, mostly develops as a result of environmental factors. Inflammation is a relatively uncommon but crucial contributor to its etiology, and inflammation is also thought to pose a risk in patients without a clinical diagnosis of inflammatory bowel disease. In cell lines, the proinflammatory cytokine interleukin-6 (IL-6) causes a cytosolic shift in the mismatch repair protein MSH3, accompanied by functional loss. This study aimed to evaluate IL-6 and MSH3 expression in 171 sporadic CRC samples by immunohistochemistry (IHC). High levels of IL-6 are hypothesized to cause MSH3 expression loss. We also explored the clinical/pathological aspects of IHC-detected MSH3 loss and the relationship between MSH3 expression and tumor-infiltrating lymphocytes (TILs). MATERIALS AND METHODS: IL-6 and MSH3 IHC and H and E slides were evaluated by two pathologists. Clinical data were obtained from the institution's database. RESULTS: A relationship between MSH3 loss and IL-6 expression was not proven (P = 0.963). MSH3 staining was significantly reduced in the patient group with high TILs (P = 0.035). We observed 104 CRC cases (60.8%) with IL-6 expression and 85 cases (49.7%) with reduced MSH3 expression. CONCLUSION: This study did not demonstrate an association between IL-6 and MSH3 expression. As MSH3 is a relatively little-known protein, further large-scale studies are needed. The use of IHC to identify patients who may benefit from anti-IL-6 therapies in CRC in the future may be critical.

5.
Appl Immunohistochem Mol Morphol ; 32(6): 285-291, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38721798

RESUMEN

Knowledge of the molecular pathways of pediatric high-grade gliomas is increasing. Gliomas with mismatch repair deficiency do not currently comprise a distinct group, but data on this topic have been accumulating in recent publications. Immunohistochemistry can effectively determine mismatch repair status, indirectly suggesting the microsatellite instability of the tumor. This study aimed to determine the number of mismatch repair-deficient pediatric high-grade gliomas in a tertiary institution and assess the relationship between the survival and mismatch repair status of the patients. It also aimed to assess the potential for further clinical studies including immunotherapy. Of 24 patients with high-grade gliomas, 3 deceased patients were mismatch repair-deficient. Mismatch repair deficiency was significantly associated with shorter survival ( P =0.004). Immunotherapy trials need to progress, and patients with mismatch repair-deficient pediatric high-grade gliomas are the most suitable candidates for such studies.


Asunto(s)
Neoplasias Encefálicas , Reparación de la Incompatibilidad de ADN , Glioma , Inmunohistoquímica , Humanos , Glioma/metabolismo , Glioma/patología , Glioma/genética , Niño , Femenino , Masculino , Preescolar , Adolescente , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Lactante , Clasificación del Tumor , Inestabilidad de Microsatélites , Síndromes Neoplásicos Hereditarios/patología , Síndromes Neoplásicos Hereditarios/metabolismo , Neoplasias Colorrectales
6.
Int J Rheum Dis ; 27(5): e15187, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38742741

RESUMEN

Thymic tumors are very rare neoplasms in children and account for less than 1% of mediastinal tumors in pediatric patients. One-third of the pediatric patients present with symptoms related to the compression of the tumor mass on the surrounding anatomic structures, and paraneoplastic syndromes such as myasthenia gravis, pure red cell aplasia, acquired hypogammaglobulinemia, and connective tissue disorders, which rarely occur in children with thymic tumors. Herein, we report a case of thymic carcinoma mimicking the symptoms of a connective tissue disease with symmetrical polyarthritis accompanying myositis, fever, weight loss, and malaise in a 15-year-old male patient. To our knowledge, this is the first case pediatric thymic carcinoma accompany with severe polyarthritis and myopathy, thus we have reviewed the current literature regarding the cases of thymic malignancies coexisting with paraneoplastic syndromes in children.


Asunto(s)
Artritis , Miositis , Síndromes Paraneoplásicos , Timoma , Neoplasias del Timo , Humanos , Masculino , Miositis/diagnóstico , Miositis/complicaciones , Síndromes Paraneoplásicos/diagnóstico , Síndromes Paraneoplásicos/etiología , Neoplasias del Timo/complicaciones , Neoplasias del Timo/diagnóstico , Adolescente , Artritis/diagnóstico , Artritis/etiología , Timoma/complicaciones , Timoma/diagnóstico , Resultado del Tratamiento , Timectomía , Biopsia
7.
Turk J Obstet Gynecol ; 21(1): 22-27, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38440964

RESUMEN

Objective: The cause of implantation defects in patients with recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL) has not been clearly established. We aimed to evaluate the immunohistochemical changes in HOXA-11, ß1 integrin, focal adhesion kinase (FAK), cluster of differentiation 44 (CD44), and extracellular matrix protein 1 (ECM1) molecules during the receptive endometrial period in patients with RIF and RPL. Materials and Methods: This study was retrospectively conducted at a university hospital. After the exclusion of cases with pathology that may cause a change in the level of receptors in the endometrium, biopsies performed during the receptive period were selected, and the patients were categorized into RPL (n=15), RIF (n=16), control (n=16) groups. All preparations were immunohistochemically stained for HOXA-11, ß1 integrin, FAK, CD44, and ECM1. Results: HOXA-11 and ß1 Integrin expression changes were similar between the RIF and control groups. However, FAK expression was significantly increased in the RIF group (p<0.01). Additionally, ECM1 and CD44 expressions were significantly decreased in the RIF group compared with the control group (p<0.01). There was no significant difference in the endometrial staining of HOXA-11, FAK, and ECM1 in patients with a history of RPL. However, ß1 Integrin and CD44 levels were significantly decreased in the RPL group compared with the control group (p<0.05). Conclusion: Implantation is a complex process, and altered adhesion mechanisms involved in endometrial receptivity may be related to defective implantation in patients with RIF and RPL. Among the adhesion molecules, the expression of CD44, ß1 integrin, FAK, and ECM1 molecules varies in inappropriate implantation compared with the normal population.

8.
Gene ; 895: 148014, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-37984536

RESUMEN

Intertissue RNA transport recently emerged as a novel signaling mechanism. In mammals, mounting evidence suggests that small RNA transfer between cells is widespread and used in various physiological contexts. In the nematode C. elegans, a similar mechanism is conferred by the systemic RNAi pathway. Members of the Systemic RNA Interference Defective (SID) family act at different steps of cellular RNA uptake and export. The limiting step in systemic RNA interference (RNAi) is the import of extracellular RNAs via the conserved double-stranded (dsRNA)-gated dsRNA channel SID-1. To better understand the role of RNAs as intertissue signaling molecules, we modified the function of SID-1 in specific tissues of C. elegans. We observed that sid-1 loss-of-function mutants are as healthy as wild-type worms. Conversely, overexpression of sid-1 in C. elegans intestine, muscle, or neurons rendered worms short-lived. The effects of intestinal sid-1 overexpression were attenuated by silencing the components of systemic RNAi sid-1, sid-2 and sid-5, implicating systemic RNA signaling in the lifespan reduction. Accordingly, tissue-specific overexpression of sid-2 and sid-5 also reduced worm lifespan. Additionally, an RNAi screen for components of several non-coding RNA pathways revealed that silencing the miRNA biogenesis proteins PASH-1 and DCR-1 rendered the lifespan of worms with intestinal sid-1 overexpression similar to controls. Collectively, our data support the notion that systemic RNA signaling must be tightly regulated, and unbalancing that process provokes a reduction in lifespan. We termed this phenomenon Intercellular/Extracellular Systemic RNA imbalance (InExS).


Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animales , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Interferencia de ARN , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Longevidad/genética , ARN Bicatenario/metabolismo , Proteínas de la Membrana/genética , Mamíferos/genética
10.
Turk Neurosurg ; 33(6): 1120-1125, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37846542

RESUMEN

AIM: To determine if previous histological grading systems were sufficient or unreliable with a limited repository of modern techniques. MATERIAL AND METHODS: The pathology reports of pediatric neurosurgery patients between 2019-2022 were accessed. Data on patients that needed unattainable further molecular investigation were extracted. Data were noted from electronic archives, including their sex, age, histologic grade, location, resection type, survival, and therapy. RESULTS: Out of 61 surgeries, 17 patients needed further investigation for a proper 2022 World Health Organization (WHO) diagnosis. Seven were deceased, and nine were alive. Two of 10 patients with low-grade gliomas and five of six patients with highgrade gliomas were deceased. Data on one foreign patient with high-grade glioma was inaccessible. The average survival was 9 months for the deceased. CONCLUSION: Modern molecular techniques such as next-generation sequencing and methylation profiling are the state-ofthe- art methods, but it is hard for developing and underdeveloped countries to utilize such methods. The classification schemes, diagnostic key figures, and treatment modalities are developed using these techniques, but the less developed world is incapable of achieving these. We are trying to hybridize the modern and classic modalities, and the results of our study show that for overall survival, there is still not much difference. More economic and feasible techniques should be produced and summarized for the rest of the world.


Asunto(s)
Neoplasias Encefálicas , Glioma , Humanos , Niño , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirugía , Estudios Retrospectivos , Glioma/diagnóstico , Glioma/genética , Glioma/cirugía
11.
Turk Patoloji Derg ; 39(3): 169-178, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37350641

RESUMEN

OBJECTIVE: In a study of Merkel cell carcinoma (MCC), a fusion transcript between MLH1 and SPATA4 was identified. This fusion has the potential to generate the inactive or dominant-negative form of the protein. Therefore, we aimed to investigate whether mismatch repair protein deficiency occurr in MCC cases or not, in addition to the overall survival association with histopathologic features. MATERIAL AND METHOD: A retrospective review of 15 patients diagnosed with a biopsy-proven Merkel Cell Carcinoma between 2012 and 2019 was performed. Mismatch repair (MMR) protein expressions were evaluated by immunohistochemistry. RESULTS: The median follow-up time was 36 months (mean 41, range 2-103 months). Six (40%) patients died during follow-up. The overall survival (OS) at 1 year, 2 years, 3 years, and 5 years were 87%, 80%, 62%, and 53%, respectively. The patients diagnosed at < 60 years had an improved OS compared to those ≥60 years of age (p=0.016). Patients in clinical stage I had better OS than patients in clinical stage IV (p=0.011). Cases with pathological tumor stage (pT) 1 had better OS than pT3 and pT4 (p=0.045). Adjuvant radiotherapy or adjuvant radiotherapy+chemotherapy treatment improved OS compared to adjuvant chemotherapy (p=0.003). MMR protein nuclear expression was intact in 12 cases available for immunohistochemical study. CONCLUSION: To the best of our knowledge, this is the second study that preferentially investigated the mismatch repair protein status of Merkel Cell Carcinoma. No mismatch repair protein deficiency of MCC cases was identified in the current study.


Asunto(s)
Carcinoma de Células de Merkel , Deficiencia de Proteína , Neoplasias Cutáneas , Humanos , Carcinoma de Células de Merkel/terapia , Carcinoma de Células de Merkel/patología , Reparación de la Incompatibilidad de ADN , Radioterapia Adyuvante , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/patología , Deficiencia de Proteína/patología , Estudios Retrospectivos , Estadificación de Neoplasias , Proteínas
12.
Appl Immunohistochem Mol Morphol ; 31(6): 371-378, 2023 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-37126387

RESUMEN

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive, primary neuroendocrine carcinoma of the skin whose main risk factors are immunosuppression, UV radiation exposure, and Merkel cell polyomavirus. Programmed death-1/programmed death ligand-1 (PD-L1)-based immunotherapy is currently the first choice for treating patients with metastatic MCC. METHODS: MCC biopsies (17) were evaluated for their nucleus and cytoplasm characteristics and growth patterns, as well as for intratumor lymphocytes, mitotic number, and lymphovascular invasion. Paraffin-embedded tissue samples of the biopsies were stained with MCPyV large T-antigen (LTag), RB1, p53, and PD-L1. RESULTS: We observed MCPyV LTag expression in 9 out of the 17 tumors, and all 9 cases were positive for RB1 ( P <0.000). p53 staining was not significantly correlated with MCPyV LTag. We observed no relationship between p53 expression and any other parameters, and PD-L1 expression was low in the MCC samples. We evaluated PD-L1 using both the combined positive score and tumor proportion score (TPS), and found that TPS was correlated with MCPyV LTag expression ( P =0.016). Tumors with tumor-infiltrating lymphocytes showed a better prognosis than those without these lymphocytes ( P =0.006). DISCUSSION: Our data demonstrated that RB1 was effective for immunohistochemically investigating the MCPyV status of tumors. TPS was superior to the combined positive score in evaluating PD-L1 in MCC. Tumor-infiltrating lymphocytes were the only parameters that were associated with survival. Further studies with larger series are required to confirm these results.


Asunto(s)
Carcinoma de Células de Merkel , Poliomavirus de Células de Merkel , Infecciones por Polyomavirus , Neoplasias Cutáneas , Humanos , Carcinoma de Células de Merkel/patología , Antígeno B7-H1/metabolismo , Poliomavirus de Células de Merkel/metabolismo , Proteína p53 Supresora de Tumor , Neoplasias Cutáneas/patología , Infecciones por Polyomavirus/complicaciones , Infecciones por Polyomavirus/metabolismo , Ubiquitina-Proteína Ligasas , Proteínas de Unión a Retinoblastoma/metabolismo
13.
J Oral Maxillofac Pathol ; 27(1): 230-232, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37234301

RESUMEN

Pleomorphic dermal sarcoma (PDS) is an undifferentiated high-grade tumour and is considered the most common primary soft tissue tumour in adults. The most common locations of PDS are the trunk, extremities and retroperitoneal regions. Skin involvement of PDS is rare, and involvement of the scalp is less common. Most cases of PDS appear as a gradually growing lesion for 1 to 2 years and are associated with ulceration and bleeding. The definitive treatment for PDS is usually surgical resection. We present an unusual case of a primary PDS involving the scalp of a 78-year-old male patient and discuss its unusual clinical presentation, dermoscopic features, histopathological correlation and its management.

14.
Sci Rep ; 13(1): 5224, 2023 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-36997624

RESUMEN

Recombinant protein-based SARS-CoV-2 vaccines are needed to fill the vaccine equity gap. Because protein-subunit based vaccines are easier and cheaper to produce and do not require special storage/transportation conditions, they are suitable for low-/middle-income countries. Here, we report our vaccine development studies with the receptor binding domain of the SARS-CoV-2 Delta Plus strain (RBD-DP) which caused increased hospitalizations compared to other variants. First, we expressed RBD-DP in the Pichia pastoris yeast system and upscaled it to a 5-L fermenter for production. After three-step purification, we obtained RBD-DP with > 95% purity from a protein yield of > 1 g/L of supernatant. Several biophysical and biochemical characterizations were performed to confirm its identity, stability, and functionality. Then, it was formulated in different contents with Alum and CpG for mice immunization. After three doses of immunization, IgG titers from sera reached to > 106 and most importantly it showed high T-cell responses which are required for an effective vaccine to prevent severe COVID-19 disease. A live neutralization test was performed with both the Wuhan strain (B.1.1.7) and Delta strain (B.1.617.2) and it showed high neutralization antibody content for both strains. A challenge study with SARS-CoV-2 infected K18-hACE2 transgenic mice showed good immunoprotective activity with no viruses in the lungs and no lung inflammation for all immunized mice.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Animales , Humanos , Ratones , SARS-CoV-2/genética , COVID-19/prevención & control , Ratones Transgénicos , Saccharomyces cerevisiae , Anticuerpos Antivirales , Anticuerpos Neutralizantes
15.
Ultrasound Q ; 39(2): 81-85, 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-36892515

RESUMEN

ABSTRACT: In this study, we aimed to investigate the correlation of stiffness values of shear-wave elastography (SWE) and histopathological prognostic factors in patients with breast cancer. Between January 2021 and June 2022, SWE images of 138 core-biopsy proven breast cancer lesions from 132 patients were retrospectively reviewed. Histopathogic prognostic factors, including tumor size, histologic grade, histologic type, hormone receptor positivity, human epidermal growth factor receptor (HER2) status, immunohistochemical subtype and Ki-67 index were documented. Elasticity values including mean and maximum elasticity ( Emean and Emax ) and lesion-to-fat ratio ( Eratio ) were recorded. The association between histopathological prognostic factors and elasticity values were assessed using Mann-Whitney U and Kruskal-Wallis test, and multiple linear regression analysis. Tumor size, histological grade, and Ki-67 index were significantly associated with the Eratio ( P < 0.05). Larger tumor size and higher Ki-67 index also showed significantly higher Emean and Emax values ( P < 0.05). However, hormone receptor positivity, HER2 status, and immunohistochemical subtype were not significantly associated with elasticity values ( P > 0.05). Multivariate logistic regression analysis revealed that tumor size was significantly associated with Emean , Emax , and Eratio values ( P < 0.05). A high Ki-67 index was also significantly associated with high Eratio values. Larger tumor size and higher Ki-67 index are independently associated with high Eratio values. Preoperative SWE may improve the performance of conventional ultrasound in predicting prognosis and treatment planning.


Asunto(s)
Neoplasias de la Mama , Diagnóstico por Imagen de Elasticidad , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Pronóstico , Diagnóstico por Imagen de Elasticidad/métodos , Estudios Retrospectivos , Antígeno Ki-67 , Hormonas , Ultrasonografía Mamaria/métodos
16.
Eur J Radiol ; 149: 110228, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35255320

RESUMEN

PURPOSE: To evaluate the European Society of Urogenital Radiology (ESUR) score, the Likert scale, tumor contact length (TCL) > 1 cm, and EPE (extraprostatic extension) grade in predicting EPE at multiparametric magnetic resonance imaging (mp-MRI). METHODS: Seventy-nine patients who underwent 3-T MRI and were histopathologically confirmed by microblocks were enrolled in this retrospective study. The index lesions were interpreted by two experienced radiologists. Apparent diffusion coefficient (ADC) values were also noted. Weighted κ statistics were used to compare interreader agreement. Univariate logistic regression analysis was performed to define independent predictors of EPE status. Multivariable logistic regression and receiver operating characteristic (ROC) analysis were performed to compare the MRI-based methods and clinical variables (ISUP grade, prostate volume and PSA density) + MRI-based methods for pathologic EPE prediction by using the area under the curve (AUC) value. RESULTS: The mean age was 64.5 years ± 6.2. 33/79 (41.8%) patients had pathologic EPE. As ESUR score showed weak interreader agreement (κ = 0.537), Likert scale, TCL, and EPE grade showed moderate agreement (κ = 0.608, κ = 0.747, κ = 0.647 respectively). Univariate ROC analysis result showed that all MRI-based score systems, mean ADC value, the ISUP grade, prostate volume, PSA density were the best variables in predicting EPE. ROC analysis results of four MRI-based methods showed good diagnostic performance. At multivariate analysis, all clinical models showed excellent diagnostic performance. CONCLUSION: All four MRI-based methods had good diagnostic performance. Furthermore, consisting of both qualitative and quantitative parameters and being less reader experience dependent, EPE grade was a promising method in predicting EPE. All clinical models showed excellent diagnostic performance.


Asunto(s)
Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata , Radiología , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Prostatectomía/métodos , Neoplasias de la Próstata/patología , Estudios Retrospectivos
17.
Biotechnol J ; 17(2): e2100332, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34870891

RESUMEN

Pichia pastoris (Komagataella phaffii) is a non-conventional Crabtree-negative yeast with the capability of reaching very high cell densities in a fed-batch fermentation process. The alcohol dehydrogenase (ADH) genes of P. pastoris involved in ethanol metabolism were identified and were previously characterized. This work aimed to extend current knowledge of the regulation of the ADH2 promoter. To this end, we first determined the upstream activator (UAS) and repressor (URS) sequences of the promoter by deletion assays. Two upstream activator sites have been identified, positioned between -900 and -801 bp, and -284 and -108 bp upstream of the ADH2 transcription start site. The sequences positioned between -361 and -262 bp had a negative effect on the promoter activity and designated a repressor sequence (URS). We then demonstrated that Mxr1 (methanol expression regulator 1) transcription factor activates the ADH2 promoter through the direct interaction with UAS regions in response to ethanol. Furthermore, five different synthetic promoters were constructed by adding or deleting the regulatory sites. These synthetic promoters were tested for extracellular xylanase production at shake flask level by inducing with ethanol. These promoter variants improved the xylanase production ranging between 165% and 200% of the native promoter. The synthetic promoter 5 (SNT5) that displayed the highest activity was further evaluated at the fermenter scale. The modification in the promoter features might have several implications for industrial processes where decoupling the cell growth and product formation is advantageous.


Asunto(s)
Alcohol Deshidrogenasa , Proteínas Fúngicas , Pichia , Regiones Promotoras Genéticas , Alcohol Deshidrogenasa/genética , Proteínas Fúngicas/genética , Regulación Fúngica de la Expresión Génica , Pichia/enzimología , Pichia/genética , Saccharomycetales
18.
J Invest Surg ; 35(5): 1062-1066, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34747308

RESUMEN

BACKGROUND: Hypospadias is a common congenital anomaly which is determined as an abnormal urethral opening on the ventral face of penis. The purpose of this rat model study was to research the effect of topically applied Aloe vera after a tubularized incised plate urethroplasty (TIPU). METHODS: The TIPU model was applied to male Wistar albino rats. A total of 30 rats were randomly grouped into 3 groups of 10. Group I was assigned as the control group, treated with 0.9% saline only twice a day for 15 days. Group II received topical Aloe vera gel once a day and Group III received Aloe vera gel twice a day. Spongiofibrosis was graded as 0: none, 1+:≤10% tissues involved, 2+:10%-49% tissues involved, 3+: ≥ 50% tissues involved. RESULTS: A higher degree of fibrosis and inflammation was determined in the Group I subjects than in Groups II and III. Fibrosis of grade 3+ was observed in 33% of the control group and not in any of the two Aloe groups (p = 0.043). Inflammation of grade 3+ was seen in 66.7% of the control group, in 10% of Group II, and in 33% of Group III (p = 0.02). CONCLUSIONS: The topical application of Aloe vera to a surgically created tubularized incised plate urethroplasty model decreased inflammation and fibrosis that may affect the success rates of this operation.


Asunto(s)
Aloe , Animales , Fibrosis , Humanos , Inflamación , Masculino , Ratas , Ratas Wistar , Uretra/cirugía , Cicatrización de Heridas
19.
Cutan Ocul Toxicol ; 40(4): 319-325, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34225552

RESUMEN

PURPOSE: To evaluate the potential toxicity of operation microscopes with halogen and light emitting diode (LED) light source on the rabbit eyes. MATERIALS AND METHODS: Thirty-two eyes of 16 male New Zealand pigmented rabbits were involved in the study. The rabbits were divided into two groups according to the type of light source applied. Only one eye of each rabbit was exposed to illumination light, unexposed fellow eyes served as the control group. Experimental groups included group 1 exposed to halogen light for 2 h and evaluated 1 day and 1 week after the illumination, group 2 exposed to LED light for two hours and evaluated 1 day and 1 week after the illumination. On the first and seventh days after exposing the light, we evaluated the rabbit corneas using in vivo confocal microscopy (IVCM). At the end of the seventh day, the Hematoxylin-eosin staining and TUNEL staining were performed to investigate the presence of apoptosis in the retina and retina pigment epithelium. RESULTS: Early IVCM findings revealed corneal epithelial cell ovalization and indistinct intercellular borders in the halogen light group. We also observed more increase in the keratocyte density index (23.7% vs 14.1%, p = 0.001, respectively) and the Bowman reflectivity index (12.4% vs 4.1%, p = 0.001, respectively) at first day of the light exposure in halogen light group compared to LED light group. However, late IVCM indicated that these findings disappeared one week later. No apoptosis was observed in the corneal and retinal layers in early and late examination groups. CONCLUSION: The present experimental study demonstrated that both halogen and LED lights, which were commonly used for microscopic eye surgery, had no sustained adverse effect on the cornea and retina of the rabbits; however, halogen light had a temporary adverse effect on corneal epithelium and stroma, which resolved within 1 week.


Asunto(s)
Epitelio Corneal/efectos de la radiación , Iluminación/efectos adversos , Microcirugia/efectos adversos , Procedimientos Quirúrgicos Oftalmológicos/efectos adversos , Complicaciones Posoperatorias/patología , Epitelio Pigmentado de la Retina/efectos de la radiación , Animales , Apoptosis , Epitelio Corneal/patología , Halógenos , Humanos , Microscopía Intravital/efectos adversos , Microscopía Intravital/instrumentación , Iluminación/instrumentación , Masculino , Microscopía Confocal/instrumentación , Microcirugia/instrumentación , Procedimientos Quirúrgicos Oftalmológicos/instrumentación , Complicaciones Posoperatorias/etiología , Conejos , Epitelio Pigmentado de la Retina/patología , Semiconductores
20.
J Sleep Res ; 30(2): e13065, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-32383252

RESUMEN

In this study, we aimed to investigate the effects of chronic sleep deprivation on mucociliary clearance, which is the primary defence mechanism of the upper airway tract and nasal mucosal histology. Forty-two Wistar Albino rats (250-300 g), 8 or 12 weeks old, were randomly assigned into three groups as follows. The first sleep-deprivation group consisted of 14 rats (A), another 14 of them were assigned to platform group (B), and the remaining 14 were included to the home cage control group (C). For the two deprivation groups (A and B), the modified multiple platform method (MMPM) was used to induce sleep deprivation for 21 days. Tc-99m MAA rhinoscintigraphy was performed to assess mucociliary clearance and the nasal histopathological changes of the sacrificed rats were also examined. Mucociliary clearance was significantly higher in sleep deprivation (A) and deprivation control (B) groups than the control group (C) (p = .037). The ratio of columnar ciliary was significantly higher in group A and B than in the control group (p = .003). The transitional epithelial ratio in groups A and B was also significantly increased compared with group C (p = .04). The control group's squamous epithelial ratio was increased compared to the sleep-deprived groups (p = .003). There was a significantly increased inflammatory response in the ciliated columnar epithelium in groups A and B compared to group C (p = .02). For the first time in the literature, we demonstrated that chronic sleep deprivation has caused a significant increase in mucociliary clearance speed and in the number of ciliary cells.


Asunto(s)
Depuración Mucociliar/fisiología , Infecciones del Sistema Respiratorio/etiología , Privación de Sueño/complicaciones , Animales , Enfermedad Crónica , Masculino , Ratas , Ratas Wistar , Infecciones del Sistema Respiratorio/patología
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