Sonlicromanol’s active metabolite KH176m normalizes prostate cancer stem cell mPGES-1 overexpression and inhibits cancer spheroid growth

xlomafota13 shared this article with you from Inoreader Sonlicromanol's active metabolite KH176m normalizes prostate cancer stem cell mPGES-1 overexpression and inhibits cancer spheroid growth Via Head and neck cancers by Xiaolan Jiang, Herma Renkema, Jan Smeitink, Julien Beyrath Aggressiveness of cancers, like prostate cancer, has been found to be associated with elevated expression of the microsomal prostaglandin E synthase-1 (mPGES-1). Here, we investigated whether KH176m (the active metabolite of sonlicromanol), a recently discovered selective mPGES-1 inhibitor, could affect prostate cancer cells-derived spheroid growth. We demonstrated that KH176m suppressed mPGES-1 expression and growth of DU145 (high mPGES-1 expression)-derived spheroids, while it had no effect on the LNCaP cell line, which has low mPGES-1 expression. By addition of exogenous PGE2, we found that the effect of KH176m on mPGES-1 expression and spheroid growth is due to the inhibition of a PGE2-driven positive feedback control-loop of mPGES-1 transcriptional regulation. Cancer stem cells (CSCs) are a subset of cancer cells exhibiting the ability of self-renewal, plasticity, and initiating and maintaining tumor growth. Our data shows that mPGES-1 is specifically expre ssed in this CSCs subpopulation (CD44+CD24-). KH176m inhibited the expression of mPGES-1 and reduced the growth of spheroids derived from the CSC. Based on the results obtained we propose selective mPGES-1 targeting by the sonlicromanol metabolite KH176m as a potential novel treatment approach for cancer patients with high mPGES-1 expression. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Metastatic Papillary Thyroid Cancer to the Liver: The Central Role of a Multidisciplinary Approach to Treatment

xlomafota13 shared this article with you from Inoreader Metastatic Papillary Thyroid Cancer to the Liver: The Central Role of a Multidisciplinary Approach to Treatment Via radioactive iodine Ochsner J. 2021 Summer;21(2):224-229. doi: 10.31486/toj.20.0067. ABSTRACT Background: Differentiated thyroid cancer (DTC) is comprised of papillary and follicular subtypes, and both have an overall excellent long-term prognosis. Patients with localized DTC that is successfully treated, usually with surgery, exhibit long-term survival well above 90%. In contrast, patients who develop distant metastatic disease have a significantly worse overall prognosis and outcome, often wi th disease that is refractory to conventional therapy such as surgery, radioactive iodine, and hormone suppression. For patients who recur with distant metastatic disease, limited effective treatment options are available, and most die of their disease within 5 years of recurrence. Case Report: We report the case of a 26-year-old female who presented with recurrent papillary thyroid cancer and a metastatic lesion isolated to the liver. Because of the extremely large size of the metastatic liver mass upon initial presentation, we took a neoadjuvant, multifaceted approach to treatment that included selective internal radioembolization therapy, an oral multikinase inhibitor, and surgical resection of the tumor mass after maximal reduction in tumor size. However, the patient died of metastatic DTC after 39 months of treatment. Conclusion: A multimodal, comprehensive approach to managing such complex patients is essential to optimize both the sequence and therapeutic approa ch to treatment. PMID:34239388 | PMC:PMC8238104 | DOI:10.31486/toj.20.0067 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Association of CD4 T cell count and optimal timing of antiretroviral therapy initiation with immune reconstitution inflammatory syndrome and all-cause mortality for HIV-infected adults with newly diagnosed pulmonary tuberculosis: a systematic review and meta-analysis

xlomafota13 shared this article with you from Inoreader Association of CD4 T cell count and optimal timing of antiretroviral therapy initiation with immune reconstitution inflammatory syndrome and all-cause mortality for HIV-infected adults with newly diagnosed pulmonary tuberculosis: a systematic review and meta-analysis Via International Journal of Clinical and Experimental Pathology Int J Clin Exp Pathol. 2021 Jun 15;14(6):670-679. eCollection 2021. ABSTRACT AIMS: CD4 T cell count and optimal timing of antiretroviral therapy (ART) during tuberculosis (TB) treatment are challenging. We conducted a meta-analysis to assess the association of CD4 T cell count and timing of ART initiation with immune reconstitution inflammatory syndrome (IRIS) and all-cause mortality of patients co-infected with HIV/TB. METHODS: We conducted an electronic search of clinical studies dated from January 1980 to December 2019 in PubMed and EMBASE. Randomized, controlled trials evaluating low-base CD4 T cell count (< 50 cells/μL) versus high-base CD4 T cell count (≥ 50 cells/μL), and/or early ART initiation (1 to 28 days after starting TB treatment) versus delayed ART initiation (≥ 28 days after starting TB treatment) were included. The primary endpoints were all-cause mortality and TB-related immune reconstitution inflammato ry syndrome (IRIS-TB). The risk ratio (RR) was calculated as a measure of intervention effect. Mantel-Haenszel method was used to estimate the RR. RESULTS: Ten trials (n = 5226) were conducted in North America, Africa, and Asia. We found that low-baseline CD4 T cell count increased the incidence of TB-associated IRIS (RR, 1.47; 95% CI, 1.24-1.75; I2 = 58%) and all-cause mortality (RR, 2.42; 95% CI, 1.71-3.42; I2 = 41%) compared with high baseline CD4 T cell count, and early ART initiation increased the incidence of TB-associated IRIS compared with delayed ART initiation (RR, 1.80; 95% CI, 1.57-2.07; I2 = 74%). However, early ART initiation did not reduce all-cause mortality (RR, 0.91; 95% CI, 0.74-1.12; I2 = 49%) compared with delayed ART initiation. CONCLUSIONS: The present study demonstrates that low-baseline CD4 T cell count (< 50 cells/μL) in patients co-infected with TB-HIV increases the incidence of TB-associated IRIS and all-cause mortality. Early ART initiation (≤ 28 days) in patients co-infected with TB-HIV increases the incidence of TB-associated IRIS. However, evidence is insufficient to refute or support a survival benefit conferred by the comparison between early ART initiation (≤ 28 days) and delayed ART initiation. PMID:34239668 | PMC:PMC8255206 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Wnt7a promotes muscle regeneration in branchiomeric orbicularis oris muscle

xlomafota13 shared this article with you from Inoreader Wnt7a promotes muscle regeneration in branchiomeric orbicularis oris muscle Via International Journal of Clinical and Experimental Pathology Int J Clin Exp Pathol. 2021 Jun 15;14(6):693-704. eCollection 2021. ABSTRACT BACKGROUND: The orbicularis oris muscle exhibits a deficiency in cleft lip patients. Compared with the somite-derived limb muscles, the regeneration performance of the branchiomeric orofacial muscle has seldom been investigated. OBJECTIVE: This study aims to explore the possibility of augmenting the orbicularis oris muscle through the stimulus of Wnt7a. METHODS: Adult rat orbicularis oris muscle and tibialis anterior muscle were injected with recombinant human Wnt7a protein. The muscles were harvested at different time points after Wnt7a delivery. Muscle regeneration-related activity, including cell proliferation, stem cell proportion, myofiber plasticity, and total fiber number, was examined. RESULTS: Adult rat orbicularis oris muscle and tibialis anterior muscle exhibit similar regeneration-related activities after Wnt7a administration. Rec ombinant human Wnt7a administration resulted in enhanced cell proliferation, stem cell expansion, and fiber type remodelling in rat orbicularis oris muscle. In addition, newly formed myofibers were detected, contributing to an increased total fiber number. CONCLUSION: Wnt7a induces vigorous regeneration in rat orbicularis oris muscle. This study helps lay a foundation for developing biotherapies to combat orofacial muscle deficiency. PMID:34239670 | PMC:PMC8255207 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Uniformly-aligned gelatin/polycaprolactone fibers promote proliferation in adipose-derived stem cells and have distinct effects on cardiac cell differentiation

xlomafota13 shared this article with you from Inoreader Uniformly-aligned gelatin/polycaprolactone fibers promote proliferation in adipose-derived stem cells and have distinct effects on cardiac cell differentiation Via International Journal of Clinical and Experimental Pathology Int J Clin Exp Pathol. 2021 Jun 15;14(6):680-692. eCollection 2021. ABSTRACT Cardiac tissue engineering is a promising technique to regenerate cardiac tissue and treat cardiovascular disease. Here we applied a modified method to generate ultrafine uniformly-aligned composite gelatin/polycaprolactone fibers that mimic functional heart tissue. We tested the physical properties of these fibers and analyzed how these composite fibrous scaffolds affected growth and cardiac lineage differentiation in rat adipose-derived stem cells (rADSCs). We found that uniformly aligned composite fiber scaffolds had an anisotropic arrangement, functional mechanical properties, and strong hydrophilicity. The anisotropic scaffolds improved cell attachment, viability, and proliferative capacity of ADSCs over randomly-aligned scaffolds. Furthermore, uniformly aligned composite fiber scaffolds increased the efficiency of cardiomyogenic differentiation, but migh t reduce the efficiency of cardiac conduction system cell differentiation in ADSCs compared to randomly-oriented scaffolds and tissue culture polystyrene. However, the randomly-oriented composite scaffolds showed no obviously facilitated effects over tissue culture polystyrene on the two cells' differentiation process. The above results indicate that the scaffold fiber alignment has a greater effect on cell differentiation than the composition of the scaffold. Together, the uniformly-aligned composite fibers displayed excellent physical and biocompatible properties, promoted ADSC proliferation, and played distinct roles in the differentiation of cardiomyogenic cells and cardiac conduction system cells from ADSCs. These results provide new insight for the application of anisotropic fibrous scaffolds in cardiac tissue engineering for both in vitro and in vivo research. PMID:34239669 | PMC:PMC8255201 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effects of different intensity of exercise on tissue injury and gene expression in obese rats

xlomafota13 shared this article with you from Inoreader Effects of different intensity of exercise on tissue injury and gene expression in obese rats Via International Journal of Clinical and Experimental Pathology Int J Clin Exp Pathol. 2021 Jun 15;14(6):705-712. eCollection 2021. ABSTRACT Weight loss is an important aspect of chronic disease prevention and management, with increasing rates of overweight and obesity worldwide. Drugs and surgery are popular approaches to lose weight. Given their potential harm to the body, exercise is an alternative widely accepted approach. However, participation in high intensity exercise entails an inherent risk of sports-related injuries. In this study, a rat model fed with high fat diet was employed to investigate the effects of different intensity of exercise prescription on both weight loss and tissue injury after exercise and to find a proper exercise prescription for losing weight with minimal tissues injuries. We inferred that 3% weight bearing might be the proper exercise prescription for high fat diet-fed rats in our experimental setting. PMID:34239671 | PMC:PMC8255194 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

miR-27a acts as an oncogene to regulate endometrial cancer progression by targeting USP46

xlomafota13 shared this article with you from Inoreader miR-27a acts as an oncogene to regulate endometrial cancer progression by targeting USP46 Via International Journal of Clinical and Experimental Pathology Int J Clin Exp Pathol. 2021 Jun 15;14(6):720-725. eCollection 2021. ABSTRACT Endometrial cancer (EC) ranks as the fourth most common diagnosed cancer type in females worldwide. MicroRNAs (miRNAs) are important regulators with crucial roles in regulating diverse biologic processes, including tumor initiation and progression. Previous studies have demonstrated that miR-27a was correlated with the tumorigenesis of various cancers. However, its expression and biologic role in EC remain to be determined. This study aimed to clarify whether miR-27a acts as an oncogene in endometrial cancer (EC) by downregulating ubiquitin specific peptidase 46 (USP46). Expression of miR-27a was measured by qRT-PCR, and the results demonstrated that miR-27a was upregulated in EC cell lines compared to normal cell lines. Cell counting kit-8 (CCK-8) and wound-healing assays demonstrated that overexpression of miR-27a significantly promoted cell proliferation an d migration. Online prediction algorithm and dual luciferase activity reporter assay revealed that USP46 acts as a direct target of miR-27a. USP46 expression was downregulated in EC cell lines during miR-27a overexpression. Collectively, our results indicated that miR-27a targets USP46 to promote EC cell proliferation and migration, suggesting an oncogene role of miR-27a in EC. PMID:34239673 | PMC:PMC8255193 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Tracking bacterial DNA patterns in septic progression using 16s rRNA gene amplicon sequencing analysis

xlomafota13 shared this article with you from Inoreader Tracking bacterial DNA patterns in septic progression using 16s rRNA gene amplicon sequencing analysis Via International Journal of Clinical and Experimental Pathology Int J Clin Exp Pathol. 2021 Jun 15;14(6):753-767. eCollection 2021. ABSTRACT Bloodstream infections remain prevalent in intensive care units, leading to a public health challenge worldwide. Routine diagnosis is mainly based on blood culture, but the technique is limited by its time-consuming process and relatively low sensitivity. Emerging molecular diagnostic tools, such as 16S metagenomics, have been developed for detecting bacteria in the blood samples of septic patients. Using a collection of 168 blood samples from 96 septic patients, 16S metagenomics method followed by bioinformatics were applied to study bacterial alterations during the pathogenesis of sepsis. Significant taxonomic variations were found between the two survival groups at different therapeutic time points through sequential 16S metagenomics research. The results on the third day during the treatment course were notably distinct among the studied groups. 16S metage nomics approach can bring novel genetic insight about microbiological fluctuations during septic progression, which may be utilized as a complementary prognostic application. Further etiologic and pathophysiologic explorations are needed to fully explain the linkage between clinical outcomes and genetic changes. PMID:34239678 | PMC:PMC8255196 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

In vitro fertilization is associated with placental accelerated villous maturation

xlomafota13 shared this article with you from Inoreader In vitro fertilization is associated with placental accelerated villous maturation Via International Journal of Clinical and Experimental Pathology Int J Clin Exp Pathol. 2021 Jun 15;14(6):734-740. eCollection 2021. ABSTRACT OBJECTIVE: Accelerated placental maturation is regarded as a sign of vascular malperfusion and is often interpreted as a compensatory response by the placenta. In vitro embryo culture affects placental development. This study assessed placental maturation in spontaneous conceived and in vitro conceived pregnancies. METHODS: Retrospective cohort study on a single center between 2014 and 2017. For this study, preterm placentas of singleton pregnancies between 24 and 36 weeks were considered. Routine placental examinations were retrospectively reviewed. RESULTS: During the considered period, 423 placentas of singleton pregnancies were assessed. Three hundred ninety-six placentas were from spontaneous conception and 20 from in vitro fertilization and embryo transfer (IVF/ET). IVF/ET was significantly associated with accelerated villous maturation (AVM) and distal villous hypoplasia (DVH) (P<0.05). CONCLUSIONS: Placental AVM and DVH were significantly associated with in vitro fertilization in singleton pregnancies. This result supports the hypothesis that AVM is a compensatory response by the placenta to improve its transport capacity in specific settings such as in vitro fertilization. PMID:34239675 | PMC:PMC8255202 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A new flexible pressure sensor contributes to the early diagnosis of acute compartment syndrome

xlomafota13 shared this article with you from Inoreader A new flexible pressure sensor contributes to the early diagnosis of acute compartment syndrome Via International Journal of Clinical and Experimental Pathology Int J Clin Exp Pathol. 2021 Jun 15;14(6):768-775. eCollection 2021. ABSTRACT Acute compartment syndrome (ACS) is a surgical emergency, caused by the sharp increase of interstitial pressure within a closed osteofascial compartment, which can impair local circulation and functions. A non-invasive sensor is needed of satisfactory sensitivity to continuously monitor the alterations of the ACS pressure, which could be used as a supplementary means in the early diagnosis of ACS. A prepared "pasting-type" flexible pressure sensor was used to establish an extracorporeal pig-skin model with a soft-tissue expander device to simulate compartment syndrome conditions. An acrylic panel was inserted into the pig skin, allowing the soft-tissue expander to expand in one direction, which is similar to the movements of a patient's bones in real life. The touch spot of the flexible pressure sensor was attached to the rind by medical tape, to record the in ternal and external pressure data. Relationships between the internal and external pressures at different thickness (0.87 mm, 3.53 mm and 3.97 mm), as well as that of the 3.97 mm thickness under various initial internal pressures (0.5 mmHg, 25 mmHg and 44 mmHg) were measured. Significant differences were observed in the range of internal pressures at various pig-skin thickness. After adding the acrylic panel, the measured ranges were significantly increased, with the lowest measurable internal pressure being 5 mmHg. Moreover, alterations in external pressure were also greater than in models without acrylic panels. The external pressure measured by the sensor was able to reflect an increase in intra-organizational pressure. This may be a new non-invasive and sustainable method for early diagnosis of ACS. PMID:34239679 | PMC:PMC8255205 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Pelvic cavity malignant solitary fibrous tumor with dedifferentiation and multifocal cytokeratin expression

xlomafota13 shared this article with you from Inoreader Pelvic cavity malignant solitary fibrous tumor with dedifferentiation and multifocal cytokeratin expression Via International Journal of Clinical and Experimental Pathology Int J Clin Exp Pathol. 2021 Jun 15;14(6):746-752. eCollection 2021. ABSTRACT Pelvic cavity small-sized malignant solitary fibrous tumors are rare. Surgeons easily misjudge these tumors as benign lesions, and they are usually resected by laparoscopic surgery. When accompanied by dedifferentiation, malignant solitary fibrous tumors are difficult to diagnose by pathologists. Here, we describe a challenging case. A 47-year-old man was accidentally found to have a pelvic mass after three months. Surgeons assumed a diagnosis of a benign tumor according to the Computed Tomography and Ultrasonography reports. The patient underwent laparoscopic surgery to resect the tumor. After the operation, the patient was diagnosed as having a malignant solitary fibrous tumor with dedifferentiation. The patient had a recurrence one year later. This pelvic cavity malignant solitary fibrous tumor was a rare case because of its dedifferentiation and cytokerati n expression. The expression of cytokeratin and the absence of vimentin and CD34 were pitfalls to diagnosis. In this case, there was still a high amount of malignancy despite the small size of the tumor. Clinical image and pathologic multidisciplinary analysis and core needle biopsies before surgery had a great effect on diagnosis and therapy of this disease. The case is a cautionary tale not only for pathologists but also for surgeons. PMID:34239677 | PMC:PMC8255199 < /div> View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.