Cofilin-1 as a potential biomarker for Mycobacterium tuberculosis infection

xlomafota13 shared this article with you from Inoreader Cofilin-1 as a potential biomarker for <em>Mycobacterium tuberculosis</em> infection Via Experimental and therapeutic medicine Exp Ther Med. 2022 Apr;23(4):253. doi: 10.3892/etm.2022.11178. Epub 2022 Feb 1. ABSTRACT Tuberculosis (TB) induced by Mycobacterium tuberculosis (M. tb), is one of the deadliest human infections worldwide. Our previous studies demonstrated cofilin-1 (CFL1) expression was significantly increased in exosomes from Mycobacterium avium (M. avium)-infected macrophages. The expression of CFL1 protein in M. tb infected hosts was investigated in the present study to predict whether CFL1 could have potential as a biomarker for M. tb infection. In the present study, the mRNA and protein expression levels of CFL1 in M. avium-infected macrophages and supernatants were analyzed via reverse transcription-quantitative PCR and western blotting. Furthermore, CFL1 expression in macrophages was knocked down in vivo, and then CFL1 expression levels in M. avium-infected macrophages and supernata nt were detected via western blotting and ELISA. In addition, CFL1 was detected in the peripheral blood mononuclear cells and plasma of patients with TB using western blotting and ELISA. The specificity and sensitivity of CFL1 as a biomarker and the association between TB infection and normal individuals were compared and analyzed using GraphPad Prism 5. CFL1 protein expression levels were significantly increased in M. avium-infected macrophages and supernatant. Meanwhile, CFL1 was upregulated in patients with TB. Bioinformatics statistics indicated the high specificity and sensitivity of CFL1 in patients with TB. Thus, these results suggest that CFL1 may act as a potential biomarker of TB infection. PMID:35261625 | PMC :PMC8855514 | DOI:10.3892/etm.2022.11178 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

PBX4 functions as a potential novel oncopromoter in colorectal cancer: a comprehensive analysis of the PBX gene family

xlomafota13 shared this article with you from Inoreader PBX4 functions as a potential novel oncopromoter in colorectal cancer: a comprehensive analysis of the PBX gene family Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):585-600. eCollection 2022. ABSTRACT Pre-B-cell leukaemia (PBX) is a transcription factor family (PBX1, PBX2, PBX3 and PBX4) that regulates important cellular functions and has been identified to be involved in human cancers. This study aimed to explore the expression of PBX genes and their clinical significance in colorectal cancer (CRC). We analysed the differential expression of PBX genes in CRC vs. normal tissue, using the Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/) and ONCOMINE platform (https://www.oncomine.org/). The UALCAN (http://ualcan.path.uab.edu/) interactive OMICS web-server was used to evaluate the epigenetic regulation of PBX genes via their promoter methylation status. We found that only PBX4 was upregulated whereas PBX1 and PBX3 were downregulated (644 tumour vs. 51 normal samples) (P<0.001). The methylation st atus of PBX4 promoter appeared to be decreased (P=1.4e-07) whereas the methylation status of PBX1 and PBX3 promoters was increased (P=3.8e-04 and P=3.2e-07, respectively) in cancer vs. normal samples. To determine the prognostic value of PBXs, we conducted a Kaplan-Meier survival analysis and multivariable COX regression. We observed that high PBX4 expression was associated with increased risk for a worse overall survival (OS) in the TCGA CRC patient cohort (n=639), (HR 1.46, 95% CI 1.14-1.88, P=0.003) adjusted for age, gender, tumour location and metastases. We conducted in vitro gene expression modulation experiments to investigate the impact of PBX4 overexpression in CRC cell (HCT116) growth. Additionally, we evaluated the RNA expression of epithelial-mesenchymal transition (EMT) and angiogenesis markers. In vitro studies showed that PBX4 overexpression increased CRC cell proliferation (P<0.001) and upregulated the expres sion of EMT markers VIM, CDH1, CDH2, ZEB1, SNAI1 (P<0.05) and angiomarker VEGFA (P<0.0001). Lastly, through the Cistrome data browser (http://dbtoolkit.cistrome.org/) we investigated putative transcriptional regulators and we performed gene set enrichment analysis in Enrichr server (https://maayanlab.cloud/Enrichr/) to identify related biological processes. Nineteen factors were identified to be putative regulators of PBX4 and gene set enrichment analysis showed that biological processes related to cell cycle and cell proliferation were enriched (GO:0051726: CDK8, JUN, JUND, and IRF1, P=0.001). In conclusion, our study identified PBX4 as a potential novel oncopromoter in CRC and its overexpression was found to be associated with increased risk for worse survival rate. PMID:35261789 | PMC:PMC8899996 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Recombinant cell-detecting RaDR-GFP in mice reveals an association between genomic instability and radiation-induced-thymic lymphoma

xlomafota13 shared this article with you from Inoreader Recombinant cell-detecting RaDR-GFP in mice reveals an association between genomic instability and radiation-induced-thymic lymphoma Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):562-573. eCollection 2022. ABSTRACT In this study, we aimed to investigate how homologous recombinant (HR)-related genomic instability is involved in ionizing radiation (IR)-induced thymic lymphoma in mice. We divided five-week-old Rosa26 Direct Repeat-GFP (RaDR-GFP) transgenic mice into non-IR control and IR groups and exposed the mice in the IR group to a 7.2 Gy dose of γ-rays, delivered in 1.8 Gy fractions, once a week for four weeks. We then estimated mouse survival and recorded their body, thymus, and spleen weights. The frequency of HR events in the chromosomes of the thymus, bone marrow, and spleen cells and the phenotype of thymic lymphoma cells were analyzed using fluorescence-activated cell sorting (FACS). We found that most mice in the IR group developed thymic lymphoma, their survival rate decreasing to 20% after 180 days of IR exposure, whereas no mice died in the non-IR control group un til day 400. The thymus and spleen weighed significantly more in the IR-4-month group than that in the non-IR group; however, we observed no significant differences between the body weights of the control and IR mice. FACS analysis indicated that the frequency of HR events significantly increased at two and four months after the last IR dose in the bone marrow and thymus cells, but not in the spleen cells of RaDR-GFP transgenic mice, suggesting that recombinant cells accumulated in the thymus upon IR exposure. This suggests that IR induces genome instability, revealed as increased HR, that drives the development of thymic lymphoma. Additionally, phenotypic analysis of lymphoma cells showed an increase in the CD4-/CD8+ (CD8SP) cell population and a decrease in the CD4+/CD8- (CD4SP) cell population in the IR-4-month group compared to that in the non-IR group, indicating that IR induces an aberrant cell phenotype characteristic of lymphoma. I n conclusion, we observed a significant increase in HR events and abnormal phenotype in thymic lymphoma cells at two and four months after IR exposure in both the thymus and bone marrow tissues, suggesting that genomic instability is involved in the early stages of thymic lymphomagenesis. Our study indicates that HR-visualizing RaDR-GFP transgenic mice can help explore the links between the molecular mechanisms of genome instability and IR-induced tumorigenesis. PMID:35261787 | PMC:PMC8899999 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The expression of cancer-testis antigen in ovarian cancer and the development of immunotherapy

xlomafota13 shared this article with you from Inoreader The expression of cancer-testis antigen in ovarian cancer and the development of immunotherapy Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):681-694. eCollection 2022. ABSTRACT Ovarian cancer is a relatively common tumor in women with the highest mortality among female reproductive system tumors. The lack of apparent early symptoms and effective screening strategies often leads to ovarian cancer being diagnosed at an advanced stage. Immunotherapy relying on tumor-associated antigens might improve the treatment of ovarian cancer. Cancer-testis antigens (CTAs) are ideal tumor-associated antigens, and MAGE-A, NY-ESO-1, CT45, and Sp17 are classic CTAs highly expressed in ovarian cancer. Here, we review the research on CTAs in ovarian cancer, including prognostic value and advances in immunotherapy, all of which are essential for developing a theoretical basis for targeted therapy strategies. PMID:35261795 | PMC:PMC8899981 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Multimodality imaging in the assessment of bone marrow-derived mesenchymal stem cell therapy for doxorubicin-induced cardiomyopathy

xlomafota13 shared this article with you from Inoreader Multimodality imaging in the assessment of bone marrow-derived mesenchymal stem cell therapy for doxorubicin-induced cardiomyopathy Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):574-584. eCollection 2022. ABSTRACT Due to their broad-spectrum effects and high antitumor efficacies, anthracycline-based chemotherapies are commonly prescribed in various solid and hematological malignancies. Doxorubicin (DOX) is one of the most highly used anthracyclines but has been shown to cause lethal cardiomyopathy in clinical practice. Studies have demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs) have the ability to rescue DOX-induced cardiomyopathy (DIC). However, novel molecular imaging techniques are required to explore the biological behaviors, safety, eventual viability, and environmental interactions of transplanted stem cells during therapy. To investigate the biological behaviors of transplanted BMSCs, we applied bioluminescence imaging (BLI) and magnetic resonance imaging (MRI) techniques to trace firefly luciferase (Fluc) and ultrasmall superparamagnetic iron oxi de (USPIO) double-labeled mouse BMSCs after injection into the heart apex in a chronic DIC mouse model. Then, we determined the optimal BMSC number for transplantation into the heart and optimized MRI parameters to evaluate transplanted BMSCs in vitro and in vivo. Our results showed that the BLI trace signal could last 7 days in the DIC mouse model, whereas the MRI signal lasted up to 3 days. However, MRI provided more detailed pathophysiological information on DIC than BLI, such as inflammation and fibrosis signs. The optimal in vivo cell number for BLI and MRI was determined to be 1×106. In conclusion, BLI combined with multimodality MRI could be used to monitor the biological behavior of BMSCs transplanted into a chronic DIC mouse model in a visual and dynamic manner. PMID:35261788 | PMC:PMC8899982 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Trastuzumab in combination with PEGylated interferon-α1b exerts synergistic antitumor activity through enhanced inhibition of HER2 downstream signaling and antibody-dependent cellular cytotoxicity

xlomafota13 shared this article with you from Inoreader Trastuzumab in combination with PEGylated interferon-α1b exerts synergistic antitumor activity through enhanced inhibition of HER2 downstream signaling and antibody-dependent cellular cytotoxicity Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):549-561. eCollection 2022. ABSTRACT The anti-HER2 monoclonal antibody trastuzumab is the mainstay of treatment for HER2-positive breast and gastric cancer, and its combination with multiple chemotherapeutic agents has represented an effective and rational strategy in the clinic. In this study, we report that trastuzumab in combination with PEGylated interferon-α1b (IFN-α1b), a polyethylene glycol (PEG)-conjugated form of a subtype of interferon alpha (IFN-α), synergistically inhibited the proliferation of HER2-positive cells, including BT-474 and SK-BR-3 breast cancer cells and NCI-N87 gastric cancer cells, and also induced their apoptosis, but had no effect on HER2-negative MDA-MB-231 breast cancer cells. Trastuzumab inhibited phosphorylation of HER2, AKT and ERK, an effect that was enhanced by PEGylated IFN-α1b, likely owing to PEGylated IFN-α1b-mediated downregulation of HER2 through the lysos omal degradation pathway. Moreover, PEGylated IFN-α1b significantly enhanced trastuzumab-mediated antibody-dependent cellular cytotoxicity (ADCC) in HER2-positive cells. Importantly, trastuzumab combined with PEGylated IFN-α1b exhibited significant synergistic antitumor activity in HER2-positive BT-474 xenografts, an effect that was associated with enhanced inhibition of HER2 expression and AKT and ERK phosphorylation. Strikingly, depletion of natural killer cells with anti-Asialo GM1 antibody abrogated the synergistic antitumor activity, indicating that augmented ADCC is essential for this synergy. Taken together, our findings indicate that both enhanced inhibition of HER2 downstream signaling and augmented ADCC contribute to the synergistic antitumor activity of trastuzumab with PEGylated IFN-α1b, and imply that combining trastuzumab with PEGylated IFN-α1b could be a promising strategy for HER2-positive cancers. PMID:35261786 | PMC:PMC8899978 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Diagnostic and therapeutic biomarkers in colorectal cancer: a review

xlomafota13 shared this article with you from Inoreader Diagnostic and therapeutic biomarkers in colorectal cancer: a review Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):661-680. eCollection 2022. ABSTRACT Colorectal cancer (CRC) is a public health concern and the second most common type of cancer among men and women causing a significant mortality. Biomarkers closely linked to the disease morbidity could holds potential as diagnostic and/or prognostic biomarker for the disease. This review provides an overview of recent advances in the search for colorectal cancer biomarkers through genomics and proteomics according to clinical function and application. Specifically, a number of biomarkers were identified and discussed. Emphasis was placed on their clinical applications relative to the diagnosis and prognosis of CRC. The discovery of more sensitive and specific markers for CRC is an urgent need, and the study of molecular targets is extremely important in this process, as they will allow for a better understanding of colorectal carcinogenesis, identification and vali dation of potential genetic signatures. PMID:35261794 | PMC:PMC8900002 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Outcomes and recurrence patterns following curative hepatectomy for hepatocellular carcinoma patients with different China liver cancer staging

xlomafota13 shared this article with you from Inoreader Outcomes and recurrence patterns following curative hepatectomy for hepatocellular carcinoma patients with different China liver cancer staging Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):907-921. eCollection 2022. ABSTRACT This study aimed to investigate outcomes and recurrence patterns after hepatectomy for hepatocellular carcinoma (HCC) patients with different China Liver Cancer staging (CNLC), and then analyze the risk factors of different recurrence patterns. A total of 731 HCC patients undergoing curative resection were reviewed from 6 independent institutions. Data on preoperative and clinicopathological parameters, operation and tumor recurrence information, recurrence management and long-term outcomes were analyzed. Our results showed that 1-, 3-, and 5-year OS rate for Ia was 96.6%, 88.5%, and 77.4%, while 1-, 3-, and 5-year of Ib was 84.2%, 65.5%, and 51.3%, respectively. Compared to Ia, the patients in IIa and IIb staging had poorer 1-, 3-, and 5-year OS and DFS. Furthermore, the 1-, 3-, and 5-year OS rate in IIIa was 59.3%, 37.3%, and 27.7%, while the 1-, 3-, and 5-year OS of IIIb was 25.6%, 12.8%, and 0%, respectively. The mostly site of recurrence after liver surgery was intrahepatic recurrence (CNLC Ia: 89.4%; Ib: 65.9%; IIa: 68.9%; IIb: 91.7%; IIIa: 63.8%). However, the CNLC IIIb patients have higher percentage of extrahepatic recurrence (56.5%). The main recurrence pattern of time course was late recurrence in CNLC Ia patients (61.1%). However, the rate of early recurrence in Ib, IIa, IIb, IIIa, IIIb patients was 69.0%, 62.2%, 62.5%, 78.3% and 95.7% respectively. In conclusion, the outcomes and recurrence patterns of HCC patients after resection vary with different CNLC staging, which defined the prognosis of patients with HCC after resection. The HCC patients with CNLC IIIa can also benefit from liver resection. The CNLC staging could be considered in forming management strategies, treatment choice and surveillance for HCC patients. PMID:35261811 | PMC:PMC8899998 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Significant association between serum Wisteria floribunda agglutinin-positive Mac-2-binding protein and prognosis of hepatocellular carcinoma after surgical treatment

xlomafota13 shared this article with you from Inoreader Significant association between serum Wisteria floribunda agglutinin-positive Mac-2-binding protein and prognosis of hepatocellular carcinoma after surgical treatment Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):601-614. eCollection 2022. ABSTRACT Serum Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP) is a novel marker for evaluating fibrosis and predicting the development of hepatocellular carcinoma (HCC). However, the role of WFA+-M2BP in the prognosis of HCC patients after curative surgery remains unknown. In this study, we aimed to evaluate the prognostic role of serum WFA+-M2BP in HCC patients after curative resection and liver transplantation. We enrolled 460 HCC patients (357 resection and 103 transplantation) to analyze the risk factors for HCC recurrence and patient's survival. We employed time-to-event models using univariate and multivariable Cox proportional hazards regression analyses and calculated the hazard ratios (HRs) and adjusted HRs with their corresponding 95% confidence intervals (CIs). The levels of WFA+-M2BP were 0.19 -14.51 COI (median 1.08) in patients of hepatectomy and 0.47-19.90 COI (median 6.0) in transplant patients. The levels of WFA+-M2BP in liver transplant patients is much higher than that of hepatectomy patients. Overall, liver fibrotic stage was positively correlated to WFA+-M2BP levels (P<0.0001). This study demonstrated that elevated WFA+-M2BP level (COI ≥0.75) was associated with a higher HCC recurrence rate in the resection group (P<0.001). Survival analysis showed that an elevated WFA+-M2BP level (COI ≥1.43) is associated with a higher mortality risk after surgical resection (P=0.0088) in the univariate analysis only. In liver transplant patients, WFA+-M2BP level (COI ≥3.81) did not predict HCC recurrence at all, but was associated poor survival after transplantation, with a borderline significance (P=0.0943). Serum WFA+-M2BP is a reliable marker for liver fibrosis in the present study. It is also reli able marker to predict prognosis of HCC after surgical resection. However, the prognostic role of WFA+-M2BP in HCC related transplants is equivocal, which is different from that of surgical resection. PMID:35261790 | PMC:PMC8899980 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Entwicklung auditiver Verarbeitungs- und Wahrnehmungsleistungen mit und ohne AVWS im Grundschulalter

xlomafota13 shared this article with you from Inoreader Entwicklung auditiver Verarbeitungs- und Wahrnehmungsleistungen mit und ohne AVWS im Grundschulalter Via Sprache · Stimme · Gehör Sprache · Stimme · Gehör 2022; 46: 44-50 DOI: 10.1055/a-1745-7502 Hintergrund Ob sich die an unauffälligen Kindern beschriebenen Reifungsprozesse des zentralen Hörsystems auch an Kindern mit auditiven Verarbeitungs- und Wahrnehmungsstörungen (AVWS) im Grundschulalter nachweisen lassen, sollte an 2 Schülerjahrgängen (1. und 4. Klasse) im Kontrollgruppenvergleich untersucht werden. Material und Methoden In die Auswertung gingen 7 Testergebnisse von 82 Erstklässlern (40 mit AVWS; 42 unauffällige Kinder) und 65 Viertklässlern (35 mit AVWS; 30 unauffällige Kinder) ein. Es wurde eine ANOVA mit dem Gesamtsummenwert aus folgenden 7 Untersuchungen sowie anschließend eine MANOVA mit den Einzeltestergebnissen durchgeführt: Göttinger Sprachaudiometrie II im Störgeräusch; dichotisches Wortpaarverstehen (Uttenweiler-Test); Phonemdifferenzierung, Phonemidentifikation, Phonemanalyse (Subtests aus Heidelberger Lautdifferenzierungstest); Zahlenfolgen-Gedächtnis (Subtest aus psycholinguistischem Entwicklungstest); Mottier-Test. Ergebnisse Die ANOVA zeigte signifikante Haupteffekte von „Schuljahr" (p < 0,001; η² = 0,418) und „Gruppe" (p < 0,001; η² = 0,690), jedoch keine Interaktionseffekte zwischen beiden. Das Ergebnis der MANOVA war ähnlich bzgl. der o. g. Haupteffekte; nur für 2 Tests (Phonemidentifikation, Phonemanalyse) wurde die Interaktion der Faktoren Schuljahr und Gruppe mit jeweils geringen Effektstärken von 3 bzw. 6 % statistisch signifikant. Diskussion Gemäß dieser Querschnittsstudie scheint der Unterschied zwischen den beiden Gruppen unabhängig vom Schuljahr zu sein. Fazit Im Grundschulalter gibt es nicht nur für unauffällige Kinder, sondern auch für solche mit AVWS Hinweise auf eine Reifung des zentralen Hörsystems. [...] Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A Comprehensive Assessment of Blood Transfusions in Elective Thyroidectomy Based on 180,483 Patients

xlomafota13 shared this article with you from Inoreader A Comprehensive Assessment of Blood Transfusions in Elective Thyroidectomy Based on 180,483 Patients Via The Laryngoscope Objectives To assess the incidence, risk factors, and complications of blood transfusions (BTs) in elective thyroidectomy patients. Methods A retrospective cohort study was conducted using the American College of Surgeons National Surgical Quality Improvement Program. Adult patients who underwent elective thyroidectomy from 2005 to 2019 were divided into two cohorts based on whether they received BT or not. Multivariable binary logistic regression models were used to identify risk factors of BT and its impact on postoperative complications. Results Of 180,483 patients, 0.13% received BT. Risk factors for BT included underweight body mass index (BMI) (adjusted odds ratio [OR] 3.179, 95% confidence interval [CI] 1.444–6.996), bleeding disorders (OR 2.121, 95% CI 1.149–3.913), anemia (OR 4.730, 95% CI 3.472–6.445), preoperative transfusion (OR 7.230, 95% CI 1.454–35.946), American Society of Anesthesiology physical statuses 3–5 (OR 3.103, 95% CI 2.143–4.492), operative time >150 min (OR 4.390, 95% CI 1.996–9.654), and inpatient thyroidectomy (OR 5.791, 95% CI 3.816–8.787). In addition, transfusion was independently associated with any postoperative complication, non-infectious, cardiac, pulmonary, renal, vascular, or infectious complications, surgical site infection, sepsis, septic shock, wound disruption, pneumonia, unplanned reoperation, prolonged length of stay, and mortality. Conclusion Recognition of risk factors of BT is imperative to identify at-risk patients and reduce transfusions by controlling modifiable risk factors such as anemia, operative time, and BMI. In cases where transfusions are still indicated, surgeons should optimize care to prevent or adequately manage transfusion-associated complications. Level of evidence 3 Laryngoscope, 2022 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.