Role of protein phosphatase 2A in kidney disease (Review)

xlomafota13 shared this article with you from Inoreader Role of protein phosphatase 2A in kidney disease (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1236. doi: 10.3892/etm.2021.10671. Epub 2021 Aug 31. ABSTRACT Kidney disease affects millions of people worldwide and is a financial burden on the healthcare system. Protein phosphatase 2A (PP2A), which is involved in renal development and the function of ion-transport proteins, aquaporin-2 and podocytes, is likely to serve an important role in renal processes. PP2A is associated with the pathogenesis of a variety of different kidney diseases including podocyte injury, inflammation, tumors and chronic kidney disease. The current review aimed to discuss the structure and function of PP2A subunits in the context of kidney diseases. How dysregulation of PP2A in the kidneys causes podocyte death and the inactivation of PP2A in renal carcinoma tissues is discussed. Inhibition of PP2A activity prevents epithelial-mesenchymal transition and attenuates renal fibrosis, creating a favorable inflammatory microenvironm ent and promoting the initiation and progression of tumor pathogenesis. The current review also indicates that PP2A serves an important role in protection against renal inflammation. Understanding the detailed mechanisms of PP2A provides information that can be utilized in the design and application of novel therapeutics for the treatment and prevention of renal diseases. PMID:34539832 | PMC:PMC8438693 | DOI:10.3892/etm.2021.10671 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Salidroside inhibits chronic myeloid leukemia cell proliferation and induces apoptosis by regulating the miR-140-5p/wnt5a/β-catenin axis

xlomafota13 shared this article with you from Inoreader Salidroside inhibits chronic myeloid leukemia cell proliferation and induces apoptosis by regulating the miR-140-5p/wnt5a/β-catenin axis Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1249. doi: 10.3892/etm.2021.10684. Epub 2021 Sep 2. ABSTRACT Salidroside, an active ingredient of Rhodiola rosea, exhibits antitumor effects in various types of cancer. However, the role of salidroside in chronic myeloid leukemia (CML) has not been elucidated. In the presents study, cell viability was assessed by CCK-8 assay, while apoptosis was detected by flow cytometry. Reverse transcription-quantitative PCR analysis was used to examine the expression levels of miR-140-5p in human CML cell lines. The expression levels of apoptosis and cell cycle-associated proteins and of the wnt5a/β-catenin signaling pathway were determined by western blot analysis. Bioinformatic analysis and luciferase reporter assays were employed to investigate the association between miR-140-5p and wnt5a. The results revealed that exposure of CML cells to salidroside (80 µM) inhibited cell proliferation and promoted apoptos is. In addition, salidroside treatment led to the upregulation of miR-140-5p expression. Furthermore, the inhibition of wnt5a/β-catenin signaling pathway and the pro-apoptotic effects induced by salidroside were attenuated by miR-140-5p silencing. Notably, wnt5a was revealed to be a direct target of miR-140-5p. The present findings indicated that salidroside exerted anti-CML effects through regulating miR-140-5p by suppressing the wnt5a/β-catenin signaling pathway. The present study provided evidence of the therapeutic role of salidroside in CML. PMID:34539845 | PMC:PMC8438695 | DOI:10.3892/etm.2021.10684 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Geniposide protects pulmonary arterial smooth muscle cells from lipopolysaccharide-induced injury via α7nAchR-mediated TLR-4/MyD88 signaling

xlomafota13 shared this article with you from Inoreader Geniposide protects pulmonary arterial smooth muscle cells from lipopolysaccharide-induced injury via α7nAchR-mediated TLR-4/MyD88 signaling Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1234. doi: 10.3892/etm.2021.10668. Epub 2021 Aug 31. ABSTRACT Geniposide is a bioactive iridoid glucoside derived from Gardenia jasminoides that has proven anti-inflammatory effects against acute lung injury. The aim of this study was to determine whether geniposide could protect pulmonary arterial smooth muscle cells (PASMCs) from lipopolysaccharide (LPS)-induced injury and to explore the participation of α7 nicotinic acetylcholine receptor (α7nAChR), which was previously reported to suppress pro-inflammatory cytokine production in LPS-stimulated macrophages. In the present study, rat PASMCs were isolated and stimulated using LPS. The effect of geniposide on LPS-induced PASMC injury was then explored. Geniposide exerted anti-apoptotic and anti-inflammatory effects on LPS-treated PASMCs, as demonstrated by the downregulation of pro-apoptotic proteins and pro-inflammatory cytokines, respectively. Fu rthermore, the α7nAChR agonist PNU282987 accentuated the protective effect of geniposide against LPS-induced injury in PASMCs by inhibiting toll-like receptor-4/myeloid differentiation primary response 88 (TLR-4/MyD88) signaling and downregulating nuclear factor (NF)-κB expression. Conversely, methyllycaconitine, an inhibitor of α7nAChR, attenuated the effects of geniposide. These findings collectively suggested that in conjunction with geniposide, the activation of α7nAChR may contribute to further mitigating LPS-induced PASMC apoptosis and inflammation. In addition, the underlying mechanisms critically involve the NF-κB/MyD88 signaling axis. These results may provide novel insights into the treatment and management of lung diseases via geniposide administration. PMID:34539830 | PMC:PMC8438699 | DOI:10.3892/etm.2021.10668 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Role of miR-139-5p in ectopic endometrial stromal cells and the underlying molecular mechanism

xlomafota13 shared this article with you from Inoreader Role of miR-139-5p in ectopic endometrial stromal cells and the underlying molecular mechanism Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1251. doi: 10.3892/etm.2021.10686. Epub 2021 Sep 2. ABSTRACT Endometriosis is an estrogen-dependent disease. Studies have shown that miR-139-5p is significantly upregulated in endometriosis lesions, but its specific role and molecule mechanism in endometriosis has not yet been reported. The malignant biological behavior of ectopic endometrial stromal cells (ESCs) is similar to that of malignant cancer cells. BBC3 (BCL2 binding component 3) is a known apoptosis inducer and it serves key roles in the regulation of cell behavior. However, the role of BBC3 in ectopic ESCs remains unknown. The present study aimed to investigate the role of miR-139-5p in the progression of endometriosis and to determine its underlying molecular mechanism of action. Ectopic, non-ectopic and normal endometrial stromal cells (ESCs) were extracted from endometrial samples, and reverse transcription-quantitative PCR was performed to d etermine microRNA (miR)-139-5p and Bcl-2 binding component 3 (BBC3) mRNA expression levels in endometrial tissue samples and ESCs. The target gene of miR-139-5p was predicted using TargetScan software and verified using a dual luciferase reporter assay. Western blotting was performed to determine BBC3 protein expression levels. Flow cytometry analysis, and MTT and Transwell assays were performed to assess cell apoptosis, viability, and migration and invasion of the cells transfected with inhibitor control, miR-139-5p inhibitor, miR-139-5p inhibitor + control-small interfering (si)RNA or miR-139-5p inhibitor + BBC3-siRNA, respectively. The results demonstrated that miR-139-5p expression levels were upregulated in ectopic endometrial samples and ESCs compared with the respective control groups. Furthermore, it was verified that BBC3 was a direct target of miR-139-5p, and both BBC3 mRNA and protein expression levels were downregulated in ectopic endometrial samples and ESCs. Both trans fection with the miR-139-5p inhibitor and BBC3-small interfering (si)RNA markedly downregulated miR-139-5p and BBC3 expression levels in ectopic ESCs, respectively. miR-139-5p inhibitor-induced upregulated BBC3 expression was reversed following transfection with BBC3-siRNA. Furthermore, the miR-139-5p inhibitor significantly decreased viability, migration and invasion, while inducing apoptosis in ectopic ESCs compared with the inhibitor control group. Notably, the aforementioned effects were reversed by knocking down BBC3 expression. In conclusion, the results of the present study suggested that miR-139-5p may play a key role in the progression of endometriosis by regulating the viability of ESCs and directly targeting BBC3. PMID:34539847 | PMC:PMC8438670 | DOI:10.3892/etm.2021.10686 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Moxibustion improves ovarian function based on the regulation of the androgen balance

xlomafota13 shared this article with you from Inoreader Moxibustion improves ovarian function based on the regulation of the androgen balance Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1230. doi: 10.3892/etm.2021.10664. Epub 2021 Aug 30. ABSTRACT The effect of androgens on follicular development and female reproduction has become an active research topic. Moxibustion is a Traditional Chinese Medicine therapy that has been reported to be able to prevent and treat numerous ovary-related problems. However, studies on the effect of moxibustion for diminished ovarian reserve (DOR) on androgen balance are still lacking. The present study aimed to assess the efficacy of moxibustion intervention prior to disease onset and at the early stage of disease in a rat model of DOR and explore the mechanisms of its effect on ovarian function. A total of 32 rats were randomly divided into four groups: Blank group, Model group (a drug-induced model of DOR), Moxibustion group 1 and Moxibustion group 2. Moxibustion was performed on the BL23 and RN4 acupoints of female rats daily for a total of 20 days (once a day, five times a week for a total of 4 weeks). The two moxibustion groups were established with different intervention times: One group was subjected to pre-disease intervention and the other group to early-disease intervention. The ovarian function was evaluated by detecting anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), estradiol (E2), testosterone (T), dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT) and androgen receptor (AR) levels in the serum or the ovary samples. To further investigate the downstream regulatory factors for AR after moxibustion treatment for pre-disease or early-disease intervention, FSH receptor (FSHR) and microRNA (miR)-125b expression in ovaries were also analyzed. The results indicated that AMH and DHT levels were reduced in the model group compared with those in the blank group, while FSH, T and DHEA levels were increased. AMH and DHT levels were increased in Moxibustion group 1 compared with those in the model group, while F SH, T and DHEA levels were reduced. There was no difference in E2 levels between Moxibustion group 1 and the model group. Compared with that in the model group, the AR content in the ovary was increased in Moxibustion group 1. There was no difference in FSHR mRNA in the ovaries between Moxibustion group 1 and the model group. miR-125b levels were significantly increased in Moxibustion group 1 as compared with those in the model group. Furthermore, AMH and DHT levels were increased in Moxibustion group 2 compared with those in the model group, while FSH, T and DHEA levels were reduced. E2 levels were significantly decreased in Moxibustion group 2 compared with those in the model group. The relative mRNA expression of AR, FSHR and miR-125b was decreased following establishment of the model. Compared with that in the model group, the AR content in the ovary was increased in Moxibustion group 2. In comparison with the blank and model groups, the FSHR content in the ovary of Moxibustion group 2 was significantly increased. miR-125b levels were not obviously altered in Moxibustion group 2 as compared with those in the model group. In addition, there was no significant difference in AMH, FSH, T and DHEA levels between the two moxibustion groups. E2 and DHT levels were higher in Moxibustion group 1 than in Moxibustion group 2. There was no difference in AR mRNA expression between the two moxibustion groups. FSHR mRNA levels were lower in Moxibustion group 1 than in Moxibustion group 2, while miR-125b mRNA levels were higher in Moxibustion group 1 than in Moxibustion group 2. In conclusion, the present study suggested that moxibustion intervention prior to disease onset and at the early disease stage was able to improve ovarian function via modulation of the AR-mediated stable equilibrium of androgens. However, the effects and mechanisms of moxibustion intervention for pre-disease and early-disease intervention of DOR appear to be different. The appropriate duration of treatment and the time-effect relationship require to be further studied. PMID:34539826 | PMC:PMC8438671 | DOI:10.3892/etm.2021.10664 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Incidence of Thyroid Dysfunction Facing Metabolic Syndrome: A Prospective Comparative Study with 9 Years of Follow-Up

xlomafota13 shared this article with you from Inoreader Incidence of Thyroid Dysfunction Facing Metabolic Syndrome: A Prospective Comparative Study with 9 Years of Follow-Up Via radioactive iodine Eur Thyroid J. 2021 Jul;10(5):390-398. doi: 10.1159/000512665. Epub 2021 Jan 27. ABSTRACT BACKGROUND: Studies assessing thyroid hormones in metabolic syndrome (MetS) patients are contradictory. Also, the effect of MetS on thyroid function over time is not yet evaluated. This study investigated the prevalence and incidence of thyroid dysfunction (TD) as well as time trends of thyroid hormones in subjects with and without MetS, during a 10-year follow-up in Tehranian adult population . METHODS: This is a prospective cohort study conducted in the framework of Tehran Thyroid Study on 5,786 subjects aged ≥20 years: 4,905 eligible participants entered the study after excluding those with corticosteroid or radioactive iodine use, pregnancy, thyrotropin (TSH) <0.1 and >10 mU/L, and missing data. Physical examinations were performed and serum concentrations of TSH, free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), fasting plasma glucose, insulin, and lipid profile were assessed at baseline and 3-year intervals during the follow-up. MetS was defined according to the Joint Interim Statement Definition. RESULTS: At baseline, there were no difference in median serum concentrations of FT4 and TSH between MetS and non-MetS group after adjusting for age, sex, BMI, smoking, and TPOAb positivity. Although there was higher risk of overt (42%) and subclinical hypothyroidism (16%) in MetS compared with non-MetS subjects, no significant difference was o bserved in adjusted ORs for any TD between 2 groups. There were also no significant differences in time trends of TSH, FT4, TPOAb positivity, and incidence rates of TDs between MetS and non-MetS groups during 10 years, after adjustment for age, sex, BMI, smoking status, and TPOAb positivity. CONCLUSION: MetS is not associated with thyroid hypofunction considering other important confounders such as age, sex, smoking, BMI, and TPOAb positivity. There is also no difference in the trend of thyroid hormones and incidence of TD between MetS and non-MetS subjects during a 10-year follow-up. PMID:34540709 | PMC:PMC8406240 | DOI:10.1159/000512665 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Intratumor Epigenetic Heterogeneity-A Panel Gene Methylation Study in Thyroid Cancer

xlomafota13 shared this article with you from Inoreader Intratumor Epigenetic Heterogeneity-A Panel Gene Methylation Study in Thyroid Cancer Via radioactive iodine Front Genet. 2021 Sep 3;12:714071. doi: 10.3389/fgene.2021.714071. eCollection 2021. ABSTRACT BACKGROUND: Thyroid cancer (TC) is the most common endocrine malignancy, and the incidence is increasing very fast. Surgical resection and radioactive iodine ablation are major therapeutic methods, however, around 10% of differentiated thyroid cancer and all anaplastic thyroid carcinoma (ATC) are failed. Comprehensive understanding the molecular mechanisms may provide new therapeutic strat egies for thyroid cancer. Even though genetic heterogeneity is rigorously studied in various cancers, epigenetic heterogeneity in human cancer remains unclear. METHODS: A total of 405 surgical resected thyroid cancer samples were employed (three spatially isolated specimens were obtained from different regions of the same tumor). Twenty-four genes were selected for methylation screening, and frequently methylated genes in thyroid cancer were used for further validation. Methylation specific PCR (MSP) approach was employed to detect the gene promoter region methylation. RESULTS: Five genes (AP2, CDH1, DACT2, HIN1, and RASSF1A) are found frequently methylated (>30%) in thyroid cancer. The five genes panel is used for further epigenetic heterogeneity analysis. AP2 methylation is associated with gender (P < 0.05), DACT2 methylation is associated with age, gender and tumor size (all P < 0.05), HIN1 methyl ation is associated to tumor size (P < 0.05) and extra-thyroidal extension (P < 0.01). RASSF1A methylation is associated with lymph node metastasis (P < 0.01). For heterogeneity analysis, AP2 methylation heterogeneity is associated with tumor size (P < 0.01), CDH1 methylation heterogeneity is associated with lymph node metastasis (P < 0.05), DACT2 methylation heterogeneity is associated with tumor size (P < 0.01), HIN1 methylation heterogeneity is associated with tumor size and extra-thyroidal extension (all P < 0.01). The multivariable analysis suggested that the risk of lymph node metastasis is 2.5 times in CDH1 heterogeneous methylation group (OR = 2.512, 95% CI 1.135, 5.557, P = 0.023). The risk of extra-thyroidal extension is almost 3 times in HIN1 heterogeneous methylation group (OR = 2.607, 95% CI 1.138, 5.971, P = 0.023). CONCLUSION: Five of twenty-four genes were found frequently methylated in human thyroid cancer. Based on 5 genes panel analysis, epigenetic heterogeneity is an universal event. Epigenetic heterogeneity is associated with cancer development and progression. PMID:34539742 | PMC:PMC8446600 | DOI:10.3389/fgene.2021.714071 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Bilateral vocal cord paralysis caused by accidental button battery ingestion in children: A case report and literature review

xlomafota13 shared this article with you from Inoreader Bilateral vocal cord paralysis caused by accidental button battery ingestion in children: A case report and literature review Via ear nose throat Ear Nose Throat J. 2021 Sep 19:1455613211043678. doi: 10.1177/01455613211043678. Online ahead of print. ABSTRACT Button battery ingestion in pediatric populations is a common occurrence with severe sequelae. Multiple case reports have established the occurrence of death, fistula formation, mucosal erosion, esophageal perforation, and bleeding post-ingestion of button batteries. However, there is a gap in the literature on the occurrence of bilateral vocal cord paralysis post -lithium battery ingestion. We present a case in which a 12-month-old male developed bilateral vocal cord paralysis following ingestion of a button battery. We compare our case to eleven other reports that exist in the literature based on age, sex, time until removal, clinical presentation, day upon which vocal cord paralysis developed, anatomic location, and post-operative course. We conclude that bilateral vocal cord paralysis is a time-sensitive complication which requires prompt diagnosis. Any child with stridor following button battery ingestion should undergo consultation with pediatric otolaryngology immediately. In addition, long-term follow-up is necessary to evaluate return of normal vocal cord function. PMID:34541933 | DOI:10.1177/01455613211043678 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A new approach using a numerical diagnostic criterion for vitiligo diagnosis with HMB-45 and Melan-A staining

xlomafota13 shared this article with you from Inoreader A new approach using a numerical diagnostic criterion for vitiligo diagnosis with HMB-45 and Melan-A staining Via International Journal of Clinical and Experimental Pathology Int J Clin Exp Pathol. 2021 Aug 15;14(8):902-907. eCollection 2021. ABSTRACT This study aims to investigate the usefulness of the Melan-A and homatropine methyl bromide-45 (HMB-45) markers in identifying melanocytes and to evaluate cut-off values for the diagnosis of vitiligo. We also aim to identify the role of remaining melanocytes when using HMB-45. We counted and confirmed melanocytes and melanin in the samples using a high-magnification microscope. The Melan-A, HMB-45, and Fontana-Masson staining methods were utilized. Descriptive statistical analysis of quantitative traits was performed. For the comparison of the two diagnostic tools, receiver operating characteristic curve and the area under the curve were evaluated. We found out that there was no significant difference observed between the two methods. The cut-off value is <27 for HMB-45 and <15 for Melan-A per 100 cells in the basal cell layer. Thus, HMB-45 is as useful as Melan-A in the diagnosis of vitiligo. PMID:34527133 | PMC:PMC8414431 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Molecular alterations differentiate microinvasive carcinoma from ductal carcinoma in situ and invasive breast carcinoma: retrospective analysis of a large single-center series

xlomafota13 shared this article with you from Inoreader Molecular alterations differentiate microinvasive carcinoma from ductal carcinoma in situ and invasive breast carcinoma: retrospective analysis of a large single-center series Via International Journal of Clinical and Experimental Pathology Int J Clin Exp Pathol. 2021 Aug 15;14(8):892-901. eCollection 2021. ABSTRACT Microinvasive carcinoma (MIC) of the breast is a rare lesion. The clinicopathologic features and biologic behavior of MIC are unclear. Whether MIC is a distinct entity or an interim stage in the progression from ductal carcinoma in situ (DCIS) to invasive breast carcinoma (IBC) remains to be determined. A retrospective review of clinicopathologic features and analysis of the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 in patients with MIC (90 cases), DCIS (268 cases) and IBC (1504 cases) was performed. Most MICs (93.3%) exhibited an intermediate to high nuclear grade, and this proportion was larger than that of DCIS (62.7%, P < 0.001) or IBC (85.4%, P = 0.036). The incidence of sentinel lymph node metastasis in MIC (12.5%) was higher than that of DCIS (1.6%, P < 0.001), but much lower than that of IBC (39.7%, P < 0.001). MICs had higher expression of HER-2 and lower expression of ER and PR compared to DCIS and IBC; and MIC was more likely to present with a HER-2+ subtype. Furthermore, DCIS exhibited greater HER-2 overexpression or gene amplification (P < 0.001) levels and lower proliferation index of Ki-67 (P < 0.001) compared to IBC. Our results suggest that the clinicopathologic and molecular phenotype of MIC are different from DCIS and IBC. Thus, MIC may be a distinct entity rather than an interim stage in the progression from DCIS to IBC. The prognosis of MIC and the biologic behavior of this uncommon subset need to be further explored. PMID:34527132< /a> | PMC:PMC8414427 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.