Skin anomalies in acromegalic patients (Review of the practical aspects)

xlomafota13 shared this article with you from Inoreader Skin anomalies in acromegalic patients (Review of the practical aspects) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1330. doi: 10.3892/etm.2021.10765. Epub 2021 Sep 20. ABSTRACT Acromegaly is a hormonal disorder which occurs as the result of growth hormone (GH) and insulin growth factor 1 (IGF-1) over-secretion; both hormones are related to skin anomalies. The skin acts as a large endocrine organ, hosting GH receptors in every cell while IGF-1 receptors are expressed only in keratinocytes. This review is a literature review of skin anomalies found in acromegaly, either related to the disease itself or associated with related complications such as secondary diabetes mellitus, or involving associated conditions such as genetic syndromes. The following clinical points are mentioned as follows. Excessive skin and enlargement of soft tissue are due to glycosaminoglycan deposits, edema, and hyperhidrosis (mostly facial and acral). Acanthosis nigricans, a body fold dermatosis associated with insulin resistance, involves local o r diffuse hyperkeratotic plaques with or without hyperpigmentation, caused by growth factors including GH/IGF-1. Other findings include cherry angiomas (due to the effects of lipid anomalies on small vessels); oily skin features with keratosis, epidermoid cysts, crochordons, pseudo-acanthosis nigricans; a potentially higher prevalence of varicose veins and psoriasis; low level of evidence for basal cell carcinoma, respective hidroadenitis suppurativa has been noted. In addition, complicated uncontrolled secondary diabetes mellitus (DM) may result in necrobiosis lipoidica diabeticorum, diabetic dermopathy, skin bacterial infections, dermatological complications of diabetic neuropathy, and nephropathy. Finally, associated hereditary syndromes may cause collagenomas, fibromas/angiofibromas, lipomas in multiple endocrine neoplasia type 1 (MEN1) syndrome; café-au-lait macules, early onset neurofibromas, juvenile xanthogranuloma (involving non-Langerhans cell histiocytes), and intertrigi nous freckling in neurofibromatosis type 1. Clinical findings are differentiated from pseudo-acromegaly such as pachydermoperiostosis. Iatrogenic rash, lipodystrophy (lipoatrophy with/without lipohypertrophy) are rarely reported after pegvisomant/somatostatin analogues or after insulin use for DM. Experiments using human cell lines have shown that GH/IGF-1 over-secretion are prone to epithelial-to-mesenchymal transition (EMT) in melanoma. In non-acromegalic subjects, the exact role of GH/IGF-1 in skin tumorigenesis is yet to be determined. Skin in acromegaly speaks for itself, either as the first step of disease identification or as a complication or part of a complex syndromic context. PMID:34630684 | PMC:PMC8495547 | DOI:10.3892/etm.2021.10765 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Metformin attenuates H2O2-induced osteoblast apoptosis by regulating SIRT3 via the PI3K/AKT pathway

xlomafota13 shared this article with you from Inoreader Metformin attenuates H<sub>2</sub>O<sub>2</sub>-induced osteoblast apoptosis by regulating SIRT3 via the PI3K/AKT pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1316. doi: 10.3892/etm.2021.10751. Epub 2021 Sep 17. ABSTRACT Osteoporosis is a common metabolic disease that has a high incidence in postmenopausal women. Studies have indicated that oxidative damage plays an important role in the development of postmenopausal osteoporosis. Metformin has been showed to have the ability to relieve excessive oxidation. The aim of the present was to determine the therapeutic effect and potential mechanism of metformin in postmenopausal osteoporosis. Oxidative damage was stimulated in vitro by the addition of H2O2 to MC3T3-E1 cells and a mouse menopausal model was also constructed. Cell viability and flow cytometry experiments were performed to determine the effects of H2O2 and metformin treatment on apoptosis. Mitochondrial membrane potential was tested by JC-1 assays. Western blotting was used to detect the expression of mit ochondrial apoptosis markers and antioxidant enzymes. Small interfering RNA was used to knockdown sirtuin3 (SIRT3), which was verified at the mRNA and protein levels. Bilateral ovariectomy was used to prepare menopausal mice, which were analyzed using micro-computed tomography. The results indicated that metformin is able to repair mitochondrial damage and inhibit the apoptosis of osteoblasts induced by H2O2, and also reverse bone mass loss in ovariectomized mice. Western blotting results demonstrated the involvement of SIRT3 in the production of antioxidant enzymes that are essential in protecting against mitochondrial injury. In addition, experiments with SIRT3 knockdown indicated that metformin reverses H2O2-induced osteoblast apoptosis by upregulating the expression of SIRT3 via the PI3K/AKT pathway. The results of the present reveal the pathogenesis of oxidative damage and the therapeutic effect of metformin in postmenopausal osteopor osis. They also suggest that SIRT3 is a potential drug target in the treatment of osteoporosis, with metformin being a candidate drug for modification and/or clinical application. PMID:34630670 | PMC:PMC8495548 | DOI:10.3892/etm.2021.10751 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effects of Psoralea corylifolia L. seed extract on AGEs-induced cell proliferation and fibrotic factor expression in mesangial cells

xlomafota13 shared this article with you from Inoreader Effects of <em>Psoralea corylifolia</em> L. seed extract on AGEs-induced cell proliferation and fibrotic factor expression in mesangial cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1332. doi: 10.3892/etm.2021.10767. Epub 2021 Sep 20. ABSTRACT Diabetic nephropathy is a microvascular complication of diabetes that is characterized by mesangial expansion and thickening of the glomerular basement membrane. The production of advanced glycation end products (AGEs) increases in diabetic patients. Activation of the receptor of AGE (RAGE) signaling pathway induces mesangial expansion via the reactive oxygen species (ROS)-mediated production of pro-inflammatory and extracellular matrix molecules. The Psoralea corylifolia L. seed (PCS) is a widely used herbal medicine with various biological activities. The current study investigated the effect of PCS extract on mesangial cell proliferation and the RAGE signaling pathway in SV40 MES 13 cells. SV40 MES 13 cells were harvested after treatment with various concentrations of PCS extract at 10 µg/ml AGEs for 24 h. The results revealed that the PCS extract inhibited AGEs-induced mesangial cell proliferation and cyclin protein expression in a concentration-dependent manner. In addition, the AGEs-induced expression of fibrotic factors, such as transforming growth factor β, fibronectin and collagen, was reduced in mesangial cells after exposure to the PCS extract. The PCS extract also reduced RAGE expression and inhibited the expression of its downstream signaling pathways, such as NADPH oxidase, intracellular ROS and phospho-NF-κB. In conclusion, the data suggested that the PCS extract attenuated AGEs-induced renal mesangial cell proliferation and fibrosis via the suppression of oxidative stress and the downregulation of inflammatory and fibrotic factor expression. PMID:34630686 | PMC:PMC8495585 | DOI:10.3892/etm.2021.10767 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

An enriched environment delays the progression from mild cognitive impairment to Alzheimer's disease in senescence-accelerated mouse prone 8 mice

xlomafota13 shared this article with you from Inoreader An enriched environment delays the progression from mild cognitive impairment to Alzheimer's disease in senescence-accelerated mouse prone 8 mice Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1320. doi: 10.3892/etm.2021.10755. Epub 2021 Sep 20. ABSTRACT A previous study demonstrated that middle-aged (5-6 months of age) senescence-accelerated mouse prone 8 (SAMP8) mice can be used as animal models of mild cognitive impairment (MCI). An enriched environment (EE) can mitigate cognitive decline and decrease the pathological changes associated with various neurodegenerative diseases. In the present study, the learning-memory abilities of SAMP8 mice during the MCI phase (5 months of age) was evaluated and neuropathological changes in the hippocampus were examined after the mice were exposed to an EE for 60 days. In the Morris water maze test, EE-exposed mice demonstrated significantly decreased escape latency and increased time spent in the target quadrant and number of platform crossings compared with control mice. Terminal deoxynucleotidyl transferase dUTP nick end labeling and Nissl staining showed that EE-exposed mice had reduced neuronal apoptosis and increased number of surviving neurons compared with control mice. Golgi staining, transmission electron microscopy, and immunohistochemical staining demonstrated that EE-exposed mice exhibited increased dendritic spine densities among secondary and tertiary apical dendrites; increases in synaptic numerical density, synaptic surface density, and expression of synaptophysin; and reduced deposition of amyloid-β (Aβ) and expression of amyloid-precursor protein (APP) in the hippocampal CA1 region compared with control mice. These results demonstrate that EE exposure effectively decreases neuronal loss and regulates neuronal synaptic plasticity by reducing the expression of APP and the deposition of Aβ in the hippocampal CA1 region, thereby mitigating cognitive decline in SAMP8 mice during the MCI phase and delaying the progression from MCI to Alzheimer's disease. PMID:34630674 | PMC:PMC8495563 | DOI:10.3892/etm.2021.10755 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Spongiotic reaction patterns in autoimmune bullous dermatoses (Review)

xlomafota13 shared this article with you from Inoreader Spongiotic reaction patterns in autoimmune bullous dermatoses (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1334. doi: 10.3892/etm.2021.10769. Epub 2021 Sep 20. ABSTRACT Spongiosis or a spongiotic reaction pattern is the histological hallmark of intercellular epidermal edema, viewed as clear spaces within the epidermis. Although considered a histopathological term, spongiosis has clinical correlations, with the variable degrees of spongiotic reaction leading to different dermatological findings. This review aimed to highlight the spongiotic reactive patterns found in different autoimmune bullous dermatoses, considering the paucity of publications in this domain. The pathogenesis of spongiosis assumes the passage of extravasated edema fluid from the dermis into the epidermis, frequently accompanied by dermal inflammatory cells, and classification of the spongiotic reaction patterns, as well as their associated spongiotic dermatitis, take into consideration the type and distribution of these inflammatory cells. It is mandatory to consider different reactive processes, specific for other skin disorders, which act as simulants of different spongiotic patterns for the diagnosis. Considering the possible transient occurrence, the heterogeneity and non-specificity of the histopathological features of these diseases, the diagnosis is very complex, requiring clinicopathological correlations and additional analyses. A deep insight into spongiosis pathogeny may open the perspectives of a classification refinement of autoimmune bullous dermatoses. PMID:34630688 | PMC:PMC8495556 | DOI:10.3892/etm.2021.10769 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Predictive factors for the recurrence of surgically excised basal cell carcinomas: A retrospective clinical and immunopathological pilot study

xlomafota13 shared this article with you from Inoreader Predictive factors for the recurrence of surgically excised basal cell carcinomas: A retrospective clinical and immunopathological pilot study Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1336. doi: 10.3892/etm.2021.10771. Epub 2021 Sep 20. ABSTRACT Basal cell carcinoma (BCC) is the most frequent form of skin cancer and is not a tumor with a lethal outcome if diagnosed and treated adequately. The gold standard for treatment is surgical excision with histologically safe margins. Even so, tumors excised with free margins may recur after a period of time. The identification of predictive factors for the recurrence of BCCs besides the localization, size and aggressive histology may be useful for the clinician. The aim of the present study was to identify clinical and pathological factors associated with recurrence in tumors with histologically free margins and assess via immunohistochemical staining, the expression of glioma-associated oncogene homolog 1 (GLI1), yes-associated protein (YAP), connective tissue growth factor (CTGF) and E-cadherin as they are involved in the development of BCCs, in the hope of identifying markers that are predictive for recurrence. In total, 8 recurrent BCCs and 38 non-recurrent tumors were analyzed. A Breslow index >2 (Se 100.0%, Sp 67.5%, P=0.008), Clark level >3 (Se 100.0%, Sp 47.5%, P<0.001), and excision margins both lateral (Se 87.5%, Sp 60.0%, P=0.04) and deep (Se 75.0%, Sp 82.5%, P<0.001) free from tumoral cells ≤1 mm proved to be predictive for recurrence in the present study. Recurrence may appear even after more than 3 years since the initial excision (Se 87.50%, Sp 70.0%, P<0.001). The expression levels of GLI1, YAP and E-cadherin were not different in the recurrent vs. non-recurrent BCCs. However, the low expression of CTGF may indicate a tumor with a higher aggressiveness. In conclusion, close follow-up of patients with excised BCCs at least annually is recommended and re-excision should be taken into consideration for locally advanced tumors especially if they are located in high-risk areas or those with histol ogically free margins <1 mm. PMID:34630690 | PMC:PMC8495561 | DOI:10.3892/etm.2021.10771 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Panax notoginseng saponins alleviate osteoporosis and joint destruction in rabbits with antigen-induced arthritis

xlomafota13 shared this article with you from Inoreader <em>Panax notoginseng</em> saponins alleviate osteoporosis and joint destruction in rabbits with antigen-induced arthritis Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1302. doi: 10.3892/etm.2021.10737. Epub 2021 Sep 16. ABSTRACT Although a number of anti-rheumatic drugs and biologics may be used to alleviate the symptoms of rheumatoid arthritis (RA), these compounds have been associated with bone loss and joint destruction; thus, alternative treatment approaches are required. In the present study, various plant extracts were evaluated for their capacity to inhibit joint destruction, and Panax notoginseng saponins (PNS), obtained from the Traditional Chinese Medicine Panax notoginseng, was identified as such a compound. Therefore, a rabbit antigen-induced arthritis (AIA) model was generated by immunization with ovalbumin in Freund's complete adjuvant, followed by treatment with PNS for 3 months. The morphology of the quadriceps femoris muscle, cartilage chondrocytes and skeletal elements was histologically observed by transmission electron microscopy (TEM), as well as micro-computed tomography. The results revealed that PNS significantly reduced the histopathological alterations associated with arthritic muscular atrophy and inflammation. In addition, TEM demonstrated that PNS protected chondrocytes from RA-associated damage. Furthermore, the bone density and microarchitecture in rabbits treated with PNS were markedly improved compared with those of the model group. Collectively, these data indicated that treatment with PNS may relieve osteoporosis and prevent joint and bone destruction in AIA. PMID:34630657 | PMC:PMC8461612 | DOI:10.3892/etm.2021.10737 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.