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.

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.

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.

Blocking tumor necrosis factor-α delays progression of chronic obstructive pulmonary disease in rats through inhibiting MAPK signaling pathway and activating SOCS3/TRAF1

xlomafota13 shared this article with you from Inoreader Blocking tumor necrosis factor-α delays progression of chronic obstructive pulmonary disease in rats through inhibiting MAPK signaling pathway and activating SOCS3/TRAF1 Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1311. doi: 10.3892/etm.2021.10746. Epub 2021 Sep 16. ABSTRACT The present study was conducted in order to study the detailed molecular mechanism of tumor necrosis factor (TNF)-α in chronic obstructive pulmonary disease (COPD). The rats were treated with cigarette smoke (CS) and lipopolysaccharide (LPS) to establish the COPD model. Next, the changes in lung injury in COPD rats with TNF-α knockdown was tested. Meanwhile, the regulation of TNF-α on MAPK pathway and its downstream molecules (SOCS3/TRAF1) was determined by western blotting. On this basis, the activation of MAPK and inhibition of SOCS3/TRAF1 was also examined. Subsequently, the lung function was tested with the plethysmograph, the cells of bronchoalveolar lavage fluid was counted and classified. Furthermore, lung tissue sections were stained with hematoxylin and eosin to verify whether the treatment of MAPK pathway and downstream molecules aff ected the effect of TNF-α knockdown on COPD. The present study showed that TNF-α knockdown could alleviate the decrease in the function and inflammatory injury of the lungs of rats with COPD. Western blot analysis verified that TNF-α knockdown could inhibit the activation of MAPK pathway and increase the expression of SOCS3/TRAF1. The following experimental results showed that the relief of lung injury caused by TNF-α knockdown could be deteriorated by activating MAPK pathway. It was also found that the symptom of COPD was decreased following transfection with sh-TNF-α but worsened by SOCS3/TRAF1 knockdown. Overall, TNF-α knockdown inhibited the activation of MAPK pathway and increased the expression of SOCS3/TRAF1, thus delaying the process of COPD. PMID:34630665 | PMC:PMC8461615 | DOI:10.3892/etm.2021.10746 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Enhanced expression of KIF4A in osteosarcoma predicts a poor prognosis and facilitates tumor growth by activation of the MAPK pathway

xlomafota13 shared this article with you from Inoreader Enhanced expression of KIF4A in osteosarcoma predicts a poor prognosis and facilitates tumor growth by activation of the MAPK pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1339. doi: 10.3892/etm.2021.10774. Epub 2021 Sep 22. ABSTRACT The present study aimed to explore the prognostic value and role of kinesin family member 4A (KIF4A) expression in human osteosarcoma. KIF4A expression was evaluated in human osteosarcoma tissues from The Cancer Genome Atlas and Gene Expression Omnibus datasets. Reverse transcription-quantitative PCR was then applied to assess KIF4A level in both osteosarcoma cell lines and tissues. The association between KIF4A expression and clinical results in patients with osteosarcoma was detected by survival analysis. MTT assays and colony formation assays were used to evaluate the effects of KIF4A on osteosarcoma cell proliferation. The results indicated that the level of KIF4A was increased and associated with a poor prognosis in osteosarcoma tissues. Knockdown of KIF4A was shown to inhibit osteosarcoma cellular proliferation by affecting the MAPK pathway . The level of KIF4A was high in the human osteosarcoma tissues and this could be considered as a tumor induction gene, which may be used as an indicator of prognosis. PMID:34630693 | PMC:PMC8495555 | DOI:10.3892/etm.2021.10774 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.