Ginseng gintonin attenuates the disruptions of brain microvascular permeability and microvascular endothelium junctional proteins in an APPswe/PSEN-1 double-transgenic mouse model of Αlzheimer's disease

xlomafota13 shared this article with you from Inoreader Ginseng gintonin attenuates the disruptions of brain microvascular permeability and microvascular endothelium junctional proteins in an APPswe/PSEN-1 double-transgenic mouse model of Αlzheimer's disease Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):310. doi: 10.3892/etm.2021.9741. Epub 2021 Feb 1. ABSTRACT It has been previously indicated that gintonin, which is a novel exogenous ginseng-derived lysophosphatidic acid (LPA) receptor ligand, restores memory dysfunctions in an APPswe/PSEN-1 double-transgenic mouse model of Alzheimer's disease (AD Tg mice) by attenuating β-amyloid plaque deposition, recovering cholinergic dysfunctions and upregulating hippocampal neurogenesis in the cortex and hippocampus. Although β-amyloid plaque depositions in AD is accompanied with disruptions of brain microvessels, including the brain-blood barrier (BBB), it is unknown whether gintonin exerts protective effects on brain microvascular dysfunctions in AD Tg mice. In the present study, the effects of gintonin-enriched fraction (GEF) on the changes in β-amyloid plaque depositions, brain permeability of Evans blue, and microvascular junctional proteins were investigate d in AD Tg mice. Long-term oral administration of GEF reduced β-amyloid plaque depositions in the cortex and hippocampus of AD Tg mice. GEF treatment also reduced the permeability of Evans blue through BBB and decreased immunoreactivity of platelet endothelial cell adhesion molecule-1 (a marker of BBB disruption) in the cortex and hippocampus of AD Tg mice in a dose-dependent manner. However, GEF elevated the protein expression of occludin, claudin-5 and zonula occludens-1, which are tight-junction proteins. The present results demonstrated that long-term oral GEF treatment not only attenuates β-amyloid plaque depositions in the brain but also exhibits protective effects against microvascular disruptions in AD Tg mice. Finally, GEF exhibits anti-AD effects through attenuation of β-amyloid plaque depositions and protection against brain microvascular damage in an AD animal model. PMID:33717253 | PMC:PMC7885069 | DOI:10.3892/etm.2021.9741 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Poricoic acid A suppresses TGF-β1-induced renal fibrosis and proliferation via the PDGF-C, Smad3 and MAPK pathways

xlomafota13 shared this article with you from Inoreader Poricoic acid A suppresses TGF-β1-induced renal fibrosis and proliferation via the PDGF-C, Smad3 and MAPK pathways Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):289. doi: 10.3892/etm.2021.9720. Epub 2021 Jan 27. ABSTRACT Renal interstitial fibrosis is the most important pathological process in chronic renal failure. Previous studies have shown that poricoic acid A (PAA), the main chemical constituent on the surface layer of the mushroom Poria cocos, has protective effects against oxidative stress and acute kidney injury. The present study aimed to investigate the potential roles of PAA on the pathological process of renal fibrosis and the associated molecular mechanism. The NRK-49F cell line was treated with transforming growth factor-β1 (TGF-β1) with or without PAA or platelet-derived growth factor C (PDGF-C). Cell Counting Kit-8 assay, western blotting and 5-ethynyl-2'-deoxyuridine immunofluorescence staining were performed to examine cell growth, protein expression and cell proliferation, respectively. Data from the present study showed that 10 µM PAA attenuated TGF-β1-induced NRK-49F cell extracellular matrix (ECM) accumulation, fibrosis formation and proliferation. Renal fibrosis with the activation of Smad3 and mitogen-activated protein kinase (MAPK) pathways were also inhibited by PAA treatment. PDGF-C reversed the inhibitory effects of PAA on TGF-β1-induced renal fibroblast proliferation and activation of the Smad3/MAPK pathway. The present study suggested that suppression of TGF-β1-induced renal fibroblast ECM accumulation, fibrosis formation and proliferation by PAA is mediated via the inhibition of the PDGF-C, Smad3 and MAPK pathways. The present findings not only revealed the potential anti-fibrotic effects of PAA on renal fibroblasts, but also provided a new insight into the prevention of fibrosis formation via regulation of the PDGF-C, Smad3 and MAPK signaling pathways. PMID:33717232 | PMC:PMC7885072 | DOI:10.3892/etm.2021.9720 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A novel combination of biallelic IFT122 variants associated with cranioectodermal dysplasia: A case report

xlomafota13 shared this article with you from Inoreader A novel combination of biallelic IFT122 variants associated with cranioectodermal dysplasia: A case report Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):311. doi: 10.3892/etm.2021.9742. Epub 2021 Feb 1. ABSTRACT Cranioectodermal dysplasia (CED) or Sensenbrenner syndrome is a very rare autosomal-recessive disease that is characterized by craniofacial, skeletal and ectodermal abnormalities. The proteins encoded by six CED-associated genes are members of the intraflagelline transport (IFT) system, which serves an essential role in the assembly, maintenance and function of primary cilia. The current study identified compound novel heterozygous IFT122 (NM_052985.3) variants in a male Chinese infant with CED. The latter variant changes the length of the protein and may result in the partial loss-of-function of IFT122. With the simultaneous presence of frameshift and stop-loss variants, the patient manifested typical CED with fine and sparse hair, macrocephaly, dysmorphic facial features and upper limb phocomelia. A number of unusual phenotypic characterist ics were additionally observed and included postaxial polydactyly of both hands and feet. The molecular confirmation of CED in this patient expands the CED-associated variant spectrum of IFT122 in CED, while the manifestation of CED in this patient provides additional clinical information regarding this syndrome. Moreover, the two variants identified in the proband provide a novel perspective into the phenotypes caused by different combinations of variants. PMID:33717254 | PMC:PMC7885081 | DOI:10.3892/etm.2021.9742 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Interleukin-1β weakens paclitaxel sensitivity through regulating autophagy in the non-small cell lung cancer cell line A549

xlomafota13 shared this article with you from Inoreader Interleukin-1β weakens paclitaxel sensitivity through regulating autophagy in the non-small cell lung cancer cell line A549 Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):293. doi: 10.3892/etm.2021.9724. Epub 2021 Jan 27. ABSTRACT Non-small cell lung cancer (NSCLC) poses a threat to human health and paclitaxel chemotherapy has been approved for the treatment of this type of cancer. However, resistance to treatment severely compromises the survival rate and prognosis of patients with NSCLC. The aim of the present study was to investigate the role of IL-1β in paclitaxel sensitivity of NSCLC cells and elucidate the underlying mechanism. The expression of IL-1β was found to be upregulated in NSCLC tissues and cells compared with healthy adjacent tissues and a normal epithelial cell line, respectively, as detected by reverse transcription-quantitative PCR and western blot analyses. Subsequently, Cell Counting Kit-8 assay and flow cytometry revealed that IL-1β weakened the sensitivity of A549 cells to paclitaxel. It was subsequently demonstrated that IL-1β induced A549 cell au tophagy, while tunicamycin-induced autophagy increased the IL-1β expression level and weakened paclitaxel sensitivity. Thus, the results revealed that IL-1β reduced the sensitivity to paclitaxel in A549 cells by promoting autophagy and suggested that IL-1β may be of value for improving the therapeutic efficacy of paclitaxel chemotherapy in NSCLC. PMID:33717236 | PMC:PMC7885084 | DOI:10.3892/etm.2021.9724 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Novel immunological and genetic factors associated with vitiligo: A review

xlomafota13 shared this article with you from Inoreader Novel immunological and genetic factors associated with vitiligo: A review Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):312. doi: 10.3892/etm.2021.9743. Epub 2021 Feb 1. ABSTRACT Vitiligo is a skin disorder characterized by depigmentation of the skin due to a lack of melanin. This condition affects men and woman of all ages and its incidence is not restricted by ethnicity or region. Vitiligo is a multifactorial disease, in which melanocytes, which serve important functions in skin pigmentation and immune processes, are impaired. There is sufficient evidence that immunological and genetic factors are primarily responsible for the destruction and dysfunction of melanocytes. Therefore, genetic DNA sequence variants that participate in skin homeostasis, pigmentation and immune response regulation, as well as altered expression patterns, may contribute to the risk of developing vitiligo. The current review presented an overview of the mechanism of pigmentation and of currently known factors involved in depigmentation, as well as the classification, epidemiology, associated comorbidities, risk factors, immunopathogenesis and several genetic and molecular changes associated with vitiligo. PMID:33717255 | PMC:PMC7885061 | DOI:10.3892/etm.2021.9743 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Hesperetin attenuates silica-induced lung injury by reducing oxidative damage and inflammatory response

xlomafota13 shared this article with you from Inoreader Hesperetin attenuates silica-induced lung injury by reducing oxidative damage and inflammatory response Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):297. doi: 10.3892/etm.2021.9728. Epub 2021 Jan 28. ABSTRACT Oxidative stress and the inflammatory response are two important mechanisms of silica-induced lung injury. Hesperetin (HSP) is a natural flavonoid compound that is found in citrus fruits and has been indicated to exhibit strong antioxidant and anti-inflammatory properties. The current study evaluated the protective effect of HSP on lung injury in rats exposed to silica. The results indicated that the degree of alveolitis and pulmonary fibrosis in the HSP-treated group was significantly decreased compared with the silica model group. The content of hydroxyproline (HYP) was also revealed to decrease overall in the HSP treated group compared with the silica model group, indicating that the degree of pulmonary fibrosis was decreased compared with the silica model group. The present study also demonstrated that HSP reduced oxidation levels of malondiald ehyde (MDA) and increased the activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-PX). Total antioxidant capacity (T-AOC) was also increased following HSP treatment, indicating that HSP can alleviate oxidative stress in the lung tissue of silica-exposed rats. In addition, HSP was revealed to inhibit the synthesis and secretion of fibrogenic factor TGF-β1, reduce the production of pro-inflammatory cytokines IL-1β, IL-4, TNF-α and increase the levels of anti-inflammatory factors IFN-γ and IL-10. The current study demonstrated that HSP can effectively attenuate silica-induced lung injury by reducing oxidative damage and the inflammatory response. PMID:3371724 0 | PMC:PMC7885076 | DOI:10.3892/etm.2021.9728 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

TRIB3 promotes oral squamous cell carcinoma cell proliferation by activating the AKT signaling pathway

xlomafota13 shared this article with you from Inoreader TRIB3 promotes oral squamous cell carcinoma cell proliferation by activating the AKT signaling pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):313. doi: 10.3892/etm.2021.9744. Epub 2021 Feb 1. ABSTRACT Tribbles pseudokinase 3 (TRIB3), a member of the tribbles-related family, has biological roles such as by acting as an oncogene or tumor suppressor gene, in various types of cancer, including colorectal cancer, breast cancer, lung cancer and renal cell carcinoma. However, the role of TRIB3 in oral squamous cell carcinoma (OSCC) is remains unclear. The current was aimed to determine the biological function of TRIB3 in OSCC progression. TRIB3 expression was examined in OSCC surgical specimens using reverse transcription-quantitative PCR and the role of TRIB3 in the proliferation capacities of OSCC cell lines was examined using crystal violet and MTT assays in vitro and tumorigenicity assays in vivo. The underlying mechanism by which TRIB3 exerts its function was investigated using western blotting. The results demonstrated that the mRNA and protein expression levels of TRIB3 were higher in human OSCC tissues compared with normal tissues. The role of TRIB3 in cell proliferation was also determined. TRIB3 overexpression significantly promoted OSCC cell proliferation, whereas TRIB3 knockdown inhibited OSCC cell proliferation compared with control cells. TRIB3 knockdown also suppressed tumor growth and decreased tumor volume in vivo compared with control cells. Moreover, the results suggested that TRIB3 overexpression increased the phosphorylation of protein kinase B (AKT) and mammalian target of rapamycin (mTOR), whereas TRIB3 knockdown decreased the phosphorylation of AKT and mTOR compared with control cells. To summarize, the present study indicated that TRIB3 promoted OSCC cell proliferation by activating the AKT signaling pathway; therefore, TRIB3 may serve as a potential target for the diagnosis and treatment of OSCC. PMID:33717256 | PMC:PMC7885083 | DOI:10.3892/etm.2021.9744 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

MicroRNA-432-5p inhibits cell migration and invasion by targeting CXCL5 in colorectal cancer

xlomafota13 shared this article with you from Inoreader MicroRNA-432-5p inhibits cell migration and invasion by targeting CXCL5 in colorectal cancer Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):301. doi: 10.3892/etm.2021.9732. Epub 2021 Jan 29. ABSTRACT MicroRNAs (miRNAs) play an important role in the occurrence and development of colorectal cancer (CRC). Evidence shows that miR-432-5p expression is decreased in various tumors and cancer cell lines. miR-432-5p can inhibit tumor invasion and metastasis, but its role in colorectal cancer is unclear. The present study demonstrated that miR-432-5p expression was decreased in colorectal cancer tissue and cell lines, and is negatively associated with invasion classification, lymph node metastasis and Tumor-Node-Metastasis stage. Kaplan-Meier survival analysis showed that low miR-432-5p expression was associated with a poor survival rate in patients with CRC. In addition, SW480 and HT-29 cells transfected with miR-432-5p mimics had decreased migration and invasion abilities, whereas miR-432-5p inhibitors had the opposite effect. The expression of C-X-C m otif chemokine ligand 5 (CXCL5), a direct target of miR-432-5p, was negatively associated with miR-432-5p expression. When CXCL5 was introduced into miR-432-5p mimic-transfected SW480 and HT-29 cells, miR-432-5p-mediated inhibition of CRC migration and invasion was reversed. Thus, the present results suggest that miR-432-5p can inhibit the migration and invasion of CRC cells by targeting CXCL5. PMID:33717244 | PMC:PMC7885074 | DOI:10.3892/etm.2021.9732 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Biological role of postoperative low level laser therapy in preventing hydroxyapatite orbital implantation exposure: A case report

xlomafota13 shared this article with you from Inoreader Biological role of postoperative low level laser therapy in preventing hydroxyapatite orbital implantation exposure: A case report Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):314. doi: 10.3892/etm.2021.9745. Epub 2021 Feb 3. ABSTRACT Conjunctival sac stenosis is the contraction of the conjunctival sac as a result of trauma or disease. The aim of the present study was to observe the clinical effects of low-level laser therapy (LLLT) combined with hydroxyapatite (HA) orbital implantation as a treatment strategy for conjunctival sac stenosis. A total of 10 patients with conjunctival sac stenosis were treated with scleral graft transplantation in conjunction with HA implantation and postoperative LLLT. In addition, a rabbit model was used to investigate the biological mechanism underlying the effects of LLLT with the aim of preventing and treating orbital implantation exposure. The right eyeball was removed, orbital implantation performed and LLLT applied to experimental groups. 99mTc-Methyl diphosphonate scanning methods were performed at different timepoints to compare the average radioactivity count of the region of interest between surgical (right) and control (left) eyes (R/L). Histopathological examination was performed 8 weeks post-surgery, followed by analysis of fiber vascularization. Following LLLT, moderate conjunctival wounds were completely healed within 2 weeks and severe stenosis wounds healed within 3 weeks. Following prosthesis implantation in the rabbit model, a significantly elevated R/L ratio was observed after 4 weeks, whereas no significant difference was observed compared with the control group at 6 and 8 weeks postoperatively. Histopathological examination revealed that all implants were fibrotic. Overall, the present study demonstrated that LLLT promoted the survival of conjunctival grafts, stimulated conjunctival incision healing and promoted early vascularization of HA implants. Clinical trial registration no: ChiCTR-DDT-12002660 (www.chictr.org/cn/). PMID:33717257 | PMC:PMC7885064 | DOI:10.3892/etm.2021.9745 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Interleukin-6 released by oral lichen planus myofibroblasts promotes angiogenesis

xlomafota13 shared this article with you from Inoreader Interleukin-6 released by oral lichen planus myofibroblasts promotes angiogenesis Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):291. doi: 10.3892/etm.2021.9722. Epub 2021 Jan 27. ABSTRACT Oral lichen planus (OLP), defined as a potential for malignant transformation, is a chronic inflammatory disease in which abnormal angiogenesis serves a role in the malignant changes of the disease. OLP-associated fibroblasts (OLP-MFs), derived from the stroma of OLP tissues, are characterized by the presence of myofibroblasts and contribute to the secretion of pro-inflammatory cytokines, which may be involved in the molecular pathogenesis of OLP. However, the associated mechanisms of angiogenesis in OLP remain unknown. The present study aimed to verify the expression of intercellular adhesion molecular 1, vascular cell adhesion molecule 1, VEGF and CD34 in OLP, and to investigate whether IL-6 secreted by OLP-MFs promoted OLP angiogenesis and the effect of its corresponding antibody inhibition. The results of the experiments demonstrated that infla mmation was present and OLP upregulated the secretion of IL-6 by OLP stromal fibroblasts, thereby enhancing OLP angiogenesis. Anti-IL-6 receptor antibody inhibited OLP-stroma IL-6 signaling and suppressed OLP angiogenesis. The antibody inhibited the inflammatory response by inhibiting the secretion of inflammatory factors, including IL-6, to suppress angiogenesis and reduce disease progression, thus indicating that this could be a potential target to develop a treatment for OLP. PMID:33717234 | PMC:PMC7885057 | DOI:10.3892/etm.2021.9722 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Chronic atrophic gastritis and intestinal metaplasia induced by high-salt and N-methyl-N'-nitro-N-nitrosoguanidine intake in rats

xlomafota13 shared this article with you from Inoreader Chronic atrophic gastritis and intestinal metaplasia induced by high-salt and N-methyl-N'-nitro-N-nitrosoguanidine intake in rats Via Experimental and therapeutic medicine Exp Ther Med. 2021 Apr;21(4):315. doi: 10.3892/etm.2021.9746. Epub 2021 Feb 3. ABSTRACT The aim of the present study was to induce chronic atrophic gastritis (CAG) with intestinal metaplasia (IM) in rats by administering saturated salt and methyl-N'-nitro-N-nitrosoguanidine (MNNG) via oral gavage. Changes in gastric mucosal blood microcirculation and activation of the cyclo-oxygenase-2 (COX-2)/hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway during CAG and IM development were investigated. After administering saturated salt and MNNG for 25 weeks, mild atrophy was detected in the stomach of model rats using hematoxylin and eosin staining. CAG with IM was successfully induced in the gastric mucosa of the model rats after 35 weeks. Gastric mucosal blood flow was decreased in comparison with controls as early as 15 weeks after treatment to induce CAG and the mRNA expression levels of COX-2, HIF-1α, vascular endothelial growth factor receptor (VEGFR)1 and VEGFR2 were increased in comparison with untreated rats as early as 25 weeks after treatment. HIF-1α, COX-2 and VEGFR2 expression levels were increased as early as 25 weeks after CAG induction treatment when compared to controls and HIF-1α, COX-2, VEGFR1 and VEGFR2 expression levels were significantly increased after 35 weeks. These findings indicated that administering saturated salt and MNNG by gavage for 35 weeks successfully induced CAG and IM in rats. Furthermore, the microcirculation was disturbed before activation of the COX-2/HIF-1α/VEGF signaling pathway. PMID:33717258 | PMC:PMC7885066 | DOI:10.3892/etm.2021.9746 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.