Paeoniflorin suppresses allergic and inflammatory responses by promoting autophagy in rats with urticaria

xlomafota13 shared this article with you from Inoreader Paeoniflorin suppresses allergic and inflammatory responses by promoting autophagy in rats with urticaria Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jun;21(6):590. doi: 10.3892/etm.2021.10022. Epub 2021 Apr 8. ABSTRACT Paeoniflorin (PF) has been reported to be effective against several skin disorders, such as allergic contact dermatitis and psoriasis; however, it remains unclear whether PF can protect against urticarial lesions. Herein, the effects of PF on rats with urticarial lesions and the possible underlying mechanism were investigated. The effects of PF administration on a rat model of ovalbumin-induced urticarial-like lesions were evaluated via pathological analysis using hematoxylin-eosin staining. Toluidine blue staining was performed to detect mast cells and ELISA was performed to determine serum histamine levels. PF-induced regulatory effects on autophagic activity and the potential underlying mechanism of this were also investigated using transmission electron microscopy, immunohistochemistry and reverse transcription-quantitative PCR. It was demonstr ated that PF suppressed allergic and inflammatory responses to improve urticarial lesions, as evidenced by the attenuation of pathological abnormalities, mast cell infiltration and histamine secretion. Mechanistically, PF treatment was found to markedly limit the production and release of inflammatory cytokine interleukin (IL)-23, while the levels of IL-17 remained unchanged. PF intervention led to an increased number of autophagosomes, along with higher levels of light chain 3B (LC3B) and Beclin-1, and lower levels of P62, indicating that PF could augment autophagic activity in urticarial lesions. PF treatment increased the expression of liver kinase B1 (LKB1) and AMP-activated protein kinase-α (AMPK-α), contributing to the PF-enhanced autophagic activity. In conclusion, PF could effectively improve urticarial lesions by inhibiting inflammatory cytokine IL-23 and increasing the autophagic activity via the LKB1/AMPK-α pathway. PMID:33884028 | PMC:PMC8056118 | DOI:10.3892/etm.2021.10022 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Microcirculatory disturbance in acute liver injury

xlomafota13 shared this article with you from Inoreader Microcirculatory disturbance in acute liver injury Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jun;21(6):596. doi: 10.3892/etm.2021.10028. Epub 2021 Apr 9. ABSTRACT Microcirculatory disturbance is thought to be involved in the pathogenesis of acute liver injury (ALI). The current study examined the pathophysiologic role of hepatic microcirculatory disturbance in patients with ALI and in mouse models of ALI. Using serum aminotransferase (ALT)/lactate dehydrogenase (LDH) ratio as a hypoxic marker, 279 patients with ALI were classified into the low ALT/LDH ratio (ALT/LDH ≤1.5) and high ALT/LDH ratio group (ALT/LDH >1.5). In the low ALT/LDH ratio group, serum ALT, LDH, fibrinogen degradation products and prothrombin time-international normalized ratio were increased relative to the high ALT/LDH ratio group. Histologically, hepatic expression of tissue factor (TF) and hypoxia-related proteins was enhanced in the low ALT/LDH ratio group, and this was accompanied by sinusoidal fibrin deposition. Sinusoidal hyper coagulation and intrahepatic hypoxia was also analyzed in two different mouse models of ALI; Concanavalin A (ConA) mice and Galactosamine/tumor necrosis factor (TNF)-α (G/T) mice. Serum ALT/LDH ratio in ConA mice was significantly lower compared with G/T mice. Pimonidazole staining revealed the upregulation of hypoxia-related proteins in ConA mice. Recombinant human soluble thrombomodulin improved liver damage in ConA mice in association with reduced sinusoidal hypercoagulation and intrahepatic hypoxia. The present study provides evidence that serum ALT/LDH ratio aids in the identification of patients with ALI and intrahepatic hypoxia as a result of microcirculatory disturbance. The results facilitate the improved understanding of the pathogenesis of ALI, thereby offering a novel therapeutic strategy against ALI, which arises from sinusoidal hypercoagulation. PMID:33884034 | PMC:PMC8056117 | DOI:10.3892/etm.2021.10028 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Downregulation of miR-588 is associated with tumor progression and unfavorable prognosis in patients with osteosarcoma

xlomafota13 shared this article with you from Inoreader Downregulation of miR-588 is associated with tumor progression and unfavorable prognosis in patients with osteosarcoma Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jun;21(6):592. doi: 10.3892/etm.2021.10024. Epub 2021 Apr 8. ABSTRACT Osteosarcoma (OS) is a primary malignant tumor characterized by a high metastatic potential and poor prognosis. The dysregulation of miR-588 has been demonstrated to serve crucial roles in the progression of numerous types of cancer. The present study aimed to investigate the expression and function of miR-588 in the development of OS. To do so, clinical samples were collected and analyzed, and in vitro experiments were conducted. A total of 104 patients with OS were recruited between 2012 and 2014. The expression of miR-588 was analyzed by reverse transcription quantitative PCR. The association between miR-588 expression and the clinicopathological characteristics and survival rate of patients with OS was evaluated. Furthermore, Cell Counting Kit-8 and Transwell assays were used to evaluate the effect of miR-588 on the proliferation and the migrat ory and invasive abilities of various OS cell lines. The results demonstrated that miR-588 expression in OS tissues and cells was significantly lower compared with normal tissues and cells. In addition, miR-588 expression was closely associated with the Musculoskeletal Tumor Society (MSTS) staging of patients with OS. miR-588 expression and MSTS staging were therefore considered as independent indicators for the prognosis of patients with OS. In addition, miR-588 downregulation significantly stimulated the proliferation and migratory and invasive abilities of OS cells. Taken together, these findings indicated that miR-588 may serve as an independent prognostic factor and tumor suppressor in OS. PMID:33884030 | P MC:PMC8056108 | DOI:10.3892/etm.2021.10024 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Dl-butylphthalide inhibits rotenone-induced oxidative stress in microglia via regulation of the Keap1/Nrf2/HO-1 signaling pathway

xlomafota13 shared this article with you from Inoreader Dl-butylphthalide inhibits rotenone-induced oxidative stress in microglia via regulation of the Keap1/Nrf2/HO-1 signaling pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jun;21(6):597. doi: 10.3892/etm.2021.10029. Epub 2021 Apr 9. ABSTRACT Activated microglia are a source of superoxide which often increases oxidative stress in the brain microenvironment, increase production of reactive oxygen species (ROS) and directly or indirectly lead to dopaminergic neuronal death in the substantia nigra. Thus superoxide contributes to the pathogenesis of Parkinson's disease (PD). Evidence suggests that mitochondria are the main source of ROS, which cause oxidative stress in cells. Levels of ROS are thus associated with the function of the mitochondrial complex. Therefore, protecting the mitochondrial function of microglia is important for the treatment of PD. Dl-butylphthalide (NBP), a compound isolated from Chinese celery seeds, has been approved by the China Food and Drug Administration for the treatment of acute ischemic stroke. Recently, NBP demonstrated therapeutic potential for PD. However , the mechanism underlying its neuroprotective effect remains unclear. The present study aimed to investigate the effect of NBP on rotenone-induced oxidative stress in microglia and its underlying mechanisms. The results demonstrated that NBP treatment significantly increased mitochondrial membrane potential and decreased ROS level in rotenone-induced microglia. Western blot analysis showed that NBP treatment promoted entry of nuclear respiratory factor-2 (Nrf2) into the nucleus, increased heme oxygenase-1 (HO-1) expression and decreased the level of the Nrf2 inhibitory protein, Kelch-like ECH-associated protein 1. Overall, the findings indicated that NBP inhibited rotenone-induced microglial oxidative stress via the Keap1/Nrf2/HO-1 pathway, suggesting that NBP may serve as a novel agent for the treatment of PD. PMID:33884035 | PMC:PMC8056112 | DOI:10.3892/etm.2021.10029 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Interferon-τ regulates the expression and function of bovine leukocyte antigen by downregulating bta-miR-204

xlomafota13 shared this article with you from Inoreader Interferon-τ regulates the expression and function of bovine leukocyte antigen by downregulating bta-miR-204 Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jun;21(6):594. doi: 10.3892/etm.2021.10026. Epub 2021 Apr 8. ABSTRACT IFN-τ is a pregnancy recognition factor that regulates embryo implantation in ruminants. IFN-τ has been suggested to be involved in the expression of microRNA (miRNA/miR) and bovine leukocyte antigen (BoLA), which is an analog of the human major histocompatibility complex class I. However, little is known about whether the miRNAs are involved in the expression of BoLA in ruminants. The present study firstly verified that bta-miR-204 was downregulated and that BoLA was upregulated in the uterine tissues of dairy cows during early pregnancy. Subsequently, luciferase reporter assays, reverse transcription-quantitative PCR and western blot analysis were used to validate BoLA as the target gene of bta-miR-204. Moreover, BoLA was markedly upregulated and bta-miR-204 was downregulated in bovine endometrial epithelial cells (bEECs) treated with IFN-τ. I n addition, the results indicated that when the expression level of BoLA was increased by IFN-τ, the expression level of programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2) was also increased. Furthermore, when BoLA was silenced in bEECs by small interfering RNA, the expression of PD-L1 and PD-L2 was not affected by IFN-τ. The expression level of PD-L1 and PD-L2 was also increased in the uterine tissues of pregnant dairy cattle. In conclusion, IFN-τ may function by suppressing the expression of bta-miR-204 to increase the expression of BoLA during the embryo implantation period in cattle. IFN-τ may induce PD-L1 and PD-L2 transcription by regulating BoLA, which may influence the T cell immune response, thereby regulating pregnant cattle immunization. PMID:33884032 | PMC:PMC8056107 | DOI:10.3892/etm.2021.10026 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Intra-articular injections of platelet-rich plasma vs. hyaluronic acid in patients with knee osteoarthritis: Preliminary follow-up results at 6-months

xlomafota13 shared this article with you from Inoreader Intra-articular injections of platelet-rich plasma vs. hyaluronic acid in patients with knee osteoarthritis: Preliminary follow-up results at 6-months Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jun;21(6):598. doi: 10.3892/etm.2021.10030. Epub 2021 Apr 11. ABSTRACT The aim of the present study was to compare the clinical and economic benefits of intra-articular injections of platelet-rich plasma (PRP) and hyaluronic acid (HA) in Chinese patients with knee osteoarthritis (OA). A total of 86 patients (42 treated with PRP and 44 with HA) were treated with three weekly intra-articular injections. The inclusion criteria included patients between 18 and 75 years of age, with chronic knee pain or swelling lasting >3 months and X-ray findings of degenerative joint alterations according to the Kellgren-Lawrence score grade I-III. Clinical examinations were performed before treatment, at 1- and 6-month post-injection intervals. International Knee Documentation Committee subjective, Western Ontario and McMaster Universities and visual analogue scale scores were determined at each examination. Adverse reactions, aver age cost, treatment time and patient satisfaction were also recorded. Compared with patients injected with HA, PRP was found to be associated with increased and more severe post-injection pain and swelling, where the duration of adverse reactions was greater in the PRP group (P=0.02). During the follow-up evaluations, both groups showed statistically significant improvements in all clinical scores from pre-injection to 1- and 6-month assessments (P<0.05). However, no significant inter-group (PRP vs. HA) differences were observed in the clinical scores between the two follow-up time points. There were also no significant differences in clinical score between the groups with regards to the Kellgren-Lawrence grade I, II or III. The average cost of PRP injections was 22.8X that of HA administration and the average treatment time was 5X that of HA, but there was no significant difference in patient satisfaction. These preliminary results indicate that although PRP injections can signi ficantly improve clinical outcome in patients with knee OA, PRP is not any more effective compared with HA. Furthermore, PRP injections are associated with higher costs and treatment times. Therefore, additional clinical studies are required before PRP injections can be considered as a first-line treatment option for knee OA. PMID:33884036 | PMC:PMC8056115 | DOI:10.3892/etm.2021.10030 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Anticancer activity of 23,24-dihydrocucurbitacin B against the HeLa human cervical cell line is due to apoptosis and G2/M cell cycle arrest

xlomafota13 shared this article with you from Inoreader Anticancer activity of 23,24-dihydrocucurbitacin B against the HeLa human cervical cell line is due to apoptosis and G2/M cell cycle arrest Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jun;21(6):601. doi: 10.3892/etm.2021.10033. Epub 2021 Apr 12. ABSTRACT [This retracts the article DOI: 10.3892/etm.2018.5710.]. PMID:33884039 | PMC:PMC8056111 | DOI:10.3892/etm.2021.10033 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Role of NGF and its receptors in wound healing (Review)

xlomafota13 shared this article with you from Inoreader Role of NGF and its receptors in wound healing (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jun;21(6):599. doi: 10.3892/etm.2021.10031. Epub 2021 Apr 11. ABSTRACT Wound healing is an important and complicated process that includes four highly integrated and overlapping phases, haemostasis, inflammation, proliferation and tissue remodelling. Nerve growth factor (NGF) was the first member of a family of neurotrophic factors to be discovered, and is an essential neurotrophic factor for the development and maintenance of the central and peripheral nervous systems. Several studies have proposed that NGF and its receptors, tropomyosin-related kinase receptor 1 and NGF receptor, are involved in the wound healing process, and are important components of the healing of several wounds both in vivo and in vitro. Topical application of NGF significantly promotes the healing of different types of wounds, including diabetic foot ulcers, pressure ulcers and corneal wounds. The present review summarizes the s tatus of NGF and its receptors in current literature, and discusses data obtained in the last few years on the healing action of NGF in cutaneous, corneal and oral wounds. PMID:33884037 | PMC:PMC8056114 | DOI:10.3892/etm.2021.10031 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Role of Notch, IL-1 and leptin expression in colorectal cancer

xlomafota13 shared this article with you from Inoreader Role of Notch, IL-1 and leptin expression in colorectal cancer Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jun;21(6):600. doi: 10.3892/etm.2021.10032. Epub 2021 Apr 11. ABSTRACT An increasing number of studies have shown that angiogenesis has an important role in the progression of cancer. The growth of a new network of blood vessels is crucial for tumor growth and metastasis, which is promoted by several proangiogenic factors. Leptin, an essential adipokine that is secreted from fat tissue, is one of these pro-angiogenic factors. It has been shown that the inhibition of leptin-induced angiogenesis resulted in decreased levels of vascular endothelial growth factor (VEGF)/VEGFR2, hypoxia inducible factor (HIF) 1α, NF-κB, IL-1 and Notch and reduced the tumor growth in breast cancer. Leptin induces angiogenesis in breast cancer either by upregulating VEGFR2 in endothelial cells or by increasing VEGF/VEGFR2 expression through the Notch, IL-1 and leptin crosstalk outcome (NILCO) pathway. NILCO is a novel mechanism that inter acts with proinflammatory and proangiogenic signals, which are critical for cell proliferation and angiogenesis in cancer. Several studies have shown that components of NILCO may affect human cancer incidence and progression. However, to the best of our knowledge, the interactions between Notch, IL-1 and leptin in human colorectal cancer have not been yet studied at the molecular level. The aim of the present study was to investigate the expression levels of genes related to the NILCO pathway in human colorectal cancer specimens. The current results demonstrated that leptin, leptin receptor (ObR) b, Notch-1, Notch-4, IL-1α, IL-1β, IL-1R, IL-6, JAK-2, STAT-1, STAT-3, VEGFA, VEGFR1, VEGFR2, TNF-α and NF-κB mRNA expression levels in the cancer tissue were increased compared with the normal tissue. No significant changes in the mRNA expression levels of Jagged-1, HIF-1α and TNF receptor 1 were observed. Western blotting revealed that the protein expression levels of IκB were incre ased in the cancer tissue compared with normal tissue, whereas HIF-1α and phosphorylated STAT-1 levels were decreased. IL-6 and VEGFA plasma concentrations were statistically raised and the leptin plasma concentration was also raised, although significantly, patients with cancer compared with control individuals. Together, the present findings indicated that Notch, IL-1 and leptin may serve a crucial role in the development of colorectal cancer. PMID:33884038 | PMC:PMC8056113 | DOI:10.3892/etm.2021.10032 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Comparison of anti-inflammatory effects of Mecasin and its constituents on lipopolysaccharide-stimulated BV2 cells

xlomafota13 shared this article with you from Inoreader Comparison of anti-inflammatory effects of Mecasin and its constituents on lipopolysaccharide-stimulated BV2 cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jun;21(6):591. doi: 10.3892/etm.2021.10023. Epub 2021 Apr 8. ABSTRACT Mecasin, a traditional medicine, contains nine herbal constituents: Curcuma longa, Salvia miltio rhiza, Gastrodia elata, Chaenomeles sinensis, Polygala tenuifolia, Paeonia japonica, Glycyrrhiza uralensis, Atractylodes japonica and processed Aconitum carmichaeli. Several biological effects of mecasin have been described both in vivo and in vitro. Previous studies have demonstrated that mecasin has anti-inflammatory effects. The purpose of the present study was to determine anti-inflammatory effects of mecasin and its natural product constituents on lipopolysaccharide (LPS)-stimulated BV2 cells by measuring nitrite and nitric oxide contents. Nitrite production levels in LPS-stimulated BV2 cells incubated with mecasin and each individual constituent of mecasin were measured. The results suggested that C. longa , P. tenuifolia and P. japonica inhibited nitrite production in a pattern similar to that of mecasin. The effect of mecasin was likely a result of synergistic effects of its natural herb constituents. PMID:33884029 | PMC:PMC8056109 | DOI:10.3892/etm.2021.10023 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.