Ultra-early electroacupuncture rehabilitation for intravenous thrombolysis-induced cerebral infarction.

OBJECTIVE: The purpose of this research was to investigate whether it is possible to perform ultra-early interventional electroacupuncture on individuals who had experienced intravenous thrombolysis prior to receiving therapy for acute cerebral infarction. PATIENTS AND METHODS: Patients who have undergone intravenous thrombolysis between July 2019 and March 2021 were eligible for participation in this study. The participants were divided into two groups; one group received electroacupuncture therapy 24 hours after their condition became stable, while the other group received treatment 48 hours after their condition became stable. Both groups received the same therapy for their respective forms of rehabilitation. The Fugl-Meyer Motion Assessment Scale (FMA) was used to assess the patients' motor function before and after therapy, as well as two weeks and one month after treatment. The scores of the FMA were recorded before and after treatment. RESULTS: After therapy, the FMI scores were higher in both groups (p<0.05), and the researchers found that the ultra-early electroacupuncture intervention was related to higher FMI ratings 2 weeks and 1 month after treatment (p<0.05). In neither of the two study groups was there any sign of a major adverse response or consequence (p>0.05). CONCLUSIONS: This research offers evidence that ultra-early interventional electroacupuncture rehabilitation therapy may be an effective and safe method of treatment for individuals who have had a cerebral infarction after receiving intravenous thrombolysis. The results lend credence to the notion that this kind of therapy should be taken into consideration as an adjunctive model for rehabilitation in patients of this type.

Recombinant Treponema pallidum protein Tp47 promoted the phagocytosis of macrophages by activating NLRP3 inflammasome induced by PKM2-dependent glycolysis.

BACKGROUND: Glycolysis is a critical pathway in cellular glucose metabolism that provides energy and participates in immune responses. However, whether glycolysis is involved in NOD-like receptor family protein 3 (NLRP3) inflammasome activation and phagocytosis of macrophages in response to Treponema pallidum infection remains unclear. OBJECTIVES: To investigate the role of glycolysis in activating the NLRP3 inflammasome for regulating phagocytosis in macrophages in response to T. pallidum protein Tp47 and its associated mechanisms. METHODS: Interactions between activation of the NLRP3 inflammasome and phagocytosis and the role of glycolysis in Tp47-treated macrophages were investigated through experiments on peritoneal macrophages and human monocytic cell line-derived macrophages. RESULTS: Activation of phagocytosis and NLRP3 inflammasome were observed in Tp47-treated macrophages. Treatment with NLRP3 inhibitor MCC950 or si-NLRP3 attenuated Tp47-induced phagocytosis. Glycolysis and glycolytic capacity were enhanced by Tp47 stimulation in macrophages, and a change in the levels of glycolytic metabolites (phosphoenolpyruvate, citrate and lactate) was induced by Tp47 in macrophages. Inhibition of glycolysis with 2-deoxy-D-glucose, a glycolysis inhibitor, decreased the activation of NLRP3. Expression of M2 isoform of pyruvate kinase (PKM2), an enzyme catalysing a rate-limiting reaction in the glycolytic pathway, was upregulated in Tp47-stimulated macrophages. Inhibition of PKM2 with shikonin or si-PKM2 decreased glycolysis and NLRP3 activation. CONCLUSION: Tp47 promotes phagocytosis in macrophages by activating the NLRP3 inflammasome, which is induced by the enhancement of PKM2-dependent glycolysis.

Diagnostic accuracy of ultrasonography for detecting gastric tube placement: an updated meta-analysis.

OBJECTIVE: This study aimed at reviewing the diagnostic accuracy of ultrasonography for detecting correct nasogastric tube placement compared with X-ray imaging as the reference standard. MATERIALS AND METHODS: This was a systematic review and meta-analysis of observational studies published between 1961 and 2022. We included studies that compared the diagnostic accuracy of ultrasound detection for nasogastric tube placement with that of X-ray imaging in adult patients who were undergoing nasogastric tube placement for any reason. We searched for published studies in the following electronic databases: Cochrane Library, PubMed, EMBASE, and Web of Science. The risk of bias was assessed using a standard procedure according to the Quality Assessment of Diagnostic Accuracy Studies-2 criteria. The results were analyzed using RevMan or Meta-Disc software to determine the adequacy and conclusiveness of the available evidence. RESULTS: Fourteen studies met our inclusion criteria. Overall, 1,812 patients were included in these studies. The results included a pooled sensitivity of 0.96 (95% confidence interval [CI] 0.94-0.97), specificity of 0.91 (95% CI 0.85-0.96), positive likelihood ratio of 5.08 (95% CI 1.49-17.39), and negative likelihood ratio of 0.08 (95% CI 0.06-0.10). This was confirmed through a summary receiver operating characteristic curve, which showed that the area under the curve was 0.96. CONCLUSIONS: We found evidence about validity of ultrasound as an efficient method for verifying nasogastric tube placement, although there is insufficient evidence to suggest that it can be used as a diagnostic tool for incorrect gastric tube placement.

Neuroprotective effects of visnagin on cerebral ischemia-reperfusion injury rats and the underlying mechanisms.

OBJECTIVE: Cerebral ischemia-reperfusion (I/R), caused by the treatments of ischemic stroke, usually leads to brain injury. Inflammation, oxidative stress, and autophagy play pivotal roles in the pathology. Visnagin presents a protective effect on I/R injured animal models of the heart, liver, kidney, and other organs. In our research, we identified the neuroprotective effects and the underlying mechanisms of visnagin in cerebral I/R injured models. MATERIALS AND METHODS: We constructed rat models of cerebral I/R injury and categorized them into 5 groups: sham operation group, I/R model group, and visnagin treatment I/R group (10, 30, 60 mg/kg). The neurological deficits of the rats were analyzed after 24 hours of reperfusion, then, the contents of glutathione peroxidase, malondialdehyde, superoxide dismutase catalase, caspase-3, nuclear factor kappa-B p65 unit, tumor necrosis factor-α, interleukin-1ß, and interleukin6 were measured in rat models. The expressions of Bcl-2 and Bax were detected by Western blot analysis. RESULTS: Our results suggested that the administration of visnagin alleviated the cognitive dysfunction, reduced the activities of inflammatory factors, promoted the protein expression of Bcl-2, and downregulated the expression of Bax in the I/R injured rat model. CONCLUSIONS: Visnagin exerts a neuroprotective effect during I/R injury in rats, the underlying mechanisms may be the effect of attenuating neuroinflammation, anti-oxidative and inhibition of apoptosis.

Autophagy promotes phagocytosis and clearance of Treponema pallidum via the NLRP3 inflammasome in macrophages.

BACKGROUND: Elucidating the mechanism of the macrophage phagocytic response will improve our knowledge of host defence against Treponema pallidum. OBJECTIVE: To explore whether autophagy promotes T. pallidum phagocytosis and clearance via the NLRP3 inflammasome in macrophages. METHODS: The interactions between autophagy and phagocytosis and the role of NLRP3 in these processes in T. pallidum-treated macrophages were investigated through experiments using human monocytic cell line (THP-1)-derived macrophages. Treponema pallidum clearance after phagocytosis was evaluated by inoculating rabbits with macrophage-treponeme mixtures. RESULTS: Activation of autophagy and phagocytosis in T. pallidum-treated macrophages occurred in a dose- and time-dependent manner. The percentage of spirochete-positive macrophages (22.34% vs. 70.93%, P < 0.001) and spirochete internalization (MFI: 9.62 vs. 20.33, P < 0.001) were notably reduced by silencing Beclin1. Inoculation of macrophage-treponeme mixtures into rabbits showed a 3.00-day delay in lesion development (17.55 ± 3.73 vs. 14.55 ± 1.99 days) and decreased lesion numbers [11 (36.7%) vs. 20 (66.7%) of 30; χ2  = 5.406, P = 0.020] in the control compared with the si-Beclin1 group. Furthermore, silencing NLRP3 decreased the mRNA and protein levels of Beclin-1 and LC3B [mRNA: 49.86% and 43.02%; protein: 22.31% and 24.24%, respectively, differing significantly from the control group (P < 0.001)] and reduced the percentage of spirochete-positive macrophages (30.29% vs. 70.53%, P < 0.001) and spirochete internalization (MFI: 9.82 vs. 19.33, P < 0.001). CONCLUSION: Treponema pallidum induces autophagy in macrophages to promote phagocytosis and clearance. The NLRP3 inflammasome modulates autophagy and phagocytosis in vitro. These data may be useful for understanding the host-pathogen relationship and establish the groundwork for strategies to combat syphilis.

LncRNA KCNQ1OT1 contributes to the cisplatin resistance of tongue cancer through the KCNQ1OT1/miR-124-3p/TRIM14 axis.

OBJECTIVE: Tongue cancer is a common malignant tumor in the oral and maxillofacial region, most of which is squamous cell carcinoma. Cisplatin (DDP) is one of the chemotherapy drugs for patients with tongue squamous cell carcinoma (TSCC). However, DDP resistance has become a major obstacle to its clinical application. Our study aimed to investigate the effects of long non-coding RNA (lncRNA) KCNQ1 overlapping transcript 1 (KCNQ1OT1) on DDP resistance of tongue cancer and the underlying mechanism. PATIENTS AND METHODS: The levels of KCNQ1OT1, miR-124-3p, and tripartite motif containing 14 (TRIM14) were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The maximum size of tumor (MTS) assay was used to detect the cell survival rates. Furthermore, the cell proliferation was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Transwell assay was performed to detect the cell migration and invasion. Western blot assay was used to detect the protein levels of Vimentin, N-cadherin, E-cadherin, and TRIM14. The functional targets of KCNQ1OT1 and miR-124-3p, miR-124-3p and TRIM14 were predicted by starBase 3.0 and TargetScan. The relationship between KCNQ1OT1 and miR-124-3p was confirmed by Dual-Luciferase reporter assay, RNA immunoprecipitation (RIP) and RNA pull-down. Further, the relationship between miR-124-3p and TRIM14 was verified by Dual-Luciferase reporter assay. Animal experiment revealed the effect of KCNQ1OT1 on DDP resistance of tongue cancer cells in vivo. RESULTS: KCNQ1OT1 was upregulated in DDP-resistant tongue cancer tissues and cells, and mainly expressed in cytoplasm. Functionally, the knockdown of KCNQ1OT1 inhibited the survival rate, proliferation, migration, invasion, and EMT of the DDP-resistant tongue cancer cells. Of note, miR-124-3p acted as a target of KCNQ1OT1 and KCNQ1OT1 could reduce the expression of miR-124-3p. Moreover, miR-124-3p targeted TRIM14 and the downregulation of TRIM14 reduced the DDP resistance of tongue cancer cells. Importantly, KCNQ1OT1 regulated the TRIM14 expression by targeting miR-124-3p. Furthermore, KCNQ1OT1 knockdown reduced the DDP-resistant tumor growth and weight through the miR-124-3p/TRIM14 axis in vivo. CONCLUSIONS: LncRNA KCNQ1OT1 promotes the DDP resistance of tongue cancer by sponging miR-124-3p to regulate TRIM14 expression.

Are nontreponemal tests suitable for monitoring syphilis treatment efficacy? Evidence from rabbit infection models.

OBJECTIVES: We aimed to characterize kinetics of non-treponamal antibody titres during the natural course of syphilis and explore their roles in monitoring syphilis treatment efficacy. METHODS: Sixty New Zealand white male rabbits were challenged with Nichols or Amoy Treponema pallidum strains, and the rapid plasma reagin (RPR) test was performed to quantify non-treponemal antibody titres during the infection course. Viable T. pallidum in the challenged rabbits was assessed with rabbit infectivity tests. RESULTS: The RPR titres of the Nichols or Amoy strain between no benzathine penicillin G (BPG) and BPG treatment subgroups displayed a similar trend: first ascending and then descending. Compared with baseline, the proportions of fourfold decline in RPR titres in the Nichols or Amoy group presented a similar result on days 30, 60 and 180 between the no BPG and BPG treatment subgroups (0%, 0/5; 80%, 4/5; 100%, 5/5; vs. 0%, 0/5; 80%, 4/5; 100%, 5/5; p 0.999; 0%, 0/5; 80%, 4/5; 80%, 4/5; vs. 40%, 2/5; 100%, 5/5; 100%, 5/5; p 0.098, respectively). Compared with the maximum baseline titre, the proportion of fourfold decline in PRR titre also showed a similar result in the two groups on days 30, 60 and 180 between the no BPG and the BPG treatment subgroups (0%, 0/5; 100%, 5/5; 100%, 5/5, vs. 40%, 2/5; 100%, 5/5; 100%, 5/5; p 0.129; 0%, 0/5; 100%, 5/5; 100%, 5/5, vs. 80%, 4/5; 100%, 5/5; 100%, 5/5; p 0.091, respectively. Moreover, regardless of whether the RPR titres presented a fourfold decline, viable T. pallidum could be detected in untreated rabbits' lymph nodes at 30, 60 and 180 days post infection, while viable T. pallidum was not detected in any of the treated rabbits' lymph nodes. CONCLUSIONS: The RPR titre increased and then decreased (even became negative) during the natural course of syphilis, similar to that seen after BPG treatment. The RPR tetre is thus a questionable indicator of syphilis treatment efficacy.

Recombinant Treponema pallidum protein Tp0136 promotes fibroblast migration by modulating MCP-1/CCR2 through TLR4.

BACKGROUND: Chancre self-healing is an important clinical feature in the early stages of syphilis infection. Wound healing may involve an important mechanism by the migration of fibroblasts filling the injured lesion. However, the specific mechanism underlying this process is still unknown. OBJECTIVES: We aimed to analyse the role of Tp0136 in the migration of fibroblasts and the related mechanism. METHODS: The migration ability of fibroblasts was detected by a wound-healing assay. RT-PCR and ELISA detected the expression of MCP-1, IL-6 and MMP-9. TLR4 expression was detected by RT-PCR. The protein levels of CCR2 and relevant signalling pathway molecules were measured by Western blotting. RESULTS: Tp0136 significantly promoted fibroblast migration. Subsequently, the levels of MCP-1 and its receptor CCR2 were increased in this process. The migration of fibroblasts was significantly inhibited by an anti-MCP-1 neutralizing antibody or CCR2 inhibitors. Furthermore, studies demonstrated that Tp0136 could activate the ERK/JNK/PI3K/NF-κB signalling pathways through TLR4 activity and that signalling pathways inhibitors could weaken MCP-1 secretion and fibroblast migration. CONCLUSIONS: These findings demonstrate that Tp0136 promotes the migration of fibroblasts by inducing MCP-1/CCR2 expression through signalling involving the TLR4, ERK, JNK, PI3K and NF-κB signalling pathways, which could contribute to the mechanism of chancre self-healing in syphilis.

Recombinant Treponema pallidum protein Tp47 induces angiogenesis by modulating the matrix metalloproteinase/tissue inhibitor of metalloproteinase balance in endothelial cells.

BACKGROUND: Although angiogenesis is an obvious pathological manifestation in the pathogenesis of syphilis, little is known about the underlying mechanisms of angiogenesis induced by reactions to Treponema pallidum antigens. OBJECTIVE: In this study, we sought to determine the role of recombinant T. pallidum Tp47 in promoting angiogenesis in endothelial cells and the related mechanism. METHODS: Evaluation of the pro-angiogenic activity of recombinant T. pallidum Tp47 in human umbilical vein endothelial cells (HUVECs) was assessed, and the balance of matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) and the mechanisms underlying the involvement of Akt/mTOR/S6 pathways in this process were explored. RESULTS: Under stimulation by Tp47, HUVECs exhibited obvious proliferation, migration and tube formation. In addition, the apparent promotion of angiogenesis by Tp47 was observed using a zebrafish embryo model. During angiogenesis, the levels of MMP-1 and MMP-10 were significantly elevated, whereas those of TIMP-1 and TIMP-2 did not change. In addition, after transfection with siRNAMMP-1 and siRNAMMP-10, migration and tube formation were significantly inhibited. Akt/mTOR/S6 signalling was found to be involved in upregulating MMP-1 and MMP-10 expression, and the sequential blockade of steps in the pathways effectively prevented Tp47-induced angiogenesis. CONCLUSION: The results reveal the underlying mechanism of angiogenesis promoted by Tp47, namely, upregulating MMP-1 and MMP-10 expression to disrupt the MMP/TIMP balance through the Akt/mTOR/S6 pathway. These findings contribute to our understanding of the pathophysiology of syphilis.

Long non-coding RNA LINC01287 promotes breast cancer cells proliferation and metastasis by activating Wnt/ß-catenin signaling.

OBJECTIVE: Long noncoding RNA (lncRNAs) frequently exhibited abnormal levels in numerous tumors and other diseases in current biological researches. LINC01287, a newly discovered lncRNA, has been found to act as an oncogene in hepatocellular carcinoma. The aim of this research was to explore the expressions and functions of LINC01287 in breast cancer (BC). PATIENTS AND METHODS: The relative expressions of LINC01287 in BC tissues and cells were determined using RT-PCR. The associations between the LINC01287 expression, the clinicopathological factors, and the overall survival of BC patients were statistically examined. The apoptosis and proliferation abilities of MCF-7 and MDA-MB-468 cells were analyzed by MTT and flow cytometry assay after LINC01287 knockdown. The effects of LINC01287 in migration and invasion were determined using wound-healing and transwell assays. The protein expressions of the Wnt/ß-catenin pathway were determined using Western blot. RESULTS: We showed that the levels of LINC01287 were significantly upregulated in BC tissues and BC cell lines, and the abnormal expressions of LINC01287 were correlated with TNM stage and lymph node metastasis. A distinct difference was observed and indicated that BC patients with higher LINC01287 expressions had significantly shorter overall survival than patients with lower LINC01287 expressions. The multivariate analysis demonstrated that LINC01287 expression was independently correlated with the overall survival. Si-LINC01287 transfection significantly inhibited the proliferation and metastasis of BC cells, and further promoted apoptosis. Besides, the knockdown of LINC01287 suppressed Wnt/ß-catenin activation and affected the expressions of ß-catenin, cyclin D1, and c-myc. CONCLUSIONS: Our findings indicated that the new lncRNA LINC01287 was correlated with poor clinical outcome and may function as a novel prognostic biomarker and therapeutic target in the development of antineoplastic therapies for BC.

Analysis of serum metabolite profiles in syphilis patients by untargeted metabolomics.

BACKGROUND: Global metabolomics analysis can provide substantial information on energy metabolism, physiology, possible diagnostic biomarkers and intervention strategies for pathogens. OBJECTIVE: To gain a better understanding of the mechanisms of syphilis and analysis of serum metabolite profiles in syphilis patients. METHODS: We conducted an untargeted metabolomics analysis of serum from 20 syphilis patients and 20 healthy controls. RESULTS: A total of 2890 molecular features were extracted from each sample, and the peak intensity of each feature was obtained. Distinct differential metabolites were identified by principal component analysis, partial least squares-discriminant analysis and hierarchical clustering analysis. Furthermore, five metabolites were identified as significantly different by Student's t-test, including trimethylamine N-oxide, l-arginine, lysoPC(18:0), betaine and acetylcarnitine. KEGG analysis showed that these differential metabolites were in various pathways, including Chagas disease, fatty acid biosynthesis, primary bile acid biosynthesis, Salmonella infection, ABC transporters, glycerophospholipid metabolism and choline metabolism. Among them, trimethylamine N-oxide was 3.922 times in patients with syphilis than healthy controls. CONCLUSION: Trimethylamine N-oxide may be used as an indicator to distinguish between syphilis patients and healthy controls. The changes in these metabolites suggest that Treponema pallidum affects the normal metabolic activity of host cells, providing some clues for elucidating the pathogenesis of T. pallidum.

Arsenic and five metal concentrations in the muscle tissue of bigeye tuna (Thunnus obesus) in the Atlantic and Indian Oceans.

White muscle concentrations of As, Cd, Cu, Fe, Se, and Zn were investigated in Atlantic- and Indian-bigeye tuna (BET) (Thunnus obesus) from 6 regions. As and Cd muscle concentrations were significantly higher in the Indian-BET than in the Atlantic-BET, whereas the Indian-BET caught in the waters off South Africa revealed the highest As, Se, and Zn muscle concentrations. Accordingly, multidimensional scaling separated them into two oceanic groups. Positive linear relationships between muscle Cd concentration and fork length (FL) were established in both oceans. For the other elements, only muscle-Fe and FL relationship was found in the Atlantic-BET. 10.3% of BET > 145 cm FL from both oceans possessed muscle Cd concentrations exceeding the food safety limit (0.1 µg g-1 wet weight) set by the European Commission. Increased Cd, Cu and Zn pollution was found in the Atlantic Ocean compared with previous data, with higher levels found in the Indian Ocean.

MiR-1271 negatively regulates AKT/MTOR signaling and promotes apoptosis via targeting PDK1 in pancreatic cancer.

OBJECTIVE: Pancreatic cancer (PC) possesses a very poor prognosis, and its pathogenesis is not fully understood. Evidence has suggested that microRNAs play important roles in cancer development and progression, the present study was designed to study the function of miR-1271 in PC. PATIENTS AND METHODS: PC tissues and adjacent normal tissues were collected from 17 patients. MiR-1271 and PDK1 expression were quantified by quantitative reverse-transcriptional polymerase chain reaction (RT-PCR). AKT/MTOR signaling activity and PDK1 protein expression were determined by Western blot. Cell viability and apoptosis were assessed by MTT assay and enzyme-linked immunosorbent assay (ELISA). Luciferase assay was used to verify whether miR-1271 directly targets PDK1. RESULTS: MiR-1271 was significantly down-regulated in PC tissues compared with that in the paired normal adjacent tissue, and its expression was up-regulated dose-dependently upon cisplatin treatment in PC cells. Overexpression of miR-1271 in these cells produced a pro-apoptotic effect, similar to what caused by cisplatin treatment. Moreover, overexpression of miR-1271 inhibited AKT/MTOR signaling, which was due to the targeting relationship between miR-1271 and PDK1. Finally, knockdown of PDK1 exerted a similar effect on apoptosis to that of miR-1271 overexpression. CONCLUSIONS: MiR-1271 is a potent tumor suppressor in PC, its pro-apoptotic function was partially mediated by reduced AKT/MTOR signaling. Targeting miR-1271 may represent an effective strategy for PC treatment.

Sponge Prokaryote Communities in Taiwanese Coral Reef and Shallow Hydrothermal Vent Ecosystems.

Previously, it was believed that the prokaryote communities of typical 'low-microbial abundance' (LMA) or 'non-symbiont harboring' sponges were merely subsets of the prokaryote plankton community. Recent research has, however, shown that these sponges are dominated by particular clades of Proteobacteria or Cyanobacteria. Here, we expand on this research and assess the composition and putative functional profiles of prokaryotic communities from LMA sponges collected in two ecosystems (coral reef and hydrothermal vent) from vicinal islands of Taiwan with distinct physicochemical conditions. Six sponge species identified as Acanthella cavernosa (Bubarida), Echinodictyum asperum, Ptilocaulis spiculifer (Axinellida), Jaspis splendens (Tetractinellida), Stylissa carteri (Scopalinida) and Suberites sp. (Suberitida) were sampled in coral reefs in the Penghu archipelago. One sponge species provisionally identified as Hymeniacidon novo spec. (Suberitida) was sampled in hydrothermal vent habitat. Each sponge was dominated by a limited set of operational taxonomic units which were similar to sequences from organisms previously obtained from other LMA sponges. There was a distinct bacterial community between sponges collected in coral reef and in hydrothermal vents. The putative functional profile revealed that the prokaryote community from sponges collected in hydrothermal vents was significantly enriched for pathways related to DNA replication and repair.

Long noncoding RNA HOXD-AS1 regulates proliferation of cervical cancer cells by activating Ras/ERK signaling pathway.

OBJECTIVE: To investigate the effects of HOXD cluster antisense RNA 1 (HOXD-AS1) in cervical cancer and its underlying mechanism. PATIENTS AND METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was used to examine the expression of HOXD-AS1 in human cervical cancer tissues. x2-test was used for analyzing the association of HOXD-AS1 expression and clinical parameters. Cell viability, colony formation capacity, and phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2) in treated HeLa and CaSki cells were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, colony formation assay, and Western blot analysis, respectively. RESULTS: The results indicated that HOXD-AS1 was upregulated in cervical cancer cells significantly. Meanwhile, HOXD-AS1 expression was involved in tumor-node-metastasis stages, lymphovascular invasion, lymph node metastasis, as well as recurrence. HOXD-AS1 knockdown remarkably suppressed cervical cancer cell proliferation, colony formation capacity, and the Ras/ERK signaling pathway in vitro. Furthermore, xenograft assays confirmed the results in vivo. CONCLUSIONS: Our data elucidate that silencing HOXD-AS1 remarkably suppresses cell growth by inactivating the Ras/ERK pathway in cervical cancer, providing a more detailed understanding of cervical cancer pathogenesis and providing a possible theoretical foundation for long non-coding RNA for the diagnosis and therapy for cervical cancer.

Tangeretin has anti-asthmatic effects via regulating PI3K and Notch signaling and modulating Th1/Th2/Th17 cytokine balance in neonatal asthmatic mice.

Asthma is a chronic allergic disease characterized by airway inflammation, airway hyper-responsiveness (AHR), and mucus hypersecretion. T-lymphocytes are involved in the pathogenesis of asthma, mediating airway inflammatory reactions by secreting cytokines. The phosphoinositide 3-kinase (PI3K) and Notch signaling pathways are associated with T cell signaling, proliferation, and differentiation, and are important in the progression of asthma. Thus, compounds that can modulate T cell proliferation and function may be of clinical value. Here, we assessed the effects of tangeretin, a plant-derived flavonoid, in experimental asthma. BALB/c mice at postnatal day (P) 12 were challenged with ovalbumin (OVA). Separate groups of mice (n=18/group) were administered tangeretin at 25 or 50 mg/kg body weight by oral gavage. Dexamethasone was used as a positive control. Tangeretin treatment reduced inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) and also restored the normal histology of lung tissues. OVA-specific IgE levels in serum and BALF were reduced. AHR, as determined by airway resistance and lung compliance, was normalized. Flow cytometry analyses revealed a reduced Th17 cell population. Tangeretin reduced the levels of Th2 and Th17 cytokines and raised IFN-γ levels. PI3K signaling was inhibited. The expressions of the Notch 1 receptor and its ligands Jagged 1 and 2 were downregulated by tangeretin. Our findings support the possible use of tangeretin for treating allergic asthma.

Down-expression of miR-373 predicts poor prognosis of glioma and could be a potential therapeutic target.

OBJECTIVE: MicroRNAs (miRNAs) are epigenetic regulators of gene expression, and their deregulation plays an important role in human cancer, including glioma. The main objective of this work was to investigate the expression level of miR-373 and its clinical significance in glioma. PATIENTS AND METHODS: The expression levels of miR-373 in glioma tissues and non-neoplastic brain tissues were measured by the qRT-PCR assay. Patients were divided into two groups based on the median miR-373 expression. The probability of differences in overall and progression-free survival as a function of time was ascertained by use of the Kaplan-Meier method. Cox regression analysis of factors potentially associated with survival was conducted to identify independent factors. RESULTS: In clinical gastric cancer samples, we found that miR-373 expression was significantly down-regulated in glioma tissues compared with non-neoplastic brain tissues (p<0.01). Reduced expression of miR-373 was associated with serum WHO grade (p=0.015) and KPS score (p=0.001). Kaplan-Meier analysis indicated that patients with low level of miR-373 expression had poorer overall survival (OS) and progression-free survival (PFS). Multivariate survival analysis verified that miR-373 expression level was an independent predictor of both OS and PFS for glioma patients. CONCLUSIONS: Our study showed miR-373 was associated to progression in glioma, and suggested it as a potential predictive factor for the prognosis of glioma.

Tangeretin has anti-asthmatic effects via regulating PI3K and Notch signaling and modulating Th1/Th2/Th17 cytokine balance in neonatal asthmatic mice

Asthma is a chronic allergic disease characterized by airway inflammation, airway hyper-responsiveness (AHR), and mucus hypersecretion. T-lymphocytes are involved in the pathogenesis of asthma, mediating airway inflammatory reactions by secreting cytokines. The phosphoinositide 3-kinase (PI3K) and Notch signaling pathways are associated with T cell signaling, proliferation, and differentiation, and are important in the progression of asthma. Thus, compounds that can modulate T cell proliferation and function may be of clinical value. Here, we assessed the effects of tangeretin, a plant-derived flavonoid, in experimental asthma. BALB/c mice at postnatal day (P) 12 were challenged with ovalbumin (OVA). Separate groups of mice (n=18/group) were administered tangeretin at 25 or 50 mg/kg body weight by oral gavage. Dexamethasone was used as a positive control. Tangeretin treatment reduced inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) and also restored the normal histology of lung tissues. OVA-specific IgE levels in serum and BALF were reduced. AHR, as determined by airway resistance and lung compliance, was normalized. Flow cytometry analyses revealed a reduced Th17 cell population. Tangeretin reduced the levels of Th2 and Th17 cytokines and raised IFN-γ levels. PI3K signaling was inhibited. The expressions of the Notch 1 receptor and its ligands Jagged 1 and 2 were downregulated by tangeretin. Our findings support the possible use of tangeretin for treating allergic asthma.