Saikosaponin A mitigates the progression of Parkinson's disease via attenuating microglial neuroinflammation through TLR4/MyD88/NF-κB pathway.

OBJECTIVE: Neuroinflammation caused by excessive microglial cell activation and the subsequent death of dopaminergic neurons plays a role in the pathogenesis of Parkinson's disease (PD). Saikosaponin A (Ssa), a triterpene saponin derived from Radix Bupleuri, has anti-inflammatory and antioxidant functions. This research aimed to investigate whether Ssa has a therapeutic effect on PD. MATERIALS AND METHODS: BV2 microglia- and SH-SY5Y cells were treated with a neurotoxin N-methyl-4- phenylpyridinium (MPP+) and Ssa. Cell viability, apoptosis, inflammatory reactions, and expression levels of oxidative stress mediators were assessed. A PD rat model was created by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), followed by the Ssa treatment. Hematoxylin-eosin (H&E) staining, Nissl staining, and immunohistochemistry were used to detect neuronal apoptosis and microglial activation. Open-field test (OFT) was performed to evaluate the locomotion of the rats. The underlying mechanism of Ssa effect in PD was explored using network pharmacology analysis and verified experimentally. RESULTS: Ssa dampened neuronal apoptosis and had anti-inflammatory and anti-oxidative stress proprieties in MPP+-treated SH-SY5Y cells and BV2 microglia. As shown in in-vivo experiments, Ssa reduced MPTP-mediated neuronal apoptosis and motor dysfunction and lowered the expression of inflammatory factors and oxidative stressors in the substantia nigra (SN) of the PD rat. Additionally, Ssa inactivated the TLR4/MyD88/NF-κB pathway. CONCLUSIONS: This study provides the first evidence that Ssa prevents dopaminergic neurodegeneration caused by microglia activation by modulating the TLR4/MyD88/NF-κB axis.

A clinical study of ultrasonic localization-assisted combined transplantation of a bilateral anterolateral thigh perforator flap for the repair of large-area skin and soft tissue defects of the extremities.

OBJECTIVE: The aim of this study was to investigate the clinical efficacy of the combined transplantation of a bilateral anterolateral thigh perforator (ALTP) flap for the repair of large-area skin and soft tissue defects of the extremities. PATIENTS AND METHODS: Twelve patients who had received bilateral ALTP flap reconstructions for large-area skin and soft tissue defects of the extremities were retrospectively analyzed. The areas of the skin and soft tissue defects were measured preoperatively (18.0×11.0 ‒ 38.0×15.0 cm2). The wounds were on the forearm, elbow, upper arm, foot, and lower leg. Color Duplex Sonography (CDS) was used to localize the site where the perforator artery of the bilateral thighs penetrated the deep fascia. The selected area was evaluated according to the number of perforating branches and the range of supply. The flap areas and repairable range were further evaluated according to the number of perforating branches detected during the operation to determine whether to retain the deep fascia. It is important to design and adjust the anastomosis of the vascular pedicle according to the specific situation on transfer of the flap to the recipient site. The donor sites of all the patients in the study were closed in the first stage. The amount of bleeding and the blood supply to the flap after vascular anastomosis were evaluated during the operation. The postoperative survival of the flap and complications, such as bleeding, infection, and arteriovenous crisis, were closely monitored. All patients were followed-up at one, three, and six months after surgery to assess their satisfaction with the appearance of the flap transplantation and the recovery of limb function. RESULTS: The bilateral ATLP flaps survived successfully in all 12 cases and all donor sites were closed in the first stage. No post-surgery complications, including hematoma, wound dehiscence, and infection, were observed at the donor sites, resulting in high patient satisfaction. CONCLUSIONS: Combined transplantation of bilateral ALTP flaps can repair large-area skin and soft tissue defects in one stage, which not only reduces the number of operations and hospitalization costs but also reduces the damage to the limbs caused by the cutting of large-area flaps from only one side. The accuracy of the surgery was improved by ultrasound-assisted localization. In summary, combined transplantation of bilateral ALTP is a rational yet effective way to repair large-area skin and soft tissue defects of the extremities.

A review of ten years of experience using dexamethasone intravitreal implants (Ozurdex) for uveitis.

Uveitis is a type of ocular inflammatory disease caused by various etiologies, for which corticosteroids are the main treatment. Dexamethasone Intravitreal implant (DEX-I) has been widely used in the treatment of uveitis across the world. Then, new indications and complications appeared. This review aims to summarize the use of DEX-I in uveitis in the past 10 years. We summarized the clinical data (baseline characteristics, efficacy and safety) and discussed controversies by retrospectively analyzing the articles and cases published in PubMed and Web of Science using the terms "Ozurdex", OR "intravitreal dexamethasone implant", AND "uveitis" from 2010 to 2022. DEX-I is effective in reducing edema, improving inflammation and improving vision when treating various conditions of uveitis including infectious, no-infectious, pediatric uveitis, and surgery-related applications. The efficacy of DEX-I as a monotherapy is related to the following: etiology and course of disease, treatment of systemic diseases, patients' toleration after multiple injections, economic situation, etc. In addition, intravitreal corticosteroids implantation may replace systemic therapy in some patients. In terms of safety, the incidence of high intraocular pressure is about 20.52%, and the incidence of cataract is about 15.51%. DEX-I can effectively treat non-infectious uveitis and some infectious uveitis such as suspected tuberculosis, and its safety is controllable. Further studies are necessary to evaluate the effect of monotherapy and to expand more indications.

Characteristics and surgical treatment of recurrence melanoma of the foot: a case report and brief literature review.

OBJECTIVE: Despite advances in plastic and reconstructive surgery, repairing soft tissue defects of the foot remains a complex surgical challenge when conventional methods cannot cover defects. We presented a case in which a free flap was used for reconstruction and reviewed the literature. PATIENTS AND METHODS: A 75-year-old woman with an acral melanoma history had a large exophytic mass on her right foot. Using PubMed, we found that reconstructive options in the literature include local flaps, fascial flaps, muscle flaps, and free flaps. RESULTS: Melanoma recurred four times at the same site after complete excision of the compound nevi in the present case. Melan A, Vimentin (+), S-100 (+), and HMB-45 positivity were found in immunohistochemical staining and increased Ki-67 proliferation. The defects in soft tissue are repaired using a free anterolateral thigh perforator flap. No complications were raised in the patient. CONCLUSIONS: Foot melanoma is difficult to be resected because it necessitates a wide excision, which can result in large defects. The free flap, in our experience, can easily be performed while preserving function and improving cosmesis. This flap is an appealing option for concealing defects in the distal extremities.

Effect of human adipose-derived mesenchymal stem cell conditioned medium on musculoskeletal pain.

OBJECTIVE: Several studies in animal models have shown the safety and effectiveness of mesenchymal stem cell conditioned medium (MSC-CM) in inflammatory lesions involving muscles and joints. PATIENTS AND METHODS: In this report, we retrospectively evaluated 16 patients who received local administration of the human adipose-derived mesenchymal stem cells conditioned medium (hAMSC-CM) for musculoskeletal chronic pain. Overall, 27 body locations expressing pain have been treated. The local administrated dose was 5 ml in the joint cavity and/or 2 ml in the other locations. The patients were asked to conduct self-evaluation of the degree of pain using a numeric rating scale (NRS) questionnaire and record the severity of pain before administration and at 15 min, 1 day, 1 week, and 4 weeks after administration. A second administration has been performed in 7 locations. The analysis was done considering two conditions: the "current pain status" and the "worst pain status in a week." RESULTS: The results showed statistically significant differences between before and after administration at each time point for "current pain status" and at 1-week and 4-week time points for "worst pain status in a week" after first administration (Tukey-Kramer test). After second administration, significant differences were found at 1-week and 4-week time points for "current pain status". No serious adverse effect was found. CONCLUSIONS: It was concluded that local administration of hAMSC-CM appears to be safe and could be expected to have effective therapeutic value against musculoskeletal chronic pain. Further studies are needed to clarify analgesic effects of hAMSC-CM and its underlying mechanism(s).

The emerging role of lncRNAs in the regulation of osteosarcoma stem cells.

OBJECTIVE: Osteosarcoma is a common bone sarcoma that often occurs in childhood and adolescence. In recent years, the efficacy of osteosarcoma treatments has been improved by adjuvant chemotherapies and surgical approaches. However, poor prognosis often occurs among osteosarcoma patients due to recurrence, metastasis, or drug resistance problems. Cancer stem cells (CSCs), a specific type of tumor malignant cells with stem cell-like properties, have been reported to be responsible for tumor origination, aggression, metastasis, recurrence, and drug resistance. CSCs have been identified in osteosarcomas treatment, which exhibits self-renewal, multi-potency, and enhanced drug resistance. Therefore, in the present narrative review, we intend to summarize the role of lncRNAs in regulating CSCs and their effectiveness in the treatment of osteosarcoma. MATERIALS AND METHODS: The databases PubMed (Medline), Web of Science, Embase, Scopus, and Cochrane Library, were used for the presented study. The keywords we used to complete our search are 'lncRNA', 'Stem cell', and 'osteosarcoma'. A total of over 800 relevant articles, with a time limit from 2010 to 2021, were identified according to search strategy. Duplicate records and review articles were excluded by their titles and abstracts. Finally, we found about 80 articles matching our inclusion criteria, which included about 13 relevant studies focusing on both the mechanism and effectiveness of osteosarcomas treatment among osteosarcoma patients. RESULTS: CD133, CD117, ALDH, and Stro-1 are validated as the stem cell biomarkers in osteosarcoma CSCs. Accumulating evidence has revealed that lncRNAs, containing HIF2PUT, SOX2-OT, MALAT1, THOR, B4GALT1-AS1, H19, PVT1, FER1L4, LINK-A, DANCR, and DLX6-AS1, play a potential role in regulating CSCs in osteosarcoma. The drug resistance, inhibition of the relapse, and metastasis in osteosarcoma could be avoided via regulating lncRNAs of targeting CSCs. CONCLUSIONS: Multiple lncRNAs regulate CSCs in osteosarcoma via various molecular mechanisms. This review demonstrated that the method of eliminating CSCs by targeting these lncRNAs is a safe, effective, and a well-tolerated way for osteosarcoma patients, which shows a broad research prospect in tumor diagnoses and therapies. However, this method should be further demonstrated by better animal models and more clinical experiments.

Outcomes of hepatic epithelioid hemangioendothelioma with different managements: a retrospective investigation.

OBJECTIVE: Hepatic epithelioid hemangioendothelioma (HEH) is an extremely rare tumor, and no standard treatment has been established yet. This study aimed to retrospectively investigate the outcomes of different managements for HEH patients. PATIENTS AND METHODS: From March 2014 to November 2019, a retrospective investigation was performed among 50 HEH patients to summarize the outcomes of different managements. Their medical records were collected, and the outcome of each management was evaluated based on radiological images. RESULTS: Of the 50 HEH patients examined, 80% were asymptomatic, and 94% had multiple intrahepatic lesions. Extrahepatic metastases were detected in 54% of patients, and 82% of patients were radiologically misdiagnosed. 16 (88.9%) of 18 patients with initial observation had progressive disease (PD). Of 12 patients with curatively intended surgery or radiofrequency ablation (RF), 10 (83.3%) of them had a recurrence. Six treated patients with interferon-α had results of 4 partial responses (PR), 1 complete response (CR), and 1 stable disease (SD). Of 6 patients with thalidomide, 4 patients had PD, and 2 patients had SD. Four patients treated with chemotherapy had 3 PD and 1 SD. Five patients treated with targeted therapy had 2 PR, 2 PD, and 1 SD. CONCLUSIONS: During our observation, we found that HEH patients had a high chance of PD. The risk of recurrence after surgery or RF was high. The encouraging result of interferon-α therapy makes it a promising treatment for HEH.

MDM4 is targeted by miR-449b-5p to promote the proliferation of endometrial carcinoma.

OBJECTIVE: Previous studies have shown the involvement of microRNA-449b-5p (miR-449b-5p) and MDM4 in tumor development. This study aims to illustrate the role of miR-449b-5p in inhibiting proliferative capacity of endometrial carcinoma (EC) by targeting MDM4. PATIENTS AND METHODS: Expression levels of miR-449b-5p and MDM4 in tumor tissues and paracancerous ones of EC patients were determined. Relationships between their levels and clinical parameters of EC patients were analyzed. Subsequently, regulatory effects of miR-449b-5p and MDM4 on proliferative capacities in KLE and HEC-1B cells were assessed by cell counting kit-8 (CCK-8) and colony formation assay, respectively. Thereafter, in vivo xenograft models were established in nude mice administrated with KLE cells overexpressing MDM4 or those with miR-449b-5p knockdown. Then, tumor weight and tumor volume were measured after mouse sacrifice. Finally, the interaction between miR-449b-5p and MDM4 was explored by Luciferase assay. RESULTS: It was found that MDM4 was upregulated and miR-449b-5p was downregulated in EC tissues. Highly expressed MDM4 and lowly expressed miR-449b-5p were unfavorable to prognosis in EC patients, manifesting as a larger tumor size, more advanced tumor stage and lower overall survival. Besides, overexpression of MDM4 enhanced in vitro proliferative capacity in EC cells and in vivo tumorigenesis in nude mice bearing EC. Similarly, knockdown of miR-449b-5p yielded similar results. Luciferase assay confirmed that MDM4 was the target gene binding to miR-449b-5p, and its level was negatively correlated with miR-449b-5p level in EC. CONCLUSIONS: MiR-449b-5p and MDM4 are downregulated and upregulated in EC species, respectively. They are closely linked to tumor size, tumor stage and overall survival in EC patients. Through negatively regulating MDM4 level, miR-449b-5p inhibits proliferative capacity in EC cells.

Visfatin relieves myocardial ischemia-reperfusion injury through activation of PI3K/Akt/HSP70 signaling axis.

OBJECTIVE: Myocardial ischemia-reperfusion injury (MIRI) is the most common complication of ischemic cardiomyopathy, which severely affects the prognosis of patients. The purpose of this study was to investigate the protective effects of visfatin on the myocardium after ischemia-reperfusion (I/R) and its mechanism. MATERIALS AND METHODS: Sprague Dawley rats were used to construct the MIRI model and visfatin was administrated intraperitoneally in rats to determine the protective effect of visfatin on myocardium after I/R. In addition, visfatin was used to treat rat myocardial cell line H9c2 cells and detect its effect on H9c2 cells. The effect of visfatin on the PI3K/Akt/HSP70 signaling axis in H9c2 cells was also detected to determine the mechanism of the myocardial protection of visfatin. RESULTS: The damage of cardiomyocytes in MIRI rats pretreated with visfatin was significantly improved compared with untreated MIRI rats. Visfatin also reduced the level of inflammation and apoptosis of cardiomyocytes in MIRI rats, reduced myocardial injury markers, and improved cardiac function. In vitro, visfatin also reduced inflammatory and apoptotic factors in H9c2 cells. In addition, visfatin also promoted the activity of the PI3K/Akt signaling pathway and increased HSP70 expression in H9c2 cells. The inhibition of the PI3K/Akt signaling pathway was found to attenuate the promotion of HSP70 by visfatin. SiRNA-HSP70 also attenuated the protective effect of visfatin on H9c2 cells. CONCLUSIONS: Visfatin reduces the inflammation and apoptosis levels of myocardial cells through the PI3K/Akt/HSP70 signaling axis, thereby reducing I/R-induced myocardial injury.

Long non-coding RNA TTN-AS1 promotes the metastasis in breast cancer by epigenetically activating DGCR8.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long non-coding RNA TTN-AS1 promotes the metastasis in breast cancer by epigenetically activating DGCR8, by P. Qiu, Y. Dou, L.-Z. Ma, X.-X. Tang, X.-L. Liu, J.-W. Chen, published in Eur Rev Med Pharmacol Sci 2019; 23 (24): 10835-10841-DOI: 10.26355/eurrev_201912_19787-PMID: 31858552" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19787.

MicroRNA-18a suppresses ovarian carcinoma progression by targeting CBX7 and regulating ERK/MAPK signaling pathway and epithelial-to-mesenchymal transition.

OBJECTIVE: Ovarian carcinoma (OC) is one prevalent fatal malignancy in gynecology. Currently, there is an imperative need to better investigate the pathogenesis of OC. Accumulating evidence has indicated that microRNAs (miRNAs) play pivotal roles in OC occurrence and development. In this study, we mainly investigated the potential roles of miR-18a in OC progression. PATIENTS AND METHODS: We first examined miR-18a expressions in OC tissue samples and cell lines using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Moreover, OC patients involved in current study were assigned into two groups based on the mean miR-18a expression level. Kaplan-Meier analysis was carried out to assess the overall survival rate of miR-18a in OC patients. Next, we investigated whether miR-18a could regulate OC cell proliferation abilities by using MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assays. Next, transwell assay was used to detect the effects of miR-18a on cell invasion and migration. We further performed Luciferase reporter assays by cotransfecting with miR-18a mimics and the Luciferase reporter vector containing CBX7 3'UTR-WT or MUT. We then performed immunohistochemistry (IHC) assays to determine the expression of CBX7 in OC tissues. RESULTS: QRT-PCR results indicated that miR-18a expressions were notably decreased in OC related cell lines and tissues. Moreover, the low miR-18a expression was related to the malignant phenotype and poor prognosis of OC patients. Overexpression of miR-18a in OC cells could prominently suppress the proliferation, migration and invasion abilities via modulating ERK/MAPK pathway and epithelial-to-mesenchymal transition (EMT). Furthermore, CBX7 was confirmed as a functional target of miR-18a, indicating that miR-18a exerted the suppressive functions in OC cells partially via the regulation of CBX7. Additionally, restoration of miR-18a remarkably reduced the OC tumor growth in vivo. CONCLUSIONS: Taken together, our study rationally suggested that miR-18a may serve as an effective diagnostic and therapeutic biomarker for OC.

Comparison of IMRT and VMAT radiotherapy planning for Graves' ophthalmopathy based on dosimetric parameters analysis.

OBJECTIVE: To compare volumetric modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) for the treatment of Graves' ophthalmopathy (GO) based on the dosimetric data. PATIENTS AND METHODS: 19 patients diagnosed with GO were recruited in this study. For each patient, a dual-partial-arc VMAT plans and a 7-fixed-field IMRT plans were replanned. Dosimetric parameters of the targets and organs at risk (OARs) originated from the two kinds of plans were compared and analyzed. RESULTS: Homogeneity index (HI) was superior in IMRT plans compared with VMAT (p=0.0014) but there was no significant statistical difference in conformity index (CI) between them (p=0.0673). IMRT plans revealed advantage in the OARs protection especially for the left and right lenses, optic nerves and eyeballs (p<0.05). CONCLUSIONS: VMAT and IMRT are both feasible techniques in radiotherapy in GO from the perspective of dosimetric parameters. Homogeneity and OAR protection were slightly superior in IMRT plans compared with VMAT plans.

LINC00675 suppresses proliferative, migration and invasion of clear cell renal cell carcinoma via the Wnt/ß-catenin pathway.

OBJECTIVE: To clarify the role of LINC00675 in affecting the progression of clear cell renal cell carcinoma (ccRCC) and its potential mechanism, thus providing effective hallmarks and therapeutic targets for the clinical treatment of ccRCC. MATERIALS AND METHODS: Differentially expressed long non-coding RNAs (lncRNAs) in renal epithelial tissues and ccRCC tissues were searched by analyzing the dataset downloaded from The Cancer Genome Atlas (TCGA) and LINC00675 was selected. LINC00675 level in ccRCC cell lines was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Overexpression model of LINC00675 model in 786-O and 769-P cells was constructed by the transfection of pcDNA3.1(+)-LINC00675 (LV-LINC00675). Changes in proliferative, migratory, and invasive capacities of 786-O and 769-P cells overexpressing LINC00675 were assessed. At last, relative levels of ß-catenin, Vimentin, and N-cadherin in ccRCC cells overexpressing LINC00675 were detected by qRT-PCR and Western blot. RESULTS: LINC00675 was downregulated in ccRCC tissues and cell lines. Overexpression of LINC00675 attenuated proliferative, migratory, and invasive capacities of 786-O and 769-P cells. Downregulation in ß-catenin after overexpression of LINC00675, while Vimentin and N-cadherin levels did not change. CONCLUSIONS: LINC00675 is downregulated in ccRCC. Overexpression of LINC00675 attenuates ccRCC to proliferate, migrate, and invade by activating the Wnt/ß-catenin pathway.

Long non-coding RNA TTN-AS1 promotes the metastasis in breast cancer by epigenetically activating DGCR8.

OBJECTIVE: Breast cancer (BC) is one of the most common fatal cancers. Recent studies have identified the vital roles of long non-coding RNAs (lncRNAs) in the development and progression of BC. This research aimed to investigate the underlying mechanisms of lncRNA TTN-AS1 in the metastasis of BC. PATIENTS AND METHODS: TTN-AS1 expression of tissues was detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) in 50 BC patients. Wound healing assay and transwell assay were used to observe the phenotypic alteration of BC cells after knockdown or overexpression of TTN-AS1. Moreover, RT-qPCR and Western blot assay were performed to discover the potential targets of TTN-AS1 in BC. RESULTS: TTN-AS1 expression in BC samples was significantly higher than that of the adjacent tissues. Besides, the migration and invasion of BC cells were markedly inhibited after TTN-AS1 was silenced, while promoted after TTN-AS1 overexpression. In addition, a remarkable decrease of DGCR8 was observed after TTN-AS1 was inhibited in BC cells, while DGCR8 was upregulated after overexpression of TTN-AS1. Furthermore, DGCR8 expression showed significant enhancement in BC tissues and was positively associated with TTN-AS1 level. CONCLUSIONS: Our study uncovered a new oncogene in BC and suggested that TTN-AS1 could enhance BC cell migration and invasion via sponging DGCR8, which provided a novel therapeutic target for the treatment of breast cancer.

Long noncoding RNA UCA1 regulates proliferation and apoptosis in multiple myeloma by targeting miR-331-3p/IL6R axis for the activation of JAK2/STAT3 pathway.

OBJECTIVE: We attempted to clarify the regulatory mechanism of UCA1/miR-331-3p/IL6R on cell progression in multiple myeloma (MM). PATIENTS AND METHODS: The expression of UCA1, miR-331-3p, and IL6R in tumor tissues and cells was measured by qRT-PCR. Cell Counting Kit-8 (CCK-8) was conducted to detect cell proliferation, and flow cytometry assay was applied to examine cell apoptosis. Protein expression of L6R, p-JAK2, p-STAT3, c-Myc, CyclinD1, Bcl-2, and Bax was detected by Western blot assay. The interaction among miR-331-3p, UCA1, and IL6R was determined by Luciferase reporter system. Murine xenograft assay was performed to confirm the biological function of UCA1 in vivo. RESULTS: The expression of UCA1 and IL6R was up-regulated, while miR-331-3p was down-regulated in MM tumors and cell lines compared with normal tissues and cells. By calculation, miR-331-3p was correlated with UCA1 or IL6R inversely. In addition, UCA1 knockdown suppressed cell proliferation and promoted apoptosis in vitro and in vivo. Luciferase reporter system confirmed the interaction between miR-331-3p and UCA1 or IL6R. More importantly, UCA1 restored miR-331-3p mediated inhibition of proliferation and promotion on apoptosis of MM cells. Consistently, IL6R rescued UCA1 knockdown caused repression on MM cell growth and elevation on apoptosis. Besides, UCA1 facilitated the activation of the JAK2/STAT3 signaling pathway by enhancing IL6R expression via targeting miR-331-3p. CONCLUSIONS: UCA1 accelerates proliferation and suppresses apoptosis in MM by targeting miR-331-3p/IL6R axis to activate JAK2/STAT3 pathway, providing potential targets for the diagnosis and therapy of MM.

PCAT1 promotes the proliferative and migratory potentials of ovarian cancer via targeting NEK2.

OBJECTIVE: The aim of this study was to clarify the potential role of PCAT1 in the occurrence and development of ovarian cancer (OC). PATIENTS AND METHODS: Expression levels of PCAT1 and NEK2 in OC tissues and cell lines were detected by quantitative Real-time polymerase chain reaction (qRT-PCR). Correlation between PCAT1 expression with tumor stage and prognosis of OC patients was analyzed. Knockdown or over-expression of PCAT1 and NEK2 were achieved by siRNA or lentivirus transfection, respectively. Subsequently, cell viability, apoptosis, cell cycle progression and migration were determined by cell counting kit-8 (CCK-8), flow cytometry and transwell assay, respectively. Furthermore, the protein levels of relative genes in Wnt pathway were detected by Western blot. RESULTS: PCAT1 was highly expressed in OC tissues and cell lines, especially in tumor tissues with stage III-IV compared with stage I-II. The prognosis of OC patients with higher expression of PCAT1 was significantly worse than those with lower expression. In vitro experiments confirmed that PCAT1 knockdown obviously inhibited proliferative and migratory potentials, whereas induced apoptosis of OC cells. No significant changes were observed in cell cycle progression of OC cells after knockdown or overexpression of PCAT1. Meanwhile, overexpression of PCAT1 remarkably upregulated the expression level of NEK2, which was the target gene of PCAT1. Interestingly, NEK2 knockdown could obviously suppress cell migration. Furthermore, Western blot results elucidated that PCAT1 knockdown could inhibit the protein levels of relative genes in Wnt pathway in OC cells. CONCLUSIONS: PCAT1 was highly expressed in OC tissues than adjacent normal tissues. PCAT1 overexpression significantly promoted proliferative and migratory potentials, whereas inhibited apoptosis of OC cells through upregulating NEK2 expression via Wnt pathway.

MiR-99a suppressed cell proliferation and invasion by directly targeting HOXA1 through regulation of the AKT/mTOR signaling pathway and EMT in ovarian cancer.

OBJECTIVE: Ovarian cancer (OC) is the third frequently tumor worldwide. MicroRNA-99a (miR-99a), acting as a tumor suppressor, has been reported to be downregulated in multiple tumors. We aimed at exploring the significant roles of miR-99a in ovarian cancer. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT-PCR) and Western blotting were applied to calculate the mRNA and protein levels of miR-99a and its target genes. Kaplan-Meier method was conducted to evaluate the overall survival of ovarian cancer patients. CCK8 and transwell assays were performed to measure the proliferative and invasive abilities. RESULTS: miR-99a, acting as a prognosis predictor, was downregulated in ovarian cancer tissues and cell lines. miR-99a mediated the expression of homeobox A1 (HOXA1) through directly targeting to the 3'-untranslated region (3'-UTR) of its mRNA in ovarian cancer cell lines. miR-99a inhibited the proliferation of ovarian cancer by AKT/mTOR pathway in vitro and in vivo, and it suppressed the invasion-mediated epithelial-mesenchymal transition (EMT) through direct targeting to the 3'-UTR of HOXA1 mRNA. CONCLUSIONS: miR-99a suppressed the proliferation through AKT/mTOR signaling pathway and the invasion-mediated EMT in ovarian cancer. The newly identified miR-99a/HOXA1/AKT/mTOR axis provides novel insight into the pathogenesis of ovarian cancer.

Has-MiR-196a-2 is up-regulated and acts as an independent unfavorable prognostic factor in thyroid carcinoma.

OBJECTIVE: To identify the role of hsa-miR-196a-2 in thyroid cancer by bioinformatics analysis. MATERIALS AND METHODS: The expression profiles of thyroid cancer was download from TCGA. The dysregulated microRNAs were obtained by edger R package. Then, the prognostic data were analyzed by K-M plot. The difference between different groups was analyzed by the t-test. At last, the biological processes of has-miR-196a-2 were obtained with GSEA. RESULTS: In this study, we found that has-miR-196a-2 was upregulated in thyroid carcinoma by analyzing the TCGA database, which was inversely proportional to the prognosis of patients with thyroid carcinoma. Univariate and multivariate COX analysis showed that has-miR-196a-2 was an independent prognostic risk factor for thyroid carcinoma. Higher expressions of has-miR-196a-2 were found in patients with older age, advanced tumor stage, lymph node metastasis, and local infiltration through the t-test. We found that has-miR-196a-2 was enriched in adherent junction, focal adhesion, and actin cytoskeleton, which are closely related to the invasion and migration of the function pathway. Moreover, it is mainly enriched in tumor progression pathways, such as the PPAR pathway and WNT pathway. CONCLUSIONS: Hsa-miR-196a-2 is overexpressed in thyroid tumors and is an independent prognostic risk factor for thyroid carcinoma.

Prevalence of pollen-induced allergic rhinitis with high pollen exposure in grasslands of northern China.

BACKGROUND: The aim of this study was to investigate the prevalence of epidemiologic and physician-diagnosed pollen-induced AR (PiAR) in the grasslands of northern China and to study the impact of the intensity and time of pollen exposure on PiAR prevalence. METHODS: A multistage, clustered and proportionately stratified random sampling with a field interviewer-administered survey study was performed together with skin prick tests (SPT) and measurements of the daily pollen count. RESULTS: A total of 6043 subjects completed the study, with a proportion of 32.4% epidemiologic AR and 18.5% PiAR. The prevalence was higher in males than females (19.6% vs 17.4%, P = .024), but no difference between the two major residential and ethnic groups (Han and Mongolian) was observed. Subjects from urban areas showed higher prevalence of PiAR than rural areas (23.1% vs 14.0%, P < .001). Most PiAR patients were sensitized to two or more pollens (79.4%) with artemisia, chenopodium, and humulus scandens being the most common pollen types, which were similarly found as the top three sensitizing pollen allergens by SPT. There were significant regional differences in the prevalence of epidemiologic AR (from 18.6% to 52.9%) and PiAR (from 10.5% to 31.4%) among the six areas investigated. PiAR symptoms were positively associated with pollen counts, temperature, and precipitation (P < .05), but negatively with wind speed and pressure P < .05). CONCLUSION: Pollen-induced AR (PiAR) prevalence in the investigated region is extremely high due to high seasonal pollen exposure, which was influenced by local environmental and climate conditions.

Colletotrichum species causing anthracnose disease of chili in China.

Anthracnose caused by Colletotrichum species is a serious disease of more than 30 plant genera. Several Colletotrichum species have been reported to infect chili in different countries. Although China is the largest chili-producing country, little is known about the species that have been infecting chili locally. Therefore, we collected samples of diseased chili from 29 provinces of China, from which 1285 strains were isolated. The morphological characters of all strains were observed and compared, and multi-locus phylogenetic analyses (ITS, ACT, CAL, CHS-1, GAPDH, TUB2, and HIS3) were performed on selected representative strains. Fifteen Colletotrichum species were identified, with C. fioriniae, C. fructicola, C. gloeosporioides, C. scovillei, and C. truncatum being prevalent. Three new species, C. conoides, C. grossum, and C. liaoningense, were recognised and described in this paper. Colletotrichum aenigma, C. cliviae, C. endophytica, C. hymenocallidis, C. incanum, C. karstii, and C. viniferum were reported for the first time from chili. Pathogenicity of all species isolated from chili was confirmed, except for C. endophytica. The current study improves the understanding of species causing anthracnose on chili and provides useful information for the effective control of the disease in China.