期刊：
Molecular Medicine Reports,2018年17(1):660-666 ISSN：1791-2997
通讯作者：
Tang, Siyuan;Su, Feng
作者机构：
[Zhu, Shilin] Hunan Univ Chinese Med, Affiliated Hosp 2, Dept Neurol, Changsha 410005, Hunan, Peoples R China.;[Tang, Siyuan] Cent S Univ, Xiang Ya Nursing Sch, 172 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China.;[Su, Feng] Cent S Univ, Xiang Ya Hosp, Dept Emergency, 87 Xiang Ya Rd, Changsha 410008, Hunan, Peoples R China.
通讯机构：
[Tang, Siyuan; Su, Feng] C;Cent S Univ, Xiang Ya Nursing Sch, 172 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China.;Cent S Univ, Xiang Ya Hosp, Dept Emergency, 87 Xiang Ya Rd, Changsha 410008, Hunan, Peoples R China.
摘要：
Diosgenin, as an essential natural steroidal saponin, can be extracted from numerous sources, primarily from fenugreek. It is an important raw material for the synthesis of steroid hormone drugs. It exhibits antitumor, antiinflammatory, antioxidation and several other significant pharmacologic actions, and is of high pharmaceutical value. In the present study, the activities and underlying mechanisms of dioscin in the inhibition of ischemic stroke in rats were investigated. Inflammatory responses wer analyzed using ELISA kits and caspase3 and caspase9 activity was analyzed using Caspase3 and caspase9 activity kits. Western blot analysis was used to measure Tolllike receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factorkappaB (NFkappaB), transforming growth factorbeta1 (TGFbeta1), highmobility group protein 1 (HMGB1), interleukin1 receptorassociated kinase 1 (IRAK1), and tumor necrosis factor receptorassociated factor 6 (TRAF6) protein expression. Dioscin inhibited infarct volume and neurological scores in the ischemic stroke rat model. The results demonstrated that dioscin reduced inflammatory responses, and suppressed the expression of TLR4, MyD88, NFkappaB, TGFbeta1, HMGB1, IRAK1, and TRAF6 in the rat ischemic stroke model. Taken together, these findings suggested that dioscin inhibited ischemic strokeinduced inflammation through inhibition of the TLR4/MyD88/NFkBinduced inflammation the rat model, which provided novel insights into the mechanisms underlying the effect of dioscin as an antiinflammatory candidate for the treatment of ischemic stroke in in the future.
摘要：
Melanin is the pigment responsible for the color of human skin and hair. Melanin serves as a double-edge sword which can exert both protective and spot-causing effects on skin. Although melanin has an important role in protecting the skin against UV damage, an excessive or uneven melanin production can lead to the formation of freckles and age spots. Isoliquiritigenin (ISL) has been reported to inhibit melanin synthesis; however, its role in melanin degradation remains unclear. In the present study, we evaluated the detailed function of ISL in melanin degradation in human epidermal keratinocytes. Since autophagy has been reported to be related to melanin degradation, we also examined the activation of autophagy by ISL treatment in keratinocytes by measurement of autophagy-related proteins, ATG7, LC3 and p62. Moreover, si-ATG7-induced ATG7 knockdown and autophagy inhibitor 3-MA decreased LC3 II protein levels and increased PMEL17, p62 and melanin levels in HaCaT cells, which could be partially reversed by ISL treatment, indicating that autophagy participated in melanin degradation. The decreased p-AKT and p-mTOR proteins upon ISL treatment indicated the involvement of PI3K/AKT/mTOR signaling in ISL-induced melanin degradation. Taken together, we demonstrated that autophagy participates in ISL-induced melanin degradation in human epidermal keratinocytes through PI3K/AKT/mTOR signaling.
摘要：
With the advent of aging, the morbidity rates of such diseases as osteoarthritis, rheumatoid arthritis, and osteoporosis has witnessed a significant increase. As a common rattan drug, sinomenine (SIN) has been widely applied for the treatment of various arthritic diseases in traditional Chinese medicine (TCM) clinics. Given that SIN has been reported to inhibit the expression of Prostaglandin E2 (PGE2) in several types of cells, in this study, the influence of SIN treatment on PGE2 expression in mesenchymal stem cells (MSCs), thereby changing the osteoprotegerin (OPG) receptor/activator for the nuclear factor-kappa B ligand (RANKL) ratio, was investigated. Our results showed that, when compared with the untreated cells, treatment with 0.25 mM SIN can down-regulate the mRNA and protein expression levels of the Prostaglandin E synthase 3 (PTGES3) or PGE2 and RANKL, while the OPG was up-regulated. After being cultured with SIN treated MSC-conditioned medium (stMSC-CM), the amount of TRAP-positive multinucleated osteoclasts differentiated from RAW264.7 cells was reduced. Also, the expression levels of specific markers for active osteoclasts were decreased when incubated with stMSC-CM. Moreover, these changes were able to be recovered when the exogenous RANKL was added to the MSC-CM culture. This indicates that the increased OPG/RANKL ratio can reduce the osteoclastogenesis of RAW264.7 cells. Our results demonstrated that SIN has an inhibitory effect on osteoclast differentiation through mechanisms involving the inhibition of the PGE2-induced OPG/RANKL ratio. SIN can also serve as a proinflammatory mediator to regulate the MSC immunosuppressive effects. Our findings suggest that SIN can be useful for the treatment of bone diseases associated with over-activity of osteoclasts. (C) 2017 Elsevier Masson SAS. All rights reserved.
期刊：
Rapid Communications in Mass Spectrometry,2017年31(5):397-410 ISSN：0951-4198
通讯作者：
Zeng, Jianguo;Zhao, Zhongzhen
作者机构：
[Liu, Xiubin; Zheng, Yajie; Liu, Yisong; Tang, Qi; Zeng, Jianguo; Zuo, Zi] Hunan Agr Univ, Natl & Prov Union Engn Res Ctr, Vet Herbal Med Resources & Initiat, Changsha 410128, Hunan, Peoples R China.;[Liang, Zhitao; Zhao, Zhongzhen] Hong Kong Baptist Univ, Sch Chinese Med, Kowloon, Hong Kong, Peoples R China.;[Zuo, Zi] Hunan Univ Chinese Med, Affiliated Hosp 2, Changsha 410005, Hunan, Peoples R China.
通讯机构：
[Zeng, Jianguo; Zhao, Zhongzhen] H;Hunan Agr Univ, Natl & Prov Union Engn Res Ctr, Vet Herbal Med Resources & Initiat, Changsha 410128, Hunan, Peoples R China.;Hong Kong Baptist Univ, Sch Chinese Med, Kowloon, Hong Kong, Peoples R China.
期刊：
Die Pharmazie,2017年72(8):461-467 ISSN：0031-7144
通讯作者：
Yang, Zhibo
作者机构：
[Zhang, Yujin; Shen, Hui; Yang, Zhibo; Liu, Wen; Tian, Yi] Hunan Univ Chinese Med, Affiliated Hosp 2, Dept Dermatol, Changsha, Hunan, Peoples R China.;[Shen, Hui] Guanxi Univ Chinese Med, Ruikang Hosp, Dept Dermatol, Nanning, Guangxi Provinc, Peoples R China.;[Yao, Xiaolei] Guanxi Univ Chinese Med, Ruikang Hosp, Dept Ophthalmol, Nanning, Guangxi Provinc, Peoples R China.;[Yang, Zhibo] 233 Caie North Rd, Changsha 410005, Hunan, Peoples R China.
通讯机构：
[Yang, Zhibo] 2;233 Caie North Rd, Changsha 410005, Hunan, Peoples R China.
摘要：
Psoriasis, a common chronic skin disorder, is characterized by hyperproliferation and aberrant differentiation of keratinocytes and infiltration of inflammatory cells into the dermis and epidermis. MicroRNAs (miRNAs) are a large family of highly conserved small non-coding RNA which regulates diverse biological process, including cell proliferation, by modulating gene expression at the posttranscriptional level. In the present study, we indicated that miR-99a was specifically downregulated in psoriatic dermatic lesions, and could inhibit HaCaT cells' proliferation; by direct targeting, miR-99a could also regulate the expression of Frizzled-5 (FZD5)/Frizzled-8 (FZD8). In addition, we found that the downstream factor of FZD5/FZD8 signaling, β-catenin, and the downstream target gene of β-catenin, cyclinD1, could be suppressed by miR-99a; the suppressive effect of miR-99a on β-catenin and cyclinD1 could be partially abolished by forced FZD5/FZD8 expression. Taken together, we assume that miR-99a inhibits HaCaT cells' proliferation by targeting FZD5/FZD8 through downstream factors β-catenin and cyclinD1, and provide diagnostic markers and a novel target for psoriasis treatment.
摘要：
Purpose. To explore the safety and efficacy of Ruiyun procedure for hemorrhoids (RPH) or RPH with the simplified Milligan-Morgan hemorrhoidectomy (sMMH) in the treatment of mixed hemorrhoids. Methods. This is a randomized, controlled, balanced, multicenter study of 3000 patients with mixed hemorrhoids. The outcomes and postoperative complications were compared between 5 types of surgeries. Results. The efficacy rate was the highest in patients who received RPH+sMMH and decreased in the following order: patients who received RPH alone, MMH alone, procedure for prolapse and hemorrhoids (PPH) alone, and PPH+sMMH (P < .05). The operation time was the shortest in patients who received RPH alone and increased in the following order: patients who received RPH+sMMH, PPH alone, MMH alone, and PPH+sMMH (P < .01). The duration of postoperative hospitalization stay was the shortest in patients who received RPH alone and increased in the following order: PPH alone, RPH+sMMH, PPH+sMMH, and MMH alone (P < .01). The incidence of postoperative hemorrhage, uroschesis, anal fissure, crissum hematoma or thrombosis, and anorectal stenosis was significantly lower in patients who received RPH+sMMH than in patients who received the other 4 types of surgical treatments (P < .05, P < .01). No significant differences in postoperative rectovaginal fistula and anal incontinence were observed between the 5 groups of patients. Conclusions. RPH with or without simplified MMH can reduce the incidence of postoperative complications and improve the curative efficacy in the treatment of patients with mixed hemorrhoids.
摘要：
The beta 1-adrenergic receptor (AR) is the primary beta-AR subtype in the heart and is the target of metoprolol (Met), which is commonly used to treat angina and hypertension. Previous studies have revealed a positive correlation between the methylation levels of the adrenoreceptor beta 1 gene (Adrb1) promoter in the myocardium with the antihypertensive activity of Met in spontaneously hypertensive rats (SHR), which affects beta 1-AR expression in H9C2 cells. The aim of the present study was to investigate the effects of myocardial beta 1-AR downregulation using short-hairpin RNA (shRNA) against Adrb1 on the antihypertensive activity of Met in SHR. Recombinant adeno-associated virus type 9 (rAAV9) vectors carrying Adrb1 shRNA (rAAV9-Adrbl) or a negative control sequence (rAAV9-NC) were generated and used to infect rat hearts via the pericardial cavity. The results of reverse transcription-quantitative polymerase chain reaction, immunohistochemistry and western blotting analyses demonstrated that cardiac beta 1-AR expression in the rAAV9-Adrbl group was significantly downregulated when compared with the rAAV9-NC group (P<0.001, P<0.001 and P=0.032, respectively). In addition, a greater reduction in systolic blood pressure (SBP) was observed in the rAAV9-NC group compared with the rAAV9-Adrbl group following Met treatment (P=0.035). Furthermore, downregulation of myocardial beta 1-AR was associated with a significant decrease in SBP (P<0.001). In conclusion, these data suggest that suppression of beta 1-AR expression in the myocardium reduces SBP and sensitivity to Met in SHR.
作者机构：
[Zeng, Bijun; Wang, Chang; Tang, Xueyong; Wang, Haizhen; Shen, Hui; Yang, Zhibo; Liu, Wen] Hunan Univ Chinese Med, Dept Dermatol, Affiliated Hosp 2, Changsha 410005, Hunan, Peoples R China.;[Shen, Hui] Guanxi Univ Chinese Med, Dept Dermatol, Ruikang Hosp, Nanning 530000, Guangxi Provinc, Peoples R China.;[Yang, Zhibo] 233 Caie North Rd, Changsha 410005, Hunan, Peoples R China.
通讯机构：
[Yang, Zhibo] 2;233 Caie North Rd, Changsha 410005, Hunan, Peoples R China.
关键词：
MiR-330;IL-22;CTNNB1;Keratinocyte;Psoriasis
摘要：
Psoriasis is a common chronic inflammatory skin disease which is characterized by hyperproliferation and aberrant differentiation of keratinocytes; however the exact pathogenesis is largely unknown. Interleukin-22 (IL-22) has demonstrated its vital role in T cell-mediated immune response by interacting with keratinocytes in the pathogenesis of psoriasis. The microRNAs (miRNAs) are a class of small noncoding RNA molecules that play important roles in cellular processes by regulating gene expression at the post-transcriptional level. MiR-330 has been reported to inhibit the proliferation and migration of mouse keratinocytes. In the present study, we indicated that miR-330 expression in lesion tissue of psoriasis patients was specifically down-regulated, and could inhibit IL-22-induced proliferation of HaCaT and HKC cell. Wnt/beta-catenin pathway plays an essential role in the pathogenesis of psoriasis. By direct targeting CTNNB1, miR-330 could significantly downregulate IL-22-induced CTNNB1 expression. In addition, we found that the downstream targets of b-catenin, CyclinD1 and Axin2, could be affected by miR-330; miR-330 could suppress CyclinD1 protein expression and rescue Axin2 protein expression. Taken together, we indicated miR-330 inhibits IL-22-induced proliferation of HaCaT and HKC cell by targeting CTNNB1 and subsequently affect the downstream factors, CyclinD1 and Axin2 for the first time, and provide diagnostic markers and a novel target for psoriasis treatment. (C) 2017 Published by Elsevier Masson SAS.
作者机构：
[He, Xiaojuan; Lu, Aiping; Niu, Xuyan; Tan, Yong; Lu, Cheng] China Acad Chinese Med Sci, Inst Basic Res Clin Med, Beijing, Peoples R China.;[Liu, Xinru; Zhang, Weidong; Zu, Xianpeng] Second Mil Med Univ, Sch Pharm, Shanghai, Peoples R China.;[Zhou, Ke] Hunan Univ Chinese Med, Affiliated Hosp 2, Changsha, Hunan, Peoples R China.;[Lu, Aiping; Zhang, Weidong; Lu, AP; Zhang, Ge; He, Bing; Bian, Zhaoxiang; Xu, Gang] Hong Kong Baptist Univ, Sch Chinese Med, Inst Adv Translat Med Bone & Joint Dis, Hong Kong, Hong Kong, Peoples R China.;[Xiao, Cheng] China Japan Friendship Hosp, Beijing, Peoples R China.
通讯机构：
[Lu, Aiping] C;[Zhang, Weidong; Lu, Aiping] S;[Zhang, G; Lu, AP] H;China Acad Chinese Med Sci, Inst Basic Res Clin Med, Beijing, Peoples R China.;Second Mil Med Univ, Sch Pharm, Shanghai, Peoples R China.
摘要：
Hyperuricemia (HU) often progresses to combine with non-alcoholic fatty liver disease (NAFLD) in the clinical scenario, which further exacerbates metabolic disorders; early detection of biomarkers, if obtained during the HU progression, may be beneficial for preventing its combination with NAFLD. This study aimed to decipher the biomarkers and mechanisms of the development of steatosis in HU. Four groups of subjects undergoing health screening, including healthy subjects, subjects with HU, subjects with HU combined with NAFLD (HU+NAFLD) and subjects with HU initially and then with HU+NAFLD one year later (HU-->HU+NAFLD), were recruited in this study. The metabolic profiles of all subjects' serum were analyzed by liquid chromatography quadruple time-of-flight mass spectrometry. The metabolomic data from subjects with HU and HU+NAFLD were compared, and the biomarkers for the progression from HU to HU+NAFLD were predicted. The metabolomic data from HU-->HU+NAFLD subjects were collected for further verification. The results showed that the progression was associated with disturbances of phospholipase metabolism, purine nucleotide degradation and Liver X receptor/retinoic X receptor activation as characterized by up-regulated phosphatidic acid, cholesterol ester (18:0) and down-regulated inosine. These metabolic alterations may be at least partially responsible for the development of steatosis in HU. This study provides a new paradigm for better understanding and further prevention of disease progression.
摘要：
The molecular and cellular mechanisms behind the involvement of inflammation in melanoma have not been fully elucidated. In this study, knockdown of Hmgb1 expression increased apoptosis, reduced invasion and p-NF-kappa B expression, but increased Klotho protein level in melanoma tumor cells. The effect of Hmgb1 knockdown was overcome by LPS. Introduction of exogenous Hmgb1 significantly decreased apoptosis, increased invasion, elevated p-NF-kappa B, but lowered Klotho protein level in melanoma cells. The effect of exogenous Hmgb1 was agonized by NF-kappa B inhibitor CAPE. Hmgb1 knockdown activated, but exogenous Hmgb1 inactivated, p-IGF1R/p-PI3K p-85/p-Akt/p-mTOR signaling. Knockdown of Klotho gene expression significantly decreased apoptosis, increased invasion in melanoma cells, and inhibited xenograft A375 tumor growth. A significantly high percentage of cells stained positive for p-NF-kappa B, but negative for Klotho, in melanoma tissues compared to normal and benign skin tissues. The positive p-NF-kappa B and negative Klotho protein expression correlated with poor prognosis in melanoma patients. Multivariate analysis revealed an independent association between p-NF-kappa B / Klotho protein level and overall survival. In conclusion, Hmgb1 can inhibit Klotho gene expression and malignant phenotype in melanoma cells through activation of NF-kappa B signaling.
摘要：
Malignant melanoma is the most aggressive type of skin cancer. RAB22A, a member of RAS oncogene family, has been found to be significantly upregulated in multiple human cancers. In the present study, we found that RAB22A mRNA expression was significantly upregulated in melanoma tissues (including 60 primary melanomas and 84 metastatic melanomas) compared to benign nevi (n = 20), which were significantly higher in metastatic melanoma tissues than primary tissues. Immunohistochemistry data further showed that the positive immunoreactivity of RAB22A was detected in 66% (95/144) melanoma tissues, but not in benign nevi. Moreover, high expression of RAB22A was significantly associated with advanced clinical stage in melanoma. Furthermore, patients with high RAB22A expression had shorter overall survival compared those with low expression of RAB22A. In-vitro study showed that RAB22A was also upregulated in melanoma cell lines WM35, A375, WM451, and SK-MEL-1, when compared with the normal melanocyte HM cells. Knockdown of RAB22A significantly reduced the proliferation, migration and invasion of melanoma A375 cells, while overexpression of RAB22A significantly promoted these malignant phenotypes. In addition, RAB22A was found to be a target of miR-203, a tumor suppressive miRNA in melanoma. Besides, miR-203 was downregulated in melanoma tissues and cell lines, when compared with benign nevi and HM cells, respectively. Taken these findings together, our study could validate an oncogenic role of RAB22A in melanoma, suggesting that RAB22A may be a potential therapeutic target for melanoma.
摘要：
The present study aimed to investigate the effect of co-culture of fibroblast-like synoviocytes (FLS) with human umbilical cord-mesenchymal stem cells (UC-MSCs) on rheumatoid arthritis (RA) and to understand the mechanisms that mediate the induced changes. FLS and UC-MSCs were isolated and cultured individually, FLS were then cultured with or without UC-MSCs. The phenotype of UC-MSCs was analyzed prior to co-culture. The UC-MSCs were successfully isolated and expanded, and exhibited a fibroblast-like morphology. Enzyme-linked immunosorbent assay (ELISA) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to determine the expression levels of interleukin (IL)-1β, IL-6, and chemokine (C-C motif) ligand (CCL)-2. The cell apoptosis rate was determined by flow cytometry. Furthermore, the RNAs of aggrecan and collagen type II were isolated and assessed in a chondrogenesis assay following co-culture for 7, 14, 21 and 28 days. Protein expression levels of apoptosis-related proteins, including B-cell lymphoma (Bcl-2), Bcl-2-associated X protein, p53 and phospho (p)-AKT, and growth differentiation factor-5 were analyzed by western blotting. ELISA and qRT-PCR demonstrated that compared with FLS cultured alone, co-culture with UC-MSCs significantly downregulates the expression levels of IL-1β, IL-6 and CCL-2. Additionally, the percentage of apoptotic cells was significantly increased in the co-cultured cells (P<0.05), and the relative RNAs levels of aggrecan and collagen type II were increased compared with FLS alone. Furthermore, the expression levels of Bcl-2 (P<0.05) and p-AKT (P<0.05) were significantly decreased, whereas, p53 (P=0.001), Bax (P<0.01) and GDF-5 (P<0.01) were increased by co-culture of FLS with UC-MSCs compared with FLS alone. In conclusion, co-culture of FLS with UC-MSCs may be important and clinically useful for the treatment of RA by inhibiting the expression of pro-inflammatory mediators, inducing apoptosis and promoting chondrogenesis.
作者：
Su, Feng;Zhu, Shilin;Ruan, Jinlan;Muftuoglu, Yagmur;Zhang, Longbo*;...
期刊：
Oncotarget,2016年7(4):4142-4154 ISSN：1949-2553
通讯作者：
Yuan, Qianying;Zhang, Longbo
作者机构：
[Su, Feng] Cent S Univ, Xiangya Hosp, Dept Emergency, Changsha, Hunan, Peoples R China.;[Zhu, Shilin] Hunan Univ Chinese Med, Affiliated Hosp 2, Changsha, Hunan, Peoples R China.;[Yuan, Qianying; Ruan, Jinlan] Huazhong Univ Sci & Technol, Dept Pharmacol, Wuhan 430074, Peoples R China.;[Muftuoglu, Yagmur; Yuan, Qianying] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA.;[Zhang, Longbo] Cent S Univ, Xiangya Hosp, Dept Neurosurg, Changsha, Hunan, Peoples R China.
通讯机构：
[Yuan, Qianying] H;[Yuan, Qianying] Y;[Zhang, Longbo] C;Huazhong Univ Sci & Technol, Dept Pharmacol, Wuhan 430074, Peoples R China.;Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA.
关键词：
Notch;RY10-4;breast cancer;resistance
摘要：
RY10-4, a novel protoapigenone analog, shows potent cytotoxicity against human breast cancer cells. However, breast cancer cell lines overexpressing human epidermal growth factor receptor 2 (HER2), SKBR3 and BT474, showed less sensitivity to RY10-4 when compared to breast cancer cells lines expressing lower levels of HER2, such as MDA-MB-231 and MCF-7 cells. This was associated with aberrant hyperactivity in Notch signaling in cells treated with RY10-4, since treatment with RY10-4 causes an increase in Notch activity by 2-to3.5-fold in SKBR3 and BT474 cell lines. The increase in activity was abrogated with a gamma-secretase inhibitor, DAPT, or with Notch1 small-interfering RNA (si-Notch1). Cell proliferation was inhibited more effectively by RY10-4 plus DAPT or si-Notch1 than either agent alone. RY10-4 plus DAPT increases apoptosis in both HER2-overexpressing cell lines by two-fold compared to RY10-4 alone, while DAPT alone has no significant effects on apoptosis. In addition, we previously found RY10-4 could inhibit tumor growth through the PI3K/AKT pathway. Here we report that the combination of RY10-4 and DAPT exhibit additive suppression on AKT phosphorylation, contributing to the anti-cancer effects. In an animal model, this combination therapy inhibits the growth of SKBR3 tumor xenografts in nude mice to a greater extent than treatment with either reagent alone. These results indicate that the aberrant activation of Notch signaling impedes the inhibitory effect of RY10-4 on HER2-amplified cell proliferation. Furthermore, these adverse effects can be prevented by treatment combining RY10-4 with a Notch pathway inhibitor.
摘要：
Objective: The aim of the present study was to investigate the effects of Longdanxiegan formula granule (LDXGFG), a Chinese traditional medicine on Toll-like receptor (TLR) pathway in recurrent genital herpes. Materials and Methods: An experimental recurrent genital herpes model was constructed using herpes guinea pig model. The effect of LDXGFG on expression levels of TLR pathway genes were detected using real-time polymerase chain reaction. Furthermore, the dendritic cells and Langerhans cells were isolated and the TLR pathway genes of these cells were assayed after LDXGFG treatment. Results: The result suggested two different expression patterns of TLR pathway genes in genital herpes and recurrent genital herpes, including upregulated genes and downregulated genes. TLR1, TLR4, TLR6, TLR7, TLR8, TLR9, and TLR10 showed a significant decrease while, TLR2, TLR3, and TLR5 increased in genital herpes and recurrent genital herpes guinea pigs. Meanwhile, the downregulated genes in genital herpes and recurrent genital herpes were stimulated by LDXGFG. By contrast, the upregulated genes decreased significantly after LDXGFG treatment. In both dendritic cells and Langerhans cells, the TLR pathway genes exhibited same pattern: the LDXGFG corrected the abnormal expression of TLR pathway genes. Conclusion: The present results suggest that LDXGFG is an alternative, inexpensive, and lasting-effect medicine for herpes simplex virus 2 infection. Copyright (C) 2016, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC.
摘要：
Numb, an endocytic adaptor, is a known cell fate determinant that participates in asymmetric cell division. The present study aimed to explore the potential roles of Numb in hepatocarcinogenesis. Numb expression was investigated in hepatocellular carcinomas (HCC) with reverse transcription-quantitative polymerase chain reaction and immunohistochemical examination; its association with the prognosis of HCC patients was analyzed. In addition, the effects of Numb deletion on proliferation of HCC cells and its relevant molecules were evaluated in Huh7 and HepG2 cells. Numb overexpression was observed in 62% of adjacent non-tumor tissues and 46% of tumor tissues. Overexpression of Numb in HCC was associated with histological grade, portal vein invasion and the number of tumors (P=0.001, 0.022 and 0.034 respectively). Multivariate analysis revealed that Numb expression was an independent prognostic indicator of HCC patients. Methylation of the Numb promoter contributed to hepatocarcinogenesis. In vitro assays demonstrated that Numb silencing resulted in inhibition of cell proliferation, induction of apoptosis, down-regulation of cyclin-dependent protein kinase 4 (CDK4) and S-phase kinase-associated protein 2 (SKP2), and upregulation of Bcl-2 homologous antagonist/killer (BAK) and cyclin-dependent kinase inhibitor 1 (p21). The present study suggests that downregulation of Numb inhibits colony formation and cell proliferation, induces apoptosis of HCC cells and independently predicts the poor prognosis of HCC patients. Thus, Numb has a potential role in the development and progression of HCC.
