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BACKGROUND: Chronic lower back pain (CLBP) is one of the most common disorders worldwide. Flash cupping has the ability to relieve CLBP; nevertheless, its impact on CLBP and the likely mechanism of action have not been studied. OBJECTIVE: The goal of this study was to assess the impact of a single, brief cupping session on CLBP and low back muscle activity using multichannel surface electromyography (sEMG). METHODS: In this randomized controlled trial, 24 patients with CLBP were enrolled and randomly assigned to the control group (treated by acupuncture) and cupping group (treated by acupuncture and flash cupping). Acupuncture was applied on the shen shu (BL23), dachang shu (BL25), and wei zhong (BL40) acupoints in both the groups. A brief cupping treatment was applied to the shen shu (BL23), qihai shu (BL24), dachang shu (BL25), guanyuan shu (BL26), and xiaochang shu (BL27) acupoints on both sides of the lower back in the cupping group. The numeric rating scale (NRS) was used to assess therapy efficacy for lower back pain (LBP) before and after treatment. Surface EMG data collected during symmetrical trunk flexion-extension movements were utilized to measure lower back muscle activity and the effectiveness of LBP therapy. RESULTS: There was no statistically significant difference (P = 0.63) in pain intensity between the two groups before and after treatment. There was a statistically significant difference (P = 0.04) between the control group and the cupping group in the sEMG topographic map parameter CoGx-To-Midline. CONCLUSION: This study established a connection between the action mechanism of flash cupping and enhanced horizontal synchronization of lower back muscular activity. [ABSTRACT FROM AUTHOR]

Flatfoot (pes planus) is a common foot deformity, and its causes are mainly related to age, gender, weight, and genetics. Previous studies have shown that custom-made insoles could have a positive effect in improving plantar pressure and symptoms in individuals with flexible flatfeet, but it remains to be explored whether they can still show benefits in daily walking on different slopes. This study aims to investigate a custom-made insole based on plantar pressure redistribution and to verify its effectiveness by gait analysis on different slopes. We recruited 10 subjects and compared the peak pressure and impulse in each area between custom-made insole (CI) and ordinary insole (OI) groups. The results illustrate that CI raises the pressure in T area, improves the ability of the subjects to move forward in the slope walking, which was beneficial to gait stability. The redistribution of pressure in MF and MH area is promoted to provide active protection for subjects. Meanwhile, CI could decrease the impulse in MF area during uphill and level walking, which effectively reduces the accumulation of fatigue during gait. Moreover, avoiding downhill walking could be able to protect foot from injury in daily life. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the effect of ZHX2 on lung cancer cells proliferation and apoptosis. MATERIALS AND METHODS: The mRNA and protein expression of ZHX2 were detected by qRT-PCR and western blot, respectively. The human lung cancer cells were divided into Control, NC, ZHX2, SB, and ZHX2 + Ani groups. The cell proliferation was detected by CCK-8 assay and the cell migration and invasion were detected by Transwell assay. Cell apoptosis was detected by flow cytometry. Apoptosis and p38MAPK signaling pathway related proteins were detected by western blot. The nude mice model of lung cancer xenograft was constructed. The tumor volume and tumor weight were measured. The expression of PCNA protein in tumor tissues was detected by immunohistochemistry. The apoptosis of tumor cells was detected by TUNEL staining. The ZHX2 and p38MAPK signaling pathway related proteins in tumor tissues were detected by western blot. RESULTS: The expression of ZHX2 gene and protein in the cancer cell lines were significantly decreased. Compared with control and NC groups, the cells proliferation, migration and invasion were inhibited in ZHX2 and SB groups, while the apoptosis and apoptosis related proteins were increased (p < 0.05). Meanwhile, compared with ZHX2 group, the tumor growth rate, volume, weight, the percentage of PCNA-positive cells, and p-P38 MAPK/P38 MAPK were increased significantly in ZHX2 + Ani group, while the apoptotic index and the expression of MMP-9 protein were significantly decreased (p < 0.05). CONCLUSION: ZHX2 could inhibit proliferation and promote apoptosis of lung cancer cells by inhibiting p38MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Estrogen-mediated high reactive oxygen species (ROS) tolerance plays an important role in driving carcinogenesis. ROS overproduction acts as the significant effector to increase genomic instability and transduce redox-related signal pathway. Especially, estrogen-mediated mitochondrial ROS promote the mutations in mitochondrial DNA (mtDNA) and the damage to mitochondrial proteins. Moreover, estrogen-mediated ROS contribute to the alteration of energy metabolism and modulate several redox-sensitive proteins responsible for cell proliferation and anti-apoptosis. On the other hand, estrogen simultaneously performs the antioxidative beneficial functions, which protects cancer cells from the potential cytotoxic effects of estrogen-mediated ROS through activation of nuclear factor-erythroid-2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) antioxidant response. Consequently, estrogen potentiates the high ROS tolerance through increase of ROS production as well as acceleration of ROS elimination, which ultimately results in estrogen-mediated carcinogenesis and malignant transformation. However, this overdependence on antioxidant response system to resist ROS-mediated cytotoxicity also represents the "Achilles' Heel" of estrogen-mediated cancer cells. In other words, the destruction of the high ROS tolerance using antioxidant inhibitors may provide a novel and efficacious measure to selectively eliminate these cancer cells without harming normal cells. Of course, it will be necessary to define the exact situation of ROS homeostasis in the different cellular microenvironment and further decipher the mechanisms of redox regulation, which is consequently used as a new avenue to optimize the clinical therapy for estrogen-mediated cancer.

Nad(p)h: quinone oxidoreductase 1 (NQO1) is an important enzyme which can catalyze the two-electron reduction of quinoid compounds into hydroquinones. NQO1 Pro187Ser polymorphism can change the enzymatic activity of NQO1, and it has been proposed to be associated with risk of esophageal cancer. We performed a meta-analysis to examine the association between NQO1 Pro187Ser polymorphism and esophageal cancer. Odds ratio (OR) with a 95% confidence interval (95% CI) was used to assess the association. Twelve case-control studies with 1,725 cases with esophageal cancer and 2,341 controls were finally included in the meta-analysis. Overall, there was an obvious association between NQO1 Pro187Ser polymorphism and esophageal cancer (allele model: OR = 1.24, 95% CI 1.06-1.46, P OR = 0.009; homozygote model: OR = 1.59, 1195% CI 1.10-2.30, P OR = 0.013; dominant model: OR = 1.31, 95% CI 1.05-1.64, P OR = 0.018). In the subgroup analysis by ethnicity, there was an obvious association between NQO1 Pro187Ser polymorphism and esophageal cancer in Asians but not in Caucasians. Therefore, the meta-analysis suggests that NQO1 Pro187Ser polymorphism is associated with esophageal cancer risk.

The tumor suppressor LKB1 gene encodes a serine-threonine kinase that regulates cell proliferation and polarity. Inactivation of LKB1 by mutations in LKB1 or loss of its expression is highly correlated with lung, ovarian, and pancreatic cancers, and WNT/β-catenin pathway is also known to be involved in many human malignancies. However, the relationship between LKB1 and WNT signaling pathway in esophageal carcinoma remains unknown. The expression of LKB1 in 62 cases of esophageal cancer patients was determined by quantitative real-time PCR. It was found that LKB1 mRNA level was significantly lower than the adjacent normal epithelium and that the LKB1 downregulation was correlating with TNM stages. Moreover, the expression of WNT target genes such as Cyclin D1, C-MYC, MMP2, and FZD2 was significantly upregulated in esophageal cancer tissues. LKB1 overexpression in TE10 cells inhibited TOPFlash luciferase reporter activity and WNT target gene expression even in the presence of WNT3A. Conversely, LKB1 knockdown enhanced WNT signaling activity in esophageal cancer cells. It was also found that LKB1 antagonized WNT signaling pathway through interaction with GSK3β to downregulate β-catenin expression level. Functional investigation revealed that LKB1 suppressed the promotion effects of WNT3A on the cell growth of TE10 cells. The LKB1 functions in regulating cell growth and WNT target genes expression were impaired by GSK3β inhibition, suggesting that LKB1 antagonized WNT-induced cell proliferation through enhancement of GSK3β activity. Together, the interaction between LKB1 and GSK3β upregulates GSK3β activity to suppress WNT-induced cell proliferation in esophageal carcinoma cells. Loss of LKB1 expression may result in the deregulation of WNT/β-catenin pathway to promote malignant progression of esophageal cancer.

p21-activated kinases (PAKs) are activated by various extracellular stimuli and, in turn, activate other kinases by phosphorylating them at specific serine/threonine residues or through protein-protein interaction. As a recently identified member of the group B PAK family, the role of PAK5 in cancer is poorly understood. In this study, we investigated the effect of PAK5 on the malignant phenotype, such as proliferation, cell cycle, apoptosis, migration, and invasion. Cell growth assay and cell cycle analysis consistently showed that knockdown of PAK5 could significantly inhibit the proliferation of breast cancer cells. Wound healing assay. migration assay, and invasion assay showed that PAK5 promoted cell migration. Furthermore, in order to elucidate the underlying mechanism of PAK5 on cellular growth and migration, we examined the protein expressions of cyclin D1, p21, early growth response protein 1 (Egr1), and matrix metalloproteinase 2 (MMP2). Our work further reveals the PAK5-Egr1-MMP2 signaling pathway to be a critical regulator of cell migration and invasion. These results suggest that PAK5 may be a potential therapeutic target for breast cancer.

Several studies have investigated the association between the Toll-like receptor 4 (TLR4) gene +896A/G polymorphism and gastric carcinogenesis, including gastric cancer and precancerous gastric lesions. However, published results are inconsistent. So, we performed a meta-analysis to assess whether the TLR4 +896A/G single-nucleotide polymorphism (SNP) is a risk factor in gastric cancer development. We searched PubMed and Embase databases for studies that reported the odds ratio (OR) and 95 % confidence interval (CI) for the association between the TLR4 +896A/G SNP and the risk of gastric cancer and/or precancerous lesions with the last update of November 2012. Data were analyzed using Review Manager (Version 5.1), and publication bias was estimated. We included 10 study populations, comprising 2,233 cases and 2,849 controls from 8 publications. The pooled OR was 2.00 (95 % CI = 1.59-2.53) for the G allelic model. Analysis stratified by different stages and anatomic sites of neoplasia resulted in a significantly increased risk associated with gastric cancer (OR = 1.87, 95 % CI = 1.44-2.44), especially the non-cardia subtype (OR = 2.03, 95 % CI = 1.51-2.72). Besides, the G allele emerged as a strong risk factor for precancerous gastric lesions (OR = 2.47, 95 % CI = 1.57-3.88). A subsequent subgroup analysis by Helicobacter pylori-positive ratio in cases (>80 %) indicated an enhancement in the association with precancerous lesions (OR = 3.43, 95 % CI = 1.92-6.13). The TLR4 +896A/G SNP is a risk factor in gastric carcinogenesis, especially in H. pylori-infected patients with precancerous lesions.

Malignant melanoma is one of the most lethal and aggressive human malignancies. Suppressed apoptosis and extraordinary invasiveness are the distinctive features that contribute to malignant melanoma. The alkylating agent temozolomide (TMZ) is one of the most effective single chemotherapeutic agents for patients with malignant melanoma, but resistance develops quickly and with high frequency. We constructed a dual-regulated oncolytic adenovirus expressing interleukin 24 (IL-24) gene (Ki67-ZD55-IL-24) by utilizing the Ki67 promoter to replace the native viral promoter of E1A gene. We investigated whether a combination of Ki67-ZD55-IL-24-mediated gene virotherapy and chemotherapy using TMZ produces increased cytotoxicity against human melanoma cells via the induction of apoptosis. Our data indicate that this novel strategy thus holds promising potentials for further developing an effective approach to treat malignant melanoma.

Interferon regulatory factor 1 (IRF1) shows tumor-suppressor activity by suppressing proliferation of cancer cells. To exert its anti-proliferative effects, this factor must ultimately control transcription of several key genes that regulate cell cycle progression. Here, we showed that Ki-67 gene is a novel proliferation-related downstream target of IRF1. IRF1 repressed Ki-67 gene transcription in a dose-dependent manner in human Ketr-3 and 786-O renal carcinoma cells. We previously cloned the Ki-67 core promoter which contained two functional Sp1 binding sites. Mutation of the two Sp1 binding sites abrogated Sp1-dependent enhancement of Ki-67 promoter activity. Forced elevation of IRF1 decreased endogenous Sp1 protein level. However, there was no effect on Sp1 mRNA level after transfected with IRF1. Our findings establish a casual series of events that connect anti-proliferative effects of IRF1 with the Ki-67 gene, which encodes a key regulator of the G1/S phase transition. It suggests that the inhibitory effect on Ki-67 gene expression mediated by decreasing level of Sp1 protein might be a novel function of the anti-tumor activity of IRF1.

Ki-67 as a cell proliferation marker is tightly associated with maintenance and regulation of the cell division. To understand the mechanism of Ki-67 gene expression and regulation, we first cloned 5'-flanking region and identified the Ki-67 core promoter. The deletion analysis and the dual luciferase reporter assay were used to locate the Ki-67 core promoter from -223 to +12 nt relative to the transcriptional initiation site, which is the TATA less, GC rich region comprised of several putative Sp1 binding sites. Compared with the hTERT promoter and Survivin promoter, the Ki-67 core promoter possessed higher transcription activity and more desirable tumor selectivity. In order to further demonstrate the contribution of transcription factor Sp1 on regulating the Ki-67 gene transcription, we confirmed three Sp1 binding sites from -170 to -145 nt, from -63 to -38 nt, and from -14 to +12 nt existed in the Ki-67 core promoter by the supershift assay. The deletion mutagenesis, together with the dual luciferase reporter assay, indicated that these Sp1 binding sites, particularly the region from -170 to -145 nt, were involved in positive regulation of the Ki-67 gene expression. Collectively, it was demonstrated that the region from -223 to +12 nt could drive the transcription of the Ki-67 gene, and the Sp1 binding site is essential to transcriptional regulation of the Ki-67 gene.

Ki-67 plays a crucial role in cell proliferation as well as maintenance or regulation of cell division. The mechanism governing the Ki-67 gene expression remains unknown. Thus, we cloned the core promoter of the human Ki-67 gene and further investigated its transcriptional regulation. The putative Sp1 binding sites were confirmed by electrophoretic mobility shift assay together with an anti-Sp1 antibody-mediated supershift assay. Deletion mutagenesis and firefly luciferase reporter gene assay demonstrated the essential contribution of Sp1 on transcriptional activation of the Ki-67 gene. In this study, we first confirm that there are three Sp1 binding sites in the Ki-67 core promoter. Two Sp1 sites (one at position -159 to -145 nt and the other at position -14 to +12 nt) are mainly involved in transcriptional regulation of the Ki-67 gene. Overexpression of Sp1 can enhance the Ki-67 promoter activity. However, down-regulation of Sp1 expression using siRNA-Sp1 and mithramycin effectively inhibits the Ki-67 gene transcription. Our results suggest that Sp1 is essential for basal promoter activity of the human Ki-67 gene. Inhibition of the Ki-67 transcriptional activity through abolishment of Sp1 may provide the useful prospect for gene therapy.