CCL2- and Notch2-mediated Central Sensitization in a Rat Chronic Pelvic Pain Model.

BACKGROUND/AIM: Chronic pelvic pain (CPP) is a common gynecological condition in women with multifactorial etiology. Some studies have revealed that patients with CPP have the same structural and functional changes in the pain matrix in the brain to patients with other types of chronic pain. However, the relationship between localized pelvic pain and changes in the structure and function of the central nervous system is still unclear. MATERIALS AND METHODS: In this study, a rat model of CPP was established by pelvic nerve ligation and behavioral tests were used to validate the model. Afterwards, we compared the expression of CCL2 in CPP and control rats and observed the changes in their behavioral patterns by blocking the expression of CCL2 in the former group. In addition, we upregulated the expression of CCL2 in human microglia cells (HMC3) to further observe the effect of CCL2 on the Notch2 pathway. RESULTS: Our results showed that the expression of chemokine ligand 2 (CCL2) in the serum exosomes, pelvic vascular endothelial cells, and cerebrospinal fluid was higher in the CPP group than the control group (p<0.05). In HMC3 treated with recombinant CCL2 protein, a significant increase in the mRNA and protein expression of Notch2 was observed. CONCLUSION: CCL2 can activate the Notch2 signaling pathway and plays an important role in the central sensitization of chronic pelvic pain.

MiR-21-5p, miR-34a, and human telomerase RNA component as surrogate markers for cervical cancer progression.

OBJECTIVE: This study aimed to demonstrate the predictive value of miR-21-5p, miR-34a, and human telomerase RNA component (hTERC) in cervical cancer (CC) development and evaluated their potential possibility for future clinical applications. METHODS: Specimens were collected from the normal cervix, cervical intraepithelial neoplasia (CIN) I, CIN II/III, cervical squamous cell carcinoma. Cytological evaluations and histopathologic examinations were conducted in all subjects, along with the assessment of human papillomavirus (HPV) DNA. The expression levels of the miR-21-5p and miR-34a were detected by RT-PCR. hTERC amplification was detected by dual-color interphase fluorescence in situ hybridization (FISH). Then miRNA, hTERC expressions were compared with the cytological and histologic examination. RESULTS: Compared to that in the benign samples, the expression of miR-21-5p and miR-34a in abnormal samples was significantly upregulated and downregulated, gradually corresponding to the severity of cervical lesions (P < 0.05). There was a trend toward an increasing amplification of hTERC with the increasing severity of cervical lesions. miR-21-5p and miR-34a expression, and hTERC amplification were more specific than HPV positivity in differentiating low-grade cervical disorders from high-grade ones (P < 0.05). CONCLUSIONS: MiR-21-5p upregulation, miR-34a downregulation, and hTERC amplification were associated with the aggressive progression of CC, which suggests that miR-21-5p, miR-34a and hTERC might serve as surrogate markers for CC progression and potential molecular targets for blockage of the development of CC.

TMPYP4 exerted antitumor effects in human cervical cancer cells through activation of p38 mitogen-activated protein kinase.

BACKGROUND: The aim of the present study was to investigate the potential effects of the 5,10,15,20-tetrakis (1-methylpyridinium-4-yl) porphyrin (TMPyP4) on the proliferation and apoptosis of human cervical cancer cells and the underlying mechanisms by which TMPyP4 exerted its actions. RESULTS: After human cervical cancer cells were treated with different doses of TMPyP4, cell viability was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) method, the apoptosis was observed by flow cytometry (FCM), and the expression of p38 mitogen-activated protein kinase (MAPK), phosphated p38 MAPK (p-p38 MAPK), capase-3, MAPKAPK2 (MK-2) and poly ADP-ribose polymerase (PARP) was measured by Western blot analysis. The analysis revealed that TMPyP4 potently suppressed cell viability and induced the apoptosis of human cervical cancer cells in a dose-dependent manner. In addition, the up-regulation of p-p38 MAPK expression levels was detected in TMPyP4-treated human cervical cancer cells. However, followed by the block of p38 MAPK signaling pathway using the inhibitor SB203580, the effects of TMPyP4 on proliferation and apoptosis of human cervical cancer cells were significantly changed. CONCLUSIONS: It was indicated that TMPyP4-inhibited proliferation and -induced apoptosis in human cervical cancer cells was accompanied by activating the p38 MAPK signaling pathway. Taken together, our study demonstrates that TMPyP4 may represent a potential therapeutic method for the treatment of cervical carcinoma.

TMPYP4 exerted antitumor effects in human cervical cancer cells through activation of p38 mitogen-activated protein kinase

BACKGROUND: The aim of the present study was to investigate the potential effects of the 5,10,15,20-tetrakis (1-methylpyridinium-4-yl) porphyrin (TMPyP4) on the proliferation and apoptosis of human cervical cancer cells and the underlying mechanisms by which TMPyP4 exerted its actions. RESULTS: After human cervical cancer cells were treated with different doses of TMPyP4, cell viability was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) method, the apoptosis was observed by flow cytometry (FCM), and the expression of p38 mitogen-activated protein kinase (MAPK), phosphated p38 MAPK (p-p38 MAPK), capase-3, MAPKAPK2 (MK-2) and poly ADP-ribose polymerase (PARP) was measured by Western blot analysis. The analysis revealed that TMPyP4 potently suppressed cell viability and induced the apoptosis of human cervical cancer cells in a dose-dependent manner. In addition, the up-regulation of p-p38 MAPK expression levels was detected in TMPyP4-treated human cervical cancer cells. However, followed by the block of p38 MAPK signaling pathway using the inhibitor SB203580, the effects of TMPyP4 on proliferation and apoptosis of human cervical cancer cells were significantly changed. CONCLUSIONS: It was indicated that TMPyP4-inhibited proliferation and -induced apoptosis in human cervical cancer cells was accompanied by activating the p38 MAPK signaling pathway. Taken together, our study demonstrates that TMPyP4 may represent a potential therapeutic method for the treatment of cervical carcinoma.

Dysregulation of miRNA-21 and their potential as biomarkers for the diagnosis of cervical cancer.

OBJECTIVE: This study aimed to characterize the miR-21 and evaluated its clinical significance. METHODS: Total RNA was extracted from 30 pairs of fresh specimens of cervical cancer and normal tissues. The expression levels of the miR-21-3p and miR-21-5p were detected by quantitative reverse transcriptase polymerase chain reaction, with U6 as the internal reference gene. We compared the expression of miR-21-3p and miR-21-5p between study group and control groups, the association between miRNA expression level and clinicopathological factors was investigated. RESULTS: The expression of miR-21-3p and miR-21-5p in HPV positive cervical cancer samples was significantly upregulated compared to that in the paired normal samples (P < 0.05); A multivariate analysis demonstrated that the expression of miR-21 was associated with clinicopathological parameters, including depth of invasion and lymph node metastasis. CONCLUSIONS: MiR-21 upregulation is associated with aggressive progression and poor prognosis in cervical cancer, which suggests that miR-21 might be identified as an independent marker for predicting the clinical outcome of cervical cancer patients.

Impact of gasless laparoscopy on circulation, respiration, stress response, and other complications in gynecological geriatrics.

This study aimed to explore the impact of gasless laparoscopy on circulation, respiration, stress response and other complications in gynecological surgery for old female patients. 40 patients (American Society of Anesthesiologists II-III, 60-70y) scheduled for elective gynecological laparoscopy were divided into non-pneumoperitoneum group (NP) and pneumoperitoneum group (P). All patients included were monitored for Compliance, Ppeak, Ppalt, MAP, CVP, HR, SpO2, blood gas analysis (pH, PaCO2, and PaO2), serum cortisol, TNF-α, and IL-6. There were significant differences in bowel tones recovery, postoperative shoulder pain, nausea, and vomiting between two groups (P < 0.05). In the P group, the levels of CVP, and Ppeak and Ppalt at both 10 minutes and 30 minutes after suspension/pneumoperitoneum were significantly higher than those in NP group (P < 0.05). When it came to Compliance, this trend was reversed (P < 0.05). As surgery was conducted, the plasma concentrations of cortisol, IL-6 and TNF-α in the P group were higher than those in the NP group (P < 0.05). Thus, for gynecological diseases of geriatrics, the effect on respiratory and circulatory function is less significant of gasless laparoscopy than in pneumoperitoneum. The stress response, recovery of bowl tone, should pain, nausea, and vomiting after surgery in gasless laparoscopy is improved than in pneumoperitoneum.