A positive feedback loop of heparanase/ syndecan1erve growth factor regulates cancer pain progression

Background@#The purpose of this research was to assess the role of heparanase (HPSE)/syndecan1 (SDC1)erve growth factor (NGF) on cancer pain from melanoma. @*Methods@#The influence of HPSE on the biological function of melanoma cells and cancer pain in a mouse model was evaluated. Immunohistochemical staining was used to analyze HPSE and SDC1. HPSE, NGF, and SDC1 were detected using western blot. Inflammatory factors were detected using ELISA assay. @*Results@#HPSE promoted melanoma cell viability, proliferation, migration, invasion, and tumor growth, as well as cancer pain, while SST0001 treatment reversed the promoting effect of HPSE. HPSE up-regulated NGF, and NGF feedback promoted HPSE. High expression of NGF reversed the inhibitory effect of HPSE down-regulation on melanoma cell phenotype deterioration, including cell viability, proliferation, migration, and invasion. SST0001 down-regulated SDC1 expression. SDC1 reversed the inhibitory effect of SST0001 on cancer pain. @*Conclusions@#The results showed that HPSE promoted melanoma development and cancer pain by interacting with NGF/SDC1. It provides new insights to better understand the role of HPSE in melanoma and also provides a new direction for cancer pain treatment.

Effect of PCIA with dexmedetomidine mixed with subanesthetic dose of ketamine on anxiety and depression in patients with advanced cancer pain / 中华麻醉学杂志

Objective:To evaluate the effect of patient-controlled intravenous analgesia (PCIA) with dexmedetomidine mixed with subanesthetic dose of ketamine on anxiety and depression in the patients with advanced cancer pain.Methods:Sixty patients of either gender with advanced cancer pain, aged 24-82 yr, with poor analgesic effect or obvious adverse reactions after three-step analgesic treatment, were selected and randomly divided into 2 groups ( n=30 each) using a random number table method: routine treatment group (group R) and dexmedetomidine mixed with ketamine group (group DK). The initial dose of morphine for PCIA was 1/3 of the oral dose in group R. In group DK, ketamine 5.4 mg/kg (90 μg·kg -1·h -1) and dexmedetomidine 6 μg/kg (0.1 μg·kg -1·h -1) were added on the basis of group R. Tropisetron 8 mg was added to analgesics and diluted to 200 ml with normal saline in both groups.The analgesic pump was programmed to deliver 4 ml with an initial dose of 4 ml, lockout interval of 15 min and background infusion at 4 ml/h.The numerical rating scale score, Ramsay sedation score, Chinese version of State-Trait Anxiety Inventory score and Beck Depression Inventory-Ⅱ score were recorded before PCIA and at 4, 12, 24 and 48 h of PCIA.The development of effective analgesia and satisfactory sedation, occurrence and degree of depression, score for patient's quality of life and satisfaction score, consumption of morphine and adverse reactions such as constipation, nausea and vomiting, agitation and respiratory depression were recorded within 48 h of PCIA. Results:Compared with group R, the NRS score was significantly decreased, the rate of effective analgesia was increased, Beck Depression Inventory-Ⅱscore and Chinese version of State-Trait Anxiety Inventory score were decreased, the incidence and degree of depression were decreased, incidence of nausea and vomiting and constipation, consumption of morphine and pressing times of PCIA pump were decreased, and the score for patient's quality of life and satisfaction score were increased in group DK ( P<0.05). Conclusion:PCIA with dexmedetomidine mixed with subanesthetic dose of ketamine can significantly enhance the analgesic effect, improve anxiety and depression, and raise the quality of life when used for the patients with advanced cancer pain.

Lactobacillus inhibit adhesion of Staphylococcus aureus to HeLa cells / 生物工程学报

To assess the ability of the previously selected human vaginal isolates of Lactobacillus crispatus (L. crispatus) T79-3, T90-1 and Lactobacillus jensenii (L. jensenii) T118-3, T231-1 to inhibit the growth of Staphylococcus aureus and block their adhesion to HeLa cells. The inhibitory bioactive substances produced by these Lactobacillus were also identified. Inhibitory substances interaction tests were carried out by using a streak-diffusion method on agar plates. Three types of interaction were performed to determine the inhibitory effect of Lactobacillus on adhesion of Staphylococcus aureus to HeLa cells: Exclusion Group (Lactobacillus and HeLa followed by pathogens), Competition Group (Lactobacillus, HeLa and pathogens together) and Displacement Group (pathogens and HeLa followed by the addition of Lactobacillus). The number of HeLa cells adhered to Staphylococcus aureus was quantified by bacteria colony counts on LB plate. The results showed that lactic acids produced by the Lactobacillus are the main substances that can inhibit Staphylococcus aureus growth and there is variation among the three types of interaction regarding the inhibitory activity against Staphylococcus aureus. The effects of Lactobacillus on blocking the adhesion to HeLa cells were concentration dependent. All four Lactobacillus isolates displayed the ability to inhibit Staphylococcus aureus growth and block Staphylococcus aureus adherence to HeLa cells. Exclusion Group was the most effective, and T79-3 showed greater capacity to block Staphylococcus aureus adherence compared with the other three isolates. The present study suggests the potential ability of L. crispatus T79-3 as probiotic for the treatment and prevention of urogenital infections in women.

Selection and genotyping of lactobacillus with potential preventive effect by repetitive element sequence-based PCR analysis / 生物工程学报

We selected and characterized isolates of Lactobacillus crispatus (L. crispatus) for potential preventing infections of the female reproductive tract. We cultured vaginal swabs from healthy volunteers on de Man, Rogosa and Sharpe (MRS) agar and identified the isolates at the species level by 16S rRNA sequence and genotyped the isolates of Lactobacillus by PCR amplification of repetitive bacterial DNA elements (rep-PCR). Furthermore, 10 L. crispatus strains were assessed for hydrogen peroxide (H2O2) and acid production. Overall 65 isolates were confirmed to be Lactobacillus by sequence analogy, among them 19 were L. crispatus, 17 were Lactobacillus jensenii and 12 were Lactobacillus fermentum. rep-PCR produced specie and strain-specific genomic fingerprints for the Lactobacillus isolates. The selected 10 L. crispatus isolates produced highly acidic environment after growth in MRS. The isolates T22-3 and T29-5 demonstrated high production of H2O2. This study indicated that there are individual differences with vaginal Lactobacillus colonization, and strain diversity within vaginal L. crispatus isolates, T22-3 and T29-5 might be candidates for restoring urogenital health environment in females.

Role of IL-1β and TNFα in the spinal cord in a murine model of bone cancer pain reduced by activation of glial cells / 中华麻醉学杂志

Objeetlve To evaluate the role of IL-1β and TNF-α in the spinal cord in a murine model of bone cancer pain(BCP)induced by activation of glial cells.Methods Three hundred and sixty male 8-10 weeks old C3H/He mice weighing 18-22 g were randomly divided into 6 groups(n=60 each):group I nomal control (group N);group Ⅱ sham operation (group S);group Ⅲ BCP+aCSF(group aCSF);group Ⅳ BCP+FC (group FC);group V BCP+MI(group MI) and group Ⅵ BCP+FC+MI (group FC-MI).BCP was produced by inieeting fibrosarcoma cells of bone into the medullary cavity of left ealcaneus bone.Intrathecal catheter was placed in the 4 BCP groups(group Ⅲ-Ⅳ).FC 0.5 nmol/5 μl or/and MI 16 μg/5 μl were injected IT once a day for 21 consecutive days after operation.The mechanical threshold to von Frey filaments was measured at 0.5 h(T0)before injection of fibrosarcoma cells and at 3,5,7,10,14,21 d(T1-6)after injection of fibrosarcoma cells.Twelve animals of each group were killed and L4.5 segment of the spinal cord was removed at T0,1,3,5,6 for determination of IL-1β and TNF-α content (by ELISA) and expression (by immuno-flurorescence) in the spinal cord. Results The mechanical threshold was significantly decreased at T1-6, while IL-1β content at T1,3,5,6 and TNF-α content at T5,6 was significantly increased in group BCP, FC, MI and FC + MI compared with those at T0 and group C (P < 0.05). Compared with group BCP, the mechanical threshold was significantly increased at T1-6 in group MI and FC + MI and at T4-6 in group FC, IL-1β content was significantly decreased at Ts,3,5,6 in group MI and FC + MI and at T5,6 in group FC and TNF-α content was significantly decreased at T5,6 in group FC, MI and FC + MI ( P < 0.05). Conclusion IL-1β and TNF-α in the spinal cord is involved in the process of glial cell activation-induced BCP.

Inhibition of microglia activation affected the maintenance of cancer pain in a murine model / 中国药理学通报

Aim To investigate the effect of intrathecal injection(it) of minocycline(MC),a selective microglia inhibitor,on the maintenance of pain in a murine model of cancer pain.Methods Forty-two male C3H/He mice were randomly divided into 3 groups(n=14 each):sham+PBS group was operated and received 10 ?l PBS injection into calcaneus medullary space;sarcoma+PBS group and sarcoma+MC group were operated and received 2?105 sarcoma cells/10 ?l PBS implantation into calcaneus medullary space.On the PID11(post-implantation day 11),10 mice were taken from each group randomly,sarcoma+PBS group and sham+PBS group were received 0.9% NS(5 ?l) it sarcoma+MC group was received MC(1 nmol,5 ?l) it Mechanical pain threshold and cold hyperalgesia assay were measured before and after it at 0.5,1,2,4,8,24 h.The last 4 mice of each group were received a normally non-noxious palpation of the ipsilateral heel 90 min on the PID12 after it,then the animals were killed and L4-6 segment of spinal cord was removed for analysing the c-fos expression(by immunohistochemistry).Results Bone cancer pain decreased the mechanical and cold pain threshold and activated the c-fos expression in the spinal cord;MC it transient attenuated bone cancer pain-induced hyperalgesia and allodynia and suppressed the expression of c-fos protein.Conclusion The activation of microglia in the spinal cord may be involved in the maintenance of bone cancer pian.