Synergistic effects of EMPs and PMPs on pulmonary vascular leakage and lung injury after ischemia/reperfusion.

BACKGROUND: Vascular leakage is an important pathophysiological process of critical conditions such as shock and ischemia-reperfusion (I/R)-induced lung injury. Microparticles (MPs), including endothelial cell-derived microparticles (EMPs), platelet-derived microparticles (PMPs) and leukocyte-derived microparticles (LMPs), have been shown to participate in many diseases. Whether and which of these MPs take part in pulmonary vascular leakage and lung injury after I/R and whether these MPs have synergistic effect and the underlying mechanism are not known. METHODS: Using hemorrhage/transfusion (Hemo/Trans) and aorta abdominalis occlusion-induced I/R rat models, the role of EMPs, PMPs and LMPs and the mechanisms in pulmonary vascular leakage and lung injury were observed. RESULTS: The concentrations of EMPs, PMPs and LMPs were significantly increased after I/R. Intravenous administration of EMPs and PMPs but not LMPs induced pulmonary vascular leakage and lung injury. Furthermore, EMPs induced pulmonary sequestration of platelets and promoted more PMPs production, and played a synergistic effect on pulmonary vascular leakage. MiR-1, miR-155 and miR-542 in EMPs, and miR-126 and miR-29 in PMPs, were significantly increased after hypoxia/reoxygenation (H/R). Of which, inhibition of miR-155 in EMPs and miR-126 in PMPs alleviated the detrimental effects of EMPs and PMPs on vascular barrier function and lung injury. Overexpression of miR-155 in EMPs down-regulated the expression of tight junction related proteins such as ZO-1 and claudin-5, while overexpression of miR-126 up-regulated the expression of caveolin-1 (Cav-1), the trans-cellular transportation related protein such as caveolin-1 (Cav-1). Inhibiting EMPs and PMPs production with blebbistatin (BLE) and amitriptyline (AMI) alleviated I/R induced pulmonary vascular leakage and lung injury. CONCLUSIONS: EMPs and PMPs contribute to the pulmonary vascular leakage and lung injury after I/R. EMPs mediate pulmonary sequestration of platelets, producing more PMPs to play synergistic effect. Mechanically, EMPs carrying miR-155 that down-regulates ZO-1 and claudin-5 and PMPs carrying miR-126 that up-regulates Cav-1, synergistically mediate pulmonary vascular leakage and lung injury after I/R. Video Abstract.

Autologous fat grafting efficacy in treating PostMastectomy pain syndrome: A prospective multicenter trial of two Senonetwork Italia breast centers.

Postmastectomy pain syndrome (PMPS) represents a common complication following breast surgery defined as a chronic neuropathic pain located in the front of the chest, in the axilla and in the upper arm that for more than 3 months after surgery. Several medications prove to be ineffective while autologous fat grafting revealed to be an innovative solution in the treatment of neuropathic pain syndromes based on retrospective studies. For this reason, we performed a prospective multicenter trial to reduce the memory bias and further increase the evidence of the results. From February 2018 to March 2019, 37 female patients aged between 18 and 80 years, underwent mastectomy or quadrantectomy with pathologic scarring and chronic persistent neuropathic pain, compatible with PMPS, are been included in the study and treated with autologous fat grafting. During the enrollment phase, patients were asked to estimate pain using the Visual Analogue Scale (VAS) and POSAS questionnaire in order to evaluate scar outcomes. The VAS scale, starting from 6.9 (1.3), decreased in the first month by 3.10 (1.59), continuing to fall by 0.83 (1.60) to 3 months and by 0.39 (2.09) at 6 months. Statistical analysis showed a significant reduction after 1 month (P < .0001) and 3 months (P < .005). All POSAS grades documented a statistically significant reduction (P < .0001) of the scores by both observers and patients. We observed that no significant association was found between age, BMI, menopausal status of patients, days from oncologic surgery to autologous fat grafting and reduction of VAS values over time while both smoking and axillary dissection were observed as the main factor significantly associated with a reduced clinical efficacy (respectively, P = .0227 and P = .0066). Our prospective multicenter trial confirms the efficacy of fat grafting in the treatment of PMPS based on the principle of regenerative medicine with a satisfactory response in terms of pain reduction and improvement of the quality of the treated tissues. Clinical questionnaires show that the cicatricial areas improve in terms of color, thickness, skin pliability, and surface irregularities. Regenerative effect is based also on the adoption of needles. The combined effect of fat grafting and needles determines a clinical full response.

Intercalated Poly (2-Acrylamido-2-methyl-1-propanesulfonic Acid) into Sulfonated Poly (1,4-Phenylene ether-ether-sulfone) Based Proton Exchange Membrane: Improved Ionic Conductivity.

A series of hybrid proton exchange membranes were synthesized via in situ polymerization of poly (2-acrylamido-2-methyl-1-propanesulfonic acid) PMPS with sulfonated poly (1,4-phenylene ether-ether-sulfone) (SPEES). The insertion of poly (2-acrylamido-2-methyl-1-propanesulfonic acid) PMPS, between the rigid skeleton of SPEES plays a reinforcing role to enhance the ionic conductivity. The synthesized polymer was chemically characterized by fourier-transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance 1H NMR spectroscopy to demonstrate the successful grafting of PMPS with the pendent polymer chain of SPEES. A variety of physicochemical properties were also investigated such as ion exchange capacity (IEC), proton conductivity, water uptake and swelling ratio to characterize the suitability of the formed polymer for various electrochemical applications. SP-PMPS-03, having the highest concentration of all PMPS, shows excellent proton conductivity of 0.089 S cm-1 at 80 °C which is much higher than SPEES which is ~0.049 S cm-1. Optimum water uptake and swelling ratio with high conductivity is mainly attributed to a less ordered arrangement polymer chain with high density of the functional group to facilitate ionic transport. The residual weight was 93.35, 92.44 and 89.56%, for SP-PMPS-01, 02 and 03, respectively, in tests with Fenton's reagent after 24 h. In support of all above properties a good chemical and thermal stability was also achieved by SP-PMPS-03, owing to the durability for electrochemical application.

De novo peroxisome biogenesis: Evolving concepts and conundrums.

Peroxisomes proliferate by growth and division of pre-existing peroxisomes or could arise de novo. Though the de novo pathway of peroxisome biogenesis is a more recent discovery, several studies have highlighted key mechanistic details of the pathway. The endoplasmic reticulum (ER) is the primary source of lipids and proteins for the newly-formed peroxisomes. More recently, an intricate sorting process functioning at the ER has been proposed, that segregates specific PMPs first to peroxisome-specific ER domains (pER) and then assembles PMPs selectively into distinct pre-peroxisomal vesicles (ppVs) that later fuse to form import-competent peroxisomes. In addition, plausible roles of the three key peroxins Pex3, Pex16 and Pex19, which are also central to the growth and division pathway, have been suggested in the de novo process. In this review, we discuss key developments and highlight the unexplored avenues in de novo peroxisome biogenesis.

Effects of transplanted circulating endothelial progenitor cells and platelet microparticles in atherosclerosis development.

BACKGROUND INFORMATION: Atherosclerosis is an inflammatory disease, in which risk factors such as hyperlipidemia and hypertension affect the arterial endothelium, resulting in dysfunction, cell damage or both. The number of circulating endothelial progenitor cells and microparticles provides invaluable outcome prediction for atherosclerosis disease. However, evidence for the therapeutic potential of endothelial progenitor cells and microparticles in atherosclerosis development is limited. Our study was designed to investigate the possible protective role of a cell therapy-based approach, using endothelial progenitor cells and the dual behaviour of circulating platelet microparticles, on atherosclerosis development in hypertensive-hypercholesterolemic hamster model. Consequently, control hamsters received four intravenous inoculations of: (1) 1×10(5) endothelial progenitor cells of healthy origins in one dose per month, during four months of diet-induced atherosclerosis, and after hypertensive-hypercholesterolemic diet for further four months; (2) in a second set of experiments, 1×10(5) endothelial progenitor cells of healthy origins or/and 1×10(5) platelet microparticles of atherosclerotic origins were inoculated every other month during hypertensive-hypercholesterolemic diet. RESULTS: Endothelial progenitor cell treatment had the following effects: (1) re-established plasmatic parameters: cholesterol and triglyceride concentrations, blood pressure, heart rate, cytokine and chemokine profiles, platelet microparticle pro-thrombotic activity and endothelial progenitor cell paracrine activity reflected by cytokine/chemokine detection; (2) reduced lipid, macrophage and microparticle accumulation in liver; (3) reduced atherosclerosis development, revealed by decreased lipid, macrophage and microparticle content of arterial wall; (4) induced the recruitment and incorporation of endothelial progenitor cells into liver and arterial wall; (5) improved arterial dysfunction by increasing contraction and relaxation; (6) reduced the protein expression of specific pro-inflammatory molecules in liver and arterial wall. Platelet microparticle transplantation aggravated the above-mentioned biomarkers and atherosclerosis process, which were partially reverted with co-inoculation of platelet microparticles and endothelial progenitor cells. CONCLUSIONS: With this study, we demonstrate in a hypertensive-hypercholesterolemic hamster model, that the endothelial progenitor cell-based therapy suppresses the development of atherosclerosis and reduces hepatic lipid and macrophage accumulation with the consequent alleviation of dyslipidaemia and hypertension. SIGNIFICANCE: Our results support the notion that increasing the number of circulating endothelial progenitor cells by different ways could be a promising therapeutic tool for atherosclerosis.

Updates on the preventions and management of post-mastectomy pain syndrome beyond medical treatment: a comprehensive narrative review.

BACKGROUND AND OBJECTIVE: With the significant advances in breast cancer treatment, the survival rates have improved. Consequently, improving the quality of life for breast cancer survivors has emerged an important issue. In this study, we examined the management of post-mastectomy pain syndrome (PMPS) in breast cancer patients thorough a comprehensive literature review. We introduce the preventive measures and pharmacotherapy for PMPS in breast cancer patients and discuss the effectiveness of psychosocial interventions. METHODS: We conducted a literature search for relevant articles in Medline ALL, Cochrane Database of Systematic Reviews, Cochrane CENTRAL, Embase, and nine other databases from October 2023 to January 2024. Chronic pain was defined as pain persisting for more than 3 months after breast cancer surgery. The search included terms related to PMPS, psychological interventions, and breast cancer. Data extraction was done independently by two reviewers, and any discrepancies will be discussed to ensure consensus or by a third reviewer. KEY CONTENT AND FINDINGS: Studies have investigated surgical anesthetics, postoperative medications, and surgical procedures for PMPS prevention, but few have focused on treatment. Our literature search about the usefulness of psychosocial interventions yielded two articles, one was about the usefulness of mindfulness and the other was about the efficacy of yoga. CONCLUSIONS: Mindfulness and yoga show potential efficacy for PMPS treatment, but the evidence is limited. More research is needed to confirm these findings and to explore other psychosocial interventions.

Post-mastectomy Pain Syndrome: A Review Article and Emerging Treatment Modalities.

Post-mastectomy pain syndrome (PMPS) is a syndrome broadly applied to the development of chronic pain after surgical breast intervention (i.e., lumpectomy and mastectomy). The incidence of PMPS is likely underreported, and this has contributed to a paucity of high-level evidence related to the treatment of the aforementioned condition. A drive to reduce the burden of opioid use has led to pain management physicians trialing a variety of strategies to help patients manage PMPS. This review discusses the latest evidence behind treatment options for PMPS, exploring medications as well as interventional techniques (e.g., nerve blocks, radiofrequency ablation, neuromodulation, and intrathecal drug delivery systems). Recent advances in neuromodulation technology are of particular interest here due to the well-localized nature of PMPS-related pain and the specificity with which modern neuromodulation techniques can generate an effect. Finally, the review proposes a framework with which to approach the care of patients with PMPS, with a specific emphasis on the early consideration of neuromodulation techniques along with functional and physical therapy to reduce patient medication burden and improve overall quality of life.

Neuromodulation for Adjunctive Treatment in Postmastectomy Pain Syndrome.

Postmastectomy pain syndrome (PMPS) affects nearly half of patients who undergo mastectomy to treat breast cancer. As the survival rate of breast cancer increases with advancements in treatment, the incidence of PMPS is also increasing. Patients with PMPS can experience unrelenting, chronic pain refractory to traditional management with oral pharmacotherapy in conjunction with nonpharmacologic treatment (physical therapy, transcutaneous electrical nerve stimulation (TENS)). Neuromodulation is an emerging treatment modality for numerous chronic pain conditions. This case report highlights the tremendous success of spinal cord stimulator placement for a patient with PMPS.

Autologous Fat Grafting for Post-mastectomy Pain Syndrome: A Systematic Review and Meta-Analysis.

Fat grafting has been described as a potential treatment for post-mastectomy pain syndrome (PMPS) following oncological breast surgery. The study's aim was to compare and contrast the current literature using a systematic review and meta-analysis to quantify the evidence. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. Databases, including MEDLINE, Google Scholar, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Central Register of Controlled Trials (CENTRAL), were searched. Data synthesis was conducted using Review Manager 5.4 (Cochrane Collaboration, London, UK), with 95% confidence intervals. All randomised controlled trials (RCT) and observational studies comparing lipofilling for PMPS were included. A total of six studies met the inclusion criteria with five articles being used in data analysis for the mean percentage reduction in visual analogue scale (VAS) score. The primary outcome measure was the mean percentage reduction in the VAS pain score. Secondary outcomes included the Neuropathic Pain Symptom Inventory (NPSI) and the quality of life assessments post treatment. Overall, a total of 266 patients received fat transfer for PMPS, and 164 were in the control group. The mean percentage reduction in VAS score was 19.8 (10.82, 28.82; p < 0.0001). Secondary outcomes, including health-related quality of life, showed good outcomes post fat transfer. This involved breast softness, cosmesis, and psychosocial well-being. The results from this meta-analysis suggest that autologous fat grafting is an efficacious treatment for reducing pain caused by PMPS. The authors suggest more high-quality trials are needed to enhance the current evidence base.

Systematic review and meta-analysis of the efficacy of general anesthesia combined with a thoracic nerve block in modified breast cancer surgery.

BACKGROUND: Breast cancer is a malignant tumor disease that poses a significant threat to women's health. In recent years, the incidence of breast cancer in China has been increasing. This report aims to explore the effects of general anesthesia combined with a thoracic nerve block in modified breast cancer surgery. METHODS: A computer-based search of PubMed, Web of Science, Embase, and the Cochrane Library was performed to identify randomized controlled studies on breast cancer, general anesthesia combined with a thoracic nerve block, modified breast cancer surgery, and other breast cancer treatments. Further search criteria included postoperative pain score, postoperative morphine equivalents given 24 hours after surgery, and operation duration. After an initial selection process, the studies were evaluated using the Jadad scale and the Cochrane Handbook for Systematic Reviews of Interventions to assess their suitability for inclusion in the subsequent meta-analysis of the experimental data, which was carried out using RevMan 5.3. RESULTS: A total of 8 studies comprising a total of 624 patients were selected for inclusion in this report. According to the meta-analysis, the analytical structure of the thoracic nerve group and the control group had a mean difference (MD) of -1.27 [95% confidence interval (CI): -1.68 to -0.86], the structure of the statistical test was Z=6.08 (P<0.00001), the MD of the total analysis structure of morphine equivalents was -2.71 (95% CI: -4.98 to -0.44), and the statistical test structure was Z=2.34 (P=0.02). DISCUSSION: General anesthesia combined with a thoracic nerve block in breast cancer surgery may effectively improve postoperative pain in patients and reduce the need for analgesic drugs. However, the outcome indicators included in this study are not sufficient. It is necessary to increase both the sample size and the number of outcome indicators to provide further theoretical evidence for the subsequent application of thoracic nerve block in modified breast cancer surgery.

Post-Mastectomy Pain Syndrome: An Up-to-Date Review of Treatment Outcomes.

BACKGROUND: Post-mastectomy pain syndrome (PMPS) is a known debilitating surgical complication. While research on prevention, risk factors, and treatments have been conducted, there remains no cohesive treatment paradigm. The aim of our study is to synthesize the existing evidence on PMPS treatment, which may facilitate the implementation of standardized, effective management strategies. METHODS: Using Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a comprehensive search was developed and translated for MEDLINE, Cochrane Library, EMBASE, CINAHL, PsycINFO, Web of Science, and ClinicalTrials.gov. The databases were searched using a combination of free terms, phrase searching, and database-specific controlled vocabulary related to PMPS. All unique records were by two independent reviewers. Publications on chronic (>3 months duration) pain after breast cancer-related surgery were included. Limited case series, case reports, and editorials were not included. RESULTS: A total of 3402 articles from the years 1946-2019 resulted from the literature search after deduplication. Twenty-seven articles met final inclusion criteria for analysis, which revealed 10 major treatment modalities: fat grafting, neuroma surgery, lymphedema surgery, nerve blocks and neurolysis, laser, antidepressants, neuromodulators, physical therapy, mindfulness-based cognitive therapy, and capsaicin. CONCLUSIONS: In this review, we present a comprehensive assessment of the treatments available for PMPS that may help guide breast surgeons and reconstructive surgeons to employ the most effective treatment strategies for these patients. This review supports the importance of multimodal, multidisciplinary care in improving the management of PMPS.

The association between urinary levels of 1,3-butadiene metabolites, cardiovascular risk factors, microparticles, and oxidative stress products in adolescents and young adults.

1,3-Butadiene (BD) is a synthetic colorless gas used in the production of synthetic rubber and polymers. Exposure to BD has been reported to increase oxidative stress and accelerate atherosclerosis in vitro and in animal studies. In occupational studies, BD exposure has been linked to cardiovascular disease (CVD). However, no previous research has been reported on whether BD exposure is associated with CVD risk factors and oxidative stress in the general population. We recruited 853 young participants to study the correlation between urinary levels of the BD metabolite, N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHBMA), CVD risk factors, serum levels of endothelial microparticles and platelet microparticles, and the urinary levels of 8-hydroxydeoxyguanosine (8-OHdG). The results showed the DHBMA levels were positively correlated with low-density lipoprotein-C, carotid intima-media thickness (CIMT), CD31+/CD42a - counts (endothelial apoptosis markers), and urinary 8-OHdG levels. Moreover, DHBMA levels were negatively correlated with CD62 P counts (platelet activation marker). The correlation between DHBMA, CIMT, and 8-OHdG was more evident when the levels of CD31+/CD42a - or CD62 P were above 50%. In conclusion, we reported that the urinary levels of DHBMA were associated with the lipid profile, CIMT, microparticles, and marker of oxidative stress in this young population. Future studies on BD exposure and atherosclerosis are needed.

Circulating Endothelial Cells, Circulating Endothelial Progenitor Cells, and Circulating Microparticles in Type 1 Diabetes Mellitus.

BACKGROUND AND AIM:: Hyperglycemia in type 1 diabetes (T1D) is accompanied by endothelial cell dysfunction which is known to contribute to the pathogenesis of cardiovascular disorders. The aim of the current study was to explore the profile of circulating endothelial progenitor cells (EPCs), circulating endothelial cells (CECs), endothelial and platelet derived micropaticles (EMPs, PMPs) and total microparticles (TMPs), in T1D children in relation to each other and to the metabolic disorders accompanying T1D. PATIENTS AND METHODS:: Thirty T1D patients and 20 age and sex matched healthy volunteers were assessed for HbA1c level and lipid profile. Quantification of CECs, EPCs, TMPs, EMPs and PMPs was done by flow cytometry. RESULTS:: The mean levels of EMPs, PMPs, TMPs and CECs were significantly higher in diabetic children compared to controls. Meanwhile, the levels of EPCs were significantly lower in diabetic children compared to controls. Both PMPs and CECs showed the highest significant differences between patients and controls and their levels were directly related to HbA1c, total cholesterol, LDL and triglycerides. A moderate correlation was observed between the frequency of PMPs and CECs. EPCs revealed negative correlations with both LDL and triglycerides. TMPs were only related to LDL, while EMPs were only related to HbA1c. CONCLUSION:: Although there is disturbance in the levels of EMPs, PMPs, TMPs, CECs and EPCs in type 1 diabetic children compared to the controls, only the levels of PMPs and CECs were closely affected by the poor glycemic control and dyslipidemia occurring in T1D; thus may contribute to a higher risk of cardiovascular diseases.

Synthesis and radiation shielding properties of polyimide/Bi2O3 composites.

Radiation shielding composites based on polyimide and Bi2O3 were synthesized. Surface and physical-mechanical properties of polyimide/Bi2O3 composites were studied. Bi2O3 particles were modified by polymethylphenylsiloxane for the uniform distribution of filler in composites. This paper presents data on the production of composites in two ways: hot- and cold-pressing. The hot-pressing method for the synthesis of composites is preferable compared to the cold-pressing method (the density increases by 10-12%, and the Vickers microhardness by 10-20%). The results show that the introduction of Bi2O3 significantly increases the thermal stability of the composites. At 680 °C, a polymer composite containing 10 wt% Bi2O3 retains 9.7% of its mass, and at 60 wt% Bi2O3, retains 58.4%. The radiation-protective characteristics of the composites with respect to gamma radiation were evaluated by experimental and theoretical methods. High radiation-protective characteristics of the composites have been established in the gamma-quanta energy range of 0.1-1 MeV.

Beyond Prescriptions Monitoring Programs: The Importance of Having the Conversation about Benzodiazepine Use.

: Internationally there is an escalation of prescription-related overdose deaths, particularly related to benzodiazepine use. As a result, many countries have implemented prescription monitoring programs (PMPs) to increase the regulation of benzodiazepine medications. PMPs centralize prescription data for prescribers and pharmacists and generate alerts to high-doses, risky combinations, or multiple prescribers with the aim to reduce inappropriate prescribing and subsequently the potential of patient harm. However, it has become clear that prescribers have been provided with minimal guidance and insufficient training to effectively integrate PMP information into their decision making around prescribing these medications. Accordingly, this paper discusses how PMPs have given rise to a range of unintended consequences in those who have been prescribed benzodiazepines (BDZs). Given that a gradual taper is generally required to mitigate withdrawal from BDZs, there are concerns that alerts from PMPs have resulted in BDZs being ceased abruptly, resulting in a range of unintended harms to patients. It is argued that best practice guidelines based upon a patient-centered framework of decision-making, need to be developed and implemented, in order to curtail the unintended consequences of PMPs. This paper outlines some key considerations when starting the conversation with patients about their BDZ use.

U.S. Opioid Epidemic: Impact on Public Health and Review of Prescription Drug Monitoring Programs (PDMPs).

OBJECTIVES: In recent years, the devastating effects of U.S. opioid epidemic has been making news headlines. This report explores background information and trends on opioid misuse, overdose fatalities and its impact on public health. In addition, various efforts to improve surveillance, timeliness of data and Prescription Drug Monitoring Program (PDMP) integration and interoperability are reviewed. METHOD: PubMed and internet searches were performed to find information on the U.S. opioid epidemic. In addition, searches were performed to retrieve information about PDMPs and state-specific mandates along with presentation slides and learnings from the 2018 National Rx Drug Abuse & Heroin Summit in Atlanta, GA. RESULTS: It is clear that the U.S. opioid epidemic has a tremendous impact on public health including the next generation of children. Various data, surveillance & technology-driven efforts including CDC-Funded Enhanced State Opioid Overdose Surveillance Program (ESOOS) and use of telemedicine for opioid use disorder treatment aim to improve prevention, treatment and targeted interventions. In addition, PDMP integration and interoperability efforts are advancing to provide prescribers meaningful decision support tools. DISCUSSION: The opioid epidemic has a complex impact on public health intertwined with variable factors such as mental health and social determinants of health. Given the statistics and studies that suggest many of the illicit opioid users start with prescription opioids, continued advancement in the area of PDMP integration and interoperability is necessary. The PDMP integrated clinical decision support systems need to supply to healthcare providers access to complete, timely and evidence-based information that can meaningfully inform prescribing decisions and communication with patients that affect measurable outcomes. CONCLUSION: While Prescription Drug Monitoring Programs (PDMPs) are valuable tools for providers in making informed prescribing decisions, the variable state mandates and varying degrees of integration and interoperability across states may limit their potential as meaningful decision support tools. Sharing best practices, challenges and lessons learned among states and organizations may inform strategic and systematic use of PDMPs to improve public health outcomes.

Expression of platelet microparticles in patients with diabetic nephropathy and its relationship with renal damage / 中国输血杂志

【Objective】 To investigate the expression levels of platelet microparticles(PMPs) in patients with diabetic nephropathy (DN) and their relationship with renal injury. 【Methods】 Thirty DN patients, 30 T2DM patients without DN and 30 healthy controls were enrolled. Flow cytometry was used to detect the quantity and phenotype of PMPs, and ELISA was used to measure the levels of plasma renin, angiotensin Ⅱ (angiotoninⅡ, AngⅡ), vascular endothelial growth factor (vascular endothelial growth factor, VEGF) and transforming growth factor-β1(transforming growth factor-β1, TGF-β1). Kidney function was determined by blood biochemistry. 【Results】 The quantity of PMPs in the DN group was (1 564±346) particles/μL, which was significantly higher than that in the non-DN group (1 246±312) particles/μL and the control group (1 223±299) particles/μL (P<0.05). The PMPs in the DN group mainly expressed CD62P and CD41a, accounting for (76.5±12.3)%. Moreover, the levels and activation of PMPs increased with the progression of DN. The quantity of PMPs was positively correlated with renin and other factors (r=0.56-0.62, P<0.05), negatively correlated with the glomerular filtration rate (GFR) (r=-0.64, P<0.05), and positively correlated with the urinary albumin excretion rate (UAE) (r=0.66, P<0.05). PMPs were also an independent influencing factor of UAE (β=12.34, P<0.05). 【Conclusion】 PMPs expression is elevated in DN patients, which may be associated with renal injury, but it is insufficient to confirm its role in the pathogenesis of DN.

Comparison of the nine polymorphic membrane proteins of Chlamydia trachomatis for their ability to induce protective immune responses in mice against a C. muridarum challenge.

OBJECTIVES: To test vaccines, formulated with novel antigens, to protect mice against Chlamydia infections. METHODS: To determine the ability of polymorphic membrane proteins (Pmps) to induce cross-species protective immune responses, recombinant fragments from all nine C. trachomatis serovar E Pmps were used to vaccinate BALB/c mice utilizing CpG-1826 and Montanide ISA 720 as adjuvants. C. muridarum recombinant MOMP and PBS, formulated with the same adjuvants, were used as positive and negative controls, respectively. Mice were challenged intranasally with 104 inclusion-forming units (IFU) of C. muridarum. Animals were weighed daily and at 10days post-challenge, they were euthanized, their lungs harvested, weighed and the number of chlamydial IFU counted. RESULTS: Following vaccination the nine Pmps elicited immune responses. Based on body weight changes, or number of IFU recovered from lungs, mice vaccinated with Pmp C, G or H were the best protected. For example, over the 10-day period, the negative control group vaccinated with PBS lost significantly more body weight than mice immunized with PmpC or G (P<0.05). C. muridarum MOMP vaccinated mice were better protected against body weight losses than any group immunized with Pmps. Also, the median number of IFU recovered from the lungs of mice vaccinated with PmpC (72×106) or PmpH (61×106) was significantly less than from mice immunized with PBS (620×106; P<0.05). As determined by the number of IFU, all Pmps elicited less protection than C. muridarum MOMP (0.078×106 IFU; P<0.05). CONCLUSIONS: This is the first time PmpC has been shown to elicit cross-species protection against a respiratory challenge. Additional work with Pmps C, G and H is recommended to determine their ability to protect animal models against genital and ocular challenges.

Platelet microparticle-mediated transfer of miR-939 to epithelial ovarian cancer cells promotes epithelial to mesenchymal transition.

Epithelial ovarian cancer (EOC) patients frequently suffer from thrombocytosis, which leads to a poor prognosis. However, the mechanism underlying platelet regulation of biological behavior in EOC remains unclear. The associations between clinicopathological characteristics and thrombocytosis in 171 EOC patients were studied, preoperative thrombocytosis was significantly associated with the stage, metastasis scope, level of preoperative CA125 and overall survival. When SKOV3 cells were cocultured with platelet microparticles (PMPs), the expression of molecules associated with epithelial-mesenchymal transition (EMT) was increased. The proliferation and migration of SKOV3 cells were also enhanced. Based on the miRNA microarray of the PMPs derived between thrombin-stimulating and apoptotic platelets, we demonstrated that over-expression or complete knockdown of miR-939 in the SKOV3 cells strengthened or weakened EMT. Secretory phospholipase A2 type IIA (sPLA2-IIa) has been shown to mediate PMPs intake by SKOV3 cells. The knockdown of sPLA2-IIa in SKOV3 cells verified that PMPs were involved in crosstalk during the regulation of cancer cells by transferring miRNA. This study revealed an important role for PMPs in the crosstalk of platelets and cancer cells through miR-939 shedding mediated by sPLA2-IIa, which enables EOC to undergo EMT and enhances cancer progression. Our findings pave the way for developing a novel therapeutic strategy for EOC targets such as PMPs, miR-939 or sPLA2-IIa.