Investigating the risk factors for isthmocele development after cesarean delivery.

BACKGROUND: Cesarean delivery rates are increasing globally, raising concerns about associated complications such as isthmocele. Isthmoceles are pouch-like defects in the anterior uterine wall at the site of a prior cesarean delivery scar. OBJECTIVE: This study aimed to determine isthmocele prevalence, associated symptoms, and risk factors among women with a history of cesarean delivery. STUDY DESIGN: This cross-sectional study evaluated 297 women with prior cesarean delivery using transvaginal ultrasound to screen for isthmocele. Data on demographics, pregnancy details, comorbidities, and indications for cesarean delivery were collected. Isthmocele was defined sonographically as any niche or defect at the hysterotomy site. Descriptive and comparative analyses identified factors associated with isthmocele. RESULTS: Isthmocele prevalence was 65.3% (n=194). Abnormal vaginal bleeding was reported in 21.1% of participants, pelvic pain by 4.1% of participants, and both by 4.1% of participants. Compared to women without isthmocele, those with isthmocele were older (35.9 vs 31.6 years), had higher body mass index (26.8 vs 25.5 kg/m2), gravidity (1.8 vs 1.3), and parity (1.7 vs 1.2). Repeat cesarean delivery was more common (30.4% vs 12.6%) and elective cesarean delivery less common (33.5% vs 67.9%) among those with isthmocele. CONCLUSION: Over half of the women with history of cesarean delivery had an isthmocele. Abnormal bleeding was common. Advanced maternal age, obesity, repeat procedures, and certain comorbidities appear to increase risk. Further research on prevention and treatment is warranted given the high prevalence.

Associations of variability in body mass index with cardiovascular outcomes in the general population: A systematic review.

In today's world, high variability of body mass index (BMI) is known as a significant global health problem that can lead to many negative impacts on the cardiovascular system, including atrial fibrillation (AF) and coronary heart disease. The current systematic review aims to elucidate the effect of variability in BMI on the risk of cardiovascular outcomes. Four databases, including PubMed, Scopus, MEDLINE, and CENTRAL, were searched. All related articles up to 10 June 2022, were obtained. Titles, abstracts, and full texts were reviewed. After screening abstracts and full texts, four articles were included in our study. In these four cohort studies, 7,038,873 participants from the USA and South Korea were involved. These articles generally considered the BMI and outcomes including cardiovascular disease, AF, and coronary heart disease. All these articles reported an association between the variability of BMI and increased risk of cardiovascular outcomes. Due to the negative impact of the high variability of BMI on the risk of cardiovascular outcomes, health policymakers and practitioners should pay more attention to the significant role of BMI in health problems and physicians might better check the variability of BMI visits to visit.

A modified schedule of multiple aeroallergen ultra-rush immunotherapy in perennial allergic rhinitis: safety, efficacy, and T lymphocyte cell population studies.

BACKGROUND: This study assessed whether a modified immunotherapy schedule for allergic rhinitis could be safe and efficient. Ultra-rush immunotherapy (URIT) rapidly desensitizes patients to aeroallergens. OBJECTIVE: We aimed to develop a modified URIT protocol in 3 days to achieve the target dose while observing whether it could improve this situation and decrease the time to achieve the maintenance dose. METHODS: The URIT was exercised in 21 patients with perennial allergic rhinitis. Premeditations were given to the patients 3 days prior to the immunotherapy and during the 3 days injections immunotherapy: pred nisolone, ranitidine, and Airokast/montelukast. Finally, the T cell population frequencies of patients prior to and after immunotherapy, including T helper 1, T helper 2, cytotoxic T lymphocytes, and regulatory T cells, were studied using flow cytometry. During the URIT protocol, 21 patients received 291 injections. RESULT: Six patients (28.6%) showed systemic reactions in our study. All systemic reactions occurred on the third day by the 1:1 dilution of the maintenance dose. These systemic reactions occurred in three patients after 13 injections, and the three remaining patients showed systemic reactions following the last injection. No systemic reaction was observed on the first and second day of the therapy, and the risk of systemic reaction with every injection was about 2%. Among the T cell populations, CD3+ and CD8+ cells decreased significantly. CONCLUSION: The findings emphasized that URIT, alongside premedication with a high dose of antihistamine, helped to achieve the maintenance dose and control clinical manifestations.

Association Between HDL2-C and HDL3-C with Cardiovascular Disease: A Nested Case-Control Study in an Iranian Population.

Background: The contribution of high-density lipoprotein cholesterol (HDL-C) subclasses to incident cardiovascular disease (CVD) and coronary heart disease (CHD) remains a subject of debate. Objectives: The objective of this study was to investigate these associations in a population with a high prevalence of dyslipidemia and CVD. Methods: In a nested case-control study, HDL-C and its subclasses (HDL2-C and HDL3-C) in 370 age and gender-matched case and control subjects were determined. This study employed multivariable-adjusted conditional logistic regression to calculate the odds ratios (ORs) for the associations between HDL-C, HDL2-C, HDL3-C, and HDL2-C/HDL3-C (both as continuous and categorical variables) with incident CVD and CHD. The present study models were adjusted for a comprehensive set of confounders, including body mass index, current smoking, hypertension, type 2 diabetes mellitus, use of lipid-lowering drugs, family history of premature CVD, non-HDL-C, and triglycerides. Results: In multivariate analysis, when considering lipoprotein parameters as continuous variables, a 1-unit increase in HDL-C and HDL3-C was associated with a reduced risk of incident CVD and CHD. For CVD, the ORs (95% confidence intervals [CI]) were 0.95 (0.92 - 0.98) and 0.95 (0.93 - 0.98) for HDL-C and HDL3-C, respectively. The corresponding values for CHD were 0.94 (0.91 - 0.97) and 0.94 (0.91 - 0.97). In the categorical approach to lipoprotein parameters, higher quartiles of HDL-C and HDL3-C, compared to the first quartile, were significantly associated with a lower risk of incident CVD and CHD. The ORs (95% CI) for the fourth quartiles were 0.43 (0.25 - 0.74, P for trend = 0.003) and 0.46 (0.27 - 0.78, P for trend = 0.005) for HDL-C and HDL3-C regarding CVD and 0.32 (0.17 - 0.59) and 0.32 (0.18 - 0.59) (all P for trend = 0.001) regarding CHD, respectively. Paradoxically, across quartiles of HDL2-C/HDL3-C, this lipid ratio was associated with a higher risk of CHD (92% higher risk in the fourth quartile). Conclusions: The results showed that HDL3-C, but not HDL2-C, was primarily responsible for the protective effect of HDL-C against CVD, particularly CHD, in Iranian adults.

Development and Psychometric Evaluation of the Motivation for Healing Scale in Patients with Cancer.

Introduction: This study was conducted to develop and validate a Motivation for Healing Scale (MHS) in Cancer. Methods: in this methodological study, the MHS draft was developed based on the approach of Waltz and colleagues using existing scales and concept analysis. The psychometric features, including face validity (qualitative and quantitative), content validity (qualitative and quantitative), structural validity (exploratory and confirmatory factors), and construct validity (convergent and discriminant validity) were assessed. Finally, the reliability was evaluated using internal consistency, and stability. Results: Based on the results of the qualitative phase, an initial item pool was generated with 55 items, Exploratory and confirmatory factor analyses were performed on the data collected from 404 patients. 25 Items were excluded during the psychometric evaluation phases. Reliability assessment and internal consistency assessment revealed that Cronbach's alpha value of the 25-item MHS was 0.912. The results of intraclass correlation coefficient (0.93, 95% CI: 0.86- 0.96) showed the stability was strong. Conclution: The 25-item MHS is a valid and reliable scale for the assessment of motivation for healing in patients with cancer.

Therapeutic Effect of Silver Nanoparticles in the Management of Diabetic Ulcers: A Systematic Review and Meta-Analysis on RCTs.

AIMS: The skin, as the body's largest organ, plays vital roles in sensory functions, temperature regulation, and protection against pathogens and injuries. Skin wounds, which disrupt its integrity, can result from various factors, including diseases such as diabetes. Diabetic foot ulcers are a severe complication of diabetes, often leading to amputations. This systematic review explores the therapeutic potential of silver nanoparticles in the management of diabetic ulcers. METHODS: Seven studies published between 2016 and 2023 were included in this review. Also, 4 studies were included in the meta-analysis. These studies investigated the application of silver nanoparticles, primarily in dressing forms, for diabetic ulcer treatment. A systematic search strategy was employed, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: The results show that silver nanoparticles do not have a significant difference in improving DFU healing rates. SilvrSTAT Gel, a dressing containing silver nanoparticles, outperformed traditional dressings, leading to a substantial percentage of ulcers healing within weeks. Comparative studies also indicated that silver nanoparticles were at least as effective as alternative treatments, such as nano-chitosan dressings, and showed potential for combination therapy with growth factors. DISCUSSION: This review underscores the promise of silver nanoparticles, a nanotechnology-based approach, in accelerating the healing of diabetic ulcers while providing antimicrobial benefits. Despite some limitations, including variations in treatment regimens and a lack of long-term outcome data, these findings show there is no clinical evidence for using Nanosilver for the healing process of DFU. CONCLUSION: Silver nanoparticles currently do not have sufficient clinical evidence for healing the DFU; however, in some studies, they had noticeable effects on the rate of wound healing.

Diagnostic value of enhanced-contrast ultrasound for cesarean scar pregnancy: A systematic review.

BACKGROUND: Cesarean scar pregnancy, an uncommon ectopic pregnancy in which the embryo is implanted in the cesarean scar, poses significant risks without prompt diagnosis and treatment. Its prevalence has risen alongside increased cesarean section rates. Despite various treatment approaches, consensus remains elusive. Ultrasonography, particularly contrast-enhanced ultrasonography, shows promise in cesarean scar pregnancy diagnosis. MAIN BODY: This systematic review, following PRISMA guidelines, explores contrast-enhanced ultrasound's diagnostic potential in cesarean scar pregnancy. We searched PubMed, Scopus, Web of Science, and Google Scholar up to August 2023. Selection involved two stages: title/abstract screening and full-text assessment. The included studies investigated contrast-enhanced ultrasound's diagnostic value in cesarean scar pregnancy, provided adequate data, and were peer-reviewed in English. Quality assessment followed the QUADAS-2 criteria. We extracted the diagnostic accuracy metrics: sensitivity, specificity, and accuracy. Out of 193 records, five studies met the inclusion criteria (2016-2020, China). Contrast-enhanced ultrasound displayed sensitivities of 77%-100% and specificities of 95%-100%. Two studies reported accuracy of 96.9%-97.8%. Compared with conventional ultrasound, contrast-enhanced ultrasound exhibited superior sensitivity, specificity, and accuracy. It also outperformed transvaginal ultrasound. CONCLUSION: Enhanced-contrast ultrasound holds promise for diagnosing and managing cesarean scar pregnancy by visualizing scar vascularization in real-time, thereby reducing severe complication risks. This review highlights contrast-enhanced ultrasound as a transformative diagnostic tool for cesarean scar pregnancy management, despite existing evidence limitations.

Anti-Cancer Effect of Dorema Ammoniacum Gum by Targeting Metabolic Reprogramming by Regulating APC, P53, KRAS Gene Expression in HT-29 Human Colon Cancer Cells.

Background: Colorectal cancer is a heterogeneous disease that leads to metabolic disorders due to multiple upstream genetic and molecular changes and interactions. The development of new therapies, especially herbal medicines, has received much global attention. Dorema ammoniacum is a medicinal plant. Its gum is used in healing known ailments. Studying metabolome profiles based on nuclear magnetic resonance 1HNMR as a non-invasive and reproducible tool can identify metabolic changes as a reflection of intracellular fluxes, especially in drug responses. This study aimed to investigate the anti-cancer effects of different gum extracts on metabolic changes and their impact on gene expression in HT-29 cell. Methods: Extraction of Dorema ammoniacum gum with hexane, chloroform, and dichloromethane organic solvents was performed. Cell inhibition growth percentage and IC50 were assessed. Following treating the cells with dichloromethane extract, p53, APC, and KRAS gene expression were determined. 1HNMR spectroscopy was conducted. Eventually, systems biology software tools interpreted combined metabolites and genes simultaneously. Results: The lowest determined IC50 concentration was related to dichloromethane solvent, and the highest was hexane and chloroform. The expression of the KRAS oncogene gene decreased significantly after treatment with dichloromethane extract compared to the control group, and the expression of tumor suppressor gene p53 and APC increased significantly. Most gene-altered convergent metabolic phenotypes. Conclusion: This study's results indicate that the dichloromethane solvent of Dorema ammoniacum gum exhibits its antitumor properties by altering the expression of genes involved in HT-29 cells and the consequent change in downstream metabolic reprogramming.

Larval therapy vs conventional silver dressings for full-thickness burns: a randomized controlled trial.

BACKGROUND: This is the first clinical trial to investigate the effectiveness of maggot debridement therapy (MDT) for full-thickness burn injuries in comparison to conventional silver dressings. METHODS: Thirty-one cases with full-thickness (grade III based on ICD-10 classifications version 2019) burns were assigned into larval therapy (15 cases) and conventional treatment (16 cases) groups. Participants in the MDT group have received loose larvae on days 0, 2, 4, and 6, while controls received a conventional regimen comprised of sharp debridement, silver sulfadiazine, antibiotic therapy, and offloading every day. The primary and secondary outcomes were defined as the time to debridement (from admission to skin autograft) and time to healing (from admission to complete healing post-skin autograft). Patients in two groups were also compared in terms of necrosis resolution, granulation, and granulation/necrosis (g/n) ratio during study time periods. RESULTS: Participants who received larvae had significantly decreased necrosis on days 2 (p = 0.028) and 4 (p = 0.023) compared to those who received control treatment. Significant differences (p < 0.001) were also observed for granulation between the two groups in favor of MDT and the fold changes of g/n in the larvae group were 5, 15, and 13 times higher than that for the conventional regimen on days 2, 4, and 6 of treatment, respectively. Strikingly, a subgroup analysis of high necrotic burns (necrosis > 50%) revealed a significant improvement (p < 0.001) for MDT compared to the control treatment. There were also significant differences (p < 0.001) for the time to debridement and time to healing between the two groups. However, bacterial contamination did not show significant changes between the two treatment regimens. CONCLUSIONS: Our findings revealed that MDT has a favorable superiority over conventional regimen for the treatment of grade-III burns, and thus further clinical trials with larger sample size are warranted to confirm these results.

FAT1 Gene Expression in Iranian Acute Lymphoid and Myeloid Leukemia Patients.

BACKGROUND: FAT atypical cadherin 1 (FAT1) is a member of the cadherin superfamily whose loss or gain is associated with the initiation and/or progression of different cancers. FAT1 overexpression has been reported in hematological malignancies. This research intended to investigate FAT1 gene expression in adult Iranian acute leukemia patients, compared to normal mobilized peripheral blood CD34+ cells. MATERIALS AND METHODS: The peripheral blast (peripheral blood mononuclear cells) cells of 22 acute myeloid leukemia (AML), 14 acute lymphoid leukemia (ALL) patients, and mobilized peripheral blood CD34+ cells of 12 healthy volunteer stem cell donors were collected. Then, quantitative real-time polymerase chain reaction (qPCR) was used to compare FAT1 gene expression. RESULTS: Overall, there were no significant differences in FAT1 expression between AML and ALL patients (p>0.2). Nonetheless, the mean expression level of FAT1 was significantly higher in leukemic patients (AML and ALL) than in normal CD34+ cells (p=0.029). Additionally, the FAT1 expression levels were significantly higher in both CD34+ and CD34- leukemic patients than in normal CD34+ cells (p=0.028). CONCLUSION: No significant differences were found between FAT1 expression in CD34+ and CD34- leukemic samples (p> 0.3). Thus, higher FAT1 expression was evident in ALL and AML leukemia cells but this appeared unrelated to CD34 expression. This suggests in a proportion of adult acute leukemia, FAT1 expression may prove to be a suitable target for therapeutic strategies.

Quantum Bohmian-Inspired Potential to Model Non-Gaussian Time Series and Its Application in Financial Markets.

We have implemented quantum modeling mainly based on Bohmian mechanics to study time series that contain strong coupling between their events. Compared to time series with normal densities, such time series are associated with rare events. Hence, employing Gaussian statistics drastically underestimates the occurrence of their rare events. The central objective of this study was to investigate the effects of rare events in the probability densities of time series from the point of view of quantum measurements. For this purpose, we first model the non-Gaussian behavior of time series using the multifractal random walk (MRW) approach. Then, we examine the role of the key parameter of MRW, λ, which controls the degree of non-Gaussianity, in quantum potentials derived for time series. Our Bohmian quantum analysis shows that the derived potential takes some negative values in high frequencies (its mean values), then substantially increases, and the value drops again for rare events. Thus, rare events can generate a potential barrier in the high-frequency region of the quantum potential, and the effect of such a barrier becomes prominent when the system transverses it. Finally, as an example of applying the quantum potential beyond the microscopic world, we compute quantum potentials for the S&P financial market time series to verify the presence of rare events in the non-Gaussian densities and demonstrate deviation from the Gaussian case.

Differentially Expressed Inflammatory Cell Death-Related Genes and the Serum Levels of IL-6 are Determinants for Severity of Coronaviruses Diseases-2019 (COVID-19).

Background: Inflammatory cell death, PANoptosis, has been suggested to orchestrate the lymphocyte decrement among coronavirus disease-2019 (COVID-19) patients. The main aim of this study was to examine the differences in the expression of key genes related to inflammatory cell death and their correlation with lymphopenia in the mild and severe types of COVID-19 patients. Materials and Methods: Eighty-eight patients (36 to 60 years old) with mild (n = 44) and severe (n = 44) types of COVID-19 were enrolled. The expression of key genes related to apoptosis (FAS-associated death domain protein, FADD), pyroptosis (ASC (apoptosis-associated speck-like protein containing caspase activation and recruitment domains (CARD)), the adapter protein ASC binds directly to caspase-1 and is critical for caspase-1 activation in response to a broad range of stimuli), and necroptosis (mixed lineage kinase domain-like, MLKL) genes were examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay, and compared between the groups. The serum levels of interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay (ELISA) assay. Results: A major increase in the expression of FADD, ASC, and MLKL-related genes in the severe type of patients was compared to the mild type of patients. The serum levels of IL-6 similarly indicated a significant increase in the severe type of the patients. A significant negative correlation was detected between the three genes' expression and the levels of IL-6 with the lymphocyte counts in both types of COVID-19 patients. Conclusion: Overall, the main regulated cell-death pathways are likely to be involved in lymphopenia in COVID-19 patients, and the expression levels of these genes could potentially predict the patients' outcome.

Comparative Analysis of Apigenin-3 Acetate versus Apigenin and Methyl-Prednisolone in Inhibiting Proliferation and Gene Expression of Th1 Cells in Multiple Sclerosis.

OBJECTIVE: In spite of the advances in therapeutic modalities, morbidity, due to multiple sclerosis (MS), still remains high. Therefore, a large body of research is endeavouring to discover or develop novel therapies with improved efficacy for treating MS patients. In the present study, we examined the immunomodulatory effects of apigenin (Api) on peripheral blood mononuclear cells (PBMCs) isolated from MS patients. We also developed an acetylated form of Api (apigenin- 3-acetate) to improve In its blood-brain barrier (BBB) permeability. Additionally, we compared its anti-inflammatory properties to original Api and methyl-prednisolone-acetate (a standard therapy), as a potential option in treating MS patients. MATERIALS AND METHODS: The current study was an experimental-interventional research. The half maximal inhibitory concentration (IC50) values for apigenin-3-acetate, apigenin, and methyl-prednisolone-acetate were determined in healthy volunteers' PBMCs (n=3). Gene expressions of T-box transcription factor (TBX21 or T-bet) and IFN-γ, as well as proliferation of T cells isolated from MS patients' PBMCs (n=5), were examined in co-cultures of apigenin-3-acetate, Api and methyl-prednisolone-acetate after 48 hours of treatment, using quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: Our findings showed that apigenin-3-acetate, apigenin, and methyl-prednisolone-acetate at concentrations of 80, 80, and 2.5 M could inhibit Th1 cell proliferation after 48 hours (P=0.001, P=0.036, and P=0.047, respectively); they also inhibited T-bet (P=0.015, P=0.019, and P=0.022) and interferon-γ (IFN-γ) gene expressions (P=0.0001). CONCLUSION: Our findings suggested that Api may have anti-inflammatory properties, possibly by inhibiting proliferation of IFN-producing Th1 cells. Moreover, comparative immunomodulatory effects were found for the acetylated version of apigenin-3-acetate versus Api and methyl-prednisolone-acetate.

Small extracellular vesicle TGF-ß in cancer progression and immune evasion.

Transforming growth factor-ß (TGF-ß) is a well-known cytokine that controls various processes in normal physiology and disease context. Strong preclinical and clinical literature supports the crucial roles of the TGF-ß in several aspects of cancer biology. Recently emerging evidence reveals that the release of TGF-ß from tumor/immune/stromal cells in small extracellular vesicles (sEVs) plays an important part in tumor development and immune evasion. Hence, this review aims to address the packaging, release, and signaling pathways of TGF-ß carried in sEVs (sEV-TGF-ß) in cancer, and to explore its underpinning roles in tumor development, growth, progression, metastasis, etc. We also highlight key progresses in deciphering the roles of sEV-TGF-ß in subverting anti-tumor immune responses. The paper ends with a focus on the clinical significance of TGF-ß carried in sEVs and draws attention to its diagnostic, therapeutic, and prognostic importance.

Protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against the omicron variant and severe disease: a systematic review and meta-regression.

BACKGROUND: The global surge in the omicron (B.1.1.529) variant has resulted in many individuals with hybrid immunity (immunity developed through a combination of SARS-CoV-2 infection and vaccination). We aimed to systematically review the magnitude and duration of the protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against infection and severe disease caused by the omicron variant. METHODS: For this systematic review and meta-regression, we searched for cohort, cross-sectional, and case-control studies in MEDLINE, Embase, Web of Science, ClinicalTrials.gov, the Cochrane Central Register of Controlled Trials, the WHO COVID-19 database, and Europe PubMed Central from Jan 1, 2020, to June 1, 2022, using keywords related to SARS-CoV-2, reinfection, protective effectiveness, previous infection, presence of antibodies, and hybrid immunity. The main outcomes were the protective effectiveness against reinfection and against hospital admission or severe disease of hybrid immunity, hybrid immunity relative to previous infection alone, hybrid immunity relative to previous vaccination alone, and hybrid immunity relative to hybrid immunity with fewer vaccine doses. Risk of bias was assessed with the Risk of Bias In Non-Randomized Studies of Interventions Tool. We used log-odds random-effects meta-regression to estimate the magnitude of protection at 1-month intervals. This study was registered with PROSPERO (CRD42022318605). FINDINGS: 11 studies reporting the protective effectiveness of previous SARS-CoV-2 infection and 15 studies reporting the protective effectiveness of hybrid immunity were included. For previous infection, there were 97 estimates (27 with a moderate risk of bias and 70 with a serious risk of bias). The effectiveness of previous infection against hospital admission or severe disease was 74·6% (95% CI 63·1-83·5) at 12 months. The effectiveness of previous infection against reinfection waned to 24·7% (95% CI 16·4-35·5) at 12 months. For hybrid immunity, there were 153 estimates (78 with a moderate risk of bias and 75 with a serious risk of bias). The effectiveness of hybrid immunity against hospital admission or severe disease was 97·4% (95% CI 91·4-99·2) at 12 months with primary series vaccination and 95·3% (81·9-98·9) at 6 months with the first booster vaccination after the most recent infection or vaccination. Against reinfection, the effectiveness of hybrid immunity following primary series vaccination waned to 41·8% (95% CI 31·5-52·8) at 12 months, while the effectiveness of hybrid immunity following first booster vaccination waned to 46·5% (36·0-57·3) at 6 months. INTERPRETATION: All estimates of protection waned within months against reinfection but remained high and sustained for hospital admission or severe disease. Individuals with hybrid immunity had the highest magnitude and durability of protection, and as a result might be able to extend the period before booster vaccinations are needed compared to individuals who have never been infected. FUNDING: WHO COVID-19 Solidarity Response Fund and the Coalition for Epidemic Preparedness Innovations.

Blockade of exosome release alters HER2 trafficking to the plasma membrane and gives a boost to Trastuzumab

Objective(s) Exosomal HER2 has been evidenced to interfere with antibody-induced anti-tumor effects. However, whether the blockade of HER2+ exosomes release would affect antibody-mediated tumor inhibition has yet to be investigated. Methods Exosomes derived from BT-474, SK-BR3 and SK-OV3 (HER2-overexpressing tumor cells) and MDA-MB-231 cells (HER2 negative) were purified and characterized by bicinchoninic acid (BCA) assay, western blotting and Transmission electron microscopy (TEM). Inhibition of exosome release was achieved by neutral sphingomyelinase-2 (nSMase-2) inhibitor, GW4869. The effects of exosome blockade on the anti-proliferative effects, apoptosis induction, and antibody-mediated cellular cytotoxicity (ADCC) activity of Trastuzumab were examined using MTT, flow cytometry, and LDH release assays. Also, the effects of exosome inhibition on the surface expression and endocytosis/internalization of HER2 were studied by flow cytometry. Results Purified exosomes derived from HER2 overexpressing cancer cells were positive for HER2 protein. Blockade of exosome release was able to significantly improve apoptosis induction, anti-proliferative and ADCC responses of Trastuzumab dose dependently. The pretreatment of Trastuzumab/purified NK cells, but not PBMCs, with HER2+ exosomes could also decrease the ADCC effects of Trastuzumab. Exosome inhibition also remarkably downregulated surface HER2 levels in a time-dependent manner, but does not affect its endocytosis/internalization. Conclusion Based on our findings, HER2+ exosomes may benefit tumor progression by dually suppressing Trastuzumab-induced tumor growth inhibition and cytotoxicity of NK cells. It seems that concomitant blocking of exosome release might be an effective approach for improving the therapeutic effects of Trastuzumab, and potentially other HER2-directed mAbs (AU)

The effects of nano-curcumin supplementation on Th2/tregulatory axis in migraine patients: a randomized, double-blind, placebo-controlled trial.

AIM: In the present study we aimed to investigate the effects of nano-curcumin supplementation on gene expression and serum levels of IL-4 and TGF-ß in migraine patients. METHODS: Forty participants with episodic migraine were randomly allocated to receive 80 mg nano-curcumin (n = 20) or placebo (n = 20) in a randomized double-blind clinical trial for two months. At the beginning and the end of the study, the interictal serum levels and gene expression of IL-4 and TGF-ß in peripheral blood mononuclear cells (PBMCs) isolated from migraine patients were measured, using ELISA and real-time PCR methods, respectively. RESULTS: Intra-group assays showed a significant rise in the gene expression of both IL-4 and TGF-ß (p < 0.05) in nano-curcumin group after two months of treatment, however the serum levels were only significantly changed for IL-4 (p < 0.05). On the contrast, inter-group assays revealed no statistical differences between nano-curcumin and placebo group in terms of IL-4 and TGF-ß gene expression, while the serum levels of IL-4 was observed to be increased significantly (p = 0.03) following two month nano-curcumin supplementation. CONCLUSION: The findings of the present trial suggest that the treatment with nano-curcumin could induce significant levels of IL-4, in favour of anti-inflammatory effects, while has a minimal effects on the both gene expression and serum levels of TGF-ß. Further studies are required to determine the exact mechanism of action of curcumin in patients with migraine.

Blockade of exosome release alters HER2 trafficking to the plasma membrane and gives a boost to Trastuzumab.

OBJECTIVE(S): Exosomal HER2 has been evidenced to interfere with antibody-induced anti-tumor effects. However, whether the blockade of HER2+ exosomes release would affect antibody-mediated tumor inhibition has yet to be investigated. METHODS: Exosomes derived from BT-474, SK-BR3 and SK-OV3 (HER2-overexpressing tumor cells) and MDA-MB-231 cells (HER2 negative) were purified and characterized by bicinchoninic acid (BCA) assay, western blotting and Transmission electron microscopy (TEM). Inhibition of exosome release was achieved by neutral sphingomyelinase-2 (nSMase-2) inhibitor, GW4869. The effects of exosome blockade on the anti-proliferative effects, apoptosis induction, and antibody-mediated cellular cytotoxicity (ADCC) activity of Trastuzumab were examined using MTT, flow cytometry, and LDH release assays. Also, the effects of exosome inhibition on the surface expression and endocytosis/internalization of HER2 were studied by flow cytometry. RESULTS: Purified exosomes derived from HER2 overexpressing cancer cells were positive for HER2 protein. Blockade of exosome release was able to significantly improve apoptosis induction, anti-proliferative and ADCC responses of Trastuzumab dose dependently. The pretreatment of Trastuzumab/purified NK cells, but not PBMCs, with HER2+ exosomes could also decrease the ADCC effects of Trastuzumab. Exosome inhibition also remarkably downregulated surface HER2 levels in a time-dependent manner, but does not affect its endocytosis/internalization. CONCLUSION: Based on our findings, HER2+ exosomes may benefit tumor progression by dually suppressing Trastuzumab-induced tumor growth inhibition and cytotoxicity of NK cells. It seems that concomitant blocking of exosome release might be an effective approach for improving the therapeutic effects of Trastuzumab, and potentially other HER2-directed mAbs. In addition, the exosome secretion pathway possibly contributes to the HER2 trafficking to plasma membrane, since the blockade of exosome secretion decreased surface HER2 levels.

The Micronecta Kirkaldy, 1897 (Hemiptera: Heteroptera: Micronectidae) of Iran, with four new records and an illustrated key to the species.

The fauna of Micronectidae (pygmy water boatmen) was investigated in Guilan Province. The present study has raised the number of micronectid species known from Iran to nine by reporting four first records for the country, including Micronecta carpatica Wrblewski, 1958, M. griseola Horvth, 1899, M. poweri (Douglas & Scott, 1869), and M. pusilla (Horvth, 1895). Morphological diagnoses for these four species are provided, accompanied by illustrations of male habitus, male genitalia, and a key to the species of Micronecta known from Iran.