Atorvastatin treatment softens human red blood cells: An optical tweezers study

Optical tweezers are proven indispensable single-cell micro-manipulation and mechanical phenotyping tools. In this study, we have used optical tweezers for measuring the viscoelastic properties of human red blood cells (RBCs). Comparison of the viscoelastic features of the healthy fresh and atorvastatin treated cells revealed that the drug softens the cells. Using a simple modeling approach, we proposed a molecular model that explains the drug-induced softening of the RBC membrane. Our results suggest that direct interactions between the drug and cytoskeletal components underlie the drug-induced softening of the cells. © 2018 Optical Society of America

Placenta Site Trophoblastic Tumor and Choriocarcinoma from Previous Cesarean Section Scar: Case Reports

Choriocarcinoma and placental site trophoblastic tumor (PSTT) are rare varieties of gestational trophoblastic disease (GTD). PSTT alone constitutes about 1-2% of all trophoblastic tumors, which presents at early reproductive age and the serum beta-hCG level is much lower than choriocarcinoma. This tumor usually invades the myometrium and its depth of penetration is a prognostic factor. The first case report is regarding a 33-year-old woman with vaginal bleeding 3 months after abortion. The ultrasound exhibited heterogeneous and hypervascular mass related to previous cesarean scar. Serum beta-hCG level was 67 mIU/ml and chemotherapy was administered. However, due to severe vaginal bleeding and no regression in mass size, total abdominal hysterectomy was performed. Histopathological examination and IHC staining confirmed PSTT from previous cesarean section. The second case report is regarding a 33-year-old woman with cervicoisthmic choriocarcinoma, which was mistaken as cesarean scar pregnancy. The ultrasonography and elevated serum beta-hCG level suggested cesarean scar pregnancy. The patient was treated with methotrexate without any effect. Eventually, cervicoisthmic choriocarcinoma was detected after hysterectomy. A diagnostic error was made leading to possible uterus perforation along with incorrect chemotherapy that resulted in a life-threatening condition. It is concluded that PSTT and choriocarcinoma are the two important differential diagnoses of sustained elevated beta-hCG when imaging evidence is also suggestive. Although PSTT and cervicoisthmic choriocarcinoma are rare, they do exist and are on the rise

Aloe emodin induces apoptosis in ER+-breast cancer cells; MCF-7 through IGF-1R signalling pathway

Two-third of breast cancer patients expressed estrogen receptors (ER)s and received endocrine treatment with established anti-estrogens such as tamoxifen. But the action and acquired resistance during treatment are largely unknown. In contrary, phytochemicals are more selective and less cytotoxic to normal cells. Accordingly, we found aloe emodin, an anthraquinone to inhibit the proliferation of ER+-breast cancer cells, MCF-7 with IC50 of 80 μM, but not affecting control breast cells, MCF-10A. Tamoxifen was non-selective to both cells with IC50 of 27 and 38 μM, respectively. Thus, we aimed to investigate the anti-proliferative mechanism of aloe emodin on MCF-7 and its underlying signalling compared to tamoxifen. Cells were treated separately with aloe emodin and tamoxifen at respective IC50 for 72 h. Apoptosis was determined using Annexin V-FITC/PI staining. The expression of insulin-like growth factor-1 receptor (IGF-1R), insulin-like growth factor binding protein (IGFBP)-2 and B-raf gene was investigated using QuantiGene 2.0 Plex assay. Paired-student t-test and ANOVA test were used to compare between untreated and treated cells on the measured parameters. Each treatment was conducted in triplicate and repeated three times. Significance was set at p<0.05. The presences of early and late apoptosis in MCF-7 were seen in both treatments. All target genes were down regulated. The anti-proliferation effect of aloe emodin on MCF-7 is similar with tamoxifen which mediates inhibition of IGF-1R signalling pathway. This suggests aloe emodin as a potential anti-cancer agent to be used in combined anti-estrogen therapy to enhance its efficacy in ER+-breast cancer treatment

Atorvastatin treatment softens human red blood cells: An optical tweezers study

Optical tweezers are proven indispensable single-cell micro-manipulation and mechanical phenotyping tools. In this study, we have used optical tweezers for measuring the viscoelastic properties of human red blood cells (RBCs). Comparison of the viscoelastic features of the healthy fresh and atorvastatin treated cells revealed that the drug softens the cells. Using a simple modeling approach, we proposed a molecular model that explains the drug-induced softening of the RBC membrane. Our results suggest that direct interactions between the drug and cytoskeletal components underlie the drug-induced softening of the cells. © 2018 Optical Society of America

Effects of bisphenol a on neonatal cardiomyocytes beating rate and morphology

Bisphenol A (BPA) has been utilised excessively at a global capacity of 2.9 billion kg/year. It is widely used in manufacturing polycarbonate polymers and epoxy resins. Hence, humans are potentially exposed to this chemical substance in their daily life. As a typical endocrine disruptor, BPA exhibits detectable hormone-like properties. Many studies have been linking BPA exposure in humans with the risk of developing cardiovascular disease, however the direct exposure of BPA on cardiomyocytes beating rates and morphology have not been entirely explored. Therefore, in this study, we aimed to investigate the effects of BPA on cells structure and function of neonatal rat cardiomyocytes culture. Cardiomyocytes were isolated from 0 to 2 days old newborn rats and treated with 0.001 to 100 µM concentration of BPA. All cardiomyocytes were subjected to immunostaining, beating frequency assessment assay, MTS assay and Scanning Electron microscopy (SEM). In immunostaining, cardiomyocytes showed positive staining for F-actin. This staining allows identification of the cells thus differentiate cardiomyocytes from other cell types. Significance effects of BPA on cardiomyocytes were observed in MTS assay (p<0.05) and beating rates (p<0.01). Significant reduction (48%-64%, ± 1.5280) was observed in beating rate of cardiomyocytes exposed to 0.1 to 100 µM of BPA. Meanwhile in MTS assay, significant reduction (54%, 0.067 ± 0.0026) in cell viability was observed in cells exposed to 0.1 µM of BPA only. Interestingly, under SEM, cardiomyocytes showed altered cell surface homogeneity after BPA exposure. Exposure of 0.1 to 100 µM BPA lead to flatten of cardiomyocytes cell surface and blurring of the cell borders. This study offers an in vitro evidence of BPA effects on cardiomyocytes morphology and beating rates, thus suggest the potential adverse effect of BPA exposure. However, further investigation would be required to understand how BPA effects normal cells morphology and beating rates of heart cells

The impacts of intrauterine Bisphenol A exposure on pregnancy and expression of miRNAs related to heart development and diseases in animal model

This study aimed to examine the impact of BPA exposure on pregnancy and foetuses on cardiac tissues and the expression of cardiac microRNAs (miRNAs) related to heart development and diseases. Pregnancy is known to be the “critical windows” in determining the offspring physical and cells development in their life after birth. The increment of the risk of cardiovascular disease (CVD) in a later stage of life has been reported by few studies demonstrated from prenatal exposure of BPA. BPA has been shown to alter miRNAs expression profiles for organ development, regeneration and metabolic functions. These alterations have been associated with the risk of CVDs. However, the associations between pregnancy outcomes and miRNAs expression in cardiac of mother- and foetuses-exposed to BPA are still not entirely explored. In BPA-exposed pregnant rat groups, a significant weight gained was observed in comparison to control (p < 0.05). Interestingly, significant changes in systolic and diastolic blood pressure between the first and third trimester of BPA-exposed pregnant rats were also observed (p < 0.05). In BPA-exposed pregnant rats, miR-499-5p was significantly altered in the heart (p < 0.01). Meanwhile, altered miR-17-5p, -208-3p, and -210-3p expressions were observed in all heart of the foetuses from BPA-exposed pregnant rats (p < 0.05). In H&E staining, BPA-exposed foetal hearts showed a sign of fibrosis while BPA-exposed pregnant rats showed muscle remnant. Masson trichrome staining further confirmed the presence of fibrosis observed in BPA-exposed foetal heart and reduced expression of cardiac troponin I (cTnI) was also observed in BPA-exposed foetal heart. In summary, altered cardiac miRNAs with histological changes were observed in both mother- and foetus-exposed BPA These findings put forward the importance of future work to further understand how prenatal BPA exposure affect foetuses in their later stage of life

Study on the growth status of mullets with viral nervous necrosis disease in the southern Caspian Sea

Mullet and mullet products have considerable economic importance at a regional level, especially around the Caspian Sea. The leaping mullet constitutes an important part of their production. This study is the first detailed work on the age and growth of the leaping mullet (Liza saliens) from September 2012 to March 2013 in the Southern coast of the Caspian Sea. Age and growth determinations were based upon the scale samples taken from 102 fish. Marginal increment analysis was used to validate age determination. The back-calculated lengths stage estimated from the scale showed no differences between in this study. The maximum age of leaping mullet in the Southern coast of the Caspian Sea was 5 years for males and 6 years for females. The von Bertalanffy growth functions were Lt=30.415(1-e-0.275(t+0.645)) for males and Lt=34.832(1-e 0.211(t+1.009)) for females. A large spread and length overlap characterized the age groups. The estimated Length Weight relationships were common for the two sexes (W=0.079L3 ). The slope (b) values of the length-weight relationship showed that weight of leaping grey mullet in Mazandaran increased associated with length in isometric. The mean condition factor for males, females and all specimens were determined as 0.908, 0.900 and 0.897, respectively. According to sex groups, the mean condition factor of males was slightlyhigher than that of females. The total length for leaping grey mullet was determined as 23.3 cm

The advancement of blood cell research by optical tweezers

Demonstration of the light radiation pressure on a microscopic level by A. Ashkin led to the invention of optical tweezers (OT). Applied in the studies of living systems, OT have become a preferable instrument for the noninvasive study of microobjects, allowing manipulation and measurement of the mechanical properties of molecules, organelles, and cells. In the present paper, we overview OT applications in hemorheological research, placing emphasis on red blood cells but also discussing OT applications for the investigation of the biomechanics of leukocytes and platelets. Blood properties have always served as a primary parameter in medical diagnostics due to the interconnection with the physiological state of an organism. Despite blood testing being a well-established procedure of conventional medicine, there are still many complex processes that must be unraveled to improve our understanding and contribute to future medicine. OT are advancing single-cell research, promising new insights into individual cell characteristics compared to the traditional approaches. We review the fundamental and practical findings revealed in blood research through the optical manipulation, stretching, guiding, immobilization, and inter-/intracellular force measurements of single blood cells

Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019

Background: Updated data on chronic respiratory diseases (CRDs) are vital in their prevention, control, and treatment in the path to achieving the third UN Sustainable Development Goals (SDGs), a one-third reduction in premature mortality from non-communicable diseases by 2030. We provided global, regional, and national estimates of the burden of CRDs and their attributable risks from 1990 to 2019. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated mortality, years lived with disability, years of life lost, disability-adjusted life years (DALYs), prevalence, and incidence of CRDs, i.e. chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis, and other CRDs, from 1990 to 2019 by sex, age, region, and Socio-demographic Index (SDI) in 204 countries and territories. Deaths and DALYs from CRDs attributable to each risk factor were estimated according to relative risks, risk exposure, and the theoretical minimum risk exposure level input. Findings: In 2019, CRDs were the third leading cause of death responsible for 4.0 million deaths (95% uncertainty interval 3.6–4.3) with a prevalence of 454.6 million cases (417.4–499.1) globally. While the total deaths and prevalence of CRDs have increased by 28.5% and 39.8%, the age-standardised rates have dropped by 41.7% and 16.9% from 1990 to 2019, respectively. COPD, with 212.3 million (200.4–225.1) prevalent cases, was the primary cause of deaths from CRDs, accounting for 3.3 million (2.9–3.6) deaths. With 262.4 million (224.1–309.5) prevalent cases, asthma had the highest prevalence among CRDs. The age-standardised rates of all burden measures of COPD, asthma, and pneumoconiosis have reduced globally from 1990 to 2019. Nevertheless, the age-standardised rates of incidence and prevalence of interstitial lung disease and pulmonary sarcoidosis have increased throughout this period. Low- and low-middle SDI countries had the highest age-standardised death and DALYs rates while the high SDI quintile had the highest prevalence rate of CRDs. The highest deaths and DALYs from CRDs were attributed to smoking globally, followed by air pollution and occupational risks. Non-optimal temperature and high body-mass index were additional risk factors for COPD and asthma, respectively. Interpretation: Albeit the age-standardised prevalence, death, and DALYs rates of CRDs have decreased, they still cause a substantial burden and deaths worldwide. The high death and DALYs rates in low and low-middle SDI countries highlights the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for tobacco control, enhancing air quality, reducing occupational hazards, and fostering clean cooking fuels are crucial steps in reducing the burden of CRDs, especially in low- and lower-middle income countries