The effect of endurance training on the level of tissue IL-6 and VEGF in mice with breast cancer

زمینه و هدف: تمرینات ورزش پتانسیلی در جهت پیشگیری از سرطان پستان دارد. هدف پژوهش حاضر بررسی اثرات پیشگیری و کمک درمانی تمرینات ورزشی بر سایتوکاین های درگیر در رگ زایی تومور سرطان پستان وابسته به گیرنده استروژن می باشد. روش بررسی: در این مطالعه مداخله ای 50 سر موش بالب سی ماده به طور تصادفی در چهار گروه قرار گرفتند. پس از آشناسازی با محیط دو گروه از موش ها به مدت 8 هفته تمرین استقامتی تداومی را انجام دادند و سپس سلول های سرطانی وابسته به استروژن (MC4-L2) به همه موش ها تزریق گردید. پس از آن یک گروه از موش های تمرین کرده و یک گروه از موش های تمرین نکرده به مدت 6 هفته، 5 روز در هفته تمرینات استقامتی را انجام دادند. حجم تومور به صورت هفتگی با کولیس دیجیتالی اندازه گیری شد. در پایان موش ها قربانی شدند و بافت تومور برداشته و سطوح سایتوکاین های اینترلوکین 6 (IL-6) و فاکتور رشد اپی تلیال عروق (VEGF) با روش الایزا اندازه گیری شد. یافته ها: بین گروه ها در میزان مقادیر IL-6 و VEGF و میزان رشد تومور تفاوت معناداری وجود داشت (001/0PP). نتیجه گیری: با توجه به افت مقادیر IL-6 و VEGF در گروه هایی که قبل از سرطانی شدن و پس از سرطانی شدن تمرینات ورزشی را انجام دادند؛ می توان گفت که تمرینات ورزشی علاوه بر نقش پیشگیرانه بسیار موثر، دارای نقش درمانی در تومورهای وابسته به گیرنده استروژن نیز می باشند

Evaluation of efficacy and safety of a polyherbal Unani formulation in diabetes mellitus type 2 (Zayābīṭus Sukkari Qism Sāni) - a randomised controlled clinical study

15-20Diabetes mellitus type 2 (Zayābīṭus Sukkari Qism Sāni) is a major health concern in 21st century. Despite tremendous advances in modern sciences, there is a lack of relatively safe and effective drug for its management. The primary objective of this study was to evaluate the efficacy and safety of a polyherbal Unani formulation containing Gurmar booti (Gymnema sylvestre), Gilo (Tinospora cordifolia) and Jamun (Syzygium cumini) in the management of Diabetes Mellitus Type 2 (DMT2). It was a randomised controlled clinical study conducted on 60 participants of DMT2 inadequately controlled by diet and exercise. The test drug was given to group-A participants (n=30) 6 g twice daily orally for 12 weeks and the standard drug metformin (500 mg) was given twice daily orally to group-B participants (n=30). It was observed that the difference between the Mean (± SD) value of fasting blood glucose (FBG), postprandial blood glucose (PPBG) and glycosylated haemoglobin (HbA1c) in Test and Control groups at the end of the study in comparison to baseline was significant (p<0.05). This study concludes that the test drug was effective in reducing FBG and PPBG significantly in diabetic participants’ at 12 weeks of treatment

Efficient Excitation of Micro/Nano Resonators and Their Higher Order Modes

We demonstrate a simple and flexible technique to efficiently activate micro/nano-electromechanical systems (MEMS/NEMS) resonators at their fundamental and higher order vibration modes. The method is based on the utilization of the amplified voltage across an inductor, L, of an LC tank resonant circuit to actuate the MEMS/NEMS resonator. By matching the electrical and mechanical resonances, significant amplitude amplification is reported across the resonators terminals. We show experimentally amplitude amplification up to twelve times, which is demonstrated to efficiently excite several vibration modes of a microplate MEMS resonator and the fundamental mode of a NEMS resonator

Plants and Small Molecules: An Up-and-Coming Synergy

The emergence of Arabidopsis thaliana as a model system has led to a rapid and wide improvement in molecular genetics techniques for studying gene function and regulation. However, there are still several drawbacks that cannot be easily solved with molecular genetic approaches, such as the study of unfriendly species, which are of increasing agronomic interest but are not easily transformed, thus are not prone to many molecular techniques. Chemical genetics represents a methodology able to fill this gap. Chemical genetics lies between chemistry and biology and relies on small molecules to phenocopy genetic mutations addressing specific targets. Advances in recent decades have greatly improved both target specificity and activity, expanding the application of this approach to any biological process. As for classical genetics, chemical genetics also proceeds with a forward or reverse approach depending on the nature of the study. In this review, we addressed this topic in the study of plant photomorphogenesis, stress responses and epigenetic processes. We have dealt with some cases of repurposing compounds whose activity has been previously proven in human cells and, conversely, studies where plants have been a tool for the characterization of small molecules. In addition, we delved into the chemical synthesis and improvement of some of the compounds described

A Phase IB open-label, dose-escalation study of NUC 1031 in combination with carboplatin for recurrent ovarian cancer

Funding: The study was funded and the investigational drug NUC-1031 was supplied by NuCana plc.Purpose: NUC-1031 is a first-in-class ProTide modification of gemcitabine. In PRO-002, NUC‑1031 was combined with carboplatin in recurrent ovarian cancer (OC). Experimental Design: NUC-1031 was administered on days 1 & 8 with carboplatin on day 1 every 3 weeks for up to 6 cycles. Four dose cohorts of NUC-1031 (500, 625 and 750 mg/m2) with carboplatin (AUC4 or 5) were investigated. Primary endpoint was RP2CD. Secondary endpoints included safety, investigator-assessed objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS) and pharmacokinetics (PK). Results: 25 women with recurrent OC, a mean of 3.8 prior lines of chemotherapy and a median platinum-free interval (PFI) of 5 months (range: 7 - 451 days) were enrolled, 15/25 (60%) platinum-resistant; 9 (36%) partially platinum-sensitive and 1 (4%) platinum-sensitive. Of the 23 response-evaluable: there was 1 confirmed complete response (CR, 4%), 5 partial responses (PR, 17%) and 8 (35%) stable disease (SD). The ORR was 26% and CBR was 74% across all doses and 100% in the RP2CD cohort. Median PFS was 27.1 weeks. NUC-1031 was stable in the plasma and rapidly generated high intracellular dFdCTP levels that were unaffected by carboplatin. Conclusions: NUC-1031 combined with carboplatin is well tolerated in recurrent OC. Highest efficacy was observed at the RP2CD of 500 mg/m2 NUC-1031 on days 1 & 8 with AUC5 carboplatin day 1, every 3 weeks for 6 cycles. The ability to deliver carboplatin at AUC5 and the efficacy of this schedule even in patients with platinum-resistant disease makes this an attractive therapeutic combination.PostprintPeer reviewe

Ascorbate-enhanced chondrogenesis of ATDC5 cells

The ATDC5 cell line exhibits the multistep chondrogenic differentiation observed during endochondral bone formation. However, it takes up to two months to complete the process of cell expansion, insulin addition to promote differentiation and further changes in culture conditions effectively to induce hypertrophy. We sought to produce consistent chondrogenesis with significant hypertrophic differentiation with simpler conditions in a more practical time period. By adding ascorbate, the prechondrogenic proliferation phase was shortened from 21 to 7 days, with production of cartilaginous nodules during the chondrogenic phase, after insulin addition, that were greater in number and larger in size. Immunohistochemistry indicated much greater matrix elaboration and the mRNA expression of sox9, aggrecan and collagen type II were all significantly increased earlier and to a much higher degree when compared with controls. Moreover, there was a robust induction of hypertrophy: Col10a1, Runx2 and Mmp13 were all induced within 7-10 days. In conclusion, addition of ascorbate to ATDC5 cultures shortened the prechondrogenic proliferation phase, produced earlier chondrogenic differentiation, heightened gene expression and robust hypertrophic differentiation, abrogating the need for extended culture times and the changes in culture conditions. This simple modification considerably enhances the practicality of this cell line for studies of chondrogenesis

Recombinant ADAMTS13 reduces abnormally up-regulated von Willebrand factor in plasma from patients with severe COVID-19

Thrombosis affecting the pulmonary and systemic vasculature is common during severe COVID-19 and causes adverse outcomes. Although thrombosis likely results from inflammatory activation of vascular cells, the mediators of thrombosis remain unconfirmed. In a cross-sectional cohort of 36 severe COVID-19 patients, we show that markedly increased plasma von Willebrand factor (VWF) levels were accompanied by a partial reduction in the VWF regulatory protease ADAMTS13. In all patients we find this VWF/ADAMTS13 imbalance to be associated with persistence of ultra-high-molecular-weight (UHMW) VWF multimers that are highly thrombogenic in some disease settings. Incubation of plasma samples from patients with severe COVID-19 with recombinant ADAMTS13 (rADAMTS13) substantially reduced the abnormally high VWF activity, reduced overall multimer size and depleted UHMW VWF multimers in a time and concentration dependent manner. Our data implicate disruption of normal VWF/ADAMTS13 homeostasis in the pathogenesis of severe COVID-19 and indicate that this can be reversed ex vivo by correction of low plasma ADAMTS13 levels. These findings suggest a potential therapeutic role for rADAMTS13 in helping restore haemostatic balance in COVID-19 patients

Haptoglobin genotype and outcome after spontaneous intracerebral haemorrhage

OBJECTIVE: Haptoglobin is a haemoglobin-scavenging protein that binds and neutralises free haemoglobin and modulates inflammation and endothelial progenitor cell function. A HP gene copy number variation (CNV) generates HP1 and HP2 alleles, while the single-nucleotide polymorphism rs2000999 influences their levels. The HP1 allele is hypothesised to improve outcome after spontaneous (non-traumatic) intracerebral haemorrhage (ICH). We investigated the associations of the HP CNV genotype and rs2000999 with haematoma volume, perihaematomal oedema (PHO) volume, functional outcome and mortality after ICH. METHODS: We included patients with neuroimaging-proven ICH, available DNA and 6-month follow-up in an observational cohort study (CROMIS-2). We classified patients into three groups according to the HP CNV: 1-1, 2-1 or 2-2 and also dichotomised HP into HP1-containing genotypes (HP1-1 and HP2-1) and HP2-2 to evaluate the HP1 allele. We measured ICH and PHO volume on CT; PHO was measured by oedema extension distance. Functional outcome was assessed by modified Rankin score (unfavourable outcome defined as mRS 3-6). RESULTS: We included 731 patients (mean age 73.4, 43.5% female). Distribution of HP CNV genotype was: HP1-1 n=132 (18.1%); HP2-1 n=342 (46.8%); and HP2-2 n=257 (35.2%). In the multivariable model mortality comparisons between HP groups, HP2-2 as reference, were as follows: OR HP1-1 0.73, 95% CI 0.34 to 1.56 (p value=0.41) and OR HP2-1 0.5, 95% CI 0.28 to 0.89 (p value=0.02) (overall p value=0.06). We found no evidence of association of HP CNV or rs200999 with functional outcome, ICH volume or PHO volume. CONCLUSION: The HP2-1 genotype might be associated with lower 6-month mortality after ICH; this finding merits further study

Production and utilization aspects of waste cooking oil based biodiesel in Pakistan

Excessive fuel demand thrusts the Pakistani government to import large volumes of fuel from foreign sources, creating adverse effects on the country's economy. Therefore, exploring an alternative to fossil fuels is unavoidable. The option of environmentally friendly fuel like biodiesel produced from indigenous waste is an additional bonus for the populous developing country like Pakistan where likelihood of waste generation is huge. There exists a potential option for sustainable biodiesel production utilizing excessive waste cooking oil available in the country which otherwise is an ecological burden. The present work is focused to sturdily vindicate the appropriateness of waste cooking oil-based biodiesel generation and utilization in Pakistan through SWOT-AHP, TOWS and PESTLE analysis. The prioritization of SWOT through AHP in view of experts’ perception displayed the strengths and opportunities in highest group priority values (Strengths: 0.51, Opportunities: 0.29). Furthermore, TOWS analysis suggests promising strategies for the sustainable implementation of commercial aspect of waste oil-based biodiesel in Pakistan. Political, Economic, Social, Technological, Legal and Environmental (PESTLE) analysis favors the strengths and opportunities factors of SWOT and TOWS strategies for the application of waste cooking oil based biodiesel in country. At the end, regional recommendations have been provided for the implementation of biodiesel production scenario in country