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2022 ◽  
Vol 34 (2) ◽  
pp. 383-388
Author(s):  
Gayatri Joshi ◽  
Abhishek Tiwari ◽  
Prashant Upadhyay

Piperine is classified as a class II drug in the biopharmaceutical classification system due to its low aqueous solubility. As a result, piperine herbosomes were created to improve the dissolution rate and in vivo liver protecting activity of piperine and physico-chemical characteristics were used to confirm herbosome formation. The piperine-herbosome formulation revealed spherical particle size of all formulations from P1-P10 and found142.4 ± 0.98 nm for best piperine-herbosome formulation (P2) and a PDI value of 0.237, indicating a homogeneous population of piperine loaded vesicles. In vitro drug release rate and percent entrapment efficiency were determined for all formulations P1-P25 and found to be 95.306 ± 0.21 and 97.306 ± 0.65 in 12 h, respectively for best piperine-herbosome formulation (P2). It exemplifies the complex’s long-term releasing capability. This information suggests that it may have a longer retention time inside the body, extending the duration of effect. The antioxidant potential of pure piperine was determined using the DPPH scavenging method, with an IC50 value of 107.59 ± 0.11 g/mL compared to a formulation with an IC50 value of 93.926 ± 0.03 g/mL. Swiss albino mice of either sex were utilized for the evaluation of hepatoprotective activity. On the 8th day, the hepatotoxicity was caused by giving a single oral dosage of CCl4 (0.5 mL) and the parameters were evaluated on the 9th day. This formulation has the best optimized based on drug content and drug entrapment. Serum glutamic oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and total bilirubin were among the biochemical markers measured. In comparison to normal control (161 ± 0.31 IU/L, 52.78 ± 0.28 IU/L, 121.12 ± 0.14 IU/L and 0.633 ± 1.44 IU/L) and P2 formulation (163.23 ± 0.49 IU/L, 66.9 ± 0.05 IU/L, 128.3 ± 1.15 IU/L and 0.645 ± 0.67 IU/L respectively).


Forests ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1794
Author(s):  
Mouna Feki ◽  
Giovanni Ravazzani ◽  
Alessandro Ceppi ◽  
Gaetano Pellicone ◽  
Tommaso Caloiero

In this paper, the FEST-FOREST model is presented. A FOREST module is written in the FORTRAN-90 programming language, and was included in the FEST-WB distributed hydrological model delivering the FEST-FOREST model. FEST-FOREST is a process-based dynamic model allowing the simulation at daily basis of gross primary production (GPP) and net primary production (NPP) together with the carbon allocation of a homogeneous population of trees (same age, same species). The model was implemented based on different equations from literature, commonly used in Eco-hydrological models. This model was developed within the framework of the INNOMED project co-funded under the ERA-NET WaterWorks2015 Call of the European Commission. The aim behind the implementation of the model was to simulate in a simplified mode the forest growth under different climate change and management scenarios, together with the impact on the water balance at the catchment. On a first application of the model, the results are considered very promising when compared to field measured data.


2021 ◽  
Vol 118 (51) ◽  
pp. e2110550118
Author(s):  
Xing Zhao ◽  
Jiliang Hu ◽  
Yiwei Li ◽  
Ming Guo

Recent studies have revealed that extensive heterogeneity of biological systems arises through various routes ranging from intracellular chromosome segregation to spatiotemporally varying biochemical stimulations. However, the contribution of physical microenvironments to single-cell heterogeneity remains largely unexplored. Here, we show that a homogeneous population of non–small-cell lung carcinoma develops into heterogeneous subpopulations upon application of a homogeneous physical compression, as shown by single-cell transcriptome profiling. The generated subpopulations stochastically gain the signature genes associated with epithelial–mesenchymal transition (EMT; VIM, CDH1, EPCAM, ZEB1, and ZEB2) and cancer stem cells (MKI67, BIRC5, and KLF4), respectively. Trajectory analysis revealed two bifurcated paths as cells evolving upon the physical compression, along each path the corresponding signature genes (epithelial or mesenchymal) gradually increase. Furthermore, we show that compression increases gene expression noise, which interplays with regulatory network architecture and thus generates differential cell-fate outcomes. The experimental observations of both single-cell sequencing and single-molecule fluorescent in situ hybridization agrees well with our computational modeling of regulatory network in the EMT process. These results demonstrate a paradigm of how mechanical stimulations impact cell-fate determination by altering transcription dynamics; moreover, we show a distinct path that the ecology and evolution of cancer interplay with their physical microenvironments from the view of mechanobiology and systems biology, with insight into the origin of single-cell heterogeneity.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Helga Vera von Bargen ◽  
María Espinosa Serrano ◽  
Daniel Martin Navarrete ◽  
Paz Ahumada Droguett ◽  
Carolina Méndez B. ◽  
...  

Abstract Objectives The SARS-CoV-2 virus continues wreaking worldwide havoc on health and between March and August 2020, the first outbreak of COVID-19 hit Chile. The pregnant population is especially vulnerable to infection. Studies have been published that associate socioeconomic status, overcrowding, and poverty with a higher prevalence of SARS-CoV-2 infection. There are few studies about the development of this pandemic in Latin American countries so far. This study seeks to show the prevalence and sociodemographic and perinatal characteristics in pregnant women at the time of delivery, comparing both groups with positive and negative COVID-19 PCR results. Methods A prospective, cross-sectional study of pregnant women who delivered at the San Juan de Dios Hospital in Santiago between April 15, 2020 and June 15, 2020. Analysis of epidemiological, sociodemographic, obstetric, perinatal and sociodemographic data of patients with positive and negative COVID-19 PCR results. Results There were 701 patients included in the study. The prevalence of those with a positive COVID-19 PCR was 9.7% and 67.7% being asymptomatic. Pre-term delivery was significantly higher in the group of positive patients (23.5%) vs. negative patients (8.7%), which was not the same rate as with cesarean sections (C-sections). A 13.2% of patients required management of the pathology in the Critical Care Unit (CCU) and there were no cases of maternal or fetal deaths. We found no significant difference between both groups when analyzing socioeconomic variables, though we noted a trend of greater overcrowding among the group of patients with infection. Conclusions The majority of pregnant patients with SARS-CoV-2 infection are asymptomatic. COVID-19 increases the rate of premature births, but this rate is not same with C-sections. Sociodemographic conditions and overcrowding do not show a higher infection rate in a homogeneous population in relation to the economic, social and demographic level.


2021 ◽  
Vol 108 (Supplement_9) ◽  
Author(s):  
Caoimhe Walsh ◽  
Fenella Welsh ◽  
Wasula Rathnaweera ◽  
Kandiah Chandrakumaran ◽  
Ashok Roy ◽  
...  

Abstract Background The risk of major haemorrhage during liver surgery has decreased considerably in the modern era. However, there remains reluctance amongst liver surgeons to give routine peri-operative chemical thromboprophylaxis, either because of the perceived risk of bleeding, or transient post-operative abnormalities in conventional coagulation studies. The aim of this study was to ask whether a defined, homogeneous population of patients undergoing liver resection for colorectal metastases (CRM) were at risk from venous thromboembolism (VTE) prior to surgery, and what the impact of liver resection was on that risk. Methods A single-centre prospective observational cohort study comparing pre-, peri- and post-operative haemostasis variables in patients undergoing liver resection for CRM. Patients with cirrhosis, history of VTE or anticoagulated were excluded, as were patients undergoing small wedge, or laparoscopic liver resections. Blood samples for coagulation assays were collected pre-operatively, peri-operatively (after transection) and first post-operative day (13–20 hours post-operatively). Pre- and post-operative Tissue Factor messenger ribonucleic acid (TFmRNA) activation was measured from peripheral blood mononuclear cells (PBMCs) using semi-quantitative polymerase chain reaction (PCR). Patients received peri-operative mechanical thromboprophylaxis until mobile, plus chemical thromboprophylaxis on the first post-operative day, after venesection. Results Of 336 hepatectomies performed October 2017-December 2019, 60 resections in 57 patients were recruited. This included 46.7% major resections, with median (interquartile range [IQR]) blood loss 150.0mls (76.3-263.7), no blood transfusions, post-operative VTE events or deaths. Patients were prothrombotic pre-operatively (high factor VIIIC and thrombin generation velocity index), an effect exacerbated post-hepatectomy. Major hepatectomies had a significantly greater drop in Protein C, rise in Factor VIIIC and von Willebrand Factor, versus minor resections (p = 0.001,0.005,0.001 respectively). Patients with transection times greater than median (40minutes), had significantly increased median (IQR) PMBC-TFmRNA expression [1.65 (0.93-2.70)2ddCt], versus quicker transections [0.99 (0.69-1.28)2ddCt, p = 0.020]. Conclusions These data show the risk of major haemorrhage in elective liver resection in a high volume unit is low and administration of chemical thromboprophylaxis within 13-20 hours of surgery is safe and effective. The study demonstrates that patients with CRM are prothrombotic pre-operatively. Furthermore, this thrombophilia is exacerbated by liver resection, and most marked in patients with longer, more complex operations. These data suggest that chemical thromboprophylaxis should be considered earlier in the patient pathway, and has resulted in a change in practice for the authors.


Author(s):  
Nina Le Bert ◽  
Wan Ni Chia ◽  
Wei Yee Wan ◽  
Alvin Kuo Jing Teo ◽  
Samuel Zeng-Rong Chong ◽  
...  

Author(s):  
Artem Minin ◽  
Igor Blatov ◽  
Valeria Lebedeva ◽  
Maxim Tuchai ◽  
Varvara Pozdina ◽  
...  

In vitro systems serve as compact and manipulate models to investigate interactions between different cell types. A homogeneous population of cells predictably and uniformly responds to external factors. In a heterogeneous cell population, the effect of external growth factors is perceived in the context of intercellular interactions. Indirect cell co-cultivation allows one to observe the paracrine effects of cells and separately analyze cell populations. The article describes an application of custom-made cell co-cultivation systems based on protein membranes separated from the bottom of the vessel by the 3d printed holder or kept afloat by a magnetic field. Using the proposed co-cultivation system, we analyzed the interaction of A549 cells and fibroblasts, in the presence and absence of growth factors. During co-cultivation of cells, the expression of genes of the activation for epithelial and mesenchymal transitions decreases. The article proposes the application of a newly available system for the co-cultivation of different cell types.


Author(s):  
Paul Manoukian ◽  
Maarten Bijlsma ◽  
Hanneke van Laarhoven

Pancreatic tumors are known to harbor an abundant and highly desmoplastic stroma. Among the various cell types that reside within tumor stroma, cancer-associated fibroblasts (CAFs) have gained a lot of attention in the cancer field due to their contributions to carcinogenesis and tumor architecture. These cells are not a homogeneous population, but have been shown to have different origins, phenotypes, and contributions. In pancreatic tumors, CAFs generally emerge through the activation and/or recruitment of various cell types, most notably resident fibroblasts, pancreatic stellate cells (PSCs), and tumor-infiltrating mesenchymal stem cells (MSCs). In recent years, single cell transcriptomic studies allowed the identification of distinct CAF populations in pancreatic tumors. Nonetheless, the exact sources and functions of those different CAF phenotypes remain to be fully understood. Considering the importance of stromal cells in pancreatic cancer, many novel approaches have aimed at targeting the stroma but current stroma-targeting therapies have yielded subpar results, which may be attributed to heterogeneity in the fibroblast population. Thus, fully understanding the roles of different subsets of CAFs within the stroma, and the cellular dynamics at play that contribute to heterogeneity in CAF subsets may be essential for the design of novel therapies and improving clinical outcomes. Fortunately, recent advances in technologies such as microfluidics and bio-printing have made it possible to establish more advanced ex vivo models that will likely prove useful. In this review, we will present the different roles of stromal cells in pancreatic cancer, focusing on CAF origin as a source of heterogeneity, and the role this may play in therapy failure. We will discuss preclinical models that could be of benefit to the field and that may contribute to further clinical development.


Author(s):  
John W Prineas ◽  
John D E Parratt

Abstract This study examined the roles of microglia and monocytes in myelin destruction in patients with early multiple sclerosis (MS). Twenty-two cases were studied; the clinical duration was <9 weeks in 10 cases. Twenty myeloid cell subtypes or categories were identified including 2 cell types not known previously to occur in demyelinating diseases. Commencing myelin breakdown in plaques and in perivascular and subpial tissues occurred in the immediate presence of infiltrating monocytes and was effected by a homogeneous population of IgG-positive Fc receptor-bearing early phagocytes interacting with abnormal myelin. Oligodendrocyte apoptosis was observed in intact myelinated tissue bordering areas of active demyelination. Capillaries in the cerebral cortex plugged by large numbers of monocytes were common in acute cases of MS and in a patient with a neuromyelitis optica variant and extreme systemic recruitment of monocytes. In an MS patient with progressive disease, microglial nodules centered on MHC-II-positive capillaries plugged by monocytes were present in the cerebral cortex. This constitutes a new gray matter lesion in MS.


2021 ◽  
pp. 001139212110392
Author(s):  
Hsin-Chieh Chang

In an era of rising global intra-regional migration, in-depth explorations of attitudes toward immigrants and immigration (ATII) in emerging migrant-receiving societies in Asia are scarce. Using Taiwan as a case of an emerging non-Western, democratic migrant-receiving context with a racially homogeneous population, aging social structure, and vibrant civic culture, this is the first study to examine receptivity to three major migrant types. The study contributes to the ATII literature and sociological research through discovering something old (perceived group threat of foreign professionals and labor migrants at the individual level), something new (link between positive attitudes toward same-sex marriage and higher receptivity to blue-collar migrants), something borrowed (civic behavior), and something context-specific (effect of the high visibility of marriage immigrants in certain places on receptivity). This study highlights the importance of uncovering patterns and mechanisms of nativity-, ethnicity-, and class-based foreigner exclusionism in emerging non-Western migrant destinations. The findings on receptivity toward intra-Asia migrants in a 21st-century Asian society illuminate possibilities for reinventing theories on the social organization of difference and the socio-cognitive construction of ethnicity, with broader relevance to inter-minority relations among Asians in traditional Western immigrant societies.


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