Micro (mi)RNAs have recently been found to play an important role in cancer biology. In order to further understand how miRNAs affect prostate tumour progression, we evaluated miRNA expression in two invasive prostate tumour lines, PC3 and DU145. We then focused our evaluation on a novel miRNA, miR-105, whose levels were significantly decreased in both tumour cell lines as compared to normal prostate epithelial cells. As miR-105 levels were reduced in prostate tumour cell lines, we restored its expression following transfection of cells with mimic constructs to over-express miR-105 in both cell lines, in order to determine its effect on various tumourigenic properties. Over-expression caused decreased tumour cell proliferation, anchorage-independent growth and invasion in vitro and inhibited tumour growth in vivo. We further identified CDK6 as a putative target of miR-105, which likely contributed to its inhibition of tumour cell growth. Our results suggest that miR-105 inhibits tumour cell proliferation and may be an interesting target to regulate tumour growth or potentially used as a biomarker to differentiate between less and more aggressive tumours in patients.

Hipodermóclise (HDC) é uma importante técnica alternativa para a administração de medicamentos e fluidos pela via subcutânea. É usada com frequência para o controle dos sintomas em pacientes em cuidados paliativos com dificuldade de acesso venoso e que são incapazes de tolerar medicação oral. No entanto, raros estudos abordaram o uso da HDC de uma forma global, para reposição hidroeletrolítica e terapia medicamentosa, tanto na forma contínua quanto intermitente, observando detalhes e complicações do seu uso. Os objetivos deste estudo incluíram caracterizar o uso da HDC para administração de medicamentos, soluções e eletrólitos e avaliar as possíveis complicações locais, identificando também outros fatores que influenciam sua ocorrência. Estudo observacional prospectivo com coleta de dados em prontuário e acompanhamento diário de pacientes internados com câncer avançado, da equipe de Cuidados Paliativos do Instituto do Câncer do Estado de São Paulo (ICESP) em uso de HDC, verificando local de punção, medicamentos administrados e possíveis complicações, acompanhando os detalhes de seu uso. A análise estatística não-paramétrica e método de regressão logística foram realizados. Foram acompanhados 99 pacientes com 243 punções, das quais 166 (68,3%) em coxa e 46 (18,9%) em abdome. Os medicamentos mais utilizados foram morfina em 122 (50,2%) punções, seguido de dipirona em 118 (48,6%) e dexametasona em 86 (35,4%). A solução mais prescrita foi a glicofisiológica em 38 (15,6%) punções, pelo seu aporte calórico. 13,6% das punções (33 de 243) tiveram complicações, sendo apenas seis casos maiores (edema). Complicações ocorreram mais frequentemente até o segundo dia da punção e foram associadas com o número (p=0,007) e o volume (p=0,042) de medicamentos administrados e também com a solução glicofisiológica (p=0,003) e os eletrólitos cloreto de potássio (p=0,037) e cloreto de sódio (p=0,013). Este estudo permitiu o conhecimento de fatores associados a complicações e propõe algumas recomendações, como: individualização da terapia, especialmente relacionada com o volume de escolha, número de medicamentos administrados e evitar a adição de eletrólitos na solução glicofisiológica / Hypodermoclysis (HDC) is an important alternative technique for the administration of drugs and fluids into the subcutaneous tissue. It is frequently used for symptom control in palliative care patients, with difficult venous access and unable to tolerate oral medications. However, few studies address the use of HDC as a whole to fluid replacement and drug therapy, both continuous and intermittent mode, observing details and complications of its use. The objectives of this study included characterizing the use of HDC to administer drugs, solutions and electrolytes and to evaluate possible local complications also identifying other factors influencing their occurrence. Prospective observational study with data collection in medical records and daily monitoring of advanced cancer inpatients of the palliative care team of São Paulo State Cancer Institute (ICESP) in use of HDC, checking infusion site, administered drugs and possible complications, following the details of its use. Non-parametrical statistical analysis and logistic regression were performed. Were followed 99 patients with 243 infusion sites, which 166 (68.3%) in the thigh and 46 (18.9%) in the abdomen. The most commonly used drugs were morphine in 122 (50.2%) infusion sites, followed by dipyrone in 118 (48.6%) and dexamethasone in 86 (35.4%). The most prescribed solution was dextrose 5%/0,9% saline in 38 (15.6%) infusion sites because of its caloric intake. 13.6% of punctures (33 of 243) had complications, only six larger cases (edema). Complications occurred mainly up to the second day of the infusion sites and were associated with the number (p=0,007) and volume (p=0,042) of drugs used as also with 5% dextrose/0.9% saline solution (p=0,003) and NaCl (p=0,037) and KCl (p=0,013) electrolytes. This study has allowed the knowledge of factors associated with complications and proposes some recommendations as: individualization of therapy especially related to the volume of choice, number of drugs administered, and avoid adding electrolytes to the 5% dextrose/0.9% saline solution

Desde o início de 1990, a enxertia de gordura na prega vocal é descrita como um método para reparar a insuficiência glótica. O objetivo deste estudo é avaliar os efeitos da aplicação tópica de mitomicina-C no processo cicatricial de enxertos autólogos de gorduras inseridos em pregas vocais de coelhos através da medida da deposição de colágeno. Vinte e oito coelhos foram submetidos a enxertia de gordura em ambas pregas vocais. As pregas vocais direitas recebeu previamente a aplicação tópica de mitomicina-C (0,4mg/ml) durante cinco minutos enquanto que as pregas vocais esquerdas formavam o grupo controle (sem mitomicina-C). Quatro grupos com 6 coelhos cada foram sacrificados com 7, 14, 30 e 90 dias após a cirurgia de enxertia. As pregas vocais foram removidas para estudo histológico com a intenção de quantificar a deposição de colágeno através da coloração por Picrossírius Red sob microscopia polarizada. A deposição de colágeno foi menor em todos os grupos de pregas vocais que receberam aplicação tópica de mitomicina-C quando comparada com as pregas vocais do grupo controle. No presente estudo, a aplicação tópica de mitomicina-C antes da enxertia de gordura reduziu significativamente a deposição de colágeno (p = 0,05). / Since the early 1990s, fat implantation in the vocal fold is described as a method of repairing glottal insufficiency. The aim of this study was to evaluate the effect of topical application of mitomycin in the healing process with collagen deposition measurement around of autologous fat implants inserted in rabbits vocal folds. Twenty-eight rabbits were submitted to a fat implant in the both vocal folds. The right vocal folds received previously topical application of mitomycin (0,4mg/ml) for five minutes and the left vocal folds were the control group (without mitomycin). Four groups of 6 rabbits each were sacrificed 7, 14, 30 and 90 days after the implantation. The samples of the vocal folds were collected for histological analysis with the purpose of quantifying the collagen deposition by Picrosirius Red stain under polarization microscopy. The collagen deposition was lower in all groups of vocal folds with topical application of mitomycin than in control groups. In the present study, the topical application of mitomycin before the fat grafts reduced significantly the collagen deposition (p = 0,05).

Diabetes mellitus tipo 2 (DM2) está associado a um estado de inflamação crônica e ativação do estresse do retículo endoplasmático (ERE). Nesse contexto, são necessários estudos para encontrar alternativas que melhorem o quadro inflamatório, como os ácidos graxos poli-insaturados ômega 3 (n-3 PUFA), um conhecido agente anti-inflamatório. Esse estudo teve por objetivo avaliar o efeito da suplementação do ácido alfa-linolênico (ALA, um n-3 PUFA) no estresse do retículo endoplasmático e no estado inflamatório no tecido adiposo subcutâneo abdominal (TASC) em pacientes com DM2. Foi conduzido um estudo duplo-cego, prospectivo, placebo-controlado. Vinte pacientes com DM2 foram randomizados para suplementação com 3g/dia de ALA ou placebo durante 60 dias. O tecido adiposo foi coletado através de punção aspirativa por agulha fina do abdome antes e após a suplementação e os genes e proteínas foram avaliados através de PCR em tempo real e western blot. Foi encontrada, após suplementação, uma redução da expressão gênica do XBP1 (20%), sXBP1 (70%) e aumento da expressão gênica do GRP78 (150%), confirmado na expressão proteica. Além disso, foi encontrado aumento da expressão gênica da adiponectina (90%) e redução da expressão gênica do IL-6 (80%) e IRS-1 (60%), sem correlação com a expressão proteica, no tempo pós-suplementação com ALA. Portanto, foi demonstrado que o ALA pode modular o ERE através da via da IRE1/XBP, levando ao aumento das chaperonas (BIP/GRP78), além de um efeito adicional na expressão gênica da adiponectina, IL-6 e IRS-1, o que pode demonstrar um potencial terapêutico do ALA em pacientes com DM2. / Type 2 diabetes mellitus (T2DM) is a state of chronic inflammation and activation of endoplasmic reticulum stress (ERS). In this context, studies are necessaries to find new possibilities to improve this inflammation such as the n-3 polyunsaturated fatty acid (n-3 PUFA) acting as an anti-inflammatory agent. In this study, we aimed to evaluate the effect of n-3 PUFA alpha-linolenic acid (ALA, a n-3 PUFA) supplementation in T2DM patients on the molecular expression of ERS genes in abdominal subcutaneous adipose tissue (SAT). We performed a placebo-controlled study, in a double-blind design with 20 T2DM patients, receiving, randomly, 3g/day of ALA or placebo for 60 days. The adipose tissue was collected by fine-needle aspiration in abdomen before and after the supplementation and the genes and proteins were evaluated by real-time PCR and western blot. It was seen, after the supplementation, a reduction in XBP1 (20%), sXBP1 (70%) and an increase in Grp78 (150%) gene expression, likewise same results in protein concentration. Furthermore, it was observed an increase in adiponectina (90%) gene expression and reduction in IL-6 (80%) and IRS-1 (60%) gene expression, with no correlation to protein expression after supplementation of ALA. Therefore, we have provided evidence that ALA may modulate ERS by the IRE1/XBP pathway leading to an increase in chaperones (BIP/GRP78), additionally its effect on adiponectina, IL-6 and IRS-1 gene expression can demonstrate a therapeutic potential in T2DM.

Micro (mi)RNAs have recently been found to play an important role in cancer biology. In order to further understand how miRNAs affect prostate tumour progression, we evaluated miRNA expression in two invasive prostate tumour lines, PC3 and DU145. We then focused our evaluation on a novel miRNA, miR-105, whose levels were significantly decreased in both tumour cell lines as compared to normal prostate epithelial cells. As miR-105 levels were reduced in prostate tumour cell lines, we restored its expression following transfection of cells with mimic constructs to over-express miR-105 in both cell lines, in order to determine its effect on various tumourigenic properties. Over-expression caused decreased tumour cell proliferation, anchorage-independent growth and invasion in vitro and inhibited tumour growth in vivo. We further identified CDK6 as a putative target of miR-105, which likely contributed to its inhibition of tumour cell growth. Our results suggest that miR-105 inhibits tumour cell proliferation and may be an interesting target to regulate tumour growth or potentially used as a biomarker to differentiate between less and more aggressive tumours in patients.

<p>Uobičajeni pristup i testiranju biolo&scaron;kog pona&scaron;anja materijala je da se počne sa jednostavnim in vitro testovima baziranim na ćelijskim kulturama. In vitro testovi citotoksičnosti su danas jedan od osnovnih načina za procenu biolo&scaron;kog odgovora na materijal jer su brži, lak&scaron;i za ponavljanje, ocenjivanje i jeftiniji u odnosu na eksperimente koji se izvode na životinjama i ljudima. Koriste se kao neka vrsta skrining testova za procenu biolo&scaron;ke sigurnosti materijala. Za razliku od ćelijskih kultura, istraživanja koja uključuju eksperimentalne životinje pružaju bolji uvid u biokompatibilnost materijala, zbog mogućnosti praćenja kompleksnog imunolo&scaron;kog odgovora živog organizma. Smatraju se neophodnim za ocenu bilo&scaron;kih odgovora na novi materijal, pre nego &scaron;to se on upotrebi na ljudima. Mnogi aspekti biolo&scaron;kog odgovora ne mogu biti reprodukovani in vitro testovima uključujući krvne interakcije, zarastanje rana, reakcije preosetljivosti, karcinogenezu, hroničnu inflamaciju. Eksperimenti na životinjama pružaju informacije o ovim tipovima efekata bez izlaganja ljudi riziku. Cilj ovog istraživanja bio je da se oceni biokompatibilnost objekata od polimera na bazi epoksi smole Accura&reg; ClearVue&trade; (hemijski sastav: 4,4&rsquo;- izopropilidendicikloheksanol, produkti oligomerne reakcije sa 1-hlor-2,3- epoksipropanom(40-65%), sme&scaron;а triaril-sulfonijum soli (50% propilen-karbonata i 50% triaril-sulfonijum heksafluoroantimonatnih soli) (1-10%) i 3-etil-3hidroksimetil-oksetan(10-20%). U oceni citotoksičnosti materijala Accura&reg; ClearVue&trade; kori&scaron;ćeni su agar diguzioni i MTT test. Oba testa rađena sun a ćelijskim kulturama L929 (mi&scaron;iji fibroblasti) i MRC-5 (humani fibroblasti). Ocena biokompatibilnosti testiranog materijala vr&scaron;ena je na osnovu urađenog testa iritacije oralne mukoze na modelu bukalne kesice hrčka, &scaron;to je definisano standardom ISO 10993-10:2010. Biokompatibilnost materijala ispitana je i implantacijom uzoraka u potkožno tkivo dorzuma pacova soja Wistar.</p> / <p>Uobičajeni pristup i testiranju biolo&scaron;kog pona&scaron;anja materijala je da se počne sa jednostavnim in vitro testovima baziranim na ćelijskim kulturama. In vitro testovi citotoksičnosti su danas jedan od osnovnih načina za procenu biolo&scaron;kog odgovora na materijal jer su brži, lak&scaron;i za ponavljanje, ocenjivanje i jeftiniji u odnosu na eksperimente koji se izvode na životinjama i ljudima. Koriste se kao neka vrsta skrining testova za procenu biolo&scaron;ke sigurnosti materijala. Za razliku od ćelijskih kultura, istraživanja koja uključuju eksperimentalne životinje pružaju bolji uvid u biokompatibilnost materijala, zbog mogućnosti praćenja kompleksnog imunolo&scaron;kog odgovora živog organizma. Smatraju se neophodnim za ocenu bilo&scaron;kih odgovora na novi materijal, pre nego &scaron;to se on upotrebi na ljudima. Mnogi aspekti biolo&scaron;kog odgovora ne mogu biti reprodukovani in vitro testovima uključujući krvne interakcije, zarastanje rana, reakcije preosetljivosti, karcinogenezu, hroničnu inflamaciju. Eksperimenti na životinjama pružaju informacije o ovim tipovima efekata bez izlaganja ljudi riziku. Cilj ovog istraživanja bio je da se oceni biokompatibilnost objekata od polimera na bazi epoksi smole Accura&reg; ClearVue&trade; (hemijski sastav: 4,4&rsquo;- izopropilidendicikloheksanol, produkti oligomerne reakcije sa 1-hlor-2,3- epoksipropanom(40-65%), sme&scaron;a triaril-sulfonijum soli (50% propilen-karbonata i 50% triaril-sulfonijum heksafluoroantimonatnih soli) (1-10%) i 3-etil-3hidroksimetil-oksetan(10-20%). U oceni citotoksičnosti materijala Accura&reg; ClearVue&trade; kori&scaron;ćeni su agar diguzioni i MTT test. Oba testa rađena sun a ćelijskim kulturama L929 (mi&scaron;iji fibroblasti) i MRC-5 (humani fibroblasti). Ocena biokompatibilnosti testiranog materijala vr&scaron;ena je na osnovu urađenog testa iritacije oralne mukoze na modelu bukalne kesice hrčka, &scaron;to je definisano standardom ISO 10993-10:2010. Biokompatibilnost materijala ispitana je i implantacijom uzoraka u potkožno tkivo dorzuma pacova soja Wistar.</p> / <p>The usual approach in testing biological behavior of materials is to start with simple in vitro tests based on cell cultures. In vitro cytotoxicity tests are one of the basic methods of assessing the biological response to material because they are faster, cheaper, easier for repeating and evaluating compared to experiments carried out on animals and humans. They are used as a kind of screening test for evaluating the biosafety of materials. Unlike cell culture, studies involving experimental animals provide better insight into the biocompatibility of materials due to the possibility of monitoring the complex immune response of a living organism. They are considered necessary for assessing the biological response to new material before it is used on humans. Many aspects of a biological response cannot be reproduced with in vitro tests, including blood interaction, wound healing, hypersensitivity reactions, carcinogenesis, chronic inflammation. Animal experiments provide information about these types of effects without exposing humans to risk.&nbsp; The aim of this study was to evaluate the biocompatibility of polymer objects on the basis of epoxy resins Accura&reg; ClearVue &trade; (chemical composition: 4.4&#39; Isopropylidenedicyclohexanol, oligomeric reaction products with 1-chloro-2.3-epoxypropane (40-65%), a mixture of triaryl sulfonium salt (50% propylene carbonate and 50% of a triarylsulfonium hexafluoroantimonate salt) (1- 10%) and 3-ethyl-3-hydroxymethyl-oxetane (10-20%). In the assessment of the cytotoxicity of materials Accura&reg; ClearVue &trade; agar diffusion and MTT tests were used. Both tests were conducted on cell cultures L929 (mouse fibroblasts) and MRC-5 (human fibroblasts). An assessment of the biocompatibility of the tested material was done on the basis of an oral mucosa irritation test on a hamster cheek pouch as defined by ISO 10993-10: 2010. The biocompatibility of the material was also tested with the implantation of a samples into the dorsal subcutaneous tissue of a Wistar rats. The subcutaneous implantation test, as one of the most reliable methods for assessing the biocompatibility of dental materials, is defined by ISO 10993-6: 2010. The study was conducted on 30 rats which were sacrificed in groups</p>

Title:. Influence of physical activity on body fat reduction Objectives: The main aim of this thesis is to verify the effect of physical activity on body fat reduction compared with a diet. Methods: Literature search, creation of intervention programs and their implementation, data analysis and graphical presentation of results. Results: Changes in body composition among different groups was not statistically significant. Effect of physical activity on body fat reduction is not confirmed - this hypothesis has been rejected Key words: The exercise program, diet, body composition, gait, energy expenditure and intake, physical activity, motivation, reduction of subcutaneous fat, data collection and analysis, exercise and diet

The gastrointestinal tract (GIT) regulates nutrient uptake, secretes hormones and has a crucial gut flora and enteric nervous system. Of relevance for these functions are the G protein-coupled receptors (GPCRs) and the solute carriers (SLCs). The Adhesion GPCR subfamily is known to mediate neural development and immune system functioning, whereas SLCs transport e.g. amino acids, fatty acids (FAs) and drugs over membranes. We aimed to comprehensively characterize Adhesion GPCR and SLC gene expression along the rat GIT. Using qPCR we measured expression of 78 SLCs as well as all 30 Adhesion GPCRs in a twelve-segment GIT model. 21 of the Adhesion GPCRs had a widespread (≥5 segments) or ubiquitous (≥11 segments) expression. Restricted expression patterns were characteristic for most group VII members. Of the SLCs, we found the majority (56 %) of these transcripts to be expressed in all GIT segments. SLCs were predominantly found in the absorption-responsible gut regions. Both Adhesion GPCRs and SLCs were widely expressed in the rat GIT, suggesting important roles. The distribution of Adhesion GPCRs defines them as a potential pharmacological target. FAs constitute an important energy source and have been implicated in the worldwide obesity increase. FAs and their ratios – indices for activities of e.g. the desaturase enzymes SCD-1 (SCD-16, 16:1n-7/16:0), D6D (18:3n-6/18:2n-6) and D5D (20:4n-6/20:3n-6) – have been associated with e.g. overall mortality and BMI. We examined whether differences in FAs and their indices in five lipid fractions contributed to obesity susceptibility in rats fed a high fat diet (HFD), and the associations of desaturase indices between lipid fractions in animals on different diets. We found that on a HFD, obesity-prone (OP) rats had a higher SCD-16 index and a lower linoleic acid (LA) proportions in subcutaneous adipose tissue (SAT) than obesity-resistant rats. Desaturase indices were significantly correlated between many of the lipid fractions. The higher SCD-16 may indicate higher SCD-1 activity in SAT in OP rats, and combined with lower LA proportions may provide novel insights into HFD-induced obesity. The associations between desaturase indices show that plasma measurements can serve as proxies for some lipid fractions, but the correlations seem to be affected by diet and weight gain.

<p>Since the late 1970s, biomedical researchers have heavily invested in the development of portable insulin pumps that allow people with Type 1 Diabetes (T1D) to carry several days-worth of insulin to be injected on an as-needed basis. That means fewer needles and syringes, making regular insulin injections less time consuming and troublesome. As insulin pump use has become more widespread over the past twenty years among people with T1D, the social and cultural effects of using these medical devices on their everyday experiences have become both increasingly apparent for individuals yet consistently absent from social and cultural studies of the disease.</p><p><br></p><p>In this dissertation, I explore the technological, medical, and cultural networks of insulin pump treatment to identify the role(s) these biomedicalized treatment acts play in the structuring of people, their bodies, and the cultural values constructed around various medical technologies. As I will show, insulin pump treatment alters people’s bodies and identities as devices become integrated as co-productive actors within patient-users’ biological and social systems. By analyzing personal interviews and digital media produced by people with T1D alongside archival materials, this study identifies compulsory patterns in the practices, structures, and narratives related to insulin pump use to center chapters around the productive (and sometimes stifling) relationship between people, bodies, technologies, and American culture.</p><p><br></p><p>By analyzing the layered and intersecting sites of insulin pump treatment together, this project reveals how medical technologies, health identities, bodies, and cultures are co-constructed and co-defined in ways that bind them together—mutually constitutive, medically compelled, cultural and social. New bodies and new systems, I argue, come with new (in)visibilities, and while this new technologically-produced legibility of the body provides unprecedented management of the symptoms and side-effects of the disease, it also brings with it unforeseen social consequences that require changes to people’s everyday lives and practices. </p>

<p>Subcutaneous administration has become a common approach for drug delivery of biotherapeutics, such as monoclonal antibodies, which is achieved mainly by absorption through the lymphatic system. This dissertation focuses on the computational modeling of the fluid flow and solute transport in the skin tissue and the quantitative investigation of lymphatic uptake. First, the various mechanisms governing drug transport and lymphatic uptake of biotherapeutics through subcutaneous injection are investigated quantitatively through high-fidelity numerical simulations, including lymphatic drainage, blood perfusion, binding, and metabolism. The tissue is modeled as a homogeneous porous medium using both a single-layered domain and a multi-layered domain, which includes the epidermis, dermis, hypodermis (subcutaneous tissue), and muscle layers. A systematic parameter study is conducted to understand the roles of different properties of the tissue in terms of permeability, porosity, and vascular permeability. The role of binding and metabolism on drug absorption is studied by varying the binding parameters for different macromolecules after coupling the transport equation with a pharmacokinetic equation. The interstitial pressure plays an essential role in regulating the absorption of unbound drug proteins during the injection, while the binding and metabolism of drug molecules reduce the total free drugs. </p> <p>  </p> <p>The lymphatic vessel network is essential to achieve the functions of the lymphatic system. Thus, the drug transport and lymphatic uptake through a three-dimensional hybrid discrete-continuum vessel network in the skin tissue are investigated through high-fidelity numerical simulations. The explicit heterogeneous vessel network is embedded into the continuum model to investigate the role of explicit heterogeneous vessel network in drug transport and absorption. The solute transport across the vessel wall is investigated under various transport conditions. The diffusion of the drug solutes through the explicit vessel wall affects the drug absorption after the injection, while the convection under large interstitial pressure dominates the drug absorption during the injection. The effect of diffusion cannot be captured by the previously developed continuum model. Furthermore, the effects of injection volume and depth on the lymphatic uptake are investigated in a multi-layered domain. The injection volume significantly affects lymphatic uptake through the heterogeneous vessel network, while the injection depth has little influence. At last, the binding and metabolism of drug molecules are studied to bridge the simulation to the experimentally measured drug clearance. </p> <p><br></p> <p>Convective transport of drug solutes in biological tissues is regulated by the interstitial fluid pressure, which plays a crucial role in drug absorption into the lymphatic system through the subcutaneous (SC) injection.  An approximate continuum poroelasticity model is developed to simulate the pressure evolution in the soft porous tissue during an SC injection. This poroelastic model mimics the deformation of the tissue by introducing the time variation of the interstitial fluid pressure. The advantage of this method lies in its computational time efficiency and simplicity, and it can accurately model the relaxation of pressure. The interstitial fluid pressure obtained using the proposed model is validated against both the analytical and the numerical solution of the poroelastic tissue model. The decreasing elasticity elongates the relaxation time of pressure, and the sensitivity of pressure relaxation to elasticity decreases with the hydraulic permeability, while the increasing porosity and permeability due to deformation alleviate the high pressure. </p> <p><br></p> <p>At last, an improved Kedem-Katchalsky model is developed to study solute transport across the lymphatic vessel network, including convection and diffusion in the multi-layered poroelastic tissue with a hybrid discrete-continuum vessel network embedded inside. The effect of different drug solutes with different Stokes radii and different structures of the lymphatic vessel network, such as fractal trees and Voronoi structure, on the lymphatic uptake is investigated. The drug solute with a small size has a larger partition coefficient and diffusivity across the openings of the lymphatic vessel wall, which favors drug absorption. The Voronoi structure is found to be more efficient in lymphatic uptake. </p> <p><br></p> <p>The systematic and quantitative investigation of subcutaneous absorption based on high-fidelity numerical simulations can provide guidance on the optimization of drug delivery systems and is valuable for the translation of bioavailability from the pre-clinical species to humans. We provide a novel approach to studying the diffusion and convection of drug molecules into the lymphatic system by developing the hybrid discrete-continuum vessel network. The study of the solute transport across the discrete lymphatic vessel walls further improves our understanding of lymphatic uptake. The novel and time-efficient computational model for solute transport across the lymphatic vasculature connects the microscopic properties of the lymphatic vessel membrane to macroscopic drug absorption. The comprehensive hybrid vessel network model developed here can be further used to improve our understanding of the diseases caused by the disturbed lymphatic system, such as lymphedema, and provide insights into the treatment of diseases caused by the malfunction of lymphatics.</p>