Rho-Kinase as a Therapeutic Target for Nonalcoholic Fatty Liver Diseases

Sousa-Lima Inês,Kim Hyun Jeong,John Jones,김영범 대한당뇨병학회 2021 Diabetes and Metabolism Journal Vol.45 No.5

Nonalcoholic fatty liver disease (NAFLD) is a major public health problem and the most common form of chronic liver disease, affecting 25% of the global population. Although NAFLD is closely linked with obesity, insulin resistance, and type 2 diabetes mellitus, knowledge on its pathogenesis remains incomplete. Emerging data have underscored the importance of Rho-kinase (Rho-associated coiled-coil-containing kinase [ROCK]) action in the maintenance of normal hepatic lipid homeostasis. In particular, pharmacological blockade of ROCK in hepatocytes or hepatic stellate cells prevents the progression of liver diseases such as NAFLD and fibrosis. Moreover, mice lacking hepatic ROCK1 are protected against obesity-induced fatty liver diseases by suppressing hepatic de novo lipogenesis. Here we review the roles of ROCK as an indispensable regulator of obesity-induced fatty liver disease and highlight the key cellular pathway governing hepatic lipid accumulation, with focus on de novo lipogenesis and its impact on therapeutic potential. Consequently, a comprehensive understanding of the metabolic milieu linking to liver dysfunction triggered by ROCK activation may help identify new targets for treating fatty liver diseases such as NAFLD.

Methylsulfonylmethane (MSM), an organosulfur compound, is effective against obesity-induced metabolic disorders in mice

Sousa-Lima, I.,Park, S.Y.,Chung, M.,Jung, H.J.,Kang, M.C.,Gaspar, J.M.,Seo, J.A.,Macedo, M.P.,Park, K.S.,Mantzoros, C.,Lee, S.H.,Kim, Y.B. W.B.Saunders [etc.] 2016 clinical and experimental Vol.65 No.10

Methylsulfonylmethane (MSM), an organosulfur compound, has been used as a dietary supplement that can improve various metabolic diseases. However, the effect of MSM on obesity-linked metabolic disorders remains unclear. The goal of the current study is to determine whether MSM has beneficial effects on glucose and lipid homeostasis in obesity-associated pathophysiologic states. High-fat diet-induced obese (DIO) and genetically obese diabetic db/db mice treated with MSM (1%-5% v/v, by drinking water) were studied. Metabolic parameters involved in glucose and lipid metabolism were determined. Treatment of DIO mice with MSM leads to a significant decrease in blood glucose levels. DIO mice treated with MSM are hypersensitive to insulin, as evidenced by decreased serum insulin and an increase in the area above the curve during an ITT. Concurrently, MSM reduces hepatic triglyceride and cholesterol contents in DIO mice. These effects are accompanied by reductions in gene expression of key molecules involved in lipogenesis and inflammation. FACS analysis reveals that MSM markedly increases the frequency of B cells and decreases the frequency of myeloid cells in peripheral blood and in bone marrow. Moreover, overnutrition-induced changes of femur microarchitecture are restored by MSM. In db/db mice, a marked impairment in glucose and lipid metabolic profiles is notably ameliorated when MSM is supplemented. These data suggest that MSM has beneficial effects on multiple metabolic dysfunctions, including hyperglycemia, hyperinsulinemia, insulin resistance, and inflammation. Thus, MSM could be the therapeutic option for the treatment of obesity-related metabolic disorders such as type 2 diabetes and fatty liver diseases.

Pathological fracture induced by Halicephalobus gingivalis (Nematoda: Rhabditida) in a horse limb

Ticiana Meireles Sousa,Hugo Shisei Toma,Antonio de Pádua Lima,Antonio Carlos Cunha Lacreta Junior,Maira Meira Nunes,Ana Paula Cassiano da Silva,Daniel Wouters,Adriana Silva Albuquerque,Mary Suzan Vara 대한기생충학ㆍ열대의학회 2024 The Korean Journal of Parasitology Vol.62 No.1

Halicephalobus gingivalis is a free-living nematode that occasionally causes infections inhorses. We report a rare case of limb fracture of horse caused by infection with H. gingivalis. An 8-year-old mare was referred to the Veterinary Hospital of the Federal Universityof Lavras with claudication grade 5 of the right hind limb, that had been started 3months ago. The patient had aseptic arthritis in the tarsal joint and edema that extendedto the quartile. The radiographic examination showed punctate osteolysis with exacerbation of bone trabeculation along the calcaneus, talus, proximal epiphysis of the thirdmetatarsal and distal epiphysis of the tibia. Treatment for arthritis was initiated, and theanimal showed a slight improvement in limb function. However, 21 days after hospitalization, due to a comminuted fracture of the tibia, it was euthanized. At necropsy, yellowish masses were found from the metatarsal to the tibia, and around the tarsal bonesand joint. Similar masses were also found in the left kidney. Numerous nematodes compatible with H. gingivalis were identified. This is the first description of a pathologicalfracture caused by H. gingivalis infection in an equine limb.

Influence of tooth position within the field of view on the intensity of cone-beam computed tomographic imaging artifacts when assessing teeth restored with various intracanal materials

Martina Gerlane de Oliveira Pinto,Saulo Leonardo Sousa Melo,Yuri Wanderley Cavalcanti,Elisa Diniz de Lima,Patrícia Meira Bento,Daniela Pita de Melo 대한영상치의학회 2020 Imaging Science in Dentistry Vol.50 No.2

Purpose: This study aimed to quantify the influence of tooth position within the field-of-view (FOV) on cone-beam computed tomography (CBCT) imaging artifacts’ intensity when assessing teeth restored with various intracanal materials. Materials and Methods: Seventy single-rooted teeth were divided into 7 groups (10 teeth per group): NiCr post (NC), AgPd post (AP), metal core fiberglass post (MCFG), fiberglass post (FG), anatomical fiberglass post (AFG), fiberglass post cemented with core build-up cement (FGCo), and anatomical fiberglass post cemented with core build-up cement (AFGCo). All posts were cemented using a regular dual-curing resin cement (Allcem), except FGCo and AFGCo which were cemented with a core build-up dual-curing resin cement (AllcemCore). Each tooth was scanned on a CS9000 in 5 positions within the FOV: a central position, anterior horizontal peripheral, peripheral superior, peripheral inferior, and posterior horizontal peripheral position. Hyperdense, hypodense, remaining teeth areas and ROI areas were quantitatively analyzed using ImageJ software. Results: Posterior horizontal peripheral position increased the intensity of artifacts on FGCo and AFGCo post groups (P<0.05), and specifically the hypodense artifact intensity on FG and AFG post groups (P<0.05). NC and AP groups presented greater intensity of artifacts than any other post groups (P<0.05). Conclusion: Artifact intensity increases in the presence of high atomic number materials and when the object is not centered within the FOV. The impact of positioning within the FOV on artifact was greater for fiberglass posts cemented with core build-up dual-curing cement than for metal posts and fiberglass posts cemented with regular dual-curing cement.

Carcass Characteristics and Qualitative Attributes of Pork from Immunocastrated Animals

Caldara, Fabiana Ribeiro,Moi, Marta,Santos, Luan Sousa Dos,Paz, Ibiara Correia De Lima Almeida,Garcia, Rodrigo Garofallo,Naas, Irenilza De Alencar,Fernandes, Alexandre Rodrigo Mendes Asian Australasian Association of Animal Productio 2013 Animal Bioscience Vol.26 No.11

An investigation was carried out to assess the carcass characteristics and meat quality aspects of immunocastrated male pigs of medium genetic potential for lean meat deposition in carcass (53 to 55%). When the crossbred Large White x Landrace pigs (n = 45) were 70 days old, they were distributed in a totally randomized design in three treatments (castrated males, females and immunocastrated males) with three replicates of five animals. The pigs were slaughtered when they were 140 days old. Carcass temperature and pH were recorded twice, at 45 min and 24 h after slaughter. The carcasses were evaluated for hot and cold carcass yield, commercial cuts yield, length and depth, back fat thickness, loin eye area and lean meat percentage. The Longissimus dorsi muscle was extracted for analysis of color ($L^*$, $a^*$, $b^*$), exudate loss, cooking loss and centesimal and sensorial analysis of the meat. There were no significant differences for the evaluated parameters between castrated males, immunocastrated males and females, except for backfat thickness between the 7th and 8th thoracic vertebra and the point P2 (lower for immunocastrated males) and carcass temperature at 45 min post slaughter (higher in immunocastrated males), however, this did not interfer with the rate of pH decrease post mortem and the meat quality. The results from this research did not indicate a benefit of immunocastration on carcass characteristics of pigs of medium genetic potential for lean meat deposition in carcass, when compared to surgical castration.

Rho-kinase/AMPK axis regulates hepatic lipogenesis during overnutrition

Huang, Hu,Lee, Seung-Hwan,Sousa-Lima, Inê,s,Kim, Sang Soo,Hwang, Won Min,Dagon, Yossi,Yang, Won-Mo,Cho, Sungman,Kang, Min-Cheol,Seo, Ji A.,Shibata, Munehiko,Cho, Hyunsoo,Belew, Getachew Debas,Bhi American Society for Clinical Investigation 2018 The Journal of clinical investigation Vol.128 No.12

Influence of tooth position within the field of view on the intensity of cone-beam computed tomographic imaging artifacts when assessing teeth restored with various intracanal materials

de Oliveira Pinto, Martina Gerlane,Melo, Saulo Leonardo Sousa,Cavalcanti, Yuri Wanderley,de Lima, Elisa Diniz,Bento, Patricia Meira,de Melo, Daniela Pita Korean Academy of Oral and Maxillofacial Radiology 2020 Imaging Science in Dentistry Vol.50 No.2

Purpose: This study aimed to quantify the influence of tooth position within the field-of-view (FOV) on cone-beam computed tomography (CBCT) imaging artifacts' intensity when assessing teeth restored with various intracanal materials. Materials and Methods: Seventy single-rooted teeth were divided into 7 groups (10 teeth per group): NiCr post (NC), AgPd post (AP), metal core fiberglass post (MCFG), fiberglass post (FG), anatomical fiberglass post (AFG), fiberglass post cemented with core build-up cement (FGCo), and anatomical fiberglass post cemented with core build-up cement (AFGCo). All posts were cemented using a regular dual-curing resin cement (Allcem), except FGCo and AFGCo which were cemented with a core build-up dual-curing resin cement (AllcemCore). Each tooth was scanned on a CS9000 in 5 positions within the FOV: a central position, anterior horizontal peripheral, peripheral superior, peripheral inferior, and posterior horizontal peripheral position. Hyperdense, hypodense, remaining teeth areas and ROI areas were quantitatively analyzed using ImageJ software. Results: Posterior horizontal peripheral position increased the intensity of artifacts on FGCo and AFGCo post groups (P<0.05), and specifically the hypodense artifact intensity on FG and AFG post groups (P<0.05). NC and AP groups presented greater intensity of artifacts than any other post groups(P<0.05). Conclusion: Artifact intensity increases in the presence of high atomic number materials and when the object is not centered within the FOV. The impact of positioning within the FOV on artifact was greater for fiberglass posts cemented with core build-up dual-curing cement than for metal posts and fiberglass posts cemented with regular dual-curing cement.

Anthraquinone as emerging contaminant: technological, toxicological, regulatory and analytical aspects

Valduga Alice Teresa,Gonçalves Itamar Luís,Saorin Puton Bruna Maria,de Lima Hennig Bruna,Sousa de Brito Edy 한국독성학회 2024 Toxicological Research Vol.40 No.1

Anthraquinone (anthracene-9,10-dione) is a multifaceted chemical used in the paper industry, in the production of synthetic dyes, in crop protection against birds and is released from fossil fuels. Additionally, the anthraquinone scaffold, when substituted with sugars and hydroxyl groups is found in plants as metabolites. Because of these multiple applications, it is produced on a large scale worldwide. However, its toxicological aspects have gained interest, due to the low limits in the foods defined by legislation. Worrying levels of anthracene-9,10-dione have been detected in wastewater, atmospheric air, soil, food packaging and more recently, in actual foodstuffs. Recent investigations aiming to identify the anthracene-9,10-dione contamination sources in teas highlighted the packaging, leaves processing, anthracene metabolism, reactions between tea constituents and deposition from the environment. In this context, this review seeks to highlight the uses, sources, biological effects, analytical and regulatory aspects of anthracene-9,10-dione.

Genetic evaluation of sheep for resistance to gastrointestinal nematodes and body size including genomic information

Torres Tatiana Saraiva,Sena Luciano Silva,Santos Gleyson Vieira dos,Figueiredo Filho Luiz Antonio Silva,Barbosa Bruna Lima,Júnior Antônio de Sousa,Britto Fábio Barros,Sarmento José Lindenberg Rocha 아세아·태평양축산학회 2021 Animal Bioscience Vol.34 No.4

Objective: The genetic evaluation of Santa Inês sheep was performed for resistance to gastrointestinal nematode infection (RGNI) and body size using different relationship matrices to assess the efficiency of including genomic information in the analyses. Methods: There were 1,637 animals in the pedigree and 500, 980, and 980 records of RGNI, thoracic depth (TD), and rump height (RH), respectively. The genomic data consisted of 42,748 SNPs and 388 samples genotyped with the OvineSNP50 BeadChip. The (co)variance components were estimated in single- and multi-trait analyses using the numerator relationship matrix (A) and the hybrid matrix H, which blends A with the genomic relationship matrix (G). The BLUP and single-step genomic BLUP methods were used. The accuracies of estimated breeding values and Spearman rank correlation were also used to assess the feasibility of incorporating genomic information in the analyses. Results: The heritability estimates ranged from 0.11±0.07, for TD (in single-trait analysis using the A matrix), to 0.38±0.08, for RH (using the H matrix in multi-trait analysis). The estimates of genetic correlation ranged from –0.65±0.31 to 0.59±0.19, using A, and from –0.42±0.30 to 0.57±0.16 using H. The gains in accuracy of estimated breeding values ranged from 2.22% to 75.00% with the inclusion of genomic information in the analyses. Conclusion: The inclusion of genomic information will benefit the direct selection for the traits in this study, especially RGNI and TD. More information is necessary to improve the understanding on the genetic relationship between resistance to nematode infection and body size in Santa Inês sheep. The genetic evaluation for the evaluated traits was more efficient when genomic information was included in the analyses. Objective: The genetic evaluation of Santa Inês sheep was performed for resistance to gastrointestinal nematode infection (RGNI) and body size using different relationship matrices to assess the efficiency of including genomic information in the analyses.Methods: There were 1,637 animals in the pedigree and 500, 980, and 980 records of RGNI, thoracic depth (TD), and rump height (RH), respectively. The genomic data consisted of 42,748 SNPs and 388 samples genotyped with the OvineSNP50 BeadChip. The (co)variance components were estimated in single- and multi-trait analyses using the numerator relationship matrix (A) and the hybrid matrix H, which blends A with the genomic relationship matrix (G). The BLUP and single-step genomic BLUP methods were used. The accuracies of estimated breeding values and Spearman rank correlation were also used to assess the feasibility of incorporating genomic information in the analyses.Results: The heritability estimates ranged from 0.11±0.07, for TD (in single-trait analysis using the A matrix), to 0.38±0.08, for RH (using the H matrix in multi-trait analysis). The estimates of genetic correlation ranged from –0.65±0.31 to 0.59±0.19, using A, and from –0.42±0.30 to 0.57±0.16 using H. The gains in accuracy of estimated breeding values ranged from 2.22% to 75.00% with the inclusion of genomic information in the analyses.Conclusion: The inclusion of genomic information will benefit the direct selection for the traits in this study, especially RGNI and TD. More information is necessary to improve the understanding on the genetic relationship between resistance to nematode infection and body size in Santa Inês sheep. The genetic evaluation for the evaluated traits was more efficient when genomic information was included in the analyses.

In Vitro Blood Flow and Cell-Free Layer in Hyperbolic Microchannels: Visualizations and Measurements

Raquel O. Rodrigues,Raquel Lopes,Diana Pinho,Ana I. Pereira,Valdemar Garcia,Stefan Gassmann,Patrícia C. Sousa,Rui Lima 한국바이오칩학회 2016 BioChip Journal Vol.10 No.1

Red blood cells (RBCs) in microchannels has tendency to undergo axial migration due to the parabolic velocity profile, which results in a high shear stress around wall that forces the RBC to move towards the centre induced by the tank treading motion of the RBC membrane. As a result there is a formation of a cell free layer (CFL) with extremely low concentration of cells. Based on this phenomenon, several works have proposed microfluidic designs to separate the suspending physiological fluid from whole in vitro blood. This study aims to characterize the CFL in hyperbolic-shaped microchannels to separate RBCs from plasma. For this purpose, we have investigated the effect of hyperbolic contractions on the CFL by using not only different Hencky strains but also varying the series of contractions. The results show that the hyperbolic contractions with a Hencky strain of 3 and higher, substantially increase the CFL downstream of the contraction region in contrast with the microchannels with a Hencky strain of 2, where the effect is insignificant. Although, the highest CFL thickness occur at microchannels with a Hencky strain of 3.6 and 4.2 the experiments have also shown that cells blockage are more likely to occur at this kind of microchannels. Hence, the most appropriate hyperbolic-shaped microchannels to separate RBCs from plasma is the one with a Hencky strain of 3. Red blood cells (RBCs) in microchannels has tendency to undergo axial migration due to the parabolic velocity profile, which results in a high shear stress around wall that forces the RBC to move towards the centre induced by the tank treading motion of the RBC membrane. As a result there is a formation of a cell free layer (CFL) with extremely low concentration of cells. Based on this phenomenon, several works have proposed microfluidic designs to separate the suspending physiological fluid from whole in vitro blood. This study aims to characterize the CFL in hyperbolic-shaped microchannels to separate RBCs from plasma. For this purpose, we have investigated the effect of hyperbolic contractions on the CFL by using not only different Hencky strains but also varying the series of contractions. The results show that the hyperbolic contractions with a Hencky strain of 3 and higher, substantially increase the CFL downstream of the contraction region in contrast with the microchannels with a Hencky strain of 2, where the effect is insignificant. Although, the highest CFL thickness occur at microchannels with a Hencky strain of 3.6 and 4.2 the experiments have also shown that cells blockage are more likely to occur at this kind of microchannels.Hence, the most appropriate hyperbolic-shaped microchannels to separate RBCs from plasma is the one with a Hencky strain of 3.