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Distraction osteogenesis (DO) is a reconstruction technique developed in the fields of oral and maxillofacial surgery and plastic surgery, addressing both vertical and horizontal bone deficiencies and enhancing soft tissue volume to facilitate subsequent dental implant placement. In this treatment method, devices are placed to stretch the bone gradually to stimulate the formation of new bone, effectively filling the existing defect to treat maxillofacial deformities or repair posttraumatic injuries. This case report presents an almost 20-year long-term follow-up of jaw defect reconstruction resulting from a gunshot injury, using DO with multiple distractors. Details on the frequency, period of DO, and subsequent implant installation in the distracted anterior jaw area are outlined. This case exhibits DO treatments that reconstructed effectively severe bone defects in the jaws. The quality of bone generated during the DO process was both functionally and esthetically satisfactory for subsequent implant rehabilitation.
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Body fat distribution is a well-established predictor of adverse medical outcomes, independent of overall adiposity. Studying body fat distribution sheds insights into the causes of obesity and provides valuable information about the development of various comorbidities. Compared to total adiposity, body fat distribution is more closely associated with risks of cardiovascular diseases. The present review specifically focuses on the sexual dimorphism in body fat distribution, the biological clues, as well as the genetic traits that are distinct from overall obesity. Understanding the sex determinations on body fat distribution and adiposity will aid in the improvement of the prevention and treatment of cardiovascular diseases (CVD).
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Adiposidade , Doenças Cardiovasculares , Tecido Adiposo/metabolismo , Distribuição da Gordura Corporal , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/genética , Feminino , Humanos , Masculino , Obesidade/metabolismo , Caracteres SexuaisRESUMO
Adipose tissue is an important organ in our body, participating not only in energy metabolism but also immune regulation. It is broadly classified as white (WAT) and brown (BAT) adipose tissues. WAT is highly heterogeneous, composed of adipocytes, various immune, progenitor and stem cells, as well as the stromal vascular populations. The expansion and inflammation of WAT are hallmarks of obesity and play a causal role in the development of metabolic and cardiovascular diseases. The primary event triggering the inflammatory expansion of WAT remains unclear. The present review focuses on the role of adipocyte progenitors (APS), which give rise to specialized adipocytes, in obesity-associated WAT expansion, inflammation and fibrosis.
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Adipócitos/metabolismo , Tecido Adiposo Branco/metabolismo , Inflamação/metabolismo , Animais , HumanosRESUMO
Pulmonary hypertension (PH) is a major disease in the broiler breeding industry. During PH, the pulmonary artery undergoes remodelling, which is caused by pulmonary vascular smooth muscle cell proliferation. CyclinD1 regulates cell proliferation. This study investigated the role of cyclinD1 in the development of PH in broilers, and which bioactivators and signalling pathway are involved in the pathological process. The PH group contained 3-4-week-old broilers with clinical PH, and the healthy group broilers from the same flock without PH. Histopathology indicated pulmonary arterial walls were thicker in the PH group compared with the healthy group. Target gene expressions of macrophage migration inhibitory factor (MIF), extracellular signal-regulated kinase (ERK), and cyclinD1 detected by quantitative real-time PCR were upregulated in the PH group compared with the healthy group. Immunohistochemistry showed MIF, phosphorylated ERK (p-ERK) and cyclinD1 were present on pulmonary vascular walls; MIF was present in the cytoplasm of arterial endothelial cells and smooth muscle cells; p-ERK and cyclinD1 were present in smooth muscle cell cytoplasm. Western blotting demonstrated that MIF, p-ERKand cyclinD1 levels were significantly higher (P < 0.01) in the PH group compared with the healthy group. In summary, increased MIF in PH broiler pulmonary arteries upregulated cyclinD1 via the ERK signalling pathway to induce pulmonary vascular smooth muscle cell proliferation, causing pulmonary artery remodelling and hypertension.
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Ciclina D1/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hipertensão Pulmonar/veterinária , Sistema de Sinalização das MAP Quinases , Fatores Inibidores da Migração de Macrófagos/metabolismo , Animais , Proliferação de Células , Galinhas , Ciclina D1/genética , Células Endoteliais/metabolismo , Células Endoteliais/patologia , MAP Quinases Reguladas por Sinal Extracelular/genética , Regulação da Expressão Gênica , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Pulmão/metabolismo , Pulmão/patologia , Fatores Inibidores da Migração de Macrófagos/genética , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Regulação para Cima , Remodelação VascularRESUMO
Objectives: The surgical guide is a static computer-assisted device used for implant surgery planning and guidance. By taking an impression and referring to the patients' three-dimensional computed tomography scan of the desired implant site, a surgical guide can be created. During surgery, the surgical guide aids in achieving the designed implant placement position and direction. We examined and evaluated the long-term clinical outcomes of implant surgery using surgical guides. Materials and Methods: This study investigated a total of 15 patients with 32 implants that were placed using surgical guides from 2009 to 2011 with a mean follow-up period extended beyond 10 years. Patient demographics and implant survival rates were recorded. We analyzed marginal bone loss (MBL) by assessing the radiographs acquired at installation, three months after installation, and one month, one, two, and five years after prosthesis delivery. Results: The mean patient age was 57.33 years at implant placement. Of the 32 implants, five implants were placed in the anterior region and 27 implants were in the posterior region. Six implants failed and three of them were replaced, resulting in an 81.25% survival rate. The mean follow-up period was 10 years and nine months. Mean MBL compared to post-installation was significantly higher than at three months after installation, and one month, one, two, and five years after prosthesis delivery. Mean MBL at three months after installation, and one month, one year, and two years were significantly higher compared to the previous visit (P<0.05). However, MBL at five years after prosthesis delivery did not differ significantly compared to at two years. Conclusion: In this study, implant rehabilitation assisted by surgical guides exhibited favorable survival rates. With the limitation of the sample amount in this study, further research and more samples are required to evaluate the long-term clinical effectiveness of surgical guides.
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Smart wearables with the capability for continuous monitoring, perceiving, and understanding human tactile and motion signals, while ensuring comfort, are highly sought after for intelligent healthcare and smart life systems. However, concurrently achieving high-performance tactile sensing, long-lasting wearing comfort, and industrialized fabrication by a low-cost strategy remains a great challenge. This is primarily due to critical research gaps in novel textile structure design for seamless integration with sensing elements. Here, an all-in-one biaxial insertion knit architecture is reported to topologically integrate sensing units within double-knit loops for the fabrication of a large-scale tactile sensing textile by using low-cost industrial manufacturing routes. High sensitivity, stability, and low hysteresis of arrayed sensing units are achieved through engineering of fractal structures of hierarchically patterned piezoresistive yarns via blistering and twisting processing. The as-prepared tactile sensing textiles show desirable sensing performance and robust mechanical property, while ensuring excellent conformability, tailorability, breathability (288 mm s-1), and moisture permeability (3591 g m-2 per day) for minimizing the effect on wearing comfort. The multifunctional applications of tactile sensing textiles are demonstrated in continuously monitoring human motions, tactile interactions with the environment, and recognizing biometric gait. Moreover, we also demonstrate that machine learning-assisted sensing textiles can accurately predict body postures, which holds great promise in advancing the development of personalized healthcare robotics, prosthetics, and intelligent interaction devices.
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Robótica , Dispositivos Eletrônicos Vestíveis , Humanos , Têxteis , Movimento (Física) , TatoRESUMO
The emergence of flexible fabric-based pneumatic actuators (FPAs) with pre-programmable motion capabilities, enhanced security and versatile interaction features significantly advances the construction of sophisticated soft robotic systems, owing to their enhanced security and versatile interaction features. Despite these promising attributes, the commercial viability of FPA products faces a considerable amount of challenges, primarily stemming from the scarcity of highly deformable fabric structures and the availability of industrial fabrication approaches. Taking inspiration from the anisotropic nature of lobster antennae, we propose a scalable and economical strategy to fabricate functional FPAs using nonwoven fabric material with superior mechanical anisotropy. This innovative method involves the adoption of tunable inelastic constrained wires sewn onto extensible nonwoven fabrics with regular wrinkles. This nonwoven fabric-based pneumatic actuator (NFPA) demonstrates specific motion profiles with curvature of over 0.6 cm-1 and output forces of over 140 cN under adjustable pressure conditions. Guided by the constrained wire combinations, NFPA enables diverse programmable motions like spiraling, assistance, and grasping. Furthermore, NFPA incorporated with specific sensors exhibits significant potential in wearable devices with real-time environmental detection for rehabilitation applications. Our work contributes a distinctive insight into the design of programmable NFPAs and enlightens an arena toward versatile soft robotic applications.
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OBJECTIVE: Accumulating evidence suggests that dysfunctional adipose tissue (AT) plays a major role in the risk of developing multiple sclerosis (MS), the most common immune-mediated and demyelinating disease of the central nervous system. However, the contribution of adipose tissue to the etiology and progression of MS is still obscure. This study aimed at deciphering the responses of AT in experimental autoimmune encephalomyelitis (EAE), the best characterized animal model of MS. RESULTS AND METHODS: We observed a significant AT loss in EAE mice at the onset of disease, with a significant infiltration of M1-like macrophages and fibrosis in the AT, resembling a cachectic phenotype. Through an integrative and multilayered approach, we identified lipocalin2 (LCN2) as the key molecule released by dysfunctional adipocytes through redox-dependent mechanism. Adipose-derived LCN2 shapes the pro-inflammatory macrophage phenotype, and the genetic deficiency of LCN2 specifically in AT reduced weight loss as well as inflammatory macrophage infiltration in spinal cord in EAE mice. Mature adipocytes downregulating LCN2 reduced lipolytic response to inflammatory stimuli (e.g. TNFα) through an ATGL-mediated mechanism. CONCLUSIONS: Overall data highlighted a role LCN2 in exacerbating inflammatory phenotype in EAE model, suggesting a pathogenic role of dysfunctional AT in MS.
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Encefalomielite Autoimune Experimental , Esclerose Múltipla , Camundongos , Animais , Encefalomielite Autoimune Experimental/patologia , Lipocalina-2/genética , Macrófagos , Esclerose Múltipla/patologia , Sistema Nervoso CentralRESUMO
Objectives: To investigate the serum, plasma and urine levels of lipocalin-2 (LCN2) variants in healthy humans and their associations with risk factors for cardiometabolic (CMD) and chronic kidney (CKD) diseases. Methods: Fifty-nine males and 41 females participated in the study. Blood and urine were collected following an overnight fasting. LCN2 variants were analyzed using validated in-house ELISA kits. Heart rate, blood pressure, lipids profile, glucose, adiponectin, high-sensitivity C-reactive protein (hsCRP), creatinine, cystatin C, and biomarkers for kidney function were assessed. Results: The levels of hLcn2, C87A and R81E in serum and urine, but not plasma, were significantly higher in men than women. Increased levels of LCN2 variants, as well as their relative ratios, in serum and plasma were positively associated with body mass index, blood pressure, triglyceride and hsCRP (P<0.05). No significant correlations were found between these measures and hLcn2, C87A or R81E in urine. However, LCN2 variants in urine, but not plasma or serum, were correlated with biomarkers of kidney function (P<0.05). Conclusions: Both the serum and plasma levels of LCN2 variants, as well as their ratios are associated with increased cardiometabolic risk, whereas those in urine are correlated with renal dysfunction. LCN2 variants represent promising biomarkers for CMD and CKD.
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Variação Genética/genética , Cardiopatias/genética , Nefropatias/genética , Lipocalina-2/genética , Adulto , Feminino , Cardiopatias/metabolismo , Humanos , Nefropatias/metabolismo , Lipocalina-2/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: 30K proteins are a major group of nutrient storage proteins in the silkworm hemolymph. Previous studies have shown that 30K proteins are involved in the anti-fungal immunity; however, the molecular mechanism involved in this immunity remains unclear. METHODS: We investigated the transcriptional expression of five 30K proteins, including BmLP1, BmLP2, BmLP3, BmLP4, and BmLP7. The five recombinant 30K proteins were expressed in an Escherichia coli expression system, and used for binding assays with fungal cells and hemocytes. RESULTS: The transcriptional expression showed that the five 30K proteins were significantly upregulated after injection of pathogen-associated molecular patterns to the fifth instar larvae, indicating the possibility of their involvement in immune response. The binding assay showed that only BmLP1 and BmLP4 can bind to both fungal cells and silkworm hemocytes. Furthermore, we found that BmLP1-coated and BmLP4-coated agarose beads promote encapsulation of hemocytes in vitro. The hemocyte encapsulation was blocked when the BmLP1-coated beads were preincubated with BmLP1 specific polyclonal antibodies. CONCLUSIONS: These results demonstrate that 30K proteins are involved in the cellular immunity of silkworms by acting as pattern recognition molecules to directly recruit hemocytes to the fungal surface.
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Diabetes mellitus (DM) is a hyperglycemia-related multifactorial condition with an elevated risk of microvascular and microvascular complications associated with this disease. The current experimental study was to examine the antidiabetic activity of streptozotocin (STZ)-induced adropin against diabetic rats by altering the PI3K/Akt and insulin signaling pathways. STZ (60 mg/kg) was used for the induction of DM and rats were divided into different groups and received the adropin (20, 40 and 80 mg/kg) and glibenclamide (10 mg/kg) till 28 days. Body weight, plasma insulin, blood glucose and food intake were estimated, respectively. Biochemical enzymes, carbohydrate enzymes, lipid parameters, AMPK and insulin signalling pathway parameters were estimated. GLUT4 and PPARγ expression were also estimated. Oral administration of adropin significantly (p < 0.001) increased the glycogen, glucose-6-phosphatase dehydrogenase, insulin, hexokinase and belittled the blood glucose level, fructose 1-6-biphosphatase, glucose-6-phosphatase at dose dependent manner. Adropin significantly (p < 0.001) reduced the level of triglyceride, cholesterol, low density lipoprotein, very low density lipoprotein and increased the level of high density lipoprotein at dose dependent manner. Adropin significantly (p < 0.001) activated the Akt, IRS-2, IRS-1, IR, p-AKT and PI3k, which are the key modulator molecules of PI3K/Akt, AMPK and insulin signalling pathway in DM rats. The current experimental study confirms the anti-diabetic effect of adropin on DM rats induced by AMPK and insulin signalling pathway against STZ.
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Proteínas Sanguíneas/farmacologia , Proteínas Sanguíneas/fisiologia , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Hipoglicemiantes , Insulina/metabolismo , Peptídeos/farmacologia , Peptídeos/fisiologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Relação Dose-Resposta a Droga , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Ratos Wistar , EstreptozocinaRESUMO
Ultrafine fibers are widely employed because of their lightness, softness, and warmth retention. Although silkworm silk is one of the most applied natural silks, it is coarse and difficult to transform into ultrafine fibers. Thus, to obtain ultrafine high-performance silk fibers, we employed anti-juvenile hormones in this study to induce bimolter silkworms. We found that the bimolter cocoons were composed of densely packed thin fibers and small apertures, wherein the silk diameter was 54.9% less than that of trimolter silk. Further analysis revealed that the bimolter silk was cleaner and lighter than the control silk. In addition, it was stronger (739 MPa versus 497 MPa) and more stiffness (i.e., a higher Young's modulus) than the trimolter silk. FTIR and X-ray diffraction results revealed that the excellent mechanical properties of bimolter silk can be attributed to the higher ß-sheet content and crystallinity. Chitin staining of the anterior silk gland suggested that the lumen is narrower in bimolters, which may lead to the formation of greater numbers of ß-sheet structures in the silk. Therefore, this study reveals the relationship between the structures and mechanical properties of bimolter silk and provides a valuable reference for producing high-strength and ultrafine silk fibers.
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OBJECTIVES: Immunodeficient mice injected with human cancer cell lines have been used for human oncology studies and anti-cancer drug trials for several decades. However, rodents are not ideal species for modelling human cancer because rodents are physiologically dissimilar to humans. Therefore, anti-tumour drugs tested effective in rodents have a failure rate of 90% or higher in phase III clinical trials. Pigs are similar to humans in size, anatomy, physiology and drug metabolism rate, rendering them a desirable pre-clinical animal model for assessing anti-cancer drugs. However, xenogeneic immune rejection is a major barrier to the use of pigs as hosts for human tumours. Interleukin (IL)-2 receptor γ (IL2RG), a common signalling subunit for multiple immune cytokines including IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21, is required for proper lymphoid development. MATERIALS AND METHODS: IL2RG-/Y pigs were generated by CRISPR/Cas9 technology, and examined for immunodeficiency and ability to support human oncogenesis. RESULTS: Compared to age-matched wild-type pigs, IL2RG-/Y pigs exhibited a severely impaired immune system as shown by lymphopenia, lymphoid organ atrophy, poor immunoglobulin function, and T- and NK-cell deficiency. Human melanoma Mel888 cells generated tumours in IL2RG-/Y pigs but not in wild-type littermates. The human tumours grew faster in IL2RG-/Y pigs than in nude mice. CONCLUSIONS: Our results indicate that these pigs are promising hosts for modelling human cancer in vivo, which may aid in the discovery and development of anti-cancer drugs.
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Sistemas CRISPR-Cas/genética , Subunidade gama Comum de Receptores de Interleucina/metabolismo , Neoplasias Cutâneas/patologia , Animais , Animais Geneticamente Modificados/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Edição de Genes , Humanos , Sistema Imunitário/metabolismo , Subunidade gama Comum de Receptores de Interleucina/antagonistas & inibidores , Subunidade gama Comum de Receptores de Interleucina/genética , Linfopenia/patologia , Melanoma/metabolismo , Melanoma/patologia , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/mortalidade , Taxa de Sobrevida , Suínos , Porco Miniatura , Transplante HeterólogoRESUMO
Identifying and comparing the chemical constituents of wild silkworm cocoon and silkworm cocoon is of great significance for understanding the domestication of silkworm. In this study, we used high temperature and high pressure and methanol-water system to extract cocoon chemical constituents. We used UHPLC-MS to identify and compare cocoon chemical constituents of wild silkworm and domestic silkworm Dazao and Haoyue strains. The cocoon metabolic fingerprints of wild silkworm and domestic silkworm Dazao and Haoyue strains were obtained by using the UHPLC-MS in the positive ion mode and negative ion mode. By annotation, we found that cocoon chemical compounds with high abundances contained amino acids, flavonoids, alkaloids, terpenes, organic acids, and lignans. PLS-DA showed that the cocoon components were significantly different among the wild silkworm and two domestic silkworm strains Dazao and Haoyue. Proline, leucine/isoleucine and phenylalanine showed significantly higher abundances in the cocoon of domestic silkworm Dazao strain than in those of wild silkworm and domestic silkworm Haoyue strain. The flavonoid secondary metabolites are abundant in the Dazao cocoon, including quercetin, isoquercetin, quercetin 3-O-sophoroside, quercetin-3-O-α-L-rhamnoside, quercetin-3-O- rutinoside, and kaempferol. The other secondary metabolites, alkaloids, terpenes and lignans, showed higher abundances in the wild silkworm cocoon than in the domestic silkworm cocoon, including neurine, candicine, pilocarpidine, artemisiifolin, eupassopin, and eudesobovatol. By exposing cocoons to UV light and observing the green fluorescence of flavonoids, we found that Dazao cocoon had the most flavonoids, and Haoyue cocoon had least flavonoids and wild silkworm cocoon had mediate flavonoids. Alkaloids and organic acids are good anti-insect and antimicrobial agents, which have high abundance in the wild silkworm cocoon and could enhance the defense ability of wild silkworm cocoon. Flavonoids are abundant in the cocoon of domestic silkworm Dazao strain, which the main factors are leading to the yellow-green cocoon of Dazao.
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Bombyx , Animais , Cromatografia Líquida de Alta Pressão , Flavonoides , Espectrometria de MassasRESUMO
OBJECTIVE: Meta analysis was used to evaluate the efficacy and safety of Dynesys and posterior decompression and fusion internal fixation for lumbar degenerative diseases. METHODS: The computer was used to retrieve the Cochrane library, Medline, Embase, CNKI, Wanfang database and Chinese biomedical literature database; and the references and main Chinese and English Department of orthopedics journals were manually searched. All the prospective or retrospective comparative studies on the clinical efficacy and safety of Dynesys and posterior decompression and fusion internal fixation were collected, so as to evaluate the methodological quality of the study and to extract the data. The RevMan 5.2 software provided by Cochrane collaboration was used for systematic evaluation. RESULTS: A total of 9 clinical studies were included, including 3 prospective randomized controlled trials(RCT) and 6 retrospective controlled observational studies, which included 692 patients, with 336 cases in Dynesys group, and 356 cases in posterior decompression and fusion internal fixation (PLIF) group. The results showed that compared with PLIF, Dynesys system significantly decreased operation time(P<0.01), intraoperative blood loss (P<0.01). Both Dynesys and PLIF groups experienced improved ODI and back/leg pain VAS scores at final follow-up, and no statistically significant difference was noted according to the two surgical procedures(P>0.05). Dynesys could remain the range of motion (ROM) of surgical segments with less increased ROM of adjacent segments compared with that of PLIF group(P<0.01). Regarding the disc height of surgical segments, no statistically significant difference was noted according to the two groups(P>0.05), but postoperative complications incidence rate in PLIF group was higher than that in Dynesys group (P<0.05). CONCLUSIONS: Both Dynesys system and PLIF can improve clinical outcomes of lumbar degenerative diseases effectively. Compared with PLIF, Dynesys could remain the range of motion(ROM) of surgical segments with less increased ROM of adjacent segments and lower complication incidence rate. But the ability to prevent adjacent segments degeneration needs more RCTs with long-term follow-up to confirm.
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Região Lombossacral , Fusão Vertebral , Humanos , Vértebras Lombares , Estudos Prospectivos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: It is well known that AMP-activated protein kinase (AMPK) is a key factor affecting the development of type 2 diabetes mellitus (T2DM). The single nucleotide polymorphism (SNP) rs2746342 in the AMPK alpha 2 subunit gene (PRKAA2) has been found to be associated with susceptibility to T2DM in the Chinese Han population. The present study further investigates the association of PRKAA2 genotypes with susceptibility to T2DM and its complication, diabetic nephropathy. METHODS: The PRKAA2 genotypes of 406 T2DM patients and 214 controls from the Chinese Han population were determined with regard to SNPs rs10789038, rs2796498 and rs2746342. The association between these SNPs and susceptibility to T2DM and diabetic nephropathy was evaluated. The clinical characteristics differed significantly between T2DM patients and controls. RESULTS: After adjustment for age, sex and body mass index, there was an obvious relationship between T2DM and both rs10789038 (odds ratio [OR] 1.634; P = 0.015) and rs2796498 (OR 0.656; P = 0.030), but not rs2746342. There was haplotype association of PRKAA2 rs10789038-rs2796498-rs2746342 with T2DM susceptibility. In addition, rs2796498 was found to be related to the susceptibility to diabetic nephropathy. CONCLUSIONS: Polymorphisms in rs10789038 and rs2796498 are associated with the susceptibility to T2DM, and rs2796498 may be related to diabetic nephropathy.
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Proteínas Quinases Ativadas por AMP/genética , Povo Asiático/genética , Diabetes Mellitus Tipo 2/genética , Nefropatias Diabéticas/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/etiologia , Feminino , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-IdadeRESUMO
We aimed to investigate whether the EC-SOD rs2536512, rs8192291 and rs1799895 polymorphisms and haplotypes are associated with T2DM in a Chinese Han population. A total of 540 Chinese Han patients with T2DM and 562 healthy subjects were enrolled in our study since October 2013, and all of them had no blood relationship. An iPlex GLOD SNP genotyping analysis of the EC-SOD rs2536512, rs8192291 and rs1799895 was carried out in a 384 well plate format using the Sequenom MassARRAY® System (Sequenom, Inc. San Diego, USA). We observed that the CT (OR=1.58, 95% CI=1.20-2.08) and TT (OR=15.27, 95% CI=4.34-53.75) genotypes of rs8192291 were associated with T2DM susceptibility compared with the CC genotype. In dominant and recessive models, rs8192291 was correlated with a moderate statistically increased susceptibility of T2DM compared with the reference genotype. The GTC, GCC and GCG haplotypes were associated with risk of T2DM. In summary, rs8192291 polymorphism and haplotypes may become a useful biomarker for prediction of the susceptibility of this disease. Further experiments are necessary to validate our results.
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Metformin is a classical oral antidiabetic drug, often recommended to be the first-choice treatment of type 2 diabetes mellitus (T2DM). Based on the previous research on STK11 and diabetes, we aimed to investigate the distributive characteristic of STK11 rs2075604 polymorphism and the potential influence of STK11 rs2075604 polymorphism on metformin efficacy among Chinese T2DM patients. There was no significant difference between T2DM patients (G = 64.8%, T = 35.2%) and healthy subjects (G = 62.7%, T = 37.2%) in STK11 rs2075604 genotype and allele frequencies. After 12 weeks of treatment, 62 patients were defined as the responders and 32 patients as nonresponders according to the decrease of HbA1c level. And the GT + TT genotype in STK11 rs2075604 can decrease HbA1c level more significantly than the GG genotype. Furthermore, the allele frequency of T in the STK11 rs2075604 was higher in the responders than the nonresponders (43.55% versus 26.56%). The T allele in the STK11 rs2075604 had a 2.133 times great chance of responding to metformin treatment. In conclusion, this study suggested that the STK11 rs2075604 genetic polymorphism was significantly associated with metformin efficacy in Chinese T2DM patients and the carriers of the T allele may gain a better therapeutic metformin efficacy compared with the G allele. This trial is registered with clinical study registration number NCT03155087.
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Extracorporeal pulsed electromagnetic field (PEMF) has been shown the ability to improve regeneration in various ischemic episodes. Here, we examined whether PEMF therapy facilitate cardiac recovery in rat myocardial infarction (MI), and the cellular/molecular mechanisms underlying PEMF-related therapy was further investigated. The MI rats were exposed to active PEMF for 4 cycles per day (8 minutes/cycle, 30 ± 3 Hz, 5 mT) after MI induction. The data demonstrated that PEMF treatment significantly inhibited cardiac apoptosis and improved cardiac systolic function. Moreover, PEMF treatment increased capillary density, the levels of vascular endothelial growth factor (VEGF) and hypoxic inducible factor-1α in infarct border zone. Furthermore, the number and function of circulating endothelial progenitor cells were advanced in PEMF treating rats. In vitro, PEMF induced the degree of human umbilical venous endothelial cells tubulization and increased soluble pro-angiogenic factor secretion (VEGF and nitric oxide). In conclusion, PEMF therapy preserves cardiac systolic function, inhibits apoptosis and trigger postnatal neovascularization in ischemic myocardium.
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Hypertension is considered as one of the major risk factors of atherosclerosis, especially for carotid artery plaque, which is a sign for cardiovascular incapacity and cerebral infarction. As adult age, systolic blood pressure (SBP or S) tends to rise and diastolic blood pressure (DBP or D) tends to fall, thus the pulse pressure (PP) will increase. The vascular injury was directly proportional to the level of SBP, and inversely proportional to DBP. But so far, studies of the vascular injury based on SBP and DBP measurement were mostly qualitative. The exact contribution of each parameter to the vascular injury has not been quantitatively identified. In this study, we employed a mathematical model to predict the risk for plaques of carotid arteries in aged people and combined the SBP, DBP and heart rate (HR) to perform a quantitative analysis. We analyzed 1672 males who were over 60-year-old and hospitalized due to atherosclerosis-related diseases and received a 24-h arterial blood pressure monitoring (ABPM) examination. These patients were divided into 19 subgroups using the ABPM data, 24-h average SBP, DBP and HR as variables based on the ascending order of the magnitude of each element. We developed a new index, namely the dynamic level (DL) which correlated best with the plaque formation of carotid arteries among all the well-established indexes for blood pressure. We demonstrated that index DL has better correlation to plaques incidence tendency (p < 0.0001) when compared to either SBP (P < 0.05) or PP (P < 0.001) alone. The risk on incidence of the plaques of carotid arteries has positive correlation with first power of SBP and -0.8 power of DBP. This model can be used clinically to predict the occurrence of plaque formation.