RESUMO
While the cellular cytosol and organelles contain attractive targets for disease treatments, it remains a challenge to deliver therapeutic biomacromolecules to these sites. This is due to the selective permeability of the plasma and endosomal membranes, especially for large and hydrophilic therapeutic cargos such as proteins and nucleic acids. In response, many different delivery systems and molecules have been devised to help therapeutics cross these barriers to reach cytosolic targets. Among them are peptide and protein-based systems, which have several advantages over other natural and synthetic materials including their ability to interact with cell membranes. In this review, we will describe recent advances and current challenges of peptide and protein strategies that leverage cell membrane association and modulation to enable cytosolic delivery of biomacromolecule cargo. The approaches covered here include peptides and proteins derived from or inspired by natural sequences as well as those designed de novo for delivery function.
Assuntos
Membrana Celular , Sistemas de Liberação de Medicamentos , Peptídeos , Humanos , Peptídeos/química , Peptídeos/metabolismo , Membrana Celular/metabolismo , Membrana Celular/química , Proteínas/química , Proteínas/metabolismo , Animais , Citosol/metabolismo , Endossomos/metabolismoRESUMO
The epidemiology of vertebral fractures (VF) in underrepresented populations is not well-documented. This cohort study was part of a longitudinal osteoporosis research project with the aim of determining the prevalence, incidence, and risk factors for VF. 401 individuals (155 men) aged 50 years and older without a clinical diagnosis of VF were took radiographs at baseline and 2 years later. VF were ascertained using the Genant's semi-quantitative method. Bone mineral density (BMD) of femoral neck and lumbar spine were measured by dual-energy X-ray absorptiometry (Hologic Inc). The association between VF and risk factors was analyzed by the multiple logistic regression. The 95% confidence interval for prevalence and incidence was estimated by exact Poisson test. At baseline, the prevalence of VF was 12.2% (n = 49, 95% CI 9.0-16.2%) and increased with advancing age with one-fifth of those aged 70 and older having a VF. During the follow-up period, we observed 6 new VF, making the incidence of 6.6/1000 person-years (n = 6, 95% CI 2.4-14.3). The risk of prevalent VF was associated with male gender (OR: 2.67; 95% CI 1.28-5.87) and T-score at the femoral neck (OR per one SD decrease: 1.1; 1.03-1.17). These data indicate that VF is common among adults, and that lower femoral neck BMD was a risk factor for VF.
Assuntos
Osteoporose , Fraturas da Coluna Vertebral , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Estudos de Coortes , Prevalência , Incidência , Vietnã , Osteoporose/diagnóstico por imagem , Osteoporose/epidemiologia , Osteoporose/complicações , Densidade Óssea , Absorciometria de Fóton/métodos , Fatores de Risco , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/lesõesRESUMO
BACKGROUND: Little is known about the trends in colorectal cancer (CRC) in Vietnam. We aimed to investigate the trends in epidemiology and anatomical subsites of CRC in Ho Chi Minh City, Vietnam. METHODS: Based on the Ho Chi Minh City Cancer Registry data during 1996-2015, we calculated the average annual percent changes (AAPCs) of the age-standardized incidence rates (ASRs) by sex, age groups, and anatomical subsites, using joinpoint regressions analysis. We further performed age-period-cohort (APC) analysis using the United States National Cancer Institute's web-based statistical tool to explore the underlying reason for the incidence trend. RESULTS: Over 20 years the overall ASR of CRC increased from 10.5 to 17.9 per 100,000, a 1.7-fold increase. CRC incidence elevated more rapidly in men (AAPC 4.7, 95%CI 2.2-7.3) than in women (AAPC 2.6, 95%CI 0.6-4.8). The highest and lowest increasing rates of ASRs were observed in the 50-64-year-old age group (AAPC 5.3, 95%CI 2.8-7.9) and < 50-year-old age group (AAPC 1.1, 95%CI -0.7 to 2.9), respectively. Regarding subsites, rectal cancer had the highest rate of increase (AAPC 3.3, 95%CI 1.0-5.7). Furthermore, the APC analysis indicated significant increases in CRC incidence in birth cohorts after 1975 in both genders. CONCLUSIONS: The CRC incidence in Ho Chi Minh City increased, with the more prominent rates being among men and older populations, in rectal subsites, and in people born after 1975. The upward trend of CRC incidence in Ho Chi Minh City may be due to the adoption of a westernized lifestyle.
Assuntos
Neoplasias Retais , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estados Unidos , Vietnã/epidemiologiaRESUMO
PURPOSE: To estimate the proportion of men and women aged 50 years and older who would be classified as "high risk" for fracture and eligible for anti-fracture treatment. METHODS: The study involved 1421 women and 652 men aged 50 years and older, who were recruited from the general population in Ho Chi Minh City, Vietnam. Fracture history was ascertained from each individual. Bone mineral density (BMD) was measured at the lumbar spine and femoral neck by DXA (Hologic Horizon). The diagnosis of osteoporosis was based on the T-scores ≤ -2.50 derived from either femoral neck or lumbar spine BMD. The 10-year risks of major fractureand hip fracture were estimated from FRAX version for Thai population. The criteria for recommended treatment were based on the US National Osteoporosis Foundation (NOF). RESULTS: The average age of women and men was ~60 yr (SD 7.8). Approximately 11% (n = 152) of women and 14% (n = 92) of men had a prior fracture. The prevalence of osteoporosis was 27% (n = 381; 95% CI, 25 to 29%) in women and 13% (n = 87; 95% CI, 11 to 16%) in men. Only 1% (n = 11) of women and 0.1% (n = 1) of men had 10-year risk of major fracture ≥ 20%. However, 23% (n = 327) of women and 9.5% (n = 62) of men had 10-year risk of hip fracture ≥ 3%. Using the NOF recommended criteria, 49% (n = 702; 95% CI, 47 to 52%) of women and 35% (n = 228; 95% CI, 31 to 39%) of men would be eligible for therapy. CONCLUSION: Almost half of women and just over one-third of men aged 50 years and older in Vietnam meet the NOF criteria for osteoporosis treatment. This finding can help develop guidelines for osteoporosis treatment in Vietnam.
Assuntos
Osteoporose/economia , Idoso , Densidade Óssea , Feminino , Fraturas Ósseas/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/complicações , Osteoporose/epidemiologia , Prevalência , Fatores de Risco , VietnãRESUMO
This study sought to define the sex-difference in trabecular and cortical bone parameters in Vietnamese individuals. The study involved 1404 women and 864 men aged between 20 and 86 years who were recruited from Ho Chi Minh City, Vietnam. Trabecular and cortical volumetric BMD were measured at the proximal tibia and proximal radius at 4%, 38%, and 66% points, using a peripheral quantitative computed tomography XCT2000 (Stratec, Germany). Polar strength strain index was estimated from cortical bone parameters. Changes in bone parameters were assessed by the multiple linear regression model. Among individuals aged 20-39 years, women had significantly lower peak trabecular BMD at both the radius (40%) and tibia (16%) than men, but the age-related reduction in trabecular BMD were similar between two sexes. For cortical BMD, peak values in women and men were comparable, but the age-related diminution was greater in women than men. At any age, polar strength strain index in women was lower than men, and the difference was mainly attributable to cortical bone area and total bone mass. We conclude that in the elderly, sex-related difference in trabecular BMD is originated during growth, but sex-related difference in cortical BMD is determined by differential age-related bone loss.
Assuntos
Densidade Óssea , Fraturas Ósseas/patologia , Osteoporose/patologia , Caracteres Sexuais , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico por imagem , Osteoporose/epidemiologia , Osteoporose/etiologia , Tomografia Computadorizada por Raios X/métodos , Vietnã/epidemiologia , Adulto JovemRESUMO
This study sought to estimate the extent of genetic influence on the variation in trabecular bone score (TBS). We found that genetic factors accounted for ~45% of variance in TBS, and that the co-variation between TBS and bone density is partially determined by genetic factors. INTRODUCTION: Trabecular bone score has emerged as an important predictor of fragility fracture, but factors underlying the individual differences in TBS have not been explored. In this study, we sought to determine the genetic contribution to the variation of TBS in the general population. METHODS: The study included 556 women and 189 men from 265 families. The individuals aged 53years (SD 11). We measured lumbar spine bone mineral density (BMD; Hologic Horizon) and then derived the TBS from the same Hologic scan where BMD was derived. A biometric model was applied to the data to partition the variance of TBS into two components: one due to additive genetic factors, and one due to environmental factors. The index of heritability was estimated as the ratio of genetic variance to total variance of a trait. Bivariate genetic analysis was conducted to estimate the genetic correlation between TBS and BMD measurements. RESULTS: TBS was strongly correlated with lumbar spine BMD (r=0.73; P<0.001). On average TBS in men was higher than women, after adjusting age and height which are significantly associated with both TBS and lumbar spine BMD. The age and height adjusted index of heritability of TBS was 0.46 (95% CI, 0.39-0.54), which was not much different from that of LSBMD (0.44; 95% CI, 0.31-0.55). Moreover, the genetic correlation between TBS and LSBMD was 0.35 (95% CI, 0.21-0.46), between TBS and femoral neck BMD was 0.21 (95% CI, 0.10-0.33). CONCLUSIONS: Approximately 45% of the variance in TBS is under genetic influence, and this effect magnitude is similar to that of lumbar spine BMD. This finding provides a scientific justification for the search for specific genetic variants that may be associated with TBS and fracture risk.
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Densidade Óssea/genética , Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/fisiologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/fisiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Osteoporose/diagnóstico por imagem , Osteoporose/epidemiologia , Osteoporose/genética , Estudos Prospectivos , Vietnã/epidemiologiaRESUMO
Greater body mass index (BMI) is associated with a greater risk of osteoarthritis (OA). This study sought to investigate whether the association is mediated by fat mass or lean mass. The study involved 170 men and 488 women aged between 20 and 90 (average age: 55) who were randomly recruited from Ho Chi Minh City, Vietnam. The presence of knee OA was radiographically diagnosed based on the Kellgren-Lawrence criteria. Lean mass (LM) and fat mass (FM) were obtained from the DXA whole body scan (Hologic QDR-4500). The relationship between OA, LM, and FM was analyzed by a series of multiple linear regression models which take into account the effects of gender and age. As expected, men and women with knee OA were older than those without OA (65 vs 51 year in men, and 64 vs 52 year in women). After adjusting for age, OA was associated with greater FM and percent body fat (PBF), but the association was only observed in women, not in men. There was no statistically significant difference in LM between OA and non-OA individuals. Moreover, after adjusting for age and BMI or PBF, bone density in OA patients was not significantly different from non-OA individuals. Women with OA of the knee have greater fat mass than non-OA individuals, and that there is no significant difference in bone density between OA and non-OA individuals. Thus, the association between body mass index and OA is mainly mediated by fat mass.
Assuntos
Composição Corporal/fisiologia , Osteoartrite do Joelho/diagnóstico por imagem , Absorciometria de Fóton , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Osteoartrite do Joelho/epidemiologia , Prevalência , Caracteres Sexuais , Adulto JovemRESUMO
Intervertebral disc degeneration (IDD) is one of the most common skeletal disorders, yet few data are available in Asian populations. We sought to assess the prevalence and pattern of radiographic IDD in a Vietnamese population. This population-based cross-sectional investigation involved 170 men and 488 women aged ≥40 years, who were randomly sampled from the Ho Chi Minh City (Vietnam). Anthropometric data, clinical history and self-reported back and neck pain were ascertained by a questionnaire. Plain radiographs (from the cervical spine, thoracic spine to the lumbar spine) were examined for the presence of disc space narrowing and/or osteophytosis using the Kellgren-Lawrence (KL) grading system. The presence of radiographic IDD was defined if the KL grade was 2 or greater in at least one disc. The prevalence of radiographic IDD was 62.4% (n = 106) in men and 54.7% (n = 267) in women. The most frequently affected site was the lumbar spine with prevalence being 50.6 and 43.2% in men and women, respectively. The prevalence of IDD increased with advancing age: 18.8% among those aged 40-49 years, and increased to 83.4% in those aged ≥60 years. Self-reported neck pain and lower back pain were found in 30 and 44% of individuals, respectively. There was no statistically significant association between self-reported neck pain and cervical spine OA. These data suggest that radiographic IDD is highly prevalent in the Vietnamese population, and that self-reported back pain is not a sensitive indicator of IDD.
Assuntos
Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , RadiografiaRESUMO
BACKGROUND AND AIM: Osteoarthritis (OA) of the knee is one of the most common skeletal disorders, yet little data are available in Asian populations. We sought to assess the prevalence and pattern of radiographic OA of the knee, and its relationship to self-reported pain in a Vietnamese population. METHODS: The study was based on a sample of 170 men and 488 women aged ≥40 years who were randomly sampled from the Ho Chi Minh City (Vietnam). Radiographs of the knee were graded from 0 to 4 according to the Kellgren and Lawrence scale. Osteoarthritis was defined as being present in a knee if radiographic grades of 2 or higher were detected. Knee pain and symptoms were ascertained by direct interview using a structured questionnaire. RESULTS: The point prevalence of radiographic OA of the knee was 34.2%, with women having higher rate than men (35.3% vs 31.2%). The prevalence of knee OA increased with advancing age: 8% among those aged 40-49 years, 30% in those aged 50-59 years, and 61.1% in those aged ≥60 years. Greater BMI was associated with higher risk of knee OA. Self-reported knee pain was found in 35% of men and 62% of women. There was a statistically significant association between self-reported knee pain and knee OA (prevalence ratio 3.1; 95% CI 2.0 to 4.6). CONCLUSIONS: These data indicate that approximately a third of Vietnamese men and women have radiographic OA in the knee, and that self-reported knee pain may be used as an indicator of knee osteoarthritis.
Assuntos
Articulação do Joelho/patologia , Osteoartrite do Joelho/epidemiologia , Dor/epidemiologia , Adulto , Fatores Etários , Idoso , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Articulação do Joelho/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/patologia , Dor/complicações , Dor/diagnóstico por imagem , Dor/patologia , Prevalência , Radiografia , Autorrelato , Fatores Sexuais , Inquéritos e Questionários , VietnãRESUMO
UNLABELLED: Based on quantitative measurements of vertebral heights, the prevalence of undiagnosed vertebral fracture in Vietnamese men and women aged 50 years and older was 23 and 26 %, respectively. BACKGROUND: The present study sought to develop reference ranges for vertebral heights and to determine the prevalence of asymptomatic vertebral fracture in Vietnamese men and women. METHODS: The study included 312 men and 657 women aged over 18 who were randomly selected from the community. The ImageJ software program was used to measure anterior height (H(a)), middle height (H(m)), and posterior height (H(p)) for each vertebra (T4 to T12 and L1 to L5). Four vertebral ratios were determined: H(a)/H(p), H(m)/H(p), H(p)/H(p + 1), and H(p)/H(p − 1). Reference ranges for the ratios were then developed by the method of Winsorized mean. Vertebral fracture was diagnosed as a ratio lower than three standard deviations from the normal mean. RESULTS: For any given vertebra, H(a), H(m), and H(p) in men were higher than in women. In both sexes, H(a) and H(m) increased in a stepwise fashion from T4 to L3 and then gradually reduced in L4L5. Vertebral heights for T4T9 tended to decrease, while vertebral height for T10L5 tended to increase with advancing age. Among those aged over 50 years, the prevalence of vertebral fracture in men was 23.3 % (95 % confidence interval (CI) 16.831.3 %) which was lower than that in women (26.5 %; 95 % CI 22.431.1 %). The prevalence increased with advancing age, such that from the age of over 70, 41 % of men and 42 % women had at least one vertebral fracture. CONCLUSION: One fourth of Vietnamese men and women aged 50 years and older have a symptomatic vertebral fracture. This prevalence is equivalent to that in Caucasian populations.