Unraveling the relationship between high-sensitivity C-reactive protein and frailty: evidence from longitudinal cohort study and genetic analysis.

BACKGROUND: This study aimed to investigate the association of high-sensitivity C-reactive protein (hs-CRP) with incident frailty as well as its effects on pre-frailty progression and regression among middle-aged and older adults. METHODS: Based on the frailty index (FI) calculated with 41 items, 6890 eligible participants without frailty at baseline from China Health and Retirement Longitudinal Study (CHARLS) were categorized into health, pre-frailty, and frailty groups. Logistic regression models were used to estimate the longitudinal association between baseline hs-CRP and incident frailty. Furthermore, a series of genetic approaches were conducted to confirm the causal relationship between CRP and frailty, including Linkage disequilibrium score regression (LDSC), pleiotropic analysis, and Mendelian randomization (MR). Finally, we evaluated the association of hs-CRP with pre-frailty progression and regression. RESULTS: The risk of developing frailty was 1.18 times (95% CI: 1.03-1.34) higher in participants with high levels of hs-CRP at baseline than low levels of hs-CRP participants during the 3-year follow-up. MR analysis suggested that genetically determined hs-CRP was potentially positively associated with the risk of frailty (OR: 1.06, 95% CI: 1.03-1.08). Among 5241 participants with pre-frailty at baseline, we found pre-frailty participants with high levels of hs-CRP exhibit increased odds of progression to frailty (OR: 1.39, 95% CI: 1.09-1.79) and decreased odds of regression to health (OR: 0.84, 95% CI: 0.72-0.98) when compared with participants with low levels of hs-CRP. CONCLUSIONS: Our results suggest that reducing systemic inflammation is significant for developing strategies for frailty prevention and pre-frailty reversion in the middle-aged and elderly population.

High sensitivity C-reactive protein and prediabetes progression and regression in middle-aged and older adults: A prospective cohort study.

BACKGROUND: This study aimed to investigate the effect of systemic inflammation, assessed by high sensitivity C-reactive protein (hs-CRP) levels, on prediabetes progression and regression in middle-aged and older adults based on the China Health and Retirement Longitudinal Study (CHARLS). METHODS: Participants with prediabetes from CHARLS were followed up 4 years later with blood samples collected for measuring fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). The level of hs-CRP was assessed at baseline and categorized into tertiles (low, middle, and high groups). Prediabetes at baseline and follow-up was defined primarily according to the American Diabetes Association (ADA) criteria. Logistic regression models were used to estimate the odds ratios (ORs) and confidence intervals (CIs). We also performed stratified analyses according to age, gender, BMI, the presence of hypertension, and the disease history of heart disease and dyslipidemia and sensitivity analyses excluding a subset of participants with incomplete data. RESULTS: Of the 2,874 prediabetes included at baseline, 834 participants remained as having prediabetes, 146 progressed to diabetes, and 1,894 regressed to normoglycemia based on ADA criteria with a 4 year follow-up. After multivariate logistics regression analysis, prediabetes with middle (0.67-1.62 mg/L) and high (>1.62 mg/L) hs-CRP levels had an increased incidence of progressing to diabetes compared with prediabetes with low hs-CRP levels (<0.67 mg/L; OR = 1.846, 95%CI: 1.129-3.018; and OR = 1.632, 95%CI: 0.985-2.703, respectively), and the incidence of regressing to normoglycemia decreased (OR = 0.793, 95%CI: 0.645-0.975; and OR = 0.769, 95%CI: 0.623-0.978, respectively). Stratified analyses and sensitivity analyses showed consistent results. CONCLUSIONS: Low levels of hs-CRP are associated with a high incidence of regression from prediabetes to normoglycemia and reduced odds of progression to diabetes.

Association of High Serum Chemerin with Bone Mineral Density Loss and Osteoporotic Fracture in Elderly Chinese Women.

BACKGROUND: Chemerin has been suggested to be a risk factor for osteoporosis; however, its relationship with osteoporotic fracture is poorly understood. Herein, we intend to explore the association between serum chemerin and osteoporotic fracture. METHODS: A total of 111 elderly women patients diagnosed with osteoporotic fracture were selected as the observation group, and 40 healthy subjects were enrolled as controls. Dual-energy X-ray absorptiometry, enzyme-linked immunosorbent assay, electrochemiluminescence immunoassay, and biochemical analysis were separately performed to determine body bone mineral density (BMD), chemerin levels, bone turnover markers, and other parameters. Pearson's correlation analysis was conducted to examine a relationship between chemerin and laboratory parameters. Moreover, the levels of chemokine-like receptor 1 (CMKLR), C-C motif chemokine receptor-like 2 (CCRL2), collagen type I alpha (COLA1), and runt-related transcription factor-2 (RUNX2) were confirmed by quantitative polymerase chain reaction, and the effect of chemerin on osteogenic differentiation of hFOB1.19 cells was indicated by tartrate-resistant acid phosphatase and alkaline phosphatase double staining. RESULTS: A higher level of chemerin was generally detected in patients with osteoporotic fracture compared with those without (P<0.05). Compared with controls, lower BMD levels and higher ß-CTx and P1NP levels were detected in patients with osteoporotic fracture (all P<0.05). Interestingly, chemerin level was negatively correlated to BMD, but positively related to P1NP and ß-CTx. Risk of osteoporotic fracture was 2.75-fold higher in subjects with each standard deviation increment of chemerin. Compared with controls, there were no significant differences in CMKLR1 and CCRL2 mRNA after incubation with osteogenic differentiation medium (all P>0.05), whereas there was a remarkable decrease of COLA1 and RUNX2 after incubation with chemerin for nine days (all P<0.05). Furthermore, prolonged incubation with chemerin enhanced osteoclast differentiation and maturation, consequently contributing to an increased risk of fracture. CONCLUSION: Chemerin is a strong and independent risk factor for osteoporosis-related fracture among elderly Chinese women.

A terpenoid phytoalexin plays a role in basal defense of Nicotiana benthamiana against Potato virus X.

Terpenoid phytoalexins function as defense compound against a broad spectrum of pathogens and pests in the plant kingdom. However, the role of phytoalexin in antiviral defense is still elusive. In this study, we identified the biosynthesis pathway of a sesquiterpenoid phytoalexin, capsidiol 3-acetate as an antiviral response against RNA virus Potato Virus X (PVX) in Nicotiana benthamiana. NbTPS1 and NbEAH genes were found strongly induced by PVX-infection. Enzymatic activity and genetic evidence indicated that both genes were involved in the PVX-induced biosynthesis of capsidiol 3-acetate. NbTPS1- or NbEAH-silenced plant was more susceptible to PVX. The accumulation of capsidiol 3-acetate in PVX-infected plant was partially regulated by jasmonic acid signaling receptor COI1. These findings provide an insight into a novel mechanism of how plant uses the basal arsenal machinery to mount a fight against virus attack even in susceptible species.