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Biomedical subjects

Bo Fu

Publications and source records attributed to Bo Fu.

18 recordsLinked to original sources

Impacts of climate-driven yield changes on the affordability of healthy diets: a modelling study.

BACKGROUND: Food security is central to global nutrition improvement and public health goals, and healthy diets represent a higher-level aspiration beyond merely avoiding hunger. Climate change poses an increasing threat to food systems by affecting crop yields and food prices. Although climate change-driven risks to hunger have been widely studied, the extent to which climate change undermines the affordability of healthy diets while accounting for socioeconomic responses and regional inequalities remains insufficiently understood. This study aimed to quantify the effects of climate change on the future affordability of healthy diets under alternative socioeconomic and climate scenarios. METHODS: We developed an integrated modelling framework that explicitly couples multimodel crop-yield projections with an integrated assessment model (Global Change Analysis Model [GCAM]). Yield responses from six global gridded crop models driven by four climate models were integrated into GCAM, allowing endogenous socioeconomic adjustments such as land-use shifts, production reallocation, and price responses to emerge under shared socioeconomic pathways (SSPs). Diet affordability was then assessed using the Food and Agriculture Organization of the UN's Cost and Affordability of a Healthy Diet framework across three socioeconomic-climate scenarios (SSP1-2.6, SSP2-4.5, and SSP3-6.0). FINDINGS: Under a high-emissions pathway (ie, SSP3-6.0), climate change was projected to render healthy diets unaffordable for a model-mean of 119 million people globally by 2100, even when CO2 fertilisation effects are included, with the upper end of the model ensemble reaching about 1·6 billion people. In contrast, climate-induced affordability losses were found to be negligible under both a low-emissions pathway (ie, SSP1-2.6; -0·3 million) and a medium-emission pathway (SSP2-4.5; +0·2 million). Under a high-emission pathway, model-mean projections indicated that diet costs could increase by up to 12% in the most affected regions by the end of the century. Under medium emissions, cost increases were projected to remain below 4%, whereas under low emissions, affordability changes were projected to be minimum across regions (within approximately 0·5%). Substantial regional disparities emerged, with the largest and most consistent affordability losses concentrated in low-income regions that contributed least to historical greenhouse gas emissions. Under SSP3-6.0, these disparities persisted particularly in regions of Africa and Asia despite projected three-to-five-fold increases in income over the century, with climate-induced disruptions to food systems increasing the number of people unable to afford a healthy diet through mid-century. INTERPRETATION: Climate change is likely to exacerbate global nutritional inequalities by disproportionately increasing the affordability risks of healthy diets in regions that have contributed least to historical greenhouse gas emissions. Under high-warming scenarios, socioeconomic development alone is insufficient to fully offset these risks, highlighting the structural vulnerability of low-income food systems to climate-driven price shocks. These findings suggest that in the absence of targeted interventions, climate change could continue to undermine progress towards equitable and health-oriented nutrition outcomes. FUNDING: Ministry of Science and Technology of the People's Republic of China; National Natural Science Foundation of China; National Aeronautics and Space Administration Goddard Institute for Space Studies Climate Impacts Group; Future of Life Institute; and Global Alliance for Improved Nutrition.

Journal Article↗

TIMP-1 transgenic mice recover from diabetes induced by multiple low-dose streptozotocin.

Type 1 diabetes results from autoimmune destruction of the insulin-producing beta-cells of pancreatic islets, of which the capacity for self-replication in the adult is too limited to restore following extensive tissue injury. Tissue inhibitor of metalloproteinase (TIMP)-1 inhibits matrix metalloproteinase activity and regulates proliferation and apoptosis of a variety of cells types, depending on the context. Here, we show that overexpression of human TIMP-1 in pancreatic beta-cells of transgenic mice counteracts the cytotoxicity and insulitis induced by multiple low-dose streptozotocin (MLDS). Nontransgenic mice developed severe hyperglycemia, hypoinsulinemia, and insulitis 2 weeks after streptozotocin administration and died within 17 weeks. However, MLDS-treated transgenic mice gradually normalized the metabolic parameters and survived. beta-Cell mass increased in parallel as a result of enhancement of beta-cell replication. Thus, our results have demonstrated for the first time that overexpression of TIMP-1 in beta-cells enhances the replication of pancreatic islets beta-cells and counteracts type 1 diabetes, indicating that the TIMP-1 gene may be a potential target to prevent, or even reverse, type 1 diabetes.

Animals↗

Electronic and fluorescence spectral studies of a novel porphyrin-polypyridyl ruthenium(II) hybrid linked by a butyl chain.

The electronic and fluorescence spectroscopic properties of a novel porphyrin-polypyridyl ruthenium(II) hybrid, [C(4)-TPP-(ip)Ru(phen)(2)](ClO(4))(2) (TPP=5,10,15,20-tetraphenylporphyrin, ip=imidazo[4,5-f][1,10]phenanthroline and phen=1,10-Phenanthroline), in which a polypyridyl ruthenium(II) moiety is linked to a porphyrin moiety by a butyl chain have been investigated and compared to its corresponding reference compounds. The studies of electronic absorption spectra have shown that there is an electronic interaction between the porphyrin moiety and the polypyridyl ruthenium(II) moiety in the hybrid. It can be found that intramolecular photoinduced electron and energy transfer processes may occur in the hybrid from the fluorescence spectra. When exciting in Soret band and Q band of porphyrin, the fluorescence quenching of the porphyrin moiety of the hybrid takes place due to electron transfer from the lowest singlet excited state (S(1)) to the appended polypyridyl rutherium(II) moiety, while the decay of S(2) (the second-excited singlet state) of the porphyrin moiety is mainly contributed to internal conversion to S(1). When exciting in MLCT band of the polypyridyl ruthenium(II) moiety, fluorescence corresponding to the polypyridyl ruthenium(II) moiety is quenched by intramolecular energy transfer from (3)MLCT of the ruthenium moiety to the lowest-energy triplet state localized on the porphyrin moiety.

Absorption↗

Signal transducers and activators of transcription 3 mediates up-regulation of angiotensin II-induced tissue inhibitor of metalloproteinase-1 expression in cultured human senescent fibroblasts.

BACKGROUND: Angiotensin II (Ang II), a principal effector of renin-angiotensin system (RAS) and increased in aging tissues, can stimulate JAK/STAT pathway via the G-protein-coupled Ang II receptor type I (AT1) and induce nuclear translocation of signal transducers and activators of transcription (STAT). To further explore the role of Ang II in aging, we examined the effect of Ang II on human replicative senescent diploid fibroblast WI-38 cells. METHODS: Human senescent WI-38 cells were incubated with Ang II, receptor antagonist PD123319, valsartan, STAT3 sense plasmid, and/or STAT3 antisense plasmids. Methods were applied including electrophoretic mobility shift assay (EMSA), Western blot, transfection, and laser scanning confocal microscopy. RESULTS: It was found that cultured human senescent WI-38 cells constitutively expressed tissue inhibitor of metalloproteinase-1 (TIMP-1), and Ang II induced TIMP-1 protein expression in both time- and dose-dependent manners. Ang II induced STAT-DNA binding activity also in both time- and dose-dependent manners. And supershift assay showed that the sis-inducing factor (SIF) band contained STAT3 proteins. STAT3 antisense oligonucleotides could inhibit both Ang II-induced STAT3-DNA binding activity as well as TIMP-1 expression. CONCLUSION: Ang II could up-regulate TIMP-1 expression through activating STAT3 signal pathway in human senescent cells, indicating that Ang II-STAT3-TIMP-1 pathway may be involved in the mechanism of sclerosis in aging tissues.

Angiotensin II↗

Downregulation of connexin 43 expression by high glucose induces senescence in glomerular mesangial cells.

Connexin 43 (Cx43) plays an important role in cell differentiation and growth control, but whether it can be regulated by high glucose and whether it can mediate in glomerular mesangial cells (GMC) the phenotype alterations that are induced by high glucose still remain to be explored. In this study, RNA interference and gene transfer techniques were used to knock down and overexpress Cx43 gene in rat GMC to determine the contribution of Cx43 to GMC senescence that was induced by high glucose. The results show that high glucose (30 mM) not only downregulated Cx43 mRNA and protein expression (P<0.05) but also increased the percentage of senescence-associated beta-galactosidase (SA-beta-gal) stained cells and expression of p21cip1 and p27kip1 (P<0.05), indicating that high glucose promoted rat GMC senescence. Knocking down Cx43 gene expression significantly increased the percentage of SA-beta-gal stained cells and p27kip1 and p21cip1 expression in GMC (P<0.05), whereas overexpression of Cx43 significantly decreased the percentage of SA-beta-gal stained cells (P<0.05). These results demonstrate for the first time that downregulation of Cx43 expression by high glucose promotes the senescence of GMC, which may be involved in the pathogenesis of diabetic nephropathy.

Animals↗

Identification of basolateral membrane targeting signal of human sodium-dependent dicarboxylate transporter 3.

Sodium-dependent dicarboxylate transporters (NaDC) include low-affinity NaDC1 and high-affinity NaDC3. Despite high similarities structurally and functionally, both are localized to opposite surfaces of renal tubular cells. The molecular mechanisms and localization signals leading to this polarized distribution remain unknown. In this study, distribution of NaDC3 in human kidney tissue was firstly observed by immunohistochemistry and immunofluorescence. Then, EGFP-fused wild-type, NH2- and COOH-terminal deletion and point mutants of NaDC3, and chimera between NaDC3 and NaDC1, were generated and transfected into polarized renal cells lines, LLC-PK1 and MDCK. Their subcellular localizations were analyzed by laser confocal microscopy. Immunolocalization results revealed that NaDC3 was expressed at basolateral membrane of human renal proximal tubular epithelia. Confocal examinations showed that wild-type NaDC3 was targeted to the basolateral membrane of MDCK and LLC-PK1. Deletion mutations indicated that the basolateral targeting signal of NaDC3 located within a short sequence AKKVWSARR of its amino-terminal cytoplasmic domain. Addition of this sequence could redirect apical NaDC1 to the basolateral membrane of LLC-PK1. Point mutagenesis revealed that mutation of either of two hydrophobic amino acids V and W in this short sequence largely redirected NaDC3 to both apical and basolateral surfaces of LLC-PK, indicating that the two hydrophobic amino acids are critical for the basolateral targeting of NaDC3. Our studies provide direct evidence of the localization of NaDC3 at the basolateral membrane of human renal proximal tubule cells and identify a di-hydrophobic amino acid motif VW as basolateral localization signal in the N-terminal cytoplasmic domain of NaDC3.

Amino Acid Sequence↗

Knockdown of fibronectin induces mitochondria-dependent apoptosis in rat mesangial cells.

Extracellular matrix (ECM) expansion and mesangial cell (MC) proliferation are prominent features of most types of glomerulosclerosis. A delicate balance between the ECM and MC regulates cell survival. Increasing evidence shows that a loss of ECM components can cause mitochondrial dysfunction and induce cell apoptosis. It is proposed that directly blocking the synthesis of ECM components could lighten ECM accumulation and suppress cell overproliferation status. Fibronectin, one of the predominant adhesive glycoproteins of the mesangial ECM, provides the survival signal for cells. Its accumulation can be observed in most types of glomerulosclerosis. In this study, angiotensin II-induced fibronectin was suppressed by an RNA interference technique. It is interesting that MC slowly underwent apoptosis after infection with a retrovirus that continuously suppressed fibronectin synthesis. It was found that MC apoptosis occurred in a mitochondria-dependent manner mainly as a result of cytochrome c release and downstream caspase-3 and -9 activation. Furthermore, it was demonstrated that fibronectin knockdown affected mitochondrial handling of Ca(2+) release from the endoplasmic reticulum. Importantly, blocking the inositol 1,4,5-triphosphate receptor with, 3,4,5-trimethoxybenzoate or decreasing Ca(2+) in the ECM with EGTA partially saved the cells from apoptosis. These studies, which explored a new method for simultaneously inhibiting MC proliferation and ECM accumulation, may represent a novel therapeutic approach to glomerulosclerosis.

Animals↗

Activation of gelatinases by fibrin is PA/plasmin system-dependent in human glomerular endothelial cells.

Evidence suggests that fibrin deposit is related to severity of glomerulonephropathy. Fibrin is considered to play an active role beyond a haemostatic plug or temporary matrix in response to injury. We have reported that fibrin induced specific morphological changes and up-regulated intercellular adhesion molecule-1 expression of glomerular endothelial cells (GECs). Changes of gelatinases activity have been implicated playing a prominent role in glomerular diseases involving matrix turnover. This study examined whether overlying fibrin influences the expression of gelatinase A and B in cultured human GECs and mechanism underlying the activation. No gelatinase activity was detectable in supernatant of cultured GECs; however, physiological concentration of fibrin (0.5-2.0 mg/ml) induced a dramatic expression of activated MMP-2 and MMP-9 at both mRNA and protein level in a dose and time dependent manner. Increased mRNA level of membrane-type 1 matrix metalloproteinases (MT1-MMPs) was also found. Interestingly, we observed that fibrin also induced the expression of tissue type plasminogen activator (tPA), urokinase type plasminogen activator (uPA) and plasminogen activator inhibitor-1 by casein zymographic and reverse zymographic analysis. Fibrin plate assay revealed the net activity was PA predominant. Serine protease inhibitor aprotinin blocked the conversion of pro-gelatinase A and B to their active forms. The results demonstrate that overlying fibrin increased the secretion of gelatinase A and B from GECs. PA/plasmin proteolytic pathways contributed to the activation of gelatinases.

Base Sequence↗

NANOG changes in mouse kidneys with age.

NANOG is essential for mouse and human embryonic stem cell (ESC) pluripotency and selfrenewal. It is also expressed in several adult murine tissues as shown by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. However, human NANOG transcripts have been isolated from adult bone marrow (EST; GenBank accession no. BF893620). Here, we study the NANOG gene expression profile in isolated mouse renal papillary cells by Northern blot and RT-PCR. The whole RNA of mouse renal cells was obtained from fresh renal tissues, renal tissues infused by phosphate-buffered saline (PBS), and isolated renal papillary cells of mouse, respectively, as well as the renal papillary tissue from 18.5 days postcoitum (d.p.c.; fetal), 1-2-week-old (young), 1-8-month-old (adult), and 24-month-old (aging) mice. Our analysis shows that a very low expression level was detected in mouse renal tissues, and the renal papillary cells express more than other tissues as determined with Northern blot and RT-PCR. These data suggest that the kidney has its own cells expressing NANOG, and loss of NANOG expression occurs in an age-dependent manner in the kidney, either due to developmental factors or aging, particularly in renal papillary tissue.

Aging↗

Effects of human Na(+)/dicarboxylate cotransporter 3 on the replicative senescence of human embryonic lung diploid fibroblasts.

To investigate the role of human Na(+)/dicarboxylate cotransporter 3 (hNaDC3) in the replicative senescence of normal human embryonic lung diploid fibroblasts (WI-38), a retroviral vector containing hNaDC3 was constructed. hNaDC3 was introduced into normal WI-38 cells through infection with the retroviral virus. Monoclones were selected with G418. The integration and expression of exotic genes were confirmed by Northern blot and Western blot. When compared with the control cells, WI-38 cells transfected with hNaDC3 cDNA showed significant suppression of growth rate (by 40%), increase of positive rate of SA-beta-gal staining, decrease of mitochondrial membrane potential, shortening of telomere length, and increase of P16 and P21 expression. The morphology characteristics of senescent fibroblasts appeared earlier. Our results have, for the first time, demonstrated that high expression of hNaDC3 may be able to, at least partly, promote the cellular senescence of human diploid fibroblasts.

Blotting, Northern↗

Expression and significance of integrin-linked kinase in cultured cells, normal tissue, and diseased tissue of aging rat kidneys.

Integrin-linked kinase (ILK) is an integrin-binding cytoplasmic protein that has been implicated in regulating numerous cellular processes and fibronectin (Fn) deposition through mediated integrin, but the expression and significance of ILK in the aging kidney have not yet been reported. We report here that mRNA and protein expression of ILK increased in primary cultured mesangial and tubular epithelial cells, and normal and unilateral ureteral obstructed kidney tissues in 28-month-old rats but not in 3-month-old rats, moreover, accompanied by the over-expression of Fn and integrin-beta1 in the aging kidney, by means of Northern blot, Western blot, and immunofluorescent double-staining immunohistochemistry. In addition, in the primary cultured kidney cells, ILK expression was positively correlated with senescence-associated beta-gal positive staining and negatively correlated with cellular proliferation. The results suggest that ILK may be involved in the fibrotic or senescent process in the aging kidney.

Aging↗

Median regression for longitudinal data.

We review and compare three estimators of median regression in linear models with longitudinal data. The estimators are constructed based on well-known ideas of weighting, decorrelating, and the working assumption of independence. Both asymptotic efficiency calculations and finite-sample Monte Carlo studies are used to assess the performance of these estimators. We find that their relative performances depend on the nature of covariates. The estimator under the working assumption of independence is computationally simple and yet has good relative performance when the covariates are invariant over time or when the within-subject correlations are small. Its relative performance in finite samples is also found to be more favourable than suggested by the asymptotic comparisons.

Analgesics↗

[Changes of STAT3 in cell replicative senescence and effects of angiotensin II on STAT3].

OBJECTIVE: To investigate the changes of STAT3 in cell replicative senescence and the effects of angiotensin II (AngII) on STAT3. METHODS: Normal human fetal lung diploid fibroblast cell line WI-38 was cultured and the senescent cell was defined with beta-gal staining. Electrophoretic mobility shift assay and Western blotting assay were used to detect the activation of STAT3 during cell replicative senescence and examine the process of STAT3 activation with AngII. RESULTS: The synthesis of STAT3 protein during the course of cell replicative senescent increased, the nuclear translocation of phosphorylated STAT3 decreased, and the activities of STAT3 binding DNA reduced. CONCLUSION: AngII induces the activation of STAT3 in both mature and senescence cell by AT(1) receptor, however, the reaction of senescent cell to AngII is weaker. The site of block may be in the nuclear translocation. AngII induces the activity of STAT3 in replicative senescence WI-38.

Active Transport, Cell Nucleus↗

Analyzing hospital length of stay: mean or median regression?

BACKGROUND: Length of stay (LOS) is an important measure of hospital activity and health care utilization, but its empirical distribution is often positively skewed. OBJECTIVE: This study reviews the mean and median regression approaches for analyzing LOS, which have implications for service planning, resource allocation, and bed utilization. METHODS: The two approaches are applied to analyze hospital discharge data on cesarean delivery. Both models adjust for patient and health-related characteristics, and for the dependency of LOS outcomes nested within hospitals. The estimation methods are also compared in a simulation study. RESULTS: For the empirical application, the mean regression results are somewhat sensitive to the magnitude of trimming chosen. The identified factors from median regression, namely number of diagnoses, number of procedures, and payment classification, are robust to high-LOS outliers. The simulation experiment shows that median regression can outperform mean regression even when the response variable is moderately positively skewed. CONCLUSION: Median regression appears to be a suitable alternative to analyze the clustered and positively skewed LOS, without transforming and trimming the data arbitrarily.

Cesarean Section↗

[Isolation, identification and in vitro culture of human glomerular mesangial cells].

OBJECTIVE: To define the optimal condition to culture human glomerular mesangial cells in vitro. METHODS: With a three-layer micropore filter device, we separated the glomerular mesangial cells from normal human, with were subjected to identification with immunohistochemical method. Fluorescein isothiocyanate (FITC) staining was performed for labeling of the monoclonal antibodies so as to identify the cells' superficial markers including factor VIII, keratin, cytokeratin, desmine, et al. Glomerular endothelial cells isolated from the same human tissues were also cultured in vitro under the same condition, serving as negative control. RESULTS AND CONCLUSION: The antibodies related to anti-factor VIII, and those of antikeratin and anticytokeratin were negative in the isolated glomerular mesangial cells, while the antibodies for desmine, anti-collagen IV, anti-fibronectin, and anti-laminin were positive, offering evidence for confirming the identification of the isolated and cultured mesangial cells.

Cell Separation↗

[Effect of antisense-tissue inhibitor of metalloproteinase-1 gene transfer on tubulointerstitial lesion in rats with unilateral ureteral obstruction].

OBJECTIVE: To observe the effect of antisense- human tissue inhibitor of metalloproteinase-1 (hTIMP-1) on tubulointerstitial lesion induced by unilateral ureteral obstruction (UUO). METHODS: Forty-two SD rats, divided into 3 groups equally, underwent UUO and received intra-ureteral injection of normal saline, empty retroviral vectors and recombinant retroviral vectors containing antisense- hTIMP-1 respectively, and were sacrificed 3 and 7 days after the operation. The expression of antisense h-TIMP-1 in rat kidney was detected by RT-PCR. Immunohistochemistry was used to detect the expression of rat TIMP-1, alpha-SMA actin (alpha-SMA), and proliferating cell nucleus antigen (PCNA) in tubulointerstitium. The relative area of renal tubulointerstitium was calculated. RESULTS: The expression of antisense-hTIMP-1 mRNA was detected in rat renal tubulointerstitum. The expressions of rat TIMP-1, alpha-SMA and PCNA were lower in the obstructed kidneys of rats treated with antisense-hTIMP-1 than those in the rats in empty vectors group and normal saline group (3 day after: 0.75 +/- 0.07 vs 1.18 +/- 0.12, 1.14 +/- 0.14, P < 0.05; 7 days after: 2.02 +/- 0.16 vs 4.07 +/- 0.57, 4.13 +/- 0.60, P < 0.01). The relative area of renal tubulointerstitium in rats treated with antisense-hTIMP-1 was smaller than those in the empty vetors group and normal saline group (3 days after: 6.0 +/- 0.7 vs 8.2 +/- 1.2, 8.2 +/- 1.3, P < 0.01; 7 days after: 16.2 +/- 1.0 vs 21.2 +/- 2.6, 21.0 +/- 2.4, P < 0.01). More renal tubules were dilated, infiltration of inflammatory cells was seen focally or diffusely, and the relative area of renal tubulointerstitium was smaller in the antisense-hTIMP-1 group than in the empty vectors group and normal saline group. No difference was seen among the degrees of dilation/atrophy of renal tubules and infiltration of inflammatory cells in the three groups. No difference was seen between the relative area of renal tubulointerstitium in empty vectors group and normal saline group. CONCLUSION: Antisense-hTIMP-1 may have beneficial effects on the tubulointerstitial lesion of obstructive nephropathy through inhibiting the expression of TIMP-1 in tubulointerstitum and the proliferation of interstitial and tubular cells.

Animals↗

New sesquiterpenes from Ligularia macrophylla.

From the roots of Ligularia macrophylla, a bisesquiterpene, ligumacrophyllal (1), and an eremophilane sesquiterpene, ligumacrophyllatin (2) were isolated. Their structures were elucidated by 2D-NMR herein. Additionally, seven known compounds (3-9) were afforded from the plant, and compound 3 was found as natural product for the first time.

Asteraceae↗