Biomedical subjects

Yi Xu

Publications and source records attributed to Yi Xu.

At least 19 recordsLinked to original sources

PubMed2026

TNFα-induced endothelial extracellular vesicles regulate astrocyte function: an integrated transcriptomic and proteomic study.

Endothelial cells and astrocytes are critical structural and functional components of the blood-brain barrier. In many neuroinflammatory diseases, endothelial cells are among the first to respond to inflammatory stimuli and release extracellular vesicles (EVs). However, whether inflammatory stimulation alters EV RNA cargo and subsequently regulates astrocyte function remains unclear. In this study, we performed integrated RNA sequencing and proteomic analyses to investigate the effects of TNFα-stimulated endothelial EVs on astrocytes. RNA profiling revealed significant alterations in EV cargo after TNFα stimulation, including 867 upregulated and 577 downregulated mRNAs, 317 upregulated and 15 downregulated lncRNAs, and 88 upregulated and 62 downregulated miRNAs. The results of functional enrichment analysis suggested that altered EV RNAs may primarily promote inflammatory responses, cell migration, and RNA splicing in astrocytes while reducing their regulatory effects on neuronal projection and calcium homeostasis. Further integrative analysis of EV RNAs and astrocytic proteomics revealed key overlapping targets, including upregulated expression of ICAM1, SOD2, TFPI2, and TNFAIP8, whereas NFKBIA expression was consistently decreased. Network analysis revealed NF-κB as the central regulatory node. Reduced levels of EV-derived NFKBIA mRNA were associated with decreased IκBα protein levels in astrocytes, which promoted NF-κB activation and inflammatory cytokine release. Finally, overexpression of IκBα in astrocytes significantly attenuated TNFα EV-induced IL-1β and IL-6 secretion. Collectively, these findings demonstrate that TNFα-stimulated endothelial EVs coordinately regulate astrocyte function through mRNA, lncRNA, and miRNA cargo and that the IκBα/NF-κB axis may be a key mechanism underlying endothelial EV-mediated inflammatory disruption of the blood-brain barrier.

Astrocytes↗

PubMed2026

Systematic analysis of the type VII secretion system in Streptococcus gallolyticus subsp. gallolyticus reveals genomic diversity and functional associations.

Streptococcus gallolyticus subsp. gallolyticus (Sgg) is an opportunistic pathobiont associated with bacteremia, infective endocarditis, and colorectal cancer. However, the genomic diversity of this subspecies and the distribution of key virulence determinants, particularly the type VII secretion system (T7SS), remain poorly characterized. Here, we performed genomic analyses of 76 Sgg strains from diverse geographic and host origins. Core- and pan-genome analyses, multi locus sequence typing, and phylogenetic reconstruction revealed dominant sequence types (STs) that correlate with geographic origin or source of isolation. Furthermore, systematic characterization of the T7SS locus identified five new T7SS subtypes and demonstrated a strong association between T7SS subtype and ST. We further expanded the known repertoire of T7SS LXG domain-containing polymorphic toxins (LXG toxins) in Sgg substantially through genome-wide searches. Distinct distribution patterns were observed for the LXG toxins across the strains. Lastly, our data indicated that T7SS subtype was significantly associated with biofilm formation capacity of Sgg strains. Together, these findings advance our understanding of Sgg genomic diversity, reveal substantial lineage-associated variation in T7SS architecture and effector repertoires, and suggest a previously unrecognized connection between T7SS and biofilm formation in Sgg.

LXG toxins↗

PubMed2006

Induction of matrix metalloproteinase-2 enhances systemic arterial contraction after hypoxia.

This study was carried out to determine the role of increased vascular matrix metalloproteinase-2 (MMP-2) expression in the changes in systemic arterial contraction after prolonged hypoxia. Rats and mice were exposed to hypoxia (10% and 8% O(2), respectively) or normoxia (21% O(2)) for 16 h, 48 h, or 7 days. Aortae and mesenteric arteries were either mounted in organ bath myographs or frozen in liquid nitrogen. MMP-2 inhibition with cyclic CTTHWGFTLC (CTT) reduced contraction to phenylephrine (PE) in aortae and mesenteric arteries from rats exposed to hypoxia for 7 days but not in vessels from normoxic rats. Similarly, CTT reduced contraction to Big endothelin-1 (Big ET-1) in aortae from rats exposed to hypoxia for 7 days. Responses to PE were reduced in hypoxic MMP-2(-/-) mice compared with MMP-2(+/+) mice. Increased contraction to Big ET-1 after hypoxia was observed in MMP-2(+/+) mice but not in MMP-2(-/-) mice. Rat aortic MMP-2 and membrane type 1 (MT1)-MMP protein levels and MMP activity were increased after 7 days of hypoxia. Rat aortic MMP-2 and MT1-MMP mRNA levels were increased in the deep medial vascular smooth muscle. We conclude that hypoxic induction of MMP-2 expression potentiates contraction in systemic conduit and resistance arteries. This may preserve the capacity to regulate the systemic circulation in the transition between the alterations in vascular tone and structural remodeling that occurs during prolonged hypoxic epochs.

Animals↗

PubMed2006

Low-calcium serum-free defined medium selects for growth of normal prostatic epithelial stem cells.

Stage-specific differentiation markers were used to evaluate the cellular composition and the origin of nonimmortalized (PrEC) and immortalized (PZ-HPV7, CA-HPV10, RWPE-1, and 957E/hTERT) human prostate cell lines. These studies documented that immortalized and nonimmortalized prostate epithelial cells established and maintained in low (i.e., <300 micromol/L) Ca(2+) serum-free defined (SFD) medium were all derived from normal nonmalignant prostate tissues and contain CD133(+)/ABCG2(+)/alpha(2)beta(1)(Hi)/p63(-)/PSCA(-)/AR(-)/PSA(-) prostate stem cells. In these cultures, prostate stem cells are able to self-renew and generate two distinct cell lineages: the minor proliferatively quiescent neuroendocrine lineage and the major transit-amplifying cell lineage. Subsequently, CD133(-)/ABCG2(-)/alpha(2)beta(1)(Hi)/p63(+)/PSCA(-)/AR(-)/PSA(-) transit-amplifying cells proliferate frequently and eventually mature into proliferatively quiescent CD133(-)/ABCG2(-)/alpha(2)beta(1)(Lo)/p63(-)/PSCA(+)/AR(-)/PSA(-) intermediate cells. Such proliferatively quiescent intermediate cells, however, do not complete their full maturation into CD133(-)/ABCG2(-)/alpha(2)beta(1)(Lo)/p63(-)/PSCA(-)/AR(+)/PSA(+) luminal-secretory cells in low Ca(2+) SFD medium. Addition of universal type I IFN and synthetic androgen (R1881) to culture medium resulted in up-regulation of androgen receptor protein expression. However, it failed to induce full differentiation of intermediate cells into AR(+)/PSA(+) luminal-secretory cells. Our results indicate that such inability of prostate epithelial cells to complete their differentiation is due to continuous expression of Notch-1 receptor and its downstream effector, Hey-1 protein, which actively suppresses differentiation via its ability to transcriptionally repress a series of genes, including the GATA family of transcription factors.

Calcium↗

PubMed2006

Tumor necrosis factor-alpha and vascular angiotensin II in estrogen-deficient rats.

Alterations in the vascular angiotensin II system may play a role in the pathophysiology of vascular disease after menopause. In previous studies we have shown that an increase in tumor necrosis factor (TNF)-alpha levels in aging rats because of estrogen deficiency may result in vascular dysfunction. In this study we investigated the effect of TNF-alpha inhibition in angiotensin II modulation of vascular function in aging female animals. Female rats approaching reproductive senescence (12 to 15 months old) were ovariectomized and treated with placebo, estrogen, or a selective TNF-alpha inhibitor (etanercept) for 4 weeks. Expression of angiotensin II in mesenteric arteries was evaluated by immunofluorescence, and the expression of angiotensin-converting enzyme and angiotensin type I receptor (AT(1)R) was investigated by Western immunoblot. Vascular function was assessed in mesenteric arteries using the myograph system, and the role of endogenous angiotensin II on adrenergic vasoconstriction was evaluated in vitro by selective AT(1)R blockade (Candesartan; 10 micromol/L). Our data demonstrate that estrogen-depleted rats have higher serum levels of TNF-alpha and greater sensitivity to phenylephrine vasoconstriction compared with estrogen-replaced animals, which was attenuated by AT(1)R blockade. In vivo TNF-alpha inhibition or estrogen replacement reduced phenylephrine constriction of mesenteric arteries and decreased the modulation of this vasoconstriction by candesartan. These functional changes were accompanied by a reduction in the vascular expression of angiotensin II, angiotensin-converting enzyme, and AT(1)R. These observations indicate that upregulation of TNF-alpha during estrogen deficiency may contribute to enhance vascular constriction by altering the vascular angiotensin II system.

Angiotensin II↗

PubMed2006

Matrix metalloproteinase-2 contributes to tumor necrosis factor alpha induced apoptosis in cultured rat cardiac myocytes.

Tumor necrosis factor alpha (TNFalpha) is associated with a higher risk of cardiovascular disease. Matrix metalloproteinase-2 (MMP-2) has been implicated in the pathophysiology of ischemic heart disease. However, the role of interactions between MMP-2 and TNFalpha, associated with cardiac apoptosis, is unknown. We hypothesized that MMP-2 will contribute to TNFalpha-induced myocardial apoptosis. After treatment with TNFalpha (1-20 ng/ml) for 24 h, or with TNFalpha (10 ng/ml) for 0, 6, 12, 24, or 48 h, MMP-2 activity, percent of TUNEL-positive myocytes, and DNA fragmentation dose, and time-dependently increased compared to control. However, TNFalpha blockade (neutralizing antibodies against human TNFalpha, 25 microg/ml) significantly reduced the activity of MMP-2 and markers of apoptosis induced by TNFalpha. Interestingly, MMP-2 antibody (30 microg/ml), or the MMP-2 inhibitors Doxycycline (Dox, 1-50 micromol/l) or GM6001 (GM, 10 micromol/l), prior to TNFalpha insult, decreased myocardial MMP-2 activity and reduced the percent of TUNEL-positive myocytes and DNA fragmentation. Moreover, MMP-2 inhibition reduced Bax expression and caspase3 activity, as well as increasing Bcl2 expression. MMP-2 inhibition was associated with decreased cardiac MMP-2 activity and decreased myocardial apoptosis induced by TNFalpha. These results suggest that MMP-2 contributes to TNFalpha-induced apoptosis in cultured rat cardiac myocytes.

Animals↗

PubMed2006

Pharmacologic basis for the enhanced efficacy of dutasteride against prostatic cancers.

PURPOSE: Prostatic dihydrotestosterone (DHT) concentration is regulated by precursors from systemic circulation and prostatic enzymes of androgen metabolism, particularly 5alpha-reductases (i.e., SRD5A1 and SRD5A2). Therefore, the levels of expression SRD5A1 and SRD5A2 and the antiprostatic cancer growth response to finasteride, a selective SRD5A2 inhibitor, versus the dual SRD5A1 and SRD5A2 inhibitor, dutasteride, were compared. EXPERIMENTAL DESIGN: Real-time PCR and enzymatic assays were used to determine the levels of SRD5A1 and SRD5A2 in normal versus malignant rat and human prostatic tissues. Rats bearing the Dunning R-3327H rat prostate cancer and nude mice bearing LNCaP or PC-3 human prostate cancer xenografts were used as model systems. Tissue levels of testosterone and DHT were determined using liquid chromatography-mass spectrometry. RESULTS: Prostate cancer cells express undetectable to low levels of SRD5A2 but elevated levels of SRD5A1 activity compared with nonmalignant prostatic tissue. Daily oral treatment of rats with the SRD5A2 selective inhibitor, finasteride, reduces prostate weight and DHT content but did not inhibit R-3327H rat prostate cancer growth or DHT content in intact (i.e., noncastrated) male rats. In contrast, daily oral treatment with even a low 1 mg/kg/d dose of the dual SRD5A1 and SRD5A2 inhibitor, dutasteride, reduces both normal prostate and H tumor DHT content and weight in intact rats while elevating tissue testosterone. Daily oral treatment with finasteride significantly (P < 0.05) inhibits growth of LNCaP human prostate cancer xenografts in intact male nude mice, but this inhibition is not as great as that by equimolar oral dosing with dutasteride. This anticancer efficacy is not equivalent, however, to that produced by castration. Only combination of dutasteride and castration produces a greater tumor inhibition (P < 0.05) than castration monotherapy against androgen-responsive LNCaP cancers. In contrast, no response was induced by dutasteride in nude mice bearing androgen-independent PC-3 human prostatic cancer xenografts. CONCLUSIONS: These results document that testosterone is not as potent as DHT but does stimulate prostate cancer growth, thus combining castration with dutasteride enhances therapeutic efficacy.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed2006

Exteroceptive suppression of temporalis muscle activity in subjects with high and low aggression traits.

STUDY AIM: There is evidence that the second exteroceptive suppression period of temporalis muscle activity (ES2) is modulated by the 5-HT neuronal activity in the brainstem, and the aggression trait is also connected with the cerebral 5-HT neuronal innervation. We therefore studied the temporalis ES2 in subjects with high and low aggression traits. METHODS: Sixty-five subjects with either low or high aggression trends, judged by clinical interview, answered the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ), the Zuckerman Sensation Seeking Scales (SSS) and the Plutchik-van Praag Depression Inventory (PVP). These also underwent a temporalis ES2 test procedure. Twenty-two subjects with a high ZKPQ aggression trait score and 27 with a low score were selected for data analysis. RESULTS: On average, the high aggression group displayed significantly reduced temporalis ES2 duration, elevated ZKPQ Impulsive Sensation Seeking, Neuroticism-Anxiety and Aggression-Hostility, and PVP scores. The personality traits were not related with either latency or duration of temporalis ES2 in any group. The PVP score, however, was negatively correlated with ES2 duration in all 49 subjects. CONCLUSIONS: This study demonstrates neurophysiologic signs of brainstem dysfunction in subjects with high aggression traits.

Adult↗

PubMed2006

Learning phonetic categories by tracking movements.

We explore in this study how infants may derive phonetic categories from adult input that are highly variable. Neural networks in the form of self-organizing maps (SOMs; ) were used to simulate unsupervised learning of Mandarin tones. In Simulation 1, we trained the SOMs with syllable-sized continuous F(0) contours, produced by multiple speakers in connected speech, and with the corresponding velocity profiles (D1). No attempt was made to reduce the large amount of variability in the input or to add to the input any abstract features such as height and slope of the F(0) contours. In the testing phase, reasonably high categorization rate was achieved with F(0) profiles, but D1 profiles yielded almost perfect categorization of the four tones. Close inspection of the learned prototypical D1 profile clusters revealed that they had effectively eliminated surface variability and directly reflected articulatory movements toward the underlying targets of the four tones as proposed by . Additional simulations indicated that a further learning step was possible through which D1 prototypes with one-to-one correspondence to the tones were derived from the prototype clusters learned in Simulation 1. Implications of these findings for theories of language acquisition, speech perception and speech production are discussed.

Humans↗

PubMed2006

Hypoxia or nutrient restriction during pregnancy in rats leads to progressive cardiac remodeling and impairs postischemic recovery in adult male offspring.

Intrauterine growth restriction (IUGR) increases the risk of developing adult-onset cardiovascular disease. We hypothesized that IUGR resulting from maternal hypoxia or nutrient restriction during late gestation will produce cardiac remodeling and impair cardiac recovery after ischemia/reperfusion (I/R) in adult male offspring aged 4 or 7 mo. Sprague-Dawley rats were randomized on day 15 of pregnancy to hypoxia (IUGR-H, 12% oxygen), nutrient restriction (IUGR-NR, 40% of control diet) or control (room air) groups. In 4-mo IUGR-H offspring, left ventricular wt/body wt ratio (LVW/BW) and right ventricular wt/BW ratio (RVW/BW) increased, in association with increased collagen I and III expression, beta and alpha myosin heavy chain (beta/alphaMHC) ratio, and decreased matrix metalloproteinase (MMP)-2 activity compared to the other groups. Left ventricular end diastolic pressure was higher in perfused hearts. Functional recovery after I/R was remarkably reduced (10+/-3%) compared to both control (39+/-5%) and IUGR-NR rats (32+/-4%). At 7 mo, both IUGR-H and IUGR-NR offspring had increased LVW/BW, collagen I and III, beta/alpha MHC ratio, and decreased cardiac recovery and MMP-2 activity compared to control. These findings suggest that hypoxia or undernutrition during development leads to pathological cardiac remodeling, diastolic dysfunction, and increased sensitivity to ischemic injury during adult life.

Animals↗

PubMed2006

Fecal Adnab-9 binding as a risk marker for colorectal neoplasia.

Adnab-9 binding in colonic tissue and effluent has been associated with an increased risk for colorectal neoplasia. We investigated if fecal binding by Adnab-9 may be used as a marker for colorectal neoplasia. A fecal-Adnab-9 ELISA was performed on samples of 249 patients and colonoscopic pathology results correlated. Fecal Adnab-9 binding was seen in 63% of patients with colorectal neoplasia (59% with colorectal cancer and 83% with adenoma), 33% with inflammatory bowel disease, 0% with hyperplastic polyps and 10% of controls. We conclude that fecal Adnab-9 binding is a promising risk marker for colorectal neoplasia.

Adenoma↗

PubMed2006

Assessment of prokaryotic collagen-like sequences derived from streptococcal Scl1 and Scl2 proteins as a source of recombinant GXY polymers.

Collagen triple helix, composed of the repeating Gly-Xaa-Yaa (GXY) sequence, is a structural element found in all multicellular animals and also in some prokaryotes. Long GXY polymers are highly regarded components used in food, cosmetic, biomedical, and pharmaceutical industries. In this study, we explore a new concept for the production of recombinant GXY polymers which are based on the sequence of "prokaryotic collagens", the streptococcal collagen-like proteins Scl1 and Scl2. Analysis of 50 Scl variants identified the amino acid distribution and GXY-repeat usage that are involved in the stabilization of the triple helix in Scls. Using circular dichroism spectroscopy and electron microscopy, we show that significantly different recombinant rScl polypeptides form stable, unhydroxylated homotrimeric triple helices that can be produced both intra- and extracellularly in the Escherichia coli. These rScl constructs containing 20 to 129 GXY repeats had mid-point melting temperatures between 32 and 39 degrees C. Altogether, Scl-derived collagens, which are different from the mammalian collagens, can form stable triple helices under physiological conditions and can be used for the production of recombinant GXY polymers with a wide variety of potential applications.

Bacterial Proteins↗

PubMed2006

Forward-illumination light-extinction technique for soot measurement.

A forward-illumination light-extinction (FILE) soot volume fraction measurement technique was developed and tested. By using a camera and a point light source in front of the flame and a diffuser behind the flame, with this technique one can achieve a two-dimensional soot concentration measurement with only one window when one is studying confined combustion. The line-of-sight quantitative soot volume fraction is obtained by calculation of the reflected light intensity with or without the presence of soot cloud. Verification of this technique was accomplished by measurement of an axisymmetric ethylene diffusion flame. The field distribution obtained by Abel inversion is presented and matched well with previous point measurements. The FILE technique has high time resolution when a high-speed camera and a copper vapor laser are adopted. All these advantages of FILE make it suitable for line-of-sight integrated, two-dimensional soot distribution of transient combustion, e.g., in the case of in-cylinder Diesel combustion.

Journal Article↗

PubMed2006

Production of weak elements in speech -- evidence from F(0) patterns of neutral tone in Standard Chinese.

Many weak elements in speech, such as schwa in English and neutral tone in Standard Chinese, are commonly assumed to be unspecified or underspecified phonologically. The surface phonetic values of these elements are assumed to derive from interpolation between the adjacent phonologically specified elements or from the spreading of the contextual phonological features. In the present study, we re-evaluate this view by investigating detailed F(0) contours of neutral-tone syllables in Standard Chinese, which are widely accepted as toneless underlyingly. We recorded sentences containing 0-3 consecutive neutral-tone syllables at two speaking rates with two focus conditions. Results of the experiment indicate that neutral-tone syllables do have a target that is independent of the surrounding tones, which is likely to be static and mid. Furthermore, the neutral tone is found to be different from the full lexical tones in the manner with which the underlying tonal target is implemented: it is slow and ineffective both in overcoming the influence of the preceding full lexical tone and in approaching its own target. Applying the recently proposed pitch target approximation model, we conclude that the neutral tone differs from the other lexical tones in Standard Chinese not only in terms of its mid target, but also in terms of the weak articulatory strength with which this target is implemented. Finally, we suggest that this new understanding is potentially applicable to other weak elements in speech.

Adult↗

PubMed2006

Increased expression of mitotic checkpoint genes in breast cancer cells with chromosomal instability.

PURPOSE: Most breast cancers have chromosomal instability that seems related to defective mitotic spindle checkpoints. Because the molecular basis of this defect is unknown, we evaluated breast cancer cell lines and tissues for possible defects involving the major mitotic checkpoint genes responsible for maintaining chromosomal stability. EXPERIMENTAL DESIGN: We analyzed sequences and expression levels (RNA and protein) of eight major spindle checkpoint genes (MAD1L1, MAD2L1, MAD2L2, BUB1, BUB1B, BUB3, CDC20, and TTK) in a panel of 12 breast cancer cell lines, most with established genetic instability and defective spindle damage checkpoint response. mRNA levels of these genes were also measured in primary tumor samples, and immunohistochemical staining was used to evaluate BUB1B protein levels in a panel of 270 additional cases of breast cancer. RESULTS: No functionally significant sequence variations were found for any of the eight genes in the breast cancer cell lines with chromosomal instability. More surprisingly, the mRNA and protein levels for these checkpoint genes are significantly higher in the genetically unstable breast cancer cell lines and in high-grade primary breast cancer tissues than in the stable (and checkpoint proficient) MCF-10A and normal mammary epithelial cells, or in normal breast tissues. In fact, overexpression of the BUB1B protein is a marker that recognizes nearly 80% of breast cancers in paraffin-embedded tissues. CONCLUSIONS: Defective mitotic spindle checkpoints in breast cancer are most likely not caused by low expression or mutations of these eight checkpoint genes. High levels of these particular transcripts could represent a cellular compensation for defects in other molecular components of the mitotic spindle damage checkpoint, and increased expression of these genes might be markers of breast cancers with chromosomal instability.

Adenocarcinoma, Mucinous↗

PubMed2006

Increase in bFGF-responsive neural progenitor population following contusion injury of the adult rodent spinal cord.

The number of neural progenitor cells, especially nestin+ cells or BrdU-uptake cells is sparse in the normal adult rodent spinal cord. However, in the present study, we show that after spinal cord injury (SCI), many ordinarily quiescent cells were activated to become nestin+ and undergo mitosis (BrdU+) in the ependymal layer as well as in the parenchyma of the spinal cord. Nestin+ cells and BrdU+ cells were in most cases immunohistochemically GFAP+, some of which displayed radial glial cell morphology and partly participated in the border formation of the lesion. The culturing of injured rat spinal cord tissues generated more neurospheres earlier than did the culturing of intact tissues, and these neurosphere cells were multipotent and bFGF-responsive. Immunohistochemical analysis showed that there existed many bFGF+ cells after SCI, the number of which were almost 15 times greater than that in an intact spinal cord. Increased bFGF production after SCI might activate quiescent progenitor cells, and thus initiate their cell proliferation. Finally, SCI to the nestin-promoter green fluorescent protein (GFP) transgenic mice showed broad proliferation of progenitor cells that were induced in the injured spinal cord. The culturing of injured spinal cord tissues from these transgenic mice provides direct evidence that neurospheres can be generated by SCI-activated nestin+ cells. Thus, the activation of bFGF-responsive progenitor cells and the concomitant increase in the population of bFGF+ cells following SCI might be beneficial for spinal cord repair if these progenitor cells are properly manipulated.

Animals↗

PubMed2006

Estrogen improves cardiac recovery after ischemia/reperfusion by decreasing tumor necrosis factor-alpha.

BACKGROUND: Estrogen has cardioprotective effects on ischemia/reperfusion (I/R). Tumor necrosis factor alpha (TNFalpha) is an inflammatory cytokine with depressor effects on myocardial function and has been suggested to mediate I/R injury. Whether cardiac TNFalpha levels are influenced by estrogen status is unknown. We investigated the effect of estrogen on TNFalpha levels and TNFalpha receptors in the ischemic heart and its role in estrogen modulation of I/R injury. METHODS: Hearts were isolated from ovariectomized Sprague-Dawley female rats that were treated with either estrogen or placebo for 4 weeks. Working heart preparations were subjected to global, no-flow ischemia (25 min) followed by reperfusion (40 min). RESULTS: I/R increased TNFalpha levels in coronary effluent and in the left ventricle (LV) of estrogen-deficient rats, which were decreased by estrogen replacement. Moreover, estrogen improved functional recovery (55.0+/-5.0% vs. 22.0+/-7.0%, P<0.05), decreased LV apoptosis, and reduced myocardial necrosis. To further evaluate the role of TNFalpha in I/R injury, a selective TNFalpha inhibitor (etanercept) was used in vitro before the ischemic insult. TNFalpha inhibition improved functional recovery (39+/-4.4% vs. 22.0+/-7.0%, P<0.05) and reduced apoptosis and myocardial necrosis in estrogen-deficient animals but did not have a summative protective effect in the hearts of estrogen-replaced animals. CONCLUSIONS: These data indicate that estrogen modulates cardiac expression of TNFalpha and TNFalpha receptors. Moreover, the cardioprotective effects of estrogen are in part mediated by regulation of TNFalpha levels in the ischemic heart.

Animals↗

PubMed2006

Expression and significance of nerve growth factor receptor p75 in rats' cathartic colonic wall.

OBJECTIVE: To investigate the expression of nerve growth factor receptor p75 in a normal and cathartic colon and its significance in the formation of the cathartic colon in rats. METHODS: Sixty Sprague-Dawley rats were equally divided into normal control group, rhubarb group and phenolphthalein group. A model of the cathartic colon was constructed by gastric infusion with rhubarb or phenolphthalein in rats. The first dose of rhubarb and phenolphthalein was both 200 mg/kg/d and was increased by 200 mg/kg/d with each passing day. The last dose of rhubarb and phenolphthalein was 3200 mg/kg/d and 4200 mg/kg/d, respectively. The transit function of colon was measured by the Chinese ink expulsion test; the p75 in colon wall was determined by the immunohistochemical method. RESULTS: The transit speed was much slower in the cathartic colon group than that in the control group. The imprinted Chinese ink length and the ratio of imprinted length/total colon length in the rhubarb-induced cathartic colon was significantly shorter than that of the control group (77.38 +/- 8.42 vs 94.25 +/- 7.07 cm, P < 0.01). Those in the phenolphthalein-induced group (83.38 +/- 9.75 cm) were also significantly shorter than those of the control group but to a lesser degree (P < 0.05). p75 was abundantly expressed in the submucosal nerve plexus and weakly expressed in the myenteric plexus. The expression of p75 was much higher in the rhubarb-induced group. The expression was strongly positive in the submucosal nerve plexus, significantly higher than that in the controls (P < 0.01). In the myenteric plexus, p75 was also highly expressed (P < 0.05). In the case of the phenolphthalein-induced group, the expression of p75 was positive in the submucosal nerve plexus but was positive in the myenteric plexus of three rats only. The remaining rats were negative or weakly positive. This was not significantly different from that of the control group. CONCLUSIONS: The abnormal expression of p75 in cathartic colon probably has some effect on the degeneration or apoptosis of neuronal cells in the enteric nerve plexus, with a subsequent pathological change of the enteric nervous system, and thus leads to abnormalities in colonic dynamics. The kind of lesion is probably associated with long-term use of irritative cathartics.

Animals↗