[Examining the pathogenesis and therapeutic strategy of keloids from the perspective of systemic inflammation].

Keloid is a disease that is difficult to cure and has a high recurrence rate. In the past, research on keloid focused on keloid cells themselves and the therapeutic strategy limited to local treatment, whereas the role of systemic factors in the process of occurrence and development of disease was usually neglected. Based on the literature reports and clinical evidence, we propose that the pro-inflammatory constitution of keloid patients can serve as a systemic factor to interact with local factors such as skin lesion, and thus leads to the initiation and development of keloid. The classical theory about close relationship between visceral malfunctions and skin diseases described in traditional Chinese medicine has provided supporting evidence. Therefore, we suggest that systemic anti-inflammatory therapy should be included in the design of future keloid therapeutic strategies and be verified by the clinical trials. Additionally, the therapeutic strategies of traditional Chinese medicine including anti-dampness, detoxing and heating removing can also be employed as a part of systemic treatment of keloids.

Effects of fasting and feeding on the fast-start swimming performance of southern catfish Silurus meridionalis.

This study investigated the effects of fasting and feeding on the fast-start escape swimming performance of juvenile southern catfish Silurus meridionalis, a sit-and-wait forager that encounters extreme fasting and famine frequently during its lifespan. Ten to 30 days of fasting resulted in no significant change in most of the variables measured in the fast-start response except a 20-30% decrease in the escape distance during the first 120 ms (D120ms ) relative to the control group (48 h after feeding). The ratio of the single-bend (SB) response (lower energetic expenditure) to the double-bend (DB) response increased significantly from 0% in the control group to 75 and 82·5% in the 20 and 30 day fasting groups, respectively. Satiated feeding (25% of body mass) resulted in a significantly lower (36·6%) maximum linear velocity (Vmax ) and a significantly lower (43·3%) D120ms than in non-fed fish (control group, 48 h after feeding). Half-satiated feeding (12·5% of body mass), however, showed no significant effects on any of the measured variables of the fast-start response relative to control fish. It is suggested that the increase in the ratio of SB:DB responses with fasting in S. meridionalis may reflect a trade-off between energy conservation and maintaining high Vmax , while variables of fast-start performance were more sensitive to feeding than fasting might be an adaptive strategy to their foraging mode and food availability in their habitat.

An interspecific comparison between morphology and swimming performance in cyprinids.

Flow regimes are believed to be of major evolutionary significance in fish. The flow regimes inhabited by cyprinids vary extensively from still flow regimes to riptide flow regimes. To test (i) whether flow-driven swimming performance and relevant morphological differentiation are present among fish species and (ii) whether evolutionary shifts between high-flow and low-flow habitats in cyprinids are associated with evolutionary trade-offs in locomotor performance, we obtained data on both steady and unsteady swimming performance and external body shape for 19 species of cyprinids that typically occur in different flow regimes (still, intermediate and riptide). We also measured the routine energy expenditure (RMR) and maximum metabolic rate (MMR) and calculated the optimal swimming speed. Our results showed that fish species from riptide groups tend to have a higher critical swimming speed (Ucrit ), maximum linear velocity (Vmax ) and fineness ratio (FR) than fish from the other two groups. However, there was no correlation between the reconstructed changes in the steady and unsteady swimming performance of the 19 species. According to the phylogenetically independent contrast (PIC) method, the Ucrit was actively correlated with the MMR. These results indicated that selection will favour both higher steady and unsteady swimming performance and a more streamlined body shape in environments with high water velocities. The results suggested that steady swimming performance was more sensitive to the flow regime and that for this reason, changes in body shape resulted more from selective pressure on steady swimming performance than on unsteady swimming performance. No evolutionary trade-off was observed between steady and unsteady swimming performance, although Ucrit and MMR were found to have coevolved. However, a further analysis within each typically occurring habitat group suggested that the trade-off that may exist between steady and unsteady swimming performance may be concealed by the effect of habitat.

Gill remodeling in crucian carp during sustained exercise and the effect on subsequent swimming performance.

Gill remodeling can be extensive in crucian carp, where up to a 7.5-fold increase in gill surface area has been observed during exposure to hypoxia through a reduction in the interlamellar cell mass (ILCM) and increased lamellar protrusion that has been hypothesized to be signaled by the need to maximize oxygen uptake under a given condition. Sustained aerobic exercise may have the greatest influence on oxygen demand in fish; however, its effect on gill remodeling in crucian carp has not been investigated. The specific objectives of this study were to determine (i) whether sustained aerobic exercise induces gill remodeling in the crucian carp, (ii) whether gill remodeling following sustained exercise affects the maximum critical swimming speed (U(crit)) and maximal oxygen consumption rate ([Formula: see text]), and (iii) whether gill remodeling following sustained exercise is associated with trade-offs related to ionoregulation. We measured [Formula: see text] in crucian carp at each step during an initial U(crit) test (U(crit1)), forced them to swim at 70% of U(crit) for 40 h, and then conducted a second U(crit) test (U(crit2)). From rest to U(crit1) (7-8 h), we observed a significant increase in protruding lamella height and area of the gills and a reduction in ILCM height and volume, likely associated with partial shedding of the ILCM, indicating that gill remodeling during exercise is rapid. Further changes were observed between U(crit1) and U(crit2), with statistically significant increases in protruding lamellar height, basal length and area, and a statistically significant reduction in protruding lamellar thickness and ILCM height and volume. Interestingly, there was no significant difference between U(crit1) and U(crit2) values, nor in maximal [Formula: see text] measured at U(crit1) and U(crit2). Furthermore, there was no significant difference in plasma osmolarity, [Na(+)], or [Cl(-)] in fish at rest, following U(crit1) or U(crit2). Thus, while these data support the hypothesis that the need to maximize oxygen uptake is an important signal for gill remodeling, which can occur quite rapidly (within 7 h at 15°C), the physiological implications of remodeling during exercise are less clear.

Effect of meal size on postprandial metabolic response in southern catfish (Silurus meridionalis).

Effect of relative meal size (0.6-24%) on specific dynamic action (SDA) was assessed in southern catfish juveniles (48.2+/-3.2 g) at 27.5 degrees C. Cutlets of freshly killed loach species were used as test diet. Energy expended during SDA was linearly correlated with relative meal size (r=0.949, p<0.001, N=47). There was no significant difference in SDA coefficient (energy expended on SDA quantified as a percentage of the energy content of the meal) among different relative meal size groups. Factorial metabolic scope increased from 1.47 to 4.08 when the relative meal size increased from 0.6% to 24%. The peak V O2 increased with meal size, but levelled when relative meal size gradually increased to the maximum. SDA duration showed a S-type (slow-fast-slow) increase course with increased meal size. The results of this study suggest that the high postprandial factorial metabolic scope and a trapezoid SDA curve might be the adaptation strategy of warm water sit-and-wait fish under the natural selection of evolution related to long-term food resources.

Cloning of the nucleic acid-binding domain of the rat HnRNP C-type protein.

A cDNA encoding the nucleic acid-binding domain of the hnRNP C-type protein has been cloned by DNA-affinity screening of pituitary-derived expression libraries. An analysis revealed sequence identity with the human C-type cDNA and demonstrated the presence of a peptide sequence contained within the single-stranded DNA-binding protein, UP2, which was absent from the human cDNA. Structural analysis of the protein encoded by the rat cDNA demonstrated a net charge of +15 with 14.56% and 6.33% lysines and arginines, respectively, and an amino acid sequence that is consistent with an extensive helix-loop-helix-turn-helix structure.

DNA recognition element required for PUF-I mediated cell-type-specific transcription of the rat prolactin gene.

The cell-type-specific transcription of the prolactin gene in vitro is mediated through the interaction of prolactin upstream factor I (PUF-I) with a 28 basepair region of the gene promoter (-63 to -36) which contains an 18 bp A+T-rich imperfect palindrome (-63 to -46). Base substitutions were introduced into 16 of the 18 palindromic residues by targeted saturation mutagenesis. The GH3 binding and in vitro transcription assays of the mutated promoters showed that base substitutions within the 5'-ATATTCA-3' sequence located at -52 to -46 were detrimental to PUF-I binding and its cell-type-specific transcriptional enhancement activity. Transcription assays of the mutated promoters performed with several nonpituitary-derived extracts demonstrated that a distal TATA box located from -59 to -53 promotes initiation at -27. Thus, the cell-type-specific cis-acting element required by PUF-I for DNA recognition is immediately adjacent to a general TATA sequence. Base substitutions that decreased +1 transcription and PUF-I binding concomitantly increased -27 initiation of RNA in vitro. We suggest that PUF-I binding in pituitary cells potentiates +1 transcription and represses alternative TATA box activity for initiation events occurring at -27. This is the first known report of a eukaryotic DNA binding protein that has both an activator and repressor activity for a single transcription unit.

Prolactin upstream factor I mediates cell-specific transcription.

DNA sequence-specific chromatography was used to purify prolactin upstream factor I (PUF-I) approximately 10,000- to 20,000-fold from rat GH3 cells. The purified transcription factor reconstituted enhanced pituitary-specific prolactin RNA synthesis in nonpituitary in vitro transcription assays. In vitro mutagenesis demonstrated that the capacity to stimulate prolactin gene transcription was directly correlated with PUF-I binding to an A+T-rich region located from -63 to -36 in the prolactin 5'-flanking DNA. We propose that PUF-I is a critical modulator of transcriptional activity in pituitary cells and has a central role in the stimulation of prolactin gene transcription in the mammalian pituitary lactotroph.

Reconstitution of cell-type-specific transcription of the rat prolactin gene in vitro.

We present evidence for the existence of prolactin upstream factor 1 (PUF-1) in rat pituitary-derived cells and demonstrate its interaction with a symmetrical DNA element located in the 5' flanking region of the gene. An in vitro expression system developed from pituitary-derived GH3 cells was used to determine that 420 base pairs (bp) of 5' flanking DNA was sufficient for cell-specific, accurate, and efficient RNA polymerase II transcription of the rat prolactin gene. Reconstitution of in vitro transcription with pituitary and nonpituitary nuclear extracts suggested that the presence of GH3 cell-specific factors mediated the activation of prolactin gene expression. We also demonstrated that a functionally stable transcription complex assembled on the prolactin promoter. Using DNase I protection procedures, we have identified the DNA-protein binding area in the prolactin 5' flanking region. GH3 nuclear extracts contain a cell-specific protein (PUF-I) that binds to a 28-bp region (-63 to -36)which contains an 18-bp imperfect palindrome (-63 to -46). The role that the interaction between PUF-I and the imperfect palindrome plays in in vitro pituitary-specific prolactin gene expression is discussed.

Progesterone and oestradiol receptor concentration and translocation in uterine tissue of rabbits treated with indomethacin.

The purpose of this study was to determine whether endogenous prostaglandins are involved in the regulation of sexual steroid receptor concentration and cytosol to nucleus translocation in the rabbit uterus. The animals were injected s.c. with indomethacin (10 mg/kg) twice daily on days 5 and 6 and on the morning of day 7 of pregnancy or pseudopregnancy and killed 2 h after the last injection. The indomethacin treatment did not change progesterone and oestradiol serum concentrations compared with animals injected with vehicle only. No differences were observed either in progesterone receptor or oestradiol (pregnant animals only) receptor concentration and intracellular distribution in endometria of indomethacin-treated or control animals. In an extended experiment indomethacin given to oestrogen-pretreated ovariectomized rabbits did not inhibit the nuclear progesterone receptor accumulation induced by a single progesterone injection. These results suggest that there is no direct relationship between prostaglandins and sexual steroid receptors in the rabbit uterus.

Prostaglandin translocation from the lumen of the rabbit uterus in vitro in relation to day of pregnancy or pseudopregnancy.

Transport of 3H-labeled prostaglandins (PGs) E2 and F2 alpha from the uterine lumen across the uterine wall has been studied in rabbit uteri in vitro in incubations lasting up to 180 min, in relation to sexual state of the rabbit, incubation temperature, intraluminal PG concentration, addition of metabolic inhibitors and time of incubation. PG accumulation by the tissue increased rapidly up to 30 min and then remained relatively constant. By 30 min, radioactivity was found in the external incubation medium, and this increased linearly with time. The translocation of PGF2 alpha was significantly greater in pseudopregnant than in pregnant animals on Day 6, whereas that of PGE2 was significantly higher in pregnant than in pseudopregnant animals on Day 6.8. In pregnant animals, both PGF2 alpha and PGE2 were translocated to the exterior more rapidly on Day 6.8 than on Days 5 or 6. Transport of PGs was reduced by low temperature, unaffected by metabolic inhibitors and only that of PGE2 increased with increased (5 microM) intraluminal concentrations. During incubation, the tissue remained viable as judged by T/M ratios (dpm tissue/dpm medium) for 204 thallium. Transport of [14C] sucrose was much slower than that of [14C] urea, which was greater than the fastest rates exhibited by the PGs. In general, amounts of radioactivity found in antimesometrial, mesometrial and lateral portions of the uterine wall, or in implantation and interimplantation areas did not differ, but more was found in the endometrium than the myometrium. PGF2 alpha was translocated unmetabolized to the external medium, while only two-thirds of the PGE2 was translocated unchanged, and one-third converted to PGF2 alpha. It is concluded that the rabbit uterus shows some selectivity in handling PGs in relation to stage of pregnancy.