Biomedical subjects

Yang Guo

Publications and source records attributed to Yang Guo.

At least 19 recordsLinked to original sources

PubMed2026

P1D6 inhibits FnBP-induced extracellular proteome remodeling: proteomic evidence for a novel intervention strategy in atopic dermatitis.

Atopic dermatitis (AD) is an inflammatory skin disorder characterized by skin barrier impairment, chronic inflammation, and intense pruritus. Staphylococcus aureus (S. aureus) critically contributes to its pathogenesis; however, the mechanistic role of its virulence factor fibronectin-binding protein (FnBP) in keratinocytes remains poorly understood. This study used bibliometric analysis and quantitative proteomics to examine the relationship. We first performed a bibliometric analysis, revealing a sustained increase in publications on S. aureus and AD, peaking at 99 articles in 2023, with hotspots focused on skin barrier function, immune inflammation, and pediatrics. Quantitative proteomics was employed to investigate how FnBP reshapes the extracellular proteome and whether the anti-α5 integrin antibody P1D6 exerts interventional effects. HaCaT cells were stimulated with recombinant FnBP alone or in combination with P1D6, followed by data-independent acquisition (DIA)-based proteomic analysis of secretome changes. Proteomic analysis identified FnBP-induced differentially expressed proteins enriched in immune- and barrier-related pathways, including cell adhesion, cell junctions, and VEGFA-VEGFR2 signaling. P1D6 intervention significantly inhibited the secretome profile and identified 241 core responsive proteins, of which approximately 52% returned to baseline levels after intervention (P > 0.05). These proteins were primarily enriched in pathways governing protein homeostasis, folding, proteasomal degradation, and interleukin-7 signaling. Notably, P1D6 modulated the downregulation of ATP5F1B and P4HB, key effectors within the interleukin-7 pathway. This study demonstrates that FnBP remodels the keratinocyte secretome by disrupting protein homeostasis, consequently inducing barrier injury and chronic inflammation related to AD, which can be effectively blocked by P1D6. Combined with bibliometric trends and proteomic evidence, this study focuses on FnBP, an underexplored virulence factor, and provides novel insights into AD pathogenesis and therapeutic interventions.

Humans↗

PubMed2025

The causal relationship between antihypertensive drugs and knee osteoarthritis: A drug target Mendelian randomization study.

Recently studies have revealed a robust association between hypertension and knee osteoarthritis (KOA), with patients likely to suffer from both conditions. We employed Mendelian randomization (MR) analysis to assess the impact of antihypertensive medications on KOA, aiming to offer clinical guidance for concomitant drug therapy and identify potential therapeutic targets for KOA. We obtained exposure instruments (instrumental variables) by locating Single-nucleotide polymorphisms related to systolic blood pressure near drug target genes. We then conducted Mendelian randomization analyses between the exposure data and genome-wide association studies data on KOA to evaluate the impact of antihypertensive drugs on KOA. We observed a significant association between decreased expression of the SLC12A2 target gene and a reduced risk of KOA (odds ratio: 0.915, 95% confidence interval: 0.869-0.964, P < .001). In this study, we find that SLC12A2 inhibitors can have a beneficial effect on KOA, and that the SLC12A2 gene may be a potential therapeutic target for KOA. These findings suggest that when treating patients with both hypertension and KOA, clinicians may consider prioritizing the use of SLC12A2 inhibitors.

Humans↗

PubMed2006

A novel fusion protein-based indirect enzyme-linked immunosorbent assay for the detection of bovine tuberculosis.

Enzyme-linked immunosorbent assay (ELISA) for diagnosis of bovine tuberculosis has been widely explored over the years. Three Mycobacterium bovis-specific antigen genes, namely, mpb70, mpb83, and esat-6 were recombined in tandem by spliced overlap extension technology and expressed in Escherichia coli to obtain the fusion protein (rM70-83-E6). Western blot analysis showed that rM70-83-E6 can specifically react with bovine tuberculosis-positive sera but not those from cattle infected with other bovine diseases such as bovine paratuberculosis. An indirect ELISA (iELISA) method was established with rM70-83-E6 as the diagnostic antigen. The diagnostic criteria were determined using 150 serum samples from healthy cattle. Analyses of 85 serum samples from cattle with bovine tuberculosis and 100 serum samples from healthy cattle demonstrated that the sensitivity of the iELISA was 69.4% (59/85) and the specificity was 96.0% (96/100). Moreover, 46 out of 67 purified protein derivative (PPD) skin test-positive samples were also positive by iELISA, giving a positive coincidence of 68.7%, while all 50 PPD skin test-negative samples were negative by iELISA, giving a negative coincidence of 100%. The total coincidence between iELISA and the PPD skin test was 82.1%. This study demonstrated that iELISA using rM70-83-E6 antigen is simple, sensitive and easy to perform and can be used to analysis of a large number of samples for serodiagnosis of bovine tubercuiosis.

Animals↗

PubMed2006

p27Kip1 and cyclin dependent kinase 2 regulate passage through the restriction point.

When quiescent cells are stimulated to reenter the cell cycle, growth factors are required only until the restriction point in G(1) phase. After this point the cell no longer requires growth factors, proliferative signaling molecules, or even protein synthesis in order to initiate DNA synthesis, which starts several hours later. Consequently, understanding the molecular nature of the restriction point constitutes one of the major goals in studies of growth regulation. We recently demonstrated that p27Kip1 (p27) regulates passage through G(1) phase in actively proliferating cultures, and initiated these studies to determine if it is also involved in passage through the restriction point following stimulation of quiescent cells. In support of this suggestion, we found that passage through the restriction point requires mitogen-dependent suppression of the high p27 levels normally present in quiescent cells. Moreover, as the culture progresses to mid-G(1) phase, the proportion of cells that pass the restriction point is increased by artificial suppression of p27 levels, while this proportion is reduced by elevation of p27 levels. p27 performs this critical function by regulating the subsequent activating phosphorylation of cyclin dependent kinase (CDK)2, which we also show is necessary for and closely associated with the initiation of DNA synthesis. We conclude that the p27 expression level at mid-G(1) phase determines when a cell passes through the restriction point, and does so by regulating subsequent CDK2 activation.

3T3 Cells↗

PubMed2006

Glycogen synthase kinase 3 has a limited role in cell cycle regulation of cyclin D1 levels.

BACKGROUND: The expression level of cyclin D1 plays a vital role in the control of proliferation. This protein is reported to be degraded following phosphorylation by glycogen synthase kinase 3 (GSK3) on Thr-286. We recently showed that phosphorylation of Thr-286 is responsible for a decline in cyclin D1 levels during S phase, an event required for efficient DNA synthesis. These studies were undertaken to test the possibility that phosphorylation by GSK3 is responsible for the S phase specific decline in cyclin D1 levels, and that this event is regulated by the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway which controls GSK3. RESULTS: We found, however, that neither PI3K, AKT, GSK3, nor proliferative signaling activity in general is responsible for the S phase decline in cyclin D1 levels. In fact, the activity of these signaling kinases does not vary through the cell cycle of proliferating cells. Moreover, we found that GSK3 activity has little influence over cyclin D1 expression levels during any cell cycle phase. Inhibition of GSK3 activity by siRNA, LiCl, or other chemical inhibitors failed to influence cyclin D1 phosphorylation on Thr-286, even though LiCl efficiently blocked phosphorylation of beta-catenin, a known substrate of GSK3. Likewise, the expression of a constitutively active GSK3 mutant protein failed to influence cyclin D1 phosphorylation or total protein expression level. CONCLUSION: Because we were unable to identify any proliferative signaling molecule or pathway which is regulated through the cell cycle, or which is able to influence cyclin D1 levels, we conclude that the suppression of cyclin D1 levels during S phase is regulated by cell cycle position rather than signaling activity. We propose that this mechanism guarantees the decline in cyclin D1 levels during each S phase; and that in so doing it reduces the likelihood that simple over expression of cyclin D1 can lead to uncontrolled cell growth.

Animals↗

PubMed2006

Histological changes of the testis and epididymis in adult rats as a result of Leydig cell destruction after ethane dimethane sulfonate treatment: a morphometric study.

AIM: To quantitatively study the histological changes of the testis and epididymis as a result of a drastic reduction of testosterone secretion. METHODS: Fourteen adult Sprague-Dawley rats were injected intraperitoneally with ethane dimethane sulfonate (EDS, 75 mg/kg) and the same number of animals were injected with normal saline as a control. At days 7 and 12 (after treatment), respectively, half of the animals from each group were killed. The testes and epididymides were removed and tissue blocks embedded in methacrylate resin. The cell number per testis was estimated using the stereological optical disector and some other parameters were obtained using other morphometric methods. RESULTS: The EDS treatment resulted in an almost complete elimination of Leydig cells but had no effect on the numbers of Sertoli cells per testis. At day 7 after EDS treatment, many elongated spermatids were retained in the seminiferous epithelium and many round spermatids could be seen in the epididymal ducts. At day 12, a looser arrangement of spermatids and spermatocytes became evident, with apparent narrow empty spaces being formed between germ cells in an approximately radial direction towards the tubule lumen; the numbers (per testis) of non-type B spermatogonia and spermatocytes were similar to controls, whereas that of type B spermatogonia increased by 59%, and that of early round, elongating and late elongated spermatids decreased by 37%, 72% and 52%, respectively. CONCLUSION: The primary spermatogenic lesions following EDS administration were (i) spermiation failure and (ii) detachment of spermatids and spermatocytes associated with impairment in spermiogenesis and meiosis.

Animals↗

PubMed2006

[Effect of intra-testicular testosterone withdrawal on the expression of alpha-catenin in the adult rat testis].

OBJECTIVE: To study the expression of alpha-catenin in the rat testis after intra-testicular testosterone withdrawal induced by injection of testosterone undecanoate (TU). METHODS: Ten adult male SD rats received vehicle (n = 5 ) or TU (19 mg/kg every 15 days, n = 5) for 130 days. Paraffin-embedded testicular sections were used for immunohistochemistry against a polyclonal anti-alpha-catenin antibody. RESULTS: In the control, alpha-catenin was expressed in the acrosome of spermatids and the cytoplasm of Leydig cells and peritubular myoid cells. In the TU-treated rat testis, Leydig cells were atrophied and the expression of alpha-catenin was markedly decreased or absent, but there was no evident change in the immunostaining of spermatids or myoid cells. CONCLUSION: Intra-testicular testosterone withdrawal-induced looser arrangement or sloughing of spermatogenic cells is not related to the adhesion molecule alpha-catenin. Alpha-catenin may be used as a cell identification marker for Leydig cells.

Animals↗

PubMed2005

Band structure and oscillatory electron-phonon coupling of Pb thin films determined by atomic-layer-resolved quantum-well states.

Using a low temperature growth method, we have prepared atomically flat Pb thin films over a wide range of film thickness on a Si-(111)-7 x 7 surface. The Pb film morphology and electronic structure are investigated in situ by scanning tunneling microscopy and angle-resolved photoemission spectroscopy. Well-defined and atomic-layer-resolved quantum-well states of the Pb films are used to determine the band structure and the electron-phonon coupling constant (lambda) of the films. We found an oscillatory behavior of lambda with an oscillation periodicity of two atomic layers. Almost all essential features in the Pb/Si(111) system, such as the growth mode, the oscillatory film stability, and the 9 monolayer envelope beating pattern, can be explained by our results in terms of the electron confinement in Pb films.

Journal Article↗

PubMed2005

The effect of formulation variables and breathing patterns on the site of nasal deposition in an anatomically correct model.

PURPOSE: This study was conducted to evaluate the effect of formulation variables and breathing patterns on aerosol distribution in the nasal cavity. METHODS: Placebo nasal spray formulations containing 0.25% w/v Avicel CL611 (viscosity = 4 cP) and 2% w/v methylcellulose (MC; viscosity = 18.2 cP) were radiolabeled with (99m)Technicium. Following spraying into a silicone nose model, through which air was drawn at one of three constant rates (0, 10, and 20 L/min) or one of two breathing profiles (representing fast and slow inhalations), aerosol deposition in the model was quantified by gamma scintigraphy. Regional deposition was expressed as horizontal[inner, middle (h), outer] and vertical distribution [upper, middle (v), lower] in the nose model. RESULTS: Compared to 2% MC, Avicel CL611 significantly increased aerosol deposition in the middle (h) region of the nasal cavity under all breathing conditions, and in the inner region at 0 and 20 L/min and with a slow inhalation. The different breathing rates showed no effect on deposition of 2% MC. However, 10 L/min significantly increased the upper deposition of Avicel compared to 0 and 20 L/min. CONCLUSIONS: Nasal sprays with a low viscosity provided greater surface coverage of the nasal mucosa than higher viscosity formulations. Changes in breathing profiles did not affect aerosol deposition in this nose model.

Administration, Intranasal↗

PubMed2005

[Clinical analysis of 16 cases of epithelioid sarcoma].

OBJECTIVE: To introduce the clinical features of a rare malignant soft tissue tumor. METHODS: Review the clinical findings, pathologic features and results of the treatment of 16 cases of the epithelioid sarcoma in extremities, which were treated in our hospital from 1992 to 2004. Analyze the follow-up results of 14 cases. RESULTS: The tumors occurred chiefly in young adults (mean age 30 years) and commonly involved soft tissue of the hand. Follow-up (average 25 months, from 1 to 112 months) information on 14 patients revealed relentless clinical course with frequent recurrence (71%). There was a significant difference between those patients in whom had a marginal and radical resection, both in recurrence rate and disease-free survival rate. CONCLUSION: It is safe to choose the radical resection of this disease after the tumor reoccurs.

Adolescent↗

PubMed2005

The regulation of S phase initiation by p27Kip1 in NIH3T3 cells.

Most eukaryotic cells become committed to divide once DNA synthesis begins. This critical event is controlled in yeast and Xenopus oocytes by the degradation of cyclin inhibitory proteins, while in mammalian cells over-expression of cyclin E or cyclin D1 promotes rapid entry into DNA synthesis. Curiously, however, this over-expression also lengthens S phase and promotes DNA damage. To directly assess the roles of the cyclin inhibitory protein p27Kip1 (p27) and of cyclin D1 in the regulation of DNA synthesis initiation in mammalian cells, we have utilized a quantitative cytometric approach for the study of cell cycle control in actively proliferating cultures. As evidence that p27 plays a direct role in regulating entry into S phase, we find that its levels fall at the time of DNA synthesis initiation in NIH3T3 cells, and that its suppression shortens G1 phase and shortens the length of the entire cell cycle. In this function, however, the action of p27 appears to be linked with cyclin D1. G1/S phase transition is efficiently blocked by p27 unless excess cyclin D1 is present. These two proteins are coordinately regulated by the cell, and are maintained at a nearly constant ratio throughout an actively proliferating culture. We propose that p27 directly regulates the initiation of DNA synthesis in NIH3T3 cells, and that cyclin D1 serves to modulate this activity.

Animals↗

PubMed2005

Phosphorylation of cyclin D1 at Thr 286 during S phase leads to its proteasomal degradation and allows efficient DNA synthesis.

Continuing proliferation requires regulation of cyclin D1 levels in each cell cycle phase. Growth factors stimulate high levels during G2 phase, which commits the cell to continue through G1 phase with sufficient cyclin D1 to initiate DNA synthesis. Upon entry into S phase, however, cyclin D1 levels rapidly decline. Our goal is to understand the mechanism and importance of this S-phase suppression. Here, we demonstrate that cyclin D1 levels decline during S phase due to reduced protein stability, without alterations in the rate of protein synthesis. This decline depends upon Thr 286, since mutation of this site eliminates the normal pattern of cyclin D1 suppression during S phase. As evidence that phosphorylation of Thr 286 is responsible for this decline, Thr 286 is shown to be more efficiently phosphorylated during S phase than in other cell cycle periods. Finally, high cyclin D1 levels during S phase are shown to inhibit DNA synthesis. This inhibitory activity presumably blocks the growth of cells with altered cyclin D1 expression characteristics. Abnormal stimulation of cyclin D1 might result in levels high enough to promote G1/S phase transition even in the absence of appropriate growth stimuli. In such cells, however, the levels of cyclin D1 would presumably be too high to be suppressed during S phase, resulting in the inhibition of DNA synthesis.

Animals↗

PubMed2005

Destabilization of cyclin D1 message plays a critical role in cell cycle exit upon mitogen withdrawal.

Cyclin D1 is critical for entry into, continuation of, and exit from the cell division cycle. Mitogen stimulation of quiescent cells induces cyclin D1 expression in a transcription-dependent manner. In actively cycling cells, on the other hand, fluctuation of cyclin D1 protein levels through the cell cycle is post-transcriptionally regulated. Cyclin D1 is expressed at low levels during S phase to allow efficient DNA synthesis, and induced to high levels in G2 phase through Ras activity to commit the cells to continuing cell cycle progression. Once induced in G2 phase, cyclin D1 expression becomes Ras independent through the next G1 phase, where it promotes G1/S transition. When mitogenic signaling is abrogated, however, cyclin D1 fails to increase during G2 phase and the cell becomes arrested in the next G1 phase. In this way, the expression levels of cyclin D1 in G2 phase determine the fate of the next cell cycle. Despite its importance of the mechanism of cyclin D1 suppression upon mitogen withdrawal is unknown. Using both quantitative fluorescence microscopy and biochemical analyses, we have found that, upon serum deprivation, cyclin D1 mRNA is downmodulated without any decline in its rate of transcription. Furthermore, cyclin D1 mRNA half-life becomes shorter when serum is removed. These results demonstrate that cyclin D1 message destabilization plays a critical role in cyclin D1 suppression during G2 phase of serum-deprived cultures, and therefore in the withdrawal from the cell cycle.

Animals↗

PubMed2005

Mechanism of anti-apoptotic action of dipfluzine on neuronal damage of the rat hippocampal CA1 region subjected to transient forebrain ischemia.

AIM: To explore the relations between anti-apoptotic role of dipfluzine (DIP) and the death signaling transduction pathway initiated by CD95 molecules, and the transcription factor involved in the transcription regulation of CD95 molecules in the hippocampal CA1 region after transient forebrain ischemia. METHODS: The rat forebrain transient ischemia model was established through 15 min ischemia followed by 3 days reperfusion by using the four-vessel method. The rats were divided randomly into five groups: sham control group, ischemia/reperfusion (I/R) group, DIP treated groups (20, 40 and 80 mg x kg(-1) body weight, ig, separately). Western blotting and RT-PCR were performed to detect the expression changes of Fas, FasL, caspase 10 p20, caspase 8, I-kappaB-alpha, and p-I-kappaB-alpha molecules in protein and mRNA levels, separately, and immunohistochemistry for molecular localization of Fas and FasL in rat hippocampus. RESULTS: The expression of Fas, FasL, and caspase 10 p20 in protein and mRNA levels increased after I/R, which was inhibited significantly after treatment with 20 and 40 mg x kg(-1) of DIP (P < 0.01). In 80 mg x kg(-1) of DIP group, the expression of Fas and FasL protein was not significantly different from that of I/R group (P > 0.05). The expression of caspase 8 and I-kappaB-alpha showed no significant differences in all groups (P > 0.05), and no gene expression was observed for p-I-kappaB-alpha protein in the study. DIP significantly affected molecular distribution of Fas and FasL protein in CA1 subregion of hippocampus. CONCLUSION: DIP inhibits the death signaling transduction pathway initiated by CD95 molecules in rat hippocampal CA1 subregion, and NF-kappaB transcription factor may not be involved in the transcription regulation of CD95 molecules after transient forebrain ischemia.

Animals↗

PubMed2004

Superconductivity modulated by quantum size effects.

We have fabricated ultrathin lead films on silicon substrates with atomic-scale control of the thickness over a macroscopic area. We observed oscillatory behavior of the superconducting transition temperature when the film thickness was increased by one atomic layer at a time. This oscillating behavior was shown to be a manifestation of the Fabry-Perot interference modes of electron de Broglie waves (quantum well states) in the films, which modulate the electron density of states near the Fermi level and the electron-phonon coupling, which are the two factors that control superconductivity transitions. This result suggests the possibility of modifying superconductivity and other physical properties of a thin film by exploiting well-controlled and thickness-dependent quantum size effects.

Journal Article↗

PubMed2004

Quantitative (stereological) study of incomplete spermatogenic suppression induced by testosterone undecanoate injection in rats.

AIM: To evaluate the key lesions in spermatogenesis suppressed partially by testosterone undecanoate (TU) treatment. METHODS: Adult male SD rats were treated with vehicle or TU (19 mg/kg) injection (i.m.) every 15 days for 130 days. The numbers of all types of cells (nuclei) in the seminiferous tubules and the interstitial tissue were estimated using a contemporary stereological tool, the optical disector. RESULTS: In response to TU treatment, the numbers of non-type B spermatogonia, type B spermatogonia and late elongated spermatids per testis were reduced to 51 %, 66 % and 14 % of the controls, respectively. The conversion ratios from type B spermatogonia to early spermatocytes and pachytene spermatocytes were not significantly affected and the ratios to the later germ cell types fell to 51 % - 65 % of the controls. Less than 1.0 % of immature round spermatids were seen sloughing into the tubule lumen, 4.0 % of elongated spermatids retained in the seminiferous epithelium, and about half of the elongated spermatid nuclei appreciably malformed. Leydig cells were atrophied but their number and the peritubular myoid cell number per testis were unchanged. CONCLUSION: Double inhibition of spermatogenesis (i.e. inhibition at spermiation and spermatogonial conversion to type B spermatogonia), a scenario seen in the monkey and human following gonadotrophin withdrawal, was not sufficiently effective for a complete spermatogenic suppression in the rat after TU treatment, probably due to ineffective inhibition of the Leydig cell population and therefore the intra-testicular testosterone levels.

Animals↗

PubMed2003

[Three-dimensional structure of collagen fibril of pigskin].

OBJECTIVE: To probe deply into the three-dimensional structure of pigskin collagen fibril and provide the basic data for using the pigskin tissue as tissue engineering material. METHODS: Scanning Probe Microscope (SPM) and Transmission Electron Microscope (TEM) were employed to study the three-dimensional structure of collagen fibril in pigskin tissue. RESULTS: Microscopy revealed that pigskin collagen fibril had periodic transverse groove (i.e. D-periodicity) which was about 67 nm. The diameter of fibril ranged from 57 to 135 nm, showing much difference among the papillary layer, reticular layer and infra-reticular layer. The length of fibril varied from 5 to 13 microns. Both ends of fibril were rotund and slightly bulgy. The fibrils assembled and the D-periodicities were homologous in flank. In axial direction fibrils were found staggered end by end. CONCLUSION: The data obtained in this study on the three-dimensional structure of pigskin collagen fibril are of significance to researches in tissue engineering materials.

Animals↗

PubMed2002

Post-transcriptional regulation of cyclin D1 expression during G2 phase.

During continuous proliferation, cyclin D1 protein is induced to high levels in a Ras-dependent manner as cells progress from S phase to G2 phase. To understand the mechanism of the Ras-dependent cyclin D1 induction, cyclin D1 mRNA levels were determined by quantitative image analysis following fluorescent in situ hybridization. Although a slight increase in mRNA expression levels was detected during the S/G2 transition, this increase could not explain the more robust induction of cyclin D1 protein levels. This suggested the involvement of post-transcriptional regulation as a mechanism of cyclin D1 protein induction. To directly test this hypothesis, the cyclin D1 transcription rate was determined by run-on assays. The transcription rate of cyclin D1 stayed steady during the synchronous transition from S the G2 phase. We further demonstrated that cyclin D1 protein levels could increase during G2 phase in the absence of new mRNA synthesis. alpha-Amanitin, a transcription inhibitor, did not suppress cyclin D1 protein elevation as the cells progressed from S to G2 phase, even though the inhibitor was able to completely block cyclin D1 protein induction during reentry into the cell cycle from quiescence. The half life of cyclin D1 protein was shortest during S phase indicating that a change in protein stability might play a role in post-translational induction of cyclin D1 in G2 phase. These data indicate a fundamental difference in the regulation of cyclin D1 production during continuous cell cycle progression and re-initiation of the cell cycle.

Amanitins↗