Biomedical subjects

Yu Gu

Publications and source records attributed to Yu Gu.

8 recordsLinked to original sources

PubMed2026

Activating mutations in ESR1 contribute to an immunosuppressive breast tumor microenvironment by dampening cytokine secretion.

Patients with estrogen receptor+ (ER+, ESR1+) breast cancer are most at risk of relapse, where activating mutations in ESR1 promote metastasis and therapeutic resistance. These patients are also disadvantaged in responding to immunotherapies, the mechanisms of which remain to be elucidated. Here, we engineered a transgenic mouse model carrying either Y541S or D542G mutation in ESR1, mirroring the 2 most common mutations seen in patients. ESR1mut tumors do not differ in the total number of immune cells yet display downregulation in immune pathways and decreased immune-modulatory cytokines, including IL-17a and IL-1β. T cells and macrophages have lower IFN-γ and antigen presentation, respectively. Mechanistically, ESR1mut negatively regulates immune modulator expression and upregulates Stat5 to dampen cytokine expression. In concordance, validation on ESR1mut patient tumors shows decreased IL-17a and IL-1β. Collectively, our findings reveal that ESR1 mutations contribute to an immunosuppressive tumor microenvironment by dampening cytokine secretion and immune cell activity.

Animals↗

PubMed2006

Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN.

Wound healing is essential for maintaining the integrity of multicellular organisms. In every species studied, disruption of an epithelial layer instantaneously generates endogenous electric fields, which have been proposed to be important in wound healing. The identity of signalling pathways that guide both cell migration to electric cues and electric-field-induced wound healing have not been elucidated at a genetic level. Here we show that electric fields, of a strength equal to those detected endogenously, direct cell migration during wound healing as a prime directional cue. Manipulation of endogenous wound electric fields affects wound healing in vivo. Electric stimulation triggers activation of Src and inositol-phospholipid signalling, which polarizes in the direction of cell migration. Notably, genetic disruption of phosphatidylinositol-3-OH kinase-gamma (PI(3)Kgamma) decreases electric-field-induced signalling and abolishes directed movements of healing epithelium in response to electric signals. Deletion of the tumour suppressor phosphatase and tensin homolog (PTEN) enhances signalling and electrotactic responses. These data identify genes essential for electrical-signal-induced wound healing and show that PI(3)Kgamma and PTEN control electrotaxis.

Animals↗

PubMed2006

[Self hearing recovery in infants with hearing loss after universal newborn hearing screening system].

OBJECTIVE: To analyze the reasons of hearing recovery of newborns and infants which were diagnosed hearing loss within 3 months old by universal newborn hearing screening (UNHS) system. METHOD: Newborns and infants born from Nov. 2001 to Jun. 2005 in Shanghai who failed UNHS were studied. Audiometric evaluations were performed in Shanghai Children's Hearing and Speech Center. Those with hearing loss were diagnosed within 3 months old and were followed-up at least 6 months. Analysis was carried out targeting for hearing recovery cases. RESULT: Six hundred and eighty-one cases failed the UNHS and were confirmed hearing loss within 3 months old. During the 6-24 months period of followed-up, 94 (13.8%) of 681 infants caught normal hearing. Among these 94 infants(115 ears), otitis media with effusion was found in 56 cases (59.6%), no reasonable cause was found in the other 38 cases (40.4%). Among the 115 ears which recovered to normal, there were 105 ears (91.3%) with primary diagnosis of mild hearing loss, 8 ears (7.0%) with moderate hearing loss and 2 ears (1.7%) with moderate-severe hearing loss. No recovery was found in the cases with primary diagnosis of severe and profound hearing loss. CONCLUSION: Newborns and infants with hearing loss diagnosed within 3 months old have possibility to recover as they are growing. The critical reasons might be self-recovery from otitis media with effusion and outcomes of central auditory system development.

Audiometry↗

PubMed2005

Optically addressed droplet-based protein assay.

We demonstrate a new method for performing protein assays with very small volumes ( approximately 1.7 muL to 14 pL). Using a laser to modify local surface energy, we manipulate, fuse, and mix droplets containing horseradish peroxidase and its substrates. A detection limit of approximately 30 attomoles of reacting enzyme was measured by optical absorption. We discuss the possibility of extending this lower limit to zeptomoles of enzyme.

Benzothiazoles↗

PubMed2005

Approaches for coupling solid-phase microextraction to nanospray.

Biocompatible solid-phase microextraction (SPME) devices were prepared using two restricted access materials (RAM) as the SPME coating. The restricted access materials were immobilized on steel and platinum wires. The selective coating eliminated most of the matrix interference, which allowed the coupling to mass spectrometry without further purification. The SPME devices were interfaced to mass spectrometry by electronanospray. Several experimental set-ups are described and discussed herein. For the in situ extraction of peptides from the tryptic digests, trypsin was immobilized both on steel wires and on the inside wall of a vial. The devices were incubated together with the RAM-SPME devices and a protein (casein) solution. After the protein digestion, the resulting peptides were analyzed by SPME/nanospray. The vial approach provided the best results; up to eight peptides could be identified which corresponds to a sequence coverage of 58%. The limit of detection of SPME/nanospray for the extraction of peptides from an aqueous solution was about 50 fmol/mL. The results demonstrate that the direct coupling of SPME to nanospray can reduce analysis time and is an attractive alternative to conventional approaches like Zip-Tip purification.

Amino Acid Sequence↗

PubMed2005

Effect of monocyte chemoattractant protein-1 and estradiol on the secretion of vascular endothelial growth factor in endometrial stromal cells in vitro.

To explore the initial activity of endometrial stromal cells (ESCs) and the participation of monocyte chemoattractant protein-1 (MCP-1) in the histogenesis of endometriosis, vascular endothelial growth factor (VEGF) secretion of ESCs and the effect of MCP-1 on VEGF secretion of ESCs were observed in vitro. The VEGF level was detected in ESC culture media and was increased significantly when E2 or MCP-1 was added to the media, especially in the presence of E2 plus MCP-1. The VEGF secretion was higher in the ESCs of women with endometriosis than in those women without endometriosis.

Adult↗

PubMed2002

[Effects of chronic cadmium loading on the testis and endocrine function of reproduction in male rats].

Sixty healthy Sprague-Dawley male rats were used and divided randomly into control group (group C), cadmium loading group with medium dose (group M) and cadmium loading group with high dose (group H). Groups C, M and H were orally dosed daily with 0, 5 and 10 mg/kg of cadmium for over 6 weeks. Effects of cadmium loading on testis and endocrine function of reproduction in male rats were studied. The results showed that the zinc content decreased slightly in testis and plasma, and the cadmium concentration increased significantly in the testis of groups M and H; while the plasma levels of cadmium and zinc had no obvious difference as compared with those of group C; daily sperm production in the testis of group H decreased markedly during week 3 of cadmium loading, and was significantly lower in groups M and H as compared to that in group C during week 6; alkaline phosphatase (ALP) in group H and lactate dehydrogenase-X (LDH-X) in groups M and H were markedly lower compared to those of group C; plasma testosterone (T) level in both cadmium loading groups decreased and was low or significantly lower than that in group C; follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels had no apparent difference between the three groups. It is suggested that the gradual accumulation of cadmium in testis tissue induced by chronic cadmium loading results in changes in some enzyme activity, a decrease in sperm production, and defect of endocrine function activity in the testis.

Alkaline Phosphatase↗

PubMed2002

[Comparative study of laparoscopically assisted myomectomy and mini- laparotomy for uterine intramural fibroids].

OBJECTIVE: To evaluate the feasibility and safety of laparoscopically assisted myomectomy (LAM) for uterine intramural fibroids. METHODS: Thirty-seven selected patients with uterine intramural fibroids with the diameters > 5 cm and < 9 cm were subjected to LAM technique, the intramural fibroid of 2 among which penetrated into the uterine cavity (< 50%). LAM was completed with a laparoscopically assisted enucleation. After the fibroid was half-scripped, the incision of puncture point at the middle of abdominal wall was expanded to 4 approximately 5 cm in length. The scripping of the fibroid and the suture of the uterine wound were completed outside the abdominal incision. The duration of operation, blood loss, intra- and post-operation complications and time to full recovery were evaluated and comparison with those in 630 patients with hysteromyoama who underwent myomectomy by laparotomy during the same period. RESULTS: The operative time in LAM group ranged from 50 min to 240 min (101 min +/- 56 min), without a significant difference in comparison with that in the group of myomectomy by laparotomy (89 min +/- 38 min, P > 0.05). However, the median of blood loss in LAM group was 50 ml, significantly less than that in the group of myomectomy by laparotomy (80 ml, P < 0.05). The incidence of pyrexia was lower and the time needed for recovery was shorter after LAM in comparison with those in the group of myomectomy by laparotomy (P < 0.001). Neither intra-operative nor post- operative complication was observed in the LAM group. Eight of the 11 cases with infertility in the LAM group were conceived at least one year after LAM. The pregnancy was uneventful and proceeded to cesarean section at the 37 approximately 38 th week. CONCLUSION: LAM operation is feasible and safe, and offers a easy-to-perform minimally invasive myomectomy technique for intramural fibroid removal with all the advantages of laparoscopic surgery and a good reconstructive outcome.

Adult↗