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Biomedical subjects

Ruiping Wang

Publications and source records attributed to Ruiping Wang.

9 recordsLinked to original sources
PubMed2026

Pharmacologic inhibition of SOX9-CDK4 by CYD-4-61 impairs gastric adenocarcinoma growth and amplifies anti-PD-1 response.

Gastric adenocarcinoma (GAC) remains a leading cause of cancer-related mortality, particularly in patients with peritoneal carcinomatosis, for whom effective therapies are limited. We investigated the therapeutic efficacy and molecular mechanism of CYD-4-61, a BAX activator, using human GAC cell lines, patient-derived xenograft models, genetically engineered mouse models, and a syngeneic mouse model. CYD-4-61 potently inhibited tumor cell proliferation, induced apoptosis, and suppressed cancer stem cell-like properties, with enhanced activity in radiation-resistant GAC cells. Mechanistically, CYD-4-61 activated the BAX-caspase pathway, leading to SOX9 protein reduction. Integrated bulk and single-cell transcriptomic analyses identified SOX9-dependent transcriptional programs as major targets of CYD-4-61. Functional rescue experiments together with chromatin immunoprecipitation and CUT&RUN analyses supported CDK4 as a SOX9-regulated gene and demonstrated suppression of the SOX9-CDK4 regulatory axis following CYD-4-61 treatment. In multiple preclinical models, CYD-4-61 significantly inhibited tumor growth and improved the therapeutic response to anti-programmed cell death protein 1 (PD-1) therapy while modulating the tumor immune microenvironment. Clinically, co-expression of SOX9 and CDK4 was associated with diffuse-type GAC and poor patient outcomes. These findings identify the BAX-SOX9-CDK4 axis as an important mechanism contributing to the antitumor activity of CYD-4-61 and provide a strong preclinical rationale for its further development as a therapeutic strategy for aggressive GAC.

Animals↗
PubMed2006

A practical VEP-based brain-computer interface.

This paper introduces the development of a practical brain-computer interface at Tsinghua University. The system uses frequency-coded steady-state visual evoked potentials to determine the gaze direction of the user. To ensure more universal applicability of the system, approaches for reducing user variation on system performance have been proposed. The information transfer rate (ITR) has been evaluated both in the laboratory and at the Rehabilitation Center of China, respectively. The system has been proved to be applicable to > 90% of people with a high ITR in living environments.

Adult↗
PubMed2005

[A novel ROI extracting technique based on wavelet transform for the detection of micro-calcifications in mammograms].

In order to preprocess mammograms for diagnosing the early cases of breast cancer and improving the computational efficiency in the computer-aided detection of micro-calcifications in mammograms, we have advanced a novel processing technique for the extraction of micro-calcification region of interest (MROI). The proposed method is based on a three-step procedure: (1) the mammogram is divided into sub-images of the same size; (2) the wavelet multi-resolution method is conducted on the sub-images, and the parameters related to wavelet transform and threshold T are discussed according to rho; (3) the classification of sub-images is determined by T. It is tested with 20 mammograms and the results show that the method can achieve a true positive rate as high as 89.7% with a false positive rate as low as 2.1%.

Breast Diseases↗
PubMed2004

Distribution of the neuropeptide FF1 receptor (hFF1) in the human hypothalamus and surrounding basal forebrain structures: immunohistochemical study.

Neuropeptides with C-terminal RFamide and their receptors NPFF1 (FF1) and NPFF2 (FF2) have been implicated in a wide variety of functions, including nociception and autonomic and neuroendocrine regulation. Recent studies indicate that the FF1, but not FF2, mRNA is highly expressed in the human hypothalamus. In the present study, localization of FF1 in the human hypothalamus and surrounding regions was studied immunohistochemically by using an antibody against human FF1 (hFF1). Brain sections from healthy 30-50-year-old individuals were used for hFF1 immunohistochemistry. The highest density of hFF1-stained cells was found in the posterior division of the bed nucleus of the stria terminalis and in the zona incerta. A moderate density of cells was observed in the perifornical nucleus, infundibular nucleus, tuberomammillary nucleus, and lateral tuberal nucleus. A lesser density was revealed in the dorsomedial hypothalamic nucleus, basal nucleus of Meynert, and anterior amygdaloid area. Only scattered hFF1 cells were found in the suprachiasmatic nucleus and hypothalamic paraventricular nucleus. hFF1 cells and fibers were absent in the supraoptic and mammillary nuclei. Single and double strands of hFF1-immunopositive punctate varicosities marked cellular processes of different caliber. The density of hFF1-immunostained fiber networks did not always coincide with that of hFF1-immunostained cells. hFF1 immunoreactivity was also found in the wall of blood vessels within most brain areas studied. Localization of hFF1 in discrete regions of the hypothalamus and extended amygdala may provide important insights into the role of amidated neuropeptides in central autonomic and neuroendocrine control in the human brain.

Adult↗
PubMed2003

Allosteric modulation of group III metabotropic glutamate receptor 4: a potential approach to Parkinson's disease treatment.

Parkinson's disease (PD) is a debilitating movement disorder that afflicts >1 million people in North America. Current treatments focused on dopamine-replacement strategies ultimately fail in most patients because of loss of efficacy and severe adverse effects that worsen as the disease progresses. The recent success of surgical approaches suggests that a pharmacological intervention that bypasses the dopamine system and restores balance in the basal ganglia motor circuit may provide an effective treatment strategy. We previously identified the metabotropic glutamate receptor 4 (mGluR4) as a potential drug target and predicted that selective activation of mGluR4 could provide palliative benefit in PD. We now report that N-phenyl-7-(hydroxylimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC) is a selective allosteric potentiator of mGluR4. This compound selectively potentiated agonist-induced mGluR4 activity in cultured cells expressing this receptor and did not itself act as an agonist. Furthermore, PHCCC potentiated the effect of l-(+)-2-amino-4-phosphonobutyric acid in inhibiting transmission at the striatopallidal synapse. Modulation of the striatopallidal synapse has been proposed as a potential therapeutic target for PD, in that it may restore balance in the basal ganglia motor circuit. Consistent with this, PHCCC produced a marked reversal of reserpine-induced akinesia in rats. The closely related analogue 7-(hydroxylimino)cyclopropachromen-1a-carboxamide ethyl ester, which does not potentiate mGluR4, had no effect in this model. These results are evidence for in vivo behavioral effects of an allosteric potentiator of mGluRs and suggest that potentiation of mGluR4 may be a useful therapeutic approach to the treatment of PD.

Allosteric Site↗
PubMed2003

Neuropeptide FF receptor 2 (NPFF2) is localized to pain-processing regions in the primate spinal cord and the lower level of the medulla oblongata.

Studies have suggested that NPFF-like peptides and their receptors play important roles in physiological and pathological conditions. Here, we show, using multiple expression modalities, that the type 2 NPFF receptor (hNPFF2) is expressed in regions of the primate spinal cord and brainstem mediating pain sensation. In situ hybridization using an NPFF2 riboprobe, and immunohistochemistry using a novel NPFF2 antibody, demonstrated strong NPFF2 expression in the superficial layer of the dorsal horn, and in the spinal trigeminal nucleus of the brainstem of the African green monkey (AGM). In addition, autoradiography using a radiolabeled NPFF analog ([125I]1DMe) revealed dense binding signal in the superficial layer of the dorsal horn in the spinal cord. The distribution pattern of hNPFF2 in the AGM spinal cord and the lower level of the brainstem are consistent with a hypothesized potential role for NPFF peptides in modulation of sensory input, opioid analgesia and morphine tolerance through spinal and supraspinal mechanisms.

Animals↗
PubMed2002

Hydroformylation of alkenes employing rhodium(i) complexes and a phosphine oxide ligand.

Following the facile synthesis of a novel phosphine oxide compound, (diphenylphosphinoyl)phenylmethanol (1), this compound was employed as a ligand in the rhodium-catalyzed hydroformylation of alkenes, with good conversions and regioselectivities. This ligand was partially resolved using an enzyme, and enantioselective hydroformylation was carried out with the addition of a rhodium(I) complex. The rhodium(I) complex containing ligand 1 was not isolated, although it was subjected to low-temperature NMR studies.

Journal Article↗
PubMed2002

Identification, localization and receptor characterization of novel mammalian substance P-like peptides.

Hemokinin-1 (HK-1) is a novel substance P (SP)-like peptide that is encoded by the preprotachykinin C (PPT-C) gene recently identified in mouse B cells and shown to be a potentially important regulator of B cell development (Nat. Immunol. 1 (2000) 392). We have now isolated and characterized the human and rat orthologs of PPT-C and examined activities of human and mouse HK-1 on the three tachykinin receptors, neurokinin-1-3 (NK1-3). The rat PPT-C polypeptide is highly homologous to mouse PPT-C and contains the same processing sites to generate predicted HK-1. The human PPT-C polypeptide is also homologous to mouse PPT-C, however, it contains two potential monobasic cleavage sites rather than a single dibasic cleavage site at the amino-terminal end of the predicted HK-1 peptide. Thus, human PPT-C has the potential to generate full length predicted HK-1 as well as a truncated version (HK-1(4-11)). Polymerase chain reaction analysis revealed that both human and mouse PPT-C were expressed in a variety of tissues with strong signals detected in the skin of both species and in the mouse brain. Binding and functional analysis indicated that human and mouse HK-1 peptides were nearly identical to SP in their overall activity profile on the three NK receptors with the most potent affinity for the NK1 receptor. The results indicate that PPT-C encodes another high affinity ligand of the NK1 receptor which may play an important role in mediating some of the physiological roles previously assigned to the NK1 receptor.

Amino Acid Sequence↗