G-protein Coupled Estrogen Receptor 1 Expression in Primary Breast Cancers and Its Correlation with Clinicopathological Variables

Hao-jun Luo,Ping Luo,Guang-lun Yang,Qiong-le Peng,Man-ran Liu,Gang Tu 한국유방암학회 2011 Journal of breast cancer Vol.14 No.3

Purpose: G-protein coupled estrogen receptor 1 (GPER) probably play important roles in the progression of breast cancer including endocrine therapeutic resistance. We evaluated GPER in primary breast cancers. Methods: Immunohistochemistry was used to detect GPER in paraffin-embedded tissues of primary breast cancers from 423 patients and GPER expression was correlated with clinicopathological factors. Results: GPER was expressed in 63.8% of specimens, coexpressed with estrogen receptor alpha (ERα) in 36.6% of tumors and was positive in 62.5% of the ERα-negative tumors. The expression of GPER had no relationship with the status of ERα, progesterone receptor and HER2. Although the expression of GPER was significantly inversely related with nodal status (p=0.045), no correlation between GPER expression and other clinicopathological variables (age, menstruation status, tumor size, stage, histologic grade, Nottingham Prognostic Index or pathological type) was found. Conclusion: GPER and ERα exhibited independent expression pattern of distribution in primary breast cancers. A long-term follow-up and a more definite molecular phenotype for ER are necessary in confirming studies.

Design of fixed dose combination and physicochemical characterization of enteric-coated bilayer tablet with circadian rhythmic variations containing telmisartan and pravastatin sodium

Luo, Daoqi,Kim, Joo Hee,Park, Chulhun,Oh, Euichaul,Park, Jun-Bom,Cui, Jing-Hao,Cao, Qing-Ri,Lee, Beom-Jin Elsevier 2017 International journal of pharmaceutics Vol.523 No.1

<P><B>Abstract</B></P> <P>The aim of this study was to investigate a fixed dose combination (FDC) of telmisartan (TEL) and pravastatin sodium (PRA) in enteric-coated bilayer tablets, which was designed for once-daily bedtime dose in order to match circadian rhythmic variations of hypertension and cholesterol synthesis and optimize the patient friendly dosing treatment. Due to the poor aqueous solubility of TEL, ternary solid dispersions (SD) consisting of TEL, polyethylene glycol 6000 (PEG 6000) and magnesium oxide (MgO) were designed to enhance its dissolution rate in intestinal fluid. MgO was added as an effective alkalizer to maintain the high microenvironmental pH of the saturated solution in the immediate vicinity of TEL particles because TEL is known to be ionizable but poorly soluble in intestinal fluid. In contrast, PRA is known to be very unstable in low pH conditions. In the SD system, TEL was present in an amorphous structure and formed an intermolecular hydrogen bonding with MgO, giving complete drug release without precipitation in intestinal fluid. In addition, the amount of hydrophilic carrier (PEG 6000) was also a factor. In the design of tablet formulation, the diluents and superdisintegrants could play a key role in release profiles. Then, to fulfill the unmet needs of the two model drugs and match circadian rhythmic variations of hypertension and cholesterol synthesis, enteric-coated bilayer tablet consisting of TEL SD and PRA was finally prepared using Acryl-EZE<SUP>®</SUP> as an enteric coating material. Prior to enteric coating, a seal coating layer (Opadry<SUP>®</SUP>, 2% weight gains) was firstly introduced to separate the core bilayer tablet from the acidic enteric coating polymers to avoid premature degradation. Dissolution profiles of finished tablets revealed that enteric-coated bilayer tablets with 6% weight gains remained intact in acidic media (pH 1.0) for 2h and then released drugs completely within 45min after switching to the intestinal media (pH 6.8). It was observed that enteric-coated bilayer tablets were stable during 3 month under the accelerated condition of 40°C/75% RH. The delayed drug release and bedtime dosage regimen using enteric-coated bilayer tablet containing TEL and PRA, matching the circadian rhythms of hypertension and hyperlipidemia can provide therapeutic benefits for elderly patients in terms of maximizing the therapeutic effects.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Northeast Asia's Future Energy Cooperation in the Context of One Belt One Road

Jun-Young Kim,Luo Hao Nan,Sun Xiao,Yang Jin,Cong Lin,Wang Xiao Ya 한국글로벌무역학회 2022 한국글로벌무역학회 학술대회자료집 Vol.2022 No.-

Resveratrol pretreatment alleviates NLRP3 inflammasome-mediated cardiomyocyte pyroptosis by targeting TLR4/MyD88/NF-κB signaling cascade in coronary microembolization-induced myocardial damage

Chang-Jun Luo,Tao Li,Hao-Liang Li,You Zhou,Lang Li 대한약리학회 2023 The Korean Journal of Physiology & Pharmacology Vol.27 No.2

Percutaneous coronary intervention and acute coronary syndrome are both closely tied to the frequently occurring complication of coronary microembolization (CME). Resveratrol (RES) has been shown to have a substantial cardioprotective influence in a variety of cardiac diseases, though its function and potential mechanistic involvement in CME are still unclear. The forty Sprague–Dawley rats were divided into four groups randomly: CME, CME + RES (25 mg/kg), CME + RES (50 mg/kg), and sham (10 rats per group). The CME model was developed. Echocardiography, levels of myocardial injury markers in the serum, and histopathology of the myocardium were used to assess the function of the cardiac muscle. For the detection of the signaling of TLR4/MyD88/NF-κB along with the expression of pyroptosisrelated molecules, ELISA, qRT-PCR, immunofluorescence, and Western blotting were used, among other techniques. The findings revealed that myocardial injury and pyroptosis occurred in the myocardium following CME, with a decreased function of cardiac, increased levels of serum myocardial injury markers, increased area of microinfarct, as well as a rise in the expression levels of pyroptosis-related molecules. In addition to this, pretreatment with resveratrol reduced the severity of myocardial injury after CME by improving cardiac dysfunction, decreasing serum myocardial injury markers, decreasing microinfarct area, and decreasing cardiomyocyte pyroptosis, primarily by blocking the signaling of TLR4/MyD88/NF-κB and also reducing the NLRP3 inflammasome activation. Resveratrol may be able to alleviate CME-induced myocardial pyroptosis and cardiac dysfunction by impeding the activation of NLRP3 inflammasome and the signaling pathway of TLR4/MyD88/NF-κB

Early Diagnosis and Management of Cerebral Venous Flow Obstruction Secondary to Transsinus Fracture after Traumatic Brain Injury

Wen-hao Wang,Jun-ming Lin,Fei Luo,Lian-shui Hu,Jun Li,Wei Huang 대한신경과학회 2013 Journal of Clinical Neurology Vol.9 No.4

Background and Purpose Cerebral venous flow obstruction (CVFO) is a fatal complication of traumatic brain injury. To compare the outcomes of patients with CVFO secondary to traumatic-brain-injury-induced transsinus fracture who were diagnosed early versus those diagnosed late in the therapeutic course. Methods In total, 403 patients with transsinus fracture were reviewed retrospectively. The patients were divided into an early-diagnosis group (n=338) and a delayed-diagnosis group (n=65).The patients submitted to 2D time-of-flight magnetic resonance venography (2D-TOF MRV) and/or CT venography (CTV), depending upon the findings of intracranial pressure monitoring, in order to identify potentially complicated CVFO. These examinations took place within 3 days of the onset of malignant intracranial hypertension symptoms in the early-diagnosis group, and after an average of 7 days in the delayed-diagnosis group. Once diagnosed, patients received intravenous thrombolytic therapy with low-dose urokinase. Patients with massive transsinus epidural hematoma, depressed fracture, or cerebral hernia were treated surgically to relieve the compression and repair any damage to the venous sinuses. Results Cerebral venous flow obstruction was much more severe in the delayed-diagnosis group than in the early-diagnosis group (p<0.001), and hence patients in the former group were given a higher dose of urokinase (p<0.001) for thrombolytic therapy. They were also significantly more likely to need surgery (48.1% vs. 20.6%, p=0.003) and had a higher mortality rate (37.0%vs. 4.1%, p<0.001). However, patients in both groups experienced a similarly favorable prognosis, not only with regard to functional outcome but also with respect to neuroradiological improvement, as evaluated by 2D-TOF MRV/CTV at the final follow-up (p=0.218). Conclusions Delayed diagnosis can result in increased risk of surgery and death in the acute phase. Thrombolytic therapy with low-dose urokinase resulted in promising improvements in both functional and neuroradiological outcomes in all of the patients in this study, regardless of the time to diagnosis. J Clin Neurol 2013;9:259-268

Nonviral delivery systems for antisense oligonucleotide therapeutics

Si Huang,Xin-Yan Hao,Yong-Jiang Li,Jun-Yong Wu,Da-Xiong Xiang,Shilin Luo 한국생체재료학회 2022 생체재료학회지 Vol.26 No.4

Antisense oligonucleotides (ASOs) are an important tool for the treatment of many genetic disorders. However, similar to other gene drugs, vectors are often required to protect them from degradation and clearance, and to accomplish their transport in vivo. Compared with viral vectors, artificial nonviral nanoparticles have a variety of design, synthesis, and formulation possibilities that can be selected to accomplish protection and delivery for specific applications, and they have served critical therapeutic purposes in animal model research and clinical applications, allowing safe and efficient gene delivery processes into the target cells. We believe that as new ASO drugs develop, the exploration for corresponding nonviral vectors is inevitable. Intensive development of nonviral vectors with improved delivery strategies based on specific targets can continue to expand the value of ASO therapeutic approaches. Here, we provide an overview of current nonviral delivery strategies, including ASOs modifications, action mechanisms, and multi-carrier methods, which aim to address the irreplaceable role of nonviral vectors in the progressive development of ASOs delivery.

Lactate potentiates angiogenesis and neurogenesis in experimental intracerebral hemorrhage

Jing Zhou,Tao Liu,Hao Guo,Hanjin Cui,Pengfei Li,Dandan Feng,En Hu,Qing Huang,Ali Yang,Jun Zhou,Jiekun Luo,Tao Tang,Yang Wang 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

Lactate accumulation has been observed in the brain with intracerebral hemorrhage (ICH). However, the outcome of lactate accumulation has not been well characterized. Here, we report that lactate accumulation contributes to angiogenesis and neurogenesis in ICH. In the first set of the experiment, a rat model of ICH was induced by injecting collagenase into the brain. The effects of lactate accumulation on the neurological function, apoptosis, and numbers of newborn endothelial cells and neurons, as well as the proliferation-associated signaling pathway, were evaluated in the rat brain. In the second set, exogenous L-lactate was infused into intact rat brains so that its effects could be further assessed. Following ICH, lactate accumulated around the hematoma; the numbers of PCNA+/vWF+ nuclei and PCNA+/DCX+ cells were significantly increased compared with the numbers in the Sham group. Moreover, ICH induced translocation of nuclear factor-kappa B (NF-κB) p65 into the nucleus, resulting in a notable upregulation of VEGF and bFGF mRNAs and proteins compared with the levels in the Sham controls. Administration of a lactate dehydrogenase inhibitor dramatically inhibited these effects, decreased the vascular density, and aggravated neurological severity scores and apoptosis after ICH. After exogenous L-lactate infusion, the numbers of PCNA+/vWF+ nuclei and PCNA+/DCX+ cells were strikingly increased compared with the numbers in the Sham controls. In addition, lactate facilitated NF-κB translocation to induce increased transcription of VEGF and bFGF. Co-infusion with an NF-κB inhibitor significantly inhibited these effects. These data suggest that lactate potentiates angiogenesis and neurogenesis by activating the NF-κB signaling pathway following ICH.

Serum Carbohydrate Antigen 19-9 as an Indicator of Liver Metastasis in Colorectal Carcinoma Cases

Dong, Hang,Tang, Jie,Li, Long-Hao,Ge, Jun,Chen, Xin,Ding, Jing,Men, Hai-Tao,Luo, Wu-Xia,Du, Yang,Li, Cong,Zhao, Feng,Chen, Ye,Cheng, Ke,Liu, Ji-Yan Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.2

Purpose: The liver is the organ to which colorectal carcinomas (CRCs) most commonly metastasize, and surgical resection has been established as the most effective and potentially curative treatment for CRC with liver metastasis (LM). Therefore, surveillance of LM is vital for improvement of prognosis of CRC patients. In this study, we aimed to explore the potential value of carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA), and marker enzymes in indicating LM with CRC. Methods: Three groups of eligible patients with metastatic cancers were retrospectively included: CRC patients with LM (CRC-LM) or without LM (CRC-NLM), and non-CRC patients with LM (NCRC-LM). All metastatic lesions were identified by CT or MRI. Data on characteristics of the patients, the primary site, the locations of metastasis, CA 19-9, CEA, and biochemical parameters were collected for analysis. Results: A total of 493 patients were retrospectively included. More alcohol consumption was found in CRC-LM than CRC-NLM. Some biochemical enzymes were found to be significantly higher in groups with LM than without (CRC-LM or NCRC-LM v.s CRC-NLM). Both CEA and CA 19-9 were much higher in CRC-LM than CRC-NLM or NCRC-LM. For CRC patients, CA 19-9, ${\gamma}$-glutamyl transpeptidase, CEA and alcohol consumption were identified as independent factors associated with LM. Conclusion: Our analysis suggested the CA 19-9 might be a potential valuable indicator for LM of CRC in the clinic.

PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1

Chen, Gang,Kim, Yong Ho,Li, Hui,Luo, Hao,Liu, Da-Lu,Zhang, Zhi-Jun,Lay, Mark,Chang, Wonseok,Zhang, Yu-Qiu,Ji, Ru-Rong NATURE AMERICA 2017 NATURE NEUROSCIENCE Vol.20 No.7

<P>Programmed cell death ligand-1 (PD-L1) is typically produced by cancer cells and suppresses immunity through the receptor PD-1 expressed on T cells. However, the role of PD-L1 and PD-1 in regulating pain and neuronal function is unclear. Here we report that both melanoma and normal neural tissues including dorsal root ganglion (DRG) produce PD-L1 that can potently inhibit acute and chronic pain. Intraplantar injection of PD-L1 evoked analgesia in naive mice via PD-1, whereas PD-L1 neutralization or PD-1 blockade induced mechanical allodynia. Mice lacking Pd1 (Pdcd1) exhibited thermal and mechanical hypersensitivity. PD-1 activation in DRG nociceptive neurons by PD-L1 induced phosphorylation of the tyrosine phosphatase SHP-1, inhibited sodium channels and caused hyperpolarization through activation of TREK2 K+ channels. PD-L1 also potently suppressed nociceptive neuron excitability in human DRGs. Notably, blocking PD-L1 or PD-1 elicited spontaneous pain and allodynia in melanoma-bearing mice. Our findings identify a previously unrecognized role of PD-L1 as an endogenous pain inhibitor and a neuromodulator.</P>

Factors Potentially Associated with Chemotherapy-induced Anemia in Patients with Solid Cancers

Cheng, Ke,Zhao, Feng,Gao, Feng,Dong, Hang,Men, Hai-Tao,Chen, Ye,Li, Long-Hao,Ge, Jun,Tang, Jie,Ding, Jing,Chen, Xin,Du, Yang,Luo, Wu-Xia,Liu, Ji-Yan Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.10

Purpose: Chemotherapy-induced anemia (CIA) is one of the most important causes of anemia in cancer patients. This study was conducted to describe the prevalence and characteristics of CIA in solid cancer patients in the Chinese population, and to explore the relationship of white blood cell (WBC) or platelet decrease with CIA. Methods: Data on age, gender, tumor diagnosis, anti-cancer treatment and blood cell analyses were available from 220 untreated non-anemic cancer patients who received at least 2 cycles of chemotherapy, and the data were analyzed to assess their relationship with CIA or its severity. Results: 139 patients (63.2%) presented anemia, most being Grade 1 or 2. Esophageal and lung cancers were associated with a high prevalence. G3/4 leucopenia and decrease of platelets were identified as independent risk factors for the occurrence of CIA. Moreover, G3/4 leucopenia, decrease of platelet and G3/4 thrombocytopenia were found to be also associated with the severity of CIA. Cisplatin-containing regimens were a main potential factor in causing CIA, although significant association was only found on univariate analysis. Conclusion: Anemia or decrease in hematoglobin are common in Chinese cancer patients receiving chemotherapy. Cisplatin-containing regimens might be an important factor influencing the occurrence of CIA. Our analysis firstly described some risk factors, such as decrease of platelets or WBCs, severity of leucopenia or thrombocytopenia, associated with the occurrence and severity of CIA.