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Biomedical subjects

R Wang

Publications and source records attributed to R Wang.

At least 19 recordsLinked to original sources

[Efficacy and safety of thoracic paravertebral block combined with thoracic nerve block for acute herpes zoster neuralgia involving upper thoracic dermatomes in middle-aged and elderly patients].

To investigate the clinical efficacy and safety of ultrasound-guided thoracic paravertebral block (TPVB) combined with pectoral nerve block (Pecs) in the treatment of acute herpetic neuralgia (AHN) involving the upper thoracic segments in middle-aged and elderly patients, a prospective study was conducted. A total of 70 middle-aged and elderly patients with upper thoracic AHN who visited the Department of Pain Medicine at Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, from June to December 2023, were enrolled and randomly divided into a control group and an experimental group using a random number table, with 35 patients in each group. The control group received TPVB once weekly for a total of 3 sessions, while the experimental group received TPVB combined with Pecs block using the same regimen. Outcome measures included the Visual Analogue Scale (VAS) for pain, Pittsburgh Sleep Quality Index (PSQI), 7-item Generalized Anxiety Disorder Scale (GAD-7), 9-item Patient Health Questionnaire (PHQ-9), treatment satisfaction score, incidence of postherpetic neuralgia (PHN), rescue analgesia, and adverse events. Assessments were conducted at 1, 4, 8, and 12 weeks post-treatment, and between-group differences were compared. Ultimately, 33 patients in the experimental group and 31 in the control group completed the follow-up and were included in the final analysis. The results showed that both groups demonstrated significant improvements in VAS scores, PSQI, GAD-7, PHQ-9, and satisfaction scores compared with baseline (all P<0.05). Compared with the control group, the experimental group exhibited significantly lower VAS scores and higher satisfaction scores at 1, 4, and 8 weeks post-treatment (P<0.05), as well as significantly lower PSQI, GAD-7, and PHQ-9 scores at 4 and 8 weeks (P<0.05). There were no statistically significant differences between the two groups in the incidence of PHN, rescue analgesia, or adverse events (all P>0.05). This study demonstrates that compared with TPVB alone, the combination of TPVB and Pecs block provides better pain relief, improves sleep quality, and alleviates anxiety and depression in middle-aged and elderly patients with upper thoracic AHN, with a favorable safety profile.

Humans↗

Prosaposin is a novel androgen-regulated gene in prostate cancer cell line LNCaP.

Androgen-regulated genes (ARG) are implicated in normal and neoplastic growth of the prostate. Recently, we reported genomic amplification and/or overexpression of a previously known neurotrophic factor, prosaposin, in androgen-independent (AI) or metastatic prostate cancer (PCa) cells and tissues. Prosaposin and/or its known active molecular derivatives (e.g., saposin C) function as a pluripotent growth factor with diverse biological activities that favor malignant phenotypes in PCa cells. In addition, prosaposin or saposin C upregulates androgen receptor (AR) and AR-target genes (i.e., prostate-specific antigen, Probasin) expression and activity in LNCaP cells. Here, we examined prosaposin as an ARG. We report that DHT treatment of LNCaP cells increases prosaposin expression. In addition, we demonstrate androgen-responsiveness of prosaposin promoter and AR occupancy to a hormone-responsive element located in the proximal region of the prosaposin promoter. Our data for the first time identify prosaposin as an ARG. This observation, together with the pleiotropic growth factor activity of prosaposin, might suggest a role for this molecule in AR-dependent progression of prostate cancer at its early or late AI-state.

Androgens↗

Cereal-based biorefinery development: integrated enzyme production for cereal flour hydrolysis.

Restructuring the traditional fermentation industry into viable biorefineries for the production of fuels, chemicals and plastics is essential in order to replace (petro)chemical processing. This work presents engineering aspects of Aspergillus awamori submerged fermentation for on-site production of an enzymatic consortium that contains glucoamylase, protease and phosphatase. The crude broth filtrate was used for the production of wheat flour hydrolysates. Improvements on traditional starch hydrolysis carried out in two stages (liquefaction and saccharification) were attempted through integration of unit operations and reduction of processing temperature and reaction duration. An initial increase of temperature to 68 degrees C and a subsequent decrease to 60 degrees C for the rest of the enzymatic hydrolysis resulted in a starch to glucose conversion yield of 94 and 92% when a wheat flour concentration and commercial starch concentration of 225 g L(-1) was used, respectively. The use of crude broth filtrates resulted in the simultaneous hydrolysis of wheat protein and phytic acid, as was indicated by the increase in free amino nitrogen and phosphorus concentration, respectively.

Aspergillus↗

Bioinspired design of dental multilayers.

This paper considers the use of bioinspired functionally graded structures in the design of dental multi-layers that are more resistant to sub-surface crack nucleation. Unlike existing dental crown restorations that give rise to high stress concentration, the functionally graded layers (between crown materials and the joins that attach them to dentin) are shown to promote significant reductions in stress and improvements in the critical crack size. Special inspiration is drawn from the low stress concentrations associated with the graded distributions in the dentin-enamel-junction (DEJ). The implications of such functionally graded structures are also discussed for the design of dental restorations.

Biomechanical Phenomena↗

Valsartan treatment reverses erectile dysfunction in diabetic rats.

In order to investigate the effect of angiotensin receptor blockage (ARB) for the treatment on diabetic erectile dysfunction (ED), we used male Sprague-Dawley rats injected with 65 mg/kg streptozotocin to induce diabetes mellitus. The diabetic rats with ED were selected by hypodermic injection of apomorphine (APO) after 8 weeks of model setting. All rats were divided into four groups: G1 (normal control rats), G2 (diabetic rats treated with normal saline), G3 (diabetic rats treated with valsartan) and G4 (diabetic rats treated with spironolactone). After treatment with drugs for 8 weeks, the rate of erection for each group was evaluated after the injection of APO. The intracavernous pressure (ICP) of each rat was then recorded before and after the electrostimulation of the major pelvic ganglion. The rates of erection and the ICP after electrostimulation for diabetic rats treated with valsartan were significantly higher than that in diabetic rats treated with normal saline and spironolactone. The ARB may be an effective therapy for diabetics with ED.

Angiotensin II↗

Ischemic preconditioning negatively regulates plenty of SH3s-mixed lineage kinase 3-Rac1 complex and c-Jun N-terminal kinase 3 signaling via activation of Akt.

Activation of Akt/protein kinase B has been recently reported to play an important role in ischemic tolerance. We here demonstrate that the decreased protein expression and phosphorylation of phosphatase and tensin homolog deleted from chromosome 10 (PTEN) underlie the increased Akt-Ser-473 phosphorylation in the hippocampal CA1 subfield in ischemic preconditioning (IPC). Co-immunoprecipitation analysis reveals that Akt physically interacts with Rac1, a small Rho family GTPase required for mixed lineage kinase 3 (MLK3) autophosphorylation, and both this interaction and Rac1-Ser-71 phosphorylation induced by Akt are promoted in preconditioned rats. In addition, we show that Akt activation results in the disassembly of the plenty of SH3s (POSH)-MLK3-Rac1 signaling complex and down-regulation of the activation of MLK3/c-Jun N-terminal kinase (JNK) pathway. Akt activation results in decreased serine phosphorylation of 14-3-3, a cytoplasmic anchor of Bax, and prevents ischemia-induced mitochondrial translocation of Bax, release of cytochrome c, and activation of caspase-3. The expression of Fas ligand is also decreased in the CA1 region. Akt activation protects against apoptotic neuronal death as shown in TUNEL staining following IPC. Intracerebral infusion of LY294002 before IPC reverses the increase in Akt phosphorylation and the decrease in JNK signaling activation, as well as the neuroprotective action of IPC. Our results suggest that activation of pro-apoptotic MLK3/JNK3 cascade can be suppressed through activating anti-apoptotic phosphoinositide 3-kinase/Akt pathway induced by a sublethal ischemic insult, which provides a functional link between Akt and the JNK family of stress-activated kinases in ischemic tolerance.

14-3-3 Proteins↗

Cigarette smoke upregulates pulmonary vascular matrix metalloproteinases via TNF-alpha signaling.

Cigarette smoke exposure causes vascular remodeling and pulmonary hypertension by poorly understood mechanisms. To ascertain whether cigarette smoke exposure affects production of matrix metalloproteinases (MMPs) in the pulmonary vessels, we exposed C57Bl/6 (C57) mice or mice lacking TNF-alpha receptors (TNFRKO) to smoke daily for 2 wk or 6 mo. Using laser capture microdissection and RT-PCR analysis, we examined gene expression of MMP-2, MMP-9, MMP-12, MMP-13, and tissue inhibitor of metalloproteinase (TIMP-1) and examined protein production by immunohistochemistry for MMP-2, MMP-9, and MMP-12 in small intrapulmonary arteries. At 2 wk, mRNA levels of TIMP-1 and all MMPs were increased in the C57, but not TNFRKO, mice, and immunoreactive protein for MMP-2, MMP-9, and MMP-12 was also increased in the C57 mice. Increased gelatinase activity was identified by in situ and bulk tissue zymography. At 6 mo, only MMP-12 mRNA levels remained increased in the C57 mice, but at a much lower level; however, MMP-2 mRNA levels increased in the TNFRKO mice. We conclude that smoke exposure increases MMP production in the small intrapulmonary arteries but that, with the exception of MMP-12, increased MMP production is transient. MMPs probably play a role in smoke-induced vascular remodeling, as they do in other forms of pulmonary hypertension, implying that MMP inhibitors might be beneficial. MMP production is largely TNF-alpha dependent, further supporting the importance of TNF-alpha in the pathogenesis of cigarette smoke-induced lung disease.

Animals↗

Systemic inhibition of tumor growth by soluble Flk-1 gene therapy combined with cisplatin.

Soluble Flk-1, a soluble vascular endothelial growth factor (VEGF) receptor, is a potent inhibitor of angiogenesis, which could restrain growth and metastasis of some experimental tumors. However, antiangiogenic agents alone cannot eradicate tumor completely, and should be combined with other therapy to enhance their effects. In this study, we evaluated the antitumor activity of the combination therapy in the immunocompetent BALB/c mice bearing H22 hepatoma and Meth A fibrosarcoma, respectively. Mice were treated with either msFlk-1 i.m. at 100 microg/mouse once every 3 days for four times from day 3 after the tumor cell injection, cisplatin cycled twice (2 mg/kg i.p. on days 4 and 11 after the tumor cell inoculation), or both agents together. Tumor growth and survival time were continually observed. Antiangiogenesis in vivo was determined by CD31 immunohistochemistry. Assessment of apoptotic cells and histological analysis was also conducted in tumor tissues. Our results showed that the combination therapy could evidently improve antitumor efficacy, including tumor growth suppression, mice survival prolongation, tumor cell apoptosis augmentation as well as neovascularization inhibition as compared with controls, without serious adverse effects. Our data suggest that the combination of DDP with msFlk-1 is more effective to suppress tumor growth in mice than either agent alone, and this combination regimen showed its potential for future clinical application.

Animals↗

Effects of Hydrocotyle sibthorpioides extract on transplanted tumors and immune function in mice.

This paper describes the effects of an ethanolic extract of Hydrocotyle sibthorpioides on transplanted tumors and immunologic function in mice. When the H. sibthorpioides extract was administered orally at a dose of 1.5 or 3.0 g/kg body wt./day for 10 days, the inhibition rates for murine hepatic carcinoma clone (Hep), sarcoma 180 crocker clone (S(180)), and uterine cervical carcinoma clone (U(14)) were significantly enhanced. The antitumor activity of H. sibthorpioides is comparable to that of the common antitumor agent 5-fluorouracil. Also, our results indicate that the H. sibthorpioides extract promoted the thymus and spleen indices, and humoral immunity of mice. These observations demonstrated that H. sibthorpioides exerted a potent inhibitory effect on the growth of tumors, in addition to mediating immunomodulatory effects in mice.

Administration, Oral↗

Transfection of Smac sensitizes tumor cells to etoposide-induced apoptosis and eradicates established human hepatoma in vivo.

A major concern in clinical treatment of cancers is resistance of tumors such as hepatocellular carcinoma (HCC) and osteosarcoma to current chemotherapy protocols. Here, we reported that overexpression of second mitochondria-derived activator of caspase (Smac) sensitized osteosarcoma cells and HCC cells in vitro to chemotherapeutic drugs-induced apoptosis. Constitutive expression of Smac resulted in enhanced Bax accumulation on mitochondria upon etoposide stimulation and inhibited Bcl-2-induced antiapoptosis activity. Thus, Smac would sensitize tumor cells to chemotherapeutic drugs in part through promoting Bax translocation to mitochondria and bypassing Bcl-2 block. Moreover, we demonstrated that blockade of Smac expression by antisense smac did not impair etoposide-induced apoptosis; however, p53-induced apoptosis was impaired in smac deficient Saos-2 cell. This suggested Smac might be required in p53-induced apoptosis. Most importantly, complete eradication of HepG2 xenografts in vivo was achieved upon combined therapy with Ad-Smac and 5-Fu. Thus, overexpression of Smac in tumor cells might be a potent strategy for cancer treatment by sensitization of tumor cells to chemotherapeutic drugs.

Animals↗

Using carbon nanotubes to absorb low-concentration hydrogen sulfide in fluid.

Hydrogen sulfide is a colorless and flammable gas under room temperature. Usually hydrogen sulfide is considered to be toxic; however, the recent research revealed that hydrogen sulfide in the cardiovascular system plays the role of a vascular dilator. The physiological role of hydrogen sulfide depends on its in vivo level. As such, the measurement of hydrogen sulfide with nano-quantity resolution becomes an important subject. Existing methods generally require bulky samples and are invasive and offline. It will be significantly helpful to measure hydrogen sulfide with a small amount of tissue in a noninvasive method The first attempt was to take a blood or serum sample with a trace amount to examine the interaction between hydrogen sulfide and carbon nanotube. The carbon nanotube is chosen because of a known fact that hydrogen sulfide can be adsorbed by activated carbon. The carbon nanotube is an excellent activated carbon in this regard. Fluorescence intensity of the carbon nanotube with and without immersion of it in a hydrogen sulfide medium was examined in the study. It was found that the intensities increase as the concentrations of hydrogen sulfide increase. Furthermore, the concentration of 10 microM hydrogen sulfide in water was successfully measured.

Absorption↗

Novel selective cytotoxicity of wild sarsaparilla rhizome extract.

Among six fractions, including total extract and fractions of hexane, ethyl acetate, butanol, water and boiling water extracted and separated from wild sarsaparilla rhizome, the hexane fraction (HRW) was the most effective in eliminating four different human cancer cell lines with cellular viability less than 6.8%. HRW exhibited the highest potency against human leukaemia cells with an IC50 (concentration that inhibited the growth rate of cells by 50%) of 3.3 +/- 0.3 microg mL(-1), which was 17.6-fold smaller than that against normal human umbilical vein endothelial cells (IC50, 58.0 +/- 1.5 microg mL(-1)). For its rich natural resources, simple extraction procedure and high yield (3.2%), HRW has the potential to be developed as a selective anti-cancer nutraceutical or pharmaceutical natural health product with low side effects and high economical return.

Antineoplastic Agents, Phytogenic↗

Increased HO-1 expression and decreased iNOS expression in the hippocampus from adult spontaneously hypertensive rats.

Brain expression of heme oxygenase (HO) and nitric oxide synthase (NOS) in hypertension may participate in the pathogenesis of hypertension-related neuronal disorders, such as vascular dementia. In the present study, expression levels of HO and NOS in spontaneously hypertensive rats (SHR) were investigated using Western immunoblotting assay. Expression level of inducible HO-1 in hippocampus of 4-wk prehypertensive SHR was about twofold of that in age-matched Sprague-Dawley (SD) rats (p < 0.01). In 23-wk SHR with fully developed hypertension, hippocampal HO-1 level was significantly greater than that of age-matched SD rats (p < 0.05), but not different from 4-wk SHR. There was no difference in expression levels of hippocampal HO-2 between SHR and SD rats at different ages. Total enzymatic activity of hippocampal HO was significantly greater in 23-wk SHR than in age-matched SD rats or 4-wk SD/SHR (p < 0.01). Although hippocampal expression of nNOS protein was relatively unchanged, iNOS expression in 23-wk SHR was about fourfold lower than that in age-matched SD rats and 4-wk SD/SHR (p < 0.01). Total enzymatic activity of hippocampal NOS was significantly lower in 23-wk SHR than in age-matched SD rats or 4-wk SD/SHR (p < 0.01). Significantly suppressed Morris water maze performance was found in 23-wk SHR in comparison with age-matched SD rats. Because SHR has been used as a model of vascular dementia and hippocampus is essential for spatial learning and memory, understanding of altered HO/CO and NOS/NO systems in the hippocampus of adult SHR may shed light on the pathogenic development of memory deficits associated with vascular dementia.

Aging↗

Reveal protein molecular structural-chemical differences between two types of winterfat (forage) seeds with physiological differences in low temperature tolerance using synchrotron-based Fourier transform infrared microspectroscopy.

Winterfat (Krascheninnikovia lanata) (forage seed) is a long-lived native shrub with superior forage quality for livestock and wildlife. The objectives of this study were to use advanced synchrotron technology [S-Fourier transform infrared microspectroscopy (FTIR)] as a novel approach to reveal protein molecular structural-chemical differences in terms of protein secondary structures between the two types of winterfat (forage) seeds, which show physiological differences in low-temperature tolerances. This experiment was performed at beamline U10B at the National Synchrotron Light Source (NSLS) in Brookhaven National Laboratory (BNL), U.S. Department of Energy (NSLS-BNL, New York). The results showed that with the synchrotron analytical technique (S-FTIR), the molecular structural-chemical makeup and characteristics of the winterfat seed tissues could be imaged and revealed. The protein secondary structures differed between the large and the small seed tissues. By using the multicomponent peaks modeling method, the results show that the large seeds contained no significant differences (P > 0.05) in percentage of beta-sheet (average 37.0%) and alpha-helix (average 24.1%). However, the large seeds contained a lower (P < 0.05) percentage of beta-turns (18.1 vs 20.1%) and a lower (P < 0.05) ratio of beta-turns to alpha-helices (0.8 vs 0.9) and beta-turns to beta-sheets (0.5 vs 0.6). Our results demonstrate the potential of highly spatially resolved synchrotron-based FTIR microspectroscopy to reveal differences of structural molecular chemistry and protein secondary structures, which are associated with seed size variation and may affect germination behaviors.

Amaranthaceae↗

Effects of oleic acid on distinct populations of neurons in the hypothalamic arcuate nucleus are dependent on extracellular glucose levels.

Pharmacological manipulation of fatty acid metabolism in the hypothalamic arcuate nucleus (ARC) alters energy balance and glucose homeostasis. Thus, we tested the hypotheses that distinctive populations of ARC neurons are oleic acid (OA) sensors that exhibit a glucose dependency, independent of whether some of these OA sensors are also glucose-sensing neurons. We used patch-clamp recordings to investigate the effects of OA on ARC neurons in brain slices from 14- to 21-day-old Sprague-Dawley (SD) rats. Additionally, we recorded spontaneous discharge rate in ARC neurons in 8-wk-old fed and fasted SD rats in vivo. Patch-clamp studies showed that in 2.5 mM glucose 12 of 94 (13%) ARC neurons were excited by 2 microM OA (OA-excited or OAE neurons), whereas six of 94 (6%) were inhibited (OA-inhibited2.5 or OAI2.5 neurons). In contrast, in 0.1 mM glucose, OA inhibited six of 20 (30%) ARC neurons (OAI0.1 neurons); none was excited. None of the OAI0.1 neurons responded to OA in 2.5 mM glucose. Thus OAI2.5 and OAI0.1 neurons are distinct. Similarly, in seven of 20 fed rats (35%) the overall response was OAE-like, whereas in three of 20 (15%) it was OAI-like. In contrast, in fasted rats only OAI-like response were observed (three of 15; 20%). There was minimal overlap between OA-sensing neurons and glucose-sensing neurons. In conclusion, OA regulated three distinct subpopulations of ARC neurons in a glucose-dependent fashion. These data suggest that an interaction between glucose and fatty acids regulates OA sensing in ARC neurons.

Action Potentials↗

Mechanisms governing the inelastic deformation of cortical bone and application to trabecular bone.

To understand the inelastic response of bone, a three-part investigation has been conducted. In the first, unload/reload tests have been used to characterize the hysteresis and provide insight into the mechanisms causing the strain. The second part devises a model for the stress/strain response, based on understanding developed from the measurements. The model rationalizes the inelastic deformation in tension, as well as the permanent strain and hysteresis. In the third part, a constitutive law representative of the deformation is selected and used to illustrate the coupled buckling and bending of ligaments that arise when trabecular bone is loaded in compression.

Animals↗

Monitoring circulatory heme level in hemin therapy for lowering blood pressure in rats.

Hemin and other heme derivatives, e.g. heme-L-lysinate (HLL) and heme-L-arginate, have been used extensively to upregulate expression of heme oxygenase and production of endogenous carbon monoxide. Hemin administration has been shown to markedly decrease high blood pressure in spontaneously hypertensive rats (SHR), but not in normotensive Wistar-Kyoto or Sprague Dawley (SD) rats. While methodology to measure serum heme levels has been established long ago, metabolism of the injected hemin or heme derivatives when used to lower blood pressure has not been investigated. In this study, metabolism of hemin or HLL after injected into the rat was monitored by measuring changes in circulatory heme levels. SHR (12-20 weeks old) had significantly higher blood pressure than age-matched SD rats. In both strains, serum heme level was negligible. Hemin or HLL injection (15 mg/kg/day, i.p.) for 5-13 days significantly lowered blood pressure of 12-weeks SHR. High blood pressure was not lowered in SHR older than 20 weeks until hemin or HLL injection period was beyond 5 days. This anti-hypertensive effect of hemin and HLL was synchronized with an increase in serum heme level, from undetectable to 4.3 micromol/l. On the other hand, hemin or HLL had no effect on blood pressure of age-matched SD rats, despite serum heme level rose to the same extent as in the treated SHR. There was no significant difference between hemin and HLL injections in terms of changes in blood pressure and serum heme level in all rats. Our study for the first time correlated changes in serum heme levels with blood pressure levels after injection of hemin or HLL in SHR and SD rats. Hemin and HLL had similar effects on blood pressure change and serum heme level. By determining serum heme levels following the administration of hemin or HLL, we can better understand mechanisms for the blood pressure lowering effect of hemin therapy. Application of this heme monitoring technology will also pave the way for clinical application of hemin therapy in treatment of different types of hypertension pathologies.

Animals↗