Rosmarinic acid Ameliorates neuronal regeneration in the bridging silicone rubber conduits of the sciatic nerve in taxol-treated rats.

Background and aim: Taxol modulates local inflammatory conditions in peripheral nerves, which may impair their regeneration and recovery when injured. This study aimed to determine the effects of rosmarinic acid (RA, a polyphenol constituent of many culinary herbs) on the regeneration of the sciatic nerves in the bridging conduits. Experimental procedure: In the cell study, RA decreased nuclear factor (NF)-κB activity induced by taxol in a dose dependency. In the animal model, taxol-treated rats were divided into 3 groups (n = 10/group): taxol (2 mg/kg body weight for 4 times) and taxol + RA (3 times/week for 4 weeks at 20 and 40 mg/kg body weight) groups. Macrophage infiltration, calcitonin gene-related peptide (CGRP) expression levels, neuronal connectivity, animal behavior, and neuronal electrophysiology were evaluated. Results and conclusion: At the end of 4 weeks, macrophage density, CGRP expression level, and axon number significantly increased in the RA group compared with the taxol group. The RA administration unaffected heat, cold plate licking latencies, and motor coordination. Moreover, the 40 mg/kg RA group had significantly larger nerve conduction velocity and less latency compared to the taxol group. This study suggested that RA could ameliorate local inflammatory conditions to augment the recovery of regenerating nerves by accelerating their regrowth and improving electrophysiological function in taxol-treated peripheral nerve injury repaired with the silicone rubber conduit.

Long-Lasting Electret Melt-Blown Nonwoven Functional Filters Made of Organic/Inorganixc Macromolecular Micron Materials: Manufacturing Techniques and Property Evaluations.

Melt-blown nonwoven fabrics for filtration are usually manufactured using polypropylene, but after a certain time period the middle layer of the mask may have a reduced effect on adsorbing particles and may not be easily stored. Adding electret materials not only increases storage time, but also shows in this study that the addition of electret can improve filtration efficiency. Therefore, this experiment uses a melt-blown method to prepare a nonwoven layer, and adds MMT, CNT, and TiO2 electret materials to it for experiments. Polypropylene (PP) chip, montmorillonite (MMT) and titanium dioxide (TiO2) powders, and carbon nanotube (CNT) are blended and made into compound masterbatch pellets using a single-screw extruder. The resulting compound pellets thus contain different combinations of PP, MMT, TiO2, and CNT. Next, a hot pressor is used to make the compound chips into a high-poly film, which is then measured with differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). The optimal parameters are yielded and employed to form the PP/MMT/TiO2 nonwoven fabrics and PP/MMT/CNT nonwoven fabrics. The basis weight, thickness, diameter, pore size, fiber covering ratio, air permeability, and tensile property of different nonwoven fabrics are evaluated in order to have the optimal group of PP-based melt-blown nonwoven fabrics. According to the results of DSC and FTIR measurements, PP and MMT, CNT, and TiO2 are completely mixed, and the melting temperature (Tm), crystallization temperature (Tc) and endotherm area are changed accordingly. The difference in enthalpy of melting changes the crystallization of PP pellets, which in turn changes the fibers. Moreover, the Fourier transform infrared (FTIR) spectroscopy results substantiate that PP pellets are well blended with CNT and MMT, according to the comparisons of characteristic peaks. Finally, the scanning electron microscopy (SEM) observation suggests that with a spinning die temperature of 240 °C and a spinning die pressure lower than 0.01 MPa, the compound pellets can be successfully formed into melt-blown nonwoven fabrics with a 10-micrometer diameter. The proposed melt-blown nonwoven fabrics can be processed with electret to form long-lasting electret melt-blown nonwoven filters.

Residual, regrowth, and new growth of radiofrequency ablation for benign thyroid nodules of different volumes: two-year follow-up results.

INTRODUCTION: Radiofrequency ablation (RFA) is recognized as an effective technique for the treatment of benign thyroid nodules (BTNs), although the long-term results are limited. This study aimed to evaluate the residual vital volume increase, regrowth, and new growth over a 2-year period after RFA among different nodule volume groups. SUBJECTS AND METHODS: This retrospective study evaluated 135 patients with 153 BTNs who underwent ultrasound guided RFA. The BTNs were categorized into small (<10 mL), medium (10-30 mL), and large (>30 mL) according to the initial volume of BTNs prior to ablation. The volume changes of each nodule were analyzed at 1, 3, 6, 12 and 24 months after RFA. New growth was defined as the growth in volume not found in the early follow-up on ultrasonography. RESULTS: The initial ablation ratio of all BTNs was 99.67%. The mean volume reduction ratio (VRR) of BTNs was 85.53% after 2-year follow-up. The small nodule group showed a lower VRR compared to the other two groups at the 1-month follow-up, and there was no difference of VRR at the subsequent follow-ups. The incidence of residual vital volume increase was 4.58%. The overall incidence of regrowth was 3.92% and the mean timing of regrowth was 16.71 months. New growth occurred in 18.95% of patients. No further treatment was required in the majority of cases. CONCLUSION: RFA achieved a clinically relevant volume reduction in different sizes of single BTNs which persisted for at least 2 years, thereby preventing the need for retreatment.

Efficacy and safety of radiofrequency ablation for primary and secondary hyperparathyroidism with or without previous parathyroidectomy: a retrospective study.

INTRODUCTION: This study aimed to investigate and compare the therapeutic efficacy and safety of ultrasound-guided radiofrequency ablation (RFA), between primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism (SHPT) patients, with or without previous parathyroidectomy (PTX). SUBJECTS AND METHODS: A total of 21 patients (7 PHPT, 14 SHPT) underwent RFA for hyperparathyroidism (HPT) at Kaohsiung Chang Gung Memorial Hospital, Taiwan. Five of the 14 SHPT patients had previously received PTX. The laboratory data, volume change of each parathyroid nodule, symptomatic scores, and complications were analyzed and compared between all groups at 1 and 7 days, and at 1, 3, 6, and 12 months after RFA. RESULTS: After RFA, the volume reduction ratio (VRR) for all patients at the last follow-up was 93.76%, and clinical symptoms significantly improved. At 12 months, all PHPT patients achieved successful treatment of intact PTH (iPTH). In SHPT patients, the mean iPTH value significantly decreased 1-day post-RFA, subsequently exhibiting a transient rebound which proceeded to decrease, with 57.1% reaching successful treatment standards. SHPT patients with PTX showed a lower complication score, shorter ablation time, higher iPTH baseline and outcomes, and lower VRR, compared to patients without PTX. The serum calcium level significantly decreased to normal range in 85.7% of all patients at 12 months. Severe hypocalcemia occurred in 23.8% at 1 week, and all were corrected with calcium supplements. CONCLUSIONS: RFA demonstrates a therapeutic efficacy similar to PTX. It can thus be considered an effective alternative treatment for PHPT, SHPT, or post-PTX patients who are unsuitable for another PTX.

Clinical Impact of Gadoxetic Acid-Enhanced Magnetic Resonance Imaging on Living Donor Liver Transplant.

BACKGROUND: Gadolinium-ethoxybenzyl-diethylene triamine pentaacetic acid (Gd-EOB-DTPA) is a newer magnetic resonance contrast that has the combined effect of conventional and liver-specific contrast. The use of Gd-EOB-DTPA may aid in management of patients with hepatocellular carcinoma (HCC) undergoing living donor liver transplant (LDLT). MATERIALS AND METHODS: We retrospectively reviewed all HCC patients who received LDLT with Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) as part of a pretransplant evaluation between October 2012 and October 2016. The detection rate and impact on decision making were assessed between multidetector-row computed tomography (MDCT) and Gd-EOB-DTPA-enhanced MRI with pathology of the explanted liver being the reference standard. RESULTS: We analyzed 25 patients with 80 nodules. Gd-EOB-DTPA-enhanced MRI showed superior detection rate for HCCs than MDCT (76.1% vs 35.8%). Among the 25 patients, 16 had additional HCCs detected by Gd-EOB-DTPA-enhanced MRI, which led to changes in therapeutic decisions in 11 patients. The recurrence rate and mortality rate were 4% (1 of 25). In the same period in our institution, the mortality rate was 13.9% (25 of 180) for those who did not receive Gd-EOB-DTPA-enhanced MRI as part of the pretransplant evaluation. CONCLUSIONS: The use of Gd-EOB-DTPA-enhanced MRI can aid in characterization of indeterminate nodules and detect more HCCs and thus more adequate downstaging and pretransplant neoadjuvant treatment ensue, which may lower the recurrence rate after LDLT.

Snail Mucus Enhances Chemosensitivity of Triple-negative Breast Cancer Via Activation of the Fas Pathway.

BACKGROUND/AIM: The poor prognosis and chemoresistance of patients with triple-negative breast cancer (TNBC) urge the development of new therapeutic strategies. Snail mucus has shown its ability against inflammation, a process closely related to tumorigenesis, suggesting a potential anti-cancer activity. MATERIALS AND METHODS: The effect and mechanisms of snail mucus on cell viability were determined by IncuCyte Live-cell analysis and molecular biological methods. The anti-cancer fractions of snail mucus were isolated and identified by medium pressure liquid chromatography (MPLC) and nuclear magnetic resonance (NMR) spectrometry analysis. RESULTS: Snail mucus significantly decreased the viability of TNBC cells with relatively lower cytotoxicity to normal breast epithelial cells and enhanced their response to chemotherapy through activation of Fas signaling by suppressing nucleolin. Two peptide fractions have been identified as the anti-cancer ingredients of the snail mucus. CONCLUSION: Snail mucus can induce programmed cell death via the extrinsic apoptotic pathway and has therapeutic potential by achieving a chemo-sensitizing effect in TNBCs.

One year follow-up of US-Guided radiofrequency ablation for low-risk papillary thyroid microcarcinoma: The first experience in Taiwan.

BACKGROUND: The incidence of papillary thyroid microcarcinoma (PTMC) has increased rapidly in recent decades, with a favorable overall prognosis. We aimed to evaluate the efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) for treating low-risk PTMC in Taiwan. METHODS: This prospective study included patients with PTMC who were ineligible or refused surgery and underwent US-guided RFA between October 2018 and June 2020. US and computed tomography (CT) were performed before RFA to assess tumor lesions and exclude cervical lymph node metastasis. Sequential US follow-up following RFA was performed after 1, 3, 6, and 12 months, and yearly thereafter. Volume reduction ratio (VRR) and complete disappearance rate of tumor at one year were evaluated. RESULTS: 13 PTMCs in 12 patients were enrolled with a mean follow-up of 16.2 ± 8.1 months (range, 1-24 months). The median largest tumor diameter and tumor volume before RFA were 0.76 cm and 0.15 ml (range, 0.02-0.37 ml). The median (interquartile range, IQR) volume and VRR at 12 months post-RFA were 0 (0, 0.03) ml (p = 0.033) and 100% (84.26%, 100%) (p = 0.008). Eight tumors (61.54%) were completely disappeared at 12 months post-RFA and no tumor recurrence, lymph nodes, or distant metastasis were noted. All tumors were successfully treated without complications. CONCLUSION: Minimally invasive US-guided RFA is an effective and safe alternative for low-risk PTMC, resulting a satisfied VRR.

Effect of genipin crosslinked chitosan scaffolds containing SDF-1 on wound healing in a rat model.

Prolonged healing is a severe problem for elderly and diabetic patients. Impaired angiogenesis, stem cell differentiation, and migration have been shown to delay wound healing. The chemokine stromal cell-derived factor-1 (SDF-1) plays an essential role in recruiting cells to wound sites and is suggested to be a candidate for tissue engineering. In this study, chitosan (CHI) scaffolds were crosslinked with nontoxic genipin (Gp) and further heparinized for SDF-1 immobilization. Then, the structures were evaluated for their physicochemical properties (porosity, swelling ratio, and water vapor transmission rate (WVTR)). The interaction between SDF-1 and heparin could sustain SDF-1 release, which has been shown to enhance human umbilical vein endothelial cell (HUVEC) 2D/3D migration. The investigation of the wound-healing activity of the SDF-1-loaded CHI scaffolds revealed a better wound recovery rate in vivo in healthy and streptozotocin-induced diabetic Sprague-Dawley (SD) rats. The histological analysis illustrated that the local of SDF-1 treatment scaffold at the wound site enhanced neovascularization. The wounds treated with SDF-1 scaffolds also exhibited higher vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-ß) expression in Western blot assays. Based on the wound-healing activity and beneficial characteristics, the SDF-1-loaded CHI scaffold demonstrates potential as a material for treating skin wounds.

Preclinical Evidence of STAT3 Inhibitor Pacritinib Overcoming Temozolomide Resistance via Downregulating miR-21-Enriched Exosomes from M2 Glioblastoma-Associated Macrophages.

BACKGROUND: The tumor microenvironment (TME) plays a crucial role in virtually every aspect of tumorigenesis of glioblastoma multiforme (GBM). A dysfunctional TME promotes drug resistance, disease recurrence, and distant metastasis. Recent evidence indicates that exosomes released by stromal cells within the TME may promote oncogenic phenotypes via transferring signaling molecules such as cytokines, proteins, and microRNAs. RESULTS: In this study, clinical GBM samples were collected and analyzed. We found that GBM-associated macrophages (GAMs) secreted exosomes which were enriched with oncomiR-21. Coculture of GAMs (and GAM-derived exosomes) and GBM cell lines increased GBM cells' resistance against temozolomide (TMZ) by upregulating the prosurvival gene programmed cell death protein 4 (PDCD4) and stemness markers SRY (sex determining region y)-box 2 (Sox2), signal transducer and activator of transcription 3 (STAT3), Nestin, and miR-21-5p and increasing the M2 cytokines interleukin 6 (IL-6) and transforming growth factor beta 1(TGF-ß1) secreted by GBM cells, promoting the M2 polarization of GAMs. Subsequently, pacritinib treatment suppressed GBM tumorigenesis and stemness; more importantly, pacritinib-treated GBM cells showed a markedly reduced ability to secret M2 cytokines and reduced miR-21-enriched exosomes secreted by GAMs. Pacritinib-mediated effects were accompanied by a reduction of oncomiR miR-21-5p, by which the tumor suppressor PDCD4 was targeted. We subsequently established patient-derived xenograft (PDX) models where mice bore patient GBM and GAMs. Treatment with pacritinib and the combination of pacritinib and TMZ appeared to significantly reduce the tumorigenesis of GBM/GAM PDX mice as well as overcome TMZ resistance and M2 polarization of GAMs. CONCLUSION: In summation, we showed the potential of pacritinib alone or in combination with TMZ to suppress GBM tumorigenesis via modulating STAT3/miR-21/PDCD4 signaling. Further investigations are warranted for adopting pacritinib for the treatment of TMZ-resistant GBM in clinical settings.

Electrospun Poly(γ⁻glutamic acid)/ß⁻Tricalcium Phosphate Composite Fibrous Mats for Bone Regeneration.

A poly(γ⁻glutamic acid)/ß⁻tricalcium phosphate (γ⁻PGA/ß⁻TCP) composite fibrous mat was fabricated using the electrospinning technique as a novel bone substitute. The mat was then cross-linked with cystamine in the presence of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide to improve its water-resistant ability. Scanning electron micrographs revealed that the γ⁻PGA/ß⁻TCP fibers had a uniform morphology with diameters ranging from 0.64 ± 0.07 µm to 1.65 ± 0.16 µm. The average diameter of the fibers increased with increasing cross-linking time. Moreover, increasing the cross-linking time and decreasing the γ⁻PGA/ß⁻TCP weight ratio decreased the swelling ratio and in vitro degradation rate of the composite fibrous mat. In vitro experiments with osteoblast-like MG-63 cells demonstrated that the mat with a γ⁻PGA/ß⁻TCP weight ratio of 20 and cross-linked time of 24 h had a higher alkaline phosphatase activity and better cell adhesion. Furthermore, the rat cranial bone defect was created and treated with the γ⁻PGA/ß⁻TCP composite fibrous mat to evaluate its potential in bone regeneration. After 8 weeks of implantation, micro computed tomography showed that the γ⁻PGA/ß⁻TCP composite fibrous mat promoted new bone growth. These observations suggest that the γ⁻PGA/ß⁻TCP composite fibrous mat has a potential application in bone tissue engineering.

Estrogen and/or Estrogen Receptor α Inhibits BNIP3-Induced Apoptosis and Autophagy in H9c2 Cardiomyoblast Cells.

The process of autophagy in heart cells maintains homeostasis during cellular stress such as hypoxia by removing aggregated proteins and damaged organelles and thereby protects the heart during the times of starvation and ischemia. However, autophagy can lead to substantial cell death under certain circumstances. BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), a hypoxia-induced marker, has been shown to induce both autophagy and apoptosis. A BNIP3-docked organelle, e.g., mitochondria, also determines whether autophagy or apoptosis will take place. Estrogen (E2) and estrogen receptor (ER) alpha (ERα) have been shown to protect the heart against mitochondria-dependent apoptosis. The aim of the present study is to investigate the mechanisms by which ERα regulates BNIP3-induced apoptosis and autophagy, which is associated with hypoxic injury, in cardiomyoblast cells. An in vitro model to mimic hypoxic injury in the heart by engineering H9c2 cardiomyoblast cells to overexpress BNIP3 was established. Further, the effects of E2 and ERα in BNIP3-induced apoptosis and autophagy were determined in BNIP3 expressing H9c2 cells. Results from TUNEL assay and Immunoflourecense assay for LC3 puncta formation, respectively, revealed that ERα/E2 suppresses BNIP3-induced apoptosis and autophagy. The Western blot analysis showed ERα/E2 decreases the protein levels of caspase 3 (apoptotic marker), Atg5, and LC3-II (autophagic markers). Co-immunoprecipitation of BNIP3 and immunoblotting of Bcl-2 and Rheb showed that ERα reduced the interaction between BNIP3 and Bcl-2 or Rheb. The results confirm that ERα binds to BNIP3 causing a reduction in the levels of functional BNIP3 and thereby inhibits cellular apoptosis and autophagy. In addition, ERα attenuated the activity of the BNIP3 promoter by binding to SP-1 or NFκB sites.

Increased Calcitonin Gene-Related Peptide and Macrophages Are Involved in Astragalus membranaceus-Mediated Peripheral Nerve Regeneration in Rats.

Astragalus membranaceus (AM) is one of 50 fundamental herbs in traditional Chinese medicine. Previous studies have shown that AM extract can be a potential nerve growth-promoting factor, being beneficial for the growth of peripheral nerve axons. We further investigated the effects of AM extract on regeneration in a rat sciatic nerve transection model. Rats were divided into three groups ([Formula: see text]): normal saline (intraperitoneal) as the control, and 1.5[Formula: see text]g/kg or 3.0[Formula: see text]g/kg of AM extract (every other day for four weeks), respectively. We evaluated neuronal electrophysiology, neuronal connectivity, macrophage infiltration, expression levels and location of calcitonin gene-related peptide (CGRP), and expression levels of both nerve growth factors (NGFs) and immunoregulatory factors. In the high-dose AM group, neuronal electrophysiological function (measured by nerve conductive velocity and its latency) was significantly improved ([Formula: see text]). Expression levels of CGRP and macrophage density were also drastically enhanced ([Formula: see text]). Expression levels of fibroblast growth factor (FGF), NGF, platelet-derived growth factor (PDGF), transforming growth factor-[Formula: see text], interleukin-1 (IL-1), and interferon (IFN)-[Formula: see text] were reduced in the high-dose AM group ([Formula: see text]), while FGF, NGF, PDGF, IL-1, and IFN-[Formula: see text] were increased in the low-dose AM group ([Formula: see text]). These results suggest that AM can modulate local inflammatory conditions, enhance nerve regeneration, and potentially increase recovery of a severe peripheral nerve injury.

Stem cells rescue cardiomyopathy induced by P. gingivalis-LPS via miR-181b.

Systemic inflammation induced by bacterial infection is one of several causative agents for cardiovascular disorders in patients with periodontal disease. Experimental results indicate that miRNAs play important roles in systemic inflammation induced by endotoxins. Further evidence states that stem cell based therapy shows potential in the treatment of inflammatory responses induced by sepsis. This study investigates if stem cells show protective effects on cardiomyocyte damage induced by porphyromonas gingivalis-LPS (Pg-LPS) through regulating miRNAs. H9c2 cardiomyoblasts and neonatal rat cardiomyocytes (NRCMs) were damaged using Pg-LPS in this study. Pg-LPS damaged H9c2 or NRCMs were then rescued using adipose-derived stem cells (ADSC). The experimental results reveal that Pg-LPS treatment is capable of inducing TLR4/NFκB axis activation, cell death signaling and IGF1R/PI3 K/Akt axis suppression. miR181b was downregulated in Pg-LPS damaged H9c2/NRCMs. All markers were improved in H9c2/NRCMs cocultured with ADSC. miR181b mimic and inhibitor confirmed that miR181b plays a central role in regulating the cardio protective effect on Pg-LPS damaged H9c2/NRCMs cocultured with ADSC. miR181b acts as potential therapeutic marker in cardiomyopathy induced by Pg-LPS. Transplantation of adipose-derived stem cells show potential in the treatment of cardiomyopathy induced by porphyromonas gingivalis endotoxin via regulation of miR181b.

Biodegradable Bisvinyl Sulfonemethyl-crosslinked Gelatin Conduit Promotes Regeneration after Peripheral Nerve Injury in Adult Rats.

In our previous study, we found that gelatin-based materials exhibit good conductivity and are non-cytotoxic. In this study, gelatin was cross-linked with bisvinyl sulfonemethyl (BVSM) to fabricate a biodegradable conduit for peripheral nerve repair. First, BVSM on the prepared conduit was characterized to determine its mechanical properties and contact angle. The maximum tensile strength and water contact angle of the gelatin-BVSM conduits were 23 ± 4.8 MPa and 74.7 ± 9°, which provided sufficient mechanical strength to resist muscular contraction; additionally, the surface was hydrophilic. Cytotoxicity and apoptosis assays using Schwann cells demonstrated that the gelatin-BVSM conduits are non-cytotoxic. Next, we examined the neuronal electrophysiology, animal behavior, neuronal connectivity, macrophage infiltration, calcitonin gene-related peptide localization and expression, as well as the expression levels of nerve regeneration-related proteins. The number of fluorogold-labelled cells and histological analysis of the gelatin-BVSM nerve conduits was similar to that observed with the clinical use of silicone rubber conduits after 8 weeks of repair. Therefore, our results demonstrate that gelatin-BVSM conduits are promising substrates for application as bioengineered grafts for nerve tissue regeneration.

Effects of swimming exercise on nerve regeneration in a rat sciatic nerve transection model.

BACKGROUND: Swimming is commonly considered to be an efficient rehabilitation exercise to treat peripheral nerve injury. However, the most effective resistance level and exercise duration is still unclear. We investigated the effects and mechanisms of swimming at various exertion levels in a rat sciatic nerve transection model. METHODS: Sciatic nerve transection rats were randomized into the following four groups based on swimming duration (from the 7th day to the 28th day post-surgery): sedentary control group (SC), S10 group (10 min/3 times/week), S20 group (20 min/3 times/week), and S30 group (30 min/3 times/week) (n = 10 each). Axon regeneration, electrophysiological properties, muscular weights, macrophage infiltration, and nerve repair associated maker, calcitonin gene-related peptide (CGRP), were measured. RESULTS: Dramatic higher successful percentages of nerve regeneration across the 10-mm gaps in swimming groups compared to the SC group. Total area of nerve regeneration significantly improved in the S10 group; however, electrophysiological properties, muscular weights, and macrophage infiltration in the regenerated nerves of rats did not differ significantly between the various exercise groups. CGRP expression was significantly increased in the spinal cord of rats in the S20 group. CONCLUSIONS: Our data indicated that CGRP-related axonal regeneration improved significantly with moderate swimming. These results should inspire new studies in physiotherapeutic practice for related human treatment.

Alpinia oxyphylla Miq. fruit extract activates IGFR-PI3K/Akt signaling to induce Schwann cell proliferation and sciatic nerve regeneration.

BACKGROUND: It is known that the medicinal herb Alpinia oxyphylla Miq. is widely used as a remedy for diarrhea as well as the symptoms accompanying hypertension and cerebrovascular disorders. Moreover, it has also been reported that Alpinia oxyphylla Miq. has beneficial effects on anti-senescence and neuro-protection. This study focuses on the molecular mechanisms by which the Alpinia oxyphylla Miq. fruits promote neuron regeneration. METHODS: A piece of silicone rubber was guided across a 15 mm gap in the sciatic nerve of a rat. This nerve gap was then filled with various doses of Alpinia oxyphylla Miq. fruits to assess their regenerative effect on damaged nerves. Further, we investigated the role of Alpinia oxyphylla Miq. fruits in RSC96 Schwann cell proliferation. RESULTS: Our current results showed that treatment with the extract of Alpinia oxyphylla Miq. fruits triggers the phosphorylated insulin-like growth factor-1 receptor- phosphatidylinositol 3-kinase/serine-threonine kinase pathway, and up-regulated the proliferating cell nuclear antigen in a dose-dependent manner. Cell cycle analysis on RSC96 Schwann cells showed that, after exposure to Alpinia oxyphylla Miq. fruit extract, the transition from the first gap phase to the synthesis phase occurs in 12-18 h. The expression of the cell cycle regulatory proteins cyclin D1, cyclin E and cyclin A increased in a dose-dependent manner. Transfection with a small interfering RNA blocked the expression of phosphatidylinositol 3-kinase and induced down-regulation both on the mRNA and protein levels, which resulted in a reduction of the expression of the survival factor B-cell lymphoma 2. CONCLUSION: We provide positive results that demonstrate that Alpinia oxyphylla Miq. fruits facilitate the survival and proliferation of RSC96 cells via insulin-like growth factor-1 signaling.

Effects of Taxol on Regeneration in a Rat Sciatic Nerve Transection Model.

Recent studies describe taxol as a candidate treatment for promoting central nerve regeneration. However, taxol has serious side effects including peripheral neurotoxicity, and little information is known about the effect of taxol on peripheral nerve regeneration. We investigated the effects of taxol on regeneration in a rat sciatic nerve transection model. Rats were divided into four groups (n = 10): normal saline (i.p.) as the control, Cremophor EL vehicle, and 2 or 6 mg/kg of taxol in the Cremophor EL solution (four times in day-2, 4, 6, and 8), respectively. We evaluated neuronal electrophysiology, animal behaviour, neuronal connectivity, macrophage infiltration, location and expression levels of calcitonin gene-related peptide (CGRP), and expression levels of both nerve growth factors and immunoregulatory factors. In the high-dose taxol group (6 mg/kg), neuronal electrophysiological function was significantly impaired. Licking latencies were significantly changed while motor coordination was unaffected. Neuronal connectivity, macrophage density, and expression levels of CGRP was dramatically reduced. Expression levels of nerve growth factors and immunoregulatory factors was also reduced, while it was increased in the low-dose taxol group (2 mg/kg). These results indicate that taxol can modulate local inflammatory conditions, impair nerve regeneration, and impede recovery of a severe peripheral nerve injury.

Anti-tumor effect of Radix Paeoniae Rubra extract on mice bladder tumors using intravesical therapy.

Radix Paeoniae Rubra (RPR) is the dried root of Paeonia lactiflora Pallas and Paeonia veitchii Lynch, and is a herbal medicine that is widely used in traditional Chinese medicine for the treatment of blood-heat and blood-stasis syndrome, similarly to Cortex Moutan. The present study identified the same three components in RPR and Cortex Moutan extracts. In addition, it has been reported that RPR has an anti-cancer effect. Bladder cancer is the seventh most common type of cancer worldwide. Due to the high recurrence rate, identifying novel drugs for bladder cancer therapy is essential. In the present study, RPR extract was evaluated as a bladder cancer therapy in vitro and in vivo. The present results revealed that RPR extract reduced the cell viability of bladder cancer cells with a half maximal inhibitory concentration of 1-3 mg/ml, and had an extremely low cytotoxic effect on normal urothelial cells. Additionally, RPR decreased certain cell cycle populations, predominantly cells in the G1 phase, and caused a clear sub-G increase. In a mouse orthotopic bladder tumor model, intravesical application of RPR extract decreased the bladder tumor size without altering the blood biochemical parameters of the mice. In summary, the present results demonstrate the anti-proliferative properties of RPR extract on bladder cancer cells, and its anti-bladder tumor effect in vivo. Compared to Cortex Moutan extract, RPR extract may provide a more effective alternative therapeutic strategy for the intravesical therapy of superficial bladder cancer.

Risk of Nongenitourinary Cancers in Patients With Spinal Cord Injury: A Population-based Cohort Study.

Little information is available regarding the risk of nongenitourinary (GU) cancers in patients with spinal cord injury (SCI). The authors conducted a nationwide population-based study to investigate whether a higher risk of non-GU cancer is seen among patients with SCI.Data retrieved from the National Health Insurance Research Database of Taiwan were used in this study. A total of 41,900 patients diagnosed with SCI between 2000 and 2011 were identified from the National Health Insurance Research Database and comprised the SCI cohort. Each of these patients was randomly frequency matched with 4 people from the general population (without SCI) according to age, sex, comorbidities, and index year. Cox proportional hazards regression analysis was used to calculate adjusted hazard ratios and 95% confidence intervals and determine how SCI affected non-GU cancer risk.No significant difference in overall non-GU cancer risk was observed between the SCI and control groups. The patients with SCI exhibited a significantly higher risk of developing esophageal, liver, and hematologic malignancies compared with those without SCI. By contrast, the SCI cohort had a significantly lower risk of colorectal cancer compared with the non-SCI cohort (adjusted hazard ratio = 0.80, 95% confidence interval = 0.69-0.93). Additional stratified analyses by sex, age, and follow-up duration revealed various correlations between SCI and non-GU cancer risk.The patients with SCI exhibited higher risk of esophageal, liver, and hematologic malignancies but a lower risk of colorectal cancer compared with those without SCI. The diverse patterns of cancer risk among the patients with SCI may be related to the complications of chronic SCI.

Risk of Aortic Dissection and Aortic Aneurysm in Patients Taking Oral Fluoroquinolone.

IMPORTANCE: Fluoroquinolones have been associated with collagen degradation, raising safety concerns related to more serious collagen disorders with use of these antibiotics, including aortic aneurysm and dissection. OBJECTIVE: To examine the relationship between fluoroquinolone therapy and the risk of developing aortic aneurysm and dissection. DESIGN, SETTING, AND PARTICIPANTS: We conducted a nested case-control analysis of 1477 case patients and 147 700 matched control cases from Taiwan's National Health Insurance Research Database (NHIRD) from among 1 million individuals longitudinally observed from January 2000 through December 2011. Cases patients were defined as those hospitalized for aortic aneurysm or dissection. One hundred control patients were matched for each case based on age and sex. EXPOSURES: Current, past, or any prior-year use of fluoroquinolone. Current use was defined as a filled fluoroquinolone prescription within 60 days of the aortic aneurysm or dissection; past use refers to a filled fluoroquinolone prescription between 61 and 365 days prior to the aortic aneurysm; and any prior-year use refers to having a fluoroquinolone prescription filled for 3 or more days any time during the 1-year period before the aortic aneurysm or dissection. MAIN OUTCOMES AND MEASURES: Risk of developing aortic aneurysm or dissection. RESULTS: A total of 1477 individuals who experienced aortic aneurysm or dissection were matched to 147 700 controls. After propensity score adjustment, current use of fluoroquinolones was found to be associated with increased risk for aortic aneurysm or dissection (rate ratio [RR], 2.43; 95% CI, 1.83-3.22), as was past use, although this risk was attenuated (RR, 1.48; 95% CI, 1.18-1.86). Sensitivity analysis focusing on aortic aneurysm and dissection requiring surgery also demonstrated an increased risk associated with current fluoroquinolone use, but the increase was not statistically significant (propensity score-adjusted RR, 2.15; 95% CI, 0.97-4.60). CONCLUSIONS AND RELEVANCE: Use of fluoroquinolones was associated with an increased risk of aortic aneurysm and dissection. While these were rare events, physicians should be aware of this possible drug safety risk associated with fluoroquinolone therapy.