Therapeutic Effect of Icaritin on Cerebral Ischemia-Reperfusion-Induced Senescence and Apoptosis in an Acute Ischemic Stroke Mouse Model.

An ischemic stroke is brain damage caused by interruption of blood supply to the brain that can cause death and long-term disability. New medical strategies or therapies are urgently needed for ischemic stroke. Icaritin (ICT) is a metabolite of icariin (ICA), which are two active flavonoid components extracted from Herba epimedii and considered neuroprotective agents in animal models of Alzheimer's disease and ischemic stroke. The therapeutic effect of ICT on ischemic still remains to be clarified. The aim of this study was to investigate the therapeutic effect of ICT on cerebral ischemia-reperfusion-associated senescence and apoptosis in a middle cerebral artery occlusion (MCAO) mouse model (ischemia for 50 min and reperfusion for 24 h). Administration of ICT after ischemia significantly reduced MCAO-induced neurological damage, infarct volume, and histopathological changes in the brain of acute ischemic stroke mice. ICT treatment could also reduce neuronal apoptosis and senescence and reversed the expression of apoptosis- and senescence-related signaling proteins. These findings suggest that ICT may have therapeutic potential to ameliorate acute ischemic stroke.

Contemporary management of pediatric spinal tumors: a single institute's experience in Taiwan in the modern era.

INTRODUCTION: Pediatric spinal tumors are unique pathologies treated by pediatric neurosurgeons. Special attention is required for the preservation of neural function and bony alignment. We reported our experience in the management of these challenging lesions. METHODS: A total of 75 pediatric patients with spinal tumors treated at the National Taiwan University Hospital from 1998 to 2018 were identified retrospectively. Clinical data, radiographic image, and pathological report were reviewed for analysis. RESULTS: There were 37 females and 38 males. The median age was 9 years. Thirty-eight tumors (50.6%) were extradural, 20 (26.7%) intradural extramedullary, and 17 (22.6%) intramedullary. The most common pathologies were glioma, ependymoma, and neuroblastoma. The rate of total and subtotal resection was 45.3% and 21.3%. Thirty-four patients (45.3%) required post-operative adjuvant therapy. Eight patients (10.6%) with spinal deformity had simultaneous tumor excision and spinal fusion surgery. Additional six (8%) patients had subsequent spinal fixation and fusion for deformity after primary tumor operation. Eighty-four percent of patients were ambulatory 3 years after operation. For patients with intradural extramedullary and intramedullary tumors, worse survival outcome was associated with tumor derived from CSF seeding and cranial involvement of spinal tumor, while poorer functional outcome was correlated with cranial involvement and adjuvant therapy with chemotherapy or radiotherapy. CONCLUSIONS: Pediatric spinal tumor surgery carries low surgical morbidity and mortality under current standard of neurosurgical practice. Post-operative adjuvant therapy is required for nearly half of the cases. Spinal deformity requires special attention and sometimes surgical correction. Contemporary management of pediatric spinal tumors enables effective ablation of the lesion and delivers favorable outcome for the majority of patients.

Inorganic Arsenic Exposure Decreases Muscle Mass and Enhances Denervation-Induced Muscle Atrophy in Mice.

Arsenic is a toxic metalloid. Infants with a low birth-weight have been observed in areas with high-level arsenic in drinking water ranging from 463 to 1025 µg/L. A distal muscular atrophy side effect has been observed in acute promyelocytic leukemia patients treated with arsenic trioxide (As2O3) for therapy. The potential of As2O3 on muscle atrophy remains to be clarified. In this study, the myoatrophic effect of arsenic was evaluated in normal mice and sciatic nerve denervated mice exposed with or without As2O3 (0.05 and 0.5 ppm) in drinking water for 4 weeks. We found that both 0.05 and 0.5 ppm As2O3 increased the fasting plasma glucose level; but only 0.5 ppm arsenic exposure significantly decreased muscle mass, muscle endurance, and cross-sectional area of muscle fibers, and increased muscle Atrogin-1 protein expression in the normal mice. Both 0.05 and 0.5 ppm As2O3 also significantly enhanced the inhibitory effects on muscle endurance, muscle mass, and cross-sectional area of muscle fibers, and increased the effect on muscle Atrogin-1 protein expression in the denervated mice. These in vivo results suggest that inorganic arsenic at doses relevant to humans may possess myoatrophic potential.

Low Intensity Pulsed Ultrasound Prevents Recurrent Ischemic Stroke in a Cerebral Ischemia/Reperfusion Injury Mouse Model via Brain-derived Neurotrophic Factor Induction.

The incidence of stroke recurrence is still higher despite the advanced progression of therapeutic treatment and medical technology. Low intensity pulsed ultrasound (LIPUS) has been demonstrated to possess therapeutic effects on neuronal diseases and stroke via brain-derived neurotrophic factor (BDNF) induction. In this study, we hypothesized that LIPUS treatment possessed therapeutic benefits for the improvement of stroke recurrence. Adult male C57BL/6J mice were subjected to a middle cerebral artery occlusion (MCAO) surgery and then followed to secondary MCAO surgery as a stroke recurrence occurred after nine days from the first MCAO. LIPUS was administered continuously for nine days before secondary MCAO. LIPUS treatment not only decreased the mortality but also significantly moderated neuronal function injury including neurological score, motor activity, and brain pathological score in the recurrent stroke mice. Furthermore, the administration of LIPUS attenuated the apoptotic neuronal cells and increased Bax/Bcl-2 protein expression ratio and accelerated the expression of BDNF in the brain of the recurrent stroke mice. Taken together, these results demonstrate for the first time that LIPUS treatment arouses the expression of BDNF and possesses a therapeutic benefit for the improvement of stroke recurrence in a mouse model. The neuroprotective potential of LIPUS may provide a useful strategy for the prevention of a recurrent stroke.

Titanium nanoparticle inhalation induces renal fibrosis in mice via an oxidative stress upregulated transforming growth factor-ß pathway.

Titanium dioxide nanoparticles (Nano-TiO2) are gradually being used extensively in clinical settings, industry, and daily life. Accumulation studies showed that Nano-TiO2 exposure is able to cause injuries in various animal organs, including the lung, liver, spleen, and kidney. However, it remains unclear whether exposure of Nano-TiO2 by inhalation causes renal fibrosis. Here, we investigated the role of reactive oxygen species (ROS)/reactive nitrogen species (RNS) related signaling molecules in chronic renal damage after Nano-TiO2 inhalation in mice. Mice were treated with Nano-TiO2 (0.1, 0.25, and 0.5 mg/week) or microparticle-TiO2 (0.5 mg/week) by nonsurgical intratracheal instillation for 4 weeks. The results showed that Nano-TiO2 inhalation increased renal pathological changes in a dose-dependent manner. No renal pathological changes were observed in microparticle-TiO2-instilled mice. Nano-TiO2 (0.5 mg/week) possessed the ability to precipitate in the kidneys, determined by transmission electron microscopy and increased serum levels of blood urea nitrogen. The expressions of markers of ROS/RNS and renal fibrosis markers, including nitrotyrosine, inducible nitric oxide synthase, hypoxia inducible factor-1α (HIF-1α), heme oxygenase 1, transforming growth factor-ß (TGFß), and collagen I, determined by immunohistochemical staining were increased in the kidneys. Furthermore, Nano-TiO2-induced renal injury could be mitigated by iNOS inhibitor aminoguanidine and ROS scavenger N-acetylcysteine treatment in transcription level. The in vitro experiments showed that Nano-TiO2 significantly and dose-dependently increased the ROS production and the expressions of HIF-1α and TGFß in human renal proximal tubular cells, which could be reversed by N-acetylcysteine treatment. Taken together, these results suggest Nano-TiO2 inhalation might induce renal fibrosis through a ROS/RNS-related HIF-1α-upregulated TGF-ß signaling pathway.

Correlating vestibular schwannoma size with vestibular-evoked myogenic potential results.

OBJECTIVES: The maximum size of the vestibular schwannoma (VS) that is compatible with preservation of the function of the vestibular nerve in performing stereotactic radiosurgery remains unclear. This study utilized ocular vestibular-evoked myogenic potential (oVEMP) and cervical VEMP (cVEMP) test results to correlate with the size of VS. DESIGN: Fifty patients with unilateral VS underwent audiometry, and caloric, oVEMP and cVEMP tests. Tumor size from magnetic resonance imaging was measured on the axial plane, and the relationships between tumor size and each test result were analyzed. RESULTS: The pure-tone average from four frequencies did not significantly predict tumor size. Alternatively, oVEMP and cVEMP responses remained significant predictors for tumor size in the regression model, namely, tumor size (cm) = 0.62 × (oVEMP response) + 1.39 × (cVEMP response), where oVEMP and cVEMP responses were regarded as binary variables, in which 1 and 0 reflect abnormal and normal responses, respectively. This model explained 76% of the variance. Accordingly, the estimated VS size exhibiting abnormal oVEMPs and cVEMPs is >2.01 (0.62 +1.39) cm. CONCLUSIONS: When VS size is <2.0 cm, preservation of the function of superior/inferior vestibular nerve indicated by the oVEMP/cVEMP test is achievable. Therefore, both oVEMP and cVEMP tests may serve as supplementary tools for determining treatment option in VS patients.

Wogonin ameliorates ER stress-associated inflammatory response, apoptotic death and renal fibrosis in a unilateral ureteral obstruction mouse model.

Wogonin, a vital bioactive compound extracted from the medicinal plant, Scutellaria baicalensis, has been wildly used for its potential in mitigating the progression of chronic diseases. Chronic kidney disease (CKD) represents a significant global health challenge due to its high prevalence, morbidity and mortality rates, and associated complications. This study aimed to assess the potential of wogonin in attenuating renal fibrosis and to elucidate the underlying molecular mechanisms using a unilateral ureteral obstruction (UUO) mouse model as a CKD mimic. Male mice, 8 weeks old, underwent orally administrated of either 50 mg/kg/day of wogonin or positive control of 5 mg/kg/day candesartan following UUO surgery. NRK52E cells were exposed to tumor growth factors-beta (TGF-ß) to evaluate the anti-fibrotic effects of wogonin. The results demonstrated that wogonin treatment effectively attenuated TGF-ß-induced fibrosis markers in NRK-52E cells. Additionally, administration of wogonin significantly improved histopathological alterations and downregulated the expression of pro-fibrotic factors (Fibronectin, α-smooth muscle actin, Collagen IV, E-cadherin, and TGF-ß), oxidative stress markers (Catalase, superoxide dismutase 2, NADPH oxidase 4, and thioredoxin reductase 1), inflammatory molecules (Cyclooxygenase-2 and TNF-α), and the infiltration of neutrophils and macrophages in UUO mice. Furthermore, wogonin treatment mitigated endoplasmic reticulum (ER) stress-associated molecular markers (GRP78, GRP94, ATF4, CHOP, and the caspase cascade) and suppressed apoptosis. The findings indicate that wogonin treatment ameliorates key fibrotic aspects of CKD by attenuating ER stress-related apoptosis, inflammation, and oxidative stress, suggesting its potential as a future therapeutic target.

A proposed method to comprehensively define outcomes in acoustic tumor patients undergoing CyberKnife management.

BACKGROUND: Vestibular assessment in patients with acoustic tumor (so-called vestibular schwannoma, VS) via ocular vestibular-evoked myogenic potential (oVEMP) and cervical VEMP (cVEMP) tests are not often discussed in the neurosurgical literature. OBJECTIVES: This study conducted physiological and morphological assessments for VS patients before and after CyberKnife radiosurgery. METHODS: Twenty patients with unilateral VS underwent a battery of tests comprising facial nerve function test, audiometry, and caloric, oVEMP and cVEMP tests before and 2 years after CyberKnife treatment at a mean dosage of 18 Gy in 3 fractions. RESULTS: The abnormal percentages of caloric, oVEMP and cVEMP tests did not significantly differ before and after Cyberknife treatment, indicating that preservation of the superior and inferior vestibular nerves can be achieved after radiosurgery. Median tumor volumes, 1.49 cm3 before treatment versus 0.97 cm3 at 2 years after treatment, differed significantly. CONCLUSIONS: The use of oVEMP and cVEMP tests in VS patients before stereotactic radiosurgery may help to evaluate the tumor origin from the superior or inferior vestibular nerve. It takes a short time and costs less, and it would be practical to make this a routine examination in VS patients having stereotactic radiosurgery.

Integration of MRI and somatosensory evoked potentials facilitate diagnosis of spinal cord compression.

This study aimed to integrate magnetic resonance imaging (MRI) and related somatosensory evoked potential (SSEP) features to assist in the diagnosis of spinal cord compression (SCC). MRI scans were graded from 0 to 3 according to the changes in the subarachnoid space and scan signals to confirm differences in SCC levels. The amplitude, latency, and time-frequency analysis (TFA) power of preoperative SSEP features were extracted and the changes were used as standard judgments to detect neurological function changes. Then the patient distribution was quantified according to the SSEP feature changes under the same and different MRI compression grades. Significant differences were found in the amplitude and TFA power between MRI grades. We estimated three degrees of amplitude anomalies and power loss under each MRI grade and found the presence or absence of power loss occurs after abnormal changes in amplitude only. For SCC, few integrated approach combines the advantages of both MRI and evoked potentials. However, integrating the amplitude and TFA power changes of SSEP features with MRI grading can help in the diagnosis and speculate progression of SCC.

Spinal metastases from non-small cell lung cancer - Is surgical extent enough by following suggestions of the Tomita and Tokuhashi scores?

BACKGROUND/OBJECTIVE: The Tomita, revised Tokuhashi and Tokuhashi lung scores are commonly used tools to predict the survival of patients with spinal metastases and to guide decisions regarding surgical treatment. These prognostic scores, however, tend to underestimate the prognosis of patients with lung cancer. We examined surgical outcome and hopefully provide a more accurate reference for management. METHODS: The consistency between predicted and actual survival was examined using the Tomita and Tokuhashi scores. Various factors that may influence survival were analyzed. Primary outcomes were overall survival (OS) and progression-free survival (PFS), defined as the ambulatory time after the initial surgery. Secondary outcomes included reoperation events, blood loss, and hospitalization days. RESULTS: One hundred seventy-two patients were enrolled. Correct survival predictions were made for 28%, 42%, and 56% with the Tomita, revised Tokuhashi, and Tokuhashi lung scores, respectively. The Tokuhashi lung scores underestimated OS by 35%-40%. Body mass index ≥20, systemic treatment-naïve, good general condition, the use of denosumab, and adenocarcinoma were found to positively affect OS and PFS. There was no significant difference between palliative decompression and excisional surgery regarding OS and PFS. CONCLUSION: Patients with spinal metastases from lung cancer had better prognosis than that predicted by the Tomita and Tokuhashi scores. Spine surgeons should acknowledge this discrepancy and treat these patients with at least the aggressiveness suggested. Patients with adenocarcinoma, amenable to target therapy, denosumab, good general condition, systemic treatment-naïve are better candidates for surgery. Those with cachexic status and unresectable visceral metastases are worse candidates.

Metastatic spinal cord compression as the first manifestation of malignancy: A retrospective study of surgical outcome from single institution.

BACKGROUND: Given the limited studies addressing the issue about the effect of different surgical modalities for metastatic spinal cord compression (MSCC) as the first malignancy manifestation, we conducted a retrospective case-control study to evaluate the surgical outcome of MSCC as the first malignancy manifestation. METHODS: A total of 128 patients who were suspected of having metastatic spinal cord compression and underwent surgery from 2008 to 2021 were enrolled in the study. All patients were categorized into either 'debulking group' or 'palliative group'. RESULTS: The primary outcome was progression-free survival (PFS). The secondary outcomes were overall survival (OS), Frankel scale, and Karnofsky scores. All the outcomes were analyzed with a data cutoff of December 31, 2021. There was a significant difference between groups in progression-free survival (PFS) (p = 0.0094). However, there was no significant difference between groups in the overall survival (OS) (p = 0.0746). Age of onset, gender, duration of symptoms, and location of spinal metastasis, initial Frankel, initial Tomita scores, and initial Karnofsky performance scale showed no significant differences between groups. CONCLUSION: In conclusion, debulking surgery was shown to provide better neurological recoveries and could be considered first in patients with metastatic spinal cord compression as the first malignancy manifestation.

Delay of Surgery for Spinal Metastasis due to the COVID-19 Outbreak Affected Patient Outcomes.

OBJECTIVE: The present study is to analyze the effects of the coronavirus disease 2019 (COVID 2019) outbreak and the subsequent lockdown on the outcomes of spinal metastasis patients. METHODS: The study was a retrospective analysis of data from a prospective cohort study. All patients underwent surgical intervention for spinal metastases between January 2019 and December 2021 and had at least 3 months of postoperative follow-up. The primary outcome was overall mortality during the 4 different stages (pre-COVID-19 era, COVID-19 pandemic except in Taiwan, national lockdown, lifting of the lockdown). The secondary outcomes were the oncological severity scores, medical/surgical accessibility, and patient functional outcome during the 4 periods as well as survival/mortality. RESULTS: A total of 233 patients were included. The overall mortality rate was 41.20%. During the Taiwan lockdown, more patients received palliative surgery than other surgical methods, and no total en bloc spondylectomy was performed. The time from surgeon visit to operation was approximately doubled after the COVID-19 outbreak in Taiwan (75.97, 86.63, 168.79, and 166.91 hours in the 4 periods, respectively). The estimated survival probability was highest after the national lockdown was lifted and lowest during the lockdown. In the multivariate analysis, increased risk of mortality was observed with delay of surgery, with emergency surgery having a higher risk with delays above 33 hours, urgent surgery (below 59 and above 111 hours), and elective surgery (above 332 hours). CONCLUSION: The COVID-19 pandemic and related policies have altered daily clinical practice and negatively impacted the survival of patients with spinal metastases.

Bioactive Flavonoids Icaritin and Icariin Protect against Cerebral Ischemia-Reperfusion-Associated Apoptosis and Extracellular Matrix Accumulation in an Ischemic Stroke Mouse Model.

Stroke, which is the second leading cause of mortality in the world, is urgently needed to explore the medical strategies for ischemic stroke treatment. Both icariin (ICA) and icaritin (ICT) are the major active flavonoids extracted from Herba epimedii that have been regarded as the neuroprotective agents in disease models. In this study, we aimed to investigate and compare the neuroprotective effects of ICA and ICT in a middle cerebral artery occlusion (MCAO) mouse model. Male ICR mice were pretreated with both ICA and ICT, which ameliorated body weight loss, neurological injury, infarct volume, and pathological change in acute ischemic stroke mice. Furthermore, administration of both ICA and ICT could also protect against neuronal cell apoptotic death, oxidative and nitrosative stress, lipid peroxidation, and extracellular matrix (ECM) accumulation in the brains. The neuroprotective effects of ICT are slightly better than that of ICA in acute cerebral ischemic stroke mice. These results suggest that pretreatment with both ICA and ICT improves the neuronal cell apoptosis and responses of oxidative/nitrosative stress and counteracts the ECM accumulation in the brains of acute cerebral ischemic stroke mice. Both ICA and ICT treatment may serve as a useful therapeutic strategy for acute ischemic stroke.

Protective Effects of Nootkatone on Renal Inflammation, Apoptosis, and Fibrosis in a Unilateral Ureteral Obstructive Mouse Model.

Nootkatone is one of the major active ingredients of Alpiniae oxyphyllae, which has been used as both food and medicinal plants for the treatment of diarrhea, ulceration, and enuresis. In this study, we aimed to investigate whether nootkatone treatment ameliorated the progression of chronic kidney diseases (CKD) and clarified its underlying mechanisms in an obstructive nephropathy (unilateral ureteral obstructive; UUO) mouse model. Our results revealed that nootkatone treatment preventively decreased the pathological changes and significantly mitigated the collagen deposition as well as the protein expression of fibrotic markers. Nootkatone could also alleviate oxidative stress-induced injury, inflammatory cell infiltration, and renal cell apoptotic death in the kidneys of UUO mice. These results demonstrated for the first time that nootkatone protected against the progression of CKD in a UUO mouse model. It may serve as a potential therapeutic candidate for CKD intervention.

Reproductive failure in wild boars associated to porcine parvovirus infection and in vivo and in vitro characterization of the causal isolate.

Investigations were made to identify the causal agent of an acute outbreak of abortions in a domesticated herd of wild boar. Only porcine parvovirus (PPV) was isolated from samples of organs from the still-born sucklings and mummified aborted fetuses. The isolated virus hemagglutinated erythrocytes of guinea pig, murine, rat, and chicken. Identity of the virus, designated the BQ strain, was confirmed by the production of a specific cytopathic effect on susceptible cells and by the results from ELISA, PCR, immunofluorescence assay, and electron microscopy. PPV BQ strain was adapted to growth in a swine testicular cell line. When inoculated into healthy sows, PPV BQ caused the same reproductive disorder observed in the affected herd.

Withaferin A protects against endoplasmic reticulum stress-associated apoptosis, inflammation, and fibrosis in the kidney of a mouse model of unilateral ureteral obstruction.

BACKGROUND: Withaferin A is a functional ingredient of a traditional medicinal plant, Withania somnifera, which has been broadly used in India for protecting against chronic diseases. This bioactive steroidal lactone possesses multiple functions such as anti-oxidation, anti-inflammation, and immunomodulation. Chronic kidney disease (CKD) is one of the major health problems worldwide with the high complication, morbidity, and mortality rates. The detailed effects and underlying mechanisms of withaferin A on CKD progression still remain to be clarified. PURPOSE: We aimed to investigate whether withaferin A treatment ameliorates the development of renal fibrosis and its related mechanisms in a CKD mouse model. METHODS: A mouse model of unilateral ureteral obstruction (UUO) was used to mimic the progression of CKD. Male adult C57BL/6J mice were orally administered with 3 mg/kg/day withaferin A for 14 consecutive days after UUO surgery. Candesartan (5 mg/kg/day) was used as a positive control. RESULTS: Both Withaferin A and candesartan treatments significantly ameliorated the histopathological changes and collagen deposition in the UUO kidneys. Withaferin A could significantly reverse the increases in the protein levels of pro-fibrotic factors (fibronectin, transforming growth factor-ß, and α-smooth muscle actin), inflammatory signaling molecules (phosphorylated nuclear factor-κB-p65, interleukin-1ß, and cyclooxygenase-2), and cleaved caspase-3, apoptosis, and infiltration of neutrophils in the UUO kidneys. The protein levels of endoplasmic reticulum (ER) stress-associated molecules (GRP78, GRP94, ATF4, CHOP, phosphorylated eIF2α, and cleaved caspase 12) were increased in the kidneys of UUO mice, which could be significantly reversed by withaferin A treatment. CONCLUSION: Withaferin A protects against the CKD progression that is, at least in part, associated with the moderation of ER stress-related apoptosis, inflammation, and fibrosis in the kidneys of CKD. Withaferin A may serve as a potential therapeutic agent for the development of CKD.

Detection of porcine parvovirus by loop-mediated isothermal amplification.

Loop-mediated isothermal amplification is a novel method for rapid amplification of DNA. It has been adopted widely for the detection of virus because of its simplicity, rapidity, and specificity. A loop-mediated isothermal amplification assay was developed for the detection of porcine parvovirus. Four primers specific for six regions of PPV non-structural protein 1 gene were designed with an online software. After amplifying at a constant temperature of 59-65 degrees C by Bst enzyme, a clear result was visible after 2.5% agarose gel electrophoresis. The sensitivity and specificity of this assay were evaluated by comparison with the polymerase chain reaction. The detection limit of the assay was shown to be equivalent to 5 PPV copies/reaction. Due to its specificity and simplicity, the assay should be a useful diagnostic tool for epidemiologic studies of PPV.

Acute sensorineural hearing loss in patients with vestibular schwannoma early after cyberknife radiosurgery.

OBJECTIVE: This study reviewed our experience in treating patients with vestibular schwannoma (VS) who had acute sensorineural hearing loss (ASHL) early after radiosurgery. PATIENTS AND METHODS: Seventy VS patients underwent cyberknife radiosurgery. Of them, 6 patients had ASHL early (<6 m) after radiosurgery (Group A), accounting for 8.6% prevalence. The remaining 64 patients without ASHL were assigned to Group B. Another 10 VS patients with tiny tumor and serviceable hearing adopted observation policy (Group C). All patients underwent a test battery for inner ear function, and tumor size was measured via MR imaging. RESULTS: The mean hearing level of Group A was 39 ±â€¯16 dB before radiosurgery, which deteriorated to 67 ±â€¯14 dB at the onset of ASHL after radiosurgery. Three months after treatment for ASHL, hearing improvement was noted in only one patient (17%). Mean tumor volumes of Group A before and after ASHL were 1.54 ±â€¯1.48 cc and 1.33 ±â€¯1.04 cc, respectively, showing non-significant difference. Receiver operating characteristic curve analysis revealed that the optimal cutoff value for tumor size was 1.45 cm for predicting absence of ASHL, with a sensitivity of 96% and a specificity of 67%. In contrast, Group C with mean tumor size of 0.64 ±â€¯0.15 cm adopted observation policy, and none of them had ASHL two years after diagnosis. CONCLUSION: Prevalence of ASHL in VS patients early after radiosurgery is 8.6%, likely due to radiation injury to the cochlear nerve. Thus, when tumor size is <1.45 cm, serviceable hearing is the criteria for determining whether observation policy (with serviceable hearing) or radiosurgery (lack of serviceable hearing) is given. For those tumor sizes ranged 1.45-3.0 cm, radiosurgery is indicated regardless of hearing level.

The antifibrotic and anti-inflammatory effects of icariin on the kidney in a unilateral ureteral obstruction mouse model.

BACKGROUND: The pathology change of renal tubulointerstitial fibrosis is a critical feature of chronic kidney disease (CKD), regardless of the primary insults. The infiltration of inflammatory cells and the consecutive secretion of profibrotic factors are frequently and conspicuously observed during the development of renal fibrosis. Icariin, an active polyphenol of the Epimedium genus, has been found to alleviate the symptoms of chronic diseases like diabetes, neurodegeneration, and heart and renal diseases. The effect and mechanism of icariin on the prevention of CKD-associated renal fibrosis still needed clarification. PURPOSE: The aims of this study were to investigate whether icariin treatment improves the development of CKD-associated renal fibrosis and its possible mechanism. METHODS: An experimental unilateral ureteral obstruction (UUO)-induced chronic renal fibrosis mouse model was used. Mice were orally administered with icariin (20 mg/kg/day) for 3 consecutive days before and 14 consecutive days after UUO surgery. RESULTS: The pathological changes, collagen deposition, and protein expressions of profibrotic factors (transforming growth factor-ß and connective tissue growth factor) and fibrotic markers (α-smooth muscle actin and fibronectin), which were significantly elevated in the kidneys of UUO mice, could be significantly reversed by icariin treatment. Icariin treatment also significantly inhibited the increased Smad2/3 and decreased E-cadherin protein expressions in the kidneys of UUO mice. Icariin treatment prominently mitigated the protein expression of proinflammatory factors like nuclear factor-κB, cyclooxygenase-2, interleukin 1-ß and prooxidative enzyme (NADPH oxidase-4), and it increased the protein expression of antioxidative enzymes (superoxide dismutase and catalase). CONCLUSION: Icariin treatment protects against CKD-associated renal fibrosis via its antifibrotic and anti-inflammatory properties. Icariin may serve as a therapeutic agent in the prevention of CKD-associated renal fibrosis.

Novel regimen through combination of memantine and tea polyphenol for neuroprotection against brain excitotoxicity.

NMDA receptors are abundant, ubiquitously distributed throughout the brain, fundamental to excitatory neurotransmission, and critical for normal CNS function. However, excessive glutamate overstimulates NMDA receptors, leading to increased intracellular calcium and excitotoxicity. Mitochondrial dysfunction associated with loss of Ca(2+)homeostasis and enhanced cellular oxidative stress has long been recognized to play a major role in cell damage associated with excitotoxicity. In this experiment, we attempted to explore whether treatment with memantine (an NMDA receptor antagonist) and tea polyphenol (an antioxidant and anti-inflammatory agent), either alone or in combination, is effective in neuroprotection in a mouse excitotoxic injury model. Memantine (10 mg/kg/day), tea polyphenol (60 mg/kg/day), or a combination (memantine 5 mg/kg/day plus tea polyphenol 30 mg/kg/day) was administered by oral gavage for 2 consecutive days before causing excitotoxic injury. Mice received a 0.3-microL NMDA [335 mM (pH 7.2)] injection into the left striatum. Locomotor activity was assessed 24 hr before and after excitotoxic injury. Brain synaptosomes were harvested 24 hr after excitotoxic injury for assessment of Na(+), K(+)-ATPase and Mg(2+)-ATPase activity, reactive oxygen species production, mitochondrial membrane potential (Delta Psi m), mitochondrial reductase activity (MTT test), and Ca(2+)concentration. The results showed that treatment with memantine could significantly rescue mitochondrial function by attenuating the decreased mitochondrial membrane potential (Delta Psi m) and mitochondrial reductase activity in mouse excitotoxic injury. Treatment with tea polyphenol could significantly decrease the increased production of synaptosomal reactive oxygen species (ROS) and thus reduced the deteriorative ROS-sensitive Na(+), K(+)-ATPase and Mg(2+)-ATPase activity. However, neither memantine nor tea polyphenol alone could significantly improve the impaired locomotor activity unless treatment was combined. Combined treatment with memantine and tea polyphenol could significantly protect mice against excitotoxic injury by reducing the increased synaptosomal ROS production, attenuating the decreased Na(+), K(+)-ATPase and Mg(2+)-ATPase activity, the mitochondrial membrane potential (Delta Psi m), the mitochondrial reductase activity, and the increased synaptosomal Ca(2+)concentration. In addition, the impairment in locomotor activity was also significantly improved. Therefore, the combined treatment of memantine and tea polyphenol is more effective in neuroprotection than either memantine or tea polyphenol alone in mouse excitotoxic injury. These findings provide useful information about the potential application of memantine and tea polyphenols in preventing clinical excitotoxic injury such as brain trauma, brain ischemia, epilepsy, and Alzheimer's disease.