Arc regulates brain damage and neuroinflammation via Sirt1 signaling following subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) accounts for only 5 % of all stroke cases, but carries a heavy burden of morbidity and mortality. Activity regulated cytoskeleton associated protein (Arc) is an immediate early gene (IEG)-coded postsynaptic protein that is involved in synaptic plasticity. Increasing evidence and our previous studies have shown that Arc might be involved in the pathological mechanism of various neurological diseases, such as traumatic brain injury (TBI). In this study, we investigated the level of Arc in cerebrospinal fluids (CSF) of aSAH patients and its potential role in brain damage following experimental SAH model. We found that the levels of Arc in aSAH patients' CSF positively correlated with Hunt-Hess (H&H) grades. Knockdown of endogenous Arc expression by small interfere RNA (siRNA) significantly increased brain edema and oxidative stress following SAH. The results of immunostaining in brain sections showed that knockdown of Arc enhanced activation of microglia and astrocytes. In congruent, generation of inflammatory cytokines following SAH was increased by Si-Arc transfection. The results of western blot analysis showed that knockdown of Arc inhibited the expression of Sirt1 and Nrf2, which was accompanied by decreased enzymatic activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px). In addition, activation of sirtuin 1 (Sirt1) via agonist SRT2104 markedly decreased the brain damage and neuroinflammation induced by Arc knockdown. In conclusion, knockdown of endogenous Arc could aggravate brain damage and neuroinflammation following experimental SAH, and Arc levels in aSAH patients' CSF might be a potential indicator of brain damage and prognosis.

Neuroprotective Effect of Ultrasound Triggered Astaxanthin Release Nanoparticles on Early Brain Injury After Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is a fatal disease. Within 72 h of SAH, the intracranial blood-brain barrier (BBB) is destroyed, and the nerve cells have responses such as autophagy, apoptosis, and oxidative stress. Antioxidation is an essential treatment of SAH. Astaxanthin (ATX) induces cells' antioxidant behaviors by regulating related signal pathways to reduce the damage of brain oxidative stress, inflammation, and apoptosis. Because of its easy degradability and low bioavailability, ATX is mainly encapsulated with stimulus-responsive nanocarriers to improve its stability, making it rapidly release in the brain and efficiently enter the lesion tissue. In this study, the ultrasonic cavitation agent perfluorocarbon (PFH), ATX, and fluorescent dye IR780 were loaded with polydopamine (PDA) to prepare a US triggered release nanoparticles (AUT NPs). The core-shell structure of AUT NPs formed a physical barrier to improve the bioavailability of ATX. AUT NPs have high ATX loading capacity and US responsiveness. The experimental results show that the AUT NPs have high stability in the physiological environment. Both US and pH stimuli can trigger the release. Under US, PFH breaks through the rigid shell. The structure of AUT NPs is destroyed in situ, releasing the loaded drugs into neuronal cells to realize the antioxidant and antiapoptotic effects. The in vivo experiment results show that the AUT NPs have good biosafety. They release the drugs in the brain under stimuli. The in vivo treatment results also show that AUT NPs have an excellent therapeutic effect. This approach presents an experimental basis for the establishment of Innovative SAH treatments.

Giant aneurysm of the bilateral vertebrobasilar junction treated by pipeline and coils: A case report and literature review.

Giant aneurysm of the posterior circulation is associated with a higher risk of rupture compared with that of the anterior circulation. Furthermore, surgical clipping and interventional embolization for giant aneurysm of the posterior circulation are more difficult and complex to perform. The present study reported on the case of a 26-year-old female who exhibited a giant spherical aneurysm of the vertebrobasilar junction (VBJ) with a maximum diameter of ~35 mm that caused cervical discomfort. In addition, the patient experienced symptoms including left-sided walking and hoarseness caused by the compression of the brainstem and the posterior cranial nerves. The risks associated with performing surgery in this area are high and the prognosis is mainly poor. The patient of the present study was treated using the Pipeline Flex device with coil embolization. As a giant aneurysm of the VBJ simultaneously affects the bilateral vertebral arteries (VAs) and basilar artery, it is a unique condition and the treatment strategy must be personalized. Based on an analysis of the hemodynamic influence on the aneurysm in the present case, the Pipeline was placed through the left VA, the coils were packed through the right VA, and finally, the right VA was proximally occluded. At 7 months after embolization, the patient's modified Rankin scale score was 1 point. Upon analysis of the hemodynamic influence on the aneurysm of the VBJ, the VA with the larger shear force on the wall of the aneurysm was selected for occlusion to simplify the treatment of the aneurysm and to maximize the probability to achieve recovery.

[Effect of modified cangfu daotan decoction in improving endometrial receptivity in infertility patients with polycystic ovarian syndrome].

OBJECTIVE: To study the effect and potential mechanism of Modified Cangfu Daotan Decoction (MCDD) on endometrial receptivity in infertility patients with polycystic ovarian syndrome (PCOS). METHODS: Totally 298 women having normal ovulation who underwent artificial insemination were recruited as the control group, and they received no drug therapy. Another 355 infertility patients with PCOS who received ovarian stimulation therapy were recruited as the treatment group. Then they were further assigned to the treatment group I (195 cases) and the treatment group II (160 cases) according to random digit table. Patients in the treatment group I received clomiphene (CC) + human menopause gonadotropin (HMG) +human chorionic gonadotropin (HCG), while those in the treatment group II received CC + HMG + HCG and additionally took modified MCDD. The therapeutic course for all was three menstrual cycles. The pregnancy ratio, the endometrial thickness, and spiral artery pulsatility index (PI), resistance index (RI), and homeostasis model assessment-insulin resistance (HOMA-IR) were measured. Furthermore, the uncoupling protein 2 (UCP2) level was tested by Western blot. RESULTS: Compared with the control group, the endometrial thickness decreased and PI and RI increased in the treatment group I (all P < 0.05). Compared with the treatment group I , the endometrial thickness increased and PI and RI decreased in the treatment group II (all P < 0.05). Compared with before treatment, HOMA-IR levels were significantly decreased in the treatment group II after treatment (P < 0.05). Compared with the control group before treatment, the HOMA-IR level increased in the treatment group I and the treatment group II before treatment (P < 0.05). Compared with the control group after treatment, the HOMA-IR level increased in the treatment group I (P < 0.05). But there was no statistical difference in the post-treatment HOMA-IR level between the control group and the treatment group II (P < 0.05). Compared with the control group, the post-treatment UCP2 level was increased in the treatment group II (P < 0.05). After one year follow-up, the pregnancy rate was 16.1% (48/298) in the control group, 23.1% (37/160) in the treatment group I, and 33.8% (66/195) in the treatment group II. Compared with the control group, the pregnancy rate was significantly increased in the treatment group II (P < 0.05). CONCLUSION: MCDD was found to be capable of increasing the pregnancy rate of infertility patients with PCOS, which might be associated with improving endometrial blood flow and insulin resistance, increasing the UCP2 expression, and finally improving the endometrial receptivity.

Involvement of reactive oxygen species and TATA box-binding protein-related factor 2 in testicular torsion/detorsion-induced injury.

OBJECTIVE: To investigate whether overproduction of reactive oxygen species after testicular torsion-detorsion injures testicular spermatogenesis by regulating expression of TATA box-binding protein-related factor 2 (TRF2), which is an essential transcription factor for spermatogenesis. Testicular torsion-detorsion causes overproduction of reactive oxygen species, which contributes to testicular injury and regulates many genes whose expression affects cell cycle regulation, cell proliferation, and apoptosis. MATERIALS AND METHODS: A total of 60 adult male Sprague-Dawley rats were divided into 3 groups of 20 rats each. The control group underwent a sham operation of the left testicle. The torsion-detorsion group received 1 hour of left testicular torsion. The scavenging reactive oxygen species group underwent the same surgical operation as the torsion-detorsion group, but superoxide dismutase and catalase, 2 well-known reactive oxygen species scavengers, were given intravenously at detorsion. The testicles were harvested 4 hours or 3 months after detorsion to measure the malondialdehyde level (a marker of reactive oxygen species), TRF2 expression, and spermatogenesis. RESULTS: Unilateral testicular torsion-detorsion significantly increased the malondialdehyde level and reduced TRF2 expression and spermatogenesis in ipsilateral testicles, suggesting that overgeneration of reactive oxygen species after testicular torsion-detorsion might downregulate TRF2 expression, leading to spermatogenic damage. In contrast, administration of superoxide dismutase and catalase significantly decreased the malondialdehyde level and increased TRF2 expression and spermatogenesis in ipsilateral testicles. These results supported the above suggestion. CONCLUSION: These findings have indicated that overproduction of reactive oxygen species after testicular torsion-detorsion can damage testicular spermatogenesis by downregulation of TRF2 expression.

Wave localization in two-dimensional porous phononic crystals with one-dimensional aperiodicity.

The localization properties of in-plane elastic waves propagating in two-dimensional porous phononic crystals with one-dimensional aperiodicity are initially analyzed by introducing the concept of the localization factor that is calculated by the plane-wave-based transfer-matrix method in this paper. The band structures characterized by using localization factors are calculated for different phononic crystals by altering matrix material properties and geometric structure parameters. Numerical results show that the effect of matrix material properties on wave localization can be ignored, while the effect of geometric structure parameters is obvious. For comparison, the periodic porous system and Fibonacci system with rigid inclusion are also analyzed. It is found that the band gaps are easily formed in aperiodic porous system, but hard for periodic porous system. Moreover, compared with aperiodic system with rigid inclusion, the wider low-frequency band gaps appear in the aperiodic porous system.

Protective effect of rutin on testicular ischemia-reperfusion injury.

PURPOSE: The pathophysiology of testicular torsion-detorsion is an ischemia-reperfusion injury caused by overgeneration of reactive oxygen species (ROS). This study aimed to investigate the effect of rutin, a well-known antioxidant, on testicular ischemia-reperfusion injury. METHODS: Sixty male Sprague-Dawley rats were randomly divided into 3 groups, each containing 20 rats. Rats in the control group underwent a sham operation of the left testis. In the torsion-detorsion group, the left testis was rotated 720° for 2 hours. Rats in the treatment group received the same surgical procedure as the torsion-detorsion group, but rutin was administered intravenously at the time of detorsion. Bilateral orchiectomy was performed on half of the rats in each experimental group at 4 hours after detorsion for measurement of malondialdehyde, an indicator of intratesticular ROS content, and for evaluation of superoxide dismutase and catalase, which are endogenous antioxidant enzymes. Orchiectomy was performed on the remaining rats at 3 months after detorsion for analysis of testicular spermatogenesis. RESULTS: Unilateral testicular torsion-detorsion caused a significant increase in malondialdehyde level and caused significant decreases in superoxide dismutase, catalase activities, and spermatogenesis in ipsilateral testes. The rats treated with rutin had a significant decrease in malondialdehyde level and had significant increases in superoxide dismutase, catalase activities, and spermatogenesis in ipsilateral testes, compared with torsion-detorsion group. CONCLUSIONS: Rutin protects testes from ischemia-reperfusion injury. The protective effect of rutin may be caused by scavenging ROS by increasing superoxide dismutase and catalase activities.

Psoralea corylifolia protects against testicular torsion/detorsion-induced ischemia/reperfusion injury.

ETHNOPHARMACOLOGICAL RELEVANCE: The pathophysiology of testicular torsion-detorsion is ischemia-reperfusion injury of the testis. In the course of testicular ischemia and reperfusion, overgeneration of reactive oxygen species is a major initiating component of the testicular spermatogenic injury. Reactive oxygen species regulate many genes whose expression affects cell-cycle regulation, cell proliferation, and apoptosis. The transcription factor cAMP-responsive element modulator-τ (CREMτ) plays an essential role in spermatogenesis. Psoralea corylifolia, a medicinal herb with anti-oxidative activity, has been used to treat male reproductive dysfunction in traditional Chinese medicine. In this study, we investigated the effect of Psoralea corylifolia on testicular torsion/detorsion-induced injury. MATERIALS AND METHODS: Sixty adult male Sprague-Dawley rats were randomly divided into 3 groups, each containing 20 rats. Rats in the control group underwent a sham operation of the left testis. In the torsion-detorsion group, the left testis was rotated 720° for 2h. Rats in the treatment group received the same surgical procedure as the torsion-detorsion group, but Psoralea corylifolia was administered orally. Bilateral orchiectomy was performed on half of the rats in each experimental group at 4h after detorsion for measurement of malondialdehyde which is an indicator of intratesticular reactive oxygen species content. Orchiectomy was performed on the remaining rats at 3 months after detorsion for analysis of testicular CREMτ expression and spermatogenesis. RESULTS: Unilateral testicular torsion-detorsion caused a significant increase in malondialdehyde level and caused significant decreases in CREMτ expression and spermatogenesis in ipsilateral testes. Psoralea corylifolia treatment significantly decreased malondialdehyde level and significantly increased CREMτ expression and spermatogenesis in ipsilateral testes, compared with torsion-detorsion group. CONCLUSIONS: These results suggest that Psoralea corylifolia may protect testicular spermatogenesis by enhancing CREMτ expression by scavenging reactive oxygen species.

Curcumin attenuates ischemia-reperfusion injury in rat testis.

OBJECTIVE: To evaluate the effect of curcumin, a potent antioxidant, on testicular ischemia-reperfusion injury caused by overgeneration of reactive oxygen species (ROS) after testicular torsion-detorsion. DESIGN: Controlled experimental study using rats. SETTING: Research laboratory. ANIMAL(S): Sixty adult male Sprague-Dawley rats. INTERVENTION(S): Rats in the control group underwent a sham operation of the left testis. In the torsion-detorsion group, the left testis was rotated 720 degrees for 2 hours. Rats in treatment group received the same surgical procedure as the torsion-detorsion group, but curcumin was administered IV at repair of testicular torsion. MAIN OUTCOME MEASURE(S): Testicular activity of xanthine oxidase, which catalyzes production of ROS; malondialdehyde level (an indicator of ROS content); protein expression level of heme oxygenase-1, which catalyzes antioxidant generation; and spermatogenesis. RESULT(S): Unilateral testicular torsion-detorsion caused significant increases in xanthine oxidase activity, malondialdehyde level, and heme oxygenase-1 protein expression level and caused a significant decrease in testicular spermatogenesis in ipsilateral testes. The rats treated with curcumin had significant decreases in xanthine oxidase activity and malondialdehyde level and had significant increases in heme oxygenase-1 protein expression level and testicular spermatogenesis in ipsilateral testes, compared with the torsion-detorsion group. CONCLUSION(S): The curcumin exerts a protective effect on testicular ischemia-reperfusion injury.

Role of cAMP-responsive element modulator-tau (CREMtau) in ipsilateral testicular injury after unilateral testicular torsion-detorsion.

OBJECTIVE: To investigate the role of cAMP-responsive element modulator-tau (CREMtau), an essential transcription factor for spermatogenesis, in ipsilateral testicular injury after unilateral testicular torsion-detorsion. DESIGN: Controlled experimental study using rats. SETTING: Research laboratory. ANIMAL(S): Twenty adult male Sprague-Dawley rats. INTERVENTION(S): Ten rats in the control group underwent a sham operation of the left testes. Ten rats in the torsion-detorsion group received 1 hour of left testicular torsion. Orchiectomy was performed on all rats 3 months after detorsion. MAIN OUTCOME MEASURE(S): Testicular spermatogenesis was evaluated by measuring testicular weight, mean seminiferous tubular diameter, number of germ cell layers, and mean testicular biopsy score. The expressions of CREMtau mRNA and protein in testes were detected by reverse transcription-polymerase chain reaction and Western blot, respectively. RESULT(S): Unilateral testicular torsion-detorsion caused significant spermatogenic damage in the ipsilateral testes, including reductions in testicular weight, mean seminiferous tubular diameter, number of germ cell layers, and mean testicular biopsy score. In ipsilateral testes with spermatogenic damage, the expressions of CREMtau mRNA and protein were also significantly reduced. CONCLUSION(S): Reduction in testicular CREMtau expression may be one of the mechanisms responsible for impairment of spermatogenesis in ipsilateral testes after unilateral testicular torsion-detorsion.

Beneficial effect of taurine on testicular ischemia-reperfusion injury in rats.

OBJECTIVES: To evaluate the effect of taurine, a potent antioxidant, on testicular ischemia-reperfusion injury due to excess reactive oxygen species produced by neutrophils after testicular torsion-detorsion. METHODS: A total of 60 adult male Sprague-Dawley rats were randomly divided into three groups, each containing 20 rats. The control group underwent a sham operation of the left testis. In the torsion-detorsion group, the left testis was rotated 720 degrees counterclockwise for 2 hours. The treatment group underwent the same surgical procedure as the torsion-detorsion group, but taurine was administered intravenously at repair of the testicular torsion. One half of the rats in each group underwent orchiectomy 4 hours after detorsion for measurement of myeloperoxidase activity, an indicator of neutrophil accumulation in the testis, and for evaluation of tissue malondialdehyde, an indicator of intratesticular reactive oxygen species content. The remainder were killed at orchiectomy 3 months after detorsion for analysis of testicular spermatogenesis. RESULTS: Unilateral testicular torsion-detorsion caused a significant increase in myeloperoxidase activity and the malondialdehyde level and a significant decrease in testicular spermatogenesis in the ipsilateral testes. The decrease in ipsilateral testicular spermatogenesis involved a reduction in testicular weight, mean seminiferous tubular diameter, number of germ cell layers, and mean testicular biopsy score. The rats treated with taurine had a significant decrease in myeloperoxidase activity and malondialdehyde level and a significant increase in testicular spermatogenesis in the ipsilateral testes compared with the torsion-detorsion group. CONCLUSIONS: The results of our study have shown that the administration of taurine exerts a beneficial effect on testicular ischemia-reperfusion injury. This effect might be partly the result of a reduction in reactive oxygen species generation by diminishing neutrophil recruitment to the testis.

[Ultrastructure and function of mitochondria in idiopathic asthenospermia: study of 151 cases].

OBJECTIVE: To explore the ultrastructure and function of mitochondria in idiopathic asthenospermia and the role thereof in the sperm activity. METHODS: Samples of sperm were collected from 151 idiopathic asthenospermia patients, 25% of whose sperms were classified as lower than grade A, were subdivided into 3 groups: Group A with the proportion of grade A sperms between 15% and 25%, Group B, with the proportion of grade A sperm between 15% and 5%, and Group C with the proportion of grade A sperm < 5%. Transmission electron microscopy was used to observe the ultrastructure of the mitochondria in the sperms. Samples of sperm were collected from 53 normal patients as control group. The levels of succinate dehydrogenase (SDH) and mitochondrial membrane potential (MMP) were detected. RESULTS: The expression rates of SDH and MMP were decreased according to the sequence of the control group, group A, Group B, and Group C with significant between any two groups (all P < 0.01). Various mitochondrial pathological changes (MPCs) emerged in Groups A, B and C, however with different frequencies of occurrence for specific MPC in specific group (chi2 = 60.85, P < 0.01). The amount of abnormal mitochondria increased significantly according to the sequence of the control group, Groups A, B and C (chi2 = 479.72, b = 0.86, P < 0.01). The severity degree of MPC increased along with the decrease of sperm viability (chi2 = 435.89, b = 0.80, P < 0.01). CONCLUSION: Various MPCs exist in idiopathic asthenospermia. There is a close association between the sperm viability and mitochondrial ultrastructure and mitochondrial function.

[Extract from Morindae officinalis against oxidative injury of function to human sperm membrane].

OBJECTIVE: To study the intervention of Morindae officinalis extract in human sperm membrane, and to study the treatment of male infertility and asthenoospermia by M. officinalis. METHOD: To select sperm with normal physiological function using the Percoll gradient centrifugation for the normal sperm model. Then separating the sperm suspension into the normal, model, and control group (Vitamin C group), and the large, medium and small dose of M. officinalis. The ROS was made from hypoxanthine-xanzine xanzine (HX-XO), and ROS, different concentrations (0.125, 0.25, 0.5 mg x mL(-1) of the extract were hatched with sperm in the oxygen environment, the sperm membrane Lipid peroxide injury were analyzed, and the function of sperm membrane were analyzed by sperm Hypoosmoticswelling (HOS) and compared with the controlled group. RESULT: In the same conditions, all the small, medium and large extracts of M. officinalis (0.125, 0.25, 0.5 g x mL(-1)) improved SOD vitality of sperm suspension, reduced the content of MDA, intervened in the injury of sperm membrane by ROS to some extent and protected some function of sperm membrane. The 0.125 mg x mL(-1) extract had no obvious difference (P > 0.05) with Vitamin C in it, but the (0.25, 0.5 mg x mL(-1)) concentration of the extract is significantly better than control Vitamin-C (P < 0.01, P < 0.001). Furthermore, there was a dependence on the dosage, the large dose (0.5 mg x mL(-1)) of M. officinalis especially protected the function of sperm membrane. CONCLUSION: The extract from M. officinalis can significantly intervene in lipin peroxidation in sperm membrane by guarding against oxidation, and protect the structure and function of sperm membrane, that is one of the mechanisms for treating male's infertility and asthenoospermia with M. officinalis.

[Protection of extract from Cuscuta japonica on human sperm acrosome and ultrastructure].

OBJECTIVE: To study the oxidation damage of active oxygen (ROS) to human sperm acrosome and ultrastructure, and study the function mechanism about Cuscuta japonica treating male's infertility and asthenoospermia. METHOD: By using the Percoll gradient centrifugation, the sperm with normal physiological function were selected for the normal sperm model, and the sperm suspension were divided into the normal group, the model group, the positive control group (Vitamin C group), and the lugh, the median and the low dose gvoups of C. japonica. The ROS made from hypoxanthine-xanzine xanzine(HX-XO) and different content (0.125, 0.25, 0.5 g x mL(-1)) of extract were incubated with sperm in the oxygen environment. The acrosomic integrity rate were calculated and the sperm acrosome and ultrastructure were observed. RESULT: The content (0.125, 0.5 g x mL(-1)) of extract had no obvious difference as compared with Vitamin C (0.25 mg x mL(-1)) in protecting the acrosome and ultrastructure, but the content (0.25 mg x mL(-1)) of extract was significantly better than Vit C (P < 0.001). CONCLUSION: The suitable content of extract from C. japonica can significantly protect the sperm membrane, the acosomic structure and the mitochondrion function from the damage caused by ROS.

Optical coherence tomography system with no high-precision scanning stage and stage controller.

Optical coherence tomography (OCT) is a novel technique for noninvasive imaging based on the use of a low-coherence interferometer. Conventionally, obtaining high-resolution images requires the use of high-precision sample and scanning stages and a stage controller for simultaneous measurement of the refractive index and the thickness of an optical sample. However, in this study a novel optical-fiber-type OCT system is developed that does not need both a high-precision scanning stage and a stage controller. Additionally, two signal demodulation processes are described. Compared with that of conventional OCT systems, the current configuration eliminates the high-precision scanning stage and stage controller and is therefore cheaper and less complex. Also, this new technique could be applied to conventional OCTs in biotissue scanning.