Hybrid kyphoplasty with short-versus intermediate- and long-segment pedicle screw fixations for the management of thoracolumbar burst fractures.

BACKGROUND: This study aimed to determine if the hybrid short-segment (HSS) technique is a good alternative to the intermediate-segment (IS) and long-segment (LS) techniques in pedicle screw fixations for acute thoracolumbar burst fractures (TLBFs). METHODS: In this retrospective evaluation, we examined 43 patients who underwent surgical treatments, including one- or two-level suprajacent (U) and infrajacent (L) pedicle screw fixations, for acute single-level TLBFs with neurological deficits between the T11 and L2 levels from July 2013 to December 2019. Among these patients, 15 individuals underwent HSS (U1L1), 12 received IS (U2L1), and 16 underwent LS (U2L2) fixations. Supplemental kyphoplasty of the fractured vertebral bodies was performed exclusively in the HSS group. Our analysis focused on assessing blood loss and surgical duration. Additionally, we compared postoperative thoracolumbar kyphotic degeneration using the data on Cobb angles on lateral radiographic images acquired at three time points (preoperatively, postoperative day 1, and follow-up). The end of follow-up was defined as the most recent postoperative radiographic image or implant complication occurrence. RESULTS: Blood loss and surgical duration were significantly lower in the HSS group than in the IS and LS groups. Additionally, the HSS group exhibited the lowest implant complication rate (2/15, 13.33%), followed by the LS (6/16, 37.5%) and IS (8/12, 66.7%) group. Implant complications occurred at a mean follow-up of 7.5 (range: 6-9), 9 (range: 5-23), and 7 (range: 1-21) months in the HSS, IS, and LS groups. Among these implant complications, revision surgeries were performed in two patients in the HSS group, two in the IS group, and one in the LS group. One patient treated by HSS with balloon kyphoplasty underwent reoperation because of symptomatic cement leakage. CONCLUSIONS: The HSS technique reduced intraoperative blood loss, surgical duration, and postoperative implant complications, indicating it is a good alternative to the IS and LS techniques for treating acute single-level TLBFs. This technique facilitates immediate kyphosis correction and successful maintenance of the corrected alignment within 1 year. Supplemental kyphoplasty with SpineJack® devices and high-viscosity bone cements for anterior reconstruction can potentially decrease the risk of cement leakage and related issues.

Endoscopic transorbital decompression for traumatic superior orbital fissure syndrome: from cadaveric study to clinical application.

PURPOSE: The endoscopic endonasal approach (EEA) is a minimally invasive and promising modality for treating traumatic superior orbital fissure (SOF) syndrome (tSOFS). Recently, the endoscopic transorbital approach (ETOA) has been considered an alternative method for reaching the anterolateral skull base. This study accessed the practicality of using the ETOA to treat SOF decompression using both cadaveric dissection and clinical application. METHODS: Bilateral anatomic dissections were performed on four adult cadaveric heads using the ETOA and EEA to address SOF decompression. The ETOA procedure for SOF decompression is described, and the extent of SOF decompression was compared between the ETOA and EEA. The clinical feasibility of the ETOA for treating SOF decompression was performed in two patients diagnosed with tSOFS. RESULTS: ETOA allowed for decompression over the lateral aspect of the SOF, from the meningo-orbital band superolaterally to the maxillary strut inferomedially. By contrast, the EEA allowed for decompression over the medial aspect of the SOF, from the lateral opticocarotid recess superiorly to the maxillary strut inferiorly. In both patients treated using the ETOA and SOF decompression, the severity of ophthalmoplegia got obvious improvement. CONCLUSIONS: Based on the cadaveric findings, ETOA provided a feasible access pathway for SOF decompression with reliable outcomes, and our patients confirmed the clinical efficacy of the ETOA for managing tSOFS.

Endoscopically assisted presigmoid retrolabyrinthine approach to the lateral mesencephalic sulcus: a cadaveric study with comparison to the variant supracerebellar infratentorial approaches.

The supracerebellar infratentorial (SCIT) approach is commonly used to gain access to the lateral mesencephalic sulcus (LMS), which has been established as a safe entry point into the posterolateral midbrain. This study describes a lateral variant of the SCIT approach, the supreme-lateral SCIT approach, for accessing the LMS through the presigmoid retrolabyrinthine craniectomy and quantitatively compares this approach with the paramedian and extreme-lateral SCIT approaches. Anatomical dissections were performed in four cadaveric heads. In each head, the supreme-lateral SCIT approach was established on one side, following a detailed description of each step, whereas the paramedian and supreme-lateral SCIT approaches were established on the other side. Quantitative measurements of the exposed posterolateral midbrain, the angles of LMS entry, and the depth of surgical corridors were recorded and compared between the three SCIT approach variants. The supreme-lateral (67.70 ± 23.14 mm2) and extreme-lateral (70.83 ± 24.99 mm2) SCIT approaches resulted in larger areas of exposure anterior to the LMS than the paramedian SCIT approach (38.61 ± 9.84 mm2); the supreme-lateral SCIT approach resulted in a significantly smaller area of exposure posterior to the LMS (65.24 ± 6.81 mm2) than the other two variants (paramedian = 162.75 ± 31.98 mm2; extreme-lateral = 143.10 ± 23.26 mm2; both P < .001). Moreover, the supreme-lateral SCIT approach resulted in a surgical corridor with a shallower depth and a smaller angle relative to the horizontal plane than the other two variants. The supreme-lateral SCIT approach is a more lateral approach than the extreme-lateral SCIT approach, providing a subtemporal approach with direct LMS visualization. The supreme-lateral SCIT offers the benefits of both subtemporal and SCIT approaches and represents a suitable option for the management of selected midbrain pathologies.

Garcinol protects SH-SY5Y cells against MPP+-induced cell death by activating DJ-1/SIRT1 and PGC-1α mediated antioxidant pathway in sequential stimulation of p-AMPK mediated autophagy.

Parkinson's disease (PD), a chronic and progressive neurodegenerative disease, can reduce the population of dopaminergic neurons in the substantia nigra. The cause of this neuronal death remains unclear. 1-Methyl-4-phenylpyridinium ion (MPP+) is a potent neurotoxin that can destroy dopaminergic (DA) neurons and promote PD. Garcinol, a polyisoprenylated benzophenone derivative, was extracted from Garcinia indica and is an important active compound it has been used as an anticancer, antioxidant, and anti-inflammatory, agent and it can suppress reactive oxygen species (ROS) mediated cell death in a PD model. Human neuroblastoma (SH-SY5Y) cells (1 × 105 cells) were treated with MPP+ (1 mM) for 24 h to induce cellular ROS production. The formation of ROS was suppressed by pretreatment with different concentrations of garcinol (0.5 and 1.0 µM) for 3 h in SH-SY5Y cells. The present study found that MPP+ treatment increased the formation of reactive oxygen species (ROS), and the increased ROS began to promote cell death in SH-SY5Y cells. However, our natural compound garcinol effectively blocked MPP+-mediated ROS formation by activating the DJ-1/SIRT1 and PGC-1α mediated antioxidant pathway. Further findings indicate that the activated SIRT1 can also regulate p-AMPK-mediated autophagy to protect the neurons from the damage it concludes that garcinol sub-sequential regulates intracellular autophagy in this model, and the productive efficacy of garcinol was confirmed by western blot analysis and MitoSOX DCFDA and MTT assays. The results showed garcinol increased protection due to the prevention of MPP+-induced ROS and the promotion of cell survival.

Cryptotanshinone protects against oxidative stress in the paraquat-induced Parkinson's disease model.

Parkinson's disease (PD) is a common neurodegenerative disorder associated with striatal dopaminergic neuronal loss in the Substantia nigra. Oxidative stress plays a significant role in several neurodegenerative diseases. Paraquat (PQ) is considered a potential neurotoxin that affects the brain leading to the death of dopaminergic neurons mimicking the PD phenotype. Various scientific reports have proven that cryptotanshinone possesses antioxidant and anti-inflammatory properties. We hypothesized that cryptotanshinone could extend its neuroprotective activity by exerting antioxidant effects. This study was designed to evaluate the effects of cryptotanshinone in both cellular and animal models of PQ-induced PD. Annexin V-PI double staining and immunoblotting were used to detect apoptosis and oxidative stress proteins, respectively. Reactive oxygen species kits were used to evaluate oxidative stress in cells. For in vivo studies, 18 B6 mice were divided into three groups. The rotarod data revealed the motor function and immunostaining showed the survival of TH+ neurons in SNpc region. Our study showed that cryptotanshinone attenuated paraquat-induced oxidative stress by upregulating anti-oxidant markers in vitro, and restored behavioral deficits and survival of dopaminergic neurons in vivo, demonstrating its therapeutic potential.

Protective effects of CHIP overexpression and Wharton's jelly mesenchymal-derived stem cell treatment against streptozotocin-induced neurotoxicity in rats.

Diabetic neuropathy is a common complication of diabetes mellitus, posing a challenge in treatment. Previous studies have indicated the protective role of mesenchymal stem cells against several disorders. Although they can repair nerve injury, their key limitation is that they reduce viability under stress conditions. We recently observed that overactivation of the carboxyl terminus of heat shock protein 70 (Hsp70) interacting protein (CHIP) considerably rescued cell viability under hyperglycemic stress and played an essential role in promoting the beneficial effects of Wharton's jelly-derived mesenchymal stem cells (WJMSCs). Thus, the present study was designed to unveil the protective effects of CHIP-overexpressing WJMSCs against neurodegeneration using in vivo animal model based study. In this study, western blotting observed that CHIP-overexpressing WJMSCs could rescue nerve damage observed in streptozotocin-induced diabetic rats by activating the AMPKα/AKT and PGC1α/SIRT1 signaling pathway. In contrast, these signaling pathways were downregulated upon silencing CHIP. Furthermore, CHIP-overexpressing WJMSCs inhibited inflammation induced in the brains of diabetic rats by suppressing the NF-κB, its downstream iNOS and cytokines signaling nexus and enhancing the antioxidant enzyme system. Moreover, TUNEL assay demonstrated that CHIP carrying WJMSCs suppressed the apoptotic cell death induced in STZ-induced diabetic group. Collectively, our findings suggests that CHIP-overexpressing WJMSCs might exerts beneficial effects, which may be considered as a therapeutic strategy against diabetic neuropathy complications.

Edible folic acid and medicinal folinic acid produce cardioprotective effects in late-stage triple-transgenic Alzheimer's disease model mice by suppressing cardiac hypertrophy and fibrosis.

Some clinical studies have indicated the patients with Alzheimer's disease (AD) display an increased risk of cardiovascular disease (CVD). Here, to examine the relationship between AD and CVDs, we investigated the changes in heart function in triple-transgenic late-stage AD model mice (3× Tg-AD; APPSwe, PS1M146V, and tauP301L). We fed the AD mice folic acid (FA) or folinic acid (FN) and analyzed the protective effects of the compounds on the heart; specifically, 20-month-old triple-transgenic AD mice, weighing 34-55 g, were randomly allocated into three groups-the AD, AD + FA, and AD + FN groups-and subject to gastric feeding with FA or FN once daily at 12 mg/kg body weight (BW) for 3 months. Mouse BWs were assessed throughout the trial, at the end of which the animals were sacrificed using carbon dioxide suffocation. We found that BW, whole-heart weight, and left-ventricle weight were reduced in the AD + FA and AD + FN groups as compared with the measurements in the AD group. Furthermore, western blotting of excised heart tissue revealed that the levels of the hypertrophy-related protein markers phospho(p)-p38 and p-c-Jun were markedly decreased in the AD + FA group, whereas p-GATA4, and ANP were strongly reduced in the AD + FN group. Moreover, the fibrosis-related proteins uPA, MMP-2, MEK1/2 and SP-1 were decreased in the heart in both AD + FN group. In summary, our results indicate that FA and FN can exert anti-cardiac hypertrophy and fibrosis effects to protect the heart in aged triple-transgenic AD model mice, particular in FN.

Unusual Cerebral Aneurysm after Stereotactic Radiosurgery to Treat Trigeminal Neuralgia.

Stereotactic radiosurgery is a treatment option for trigeminal neuralgia. This procedure is minimally invasive, but tumor development and facial numbness have been reported. Here, we report an unusual presentation after stereotactic radiosurgery to treat trigeminal neuralgia. A 60-year-old man demonstrated typical signs for type 1 trigeminal nerve neuralgia and was treated with medication for 5 years. Owing to an intolerance to that medication, he received stereotactic radiosurgery with 66 Gy. During a 9-year follow-up exam, dizziness with a spinning sensation was reported and a right superior cerebellar thrombosed aneurysm was diagnosed. He received transarterial embolization with coiling of aneurysm and subsequently reported no complications on follow-up exams. Although stereotactic radiosurgery is a promising treatment for trigeminal neuralgia, aneurysm development may be considered a possible complication. Long-term follow-up care of these patients should be considered. To understand the relationship between radiosurgery and the potential development of a cerebral aneurysm, further research is needed.

Endoscopic transcanal transpetrosal approach to the petroclival region: a cadaveric study with comparison to the Kawase approach.

This study introduces expanded application of the endoscopic transcanal approach with anterior petrosectomy (ETAP) in reaching the petroclival region, which was compared through a quantitative analysis to the middle fossa transpetrosal-transtentorial approach (Kawase approach). Anatomical dissections were performed in five cadaveric heads. For each head, the ETAP was performed on one side with a detailed description of each step, while the Kawase approach was performed on the contralateral side. Quantitative measurements of the exposed area over the ventrolateral surface of the brainstem, and of the angles of attack to the posterior margin of the trigeminal nerve root entry zone (CN V-REZ) and porus acusticus internus (PAI) were obtained for statistical comparison. The ETAP provided significantly larger exposure over the ventrolateral surface of the pons (93.03 ± 21.87 mm2) than did the Kawase approach (34.57 ± 11.78 mm2). In contrast to the ETAP, the Kawase approach afforded greater angles of attack to the CN V-REZ and PAI in the vertical and horizontal planes. The ETAP is a feasible and minimally invasive procedure for accessing the petroclival region. In comparison to the Kawase approach, the ETAP allows for fully anterior petrosectomy and larger exposure over the ventrolateral surface of the brainstem without passing through the cranial nerves or requiring traction of the temporal lobe.

Cerebral air embolism after percutaneous kyphoplasty: a rare case report.

Cerebral air embolism (CAE) is considered as a rare complication during the routine medical procedures in the literature review. We reported a very rare complication of CAE after the percutaneous kyphoplasty (PKP) for the treatment of acute vertebral compression fracture.

Quantitative comparison of endoscopically assisted endonasal, sublabial and transorbital transmaxillary approaches to the anterolateral skull base.

OBJECTIVES: The aim of this anatomical study is to make quantitative comparison among three endoscopic approaches, encompassing contralateral endonasal transseptal transmaxillary transpterygoid approach (contralateral EEA), endoscopic sublabial transmaxillary transalisphenoid (Caldwell-Luc) approach and endoscopic transorbital transmaxillary approach through inferior orbital fissure (ETOA), to the anterolateral skull base for assisting preoperative planning. DESIGN & PARTICIPANTS: Anatomical dissections were performed in four adult cadaveric heads bilaterally using three endoscopic transmaxillary approaches described above. SETTING: Skull Base Laboratory at the National Defense Medical Center. MAIN OUTCOME MEASURES: The area of exposure, angles of attack and depth of surgical corridor of each approach were measured and obtained for statistical comparison. RESULTS: The ETOA had significantly larger exposure over middle cranial fossa (731.40 ± 80.08 mm2 ) than contralateral EEA (266.60 ± 46.74 mm2 ) and Caldwell-Luc approach (468.40 ± 59.67 mm2 ). In comparison with contralateral EEA and Caldwell-Luc approach, the ETOA offered significantly greater angles of attack and shorter depth of surgical corridor (P < .05 for all comparisons). CONCLUSIONS: The ETOA is the superior choice for target lesion occupying multiple compartments with its epicentre located in the middle cranial fossa or superior portion of infratemporal fossa.

Epigallocatechin-3-gallate preconditioned Adipose-derived Stem Cells confer Neuroprotection in aging rat brain.

Aging is the most important current issue and is usually accompanied by complications, such as cardiovascular disorders and neurodegenerative diseases, which are the leading causes of death worldwide and the second major cause of death in Taiwan. In this study, we have investigated the protective effect of adipose-derived mesenchymal stem cells (ADSCs) and the role of epigallocatechin gallate (EGCG) in enhancing this effect in aging cerebral cortex of rats. Further, we attempted to elucidate the molecular mechanism through which EGCG influences the protective effects of ADSC. ADSCs, co-cultured with EGCG, were injected into 20-month-old Wistar rats. Hematoxylin and eosin staining of the cerebral cortex revealed noticeable neurogenic activity and visible improvements in the integrity of the pre-frontal cortex tissue, compared to that in rats treated with ADSCs alone. Western blot analysis confirmed that ADSC, co-cultured with EGCG, enhanced cell survival via the p-Akt pathway and improved mitochondrial biogenesis via the SIRT-1 pathway. Moreover, it increased the available brain-derived neurotrophic factor to a higher degree than that in the ADSC group. Furthermore, western blotting showed that EGCG improved the antioxidant activity of the ADSCs in the cortex tissues via the Nrf-2 and HO-1 pathway. Based on these findings, we propose that this variation in stem cell treatment may facilitate functional recovery and enhanced neuroprotection in aged brains.

Dipeptide IF prevents the effects of hypertension-induced Alzheimer's disease on long-term memory in the cortex of spontaneously hypertensive rats.

Hypertension (HTN) is one of the most prevalent chronic conditions; it can damage blood vessels and rupture blood vessels can trap in small vessels. This blockage can prevent blood flow and oxygen delivery to brain cells and can result in Alzheimer's disease (AD). HTN- and AD-mediated long-time memory loss and its treatment remain poorly understood. Plant-derived natural compounds are alternative solutions for effectively treating diseases without any side effects. This study revealed that bioactive peptides extracted from potato hydrolysis suppress HTN-mediated long-term memory (LTM) loss and cell apoptosis, thus improving memory formation and neuronal cell survival in the spontaneously hypertensive rat (SHR) rat model. SHR rats were treated with bioactive peptide IF (10 mg/kg orally) and angiotensin-converting enzyme inhibitors (5 mg/kg orally). In this study, we evaluated the molecular expression levels of BDNF-, GluR1-, and CREB-mediated markers protein expression in 24-week-old SHR rats. The study result showed that HTN-induced AD regulated long-term memory (LTM) loss and neuronal degeneration in the SHR animals. The bioactive peptide-treated animals showed an elevated level of survival proteins. Bioactive peptide IF activate CREB-mediated downstream proteins to regulate synaptic plasticity and neuronal survival in the SHR rat model.

LPS-enhanced IGF-IIR pathway to induce H9c2 cardiomyoblast cell hypertrophy was attenuated by Carthamus tinctorius extract via IGF-IR activation.

The use of herbs as alternative cardiovascular disease treatment has attracted a great deal of attention owing to their lower toxicity. Whether Carthamus tinctorius extract prevent cardiomyoblast cell hypertrophy remains unclear. The present study was performed to investigate the effect of C tinctorius extract (CTF) on rat cardiomyoblast cell H9c2 and the possible molecular mechanisms. H9c2 cells were treated with lipopolysaccharide (LPS; 2 µg/mL) for 12 hours, subsequently treated with CTF (1-25 µg/mL) The incubation continued for another 24 hours, and the cells were analyzed with actin staining assay, western blot analysis, and siRNA transfection assays. In the present study, the increased cell size induced by LPS was significantly decreased by pretreating at a concentration of 1-25 µg/mL CTF. It was found that CTF could inhibit cardiac hypertrophy induced by LPS and decrease hypertrophic proteins calcineurin, p-GATA-4, GATA-4, atrial natriuretic peptide, and B-type natriuretic peptide levels in H9c2 cells. Additionally, LPS-induced insulin-like growth factor-II receptor (IGF-IIR) hypertrophy pathway was downregulated by CTF. Moreover, IGF-IR siRNA or inhibitors both reversed the CTF effects, confirming that CTF activates IGF-1R to prevent LPS-induced H9c2 cardiomyoblast cell hypertrophy. The current findings indicate that CTF activates IGF-IR to inhibit IGF-IIR signaling pathway which resulted in reducing H9c2 cardiomyoblast cell hypertrophy induced by LPS.

Endoscopic transorbital transtentorial approach to middle incisural space: preclinical cadaveric study.

BACKGROUND: Endoscopic transorbital approach is a novel development of minimally invasive skull base surgery. Recently, anatomical studies have started to discuss the expanded utilization of endoscopic transorbital route for intracranial intradural lesions. The goal of this cadaveric study is to assess the feasibility of endoscopic transorbital transtentorial approach for exposure of middle incisural space. METHODS: Anatomical dissections were performed in four human cadaveric heads (8 sides) using 0- and 30-degree endoscopes. A stepwise description of endoscopic transorbital transtentorial approach to middle incisural space and related anatomy was provided. RESULTS: Orbital manipulation following superior eyelid crease incision with lateral canthotomy and cantholysis established space for bone drilling. Extradural stage consisted of extensive drilling of orbital roof of frontal bone, lessor, and greater wings of sphenoid bone. Intradural stage was composed of dissection of sphenoidal compartment of Sylvian fissure, lateral mobilization of mesial temporal lobe, and penetration of tentorium. A cross-shaped incision of tentorium provided direct visualization of crural cistern with anterolateral aspect of cerebral peduncle and upper pons. Interpeduncular cistern, prepontine cistern, and anterior portions of ambient and cerebellopontine cisterns were exposed by 30-degree endoscope. CONCLUSION: The endoscopic transorbital transtentorial approach can be used as a minimally invasive surgery for exposure of middle incisural space. Extensive drilling of sphenoid wing and lateral mobilization of mesial temporal lobe are the main determinants of successful dissection. Further studies are needed to confirm the clinical feasibility of this novel approach.

Endoscopic transorbital approach to anterolateral skull base through inferior orbital fissure: a cadaveric study.

BACKGROUND: Endoscopic transorbital approach (eTOA) has been announced as an alternative minimally invasive surgery to skull base. Owing to the inferior orbital fissure (IOF) connecting the orbit with surrounding pterygopalatine fossa (PPF), infratemporal fossa (ITF), and temporal fossa, the idea of eTOA to anterolateral skull base through IOF is postulated. The aim of this study is to access its practical feasibility. METHODS: Anatomical dissections were performed in five human cadaveric heads (10 sides) using 0-degree and 30-degree endoscopes. A stepwise description of eTOA to anterolateral skull base through IOF was documented. The anterosuperior corner of the maxillary sinus in the horizontal plane of the upper edge of zygomatic arch was defined as reference point (RP). The distances between the RP to the foramen rotundum (FR), foramen ovale (FO), and Gasserian ganglion (GG) were measured. The exposed area of anterolateral skull base in the coronal plane of the posterior wall of the maxillary sinus was quantified. RESULTS: The surgical procedure consisted of six steps: (1) lateral canthotomy with cantholysis and preseptal lower eyelid approach with periorbita dissection; (2) drilling of the ocular surface of greater sphenoid wing and lateral orbital rim osteotomy; (3) entry into the maxillary sinus and exposure of PPF and ITF; (4) mobilization of infraorbital nerve with drilling of the infratemporal surface of the greater sphenoid wing and pterygoid process; (5) exposure of middle cranial fossa, Meckel's cave, and lateral wall of cavernous sinus; and (6) reconstruction of orbital floor and lateral orbital rim. The distances measured were as follows: RP-FR = 45.0 ± 1.9 mm, RP-FO = 55.7 ± 0.5 mm, and RP-GG = 61.0 ± 1.6 mm. In comparison with the horizontal portion of greater sphenoid wing, the superior and inferior axes of the exposed area were 22.3 ± 2.1 mm and 20.5 ± 1.8 mm, respectively. With reference to the FR, the medial and lateral axes of the exposed area were 11.6 ± 1.1 mm and 15.8 ± 1.6 mm, respectively. CONCLUSIONS: The eTOA through IOF can be used as a minimally invasive surgery to access whole anterolateral skull base. It provides a possible resolution to target lesion involving multiple compartments of anterolateral skull base.

Carthamus tinctorius L. extract activates insulin-like growth factor-I receptor signaling to inhibit FAS-death receptor pathway and suppress lipopolysaccharides-induced H9c2 cardiomyoblast cell apoptosis.

Carthamus tinctorius L. (Compositae) is used in Chinese medicine to treat heart disease and inflammation. In our previous study, we found that C. tinctorius L. inhibited lipopolysaccharides (LPS)-induced tumor necrosis factor-alpha (TNF-α) activation, JNK expression, and apoptosis in H9c2 cardiomyoblast cells. The present study was performed to investigate the protective effect of C. tinctorius extract (CTF) on LPS-challenged H9c2 myocardioblast cell and to explore the possible underlying mechanism. Cell viability assay showed that LPS treatment decreased the cell viability of H9c2 cell, whereas CTF treatment reversed LPS cytotoxicity in a dose-dependent manner, especially in the LPS + CTF 25 (µg/mL) group. LPS treatment-induced apoptosis was determined by transferase-mediated dUTP nick end labeling assay, and by Western blot. LPS-induced apoptotic bodies were decreased following CTF treatment. Expression of TNF-α, FAS-L, FAS, FADD, caspase-8, BID, and t-BID was significantly increased in LPS-treated H9c2 cells. In contrast, it was significantly suppressed by the administration of CTF extract. In addition, CTF treatment activates antiapoptotic proteins, Bcl-2 and p-Bad, and downregulates Bax, cytochrome-c, caspase-9, caspase-3, and apoptosis-inducing factor expression. Furthermore, CTF exerted cytoprotective effects by activating insulin-like growth factor-I (IGF-I) signaling pathway leading to downregulation of the apoptotic proteins involved in FAS death receptor pathway. In addition, AG1024 and IGF-I receptor (IGF-IR) inhibitor and siRNA silencing reverses the effect of CTF implying that CTF functions through the IGF-IR pathway to inhibit LPS-induced H9c2 apoptosis. These results suggest that treatment with CTF extract prevented the LPS-induced apoptotic response through IGF-I pathway.

Bioactive Peptide VHVV Upregulates the Long-Term Memory-Related Biomarkers in Adult Spontaneously Hypertensive Rats.

Hypertension is one of the growing risk factors for the progression of long-term memory loss. Hypertension-mediated memory loss and treatment remain not thoroughly elucidated to date. Plant-based natural compounds are an alternative solution to treating human diseases without side effects associated with commercial drugs. This study reveals that bioactive peptides extracted from soy hydrolysates mimic hypertension-mediated memory loss and neuronal degeneration and alters the memory molecular pathway in spontaneously hypertensive rats (SHR). The SHR animal model was treated with bioactive peptide VHVV (10 mg/kg/oral administration) and angiotensin-converting-enzyme (ACE) inhibitors (5 mg/kg/oral administration) for 24 weeks. We evaluated molecular level expression of brain-derived neurotrophic factor (BDNF), cAMP response element binding protein (CREB), and survival markers phospho-protein kinase B (P-AKT) and phosphoinositide 3-kinase (PI3K) after 24 weeks of treatment for SHR in this study. Western blotting, hematoxylin and eosin (H&E) staining, and immunohistochemistry showed long-term memory loss and neuronal degeneration in SHR animals. Bioactive peptide VHVV-treated animals upregulated the expression of long-term memory-relate proteins and neuronal survival. Spontaneously hypertensive rats treated with oral administration of bioactive peptide VHVV had activated CREB-mediated downstream proteins which may reduce hypertension-mediated long-term memory loss and maintain neuronal survival.

Short-term hypoxia upregulated Mas receptor expression to repress the AT1 R signaling pathway and attenuate Ang II-induced cardiomyocyte apoptosis.

Hypertension-stimulated cardiac hypertrophy and apoptosis play critical roles in the progression of heart failure. Our previous study suggested that hypertensive angiotensin II (Ang II) enhanced insulin-like growth factor receptor II (IGF-IIR) expression and cardiomyocyte apoptosis, which are involved JNK activation, sirtuin1 (SIRT1) degradation, and heat-shock transcription factor 1 (HSF1) acetylation. Moreover, previous studies have implied that short-term hypoxia (STH) might exert cardioprotective effects. However, the effects of STH on Ang II-induced cardiomyocyte apoptosis remain unknown. In this study, we found that STH reduced myocardial apoptosis caused by Ang II via upregulation of the Mas receptor (MasR) to inhibit the AT1 R signaling pathway. STH activates MasR to counteract the Ang II pro-apoptotic signaling cascade by inhibiting IGF-IIR expression via downregulation of JNK activation and reduction of SIRT1 degradation. Hence, HSF could remain deacetylated, and repress IGF-IIR expression. These effects decrease the activation of downstream pro-apoptotic and hypertrophic cascades and protect cardiomyocytes from Ang II-induced injury. In addition, we also found that silencing MasR expression enhanced Ang II-induced cardiac hypertrophy and the apoptosis signaling pathway. These findings suggest a critical role for MasR in cardiomyocyte survival. Altogether, our findings indicate that STH protects cardiomyocytes from Ang II-stimulated apoptosis. The protective effects of STH are associated with the upregulation of MasR to inhibit AT1 R signaling. STH could be a potential therapeutic strategy for cardiac diseases in hypertensive patients.

The preventive effects of edible folic acid on cardiomyocyte apoptosis and survival in early onset triple-transgenic Alzheimer's disease model mice.

In recent years, neuropathological and epidemiological studies have indicated an association between Alzheimer's disease (AD) and several cardiovascular risk factors. In this study, the cardio-protective effects of folic acid (FA) in early stage AD was elucidated using a triple-transgenic (3xTg) Alzheimer's mouse model. Eleven-month-old C57BL/6 mice and 3xTg mice were assigned to five groups. During the four-month treatment period, the low-FA treatment group received FA through their diet, and the high-FA treatment groups received 3 mg/dl folate in drinking water and were also gastric-fed 1.2 mg/kg folate every day. In the C57B1/6J mice, treatment with high doses of FA (HFA) did not show any considerable effect compared to the control group or the low-dose dietary FA treatment group. However, Alzheimer's mice treated with HFA showed enhanced cardio-protection. Western blot analysis revealed that FA treatment restored SIRT1 expression, which was suppressed in 3xTg mice, through enhanced AMPK expression. FA significantly enhanced the IGF1 receptor survival mechanism in the hearts of the 3xTg mice and suppressed the expression-intrinsic and extrinsic apoptosis-associated proteins. The results suggest that FA intake may significantly alleviate cellular pathological events in the heart associated with AD.