Bee Venom Activates the Nrf2/HO-1 and TrkB/CREB/BDNF Pathways in Neuronal Cell Responses against Oxidative Stress Induced by Aß1-42.

Honeybee venom has recently been considered an anti-neurodegenerative agent, primarily due to its anti-inflammatory effects. The natural accumulation of amyloid-beta (Aß) in the brain is reported to be the natural cause of aging neural ability downfall, and oxidative stress is the main route by which Aß ignites its neural toxicity. Anti-neural oxidative stress is considered an effective approach for neurodegenerative therapy. To date, it is unclear how bee venom ameliorates neuronal cells in oxidative stress induced by Aß. Here, we evaluated the neuroprotective effect of bee venom on Aß-induced neural oxidative stress in both HT22 cells and an animal model. Our results indicate that bee venom protected HT22 cells against apoptosis induced by Aß1-42. This protective effect was explained by the increased nuclear translocation of nuclear factor erythroid 2-like 2 (Nrf2), consequently upregulating the production of heme oxygenase-1 (HO-1), a critical cellular instinct antioxidant enzyme that neutralizes excessive oxidative stress. Furthermore, bee venom treatment activated the tropomyosin-related kinase receptor B (TrkB)/cAMP response element-binding (CREB)/brain-derived neurotrophic factor (BDNF), which is closely related to the promotion of cellular antioxidant defense and neuronal functions. A mouse model with cognitive deficits induced by Aß1-42 intracerebroventricular (ICV) injections was also used. Bee venom enhanced animal cognitive ability and enhanced neural cell genesis in the hippocampal dentate gyrus region in a dose-dependent manner. Further analysis of animal brain tissue and serum confirmed that bee venom reduced oxidative stress, cholinergic system activity, and intercellular neurotrophic factor regulation, which were all adversely affected by Aß1-42. Our study demonstrates that bee venom exerts antioxidant and neuroprotective actions against neural oxidative stress caused by Aß1-42, thereby promoting its use as a therapeutic agent for neurodegenerative disorders.

Prospective Cohort Study with a 2-Year Follow-up of Clinical Results, Fusion Rate, and Muscle Bulk for Uniportal Full Endoscopic Posterolateral Transforaminal Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective cohort study. PURPOSE: Postoperative evaluation of the cross-sectional area of paraspinal muscle and clinical findings in patients who had interlaminar route uniportal full endoscopic posterolateral transforaminal lumbar interbody fusion (EPTLIF) after 2 years. OVERVIEW OF LITERATURE: There are limited short-term follow-up studies on efficacy, safety, and physiological changes with a 2-year follow-up. There is no study on paraspinal muscle cross-sectional area change in patients who had undergone uniportal EPTLIF. METHODS: We evaluated patients who underwent EPTLIF with a minimum 24-month follow-up. Clinical parameters of the Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) were measured at the preoperative, 1-week postoperative mark, postoperative 3-month mark, and final follow-up. Preoperative and 1-year postoperative magnetic resonance imaging measurement of preoperative and postoperative Kjaer grade, right and left psoas muscle mass area, and right and left paraspinal muscle mass area was performed. RESULTS: EPTLIF with a minimum 24-month follow-up of 35 levels was included. The complication rate was 6%, and the mean Bridwell's fusion grade was 1.37 (1-2). There was statistically significant improvement at 1 week, 3 months, and 2 years in VAS (4.11±1.23, 4.94±1.30, and 5.46±1.29) and in ODI (40.34±10.06, 46.69±9.14, and 49.63±8.68), respectively (p <0.05). Successful operation rate with excellent and good MacNab's criteria at 2 years was 97%. There was an increment of statistically significant bilateral psoas muscle cross-sectional area, right side (70.03±149.1 mm²) and left side (67.59±113.2 mm²) (p <0.05). CONCLUSIONS: Uniportal EPTLIF achieved good fusion and improved clinical outcomes with favorable paraspinal musculature bulk at the 2-year follow-up.

Analgesic effects and metabolome analyses of laser- and electro-acupuncture combined therapies in paclitaxel-induced neuropathic pain model.

Introduction: Allodynia, which can be induced by paclitaxel administration, is the presence of pain as a result of a stimulus that does not usually provoke pain. Many studies have investigated the analgesic efficacy of acupuncture, including laser acupuncture (LA) and electroacupuncture (EA). Although pain-related diseases are relatively common, few studies have analyzed the analgesic effects and mechanisms of LA combined with EA. The purpose of this study was to investigate the therapeutic effect and mechanism of manual acupuncture (MA), EA, LA, and combined therapy (LA + EA) in a paclitaxel-induced allodynia rat model. Methods: A total of 56 rats were classified into eight groups: a normal (Nor, n = 7), a control (Con, n = 7), an MA (n = 7), an EA (n = 7), a 650-nm LA (650LA, n = 7), an 830-nm LA (830LA, n = 7), a 650-nm LA combined with EA (650LA + EA, n = 7), and an 830-nm LA combined with EA group (830LA + EA, n = 7). Allodynia was induced by intraperitoneal injection of 2 mg/kg of paclitaxel every other day for a total of four times except the Nor group. Acupuncture treatments were conducted at the points of Jungwan (CV12) and Joksamni (ST36) once every other day for 6 min, for a total of nine times. Withdrawal response reaction times and force intensity of the foot were measured before the start of the experiment, after the 4th paclitaxel administration (day 8), and after the 9th and last treatment (day 15). On the 16th day, mRNA and protein expression in the spinal nerves was assessed, and a metabolome analysis of the animals' feces was performed. Results and discussion: Our analyses show that 650LA + EA treatment resulted in an upregulation of protein expression related to pain relief and nerve regeneration, whereas 830LA + EA treatment led to significant changes in metabolomes. This study demonstrates that a combination treatment of EA and LA can suppress allodynia and promote upregulation of protein expression related to nerve regeneration and is effective in changing the intestinal microbiome. Further large-scale research is required to assess the exact mechanism underlying the therapeutic effect of this combination treatment in pain-related diseases.

Remodeling of Epidural Fluid Hematoma after Uniportal Lumbar Endoscopic Unilateral Laminotomy with Bilateral Decompression: Comparative Clinical and Radiological Outcomes with a Minimum Follow-up of 2 Years.

STUDY DESIGN: Retrospective cohort study. PURPOSE: To evaluate the clinical and radiological effects of epidural fluid hematoma in the medium term after lumbar endoscopic decompression. OVERVIEW OF LITERATURE: There is limited literature comparing the effect of postoperative epidural fluid hematoma after uniportal endoscopic decompression. METHODS: Magnetic resonance imaging (MRI) and clinical evaluation were performed for patients with single-level uniportal endoscopic lumbar decompression with a minimum follow-up of 2 years. RESULTS: A total of 126 patients were recruited with a minimum follow-up of 26 months. The incidence of epidural fluid hematoma was 27%. Postoperative MRI revealed a significant improvement in the postoperative dura sac area at postoperative day 1 and at the upper endplate at 6 months in the hematoma cohort (39.69±15.72 and 26.89±16.58 mm2) as compared with the nonhematoma cohort (48.92±21.36 and 35.1±20.44 mm2), respectively (p <0.05); and at the lower endplate on postoperative 1 day in the hematoma cohort (51.18±24.69 mm2) compared to the nonhematoma cohort (63.91±27.92 mm2) (p <0.05). No significant difference was observed in the dura sac area at postoperative 1 year in both cohorts. The hematoma cohort had statistically significant higher postoperative 1-week Visual Analog Scale (VAS; 3.32±0.68) pain and Oswestry Disability Index (ODI; 32.65±5.56) scores than the nonhematoma cohort (2.99±0.50 and 30.02±4.84, respectively; p <0.05). No significant difference was found at the final follow-up VAS, ODI, and MRI dura sac area. CONCLUSIONS: Epidural fluid hematoma is a common early postoperative MRI finding in lumbar endoscopic unilateral laminotomy with bilateral decompression. Conservative management is the preferred treatment option for patients who do not have a neurological deficit. Symptoms last only a few days and are self-limiting. A common endpoint is a remodeled fluid hematoma and the subsequent expansion of the dura sac area.

Remodeling Pattern of Spinal Canal after Full Endoscopic Uniportal Lumbar Endoscopic Unilateral Laminotomy for Bilateral Decompression: One Year Repetitive MRI and Clinical Follow-Up Evaluation.

Objective: There is limited literature on repetitive postoperative MRI and clinical evaluation after Uniportal Lumbar Endoscopic Unilateral Laminotomy for Bilateral Decompression. Methods: Clinical visual analog scale, Oswestry Disability Index, McNab's criteria evaluation and MRI evaluation of the axial cut spinal canal area of the upper end plate, mid disc and lower end plate were performed for patients who underwent single-level Uniportal Lumbar Endoscopic Unilateral Laminotomy for Bilateral Decompression. From the evaluation of the axial cut MRI, four types of patterns of remodeling were identified: type A: continuous expanded spinal canal, type B: restenosis with delayed expansion, type C: progressive expansion and type D: restenosis. Result: A total of 126 patients with single-level Uniportal Lumbar Endoscopic Unilateral Laminotomy for Bilateral Decompression were recruited with a minimum follow-up of 26 months. Thirty-six type A, fifty type B, thirty type C and ten type D patterns of spinal canal remodeling were observed. All four types of patterns of remodeling had statistically significant improvement in VAS at final follow-up compared to the preoperative state with type A (5.59 ± 1.58), B (5.58 ± 1.71), C (5.58 ± 1.71) and D (5.27 ± 1.68), p < 0.05. ODI was significantly improved at final follow-up with type A (49.19 ± 10.51), B (50.00 ± 11.29), C (45.60 ± 10.58) and D (45.60 ± 10.58), p < 0.05. A significant MRI axial cut increment of the spinal canal area was found at the upper endplate at postoperative day one and one year with type A (39.16 ± 22.73; 28.00 ± 42.57) mm2, B (47.42 ± 18.77; 42.38 ± 19.29) mm2, C (51.45 ± 18.16; 49.49 ± 18.41) mm2 and D (49.10 ± 23.05; 38.18 ± 18.94) mm2, respectively, p < 0.05. Similar significant increment was found at the mid-disc at postoperative day one, 6 months and one year with type A (55.16 ± 27.51; 37.23 ± 25.88; 44.86 ± 25.73) mm2, B (72.83 ± 23.87; 49.79 ± 21.93; 62.94 ± 24.43) mm2, C (66.85 ± 34.48; 54.92 ± 30.70; 64.33 ± 31.82) mm2 and D (71.65 ± 16.87; 41.55 ± 12.92; 49.83 ± 13.31) mm2 and the lower endplate at postoperative day one and one year with type A (49.89 ± 34.50; 41.04 ± 28.56) mm2, B (63.63 ± 23.70; 54.72 ± 24.29) mm2, C (58.50 ± 24.27; 55.32 ± 22.49) mm2 and D (81.43 ± 16.81; 58.40 ± 18.05) mm2 at postoperative day one and one year, respectively, p < 0.05. Conclusions: After full endoscopic lumbar decompression, despite achieving sufficient decompression immediately postoperatively, varying severity of asymptomatic restenosis was found in postoperative six months MRI without clinical significance. Further remodeling with a varying degree of increment of the spinal canal area occurs at postoperative one year with overall good clinical outcomes.

Evaluation of Two Methods (Inside-Out/Outside-In) Inferior Articular Process Resection for Uniportal Full Endoscopic Posterolateral Transforaminal Lumbar Interbody Fusion: Technical Note.

Objective: There is limited literature comparing the uniportal full endoscopic posterolateral transforaminal lumbar interbody fusion outside-in approach (ETLIF (O)) with the inside-out approach (ETLIF (I)). Methods: Radiological evaluation was performed on disc height restoration and coronal wedging angle, and operation time (inferior articular process resection time/total operation time) and clinical evaluation were made. Result: 48 cases of inside-out and 38 cases of outside-in cases were included. Compared to inside-out, the outside-in approach had significantly less operative time required to resect inferior articular process: 36.55 ± 10.37, and total operative time: 87.45 ± 20.14 min compared to 49.83 ± 23.97 and 102.56 ± 36.53 min, respectively, for the inside-out approach, p < 0.05. Compared to the preoperative state, both cohorts achieved significant improvement of VAS and ODI at post-operative 1 week, 3 months and at final follow up. Both cohorts achieved statistically significant increased disc height with 5.00 ± 2.87 mm, 5.49 ± 2.33 mm and statistically significant improvement in coronal wedge angle with 1.76 ± 1.63°, 3.24 ± 2.92° in the inside-out and outside-in approaches respectively. Conclusions: Complete removal of inferior articular process is the key part of endoscopic fusion with two methods that can be applied: an inside-out approach or an outside-in approach. Comparing both techniques, the outside-in approach has a shorter operative time required for inferior articular process resection and total length of operation with similar good clinical and radiological outcomes.