Calycosin Enhances Heat Shock Related-Proteins in H9c2 Cells to Modulate Survival and Apoptosis against Heat Shock.

Heat shock proteins (HSPs), which function as chaperones, are activated in response to various environmental stressors. In addition to their role in diverse aspects of protein production, HSPs protect against harmful protein-related stressors. Calycosin exhibits numerous beneficial properties. This study aims to explore the protective effects of calycosin in the heart under heat shock and determine its underlying mechanism. H9c2 cells, western blot, TUNEL staining, flow cytometry, and immunofluorescence staining were used. The time-dependent effects of heat shock analyzed using western blot revealed increased HSP expression for up to 2[Formula: see text]h, followed by protein degradation after 4[Formula: see text]h. Hence, a heat shock damage duration of 4[Formula: see text]h was chosen for subsequent investigations. Calycosin administered post-heat shock demonstrated dose-dependent recovery of cell viability. Under heat shock conditions, calycosin prevented the apoptosis of H9c2 cells by upregulating HSPs, suppressing p-JNK, enhancing Bcl-2 activation, and inhibiting cleaved caspase 3. Calycosin also inhibited Fas/FasL expression and activated cell survival markers (p-PI3K, p-ERK, p-Akt), indicating their cytoprotective properties through PI3K/Akt activation and JNK inhibition. TUNEL staining and flow cytometry confirmed that calycosin reduced apoptosis. Moreover, calycosin reversed the inhibitory effects of quercetin on HSF1 and Hsp70 expression, illustrating its role in enhancing Hsp70 expression through HSF1 activation during heat shock. Immunofluorescence staining demonstrated HSF1 translocation to the nucleus following calycosin treatment, emphasizing its cytoprotective effects. In conclusion, calycosin exhibits pronounced protective effects against heat shock-induced damages by modulating HSP expression and regulating key signaling pathways to promote cell survival in H9c2 cells.

Transaxillary endoscopic subfascial operation for persistent muscular torticollis in pediatric patients: A 13-year retrospective study in Taiwan.

BACKGROUND: The endoscopic surgery for persistent muscular torticollis has been well-described and most are subcutaneous working caverns. As the sternocleidomastoid muscle is located beneath the deep cervical fascia that corresponds to the pectoral fascia, this study aimed to review our results of the transaxillary approach under the pectoral fascia and the deep cervical fascia. METHODS: Between November 2009 and January 2022, pediatric patients with persistent muscular torticollis receiving transaxillary endoscopic subfascial operation were retrospectively reviewed and analyzed. RESULTS: There were thirty-three consecutive patients with median age of 6.5 years (range, 5.5 months-15.7 years). The median operating time was 90.0 min. With a median follow-up of 14.8 months (range, 5.0-127.7), the final outcomes showed excellent-to-good results in 90.9%, fair results in 6.1%, and poor results in 3.0%. Univariate analysis revealed that the long-term outcomes of the operation were independent of gender, age, involved side and previously open myotomy (p = 0.662, 0.818, 0.740 and 0.596, respectively). CONCLUSIONS: The subfascial working cavern would be technically achievable for the transaxillary endoscopic approach with good functional and cosmetic outcomes.

Intraoperative Hemodynamic Instability and Higher ASA Classification Increase the Risk of Developing Non-Surgical Complications following Orthopedic Surgeries.

(1) Background: Either pre-operative physical status or unstable hemodynamic changes has been reported to play a potential role in causing vital organ dysfunction. Therefore, we intended to investigate the impact of the American Society of Anesthesiologist (ASA) classification and intraoperative hemodynamic instability on non-surgical complications following orthopedic surgery. (2) Methods: We collected data on 6478 patients, with a mean age of 57.3 ± 16, who underwent orthopedic surgeries between 2018 and 2020. The ASA classification and hemodynamic data were obtained from an anesthesia database. Non-surgical complications were defined as a dysfunction of the vital organs. (3) Results: ASA III/IV caused significantly higher odds ratios (OR) of 17.49 and 40.96, respectively, than ASA I for developing non-surgical complications (p < 0.001). Non-surgical complications were correlated with a 20% reduction in systolic blood pressure (SBP), which was intraoperatively compared to the pre-operative baseline ((OR) = 1.38, p = 0.02). The risk of postoperative complications increased with longer durations of SBP < 100 mmHg, peaking at over 20 min ((OR) = 1.33, p = 0.34). (4) Conclusions: Extended intraoperative hypotension and ASA III/IV caused a significantly higher risk of adverse events occurring within the major organs. The maintenance of hemodynamic stability prevents non-surgical complications after orthopedic surgeries.

Biomechanical Analysis of Titanium Dental Implants in the All-on-4 Treatment with Different Implant-Abutment Connections: A Three-Dimensional Finite Element Study.

The type of implant-abutment connection is one of the factors influencing the distribution of occlusal forces. This study aims to investigate the biomechanical performance of the mandibular all-on-4 treatment with different implant-abutment connections. Two connection types with 30° abutments and 18-mm implant fixtures were chosen for the posterior implants of the all-on-4 assembly. For the external hexagon connection (EHC) group, the implants with 4 mm in diameter were used. For the internal hexagon connection (IHC) group, we selected implants with 4.3 mm in diameter. A vertical force of 190 N was applied to the cantilever region. The FEA results indicated that the most stressed region in the two groups was prosthetic screws, followed by multi-unit abutments (MUAs). The lowest values of von Mises stress were both observed on the bone. The peak stress value of the implant screw and implant fixture in the EHC group were 37.75% and 33.03% lower than the IHC group, respectively. For stress distribution patterns, the load force tended to be concentrated at locations where components were interconnected. The EHC and IHC are clinically durable under the tested loading conditions, but the prosthetic screws and MUAs can be the weak point on the posterior implant within the mandibular all-on-four assembly. The peak stress values of implant screw and implant fixture in the EHC groups were lower than the IHC group.

CD24+LCN2+ liver progenitor cells in ductular reaction contributed to macrophage inflammatory responses in chronic liver injury.

BACKGROUND: CD24+CK19+/CD24+SOX9+ resident liver cells are activated and expanded after chronic liver injury in a ductular reaction. However, the sources and functions of these cells in liver damage remain disputed. RESULTS: The current study combined genetic lineage tracing with in vitro small-molecule-based reprogramming to define liver progenitor cells (LPCs) derived from hepatic parenchymal and non-parenchymal tissues. tdTom+ hepatocytes were isolated from ROSA26tdTomato mice following AAV8-Tbg-Cre-mediated recombination, EpCAM+ biliary epithelial cells (BECs) from wild-type intrahepatic bile ducts and ALB/GFP-EpCAM- cells were isolated from AlbCreERT/R26GFP mice. A cocktail of small molecules was used to convert the isolated cells into LPCs. These in vitro cultured LPCs with CD24 and SOX9 expression regained the ability to proliferate. Transcriptional profiling showed that the in-vitro cultured LPCs derived from the resident LPCs in non-parenchymal tissues expressed Lipocalin-2 (Lcn2) at high levels. Accordingly, endogenous Cd24a+Lcn2+ LPCs were identified by integration of sc-RNA-sequencing and pathological datasets of liver dysfunction which indicates that LPCs produced by ductular reactions might also originate from the resident LPCs. Transplantation of in-vitro cultured Cd24a+Lcn2+ LPCs into CCl4-induced fibrotic livers exacerbated liver damage and dysfunction, possibly due to LCN2-dependent macrophage inflammatory response. CONCLUSIONS: CD24+LCN2+ LPCs constituted the expanding ductular reaction and contributed to macrophage-mediated inflammation in chronic liver damage. The current findings highlight the roles of LPCs from distinct origins and expose the possibility of targeting LPCs in the treatment of chronic hepatic diseases.

Reverse Torque Value of Angulated Screw Channel Abutment before and after Cyclic Loading: An In Vitro Study.

This in vitro experiment aimed to understand the difference in preload acting on an abutment screw under different angles of angulated screw-retained crown and the performance after cyclic loading. In total, thirty implants with angulated screw channel (ASC) abutments were divided into two parts. The first part consisted of three groups: a 0° access channel with a zirconia crown (ASC-0) (n = 5), a 15° access channel with a specially designed zirconia crown (sASC-15) (n = 5), and a 25° access channel with a specially designed zirconia crown (sASC-25) (n = 5). The reverse torque value (RTV) was measured at 0° for each specimen. The second part consisted of three groups: a 0° access channel with a zirconia crown (ASC-0) (n = 5); a 15° access channel with a zirconia crown (ASC-15) (n = 5), and a 25° access channel with a zirconia crown (ASC-25) (n = 5). The manufacturer's recommended torque was applied to each specimen, and baseline RTV was measured before cyclic loading. Each ASC implant assembly was cyclically loaded at 0 to 40 N with 1 million cycles at 10 Hz. RTV was measured after cyclic loading. Kruskal-Wallis test and Jonckheere-Terpstra test were used for statistical analysis. All specimens were examined under a digital microscope and scanning electron microscope (SEM) to observe the wear of the screw head before and after the whole experiment. A significant difference in the different percentages of straight RTV (sRTV) between the three groups was found (p = 0.027). The angle of ASC to the different percentages of sRTV showed a significant linear trend (p = 0.003). No significant differences were found in RTV difference after cyclic loading among the ASC-0, ASC-15, and ASC-25 groups (p = 0.212). The ASC-25 group had the most serious degree of wear based on a digital microscope and SEM examination. The ASC angle will affect the actual preload acting on a screw: the larger the ASC angle, the smaller the preload. The performance of the angled ASC groups in RTV difference was comparable to that of 0° ASC after cyclic loading.

Effects of Marginal Bone Loss Progression on Stress Distribution in Different Implant-Abutment Connections and Abutment Materials: A 3D Finite Element Analysis Study.

Peri-implantitis is a common implant-supported prosthesis complication, and marginal bone loss affects the stress distribution in implant systems. This three-dimensional finite element analysis study investigated how bone loss affects the implant assembly; in particular, models including two implant systems with different connection systems (external or internal hexagon), abutment materials (titanium or zirconia), and bone loss levels (0, 1.5, 3, or 5 mm) were created. We observed that the maximum von Mises stress distinctly increased in the groups with bone loss over 1.5 mm compared to the group without bone loss, regardless of the connection system or abutment material used. Moreover, the screw stress patterns with bone loss progression were determined more by the connection systems than by the abutment materials, and the magnitude of the stress on the fixture was affected by the connection systems with a similar pattern. The highest stress on the screw with the external hexagon connection system increased over 25% when bone loss increased from 3 to 5 mm, exceeding the yield strength of the titanium alloy (Ti-6Al-4V) when 5 mm bone loss exists; clinically, this situation may result in screw loosening or fracture. The highest stress on the fixture, exceeding the yield strength of pure titanium, was noted with the internal hexagon connection system and 1.5 mm bone loss. Titanium and zirconia abutments-both of which are clinically durable-presented similar screw and fixture stress patterns. Therefore, clinicians should pay more attention to maintaining the peri-implant bone to achieve the long-term stability of the implant-supported prosthesis.

Effect of Marginal Bone Integrity and Aftermarket Abutment Screws on Dental Implant Systems-A Preliminary Study with Finite Element Method.

Bone resorption around implants is quite common, and the maturity and popularization of computer-aided design and computer-aided manufacturing (CAD/CAM) technology have made the use of aftermarket abutment screws more widespread. This study aimed to explore the biomechanical influence of these two common factors on the internal stress of an implant system using three-dimensional finite element analysis (3D FEA). The FEA results indicated that under the same loading conditions, the use of an aftermarket screw had the greatest impact on the screw itself among the three components of the implant system, while the maximum stress increased by 6.3% and 10.5% in the bone integrity and bone loss models, respectively. Moreover, the marginal bone loss models had the greatest impact on the implant fixture, with a maximum stress increase of 51.8% on average. Evidently, the influence of bone loss might be far greater than that of the aftermarket screw; however, any factor could be enough to cause clinical failure. Therefore, we should pay more attention to the maintenance of the long-term peri-implant marginal bone integrity.

Coenzyme Q10 Supplementation Increases Removal of the ATXN3 Polyglutamine Repeat, Reducing Cerebellar Degeneration and Improving Motor Dysfunction in Murine Spinocerebellar Ataxia Type 3.

Coenzyme Q10 (CoQ10), a well-known antioxidant, has been explored as a treatment in several neurodegenerative diseases, but its utility in spinocerebellar ataxia type 3 (SCA3) has not been explored. Herein, the protective effect of CoQ10 was examined using a transgenic mouse model of SCA3 onset. These results demonstrated that a diet supplemented with CoQ10 significantly improved murine locomotion, revealed by rotarod and open-field tests, compared with untreated controls. Additionally, a histological analysis showed the stratification of cerebellar layers indistinguishable from that of wild-type littermates. The increased survival of Purkinje cells was reflected by the reduced abundance of TUNEL-positive nuclei and apoptosis markers of activated p53, as well as lower levels of cleaved caspase 3 and cleaved poly-ADP-ribose polymerase. CoQ10 effects were related to the facilitation of the autophagy-mediated clearance of mutant ataxin-3 protein, as evidenced by the increased expression of heat shock protein 27 and autophagic markers p62, Beclin-1 and LC3II. The expression of antioxidant enzymes heme oxygenase 1 (HO-1), glutathione peroxidase 1 (GPx1) and superoxide dismutase 1 (SOD1) and 2 (SOD2), but not of glutathione peroxidase 2 (GPx2), were restored in 84Q SCA3 mice treated with CoQ10 to levels even higher than those measured in wild-type control mice. Furthermore, CoQ10 treatment also prevented skeletal muscle weight loss and muscle atrophy in diseased mice, revealed by significantly increased muscle fiber area and upregulated muscle protein synthesis pathways. In summary, our results demonstrated biochemical and pharmacological bases for the possible use of CoQ10 in SCA3 therapy.

The Effect of an Er, Cr: YSGG Laser Combined with Implantoplasty Treatment on Implant Surface Roughness and Morphologic Analysis: A Pilot In Vitro Study.

Although laser irradiation and implantoplasty (IP) are both treatment options for peri-implantitis, no studies have yet combined these two treatment solutions. The aim of this study was to identify the effect of an Er, Cr: YSGG laser on the IP surface. In experiment 1, TiUnite anodized surface implants were treated with an Er, Cr: YSGG laser at 0.5 to 2 W on the panel energy setting and 20 Hz under water irrigation. In experiment 2, all implant surfaces were treated with the IP procedure first, then irradiated with the Er, Cr: YSGG laser. All samples were analyzed by stereomicroscopy, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), and surface topography. Stereomicroscopy and SEM revealed no obvious surface change at any energy setting once the surface was polished with the IP procedure, whereas damage was caused to the TiUnite original implant surface when the Er, Cr: YSGG laser panel energy was set at 1 W or higher. EDS showed no significant difference in element composition once the surface was polished with the IP procedure, while a compositional change was detected when the Er, Cr: YSGG laser panel energy was set to 0.5 W or higher to irradiate the original TiUnite surface. Surface roughness may be related to laser irradiation energy, but no significant changes occurred following IP. These results indicated that the Er, Cr: YSGG laser may have little effect on the post-IP surface compared with the virgin TiUnite surface.

In Vitro Efficacy and Molecular Mechanism of Curcumin Analog in Pathological Regulation of Spinocerebellar Ataxia Type 3.

Unlike other nuclear factor erythroid-2-related factor 2 (Nrf2) activators, the mechanism of action of curcumin analog, ASC-JM17 (JM17), in regulating oxidative homeostasis remains unknown. Spinocerebellar ataxia type 3 (SCA3) is an inherited polyglutamine neurodegenerative disease caused mainly by polyglutamine neurotoxicity and oxidative stress. Presently, we compared actions of JM17 with those of known Nrf2 activators, omaveloxolone (RTA-408) and dimethyl fumarate (DMF), using human neuroblastoma SK-N-SH cells with stable transfection of full-length ataxin-3 protein with 78 CAG repeats (MJD78) to clarify the resulting pathological mechanism by assaying mitochondrial function, mutant ataxin-3 protein toxicity, and oxidative stress. JM17, 1 µM, comprehensively restored mitochondrial function, decreased mutant protein aggregates, and attenuated intracellular/mitochondrial reactive oxygen species (ROS) levels. Although JM17 induced dose-dependent Nrf2 activation, a low dose of JM17 (less than 5 µM) still had a better antioxidant ability compared to the other Nrf2 activators and specifically increased mitochondrial superoxide dismutase 2 in an Nrf2-dependent manner as shown by knockdown experiments with siRNA. It showed that activation of Nrf2 in response to ROS generated in mitochondria could play an import role in the benefit of JM17. This study presents the diversified regulation of JM17 in a pathological process and helped develop more effective therapeutic strategies for SCA3.

A Retrospective Analysis of Implants with Low Insertion Torque in Immediately Loaded Full-Arch Fixed Prostheses with Corresponding Occlusal Schemes.

PURPOSE: Poor alveolar bone quality and quantity may cause low insertion torque during implant placement; therefore, a delicate occlusal design is important for the immediate loading procedure. This retrospective clinical study aimed to investigate (1) the proportion of implants with a low insertion torque between the maxilla and mandible, (2) factors affecting implants with a low insertion torque, and (3) survival rates of implants with a low insertion torque value (< 35 Ncm) using different occlusal designs with full-arch fixed prostheses supported by immediately loaded implants. MATERIALS AND METHODS: Between 2013 and 2017, patients who received full-arch reconstructions were treated with immediately loaded one-piece fixed prostheses supported by four to six implants. Full-arch fixed prostheses with at least one immediately loaded regular implant with a low insertion torque value were included in this study. The fixed provisional acrylic prosthesis with a rigid framework was delivered within 3 to 5 days after surgery. According to the distribution of implants with low insertion torque, provisional prostheses were divided into three groups with different occlusal schemes. Definitive prostheses were fabricated after 3 months of loading. RESULTS: A total of 144 patients were treated; 608 and 304 regular implants were inserted in 118 maxillae and 76 mandibles, respectively. Moreover, 42 patients (11 men and 31 women) with 39 maxillae and 4 mandibles were included in this study. The proportion of implants with low insertion torque values in the maxilla was significantly greater than that in the mandible (10.5% vs 1.6%, respectively, P < .001). Implant length and low insertion torque value had no significant correlation (P = .948). Implants with a 3.3-mm diameter (narrow platform) had a greater proportion of low insertion torque values than 4-mm-wide implants (P = .002). Implants placed in a fresh socket had a greater proportion of insertion torque values ≥ 35 Ncm (P = .023). The overall cumulative implant survival rate was 98.6%. Groups 1, 2, and 3 had 14, 23, and 6 provisional prostheses, respectively. The survival rates for implants with insertion torque values < 35 Ncm and ≥ 35 Ncm were 98.4% and 98.7%, respectively, and were not significantly different (P = .866). All prostheses were still functioning during the mean follow-up of 3.7 ± 1.2 years. CONCLUSION: The high cumulative implant survival rate indicated that implants with a low insertion torque in immediately loaded full-arch provisional prostheses did not jeopardize the outcomes after a corresponding occlusal scheme was used.

Genome-wide methylation profiling of early colorectal cancer using an Illumina Infinium Methylation EPIC BeadChip.

BACKGROUND: DNA methylation is a part of epigenetic modification, that is closely related to the growth and development of colorectal cancer (CRC). Specific methylated genes and methylated diagnostic models of tumors have become current research focuses. The methylation status of circulating DNA in plasma might serve as a potential biomarker for CRC. AIM: To investigate genome-wide methylation pattern in early CRC using the Illumina Infinium Human Methylation 850K BeadChip. METHODS: The 850K Methylation BeadChip was used to analyze the genome-wide methylation status of early CRC patients (n = 5) and colorectal adenoma patients (n = 5). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analyses were performed on the selected differentially methylated sites to further discover candidate methylation biomarkers in plasma. RESULTS: A total of 1865 methylated CpG sites with significant differences were detected, including 676 hypermethylated sites and 1189 hypomethylated sites. The distribution of these sites covered from the 1st to 22nd chromosomes and are mainly distributed on the gene body and gene promoter region. GO and KEGG enrichment analysis showed that the functions of these genes were related to biological regulation, molecular binding, transcription factor activity and signal transduction pathway. CONCLUSION: The study demonstrated that the Illumina Infinium Human Methylation 850K BeadChip can be used to investigate genome-wide methylation status of plasma DNA in early CRC and colorectal adenoma patients.

Biomechanical Evaluation of Bone Atrophy and Implant Length in Four Implants Supporting Mandibular Full-Arch-Fixed Dentures.

Residual alveolar ridge resorption often occurs after tooth extraction, which causes issues requiring further prothesis rehabilitation. A treatment concept referred to as all-on-four, involving fixed dentures supported with four implants, was recently developed. The current study aimed to determine the effect of changing bone atrophy and implant length in all-on-four treatments on stress and strain in the surrounding bone of the implant. A three-dimensional finite element method was used in this research. The stress analysis was conducted with von Mises stress values. Two types of synthetic jawbone models with mild and moderate atrophy were used. Furthermore, two different implant lengths with a similar implant design and diameter were selected, and they were classified into eight models. Then, the bone model was assessed via a computed tomography (CT) scan and was transformed into a virtual model in Geomagic and SolidWorks with implant rebuilding. After modifying bone atrophy, the von Mises stresses in the surrounding bone of the implant were as follows: mild type 2 < mild type 3 < moderate type 3 < moderate type 4. The bone quantity change rate increased more than when bone conditions were limited. Compared with changes in implant lengths, the stresses in the peri-implant surrounding bone were generally higher in the 9 mm implant length group than in the 11.5 mm group. However, the results did not significantly differ. In conclusion, the von Mises stress and strain increased in the models with moderate atrophy and low-density trabecular bone. Hence, bone atrophy and its presurgical diagnosis in long-term implant prognosis are crucial.

Applications of triplex DNA nanostructures in sensor development.

Triplex DNA nanostructures are one of the most emerging and fascinating self-assembled nanostructures due to their unique nanoparticle-like organization and inherit characteristics. They have attracted numerous interests recently because of their versatile and powerful utility in diverse areas of science and technology, such as clinical or disease diagnosis and stimuli-based drug delivery. This review addresses particularly the utilization of DNA triplexes in the development of biosensors for detecting nucleic acid; strategies in sensing pH, protein activity, ions, or molecules. Finally, an outlook for potential applications of triplex DNA nanoswitches is provided.

Comparing the Fracture Resistance and Modes of Failure in Different Types of CAD/CAM Zirconia Abutments with Internal Hexagonal Implants: An In Vitro Study.

Three groups of zirconia abutments (n = 5) consisting of different connection designs or manufacturers were investigated (All-Zr, ASC-Zr, and AM-Zr groups). All-electric dynamic test instruments were used to place static loading on a specimen with a crosshead speed set at 1 mm/min. A Kruskal-Wallis test and a post hoc Mann-Whitney U test were used for statistical evaluation. The mean fracture resistance was 252.37 ± 82.79 N for the All-Zr group, 384.62 ± 45.24 N for ASC-Zr group, and 361.83 ± 90.31 N for the AM-Zr group. The difference of fracture resistance between the three groups was marginally significant (Kruskal-Wallis test, p = 0.054), with the ASC zirconia abutment tending to have higher fracture resistance than the full zirconia abutment. The modes of failure among the three types of abutments are different. The All-Zr group showed an oblique fracture line starting from the buccal aspect at the region of the implant platform. While the ASC-Zr and AM-Zr groups showed a relatively horizontal fracture line with a greater distance from the implant platform. The titanium inserts cannot significantly improve the fracture resistance of the zirconia abutment. However, they may alter the modes of failure, allowing buccal fracture surfaces of the zirconia abutments to be placed away from the implant platform, thereby protecting the implant-abutment connection.

Intranasal delivery of mitochondria for treatment of Parkinson's Disease model rats lesioned with 6-hydroxydopamine.

The feasibility of delivering mitochondria intranasally so as to bypass the blood-brain barrier in treating Parkinson's disease (PD), was evaluated in unilaterally 6-OHDA-lesioned rats. Intranasal infusion of allogeneic mitochondria conjugated with Pep-1 (P-Mito) or unconjugated (Mito) was performed once a week on the ipsilateral sides of lesioned brains for three months. A significant improvement of rotational and locomotor behaviors in PD rats was observed in both mitochondrial groups, compared to sham or Pep-1-only groups. Dopaminergic (DA) neuron survival and recovery > 60% occurred in lesions of the substantia nigra (SN) and striatum in Mito and P-Mito rats. The treatment effect was stronger in the P-Mito group than the Mito group, but the difference was insignificant. This recovery was associated with restoration of mitochondrial function and attenuation of oxidative damage in lesioned SN. Notably, P-Mito suppressed plasma levels of inflammatory cytokines. Mitochondria penetrated the accessory olfactory bulb and doublecortin-positive neurons of the rostral migratory stream (RMS) on the ipsilateral sides of lesions and were expressed in striatal, but not SN DA neurons, of both cerebral hemispheres, evidently via commissural fibers. This study shows promise for intranasal delivery of mitochondria, confirming mitochondrial internalization and migration via RMS neurons in the olfactory bulb for PD therapy.