Physiological and molecular mechanisms of ZnO quantum dots mitigating cadmium stress in Salvia miltiorrhiza.

This study delved into the physiological and molecular mechanisms underlying the mitigation of cadmium (Cd) stress in the model medicinal plant Salvia miltiorrhiza through the application of ZnO quantum dots (ZnO QDs, 3.84 nm). A pot experiment was conducted, wherein S. miltiorrhiza was subjected to Cd stress for six weeks with foliar application of 100 mg/L ZnO QDs. Physiological analyses demonstrated that compared to Cd stress alone, ZnO QDs improved biomass, reduced Cd accumulation, increased the content of photosynthetic pigments (chlorophyll and carotenoids), and enhanced the levels of essential nutrient elements (Ca, Mn, and Cu) under Cd stress. Furthermore, ZnO QDs significantly lowered Cd-induced reactive oxygen species (ROS) content, including H2O2, O2-, and MDA, while enhancing the activity of antioxidant enzymes (SOD, POD, APX, and GSH-PX). Additionally, ZnO QDs promoted the biosynthesis of primary and secondary metabolites, such as total protein, soluble sugars, terpenoids, and phenols, thereby mitigating Cd stress in S. miltiorrhiza. At the molecular level, ZnO QDs were found to activate the expression of stress signal transduction-related genes, subsequently regulating the expression of downstream target genes associated with metal transport, cell wall synthesis, and secondary metabolite synthesis via transcription factors. This activation mechanism contributed to enhancing Cd tolerance in S. miltiorrhiza. In summary, these findings shed light on the mechanisms underlying the mitigation of Cd stress by ZnO QDs, offering a potential nanomaterial-based strategy for enhancing Cd tolerance in medicinal plants.

Efficacy and Safety of Traditional Chinese Medicines as a Complementary Therapy Combined With Chemotherapy in the Treatment of Gastric Cancer: An Overview of Systematic Reviews and Meta-Analyses.

BACKGROUND: In China, traditional Chinese medicines (TCMs), as a complementary therapy combined with chemotherapy, is widely used in the treatment of gastric cancer (GC). In order to systematically evaluate and synthesize existing evidence to provide a scientific basis for the efficacy and safety of this complementary therapy, we present an overview of systematic reviews (SRs) and meta-analyses (MAs) on the topic of TCMs as a complementary therapy in combination with chemotherapy for the treatment of GC. METHODS: SRs/MAs on TCMs combined with chemotherapy for GC were comprehensively searched in 8 databases. Methodological quality, risk of bias, reporting quality, and quality of evidence were assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic (ROBIS) scale, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA 2020), as well as the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: Thirteen published SRs/MAs were included in our study. In terms of methodology, all SRs/MAs were considered to be of very low quality. Only 3 SRs/MAs has been assessed as low risk of bias. None of the SRs/MAs has been fully reported on the checklist. A total of 97 outcome indicators extracted from the included SRs/MAs were evaluated, and only 1 item was assessed as high quality. CONCLUSIONS: TCMs may be an effective and safe complementary therapy in combination with chemotherapy for the treatment of GC. However, this conclusion must be treated with caution as the quality of the evidence provided by SRs/MAs is generally low.

Construction of site-specific magnetic Z-scheme CdS/Fe3O4@N-doped graphene aerogel microtube/N-doped TiO2 with porous structure: enhanced catalytic performance in photo-Fenton reaction.

The development of composite photocatalysts with high charge transfer efficiency, great visible light absorption, and quick recovery has aroused the interest of many researchers. Herein, based on the hydrothermal assisted vacuum freeze drying method, CdS, Fe3O4, and N-TiO2 were, respectively, fixed in the inner, middle, and outer layers of nitrogen-doped graphene aerogel for preparation of the site-specific magnetic porous Z-scheme CdS/Fe3O4@N-doped graphene aerogel microtube/N-doped TiO2 (CdS/Fe3O4@NGAM/N-TiO2) photocatalyst. For the composite, Fe3O4@NGAM carrier with porous and tubular structure not only helps the recycle and reactants/productions mass transport in the photocatalytic process but also ensures the well-steered transfer of electrons and holes from CdS and N-TiO2 in the Z-type heterojunction system, greatly improving the separation of photogenerated carriers. Besides, Fe3O4 can also work as a Fenton catalyst to activate hydrogen peroxide which is generated in situ by CdS. Thus, the CdS/Fe3O4@NGAM/N-TiO2 composite presents excellent degradation efficiencies towards methyl orange ((MO) 98% removal rate within 50 min), bisphenol A ((BPA) 96% removal rate within 50 min), tetracycline hydrochloride ((TCH) 96% removal rate within 120 min) and strong stabilities after 6 cycles. The free radical removal experiments show that ·O2- and ·OH are the main active substances of catalysis, which further confirms the synergistic effect of photocatalysis and Fenton catalysis.

Carbon Dioxide Fractional Laser Treatment Induces Lgr5+ Stem Cell Activation and Hair Regrowth Through the Canonical Wnt/ß-Catenin Pathway.

BACKGROUND: Different types of alopecia have negative impacts on patients. Recently, some kinds of laser or light therapies have been reported to effectively alleviate hair loss. Carbon dioxide fractional laser (CO2FL) treatment is one of the most effective laser treatments, but its beneficial effects and exact mechanism in hair regrowth have not been reported in detail. The purpose of this study was to investigate the effect and molecular mechanism further. METHODS: C57 and Lgr5-Cre: Rosa-mTmG mouse models of hair regrowth were established by CO2FL treatment, and the parameters that induced the best effect were determined. Tissues were harvested on the day prior to the treatment day and on days 3, 5, 7, 10 and 14 after CO2FL. H&E and immunofluorescence staining, RNA sequencing (RNA-seq), quantitative real-time polymerase chain reaction (qPCR), Western blotting (WB) and related inhibitor were used to determine the molecular mechanism underlying the effect of CO2FL treatment on the hair cycle and hair regrowth. In clinical trial, five participants were treated three sessions at 1-month intervals to obverse the effects. RESULTS: Hair regrew and covered the treatment area on the tenth day after CO2FL treatment with the best parameters, while the control group showed signs of hair growth on the 14th day. H&E and immunofluorescence staining showed that the transition of hair follicles (HFs) from telogen to anagen was accelerated, and the rapid activation and proliferation of Lgr5+ hair follicle stem cells (HFSCs) were observed in the treatment group. The RNA-seq, qPCR and WB results indicated that the Wnt pathway was significantly activated after CO2FL treatment. Improvement achieved with CO2FL treatment in clinical trial. CONCLUSIONS: The results of this study suggest that CO2FL treatment can promote hair regrowth by activating Lgr5+ HFSCs and upregulating the Wnt/ß-catenin pathway. Clinical trial results demonstrated that CO2FL treatment will be a promising therapeutic regimen for alopecia. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Is remnant preservation in anterior cruciate ligament reconstruction superior to the standard technique? An overview of systematic reviews.

BACKGROUND: Anterior cruciate ligament injury is a common knee joint injury. Anterior cruciate ligament reconstruction is a common surgical treatment to treat anterior cruciate ligament injury. It may have certain advantages to retain the ligament stump during the operation, but the results of systematic evaluation on whether to retain the ligament stump are different. The conclusion is still controversial, and the quality needs to be strictly evaluated. OBJECTIVE: To evaluate the methodological quality, risk of bias, reporting quality and evidence quality of the systematic review of remnant preservation in anterior cruciate ligament reconstruction, and to provide reference for clinical work. METHODS: We systematically searched the system evaluations in 8 electronic databases, the languages were limited to Chinese and English, and the time limit was from the establishment of the database to June 2023. Two reviewers independently screened literature and extracted data. The methodological quality, risk of bias, reporting quality and quality of evidence were evaluated by AMSTAR-2, ROBIS, PRISMA and GRADE tools. RESULTS: A total of 14 systematic reviews were included. The evaluation of results showed that the methodological quality of the included systematic reviews was relatively low, of which 5 were low quality and 9 were critically low quality. A small number of systematic reviews were low risk of bias. The system evaluation reports are relatively complete, but the lack of program registration is a common problem. A total of 111 pieces of clinical evidence were extracted from the included 14 systematic reviews. The quality of evidence was generally low, with only 7 pieces of high-quality evidence, 45 pieces of medium-quality evidence, and the rest were low and very low-quality evidence. Among the reasons for relegation, imprecision is the most common, followed by inconsistency and indirectness. The existing evidence shows that patients after anterior cruciate ligament reconstruction with remnant preservation have certain advantages in knee joint function, joint stability and proprioception recovery, which may be a more effective surgical method. However, it may also increase the incidence of postoperative complications and adverse reactions. CONCLUSION: Compared with Standard Technique, Remnant Preservation in Anterior Cruciate Ligament Reconstruction has more advantages in restoring joint function and stability and proprioception. But the potential risks should also be considered by surgeons. At present, the quality of evidence is generally low, and the reliability of the conclusion is insufficient. It still needs to be verified and further in-depth research is needed.

The effect of acupuncture on recovery after colorectal cancer resection: A systematic review meta-analysis of randomized controlled trials.

BACKGROUND: To evaluate the efficacy and safety of acupuncture by systematically reviewing the literature on colorectal cancer resection. METHODS: Seven electronic databases were searched from inception to February 28, 2023. Randomized controlled trials on acupuncture in patients after CRC resection were included. Two reviewers independently selected relevant trials, extracted data, and assessed the risk of bias. A random-effects meta-analysis model was used to obtain summary effect estimates. The data were pooled and analyzed using RevMan 5.3. The heterogeneity of selected studies was evaluated by evaluating the I-squared (I2) statistics. RESULTS: Twenty-two studies with 1878 patients were included. Results of the meta-analysis showed there was a low level evidence that acupuncture may improve early postoperative symptoms, such as time to first flatus (n = 876, MD -0.77h, 95% CI -1.22 to -0.33 h, I2 = 89%), time to first bowel movement (n = 671, MD -1.41h, 95% CI -2.20 to -0.63 h, I2 = 95%), time to first defecation (n = 556, MD -1.03h, 95% CI -1.88 to -0.18 h, I2 = 95%), and nausea/vomiting (n = 1488, RR 0.72, 95% CI 0.59-0.89, I2 = 49%) compared with usual care and sham acupuncture. However, there were no statistically significant differences in postoperative pain (n = 1188, MD-0.21, 95% CI -0.59 to 0.17, I2 = 74%). And there was no sufficient evidence of improving long-term functional outcomes. There was substantial heterogeneity across trials. The adverse events associated with acupuncture stimulation were minor in include studies. CONCLUSION SUBSECTIONS: There is currently low-level evidence supporting the use of acupuncture on postoperative symptoms for patients after colorectal cancer resection. More investigations should be established based on the STRICTA statement strictly.

Transcription Factor BCL11A Regulates Schwann Cell Behavior During Peripheral Nerve Regeneration.

Nerve injury-induced Schwann cell dedifferentiation helps to construct a favorable microenvironment for axon growth. Transcription factors regulate cell reprogramming and thus may be critical for Schwann cell phenotype switch during peripheral nerve regeneration. Here, we show that transcription factor B-cell lymphoma/leukemia 11A (BCL11A) is up-regulated in Schwann cells of injured peripheral nerves. Bcl11a silencing suppresses Schwann cell viability, decreases Schwann cell proliferation and migration rates, and impairs the debris clearance ability of Schwann cells. Reduced Bcl11a in injured peripheral nerves results in restricted axon elongation and myelin wrapping, leading to recovery failure. Mechanistically, we demonstrate that BCL11A may mediate Schwann cell activity through binding to the promoter of nuclear receptor subfamily 2 group F member 2 (Nr2f2) and regulating Nr2f2 expression. Collectively, we conclude that BCL11A is essential for Schwann cell activation and peripheral nerve regeneration, providing a potential therapeutic target for the treatment of peripheral nerve injury.

Integrated Multiomics and Synergistic Functional Network Revealed the Mechanism in the Tolerance of Different Ecotypes of Salvia miltiorrhiza Bge. to Doxycycline Pollution.

Tetracycline pollution in soil irreversibly damages the biosafety of plants by inhibiting the mitochondrial function. Some traditional Chinese medicine (TCM) plants, such as Salvia miltiorrhiza Bunge, have a strong tolerance to mitochondrial damage. We comprehensively compared the doxycycline (DOX) tolerances of two ecotypes of S. miltiorrhiza in the Sichuan and Shandong provinces and found that the Sichuan ecotype had a lower yield reduction, more stable accumulation of medicinal ingredients, higher mitochondrial integrity, and a more robust antioxidant system. The synergetic response networks under DOX pollution of both ecotypes were constructed using RNA sequencing and ultrahigh-performance liquid chromatography-tandem mass spectrometry. The differentiation of the downstream pathways of aromatic amino acids (AAAs) produced variations in the DOX tolerance of S. miltiorrhiza in different regions. The Sichuan ecotype maintained redox homeostasis and xylem development by activating salvianolic acid and indole biosynthesis, while the Shandong ecotype balanced chemical and mechanical defenses by regulating the flavonoid biosynthesis. Rosmarinic acid, a downstream AAA molecule, maintains the mitochondrial homeostasis of plant seedlings under DOX pollution by targeting the ABCG28 transporter. We also highlight the significance of downstream AAA small molecules in guiding the development of bio-based environmental pollution remediation agents.

MoS2/polyaniline (PANI)/polyacrylonitrile (PAN)@BiFeO3 bilayer hollow nanofiber membrane: Photocatalytic filtration and piezoelectric effect enhancing degradation and disinfection.

A novel MoS2/polyaniline (PANI)/polyacrylonitrile (PAN)@BiFeO3 bilayer hollow nanofiber membrane (PPBM-H) was successfully synthesized by coaxial electrospinning technique. In the nanofiber, BiFeO3 nanoparticles (NPs) and MoS2 nanosheets (NSs) were loaded in the middle and outer layers of the PANI/PAN composites, respectively, which constructs a type II heterojunction with spatially separated microtopography, thus significantly improving the charge separation in photocatalysis. Moreover, the hollow structure and the vast number of exposed groups on the surface of PPBM-H help to improve the mass transfer efficiency and pollutant adsorption performance in wastewater treatment. In addition, PPBM-H can generate H2O2 by in-situ activation of BiFeO3/MoS2 for photo-Fenton catalysis, enabling Fe3+ and Fe2+ recycling. Also, PPBM-H can produce piezoelectric polarisation under ultrasonic excitation, which can further enhance the efficiency of electron/hole separation and transfer, and induce the generation of active free radicals. Owing to its wonderful self-cleaning effect, the PPBM-H has good mechanical strength (2.95 Mpa), hydrophilicity (11.6°), water flux (1248 L·m-2·h-1), BSA rejection (98.8 %), and exhibits distinguished photocatalytic filtration efficiencies (99.5 % tetracycline hydrochloride (TCH) and 99.9 % methyl orange (MO) within 60 min), piezo-photocatalysis (99.2 % TCH within 2 h), disinfection performance for Escherichia coli (E. coli) (100 %, within 60 min).

Preparation of site-specific Z-scheme g-C3N4/PAN/PANI@LaFeO3 cable nanofiber membranes by coaxial electrospinning: Enhancing filtration and photocatalysis performance.

The coaxial electrospinning method for preparation of g-C3N4/polyacrylonitrile (PAN)/polyaniline (PANI)@LaFeO3 cable fiber membrane (PC@PL) was designed for adsorption-filtration-photodegradation of pollutants. A series of characterization results show that LaFeO3 and g-C3N4 nanoparticles (NPs) are respectively loaded in the inner and outer layers of PAN/PANI composite fibers to construct the site-specific Z-type heterojunction system with spatially separated morphologies. The PANI in cable not only possesses abundant exposed amino/imino functional groups for adsorption of contaminant molecules but also due to the excellent electrical conductivity works as a redox medium for collecting and consuming the electrons and holes from LaFeO3 and g-C3N4, which can efficiently promote photo-generated charge carriers separation and improve the catalytic performance. Further investigations demonstrate that as a photo-Fenton catalyst LaFeO3 in PC@PL catalyzes/activates the H2O2 generated in situ by LaFeO3/g-C3N4, further enhancing the decontamination efficiency of the PC@PL. The porous, hydrophilic, antifouling, flexible and reusable properties of the PC@PL membrane significantly enhance the mass transfer efficiency of reactants by filtration effect and increase the amount of dissolved oxygen, thus producing massive •OH for degradation of pollutants, which maintains the water flux (1184 L m-2. h-1 (LMH)) and the rejection rate (98.5%). Profiting from its unique synergistic effect of adsorption, photo-Fenton and filtration, PC@PL exhibits wonderful self-cleaning performance and distinguished removal rate for methylene blue (97.0%), methyl violet (94.3%), ciprofloxacin (87.6%) and acetamiprid (88.9%) within 75 min, disinfection (100% Escherichia coli (E. coli) and 80% Staphylococcus aureus (S.aureus) inactivation)) and excellent cycle stability.

Transcriptional Control of Peripheral Nerve Regeneration.

Transcription factors are master regulators of various cellular processes under diverse physiological and pathological conditions. Many transcription factors that are differentially expressed after injury to peripheral nerves play important roles in nerve regeneration. Considering that rapid and timely regrowth of injured axons is a prerequisite for successful target reinnervation, here, we compile transcription factors that mediates axon elongation, including axon growth suppressor Klf4 and axon growth promoters c-Myc, Sox11, STAT3, Atf3, c-Jun, Smad1, C/EBPδ, and p53. Besides neuronal changes, Schwann cell phenotype modulation is also critical for nerve regeneration. The activation of Schwann cells at early time points post injury provides a permissive microenvironment whereas the re-differentiation of Schwann cells at later time points supports myelin sheath formation. Hence, c-Jun and Sox2, two critical drivers for Schwann cell reprogramming, as well as Krox-20 and Sox10, two essential regulators of Schwann cell myelination, are reviewed. These transcription factors may serve as promising targets for promoting the functional recovery of injured peripheral nerves.

Identification of Salvia miltiorrhiza Bunge with high and low cadmium accumulation and insight into the mechanisms of cadmium accumulation.

Salvia miltiorrhiza Bunge is used as a Chinese herbal medicine (CHM) particularly its roots. No relevant reports at home and abroad have been made on the mechanism of cadmium (Cd) accumulation in S. miltiorrhiza. The Cd accumulation characteristics of S. miltiorrhiza from main cultivation areas in China were evaluated for the first time to obtain high and low Cd accumulation in S. miltiorrhiza roots. Results showed obvious differences in the Cd enrichment capacity of S. miltiorrhiza from different cultivation areas. We took the lead in identifying the germplasm resources of S. miltiorrhiza with high and low Cd accumulation, that is, S. miltiorrhiza roots from Pingyi Shangdong (SDPY) belongs to the resource with high Cd accumulation (SDPY-H) and that from Zhongjiang Sichuan (SCZJ) is the resources with low Cd accumulation (SCZJ-L) based on relevant physiological and biochemical indexes. Although the Cd content of SDPY-H was apparently higher than that from SCZJ-L, its translocation factor from root to aboveground part is significantly lower than that in SCZJ-L. Therefore, planting SCZJ-L is not only an economic and effective way to use Cd in slightly and moderately polluted soil, but also its aboveground part can be used for phytoremediation. Changes in Cd content before and after the use of transpiration inhibitor indicate that SDPY-H enriched Cd through the symplastic pathway, whereas SCZJ-L mainly enriched Cd through the apoplastic pathways. In addition, the role of the symplastic pathway in SCZJ-L is weaker than that in SDPY-H, which were preliminarily revealed by fluorescent quantitative polymerase chain reaction. The significant reduction of the SmNramps transcription expression amount is one of the reasons for the low Cd accumulation of SCZJ-L.

Metabolism-related MOGS Gene is Dysregulated After Peripheral Nerve Injury and Negatively Regulates Schwann Cell Plasticity.

Cellular metabolism is essentially linked to tissue remodeling and organ regeneration. MOGS, a gene that encodes cellular metabolism-related protein mannosyl-oligosaccharide glucosidase, was found to be upregulated in nerve segments after peripheral nerve injury. Bioinformatic analyses identified upstream regulators of MOGS and MOGS-associated genes and indicated the significant involvement of cellular metabolism in peripheral nerve regeneration. Functional assessment showed that siRNA-mediated knockdown of MOGS led to elevated proliferation, migration, and differentiation of Schwann cells, indicating the negative regulation of MOGS on Schwann cell plasticity. Schwann cells transfected with MOGS siRNA also showed lower expression of fatty acid synthase (FASN), demonstrating that dysregulated MOGS in Schwann cells may affect neuronal behavior through the metabolic coupling between Schwann cells and axons. Taken together, this study demonstrated that MOGS may be a key regulating factor of Schwann cells and neuronal phenotype during peripheral nerve regeneration.

Ultrasonic-Assisted Aqueous Two-Phase Extraction Combined with Macroporous Resin Enrichment of Lignans from Flaxseed Meal and Their Antioxidant Activities.

BACKGROUND: Secoisolariciresinol diglucoside (SDG) is a natural antioxidant generally extracted from flaxseed, which is one of the most important oil crops in China, the by-product of the flaxseed oil, i.e., flaxseed meal still contains a lot of lignans. However, flaxseed meal is generally treated as waste, resulting in a huge waste of resources. OBJECTIVE: To establish an efficient and convenient method for extraction and purification of lignans from flaxseed meal. METHODS: First, we used response surface methodology (RSM) to optimize the extraction conditions of the ultrasonic-assisted (UA) aqueous two-phase system (ATPS), and we obtained the purified extracts by macroporous resin purification (MRP). Second, the antioxidant ability of the extracts was studied in vitro. RESULTS: The best extraction conditions obtained were as follows: 9.0% (w/w) sodium hydroxide; 30.0% (w/w) isopropanol; extraction time, 39 min; liquid-to-solid ratio, 52.0 mL/g; ultrasonic wave, 560 W; and extraction temperature, 40°C. Under the optimal conditions, the purity of crude extracts (SDG-APTS-C) reached 21.5%. The desorption conditions of MRP were as follows: eluting 3 BV with ultrapure water, and then eluting with 25% ethanol at 2 BV (bed volume)/h to collect eluents. The purified extracts (SDG-ATPS-P) had a purity quotient of 73.9%, which was 52.4% higher than that of SDG-ATPS-C. Additionally, experiments conducted revealed that SDG-ATPS-C and SDG-ATPS-P could effectively remove DPPH (2,2-Diphenyl-1-picrylhydrazyl), ABTS （2,-Azinobis-3-ethylbenzthiazoline-6-sulphonate）, and hydroxyl free radicals in vitro. CONCLUSIONS: The method was validated for extracting SDG from flaxseed meal, thus achieving the reuse of flaxseed meal. HIGHLIGHTS: This research provides some references for the application of UAATPS combined with MRP in natural products.

Single-cell analyses reveal the differentiation shifts of Schwann cells in neonatal rat sciatic nerves.

Schwann cells provide essential physical and chemical support for neurons and play critical roles in the peripheral nervous system. To acquire an enhanced understanding of the genetic characteristics of Schwann cells, we analyzed single-cell transcriptional profiling of Schwann cells in neonatal rat sciatic nerves, ordered the pseudotemporal states of Schwann cells, and determined the magnitude of RNA velocity vectors as well as cell cycle stages of Schwann cell subtypes. We discovered the cellular heterogeneity of Schwann cells in neonatal rat sciatic nerves, revealed the dynamic changes of Schwann cell subtypes, and pointed out the differentiation trajectory from Timp3- and Col5a3-expressing Schwann cell subtype 3 to other Schwann cell subtypes. The functional interpretation further indicated that subtype 3 Schwann cells display genetic signatures of DNA replication and the acquisition of mesenchymal traits. Our study presents a transcriptional summarization of the differentiation states of Schwann cell subtypes in neonatal rat sciatic nerves at single-cell resolution and may serve as a foundation for a deeper comprehension of the involvement of Schwann cells in the development and regeneration of peripheral nerves.

Three-Dimensional Arterial Distribution Over the Midline of the Nasal Bone.

BACKGROUND: A comprehensive understanding of arterial variations around the midline of the nose is of great importance for the safety of filler injection. OBJECTIVES: The aim of the study was to clearly define the 3-dimensional location of the arteries along the midline of the nasal bone. METHODS: The arterial structures overlapping the nasal bone along the midline were observed in 79 cadavers. RESULTS: The present study found that 0 to 3 named arteries per nose segment could be identified. All the arterial structures were located in or above the superficial musculoaponeurotic system layer overlapping the nasal bone. The probability of encountering named arteries at 5 defined points, P1 to P5, was 5/79 (6.3%), 4/79 (5.1%), 1/79 (1.3%), 6/79 (7.6%), and 9/79 (11.4%), respectively. The depth of the main arterial trunk was 1.2 ± 0.4 mm, 1.6 ± 0.6 mm, 1.8 ± 0 mm, 1.0 ± 0.4 mm, and 0.9 ± 0.5 mm below the skin at P1 to P5, respectively. CONCLUSIONS: The authors confirmed that sub-superficial musculoaponeurotic system injection along the midline through a needle is anatomically reliable and that a technique with 1 entry point through the rhinion via a cannula can easily keep the needle sufficiently deep for safe nasal filler injection.

Dysregulated miR-29a-3p/PMP22 Modulates Schwann Cell Proliferation and Migration During Peripheral Nerve Regeneration.

Schwann cells switch to a repair phenotype following peripheral nerve injury and create a favorable microenvironment to drive nerve repair. Many microRNAs (miRNAs) are differentially expressed in the injured peripheral nerves and play essential roles in regulating Schwann cell behaviors. Here, we examine the temporal expression patterns of miR-29a-3p after peripheral nerve injury and demonstrate significant up-regulation of miR-29a-3p in injured sciatic nerves. Elevated miR-29a-3p inhibits Schwann cell proliferation and migration, while suppressed miR-29a-3p executes reverse effects. In vivo injection of miR-29a-3p agomir to rat sciatic nerves hinders the proliferation and migration of Schwann cells, delays the elongation and myelination of axons, and retards the functional recovery of injured nerves. Mechanistically, miR-29a-3p modulates Schwann cell activities via negatively regulating peripheral myelin protein 22 (PMP22), and PMP22 extensively affects Schwann cell metabolism. Our results disclose the vital role of miR-29a-3p/PMP22 in regulating Schwann cell phenotype following sciatic nerve injury and shed light on the mechanistic basis of peripheral nerve regeneration.

miR-328a-3p stimulates endothelial cell migration and tubulogenesis.

Endothelial cells have important biological roles after peripheral nerve injury by forming blood vessels within the nerve gap and guiding Schwann cell migration. MicroRNAs (miRNAs/miRs) affect cellular behavior and regulate a wide variety of physiological and pathological activities, including peripheral nerve regeneration. Emerging studies have identified the essential roles of miRNAs in the phenotype modulation of Schwann cells, while the effects of miRNAs on endothelial cells have remained to be thoroughly investigated. miR-328a-3p was differentially expressed in peripheral nerve stumps after nerve injury. In the present study, the effects of miR-328a-3p on biological functions of endothelial cells were determined by transfecting cultured human umbilical vein endothelial cells (HUVECs) with miR-328a-3p mimics or inhibitor. Transfection with miR-328a-3p mimics led to slightly decreased HUVEC proliferation and robustly increased HUVEC migration and tubulogenesis, while transfection with miR-328a-3p inhibitor led to opposite results. Using bioinformatics analysis, potential regulators and effectors of miR-328a-3p were further discovered and a miR-328a-3p-centered competing endogenous RNA network was constructed. Collectively, the present study demonstrated that dysregulated miR-328a-3p after peripheral nerve injury may affect the migration and angiogenesis of endothelial cells and contribute to peripheral nerve regeneration.

Leukemia inhibitory factor regulates Schwann cell proliferation and migration and affects peripheral nerve regeneration.

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine that stimulates neuronal development and survival. Our previous study has demonstrated that LIF mRNA is dysregulated in the peripheral nerve segments after nerve injury. Here, we show that LIF protein is abundantly expressed in Schwann cells after rat sciatic nerve injury. Functionally, suppressed or elevated LIF increases or decreases the proliferation rate and migration ability of Schwann cells, respectively. Morphological observations demonstrate that in vivo application of siRNA against LIF after peripheral nerve injury promotes Schwann cell migration and proliferation, axon elongation, and myelin formation. Electrophysiological and behavior assessments disclose that knockdown of LIF benefits the function recovery of injured peripheral nerves. Differentially expressed LIF affects the metabolism of Schwann cells and negatively regulates ERFE (Erythroferrone). Collectively, our observations reveal the essential roles for LIF in regulating the proliferation and migration of Schwann cells and the regeneration of injured peripheral nerves, discover ERFE as a downstream effector of LIF, and extend our understanding of the molecular mechanisms underlying peripheral nerve regeneration.

Betacellulin regulates peripheral nerve regeneration by affecting Schwann cell migration and axon elongation.

BACKGROUND: Growth factors execute essential biological functions and affect various physiological and pathological processes, including peripheral nerve repair and regeneration. Our previous sequencing data showed that the mRNA coding for betacellulin (Btc), an epidermal growth factor protein family member, was up-regulated in rat sciatic nerve segment after nerve injury, implying the potential involvement of Btc during peripheral nerve regeneration. METHODS: Expression of Btc was examined in Schwann cells by immunostaining. The function of Btc in regulating Schwann cells was investigated by transfecting cultured cells with siRNA segment against Btc or treating cells with Btc recombinant protein. The influence of Schwann cell-secreted Btc on neurons was determined using a co-culture assay. The in vivo effects of Btc on Schwann cell migration and axon elongation after rat sciatic nerve injury were further evaluated. RESULTS: Immunostaining images and ELISA outcomes indicated that Btc was present in and secreted by Schwann cells. Transwell migration and wound healing observations showed that transfection with siRNA against Btc impeded Schwann cell migration while application of exogenous Btc advanced Schwann cell migration. Besides the regulating effect on Schwann cell phenotype, Btc secreted by Schwann cells influenced neuron behavior and increased neurite length. In vivo evidence supported the promoting role of Btc in nerve regeneration after both rat sciatic nerve crush injury and transection injury. CONCLUSION: Our findings demonstrate the essential roles of Btc on Schwann cell migration and axon elongation and imply the potential application of Btc as a regenerative strategy for treating peripheral nerve injury.