Local Injection Research Articles

Prevalence of priformis syndrome in sciatica patients: Predictability of specific tests and radiological findings for diagnosis.

The traditional approach for diagnosing piriformis syndrome (PS) is to rule out other causes of sciatica. This approach may lead to unnecessary radiological examinations and a waste of time. In contrast to the traditional approach, we aimed to first exclude PS and determine its prevalence by injecting patients with priformis tenderness. This observational cross-sectional study included patients diagnosed with PS who had sciatica and tenderness on palpation of the priformis muscle and whose pain was reduced by at least 50% with local injection. Age, sex, pain duration, presence of tenderness in the piriformis muscle, Freiberg test, PACE sign, FADIR, Visual Analog Scale (VAS) score, Douleur Neuropathique 4 Questions (DN4) score, and radiological findings were compared between patients who responded and those who did not respond to the priformis injection. A total of 110 patients with sciatica were evaluated, of whom 66 with tenderness on palpation of the primiformis muscle underwent local injection. In 27 of the 66 patients (40.9%), a decrease in the NRS score of >50% was observed after injection, and PS was diagnosed. There were no statistically significant differences in age, sex, pain duration, Pace, FADIR test positivity, radiological findings, NRS, and DN4 scores, but Freiberg test positivity was statistically higher in patients diagnosed with PS. PS is more common than is thought to be a cause of sciatica. A positive Freiberg test is predictive for the diagnosis of PS, but it should be confirmed by tenderness of the priformis muscle and local injection. Many pathologies can be detected incidentally radiographically in PS; however, they are not predictive of the diagnosis.

New Frontiers in Wide-Awake Surgery.

After studying this article, the participant should be able to: 1. Explain the most important benefits of wide-awake surgery to patients. 2. Tumesce large parts of the body with minimal pain local anesthesia injection technique to eliminate the need for sedation for many operations. 3. Apply tourniquet-free surgery to upper and lower limb operations to avoid the sedation required to tolerate tourniquet pain. 4. Move many procedures out of the main operating room to minor procedure rooms with no increase in infection rates to decrease unnecessary cost and solid waste in surgery. Three disruptive innovations are changing the landscape of surgery: (1) minimally painful injection of large-volume, low-concentration tumescent local anesthesia eliminates the need for sedation for many procedures over the entire body; (2) epinephrine vasoconstriction in tumescent local anesthesia is a good alternative to the tourniquet and proximal nerve blocks in extremity surgery (sedation for tourniquet pain is no longer required for many procedures); and (3) evidence-based sterility and the elimination of sedation enable many larger procedures to move out of the main operating room into minor procedure rooms with no increase in infection rates. This continuing medical education article explores some of the new frontiers in which these changes affect surgery all over the body.

ROS-Responsive Injectable Hydrogel Loaded with SLC7A11-modRNA Inhibits Ferroptosis and Mitigates Intervertebral Disc Degeneration in Rats.

Intervertebral disc degeneration (IVDD) is the primary cause of low back pain, with oxidative stress being a recognized factor that causes its development. Presently, low back pain imposes a significant global economic burden. However, the effectiveness of treatments for IVDD remains extremely limited. Therefore, this study aims to explore innovative and effective IVDD treatments by focusing on oxidative stress as a starting point. In this study, an injectable reactive oxygen species-responsive hydrogel (PVA-tsPBA@SLC7A11 modRNA) is developed, designed to achieve rapid loading and selective release of chemically synthesized modified mRNA (modRNA). SLC7A11 modRNA is specifically used to upregulate the expression of the ferroptosis marker SLC7A11. The local injection of PVA-tsPBA@SLC7A11 modRNA into the degenerated intervertebral disc (IVD) results in the cleavage of PVA-tsPBA, leading to the release of enclosed SLC7A11 modRNA. The extent of SLC7A11 modRNA release is directly proportional to the severity of IVDD, ultimately ameliorating IVDD by inhibiting ferroptosis in nucleus pulposus cells (NPCs). This study proposes an innovative system of PVA-tsPBA hydrogel-encapsulated modRNA, representing a potential novel treatment strategy for patients with early-stage IVDD.

Local ozone injection compared to local glucocorticoid injection in carpal tunnel syndrome: A randomized controlled trial.

This study aimed to compare the effectiveness of local ozone (O3) injection versus corticosteroid injection in the treatment of mild to moderate carpal tunnel syndrome (CTS). This double-blind randomized controlled trial was performed on 42 patients (9 males, 33 females; mean age: 46.7±2.1 years; range, 18 to 70 years) with mild to moderate CTS between May 2021 and June 2021. The corticosteroid group (n=21) was injected with 40 mg triamcinolone, and in the O3 group B (n=21), 4 mL of a 10 mcg/mL oxygen (O2)-O3 mixture was injected. Symptom severity and functional impairments were assessed using a Visual Analog Scale and Boston Carpal Tunnel Questionnaire. Electrodiagnostic and ultrasonographic parameters were obtained at baseline and eight weeks after the procedure. The O2-O3 solution improved pain and Boston Carpal Tunnel Questionnaire score after eight weeks (p<0.001); however, the change was nonsignificant compared to the corticosteroid group (p>0.05). Sensory nerve and compound muscle action potential latencies were not significantly changed eight weeks after O2-O3 injection (p>0.05), while both were significantly decreased in the steroid injection group (p<0.001). Volar bulging and median nerve cross-section surface area were not improved after O2-O3 injection, while the improvement was significant in the corticosteroid arm (p=0.02). Symptoms in patients with mild to moderate CTS may be alleviated by local O2-O3 injection; however, electrodiagnostic and ultrasonographic indices may be unchanged. Corticosteroid local injection may alleviate patient symptoms along with electrodiagnostic and ultrasonographic parameters.

Hydrogels promote periodontal regeneration.

Periodontal defects involve the damage and loss of periodontal tissue, primarily caused by periodontitis. This inflammatory disease, resulting from various factors, can lead to irreversible harm to the tissues supporting the teeth if not treated effectively, potentially resulting in tooth loss or loosening. Such outcomes significantly impact a patient's facial appearance and their ability to eat and speak. Current clinical treatments for periodontitis, including surgery, root planing, and various types of curettage, as well as local antibiotic injections, aim to mitigate symptoms and halt disease progression. However, these methods fall short of fully restoring the original structure and functionality of the affected tissue, due to the complex and deep structure of periodontal pockets and the intricate nature of the supporting tissue. To overcome these limitations, numerous biomaterials have been explored for periodontal tissue regeneration, with hydrogels being particularly noteworthy. Hydrogels are favored in research for their exceptional absorption capacity, biodegradability, and tunable mechanical properties. They have shown promise as barrier membranes, scaffolds, carriers for cell transplantation and drug delivery systems in periodontal regeneration therapy. The review concludes by discussing the ongoing challenges and future prospects for hydrogel applications in periodontal treatment.

Potential use of pinenes to improve localized insecticide injections targeting the western drywood termite (Blattodea: Kalotermitidae).

The western drywood termite, Incisitermes minor (Hagen), causes significant economic damage to wood structures in the United States of America, especially California. When infestation is not widespread, localized insecticide injections may be useful for remedial control. However, the extensive gallery structure of drywood termites and their tendency to aggregate at specific parts of the galleries can impact the efficacy of localized insecticide injection. Chemicals that attract termites from a distance may improve the localized insecticide injection by increasing the number of termites contacting the insecticide residues. Two volatile terpenes, α-pinene and β-pinene, commonly found in many coniferous timber trees, were applied to artificial termite galleries to determine if termites were attracted from their original aggregation site. Furthermore, we examined if adding these pinenes would improve the overall efficacy of some insecticide products for drywood termite control. Behavioral assay results showed that the treatment with pinenes increased the likelihood that drywood termites would leave their original aggregation site and contact the treated part of the gallery. When tested with the pesticide products applied in a small area away from the termite aggregation, β-pinene significantly accelerated the time course of mortality for the aqueous fipronil. The efficacy of disodium octaborate tetrahydrate dust was not influenced by the addition of pinenes. Implications for drywood termite management and future research directions are discussed.

Triamcinolone injection in the treatment of lid retraction for thyroid-associated ophthalmopathy: A systematic review.

Lid retraction is one of the most common symptoms of Thyroid-Associated Ophthalmopathy (TAO), which potentially precipitates various complications, such as dry eyes, exposure keratopathy, and cosmetic concerns. Local corticosteroid injections, such as triamcinolone, have been proposed as a choice of treatment for TAO. This approach may be a favorable alternative for patients intolerant to the systemic effects of high-dose methylprednisolone. However, the efficacy of this intervention remains unestablished. Hence, our review aims to evaluate the efficacy of triamcinolone injection in reducing lid retraction. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and was conducted in three databases (PubMed, Science Direct, and ProQuest). This review included studies that use local triamcinolone injections for patients with thyroid-associated ophthalmopathy. The outcome of interest in this review is lid retraction parameters. From six studies, a total of 392 patients were included. All studies showed significant improvement in lid retraction in the patient who received triamcinolone (all p < 0.05) as shown by ΔMRD (-0.93 mm in 1 month and -1.38 mm in 3 months), ΔMLD (-1.98 mm at 6 months), and Δpalpebral fissure height (-1.68 in 1 month). The majority of studies showed rapid improvement in lid retraction in the first month of therapy. Triamcinolone injection is an effective therapy for lid retraction related to thyroid-associated ophthalmopathy.

Early effectiveness of local injection of multimodal drug cocktail during anterior cruciate ligament reconstruction and its influence on cartilage

To explore the early effectiveness and influence on cartilage of local injection of multimodal drug cocktail (MDC) during anterior cruciate ligament reconstruction (ACLR). Between February 2022 and August 2023, patients undergone arthroscopic ACLR using autologous hamstring tendons were selected as the study subjects. Among them, 90 patients met the selection criteria and were randomly divided into 3 groups ( n=30) according to the different injection drugs after ligament reconstruction. There was no significant difference in baseline data such as gender, age, body mass index, surgical side, disease duration, preoperative thigh circumference, and preoperative levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), IL-1, matrix metalloproteinase 3 (MMP-3), MMP-13, and aggrecan (ACAN) in synovial fluid between groups ( P>0.05). After the ligament reconstruction during operation, corresponding MDC (consisting of ropivacaine, tranexamic acid, and betamethasone in group A, and ropivacaine, betamethasone, and saline in group B) or saline (group C) were injected into the joint and tendon site, respectively. The length of hospital stay, postoperative tramadol injection volume, incidence of complications, degree of knee joint swelling and range of motion, visual analogue scale (VAS) score, International Knee Documentation Committee (IKDC) score, Lyshlom score, and Hospital for Special Surgery (HSS) score were recorded and compared between groups. The T2 * values in different cartilage regions were detected by MRI examination and the levels of TNF-α, IL-6, IL-1, MMP-3, MMP-13, and ACAN in synovial fluid were detected by ELISA method. The patients in group A, B, and C were followed up (12.53±3.24), (13.14±2.87), and (12.82±3.32) months, respectively. All incisions healed by first intention. Compared with group C, group A and group B had shorter length of hospital stay, less tramadol injection volume, and lower incidence of complications, showing significant differences ( P<0.05); there was no significant difference between group A and group B ( P>0.05). The degree of knee swelling in group A was significantly less than that in group B and group C ( P<0.05), but there was no significant difference between group B and group C ( P>0.05). At 3, 6, 12, 24, and 48 hours after operation, VAS scores of group A and group B were significantly lower than those of group C ( P<0.05); at 72 hours after operation, there was no significant difference among the three groups ( P>0.05). At 3 days, 14 days, and 1 month after operation, the range of motion of knee joint in group A were significantly better than those in group C ( P<0.05), and there was no significant difference between the other groups ( P>0.05). At 1 month after operation, the IKDC score of group A and group B was significantly higher than that of group C ( P<0.05); there was no significant difference among the three groups at other time points ( P>0.05). There was no significant difference in Lyshlom score and HSS score among the three groups at each time point ( P>0.05). At 14 days after operation, the levels of IL-1 and IL-6 in the synovial fluid in groups A and B were significantly lower than those in group C ( P<0.05). There was no significant difference in the levels of TNF-α, MMP-3, MMP-13, and ACAN between groups A and B ( P>0.05). At 1 month after operation, there was no significant difference in the above indicators among the three groups ( P>0.05). At 3, 6, and 12 months after operation, there was no significant difference in the T2 * values of different cartilage regions among the three groups ( P>0.05). Injecting MDC (ropivacaine, tranexamic acid, betamethasone) into the joint and tendon site during ACLR can achieve good early effectiveness without significant impact on cartilage.

Effects of local reduction of endogenous α-synuclein using antisense oligonucleotides on the fibril-induced propagation of pathology through the neural network in wild-type mice

In Parkinson's disease and other synucleinopathies, fibrillar forms of α-synuclein (aSyn) are hypothesized to structurally convert and pathologize endogenous aSyn, which then propagates through the neural connections, forming Lewy pathologies and ultimately causing neurodegeneration. Inoculation of mouse-derived aSyn preformed fibrils (PFFs) into the unilateral striatum of wild-type mice causes widespread aSyn pathologies in the brain through the neural network. Here, we used the local injection of antisense oligonucleotides (ASOs) against Snca mRNA to confine the area of endogenous aSyn protein reduction and not to affect the PFFs properties in this model. We then varied the timing and location of ASOs injection to examine their impact on the initiation and propagation of aSyn pathologies in the whole brain and the therapeutic effect using abnormally-phosphorylated aSyn (pSyn) as an indicator. By injecting ASOs before or 0–14 days after the PFFs were inoculated into the same site in the left striatum, the reduction in endogenous aSyn in the striatum leads to the prevention and inhibition of the regional spread of pSyn pathologies to the whole brain including the contralateral right hemisphere. ASO post-injection inhibited extension from neuritic pathologies to somatic ones. Moreover, injection of ASOs into the right striatum prevented the remote regional spread of pSyn pathologies from the left striatum where PFFs were inoculated and no ASO treatment was conducted. This indicated that the reduction in endogenous aSyn protein levels at the propagation destination site can attenuate pSyn pathologies, even if those at the propagation initiation site are not inhibited, which is consistent with the original concept of prion-like propagation that endogenous aSyn is indispensable for this regional spread. Our results demonstrate the importance of recruiting endogenous aSyn in this neural network propagation model and indicate a possible potential for ASO treatment in synucleinopathies.

A Prospective Self-controlled Clinical Trial of Nonactivated Low Leukocyte PRP in Female Pattern Hair Loss Patients of Childbearing Age.

Alopecia significantly affects the mental health and social relationship of women since childbearing age, highlighting the need for a safe, effective, and convenient treatment. The authors have conducted a prospective self-controlled trial involving 15 female patients at childbearing age with alopecia. These patients received a subcutaneous scalp injection of platelet-rich plasma once every 4 weeks for 3 treatments in total. Outcome measurements were included below: changes in hair density (hair/cm 2 ), hair follicle density (hair follicle/cm 2 ), and overall photographic assessment (improved or not) at 4, 12, and 24 weeks right after the first treatment. Comparing the photographs taken before and after the intervention, 67% of patients' hair density increased from 151 ± 39.82 hairs/cm 2 (preintervention) to 170.96 ± 37.14 hairs/cm 2 (at 24-week follow-up), representing an approximate increase of 19 hairs/cm 2 . Meanwhile, hair follicle density increased by approximately 15 follicles/cm 2 after 24 weeks since the first treatment, rising from 151.04 ± 41.99 follicles/cm 2 to 166.72 ± 37.13 follicles/cm 2 . The primary adverse reactions observed were local swelling and pain due to injections. Local injection of nonactivated platelet-rich plasma with low leukocytes concentration could be an effective strategy to alleviate alopecia symptoms in female patients.

Nanoparticles for the treatment of spinal cord injury.

Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.

Differential Regulation of DC Function, Adaptive Immunity, and MyD88 Dependence by MF59 and AS03-like Adjuvants.

MF59 and AS03 are squalene emulsion-based vaccine adjuvants with similar compositions and droplet sizes. Despite their broad use in licensed influenza vaccines, few studies compared their adjuvant effects and action mechanisms side by side. Considering the majority of adjuvants act on dendritic cells (DCs) to achieve their adjuvant effects, this study compared MF59 and AS03-like adjuvants (AddaVax and AddaS03, respectively) to enhance antigen uptake, DC maturation, ovalbumin (OVA) and seasonal influenza vaccine-induced immune responses. Considering MF59 was reported to activate MyD88 to mediate its adjuvant effects, this study also investigated whether the above-explored adjuvant effects of AddaVax and AddaS03 depended on MyD88. We found AddaVax more potently enhanced antigen uptake at the local injection site, while AddaS03 more potently enhanced antigen uptake in the draining lymph nodes. AddaS03 but not AddaVax stimulated DC maturation. Adjuvant-enhanced antigen uptake was MyD88 independent, while AddaS03-induced DC maturation was MyD88 dependent. AddaVax and AddaS03 similarly enhanced OVA-induced IgG and subtype IgG1 antibody responses as well as influenza vaccine-induced hemagglutination inhibition antibody titers, whileAddaS03 more potently enhanced OVA-specific IgG2c antibody responses. Both adjuvants depended on MyD88 to enhance vaccine-induced antibody responses, while AddaVax depended more on MyD88 to achieve its adjuvant effects. Our study reveals similarities and differences of the two squalene emulsion-based vaccine adjuvants, contributing to our improved understanding of their action mechanisms.

Smart management of pressure regulating stations to maximize hydrogen injection in a gas distribution network

Gas distribution networks traditionally maintain constant pressure setpoints at regulating stations, ensuring a consistent supply to end-users with a high safety margin. However, the prospect of hydrogen injection in the gas networks necessitates rethinking operational strategies. This study examines the environmental and fluid-dynamic implications of implementing a smart pressure management approach in regulating stations within a distribution network with a localized hydrogen injection. The research introduces a novel simulation-based optimization algorithm, incorporating a steady-state fluid-dynamic model with hydrogen tracking, used to optimize the pressure setpoints in the stations. The algorithm is applied to a two-pressure levels looped gas network with multiple gas supply nodes and a single hydrogen injection. The test case results reveal that utilizing dynamic pressure setpoints leads to a 22% increase in hydrogen penetration compared to standard operation. Therefore, this study highlights that smart pressure modulation in a gas network with hydrogen injection can unlock a latent decarbonization potential, while simultaneously adhering to safety limits.

Transurethral water vapour thermal therapy for benign prostatic hyperplasia under local anaesthesia alone: initial experience in Chinese patients.

This study evaluated the perioperative and early postoperative outcomes of transurethral water vapour thermal therapy (WVTT) under local anaesthesia alone for benign prostatic enlargement in Chinese patients. This retrospective review of transurethral WVTT for benign prostatic enlargement focused on 50 Chinese patients who exhibited clinical indications (acute retention of urine or symptomatic lower urinary tract symptoms due to benign prostatic enlargement) for surgical treatment between June 2020 and December 2021 in Hong Kong. Exclusion criteria included active urinary tract problems and urological malignancies. Follow-up was conducted at 3 months postoperatively. The median patient age was 71.5 years. The mean preoperative prostatic volume was 56.7 mL. The mean operation time was 25.1 minutes. All procedures were performed under local anaesthesia alone. The mean pain scores for transrectal ultrasound probe insertion, transperineal local anaesthesia injection, and transurethral WVTT were 2, 5, and 4, respectively. Forty-nine patients (98%) were discharged on the same day with a urethral catheter. Forty-eight patients (96%) successfully completed a trial without catheter within 3 weeks postoperatively. Five patients (10%) had unplanned hospital admission within 30 days postoperatively due to surgical complications (Clavien-Dindo grade 1). Transurethral WVTT, an advanced surgical treatment for benign prostatic enlargement, is a safe procedure that relieves lower urinary tract symptoms with minimal hospital stay. It can be performed in an office-based setting under local anaesthesia, maximising utilisation of the surgical theatre.

Knockdown of PHOX2B in the retrotrapezoid nucleus reduces the central CO2 chemoreflex in rats

PHOX2B is a transcription factor essential for the development of different classes of neurons in the central and peripheral nervous system. Heterozygous mutations in the PHOX2B coding region are responsible for the occurrence of Congenital Central Hypoventilation Syndrome (CCHS), a rare neurological disorder characterised by inadequate chemosensitivity and life-threatening sleep-related hypoventilation. Animal studies suggest that chemoreflex defects are caused in part by the improper development or function of PHOX2B expressing neurons in the retrotrapezoid nucleus (RTN), a central hub for CO2 chemosensitivity. Although the function of PHOX2B in rodents during development is well established, its role in the adult respiratory network remains unknown. In this study, we investigated whether reduction in PHOX2B expression in chemosensitive neuromedin-B (NMB) expressing neurons in the RTN altered respiratory function. Four weeks following local RTN injection of a lentiviral vector expressing the short hairpin RNA (shRNA) targeting Phox2b mRNA, a reduction of PHOX2B expression was observed in Nmb neurons compared to both naive rats and rats injected with the non-target shRNA. PHOX2B knockdown did not affect breathing in room air or under hypoxia, but ventilation was significantly impaired during hypercapnia. PHOX2B knockdown did not alter Nmb expression but it was associated with reduced expression of both Task2 and Gpr4, two CO2/pH sensors in the RTN. We conclude that PHOX2B in the adult brain has an important role in CO2 chemoreception and reduced PHOX2B expression in CCHS beyond the developmental period may contribute to the impaired central chemoreflex function.

Knockdown of PHOX2B in the retrotrapezoid nucleus reduces the central CO2 chemoreflex in rats.

PHOX2B is a transcription factor essential for the development of different classes of neurons in the central and peripheral nervous system. Heterozygous mutations in the PHOX2B coding region are responsible for the occurrence of Congenital Central Hypoventilation Syndrome (CCHS), a rare neurological disorder characterised by inadequate chemosensitivity and life-threatening sleep-related hypoventilation. Animal studies suggest that chemoreflex defects are caused in part by the improper development or function of PHOX2B expressing neurons in the retrotrapezoid nucleus (RTN), a central hub for CO2 chemosensitivity. Although the function of PHOX2B in rodents during development is well established, its role in the adult respiratory network remains unknown. In this study, we investigated whether reduction in PHOX2B expression in chemosensitive neuromedin-B (NMB) expressing neurons in the RTN altered respiratory function. Four weeks following local RTN injection of a lentiviral vector expressing the short hairpin RNA (shRNA) targeting Phox2b mRNA, a reduction of PHOX2B expression was observed in Nmb neurons compared to both naive rats and rats injected with the non-target shRNA. PHOX2B knockdown did not affect breathing in room air or under hypoxia, but ventilation was significantly impaired during hypercapnia. PHOX2B knockdown did not alter Nmb expression but it was associated with reduced expression of both Task2 and Gpr4, two CO2/pH sensors in the RTN. We conclude that PHOX2B in the adult brain has an important role in CO2 chemoreception and reduced PHOX2B expression in CCHS beyond the developmental period may contribute to the impaired central chemoreflex function.

CircCDK13-loaded small extracellular vesicles accelerate healing in preclinical diabetic wound models

Chronic wounds are a major complication in patients with diabetes. Here, we identify a therapeutic circRNA and load it into small extracellular vesicles (sEVs) to treat diabetic wounds in preclinical models. We show that circCDK13 can stimulate the proliferation and migration of human dermal fibroblasts and human epidermal keratinocytes by interacting with insulin-like growth factor 2 mRNA binding protein 3 in an N6-Methyladenosine-dependent manner to enhance CD44 and c-MYC expression. We engineered sEVs that overexpress circCDK13 and show that local subcutaneous injection into male db/db diabetic mouse wounds and wounds of streptozotocin-induced type I male diabetic rats could accelerate wound healing and skin appendage regeneration. Our study demonstrates that the delivery of circCDK13 in sEVs may present an option for diabetic wound treatment.

Human Adipose-Derived Mesenchymal Stem Cells Colonize and Promote Healing of Leprosy Ulcer by Inducing Neuro-Vascularization.

Leprosy ulcer is a chronic and recurrent disease resulting from nerve injury. While existing treatments partially facilitate ulcer healing, they exhibit limited ability to address localized nerve repair, leading to a risk of recurrence. Moreover, there is a dearth of animal models to evaluate the preclinical efficacy and safety of novel therapeutic approaches. Over the years, adipose-derived mesenchymal stem cells have been extensively employed in regenerative medicine as an optimal cell therapy source for fostering skin ulcer healing. They have also demonstrated the capacity to enhance nerve regeneration in in vitro experiments and clinical trials. In this study, we established a NU/NU mouse foot pad leprosy ulcer model, transplanted human adipose-derived stem cells (hADSCs) into leprosy ulcers via local injection, and conducted subsequent follow-up. Our findings revealed that hADSCs persisted in the leprosy ulcer and facilitated the healing process. In this respect, gross observation and histological analysis revealed increased granular formation, collagen synthesis, and re-epithelialization in the local ulcer area. RNA-Seq data revealed that the upregulated differential genes resulting from the transplantation intervention were not only enriched in pathways related to re-epithelialization and collagen synthesis but also contributed to local nerve regeneration. Furthermore, immunofluorescence assays revealed the increased expression of angiogenesis markers-CD31 and VEGFa, cell proliferation markers-Ki67 and TGF-β, and nerve regeneration markers-β3-tubulin, SOX10, NGF, and NT-3. These results underscore the potential of hADSCs in promoting the healing of leprosy ulcers and offer valuable preclinical data for their prospective clinical application.

PROSPECTIVE STUDY ON THE EFFECTIVENESS OF PLATELET-RICH PLASMA IN MANAGING CHRONIC PLANTAR FASCIITIS

Objectives: The objectives of this study were as follows: (1) Assess the impact of a single dose of platelet-rich plasma (PRP) injection on visual analog scale (VAS) scores for heel pain. (2) Evaluate the functional outcome scores following PRP treatment for chronic plantar fasciitis. (3) Measure and confirm the restoration of plantar fascia thickness through ultrasound (USG) assessments. (4) Determine the safety and viability of local PRP injection as a treatment option for individuals with chronic plantar fasciitis. Methods: This hospital-based prospective case series, spanning January 2019 to January 2020, enrolled 40 participants aged 25–65 with unilateral, persistent plantar fasciitis resistant to conservative treatment. Exclusion criteria included BMI ≥30, various pathologies, and recent injections. Ethical clearance was obtained, and participants received autologous PRP injections, with ultrasound measuring plantar fascia thickness. Post-injection, patients were monitored for adverse reactions, initiated stretching exercises, and progressed to weight-bearing activities after 6 weeks. Results: The study cohort, averaging 45 years (standard deviation [SD] 7.7), primarily comprised females with the right-foot prevalence. Symptom duration averaged 20 weeks (SD 4.5). Pre-injection VAS scores (6.7±1.2) significantly improved at 6 weeks (2.9±0.6) and 12 weeks (2.0±0.9) post-PRP injection (p&lt;0.001). Plantar fascia thickness reduced from 5.1 mm (SD 0.6) to 4.1 mm (SD 0.5) at 12 weeks (p&lt;0.001) and regular foot thickness: 3.7 mm (SD 0.5). Conclusion: The study reveals that a singular PRP injection brings about substantial and clinically meaningful enhancements in heel pain, functional outcomes, and the restoration of plantar fascia thickness, supported by ultrasound measurements. This underscores local PRP injection as a viable and safe therapeutic choice for those grappling with chronic plantar fasciitis.

OTULIN of exosomes derived from Schwann cells promotes peripheral nerve injury repair by regulating macrophage polarization via deubiquitination of ERBB2

A significant public health burden is peripheral nerve damage (PNI), which is frequently brought on by trauma. Macrophages were essential to the effective regeneration of nerves and restoration of function. It is still not entirely understood how macrophages and Schwann cells interact after damage during remyelination. Here, we established an inflammatory model in bone marrow-derived macrophages (BMDMs) and a rat sciatic nerve damage model to investigate the possible relationship between lipopolysaccharides (LPS)-induced exosomes derived from Schwann cells (LPS SCs-Exos) and peripheral nerve repair. The pro-inflammatory macrophage was changed into a pro-regeneration macrophage by LPS SC-Exos. Notably, it was discovered that SC-Exos had a substantial enrichment of OTULIN. OTULIN was a key mediator in the regulatory effects of LPS SC-Exos by deubiquitinating ERBB2 and preventing its degradation. The local injection of SC-Exos into the nerve damage site led in a faster functional recovery, axon regeneration and remyelination, and an increased M2 macrophage polarization, whereas OTULIN knockdown reversed these effects in vivo. Our results indicate that LPS SC-Exos may offer a therapeutic avenue for peripheral nerve regeneration by promoting macrophage polarization toward an M2 phenotype through the shuttling of OTULIN and deubiquitination of ERBB2. Significance statementOTULIN protein from SC-Exos mediated the macrophages polarization and axonal growth in BMDMs through promoting ubiquitination of ERBB2 and triggering the degradation of ERBB2. The findings offered prospective therapeutic hints for PNI therapy approaches that target axonal regrowth.