Periplaneta americana extract promotes infectious diabetic ulcers wound healing by downregulation of LINC01133/SLAMF9.

Wound healing in diabetic ulcers remains a significant clinical challenge, primarily due to bacterial infection and impaired angiogenesis. Periplaneta americana extract (PAE) has been widely used to treat diabetic wounds, yet its underlying mechanisms are not fully understood. This study aimed to elucidate these mechanisms by analyzing long non-coding RNA (lncRNA) expressions in the wound tissues from diabetic anal fistula patients treated with or without PAE, using high-throughput sequencing. Peripheral blood monocytes from patients were differentiated into M0 macrophages with human macrophage colony-stimulating factor (hM-CSF) and subsequently polarized into M1 macrophages with lipopolysaccharide. The results indicated that LINC01133 and SLAMF9 were downregulated in wound tissues of patients treated with PAE. Furthermore, PAE suppressed M1 macrophage polarization and enhanced human umbilical vein endothelial cell (HUVEC) proliferation, migration, and angiogenesis. These effects were diminished when LINC01133 or SLAMF9 were overexpressed. Mechanistically, LINC01133 was shown to upregulate SLAMF9 through interaction with ELAVL1. Overexpression of SLAMF9 reversed the effects of LINC01133 silencing on macrophage polarization and HUVEC functions. In conclusion, PAE facilitates the healing of infected diabetic ulcers by downregulating the LINC01133/SLAMF9 pathway.

Development of a measuring app for systemic sclerosis-related digital ulceration (SALVE: Scleroderma App for Lesion VErification).

OBJECTIVES: To test the hypothesis that photographs (in addition to self-reported data) can be collected daily by patients with systemic sclerosis (SSc) using a smartphone app designed specifically for digital lesions, and could provide an objective outcome measure for use in clinical trials. METHODS: An app was developed to collect images and patient reported outcome measures (PROMS) including Pain score and the Hand Disability in Systemic Sclerosis-Digital Ulcers (HDISS-DU) questionnaire. Participants photographed their lesion(s) each day for 30 days and uploaded images to a secure repository. Lesions were analysed both manually and automatically, using a machine learning approach. RESULTS: 25 patients with SSc-related digital lesions consented of whom 19 completed the 30-day study, with evaluable data from 27 lesions. Mean (standard deviation [SD]) baseline Pain score was 5.7 (2.4) and HDISS-DU 2.2 (0.9), indicating high lesion and disease-related morbidity. 506 images were used in the analysis (mean number of used images per lesion 18.7, SD 8.3). Mean (SD) manual and automated lesion areas at day 1 were 11.6 (16.0) and 13.9 (16.7) mm2 respectively. Manual area decreased by 0.08mm2 per day (2.4mm2 over 30 days) and automated area by 0.1mm2 (3.0mm2 over 30 days). Average gradients of manual and automated measurements over 30 days correlated strongly (r = 0.81). Manual measurements were on average 40% lower than automated, with wide limits of agreement. CONCLUSION: Even patients with significant hand disability were able to use the app. Automated measurement of finger lesions could be valuable as an outcome measure in clinical trials.

Diabetic Foot Osteomyelitis in Patients with and without Peripheral Arterial Disease: Two Different Diseases?

The aim of the current study was to evaluate the outcomes of patients with diabetic foot osteomyelitis (DFO), comparing subjects with and without peripheral arterial disease (PAD). The study is a prospective study including a population of patients affected by a DFO located in the forefoot. All patients were managed by a surgical conservative approach defined by the removal of the infected bone, in association with the antibiotic therapy. Patients were divided into two groups: those with PAD (neuro-ischaemic DFO) and those without (neuropathic DFO). After 1 year of follow-up, the following outcome were evaluated and compared between groups: healing, healing time, minor amputation, major amputation, hospitalization, need for surgical re-intervention. Overall, 166 patients were included, 87(52.4%) of them had neuro-ischaemic DFO and 79 (47.6%) neuropathic DFO. Patients with neuro-ischaemic DFO in comparison to neuropathic DFO were older (72.5 ± 9 vs 64.1 ± 15.5 years, P < .0001), had longer diabetes duration (21.8 ± 5.6 vs 16.4 ± 7.6 years, P < .0001), higher rate of dialysis (13.8 vs 1.3%, P = .001) and ischaemic heart disease (79.3 vs 12.7%, P < .0001). Outcomes for neuro-ischaemic DFO and neuropathic DFO were: healing (96.5 vs 97.5%, P = .7), healing time (7.8 ± 6.2 vs 5.7 ± 3.7 weeks, P = .01), minor amputation (16.1 vs 3.8%, P = .006), major amputation (0 vs 0%, ns), hospitalization (90.8 vs 51.9%, P < .0001), surgical re-intervention (14.9 vs 8.8%, P = .004) respectively. In addition, PAD resulted in an independent predictor of minor amputation, hospitalization, and surgical re-intervention. DFO in patients with PAD was characterized by longer healing time, more cases of minor amputation, hospitalization, and surgical re-intervention. PAD independently predicted the risk of minor amputation, hospitalization, and surgical re-intervention, while it was not associated with the healing rate.

Axial Ablation versus Terminal Interruption of the Reflux Source (AAVTIRS): A Randomised Controlled Trial.

INTRODUCTION: Treatment of reflux has been shown to improve time to healing of Venous Leg Ulcers (VLU). Terminal Interruption of the Reflux Source (TIRS) treats reflux within the plexus of veins around an active VLU using foam sclerotherapy. The efficacy of TIRS in managing VLU has never been tested. METHODS: We performed a pragmatic, single centre, assessor-blinded, randomised controlled trial comparing endovenous ablation of the axial superficial veins (Axial Ablation-AA) vs TIRS. Patients of any age with VLU of any duration were eligible. RESULTS: 98 Participants were randomised to AA or TIRS. 39/55, 70.9% (95%CI; 57.1-82.37) healed their VLU in the AA group, while 29/39, 74.36% (95%CI; 57.87-86.96) healed their VLU in the TIRS group, P = 0.45.4 were lost to follow-up. Median time to ulcer healing was 84 days (95%CI; 74.67-93.33) in the axial ablation group and 84 days (95%CI; 73.02-94.98) in the TIRS group. Hazard Ratio for ulcer healing with AA vs TIRS was 0.96 (95%CI 0.59-1.56). There were no significant quality of life differences. CONCLUSION: The AAVTIRS trial did not show that axial ablation was superior to TIRS in the primary outcome of number of VLU healed in 6 months, or time to VLU healing. This trial is not powered to show non-inferiority. TIRS is a viable option for treatment of VLU. Further investigation is necessary before it can be recommended as an alternative to axial ablation.Trial registered at clinicaltrials.gov NCT04484168.

Thymic stromal lymphopoietin and digital microvascular damage in systemic sclerosis patients: A pilot study.

BACKGROUND: Systemic sclerosis (SSc) is a complex autoimmune connective-tissue disease, characterised by vasculopathy and fibrosis of the skin and internal organs. Activation of microvascular endothelial cells (ECs) causes the intimal hyperplasia that characterises the vascular remodelling in SSc. The most frequent complication of SSc is the development of digital ulcers (DUs). Thymic stromal lymphopoietin (TSLP) may trigger fibrosis and sustain vascular damage. Aim of this study was to evaluate the correlation between serum level of TSLP and DUs. METHODS: 75 consecutive SSc patients were enrolled and serum TSLP levels were measured. The presence of history of DUs (HDU) was evaluated. Recurrent new DUs were defined as the presence of at least 3 episodes of DUs in a 12-months follow up period. The risk of developing new DUs was calculated by applying the capillaroscopic skin ulcer risk index (CSURI). RESULTS: The median value of TSLP was higher in patients with HDU than patients without HDU [181.67 pg/ml (IQR 144.67; 265.66) vs 154.67 pg/ml (IQR 110.67; 171.33), p < 0.01]. The median value of TSLP was higher in patients with an increased CSURI index than patients without an increased CSURI [188 pg/ml (IQR 171.33; 246.33) vs 159.33 pg/ml (IQR 128.67; 218), p < 0.01]. Kaplan-Meier curves demonstrated that free survival from new DUs was significantly (p < 0.01) lower in SSc patients with increased TSLP serum levels. CONCLUSION: TSLP might have a key role in digital microvascular damage of SSc patients.

Dehydrated Amnion Chorion Membrane versus standard of care for diabetic foot ulcers: a randomised controlled trial.

OBJECTIVE: Diabetic foot ulcers (DFUs) continue to challenge wound care practitioners. This prospective, multicentre, randomised controlled trial (RCT) evaluated the effectiveness of a dehydrated Amnion Chorion Membrane (dACM) (Organogenesis Inc., US) versus standard of care (SoC) alone in complex DFUs in a challenging patient population. METHOD: Subjects with a DFU extending into dermis, subcutaneous tissue, tendon, capsule, bone or joint were enrolled in a 12-week trial. They were allocated equally to two treatment groups: dACM (plus SoC); or SoC alone. The primary endpoint was frequency of wound closure determined by a Cox analysis that adjusted for duration and wound area. Kaplan-Meier analysis was used to determine median time to complete wound closure (CWC). RESULTS: The cohort comprised 218 patients, and these were split equally between the two treatment groups with 109 patients in each. A Cox analysis showed that the estimated frequency of wound closure for the dACM plus SoC group was statistically superior to the SoC alone group at week 4 (12% versus 8%), week 6 (22% versus 11%), week 8 (31% versus 21%), week 10 (42% versus 27%) and week 12 (50% versus 35%), respectively (p=0.04). The computed hazard ratio (1.48 (confidence interval: 0.95, 2.29) showed a 48% greater probability of wound closure in favour of the dACM group. Median time to wound closure for dACM-treated ulcers was 84 days compared to 'not achieved' in the SoC-treated group (i.e., ≥50% of SoC-treated DFUs failed to heal by week 12; p=0.04). CONCLUSION: In an adequately powered DFU RCT, dACM increased the frequency, decreased the median time, and improved the probability of CWC when compared with SoC alone. dACM demonstrated beneficial effects in DFUs in a complex patient population. DECLARATION OF INTEREST: This study was funded by Organogenesis Inc., US. JC serves as a consultant and speaker for Organogenesis. RDD serves as a speaker for Organogenesis. OMA and MLS serve as consultants for Organogenesis. The authors have no other conflicts of interest to declare.

Analysis of factors influencing the recurrence of diabetic foot ulcers.

OBJECTIVE: The aim of this study is to investigate the factors influencing the recurrence of diabetic foot ulcers (DFU) and provide guidance for reducing the recurrence rate. METHODS: A total of 211 patients diagnosed with DFU who were hospitalized and discharged from the hospital from October 2015 to January 2020 were included as the study cohort. Participants were divided into two groups according to whether the foot ulcer recurred during the 2-year follow-up period: a recurrence group (n = 84) and a non-recurrence group (n = 127). The following data were collected and analyzed for the two groups of patients: general information, foot information, laboratory indicators, diabetes comorbidities, and complications. RESULTS: (1) The overall recurrence rate of diabetic foot ulcers (DFU) within 2 years was 39.8%, indicating a high recurrence rate. (2) Significant differences were observed between the two patient groups in terms of BMI, HbA1c, TBIL, CRP, financial situation, foot deformity, first ulcer on the sole of the foot, previous amputation history, Wagner grade of the first ulcer, osteomyelitis, DFU duration (>60 days), lower limb vascular reconstruction, peripheral arterial disease (PAD), and diabetic peripheral neuropathy (DPN) (t = 2.455; Z = -1.988, -3.731, -3.618; χ2 = 7.88, 5.004, 3.906, 17.178, 16.237, 5.007, 24.642, 4.782, 29.334, 10.253). No significant differences were found for the other indicators. (3) Logistic regression analysis revealed that TBIL (OR = 0.886, p = 0.036) was a protective factor against ulcer recurrence. In contrast, PAD, previous amputation history, DPN, and the first ulcer on the sole of the foot (OR = 3.987, 6.758, 4.681, 2.405; p < 0.05 or p < 0.01) were identified as risk factors for ulcer recurrence. CONCLUSION: Early screening and preventive education targeting high-risk factors such as DPN, PAD and the initial ulcer location on the sole of the foot are essential to mitigate the high long-term recurrence rate of DFU. Furthermore, the protective role of TBIL in preventing ulcer recurrence underscores the importance of monitoring bilirubin levels as part of a comprehensive management strategy for DFU patients.

Adipose-derived stem cells in diabetic foot care: Bridging clinical trials and practical application.

Diabetic foot ulcers (DFUs) pose a critical medical challenge, significantly im-pairing the quality of life of patients. Adipose-derived stem cells (ADSCs) have been identified as a promising therapeutic approach for improving wound healing in DFUs. Despite extensive exploration of the mechanical aspects of ADSC therapy against DFU, its clinical applications remain elusive. In this review, we aimed to bridge this gap by evaluating the use and advancements of ADSCs in the clinical management of DFUs. The review begins with a discussion of the classification and clinical management of diabetic foot conditions. It then discusses the current landscape of clinical trials, focusing on their geographic distribution, reported efficacy, safety profiles, treatment timing, administration techniques, and dosing considerations. Finally, the review discusses the preclinical strategies to enhance ADSC efficacy. This review shows that many trials exhibit biases in study design, unclear inclusion criteria, and intervention protocols. In conclusion, this review underscores the potential of ADSCs in DFU treatment and emphasizes the critical need for further research and refinement of therapeutic approaches, with a focus on improving the quality of future clinical trials to enhance treatment outcomes and advance the field of diabetic wound care.

The impact of statin therapy on the healing of diabetic foot ulcers: a case-control series.

BACKGROUND: Diabetic foot ulcers (DFU) are a costly complication of diabetes mellitus (DM), with significant implications for the patient and the healthcare professionals that treat them. The primary objective of this study was to evaluate if there were improved healing rates in patients with a DFU that were taking a statin medication compared to those patients with a DFU who were not taking a statin medication. Secondary outcomes assessed were correlations with wound healing or statin use on data obtained from retrospective chart review. METHODS: A case-control series was performed to obtain appropriate demographic information, comorbid conditions, laboratory values, and physical examination findings. From the time of presentation with DFU, these patients were followed for 12 weeks to evaluate for healing. Healing was defined as full epithelialization of the DFU with no further drainage. Wound healing and statin use correlation testing was then done for collected variables and each cohort. Chi square and Pearson correlation were then performed to identify any significant correlations. All p-values were two-sided, and findings were considered statistically significant at p < 0.05. RESULTS: Our study identified 109 patients, 75 patients with a DFU on statin medication and 34 patients with a DFU not on statin medication. The statin cohort was more likely to be older, less than 5-year duration of diabetes, have more comorbidities, decreased low-density lipoprotein (LDL) cholesterol, and decreased total cholesterol (p < 0.05). Among those patients taking a statin medication, 48.0% (36/75) healed their DFU within 12 weeks. Among those patients not taking a statin medication, 44.1% (15/34) healed their DFU within 12 weeks. No correlation was noted between wound healing and statin use (p = 0.7). For wound healing, a negative correlation was noted for prior minor amputations (p < 0.05). For statin use, correlations were noted for age, duration of DM, LDL cholesterol level, total cholesterol level, HTN, CAD, and HLD (p < 0.05). CONCLUSIONS: Statin medication use did not influence DFU healing rates between cohorts. There was a correlation noted between wound healing and prior minor amputations and between statin use and age, duration of DM, LDL cholesterol, total cholesterol, HTN, CAD and HLD. Additionally, we observed no correlation between DFU healing rates and use of a statin medication.

Patient-reported outcome survey of user-experiences in the spinal cord injured-community with MPPT for treating wounds and pressure injuries and for controlling soft tissue infection caused by osteomyelitis.

Background: People with spinal cord injury (SCI) are at high risk of developing pressure injuries. Reports in the SCI-community had indicated that a new class of wound treatment, MPPT (micropore-particle-technology), was effective in treating pressure injuries. The British Spinal Injuries Association therefore conducted a survey among MPPT-users to learn from their experiences. Methods: Online survey restricted to individuals with spinal cord injury. Participants were requested to identify themselves to permit validation of statement. Results: The survey had 41 respondents reporting on a total of 49 wounds of which the two main categories were wounds (n = 33), primarily pelvic pressure ulcers; and draining fistulas (n = 9) caused by osteomyelitis. All wounds reported had reached full closure. Median duration of MPPT use and time to closure were 3 and 4 weeks for acute wounds (<6 weeks old) and 8 and 10 weeks for chronic wounds, respectively. On draining fistulas, MPPT had been used to reduce wound size, remove soft tissue infection, avoid sepsis, reduce autonomic dysreflexia, improve overall health, and avoid bed rest, whilst waiting for surgery. Comments on MPPT were 84% highly positive, 11% positive, and 0% negative. No adverse events were reported. Conclusions: MPPT achieved a 100% closure rate of acute and chronic wounds, and, in draining fistulas, effectively controlled soft tissue infection resulting from osteomyelitis. MPPT does not require bed rest and is suitable for self-care and telemedicine, promoting independence and higher quality-of-life. The findings strongly agree with a recent clinical study of MPPT.

A Challenging Case of Reactive Angioendotheliomatosis.

Introduction: Reactive angioendotheliomatosis (RAE) is a rare, benign, angioproliferative disorder with poorly understood aetiopathogenesis. It is characterised by vascular occlusion that occurs in patients with coexistent systemic or autoimmune disease. Case Presentation: A 60-year-old female presented with an 8-week history of a painful, non-healing, and non-traumatic ulcer on the left thigh. Her past medical history included smoking, peripheral vascular disease (PVD) and previously treated rectal squamous cell carcinoma. The diagnosis of pyoderma gangrenosum with superimposed cellulitis was considered and treatment with oral antibiotics was initiated. Following failure to improve, a biopsy was undertaken leading to the diagnosis of RAE. The patient was referred for urgent consideration of surgical correction of PVD, but was deemed unsuitable for surgical treatment due to a poor performance status. The patient was treated with conservative measures, but her condition rapidly deteriorated and she passed away a few weeks later. Conclusion: RAE is notorious for mimicking a wide spectrum of diseases. It is an important differential diagnosis to consider in patients with non-healing ulceration and underlying systemic or autoimmune disorders. Our case raises awareness of this rare condition and the mortality that it carries if left untreated. In an attempt to reverse disease progression and mortality, we urge clinicians to attempt surgical correction of PVD even when faced with multiple comorbidities and poor performance status.

Effect of Using Photobiomodulation (660 Nanometers) for the Treatment of Diabetic Ulcers: Protocol for a Randomized Controlled Trial.

Diabetic foot ulcers (DFUs) result in tissue damage or impairment of deeper structures that affect quality of life. The impacts are numerous, and even after a long treatment period, 65% of patients experience recurrence. Among the interventions used to accelerate the healing process of DFUs, photobiomodulation therapy (PBMT) is a painless, noninvasive, and low-cost treatment. To achieve effective therapeutic results optimal PBMT parameters are necessary. The positive effect of PBMT on diabetic cells may be dependent on fluence (J/cm2) and wavelength (nm). This double-blind, randomized clinical trial will be conducted at the University Clinic of Physical Therapy. One hundred patients will be randomly placed in 4 groups. A Laserpulse Ibramed (Helium-Neon, HeNe, 660 nm) with 20 W power will be used (continuous mode), with doses stipulated for each treatment group (GL1, 4 J/cm2; GL2, 8 J/cm2; GL3, 12 J/cm2) and Endophoton KLD GaAs 904 nm (ST, 10 J/cm2) for 2 nonconsecutive days per week for 10 weeks, for a total of 20 sessions. The primary outcomes will be ulcer healing rate and University of Texas classification scores. Patients' DFUs will be assessed on the 1st day, 5 weeks, and 10 weeks of treatment then 1 month after the end of treatment. This study may aid effective clinical decision-making for the management of DFUs.

A Double-Blind Study on the Effectiveness of Polarized Light Therapy in the Treatment of Venous leg Ulcers-Pilot Study.

Vein diseases are one of the most common civilization diseases. The most advanced form chronic venous insufficiency are venous leg ulcers. The study included 40 patients, 20 male (50%) and 20 female (50%) in age between 52 and 88 years (mean age: 68.00 ± 8.55 years) with venous leg ulcers lasting 12.50 ± 5.45 months. Patients were distributed randomly in a double-blind study into two equal groups including 20 patients each (group 1-polarized light therapy and group 2-sham exposure). Patients from both groups received routine pharmacological treatment, specialistic medical dressings and compression therapy. In addition, patients were exposed to a cycle of polarized light therapy procedures or to sham exposures (30 procedures performed in two series of 15 procedures). Wound surface area was evaluated by computerized planimetry and pain intensity was assessed with the use of Visual Analog Scale (VAS) before and after therapy (2.5 months). The analysis showed a statistically significant reduction of surface ulcers area between groups 1 and 2. The median (IQR) size of wounds in group 1 was 2.4 (1.95-2.9) cm2, in group 2; 2.8 (2.6-3.1) cm2 (p = 0.038). The level of pain (VAS) after treatment was assessed in group 1, median (IQR): 2 (2-3) points, in group 2 4.5 (4-5) points; and the observed difference was also statistically significant (p < 0.001). In group 1, after treatment, the area of ulcers decreased-median (IQR): 33.05 (28.7-41.48) %, in group 2 by 18.99 (15-24.4) % (p < 0.001). In group 1, the pain intensity measured using the VAS scale decreased with a median (IQR): 71.42 (61.25-71.42) %, in group 2: 37.5 (28.57-50) % (p < 0.001). Complex therapy with polarized light therapy added to standard care was more effective than standard care alone in reducing of ulcers surface area and intensity of pain ailments in patients with chronic venous leg ulcers.

Ibuprofen-Induced Pancytopenia and Erythema Multiforme in an Elderly Female Patient.

Erythema multiforme (EM) is a delayed, cell-mediated cutaneous disease with varying clinical manifestations. It is most commonly associated with infections but can also be associated with medications, vaccines, and autoimmune diseases. Non-steroidal anti-inflammatory Drugs (NSAIDs) are commonly used analgesics that have rare associations with EM and pancytopenia. These adverse reactions to NSAIDs can obscure definitive diagnosis due to their rarity. We present a case where an elderly female patient taking 600mg of ibuprofen up to four times a day for shoulder bursitis developed EM and pancytopenia. In this case, a 75-year-old female with a medical history of atrial fibrillation, essential hypertension, non-insulin-dependent type 2 diabetes mellitus, and ischemic stroke with residual right-sided visual impairment presented to our Emergency Department in 2023 with neck swelling, skin rash, and ulceration of the oral cavity. She reported a generalized, targetoid body rash that occurred 15 days after she started taking ibuprofen regularly for left shoulder bursitis. No other medications were started before, after, or during this time period. CBC on admission was remarkable for a white blood cell count of 1.5x109/L, hemoglobin of 6.5 g/dL, and platelet count <10x109/L, consistent with pancytopenia. Ibuprofen was discontinued, and the patient was treated supportively with analgesia and packed red blood cell transfusions. Testing for HIV, antinuclear antibodies (ANA) panel, Hepatitis panel, and copper and zinc levels were negative. A biopsy of a targetoid lesion on the skin showed changes consistent with EM. Esophagogastroduodenoscopy revealed no actively bleeding lesions or ulcers in the stomach mucosa. The patient's blood counts eventually recovered with supportive treatment, and symptomatology improved. The patient was discharged six days after admission. Healthcare professionals should be aware of rare hematologic and immunologic side effects of NSAIDs, which may often be overlooked and misdiagnosed. More studies are needed to build on our wealth of knowledge regarding the etiology and management of EM, Steven Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN).

Herpes Simplex Virus (HSV)-Induced Erythema Multiforme: A Rare Case Report.

A polymorphous recurrent eruption mostly composed of macules, bullae, papules, and target lesions, which are often distributed symmetrically and can spread to distant extremities, and oral mucosae are the features associated with erythema multiforme (EM). Herpes simplex virus (HSV) is a common condition that is associated with EM and manifests in late adulthood. It shows recurrence and is usually diagnosed clinically. Following is a case of HSV-associated EM. A 45-year-old patient visited the outpatient department with complaints of oral ulceration and associated pain and burning sensation. The patient also reported that similar ulcers were seen two months prior to her visit, which resolved on their own and the recurrence was seen two days prior to the visit. The recurrence occurred with more severity of pain and inflammation as compared to previous ulcers. The patient was kept on a combination therapy of antivirals, steroids, silymarin, and multivitamins for four visits with a tapering dose of steroids. Post-treatment, there was no recurrence till date and the patient is able to perform mastication as well as deglutition without any pain or burning sensation.

Self-Assembled Fibroblast Growth Factor Nanoparticles as a Therapeutic for Oxidant-Induced Neuronal and Skin Cell Injury.

Traumatic brain injury (TBI) and spinal cord injury (SCI) are neurological conditions that result from immediate mechanical injury, as well as delayed injury caused by local inflammation. Furthermore, TBI and SCI often lead to secondary complications, including pressure wounds of the skin, which can heal slowly and are prone to infection. Pressure wounds are localized areas of damaged tissue caused by prolonged pressure on the skin due to immobility and loss of neurological sensation. With the aim to ameliorate these symptoms, we investigated whether fibroblast growth factors 2 (FGF-2) could contribute to recovery. FGF-2 plays a significant role in both neurogenesis and skin wound healing. We developed a recombinant fusion protein containing FGF-2 linked to elastin-like polypeptides (FGF-ELP) that spontaneously self-assembles into nanoparticles at around 33 °C. The nanoparticle's size was ranging between 220 and 250 nm in diameter at 2 µM. We tested this construct for its ability to address neuronal and skin cell injuries. Hydrogen peroxide was used to induce oxidant-mediated injury on cultured neuronal cells to mimic the impact of reactive oxidants released during the inflammatory response in vivo. We found that FGF-ELP nanoparticles protected against hydrogen peroxide-mediated injury and promoted neurite outgrowth. In the skin cell models, cells were depleted from serum to mimic the reduced levels of nutrients and growth factors in chronic skin wounds. FGF-ELP increased the proliferation and migration of human keratinocytes, fibroblasts, and endothelial cells. FGF-ELP is, therefore, a potentially useful agent to provide both neuroprotection and promotion of cellular processes involved in skin wound healing.

Integrating bioinformatics and multiple machine learning to identify mitophagy-related targets for the diagnosis and treatment of diabetic foot ulcers: evidence from transcriptome analysis and drug docking.

Background: Diabetic foot ulcers are the most common and serious complication of diabetes mellitus, the high morbidity, mortality, and disability of which greatly diminish the quality of life of patients and impose a heavy socioeconomic burden. Thus, it is urgent to identify potential biomarkers and targeted drugs for diabetic foot ulcers. Methods: In this study, we downloaded datasets related to diabetic foot ulcers from gene expression omnibus. Dysregulation of mitophagy-related genes was identified by differential analysis and weighted gene co-expression network analysis. Multiple machine algorithms were utilized to identify hub mitophagy-related genes, and a novel artificial neural network model for assisting in the diagnosis of diabetic foot ulcers was constructed based on their transcriptome expression patterns. Finally, potential drugs that can target hub mitophagy-related genes were identified using the Enrichr platform and molecular docking methods. Results: In this study, we identified 702 differentially expressed genes related to diabetic foot ulcers, and enrichment analysis showed that these genes were associated with mitochondria and energy metabolism. Subsequently, we identified hexokinase-2, small ribosomal subunit protein us3, and l-lactate dehydrogenase A chain as hub mitophagy-related genes of diabetic foot ulcers using multiple machine learning algorithms and validated their diagnostic performance in a validation cohort independent of the present study (The areas under roc curve of hexokinase-2, small ribosomal subunit protein us3, and l-lactate dehydrogenase A chain are 0.671, 0.870, and 0.739, respectively). Next, we constructed a novel artificial neural network model for the molecular diagnosis of diabetic foot ulcers, and the diagnostic performance of the training cohort and validation cohort was good, with areas under roc curve of 0.924 and 0.840, respectively. Finally, we identified retinoic acid and estradiol as promising anti-diabetic foot ulcers by targeting hexokinase-2 (-6.6 and -7.2 kcal/mol), small ribosomal subunit protein us3 (-7.5 and -8.3 kcal/mol), and l-lactate dehydrogenase A chain (-7.6 and -8.5 kcal/mol). Conclusion: The present study identified hexokinase-2, small ribosomal subunit protein us3 and l-lactate dehydrogenase A chain, and emphasized their critical roles in the diagnosis and treatment of diabetic foot ulcers through multiple dimensions, providing promising diagnostic biomarkers and targeted drugs for diabetic foot ulcers.

Combined treatment of umbilical cord Wharton's jelly-derived mesenchymal stem cells and platelet-rich plasma for a surgical patient with hospital-acquired pressure ulcer: a case report and literature review.

Hospital-acquired pressure ulcers (HAPUs) are still an important worldwide issue related to the safety and quality of patient care, which are among the top five adverse events reported. Patients who develop HAPUs have longer stays in the hospital than necessary, are at a greater risk of infections, and are more likely to die. Surgical patients are prone to developing PUs because they often remain immobile for extended periods of time, and their surgical procedures may limit the flow of blood oxygen and nutrition and lead to a decrease in muscle tone. Mesenchymal stem cells (MSCs) represent an attractive stem cell source for tissue regeneration in clinical applications, which have been demonstrated to improve wound healing through re-epithelialization, increased angiogenesis, and granulation tissue formation. Here, we present the case of an emergency surgical patient who developed an ulcer on the right heel during hospitalization. The human umbilical cord Wharton's jelly-derived MSCs (WJ-MSCs) re-suspended in platelet-rich plasma (PRP) were injected into ulcer margins. Four days after the WJ-MSC application, the patient showed progressive healing of the PU. From days 4 to 33, granulation tissue formation and re-epithelialization were clearly observed. The ulcer was almost healed completely on day 47, and the pain in the patient's wound area also decreased. Thus, intradermal transplantation of WJ-MSCs and PRP was safe and effective for treatment in patients with pressure ulcers. WJ-MSCs, together with PRP, may offer a promising treatment option for wound healing.