Lesion Site Research Articles

Takayasu arteritis presenting with large cerebral infarction in a 39-year-old Syrian woman: a case report

Introduction and importance: Takayasu Arteritis (TA) is a rare chronic inflammatory disease of unknown etiology that primarily affects large vessels, such as the aorta and its major branches. The disease typically presents with diverse symptoms, depending on the site and degree of arterial lesions. Delayed diagnosis is common, especially in younger populations. Case presentation: A 39-year-old Syrian female presented with an initial stroke. She had no prior medical history and was otherwise healthy. On examination, she had an absent left radial pulse, a carotid bruit, and muscle weakness. Blood tests showed an elevated ESR and CRP. Computed tomography of the brain revealed a right large cerebral infarction. Multislice computed tomography angiography showed diffuse arterial wall thickening, stenosis, and occlusion of several major vessels, including the left internal carotid artery, right internal carotid artery, and left subclavian artery. Clinical discussion: The patient was diagnosed with TA based on the American College of Rheumatology criteria. She was treated with prednisolone, methotrexate, and aspirin, and her symptoms improved significantly. Conclusion: This case highlights the importance of considering TA in the differential diagnosis of ischemic stroke, especially in young patients with atypical presentations. Early identification and management are essential to preclude critical sequelae.

Surgical treatment of cavernous malformation-related epilepsy in children: case series, systematic review, and meta-analysis.

Cerebral cavernous malformations (CCMs) are cerebral vascular lesions that occasionally occur with seizures. We present a retrospective case series from IRCCS Gaslini Children's Hospital, a systematic review, and meta-analysis of the literature with the goal of elucidating the post-surgery seizure outcome in children with CCMs. a retrospective review of children with cavernous malformation related epilepsy who underwent surgery at Gaslini Children's Hospital from 2005 to 2022 was conducted. We also conducted a comprehensive search on PubMed/MEDLINE and Scopus databases from January 1989 to August 2022. Inclusion criteria were: presence of CCMs-related epilepsy, in under 18 years old subjects with a clear lesion site. Presence of post-surgery seizure outcome and follow-up ≥ 12 months. we identified 30 manuscripts and 223 patients with CCMs-related epilepsy, including 17 patients reported in our series. We identified 85.7% Engel class I subjects. The risk of expected neurological deficits was 3.7%; that of unexpected neurological deficits 2.8%. We found no statistically significant correlations between Engel class and the following factors: site of lesion, type of seizure, drug resistance, duration of disease, type of surgery, presence of multiple CCMs. However, we found some interesting trends: longer disease duration and drug resistance seem to be more frequent in subjects in Engel class II, III and IV; multiple cavernomas would not seem to influence seizure outcome. epilepsy surgery in children with CCMs is a safe and successful treatment option. Further studies are necessary to define the impact of clinical features on seizure prognosis.

In situ lesion recovery of Scleractinian branching coral wild colonies from asexual coral propagation

As coral reefs worldwide continue to degrade due to natural and anthropogenic threats, coral restoration efforts have been rapidly growing in recent decades to maintain the ecological function of coral reefs. In Malaysia, asexual propagation by fragmenting branches from healthy Acropora wild colonies is becoming the norm, but other coral genera are rarely considered in restoration efforts despite the need to enhance diversity and reef resilience. Additionally, restoration efforts in Malaysia mainly focus on the recovery of coral fragments in nurseries while overlooking the wild coral colonies they were sourced from. Lesion recovery from physical damage should be investigated to maximise restoration success and to ensure the wild coral populations do not degrade due to fragmentation from coral propagation efforts. To address this, we investigated the recuperation capabilities of two branching coral species, Acropora muricata and Echinopora horrida, in a shallow reef (<8 m) of Pulau Rawa, Johor, Malaysia. Coral colonies were induced with physical damage, and lesion recovery was measured via lesion site closure, colour score and relative growth of the broken colonies (n=30) over 129 days. The lesion site of A. muricata closed significantly more at 99.94±0.04SE%, compared to E. horrida with 86.97±3.53SE%. When compared to E. horrida, A. muricata had achieved full colour recovery by day 27 and more than double the value of relative growth (9.7 %). The differences in lesion recovery capabilities between A. muricata and E. horrida are hypothesised to be attributed to their different life adaptive strategies where A. muricata is an r adaptive strategist and E. horrida is a K adaptive strategist. The findings imply that future coral restoration efforts should investigate the recovery capabilities of the wild coral colonies before starting coral propagation efforts to prevent partial mortality of wild colonies and maintain species diversity and ecological functions of the reef.

Plane-wave medical image reconstruction based on dynamic Criss-Cross attention and multi-scale convolution.

Plane-wave imaging is widely employed in medical imaging due to its ultra-fast imaging speed. However, the image quality is compromised. Existing techniques to enhance image quality tend to sacrifice the imaging frame rate. The study aims to reconstruct high-quality plane-wave images while maintaining the imaging frame rate. The proposed method utilizes a U-Net-based generator incorporating a multi-scale convolution module in the encoder to extract information at different levels. Additionally, a Dynamic Criss-Cross Attention (DCCA) mechanism is proposed in the decoder of the U-Net-based generator to extract both local and global features of plane-wave images while avoiding interference caused by irrelevant regions. In the reconstruction of point targets, the experimental images achieved a reduction in Full Width at Half Maximum (FWHM) of 0.0499 mm, compared to the Coherent Plane-Wave Compounding (CPWC) method using 75-beam plane waves. For the reconstruction of cyst targets, the simulated image achieved a 3.78% improvement in Contrast Ratio (CR) compared to CPWC. The proposed model effectively addresses the issue of unclear lesion sites in plane-wave images.

Comparative model of minimal spinal cord injury reveals a rather anti-inflammatory response in the lesion site as well as increased proliferation in the central canal lining in the neonates compared to the adult rats.

Spinal cord injury (SCI) resulting from trauma decreases the quality of human life. Numerous clues indicate that the limited endogenous regenerative potential is a result of the interplay between the inhibitory nature of mature nervous tissue and the inflammatory actions of immune and glial cells. Knowledge gained from comparing regeneration in adult and juvenile animals could draw attention to factors that should be removed or added for effective therapy in adults. Therefore, we generated a minimal SCI (mSCI) model with a comparable impact on the spinal cord of Wistar rats during adulthood, preadolescence, and the neonatal period. The mechanism of injury is based on unilateral incision with a 20ga needle tip according to stereotaxic coordinates into the dorsal horn of the L4 lumbar spinal segment. The incision should harm a similar amount of gray matter on a coronal section in each group of experimental animals. According to our results, the impact causes mild injury with minimal adverse effects on the neurological functions of animals but still has a remarkable effect on nervous tissue and its cellular and humoral components. Testing the mSCI model in adults, preadolescents, and neonates revealed a rather anti-inflammatory response of immune cells and astrocytes at the lesion site, as well as increased proliferation in the central canal lining in neonates compared with adult animals. Our results indicate that developing nervous tissue could possess superior reparative potential and confirm the importance of comparative studies to advance in the field of neuroregeneration.

Clinical features and treatment of heterotopic pancreas in children: a multi-center retrospective study

ObjectiveHeterotopic pancreas, an uncommon condition in children, can present with diagnostic and treatment challenges. This study aimed to evaluate the clinical features and treatment options for this disorder in pediatric patients.MethodsWe conducted a retrospective analysis, including patients diagnosed with heterotopic pancreas at four tertiary hospitals between January 2000 and June 2022. Patients were categorized into symptomatic and asymptomatic groups based on clinical presentation. Clinical parameters, including age at surgery, lesion size and site, surgical or endoscopic approach, pathological findings, and outcome, were statistically analyzed.ResultsThe study included 88 patients with heterotopic pancreas. Among them, 22 were symptomatic, and 41 were aged one year or younger. The heterotopic pancreas was commonly located in Meckel’s diverticulum (46.59%), jejunum (20.45%), umbilicus (10.23%),ileum (7.95%), and stomach (6.82%). Sixty-six patients had concomitant diseases. Thirty-three patients had heterotopic pancreas located in the Meckel’s diverticulum, with 80.49% of cases accompanied by gastric mucosa heterotopia (GMH). Patients without accompanying GMH had a higher prevalence of heterotopic pancreas-related symptoms (75%). Treatment modalities included removal of the lesions by open surgery, laparoscopic or laparoscopic assisted surgery, or endoscopic surgery based on patient’s age, the lesion site and size, and coexisting diseases.ConclusionsOnly one-fourth of the patients with heterotopic pancreas presented with symptoms. Those located in the Meckel’s diverticulum have commonly accompanying GMH. Open surgical, laparoscopic surgical or endoscopic resection of the heterotopic pancreas is recommended due to potential complications. Future prospective multicenter studies are warranted to establish rational treatment options.

Axonal autophagic vesicle transport in the rat optic nerve in vivo under normal conditions and during acute axonal degeneration

Neurons pose a particular challenge to degradative processes like autophagy due to their long and thin processes. Autophagic vesicles (AVs) are formed at the tip of the axon and transported back to the soma. This transport is essential since the final degradation of the vesicular content occurs only close to or in the soma. Here, we established an in vivo live-imaging model in the rat optic nerve using viral vector mediated LC3-labeling and two-photon-microscopy to analyze axonal transport of AVs. Under basal conditions in vivo, 50% of the AVs are moving with a majority of 85% being transported in the retrograde direction. Transport velocity is higher in the retrograde than in the anterograde direction. A crush lesion of the optic nerve results in a rapid breakdown of retrograde axonal transport while the anterograde transport stays intact over several hours. Close to the lesion site, the formation of AVs is upregulated within the first 6 h after crush, but the clearance of AVs and the levels of lysosomal markers in the adjacent axon are reduced. Expression of p150Glued, an adaptor protein of dynein, is significantly reduced after crush lesion. In vitro, fusion and colocalization of the lysosomal marker cathepsin D with AVs are reduced after axotomy. Taken together, we present here the first in vivo analysis of axonal AV transport in the mammalian CNS using live-imaging. We find that axotomy leads to severe defects of retrograde motility and a decreased clearance of AVs via the lysosomal system.

A modified supraclavicular artery island flap for reconstruction of oral and maxillofacial defects

ObjectiveTo overcome the limitation of the supraclavicular artery island flap (SCAIF), we describe a modified SCAIF which incorporates a portion of the upper trapezius and the superficial branch of the transverse cervical artery (TCA) for the reconstruction of oral and maxillofacial defects. Study designThe modified SCAIF was used on 20 patients at our hospital between April 2013 to August 2022. All patients underwent resection of the primary lesion site and immediate reconstruction with the modified SCAIF. Demographic data and flap details were recorded. Complications were assessed for at least a 6-month follow-up period. ResultsThis study included 20 patients. The mean flap harvest time was 50 minutes. The mean flap length was 6.0 cm, and the mean flap width was 5.0 cm. All flaps of 20 cases survived with good appearance, and no shoulder morbidity was found during a follow-up period of at least 6 months. ConclusionThe modified SCAIF is a versatile and reliable local flap option for moderate to large reconstruction in this special region after resection of the primary lesions. We found this simple flap design has overcome the limitations of the traditional one with a reliable blood supply and adequate tissue for larger defects.

Toward Automating Diagnosis of Middle- and Inner-ear Mechanical Pathologies With a Wideband Absorbance Regression Model.

During an initial diagnostic assessment of an ear with normal otoscopic exam, it can be difficult to determine the specific pathology if there is a mechanical lesion. The audiogram can inform of a conductive hearing loss but not the underlying cause. For example, audiograms can be similar between the inner-ear condition superior canal dehiscence (SCD) and the middle-ear lesion stapes fixation (SF), despite differences in pathologies and sites of lesion. To gain mechanical information, wideband tympanometry (WBT) can be easily performed noninvasively. Absorbance, the most common WBT metric, is related to the absorbed sound energy and can provide information about specific mechanical pathologies. However, absorbance measurements are challenging to analyze and interpret. This study develops a prototype classification method to automate diagnostic estimates. Three predictive models are considered: one to identify ears with SCD versus SF, another to identify SCD versus normal, and finally, a three-way classification model to differentiate among SCD, SF, and normal ears. Absorbance was measured in ears with SCD and SF as well as normal ears at both tympanometric peak pressure (TPP) and 0 daPa. Characteristic impedance was estimated by two methods: the conventional method (based on a constant ear-canal area) and the surge method, which estimates ear-canal area acoustically.Classification models using multivariate logistic regression predicted the probability of each condition. To quantify expected performance, the condition with the highest probability was selected as the likely diagnosis. Model features included: absorbance-only, air-bone gap (ABG)-only, and absorbance+ABG. Absorbance was transformed into principal components of absorbance to reduce the dimensionality of the data and avoid collinearity. To minimize overfitting, regularization, controlled by a parameter lambda, was introduced into the regression. Average ABG across multiple frequencies was a single feature.Model performance was optimized by adjusting the number of principal components, the magnitude of lambda, and the frequencies included in the ABG average. Finally, model performances using absorbance at TPP versus 0 daPa, and using the surge method versus constant ear-canal area were compared. To estimate model performance on a population unknown by the model, the regression model was repeatedly trained on 70% of the data and validated on the remaining 30%. Cross-validation with randomized training/validation splits was repeated 1000 times. The model differentiating between SCD and SF based on absorbance-only feature resulted in sensitivities of 77% for SCD and 82% for SF. Combining absorbance+ABG improved sensitivities to 96% and 97%. Differentiating between SCD and normal using absorbance-only provided SCD sensitivity of 40%, which improved to 89% by absorbance+ABG. A three-way model using absorbance-only correctly classified 31% of SCD, 20% of SF and 81% of normal ears. Absorbance+ABG improved sensitivities to 82% for SCD, 97% for SF and 98% for normal. In general, classification performance was better using absorbance at TPP than at 0 daPa. The combination of wideband absorbance and ABG as features for a multivariate logistic regression model can provide good diagnostic estimates for mechanical ear pathologies at initial assessment. Such diagnostic automation can enable faster workup and increase efficiency of resources.

Development and Validation of a Liquid Chromatography-Tandem Mass Spectrometry Method for Screening Potential Citrate Lyase Inhibitors from a Library of Marine Compounds.

Tuberculosis, a persistent illness caused by Mycobacterium tuberculosis, remains a significant global public health challenge. The widespread use of anti-tuberculosis drugs has resulted in the emergence of drug-resistant strains, which complicates treatment efforts. Addressing this issue is crucial and hinges on the development of new drugs that can effectively target the disease. This involves identifying novel therapeutic targets that can disrupt the bacterium's survival mechanisms in various environments such as granulomas and lesions. Citrate lyase, essential for the survival of Mycobacterium species at lesion sites and in granulomatous conditions, is a potential target for the treatment of tuberculosis. This manuscript aimed to construct an efficient enzyme inhibitor screening platform using ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF MS). This system can accurately identify compounds with enzyme inhibitory activity from a library of marine terpenoids and phenolic compounds. Utilizing the screened herbal enzyme inhibitors as a starting point, we analyzed their chemical structures and skillfully built a library of marine compounds based on these structures. The results showed that all of the tested compounds from the phenolics library inhibited citrate lyase by more than 50%, and a significant portion of terpenoids also demonstrated inhibition, with these active terpenoids comprising over half of the terpenoids tested. The study underscores the potential of marine-derived phenolic and terpenoid compounds as potent inhibitors of citrate lyase, indicating a promising direction for future investigations in treating tuberculosis and associated disorders.

Lung Metastasectomy: Where Do We Stand? Results from an Italian Multicentric Prospective Database.

Background/Objectives: The surgical resection of pulmonary metastases is considered a therapeutic option in selected cases. In light of this, we present the results from a national multicenter prospective registry of lung metastasectomy. Methods: This retrospective analysis involves data collected prospectively and consecutively in a national multicentric Italian database, including patients who underwent lung metastasectomy. The primary endpoints were the analysis of morbidity and overall survival (OS), with secondary endpoints focusing on the analysis of potential risk factors affecting both morbidity and OS. Results: A total 470 lung procedures were performed (4 pneumonectomies, 46 lobectomies/bilobectomies, 13 segmentectomies and 407 wedge resections) on 461 patients (258 men and 203 women, mean age of 63.1 years). The majority of patients had metastases from colorectal cancer (45.8%). In most cases (63.6%), patients had only one lung metastasis. A minimally invasive approach was chosen in 143 cases (30.4%). The mean operative time was 118 min, with no reported deaths. Morbidity most frequently consisted of prolonged air leaking and bleeding, but no re-intervention was required. Statistical analysis revealed that morbidity was significantly affected by operative time and pulmonary comorbidities, while OS was significantly affected by disease-free interval (DFI) > 24 months (p = 0.005), epithelial histology (p = 0.001) and colorectal histology (p = 0.004) during univariate analysis. No significant correlation was found between OS and age, gender, surgical approach, surgical extent, surgical device, the number of resected metastases, lesion diameter, the site of lesions and nodal involvement. Multivariate analysis of OS confirmed that only epithelial histology and DFI were risk-factors, with p-values of 0.041 and 0.031, respectively. Conclusions: Lung metastasectomy appears to be a safe procedure, with acceptable morbidity, even with a minimally invasive approach. However, it remains a local treatment of a systemic disease. Therefore, careful attention should be paid to selecting patients who could truly benefit from surgical intervention.

Nontuberculous mycobacterial disease in children: A systematic review and meta-analysis

BackgroundThe prevalence of nontuberculous mycobacterial (NTM) disease in children is increasing worldwide. The clinical manifestations of pediatric NTM patients are significantly different from those of adult patients, but the knowledge of the disease is generally poor. MethodsEnglish databases (PubMed, Web of Science, Embase, BIOSIS) and Chinese databases (CNKI, Wanfan, VIP) were searched on October 15th, 2022. All the articles of cross-sectional and cohort studies reporting the species composition and lesion site of the NTM disease in children using well-recognized NTM species identification methods were taken into account. Using a random effects model, we assessed the disease lesion sites and the prevalence of different NTM species in pediatric NTM disease. Sources of heterogeneity were analyzed using Cochran's Q and the I2 statistic. All analyses were performed using CMA V3.0. ResultsThe prevalence rates of NTM disease in children ranged between 0.6 and 5.36/100,000 in different countries, and Europe reported the highest prevalence rate. The most common clinical lesion site was lymph node, accounting for 71.1 % (55.0 %–83.2 %), followed by lung (19.3 %, 9.8%–34.4 %）and then skin and soft tissue (16.6 %,13.5%–20.3 %). Mycobacterium avium complex (MAC) was the most isolated NTM pathogen in children, accounting for 54.9 % (39.4%–69.6 %). Inconsistent with adult patients, Mycobacterium avium accounted for a dominant proportion in MAC than Mycobacterium intracellulare. ConclusionsThe lymph node was the most affected organ in pediatric NTM disease, while Mycobacterium avium was the most isolated pathogenic species in children.

Investigating the Functional Performance of Plantago Ovate Plant as a Drug Carrier in a Targeted Drug Delivery System

The drug delivery systems that were used in the past were done without any control over the time, place and speed of drug release, and this caused the amount of drug released in the blood to fluctuate, that is, the concentration of the drug in the blood could vary from The therapeutic range will be exceeded and its side effects will also increase. Therefore, with targeted medicine, it is possible to control the place of drug release, its speed and time, and minimize the side effects caused by the drug. In this regard, in this research, the natural hydrogel extracted from the Plantago ovate plant as one of the drug carriers in the body environment in order to increase the efficiency and reduce the degradation of the drug, prevent the side effects caused by the use of the drug and increase the access to the drug and improve Its effect was investigated at the lesion site. In this context, after extracting the natural hydrogel from Plantago ovate plant, the swelling rate of Plantago ovate gel powder was investigated at different pH, the FT-IR spectrum obtained from Plantago ovate hydrogel and the swelling rate of Plantago ovate mucilage at different pH were investigated. Therefore, the obtained results indicate that natural polysaccharides can be used as a natural drug carrier in drug delivery systems due to their high biocompatibility in the body environment, non-toxicity and cheapness.

Alterations of tactile and anatomical spatial representations of the hand after stroke

Stroke often causes long-term motor and somatosensory impairments. Motor planning and tactile perception rely on spatial body representations. However, the link between altered spatial body representations, motor deficit and tactile spatial coding remains unclear. This study investigates the relationship between motor deficits and alterations of anatomical (body) and tactile spatial representations of the hand in 20 post-stroke patients with upper limb hemiparesis. Anatomical and tactile spatial representations were assessed from 10 targets (nails and knuckles) respectively cued verbally by their anatomical name or using tactile stimulations. Two distance metrics (hand width and finger length) and two structural measures (relative organization of targets positions and angular deviation of fingers from their physical posture) were computed and compared to clinical assessments, normative data and lesions sites. Over half of the patients had altered anatomical and/or tactile spatial representations. Metrics of tactile and anatomical representations showed common variations, where a wider hand representation was linked to more severe motor deficits. In contrast, alterations in structural measures were not concomitantly observed in tactile and anatomical representations and did not correlate with clinical assessments. Finally, a preliminary analysis showed that specific alterations in tactile structural measures were associated with dorsolateral prefrontal stroke lesions. This study reveals shared and distinct characteristics of anatomical and tactile hand spatial representations, reflecting different mechanisms that can be affected differently after stroke: metrics and location of tactile and anatomical representations were partially shared while the structural measures of tactile and anatomical representations had distinct characteristics.

Synergies of co-infecting pathogens, sea lice (Lepeophetheirus salmonis) and Moritella viscosa, are impacted by exposure order, and host response to initial infection

Sea lice infestations and winter ulcer disease caused by Moritella viscosa are two major challenges for the Atlantic salmon (Salmo salar) aquaculture industry. Despite their common tropisms for the skin/muscle, we know very little about the interaction between these two significant pathogens. The objective of this study was to elucidate the transcriptomic response of Atlantic salmon to sea louse (Lepeophtheirus salmonis) and M. viscosa under single infection and different scenarios of co-infection (i.e., first, L. salmonis and then, M. viscosa and vice versa). After exposure, sampling was performed from the infestation site as well as the adjacent area on fish skin, followed by transcriptome analysis. RNA-seq analysis revealed that infection with either L.salmonis or M. viscosa induced a significant immune response from the skin and resulted in extensive transcriptomic changes. More differentially expressed genes (DEGs) were detected at M. viscosa lesion sites compared to L. salmonis attachment sites. In addition, the effect of the infection order was evaluated. Interestingly, we found that primary infection with lice was associated with a significantly higher number of DEGs during the co-infection process on fish skin compared to the fish first infected with M. viscosa (721 and 5336 DEGs from lice attachment and M. viscosa lesion sites, respectively, vs 291 and 3601 DEGs from lice attachment and M. viscosa lesion sites, respectively). We also found that lice infection caused localized effects on the skin of Atlantic salmon, while single infection with M. viscosa caused a moderate systemic impact and inhibited the tissue repair function of the skin, leading to severe ulceration. In addition, the C-type lectin receptor signaling pathway was drastically activated at the lice attachment sites during both lice alone- and co-infections, regardless of the order of infections, and similar results were observed in M. viscosa infection at both lesion and adjacent sites, indicating that this pathway played an essential role for immunity in Atlantic salmon. A more intense inflammatory and immune response was also observed at M. viscosa lesion sites. These results will promote our understanding of the immune interactions between L. salmonis and M. viscosa during the co-infection process and provide insights for the development of preventive and treatment strategies for these pathogens in salmonid aquaculture.

Stem cell exosome-loaded Gelfoam improves locomotor dysfunction and neuropathic pain in a rat model of spinal cord injury.

Spinal cord injury (SCI) is a debilitating illness in humans that causes permanent loss of movement or sensation. To treat SCI, exosomes, with their unique benefits, can circumvent limitations through direct stem cell transplantation. Therefore, we utilized Gelfoam encapsulated with exosomes derived from human umbilical cord mesenchymal stem cells (HucMSC-EX) in a rat SCI model. SCI model was established through hemisection surgery in T9 spinal cord of female Sprague-Dawley rats. Exosome-loaded Gelfoam was implanted into the lesion site. An in vivo uptake assay using labeled exosomes was conducted on day 3 post-implantation. Locomotor functions and gait analyses were assessed using Basso-Beattie-Bresnahan (BBB) locomotor rating scale and DigiGait Imaging System from weeks 1 to 8. Nociceptive responses were evaluated through von Frey filament and noxious radiant heat tests. The therapeutic effects and potential mechanisms were analyzed using Western blotting and immunofluorescence staining at week 8 post-SCI. For the in vivo exosome uptake assay, we observed the uptake of labeled exosomes by NeuN+, Iba1+, GFAP+, and OLIG2+ cells around the injured area. Exosome treatment consistently increased the BBB score from 1 to 8 weeks compared with the Gelfoam-saline and SCI control groups. Additionally, exosome treatment significantly improved gait abnormalities including right-to-left hind paw contact area ratio, stance/stride, stride length, stride frequency, and swing duration, validating motor function recovery. Immunostaining and Western blotting revealed high expression of NF200, MBP, GAP43, synaptophysin, and PSD95 in exosome treatment group, indicating the promotion of nerve regeneration, remyelination, and synapse formation. Interestingly, exosome treatment reduced SCI-induced upregulation of GFAP and CSPG. Furthermore, levels of Bax, p75NTR, Iba1, and iNOS were reduced around the injured area, suggesting anti-inflammatory and anti-apoptotic effects. Moreover, exosome treatment alleviated SCI-induced pain behaviors and reduced pain-associated proteins (BDNF, TRPV1, and Cav3.2). Exosomal miRNA analysis revealed several promising therapeutic miRNAs. The cell culture study also confirmed the neurotrophic effect of HucMSCs-EX. Implantation of HucMSCs-EX-encapsulated Gelfoam improves SCI-induced motor dysfunction and neuropathic pain, possibly through its capabilities in nerve regeneration, remyelination, anti-inflammation, and anti-apoptosis. Overall, exosomes could serve as a promising therapeutic alternative for SCI treatment.

Role of Neutrophils as Therapeutic Targets in Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a major health problem. It is one of the most common types of stroke and results in mortality in approximately half of patients. More than half of the fatalities occur in the first 2 days. In addition to the mass effect after ICH hemorrhage, complex pathophysiological mechanisms such as intracranial vessel vasospasm, microthrombosis, and inflammatory immune reaction also increase brain damage. Both resident (including microglia and astrocytes) and circulating immune cells (including neutrophils, macrophages, and lymphocytes) involved in the inflammatory process. The inflammatory response is especially harmful in the acute phase due to harmful substances secreted by infiltrating immune cells. The inflammatory response also has beneficial effects, especially in the later stages. Their role in pathophysiology makes immune cells important therapeutic targets. General immunosuppressive approaches and depleting cell groups such as neutrophils or keeping them away from the lesion site may not be sufficient to prevent poor outcomes after ICH. This is most likely because they suppress anti-inflammatory activities and pro-inflammatory effects. Instead, directing immune cells to the beneficial subpopulation seems like a more rational solution. The pro-inflammatory N1 subpopulation of neutrophils damages the tissue surrounding ICH. In contrast, the N2 subpopulation is associated with anti-inflammatory reactions and tissue repair. Studies show that when neutrophils are polarized toward the N2 subpopulation, clinical outcomes improve and the volume of the infarct decreases. However, more research is still needed. This study aims to evaluate the role of neutrophils as immunotherapeutic targets in ICH in light of current knowledge.

Laser Forced Dehydration of Benign Vascular Lesions of the Oral Cavity: A Valid Alternative to Surgical Techniques.

Background and Objectives: Low-flow vascular lesions are commonly encountered in the oral cavity and may require removal due to aesthetic concerns, repeated bleeding or a cluttering sensation. Laser devices represent an excellent aid due to their affinity with blood and to their biostimulating properties and have been substituting traditional excision in selected cases. Materials and Methods: In this study, 30 patients presenting with low-flow oral vascular lesions were included. The lesions were clinically evaluated as follows: lesion's site, reason for treatment, lesion's dimensions, confirmation of positive diascopy via compression with a glass slide and photograph. The lesions were treated with laser forced dehydration (LFD) and then followed-up after 3 weeks, 6 months and 1 year. The laser source was a K-Laser Blu Derma (Eltech, K-Laser S.r.l., Via Castagnole, 20/H, Treviso, Italy). In the case of incomplete healing, a further protocol was performed at the three-week follow-up, and a further follow-up was scheduled for three weeks after. The following aspects were evaluated at each appointment: pain, using a Numeric Rating Scale (NRS) from 0 to 10 (0 = no pain, 10 = worst pain ever); the need to take painkillers (day of intervention and during follow-up); bleeding (yes/no); scar formation. Results: Complete regression was obtained in all patients, with no side effects. Only one patient required a second LFD protocol. NRS was 0 for all patients for the whole duration of the follow-up. None of the patients took painkillers on the day of the intervention and during the follow-up. One patient declared slight bleeding the day of the intervention, which she easily managed at home. One patient showed a small non-retracting and non-painful scar at the three-week follow-up. No recurrences were found after six months and one year. Conclusions: LFD targets endogenous chromophores, minimizing damage to adjacent tissue and limiting side effects. LFD is effective and could be considered a conservative alternative to traditional excision in low-flow lesions.

Treating epidermolytic ichthyosis and ichthyosis with confetti with epidermal autografts cultured from revertantskin.

No efficient treatment has yet been established for epidermolytic ichthyosis (EI), which is caused by pathogenic variants of KRT1 or KRT10. Patients with ichthyosis with confetti (IWC) have multiple normal-appearing spots, caused by the revertant somatic recombination of pathogenic variants that occurs at each spot independently. Additionally, some patients with EI have large areas of normal skin due to revertant postzygotic mosaicism. To assess the feasibility of transplanting cultured epidermal autografts (CEAs) produced from revertant epidermal keratinocytes in patients with EI and IWC. We performed a clinical trial of treatment with CEAs produced from each patient's own revertant epidermal keratinocytes as a proof-of-concept study. This was a single-arm, open, unmasked, uncontrolled, single-assignment, treatment-purpose study. The primary outcome was the percentage area that lacked recurrence of ichthyosis lesions 4 weeks after the final transplant. The secondary outcome was the percentage area lacking recurrence of ichthyosis lesions 24 weeks after the initial transplantation. The trial was registered with the Japan Registry of Clinical Trials (jRCTb041190097). We successfully produced CEAs from genetically confirmed revertant skin from two patients with mosaic EI and from one patient with IWC and confirmed by amplicon sequencing and droplet digital polymerase chain reaction analysis that the CEAs mainly consisted of revertant wild-type cells. Single-cell RNA sequencing analysis confirmed the normal proliferation and safety profiling of CEAs. CEAs were transplanted onto desquamated lesional sites in the patients. Four weeks post-transplantation, the percentage area lacking recurrence of ichthyosis lesions in the three patients was 40%, 100% and 100% respectively, although recurrence of ichthyosis lesions was seen at the site of CEA transplantation in all three patients at 24 weeks post-transplantation. CEAs from normal skin have the potential to be a safe and local treatment option for EI and IWC.

Readily Available Oral Prebiotic Protein Reactive Oxygen Species Nanoscavengers for Synergistic Therapy of Inflammation and Fibrosis in Inflammatory Bowel Disease.

A significant gap exists in the demand for safe and effective drugs for inflammatory bowel disease (IBD), and its associated intestinal fibrosis. As oxidative stress plays a central role in the pathogenesis of IBD, astaxanthin (AST), a good antioxidant with high safety, holds promise for treating IBD. However, the application of AST is restricted by its poor solubility and easy oxidation. Herein, different protein-based nanoparticles (NPs) are fabricated for AST loading to identify an oral nanovehicle with potential clinical applicability. Through systematic validation via molecular dynamics simulation and in vitro characterization of properties, whey protein isolate (WPI)-driven NPs using a simple preparation method without the need for cross-linking agents or emulsifiers were identified as the optimal carrier for oral AST delivery. Upon oral administration, the WPI-driven NPs, benefiting from the intrinsic pH sensitivity and mucoadhesive properties, effectively shielded AST from degradation by gastric juices and targeted release of AST at intestinal lesion sites. Additionally, the AST NPs displayed potent therapeutic efficacy in both dextran sulfate sodium (DSS)-induced acute colitis and chronic colitis-associated intestinal fibrosis by ameliorating inflammation, oxidative damage, and intestinal microecology. In conclusion, the AST WPI NPs hold a potential therapeutic value in treating inflammation and fibrosis in IBD.