A functional hydrogel of dopamine-modified gelatin with photothermal properties for enhancing infected wound healing.

Infected skin wound has gradually become a prevalent injury that affects overall health. Currently, biomaterials with good adhesion, efficient antibacterial properties, and angiogenesis are considered as a suitable way to effectively heal infected wound. Herein, a multifunctional hydrogel comprising gelatin, dopamine (DA), and ferric ions (Fe3+) was developed for infected wound healing. The modified gelatin-dopamine (Gel-DA) enhanced adhesive capability. Subsequently introducing ferric ions (Fe3+) to form Gel-DA-Fe3+ hydrogels by Fe3+ and catechol coordination bonds. The designed hydrogels demonstrated multifaceted functionality, encompassing photothermal antibacterial, angiogenesis, and so on. The introduction of DA enhanced the adhesion of Gel-DA-Fe3+ to the skin surface and might serve as a physical barrier to seal wound. Meanwhile, DA and Fe3+ jointly endowed good photothermal effects to composite hydrogels, which could eliminate over 95 % of bacteria. In vitro results revealed that Gel-DA-Fe3+ hydrogels had good biocompatibility and promoted HUVECs migration and tube formation. Furthermore, in vivo studies confirmed that Gel-DA-Fe3+ hydrogels markedly expedited the wound healing of rats through eradicating bacteria, accelerating the deposition of collagen, and promoting angiogenesis. What's more, Gel-DA-Fe3+ hydrogels under near-infrared laser had a more pronounced ability for wound healing. Therefore, Gel-DA-Fe3+ hydrogels had great potential for application in bacteria-infected wound healing.

Composite Hydrogel Dressings with Enhanced Mechanical Properties and Anti-Inflammatory Ability for Effectively Promoting Wound Repair.

Background: Hydrogel dressings have been used as a crucial method to keep the wound wet and hasten the healing process. Due to safety concerns regarding the gel components, low mechanical adhesiveness, and unsatisfactory anti-inflammatory capacity qualities for practical uses in vivo, leading to the clinical translation of wound dressings is still difficult. Methods: A type of composite hydrogel (acrylamide/polyethylene glycol diacrylate/tannic acid, ie, AM/PEGDA/TA) by double bond crosslinking, Schiff base, and hydrogen bond interaction is proposed. The mechanical characteristics, adhesiveness, and biocompatibility of the hydrogel system were all thoroughly examined. Additionally, a full-thickness cutaneous wound model was employed to assess the in vivo wound healing capacity of resulting hydrogel dressings. Results: Benefiting the mechanism of multiple crosslinking, the designed composite hydrogels showed significant mechanical strength, outstanding adhesive capability, and good cytocompatibility. Moreover, the hydrogel system also had excellent shape adaptability, and they can be perfectly integrated into the irregularly shaped wounds through a fast in situ forming approach. Additional in vivo tests supported the findings that the full-thickness wound treated with the composite hydrogels showed quicker epithelial tissue regeneration, fewer inflammatory cells, more collagen deposition, and greater levels of platelet endothelial cell adhesion molecule (CD31) expression. Conclusion: These above results might offer a practical and affordable product or method of skin wound therapy in a medical context.

Oncogenic DNA methyltransferase 1 activates the PI3K/AKT/mTOR signalling by blocking the binding of HSPB8 and BAG3 in melanoma.

Abnormal DNA methylation has been observed in multiple malignancies, including melanoma. In this study, we initially noticed the overexpression of DNA methyltransferase 1 (DNMT1) in melanoma samples in bioinformatics analysis and, subsequently, validated it in the purchased melanoma cell lines. After treatment with short-hairpin RNAs or Decitabine (a DNA methylation inhibitor), silencing of DNMT1 was demonstrated to suppress cell viability and invasive and migratory potentials as well as to augment apoptosis and autophagy in melanoma cells. To further explore the downstream mechanisms, we revealed that DNMT1 inhibited HSPB8 expression through augmenting HSPB8 methylation, thereby suppressing the binding between HSPB8 and BAG3. Then, we elucidated through a series of gain- and loss- of function assays that the interplay of HSPB8 and BAG3 blocked the PI3K/AKT/mTOR pathway, thereby repressing the malignant phenotypes of melanoma cells and contributing to melanoma cell apoptosis and autophagy. We further established a mouse model of melanoma and substantiated that DNMT1 enhanced the in vivo tumorigenesis of melanoma cells via activation of the PI3K/AKT/mTOR pathway through repressing the binding between HSPB8 and BAG3. Taken together, our data supported that DNMT1 repressed the binding between HSPB8 and BAG3 and activated the PI3K/AKT/mTOR pathway, thus playing a tumour-promoting role in melanoma.

NEAT1 in bone marrow mesenchymal stem cell-derived extracellular vesicles promotes melanoma by inducing M2 macrophage polarization.

Bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles (EVs) reportedly play an important role in melanoma pathogenesis. This study aimed to explore the mechanisms of EVs-carried long non-coding RNA (lncRNA) NEAT1 involvement in melanoma. Gain- and loss-of-function experiments were performed to determine biological characteristics of A-375 melanoma cells. Bioinfomatic prediction, RNA immunoprecipitation (RIP), and dual luciferase reporter gene experiments were applied to investigate the roles of NEAT1 and microRNA-374a-5p (miR-374a-5p), and leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4). A subcutaneous tumor model was constructed using nude mice, and in vivo fluorescence imaging was used to observe the effect of NEAT1 on the growth and metastasis of melanoma cells in vivo. The results indicated that BMSC-EVs could be internalized by macrophages to promote the expression of macrophages M2 markers. M2 type macrophages promoted malignancy of melanoma cells. NEAT1 derived from BMSC-EVs promoted the progression of melanoma by promoting M2 polarization of macrophages. NEAT1 inhibits miR-374 expression, while miR-374 could upregulate LGR4-dependent IQGAP1 expression. The tumor-inhibiting effect of NEAT1 silencing was validated in the nude mouse xenograft model. Collectively, the results demonstrated that BMSC-EVs carrying NEAT1 can promote the progression of melanoma by inducing M2 polarization of macrophages, and thus may be considered as a potential target for melanoma therapeutics.

Biomechanical study of the C5-C8 cervical extraforaminal ligaments.

BACKGROUND: The anatomical distribution of the extraforaminal ligaments in the cervical intervertebral foramina has been well studied. However, detailed descriptions of the biomechanical characteristics of these ligaments are lacking. METHODS: The paravertebral muscles were dissected, and the extraforaminal ligaments and nerve roots were identified. The C5 and C7 or C6 and C8 cervical nerve roots on both sides were randomly selected, and a window was opened on the vertebral lamina to expose the posterior spinal nerve root segments. Five needles were placed on the nerve root and the bone structure around the intervertebral foramen; the distal end of the nerve root was then tied with silk thread, and the weights were connected across the pulley. A weight load was gradually applied to the nerve root (50 g/time, 60 times in total). At the end of the experiment, segments of the extraforaminal ligaments were selectively cut off to compare the changes in nerve root displacement. RESULTS: The displacement of the C5, C6, C7, and C8 nerve roots increases with an increasing traction load, and the rate of change of nerve root displacement in the intervertebral foramen is smaller than that in the nerve root on the outside area (p < 0.05). Extraforaminal ligaments can absorb part of the pulling load of the nerve root; the C5 nerve root has the largest load range. CONCLUSIONS: Cervical extraforaminal ligaments can disperse the tension load on the nerve root and play a role in protecting the nerve root. The protective effect of the C5 nerve root was the strongest, and this may anatomically explain why the C5 nerve roots are less prone to simple avulsion.

MCM7 silencing promotes cutaneous melanoma cell autophagy and apoptosis by inactivating the AKT1/mTOR signaling pathway.

Cutaneous melanoma (CM) has become a major public health concern. Studies illustrate that minichromosome maintenance protein 7 (MCM7) participate in various diseases including skin disease. Our study aimed to study the effects of MCM7 silencing on CM cell autophagy and apoptosis by modulating the AKT threonine kinase 1 (AKT1)/mechanistic target of rapamycin kinase (mTOR) signaling pathway. Initially, microarray analysis was used to screen the CM-related gene expression data as well as differentially expressed genes. Subsequently, MCM7 expression vector and lentivirus RNA used for MCM7 silencing (LV-shRNA-MCM7) were constructed, and these vectors, dimethyl sulfoxide (DMSO) and AKT activator SC79 were then introduced into CM cell line SK-MEL-2 to validate the role of MCM7 in cell autophagy, viability, apoptosis, cell cycle, migration, and invasion. To further investigate the regulatory mechanisms of MCM7 in CM progress, the expression of MCM7, AKT1, mTOR, cyclin D1, as well as autophagy and apoptosis relative factors, such as LC3B, SOD2, DJ-1, p62, Bcl-2, Bax, and caspase-3 in melanoma cells was determined. MCM7 might mediate the AKT1/mTOR signaling pathway to influence the progress of melanoma. MCM7 silencing contributed to the increased expression of Bax, capase-3, and autophagy-related genes (LC3B, SOD2, and DJ-1), but decreased the expression of Bcl-2, which suggested that MCM7 silencing promoted autophagy and cell apoptosis. At the same time, MCM7 silencing also attenuated cell viability, invasion, and migration, and reduced the cyclin D1 expression and protein levels of p-AKT1 and p-mTOR. Taken together, MCM7 silencing inhibited CM via inactivation of the AKT1/mTOR signaling pathway.

Subcutaneous botulinum toxin-A injection for treating postherpetic neuralgia.

Postherpetic neuralgia (PHN) is a debilitating disease characterized by continuous, intense pain following an outbreak of herpes zoster. The pain associated with PHN can severely affect a patient's quality of life, quality of sleep, and ability to participate in activities of daily living. The aim of this study was to explore the clinical efficacy of the subcutaneous injection of botulinum toxin-A (BTX-A) for the treatment of PHN. Thirteen patients with PHN were enrolled in this study and treated once with BTX-A. The effects of BTX-A on pain were measured with the visual analogue scale (VAS) 1, 2, 4, 8, 12, and 16 weeks after administration. Compared with pretreatment scores, VAS pain scores decreased at 2 weeks post-treatment in all patients. All patients felt varying degrees of pain relief but remained comfortable. Compared with oral analgesic drugs, VAS scores were significantly different at 2, 4, 8, 12, and 16 weeks post-treatment (p < .05). These results demonstrated that subcutaneous administration of BTX-A can decrease pain in patients with PHN.

Photodynamic therapy combined with antifungal drugs against chromoblastomycosis and the effect of ALA-PDT on Fonsecaea in vitro.

BACKGROUND: Chromoblastomycosis is a chronic skin and subcutaneous fungal infection caused by dematiaceous fungi and is associated with low cure and high relapse rates. In southern China, Fonsecaea monophora and Fonsecaea pedrosoi are the main causative agents. PRINCIPAL FINDINGS: We treated 5 refractory and complex cases of chromoblastomycosis with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with oral antifungal drugs. The lesions improved after 4 to 9 sessions of ALA-PDT treatment at an interval of one or two weeks, and in some cases, mycological testing results became negative. The isolates were assayed for susceptibility to antifungal drugs and ALA-PDT in vitro, revealing sensitivity to terbinafine, itraconazole and voriconazole, with ALA-PDT altering the cell wall and increasing reactive oxygen species production. CONCLUSIONS: These results provide the basis for the development of a new therapeutic approach, and ALA-PDT combined with oral antifungal drugs constitutes a promising alternative method for the treatment of refractory and complex cases of chromoblastomycosis.

Human Chrysomya bezziana myiasis: A systematic review.

BACKGROUND: Myiasis due to Old World screw-worm fly, Chrysomya bezziana, is an important obligate zoonotic disease in the OIE-list of diseases and is found throughout much of Africa, the Indian subcontinent, southeast and east Asia. C. bezziana myiasis causes not only morbidity and death to animals and humans, but also economic losses in the livestock industries. Because of the aggressive and destructive nature of this disease in hosts, we initiated this study to provide a comprehensive understanding of human myiasis caused by C. bezziana. METHODS: We searched the databases in English (PubMed, Embase and African Index Medicus) and Chinese (CNKI, Wanfang, and Duxiu), and international government online reports to 6th February, 2019, to identify studies concerning C. bezziana. Another ten human cases in China and Papua New Guinea that our team had recorded were also included. RESULTS: We retrieved 1,048 reports from which 202 studies were ultimately eligible for inclusion in the present descriptive analyses. Since the first human case due to C. bezziana was reported in 1909, we have summarized 291 cases and found that these cases often occurred in patients with poor hygiene, low socio-economic conditions, old age, and underlying diseases including infections, age-related diseases, and noninfectious chronic diseases. But C. bezziana myiasis appears largely neglected as a serious medical or veterinary condition, with human and animal cases only reported in 16 and 24 countries respectively, despite this fly species being recorded in 44 countries worldwide. CONCLUSION: Our findings indicate that cryptic myiasis cases due to the obligate parasite, C. bezziana, are under-recognized. Through this study on C. bezziana etiology, clinical features, diagnosis, treatment, epidemiology, prevention and control, we call for more vigilance and awareness of the disease from governments, health authorities, clinicians, veterinary workers, nursing homes, and also the general public.

Clinical efficacy of paiteling in the treatment of condyloma acuminatum infected with different subtypes of HPV.

Condyloma acuminatum (CA) is a type of mucosal benign hyperplasia skin disease that is caused by human papillomavirus (HPV) infection, which mainly occurs in the genitalia and anus. The aim of the present study was to explore the clinical efficacy underlying the traditional Chinese medicine paiteling in the treatment of CA via the detection of HPV. One hundred CA patients were enrolled in the current study and were externally treated with paiteling for 5 weeks. HPV subtypes were examined both before the treatment and at 6 months after the treatment. After the external paiteling therapy, 92 cases were cured, and the apparent efficiency was 92.0% (92/100), while 8 cases exhibited recurrence. Before the external paiteling therapy, the numbers of cases of low-risk, high-risk, and mixed types of HPV were 40, 35, and 25, respectively. At 6 months after treatment, the numbers of negative cases of low-risk, high-risk, and mixed types of HPV were 38, 32, and 20, respectively. The results demonstrated that external paiteling treatment has a good curative effect on the treatment of CA.

[Long-pulsed 1064 nm Nd: YAG laser combined with terbinafine against chromoblastomycosis caused by Fonsecaea nubica and the effect of laser therapy in a Wistar rat model].

We report a case of chromoblastomycosis caused by Fonsecaea nubica, which was successfully treated by long-pulsed 1064 nm Nd: YAG laser combined with terbinafine. A 60-year-old man was admitted for the presence of a 30 mm×40 mm erythematous plaque on the dorsum of his right hand for about 10 months without any subjective symptoms. Both microscopic examination and tissue biopsy of the lesion showed characteristic sclerotic bodies of chromoblastomycosis. Lesion tissue culture on SDA at 26 ℃ for 2 weeks resulted in a black colony, and slide culture identified the isolate as Fonsecaea species. ITS sequence analysis of the isolate showed a 99% homology with F. nubica strain KX078407. The in vitro susceptibility of the isolate to 9 antifungal agents was determined using the microdilution method according to the guidelines of CLSI M38-A2 protocol, and terbinafine showed the lowest MIC (0.125 µg/ml). We subsequently established a Wistar rat model of chromoblastomycosis using the clinical isolate F. nubica and treated the rats with long-pulsed 1064 nm Nd: YAG laser (pulse width of 3.0 ms, fluence of 24 J/cm2, spot size of 3 mm, frequency of 4 Hz, repeated 3 times at an interval of 30 s) twice a week for a total of 8 sessions. Although the laser treatment alone was not able to eliminate the fungi, histopathological examination showed the aggregation of numerous lymphocytes in the local affected tissue, indicating an immune response that consequently facilitate the regression of the lesion. The patient was successfully treated by long-pulsed 1064 nm Nd: YAG laser once a week combined with terbinafine (0.25 /bid) for 8 weeks, and follow-up for 20 months did not reveal any signs of recurrence.

Anatomic morphology and clinical significance of intraforaminal ligaments of the cervical spine.

The cause of cervical spondylotic radiculopathy could be related to the intraforaminal ligaments (IFLs) of the cervical spine. The aim of this study is to identify and describe the IFLs and assess their clinical significance. Six intact cervical spine specimens from adult embalmed cadavers were dissected to expose the cervical nerve roots and their surrounding intraforaminal tissues fully. From the C1-C2 to the C7-T1 intervertebral foramina (IVF), the connective structures between each nerve root and its surrounding foraminal wall were examined under a surgical microscope. The morphology, number, and attachment points of the IFLs of each segment were documented, and the length, width, or diameter and thickness of the ligaments were measured with a vernier caliper. IFLs were observed in all 84 IVFs of the cervical spine. According to their locations, they can be divided into two categories: the first is entrance-zone IFLs, which are radially distributed around the nerve root; the second is mid-zone IFLs, which are thin, strip-shaped fibrous tissues intertwined around the nerve roots, the number of ligaments being considerable but difficult to quantify. Ligament structures have been identified in the IVF of the cervical spine. Under physiological conditions, they could be protective in maintaining the position, shape, and function of nerve roots. However, under pathological conditions, the IFLs of the cervical spine could aggravate the symptoms of cervical nerve root radicular pain associated with other types of compression. Clin. Anat. 32:654-660, 2019. © 2019 Wiley Periodicals, Inc.

[Effect of 0.9-ms 1064-nm Nd:YAG laser combined with itraconazole for treatment of toenail onychomycosis].

OBJECTIVE: To evaluate the efficacy and safety of 0.9-ms 1064-nm Nd:YAG laser alone or combined with itraconazole for treatment of toenail onychomycosis. METHODS: A total of 37 patients with onychomycosis (178 toenails) were randomly assigned to groups A and B, and each group was further divided into different subgroups according to the Scoring Clinical Index of Onychomycosis (SCIO) and Onychomycosis Severity Index (OSI) scoring. All the patients were treated with 0.9-ms Nd:YAG laser once a week for 8 times. The patients in group A were treated with laser alone, and those in group B were treated with laser combined with itraconazole. The clinical effect, clinical scores, appearance of the toenails and adverse reactions in the two groups were analyzed, and the patients' satisfaction rate was also investigated. RESULTS: At the 12th months of follow-up, the clinical response rate and mycological cure rate in group A were 31.33% and 30.00%, respectively, similar to the rates in group B (35.79% and 41.18%, respectively) (P>0.05). After the treatments, the SCIO and OSI scores showed no significant changes in group A (P>0.05) but both increased significantly in group B (P<0.05). The response rates did not differ significantly among the subgroups with SCIO<12 or with OSI<16 (P>0.05), but showed significant differences among the subgroups with SCIO≥12 or with OSI≥16 (P<0.05). Of the total of 178 toenails, 33.71%, 74.72% and 70.79% toenails showed improvements in terms of clear nail growth, shape and color, respectively. The overall patients' satisfaction rate was 62.16%, and no adverse reactions related with the therapy were recorded in these patients. CONCLUSION: For treatment of toenail onychomycosis, 0.9-ms 1064-nm Nd:YAG laser can effectively improve the aesthetic appearance of the toenails, and a combined treatment with Nd:YAG laser and itraconazole can be better option in severe cases of onychomycosis.

A Case Report of Widespread Majocchi's Granuloma in a Patient with Systemic Lupus Erythematosus.

Majocchi's granuloma is an intracutaneous or subcutaneous granulomatous inflammation caused by invasion of dermatophytic fungus, especially Trichophyton rubrum. This type of lesion is misdiagnosed frequently without proper auxiliary examination. Here, we report a case of widespread Majocchi's granuloma caused by T. rubrum in a 35-year-old woman with systemic lupus erythematosus for 9 years. The patient was initially misdiagnosed as SLE-associated skin lesions, which delayed her treatment and resulted in severe multiple disseminated lesions. After confirmed as Majocchi's granuloma, the patient was cured after 11-month treatment with terbinafine.

[Efficacy and safety of long pulse 1064 nm Nd:YAG laser for treatment of onychomycosis of the toenails].

OBJECTIVE: To evaluate the efficacy and safety of long pulse 1064 nm Nd:YAG laser therapy in the treatment of onychomycosis of the toenails. METHODS: A total of 104 patients with onychomycosis (461 toenails) were divided by age into ≥60 years group and <60 years group, and each group was further divided into subgroups according to Scoring Clinical Index of Onychomycosis (SCIO) scoring and the location of the compromised toenails. All the toenails were treated with 10 to12 sessions of long pulse 1064 nm Nd:YAG laser therapy at the interval of 1 week. All the patients were followed up for 48 weeks after the initial treatment to assess the clinical efficacy and adverse reactions. RESULTS: The overall clinical response rate in these patients was 72.5% by the end of the 48-week follow-up. In patients aged <60 years, the clinical response rate and mycological cure rate were significantly higher than the rates in patients aged ≥60 years (P<0.05). No significant differences were observed in the response rates between different SCIO subgroups (P>0.05); the 2nd to 4th toenails showed better outcomes after the therapy than the 1st and 5th toenails (P<0.05). No adverse reactions related with the therapy were recorded in these patients. CONCLUSION: Long pulse 1064 nm Nd:YAG laser is an effective and safe approach for treatment of onychomycosis of the toenails.