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Holistic Approach in the Treatment of Actinic Keratosis: Benefits and Disadvantages of 5-Fluorouracil, Imiquimod, Diclofenac and Curaderm
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作者 Bill Elliot Cham 《International Journal of Clinical Medicine》 2023年第7期319-331,共13页
Background Actinic keratosis is the most prevalent premalignant skin disorder in the white population. Current guidelines provide no clear recommendations about preferred treatments. Methods The parameters;effectivene... Background Actinic keratosis is the most prevalent premalignant skin disorder in the white population. Current guidelines provide no clear recommendations about preferred treatments. Methods The parameters;effectiveness, treatment duration, recurrence, side effects and cost of treatment were investigated for three frequently used topical therapies which were then compared with a most recent developed topical therapy. Published clinical data obtained from the literature was used to compare these parameters for 5-fluorouracil, imiquimod and diclofenac and relate them with the newly developed Curaderm. Results A wide variation in the concentrations of the active anti-keratotic ingredients, application frequency, duration of treatment, recurrence rates and cost of treatment exist between the different topical therapies. The efficacy rates and side effects were less variable. Overall, Curaderm is the most suitable treatment for actinic keratosis. Clinical evidence is presented illustrating the effects of Curaderm on field-directed treatments and solitary treatments of actinic keratoses. Conclusions Current medical guidelines do not provide clear recommendations on which treatment approach for actinic keratosis is preferred. Direct head-to-head comparison between treatments with emphasis on efficacy, safety, treatment duration, compliance, convenience, cosmetic outcome, patient acceptance and cost should be available to the patient, the practising physician, healthcare system and should assist in therapeutic treatment guidelines and policymaking. Given the very favourable profiles of these parameters with Curaderm when compared with other home-based treatments, it should be considered that Curaderm is first-in-line. 展开更多
关键词 actinic Keratosis Skin Cancer 5-FLUOROURACIL IMIQUIMOD DICLOFENAC Curaderm EFFICACY RECURRENCE Cost
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Solasodine Glycosides: A Topical Therapy for Actinic Keratosis. A Single-Blind, Randomized, Placebo-Controlled, Parallel Group Study with Curaderm<sup>BEC5</sup> 被引量:3
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作者 Bill E. Cham 《Journal of Cancer Therapy》 2013年第2期588-596,共9页
Background: Untreated actinic keratosis can advance to squamous cell carcinoma, which in turn is associated with a risk of metastasis. Current treatments for actinic keratosis have many shortcomings. This communicatio... Background: Untreated actinic keratosis can advance to squamous cell carcinoma, which in turn is associated with a risk of metastasis. Current treatments for actinic keratosis have many shortcomings. This communication describes the efficacy and safety of a topical cream therapy, CuradermBEC5, containing solasodine glycosides (0.005%) for actinic keratosis.Methods: Randomly assigned patients with actinic keratosis on the face, trunk or extremities received so-lasodine glycosides cream (CuradermBEC5) or placebo (vehicle) that was self-applied to the lesions and covered with an occlusive dressing (micropore) twice daily for 3 consecutive days. Complete clearance and local reactions were as-sessed at 56 days with follow-up periods of 6 months and 1 year. Results: The rate of complete clearance at day 56 was higher with solasodine glycosides than with placebo (92% vs. 38%, P 0.001). The absolute success rates after 1 year follow-up were 82% for solasodine glycosides and 18% for placebo. No differences in local reactions were obtained when solasodine glycosides and placebo were compared. Local reactions in both groups peaked at days 2 and 3 with local pain as the major event. The pain associated with treatments lasted approximately 10 minutes after application of solasodine glycosides and placebo. Complete reepithelialization occurred two weeks after treatment. Adverse events were generally mild to moderate in intensity and resolved without sequelae. Conclusions: Solasodine glycosides cream applied topically twice daily with a dressing for 3 days is effective for the treatment of actinic keratoses. 展开更多
关键词 SOLASODINE GLYCOSIDES SOLAMARGINE Solasonine actinic KERATOSIS Apoptosis Skin Cancer Clinical Trial CuradermBEC5
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Actinic prurigo of the lip: Two case reports 被引量:1
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作者 Ana MO Miranda Thiago M Ferrari +3 位作者 Juliana T Werneck Arley Silva Junior Karin S Cunha Eliane P Dias 《World Journal of Clinical Cases》 SCIE 2014年第8期385-390,共6页
Actinic prurigo is a photodermatosis that can affect the skin, conjunctiva and lips. It is caused by an abnormal reaction to sunlight and is more common in high-altitude living people, mainly in indigenous descendants... Actinic prurigo is a photodermatosis that can affect the skin, conjunctiva and lips. It is caused by an abnormal reaction to sunlight and is more common in high-altitude living people, mainly in indigenous descendants. The diagnosis of actinic prurigo can be challenging, mainly when lip lesions are the only manifestation, which is not a common clinical presentation. The aim of this article is to report two cases of actinic prurigo showing only lip lesions. The patients were Afro-American and were unaware of possible Indian ancestry. Clinical exam, photographs, videoroscopy examination and biopsy were performed, and the diagnosis of actinic prurigo was established. Topical corticosteroid and lip balm with ultraviolet protection were prescribed with excellent results. The relevance of this report is to show that although some patients may not demonstrate the classical clinical presentation of actinic prurigo, the associated clinical and histological exams are determinants for the correct diagnosis and successful treatment of this disease. 展开更多
关键词 actinic PRURIGO FOLLICULAR CHEILITIS PHOTODERMATOSIS HIGH-ALTITUDE LIP diseases
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Expression of matrix metalloproteinases 9 and 12 in actinic cheilitis 被引量:1
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作者 Athanasios K Poulopoulos Dimitrios Andreadis Anastasios K Markopoulos 《World Journal of Experimental Medicine》 2013年第3期43-49,共7页
AIM: To investigate the role of matrix-degrading metalloproteinases 9, 12(MMPs), as mediators of functional connective tissue damage in actinic cheilitis.METHODS: Thirty five formalin-fixed, paraffin embedded specimen... AIM: To investigate the role of matrix-degrading metalloproteinases 9, 12(MMPs), as mediators of functional connective tissue damage in actinic cheilitis.METHODS: Thirty five formalin-fixed, paraffin embedded specimens of actinic cheilitis, and twelve specimens of normal lower lip vermillion, which were obtained by the archives of the Department of Oral Medicine and Maxillofacial Pathology, were examined. From each block, 5 μm thick sections were cut and routinely stained with Hematoxylin and Eosin. Immunohistochemical studies were performed on 4-μm thick sections of formalin-fixed paraffin embedded actinic cheilitis lesions and of normal lower lip vermillion, for MMP-9 and MMP-12 in serial sections of our specimens. Appropriate positive and negative controls were performed to confirm the specificity of the staining reaction. MMP immunohistochemistry was evaluated using a semiquantitative immunoreactive score.RESULTS: Haematoxylin and eosin staining revealedin actinic cheilitis lesions atrophic stratified squamous cell epithelium, or focally and irregularly hyperplastic of variable thickness, in some areas was observed marked keratin production. Varying degrees of epithelial dysplasia were noticed with a wide spectrum of change within the same specimen. Characteristic was the appearance of chronic inflammatory infiltration, and a band of amorphous acellular, basophilic change like solar elastosis(elastin replacement of collagen). In normal lower lip specimens weak and scanty positive expression of MMP-9 and MMP-12 was observed. Anti-MMP-9 antibody showed a weak reaction, in actinic cheilitis lesions, focal in the elastotic material, in chronic inflammatory cells and mostly in macrophages and neutrophils. Strong and in some cases diffused immunohistochemical expression of MMP-12 was detected in actinic cheilitis lesions in the areas of the fragmented, distorted and thickened elastic fibers. MMP-12 was also expressed in chronic inflammatory cells and mostly macrophages. MMP-12 was significantly higher in actinic cheilitis specimens compared with the normal lower lip specimens(P = 0.0029).CONCLUSION: Our results suggest that especially MMP-12 may play an important role in remodeling events occurring in the connective tissue during long-term exposure to sunlight in the actinic cheilitis lesions. 展开更多
关键词 actinic CHEILITIS Metalloproteinase-9 Metalloproteinase-12 IMMUNOHISTOCHEMISTRY
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Factors influencing response to ingenol mebutate therapy for actinic keratosis of face and scalp
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作者 Nevena Skroza Ilaria Proietti +7 位作者 Nicoletta Bernardini Veronica Balduzzi Alessandra Mambrin Anna Marchesiello Ersilia Tolino Sara Zuber Giuseppe La Torre Concetta Potenza 《World Journal of Clinical Oncology》 CAS 2017年第5期405-411,共7页
AIM To determine factors independently influencing response to ingenol mebutate therapy and assess efficacy on clinical setting of non-hypertrophic non-hyperkeratotic actinic keratosis (AK).METHODS Consecutive patient... AIM To determine factors independently influencing response to ingenol mebutate therapy and assess efficacy on clinical setting of non-hypertrophic non-hyperkeratotic actinic keratosis (AK).METHODS Consecutive patients affected by non-hypertrophic non-hyperkeratotic AKs of the face or scalp were enrolled to receive ingenol mebutate 0.015% gel on a selected skin area of 25 cm^2 for 3 consecutive days.Local skin reactions were calculated at each follow up visit using a validated composite score.Efficacy was evaluated by the comparison of clinical and dermoscopic pictures before the treatment and at day 57,and classified as complete,partial and poor response.RESULTS A number of 130 patients were enrolled,of which 101(77.7%) were treated on the face,while 29 (22.3%) on the scalp.The great majority of our study population (n = 119,91.5%) reached at least a 75% clearance of AKs and,in particular,58 patients (44.6%) achieved a complete response while 61(46.9%) a partial one.Logistic backward multivariate analysis showed that facial localization,level of local skin reaction (LSR) at day 2,the highest LSR values and level of crusts at day 8 were factors independently associated with the achievement of a complete response.CONCLUSION Ingenol mebutate 0.015% gel,when properly applied,is more effective on the face than on the scalp and efficacy is directly associated to LSR score. 展开更多
关键词 Ingenol mebutate actinic KERATOSIS FACIAL and SCALP LESIONS SKIN REACTIONS Dermoscopic feature
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Effects of a New Human Recombinant MnSOD in the Treatment of Photoaging and Actinic Keratosis
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作者 Maria Grazia Ruggiero Maria Laura Pollio +4 位作者 Antonietta Schiattarella Antonella Borrelli Aldo Mancini Alessandra Pica Patrizia Forgione 《Journal of Cancer Therapy》 2013年第6期56-59,共4页
Physiological processes, as aerobic metabolism and inflammatory response, generate reactive oxygen species (ROS) that may induce cellular injury when their amount is increased and antioxidant defense mechanisms are ov... Physiological processes, as aerobic metabolism and inflammatory response, generate reactive oxygen species (ROS) that may induce cellular injury when their amount is increased and antioxidant defense mechanisms are overwhelmed. Also, ROS are generated following UV skin irradiation able to deplete the natural antioxidant defenses in the skin. The increase in exposure to UV may lead to photoaging and precancerous skin lesions (actinic keratosis). New antioxidant strategies in the prevention and therapy of skin lesions are urgently needed. In this study, we evaluated the antioxidant efficacy of a recombinant form of human manganese superoxide dismutase able to inhibit reactive oxygen species production in some patients affected by severe photoaging and actinic keratosis. 展开更多
关键词 PHOTOAGING actinic KERATOSIS MNSOD SKIN Cancer LESIONS
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Actinic lichen planus: a presentation, deviant from the conventional
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作者 Anupama Ghosh Anupam Das +1 位作者 Dhiraj Kumar Ramesh Chandra Gharami 《World Journal of Dermatology》 2014年第1期4-5,共2页
Actinic lichen planus, a variant of lichen planus usually in people living in the tropics, presents as annular or discoid patches over the sun-exposed regions. We present here a case of actinic lichen planus with papu... Actinic lichen planus, a variant of lichen planus usually in people living in the tropics, presents as annular or discoid patches over the sun-exposed regions. We present here a case of actinic lichen planus with papules and plaques over the malar region and dorsum of nose- a rare presentation of this entity. 展开更多
关键词 actinic LICHEN Planus UNUSUAL PRESENTATION
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Basosquamous Cell Carcinoma of the Lower Lip Arising from Actinic Cheilitis: Case Report and up Date
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作者 Ana Maria de Oliveria Miranda Thiago de Miranda Ferrari +3 位作者 Daniel Cohen Goldemberg Luciana Pantaleao Andrea Pires Eliane Pedra Dias 《International Journal of Clinical Medicine》 2013年第12期21-24,共4页
Background: Basosquamous carcinoma (BSC) is a rare non-melanoma skin cancer, considered to be a subtype of basal cell carcinoma (BCC). BSC often produces distant metastases with a higher risk of recurrence than that o... Background: Basosquamous carcinoma (BSC) is a rare non-melanoma skin cancer, considered to be a subtype of basal cell carcinoma (BCC). BSC often produces distant metastases with a higher risk of recurrence than that of BCC which is not commonly found in the lip. Case Report: A 57-year-old white female patient presented an ulcer on her lower lip that had an ongoing development for over six months. Physical examination, photo documentation, videoroscopy, scraped cytology, toluidine blue test, and biopsy of the ulcer were carried out. Results: Upon physical examination we observed an actinic cheilitis associated with the ulcer. Videoroscopy revealed the presence of fissures and erosion that had not been seen by oroscopy. Toluidine blue test was only positive for the region of the ulcer. Cytological analysis revealed rare nests compatible with carcinoma. Histopathology of the biopsy revealed a carcinoma with nests lined by basal cells associated with areas of squamous differentiation. The patient was then referred to surgery for the removal of the BCC. Analysis of the specimen showed free surgical margins and the immunohistochemical panel did not confirm the initial diagnosis of BCC, indicating a subtype of BSC. After surgery, the patient has been followed by periodic consultations. She is well and without further complications. Coments: BSC is considered to be an aggressive and rare tumor affecting mainly upper face and primarily affects men over 60 years of age. Since our patient is a woman presenting the lesion in the lower lip, this highlights the unusual and interesting presentation of this case report. 展开更多
关键词 Basosquamous Carcinoma LIP actinic Cheilitis Basal Cell Carcinoma
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Actinic Superficial Folliculitis after Sun Exposure in a 29-Year-Old Woman
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作者 Rute Lopes Caçola Pedro Caiano Gil 《Case Reports in Clinical Medicine》 2016年第4期115-119,共5页
The authors report the clinical case of a 29-year-old Caucasian woman who presented with clinicopathological findings and a previous outbreak all suggestive of actinic superficial folliculitis, a rarely reported and p... The authors report the clinical case of a 29-year-old Caucasian woman who presented with clinicopathological findings and a previous outbreak all suggestive of actinic superficial folliculitis, a rarely reported and probably misdiagnosed phototoxic sun-induced dermatosis first described by Nieboer in 1985. Despite the exuberance of this cutaneous eruption, it is usually auto-limited, reinforcing the importance of its knowledge, for eviction of unnecessary diagnostic tests and therapies. Mechanisms of pathogenesis postulated include ultraviolet A radiation and local heat. This photodermatosis presents as monomorphic, superficial, pustular, and non-pruritic folliculitis affecting the upper body but not the face, usually arising on neck, back, shoulders and upper trunk. The follicular pustules emerge 24 - 72 h after intense exposure to heat and/or sunlight and fade spontaneously in 5 - 10 days, without scarring. This patient showed a 48-hour latency period;the number of pustules and area of the body affected were proportional to the duration of the sunlight exposure;the eruption lasted approximately 10 days. Actinic superficial folliculitis has a specific histology with follicular subcorneal sterile pustules and a mixed inflammatory infiltrate around hair follicles, probably secondary to keratinocytes and Langerhans cells involvement in the immunomodulatory actions of ultraviolet radiation. Recurrence under identical conditions may occur, after a latency period of at least 4 weeks, but usually about 1 year. Actinic superficial folliculitis and related follicular conditions are probably underdiagnosed and subsequently there is insufficient scientific information available to clinicians. Being familiar with these entities is of the utmost importance, since it can be crucial for their management. 展开更多
关键词 actinic Superficial Folliculitis Subcorneal Sterile Pustules Sun Exposure PHOTODERMATOSIS
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Actinic Cheilitis: Clinical Characteristics Observed in 75 Patients and a Summary of the Literature of This Often Neglected Premalignant Disorder
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作者 Ana Maria de Oliveira Miranda Thiago de Miranda Ferrari +2 位作者 Taiana Campos Leite Karin Soares Goncalves Cunha Eliane Pedra Dias 《International Journal of Clinical Medicine》 2014年第21期1337-1344,共8页
Actinic cheilitis can progress to squamous cell carcinoma in 20% of cases. The purpose of this study was to identify the clinical characteristics of 75 patients with actinic cheilitis and to summarise the current lite... Actinic cheilitis can progress to squamous cell carcinoma in 20% of cases. The purpose of this study was to identify the clinical characteristics of 75 patients with actinic cheilitis and to summarise the current literature concerning actinic cheilitis. A total of 75 patients were evaluated over a 3-year period. The medical history, physical examination results and images were collected from each patient. Demographic data were collected and analysed. To review the literature, the relevant data were collected from scientific journals in the last 30 years. The mean age of the patients was 56 years old;42 patients (56%) were female, and 66 patients (88%) were white. Nineteen (25.3%) patients reported at least one symptom, including pain, burning and itching. Sixty-five (86.7%) patients presented actinic cheilitis only in the lower lip. All of the patients reported sun exposure, and 44 (58.6%) patients were exposed for more than 10 years. The main clinical aspects investigated and analysed included dryness (100%), flaking (72%) and white lesions (57.3%). Lip assessment is extremely important in medical and dental care. From the 15 lesions assessed in the presence of actinic cheilitis, the most common clinical characteristics observed were dryness, flaking and white lesions. It is imperative to know the clinical aspects that may be encountered in actinic cheilitis in order to achieve early diagnosis, thus avoiding lip squamous cell carcinoma transformation. 展开更多
关键词 actinic Cheilitis Lip Cancer Sun Exposure Premalignant Disorder
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Actinic keratosis and field cancerization
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作者 Selma Emre 《World Journal of Dermatology》 2016年第2期115-124,共10页
While actinic keratoses(AKs) have been considered precancerous until recently for being able to turn into squamous cell carcinomas(SCCs), it is now agreed that it would be more appropriate to call them cancerous. Alth... While actinic keratoses(AKs) have been considered precancerous until recently for being able to turn into squamous cell carcinomas(SCCs), it is now agreed that it would be more appropriate to call them cancerous. Although not all AKs turn into SCC and some of them may even have a spontaneous regression, there is an obvious association between SCC and AK. Approximately 90% of SCs have been reported to develop from AKs and AKs are the preinvasive form of SCCs. The presence of two or more AKs on a photodamaged skin is an indicator of field cancerization and represents an increased risk of invasive SCC. All lesions should be treated since it cannot be foreseen which of the lesions will regress and which will progress to SCC. AK can be a single lesion or it can involve multiple lesions in a field of cancerization; thus, AK treatment is grouped under two headings:(1) Lesion-specific treatment; and (2) Field-targeted treatment. Lesion-specific treatments are practicable in patients with a small number of clinically visible and isolated lesions. These treatments including cryotherapy, surgical excision, shave excision, curettage and laser are based on physical destruction of the visible lesions. Field-targeted treatments are effective in the treatment of visible lesions, subclinical lesions and keratinocyte changes in the areas surrounding the visible lesions. Field targeted treatment options are topical imiquimod cream, 5% 5-fluorouracil cream, ingenol mebutate, diclofenac gel, resimiquimod and photodynamic therapy. 展开更多
关键词 actinic keratosis Squamous cell carcinoma in situ Field cancerization
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The Value of Excipients and the Required Understanding of the Biological System in Product Development: An Impactful Example of Curaderm, a Topical Skin Cancer Treatment
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作者 Tania Robyn Chase Kai Elliot Cham Bill Elliot Cham 《International Journal of Clinical Medicine》 CAS 2024年第2期68-87,共20页
The incidences of nonmelanoma skin cancer are increasing worldwide, and the ongoing war on its treatment necessitates the development of effective and non-invasive methods. Through basic and clinical research, non-inv... The incidences of nonmelanoma skin cancer are increasing worldwide, and the ongoing war on its treatment necessitates the development of effective and non-invasive methods. Through basic and clinical research, non-invasive treatments like Curaderm have been developed, leading to improved quality of life for patients. Excipients, previously considered inactive ingredients, play a crucial role in enhancing the performance of topical formulations. The development of Curaderm emphasizes the importance of understanding the interactions between active ingredients, excipients, and the biological system to create effective and affordable pharmaceutical formulations. The systematic approach taken in the development of Curaderm, starting from the observation of the anticancer activity of natural solasodine glycosides and progressing through toxicological and efficacy studies in cell culture, animals, and humans, has provided insights into the pharmacokinetics and pharmacodynamics of solasodine glycosides. It is crucial to determine these pharmacological parameters within the skin’s biological system for maximal effectiveness and cost-effectiveness of a skin cancer treatment. Curaderm, as a topical treatment for nonmelanoma skin cancer, offers benefits beyond those obtained from other topical treatments, providing hope for improved quality of life for patients. 展开更多
关键词 Curaderm BEC Solasodine Glycosides SOLAMARGINE Apoptosis Skin Cancer actinic Keratosis KERATOACANTHOMA Basal Cell Carcinoma Squamous Cell Carcinoma
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Gold Standard for Skin Cancer Treatment: Surgery (Mohs) or Microscopic Molecular-Cellular Therapy (Curaderm)?
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作者 Bill Elliot Cham 《Journal of Cancer Therapy》 2024年第2期33-47,共15页
Non-melanoma skin cancers or keratinocyte cancers such as basal cell carcinoma and squamous cell carcinoma make up approximately 80% and 20% respectively, of skin cancers with the 6 million people that are treated ann... Non-melanoma skin cancers or keratinocyte cancers such as basal cell carcinoma and squamous cell carcinoma make up approximately 80% and 20% respectively, of skin cancers with the 6 million people that are treated annually in the United States. 1 in 5 Americans and 2 in 3 Australians develop skin cancer by the age of 70 years and in Australia it is the most expensive, amassing $1.5 billion, to treat cancers. Non-melanoma skin cancers are often self-detected and are usually removed by various means in doctors’ surgeries. Mohs micrographic surgery is acclaimed to be the gold standard for the treatment of skin cancer. However, a novel microscopic molecular-cellular non-invasive topical therapy described in this article, challenges the status of Mohs procedure for being the acclaimed gold standard. 展开更多
关键词 Skin Cancer Basal Cell Carcinoma Squamous Cell Carcinoma Mohs Surgery Microscopic Molecular-Cellular Curaderm actinic Keratosis COSMESIS
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PCDH17 restricts dendritic spine morphogenesis by regulating ROCK2-dependent control of the actin cytoskeleton,modulating emotional behavior 被引量:1
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作者 Laidong Yu Fangfang Zeng +14 位作者 Mengshu Fan Kexuan Zhang Jingjing Duan Yalu Tan Panlin Liao Jin Wen Chenyu Wang Meilin Wang Jialong Yuan Xinxin Pang Yan Huang Yangzhou Zhang Jia-Da Li Zhuohua Zhang Zhonghua Hu 《Zoological Research》 SCIE CSCD 2024年第3期535-550,共16页
Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of posts... Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric disorders.Protocadherin 17(PCDH17)is associated with major mood disorders,including bipolar disorder and depression.However,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain elusive.In this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory neurons.Selective overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in mice.Mechanistically,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)organization.Specifically,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development.Hence,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders. 展开更多
关键词 Synapse development Dendritic spine Mood disorder Actin cytoskeleton Animal behavior
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Scinderin promotes glioma cell migration and invasion via remodeling actin cytoskeleton 被引量:1
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作者 Xin Lin Zhao Zhao +1 位作者 Shu-Peng Sun Wei Liu 《World Journal of Clinical Oncology》 2024年第1期32-44,共13页
BACKGROUND Glioma is one of the most common intracranial tumors,characterized by invasive growth and poor prognosis.Actin cytoskeletal rearrangement is an essential event of tumor cell migration.The actin dynamics-rel... BACKGROUND Glioma is one of the most common intracranial tumors,characterized by invasive growth and poor prognosis.Actin cytoskeletal rearrangement is an essential event of tumor cell migration.The actin dynamics-related protein scinderin(SCIN)has been reported to be closely related to tumor cell migration and invasion in several cancers.AIM To investigate the role and mechanism of SCIN in glioma.METHODS The expression and clinical significance of SCIN in glioma were analyzed based on public databases.SCIN expression was examined using real-time quantitative polymerase chain reaction and Western blotting.Gene silencing was performed using short hairpin RNA transfection.Cell viability,migration,and invasion were assessed using cell counting kit 8 assay,wound healing,and Matrigel invasion assays,respectively.F-actin cytoskeleton organization was assessed using F-actin staining.RESULTS SCIN expression was significantly elevated in glioma,and high levels of SCIN were associated with advanced tumor grade and wild-type isocitrate dehydrogenase.Furthermore,SCIN-deficient cells exhibited decreased proliferation,migration,and invasion in U87 and U251 cells.Moreover,knockdown of SCIN inhibited the RhoA/focal adhesion kinase(FAK)signaling to promote F-actin depolymerization in U87 and U251 cells.CONCLUSION SCIN modulates the actin cytoskeleton via activating RhoA/FAK signaling,thereby promoting the migration and invasion of glioma cells.This study identified the cancer-promoting effect of SCIN and provided a potential therapeutic target for the treatment of glioma. 展开更多
关键词 GLIOMA Scinderin Actin cytoskeleton RhoA/FAK signaling DEPOLYMERIZATION
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Dynamics of perinuclear actin ring regulating nuclear morphology
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作者 Haoxiang YANG Houbo SUN +2 位作者 Jinghao SHEN Hao WU Hongyuan JIANG 《Applied Mathematics and Mechanics(English Edition)》 SCIE EI CSCD 2024年第8期1415-1428,共14页
Cells are capable of sensing and responding to the extracellular mechanical microenvironment via the actin skeleton.In vivo,tissues are frequently subject to mechanical forces,such as the rapid and significant shear f... Cells are capable of sensing and responding to the extracellular mechanical microenvironment via the actin skeleton.In vivo,tissues are frequently subject to mechanical forces,such as the rapid and significant shear flow encountered by vascular endothelial cells.However,the investigations about the transient response of intracellular actin networks under these intense external mechanical forces,their intrinsic mechanisms,and potential implications are very limited.Here,we observe that when cells are subject to the shear flow,an actin ring structure could be rapidly assembled at the periphery of the nucleus.To gain insights into the mechanism underlying this perinuclear actin ring assembly,we develop a computational model of actin dynamics.We demonstrate that this perinuclear actin ring assembly is triggered by the depolymerization of cortical actin,Arp2/3-dependent actin filament polymerization,and myosin-mediated actin network contraction.Furthermore,we discover that the compressive stress generated by the perinuclear actin ring could lead to a reduction in the nuclear spreading area,an increase in the nuclear height,and a decrease in the nuclear volume.The present model thus explains the mechanism of the perinuclear actin ring assembly under external mechanical forces and suggests that the spontaneous contraction of this actin structure can significantly impact nuclear morphology. 展开更多
关键词 mechanical force actin dynamics perinuclear actin ring compressive stress NUCLEUS
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Dietary xylo‑oligosaccharides and arabinoxylans improved growth efficiency by reducing gut epithelial cell turnover in broiler chickens
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作者 Carla Castro Shahram Niknafs +3 位作者 Gemma Gonzalez‑Ortiz Xinle Tan Michael R.Bedford Eugeni Roura 《Journal of Animal Science and Biotechnology》 SCIE CAS CSCD 2024年第3期1325-1335,共11页
Background One of the main roles of the intestinal mucosa is to protect against environmental hazards.Supple-mentation of xylo-oligosaccharides(XOS)is known to selectively stimulate the growth of beneficial intestinal... Background One of the main roles of the intestinal mucosa is to protect against environmental hazards.Supple-mentation of xylo-oligosaccharides(XOS)is known to selectively stimulate the growth of beneficial intestinal bacteria and improve gut health and function in chickens.XOS may have an impact on the integrity of the intestinal epithelia where cell turnover is critical to maintain the compatibility between the digestive and barrier functions.The aim of the study was to evaluate the effect of XOS and an arabinoxylan-rich fraction(AXRF)supplementation on gut func-tion and epithelial integrity in broiler chickens.Methods A total of 128 broiler chickens(Ross 308)were assigned into one of two different dietary treatments for a period of 42 d:1)control diet consisting of a corn/soybean meal-based diet;or 2)a control diet supplemented with 0.5%XOS and 1%AXRF.Each treatment was randomly distributed across 8 pens(n=8)with 8 chickens each.Feed intake and body weight were recorded weekly.On d 42,one male chicken per pen was selected based on aver-age weight and euthanized,jejunum samples were collected for proteomics analysis.Results Dietary XOS/AXRF supplementation improved feed efficiency(P<0.05)from d 1 to 42 compared to the con-trol group.Proteomic analysis was used to understand the mechanism of improved efficiency uncovering 346 dif-ferentially abundant proteins(DAP)(Padj<0.00001)in supplemented chickens compared to the non-supplemented group.In the jejunum,the DAP translated into decreased ATP production indicating lower energy expenditure by the tissue(e.g.,inhibition of glycolysis and tricarboxylic acid cycle pathways).In addition,DAP were associated with decreased epithelial cell differentiation,and migration by reducing the actin polymerization pathway.Put-ting the two main pathways together,XOS/AXRF supplementation may decrease around 19%the energy required for the maintenance of the gastrointestinal tract.Conclusions Dietary XOS/AXRF supplementation improved growth efficiency by reducing epithelial cell migration and differentiation(hence,turnover),actin polymerization,and consequently energy requirement for maintenance of the jejunum of broiler chickens. 展开更多
关键词 ACTIN ARABINOXYLANS BROILER Cell turnover Energy metabolism JEJUNUM Xylo-oligosaccharides
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The interaction between KIF21A and KANK1 regulates dendritic morphology and synapse plasticity in neurons
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作者 Shi-Yan Sun Lingyun Nie +5 位作者 Jing Zhang Xue Fang Hongmei Luo Chuanhai Fu Zhiyi Wei Ai-Hui Tang 《Neural Regeneration Research》 SCIE CAS 2025年第1期209-223,共15页
Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at th... Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains unknown.In this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines.Furthermore,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity.Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1.Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive abilities.Taken together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function. 展开更多
关键词 ACTIN CYTOSKELETON dendrite KANK1 KIF21A MICROTUBULE spine morphology SPINE synaptic plasticity talin1
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Suppression of hepatic steatosis in non-alcoholic steatohepatitis model by modified Xiaoyao San formula:Evidence,mechanisms and perspective
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作者 Nabil Eid Payal Bhatnagar +1 位作者 Li-Li Chan Marina Garcia-Macia 《World Journal of Hepatology》 2024年第10期1208-1212,共5页
In this letter,we comment on a recent publication by Mei et al,in the World Journal of Hepatology,investigating the hepatoprotective effects of the modified Xiaoyao San(MXS)formula in a male rat model of non-alcoholic... In this letter,we comment on a recent publication by Mei et al,in the World Journal of Hepatology,investigating the hepatoprotective effects of the modified Xiaoyao San(MXS)formula in a male rat model of non-alcoholic steatohepatitis(NASH).The authors found that MXS treatment mitigated hepatic steatosis and inflam-mation in the NASH model,as evidenced by the reduction in lipid droplets(LDs),fibrosis markers and lipogenic factors.Interestingly,these hepatoprotective effects were associated with androgen upregulation(based on metabolomics analysis of male steroid hormone metabolites),adenosine 5’-monophosphate-activated protein kinase(AMPK)activation,and restoration of phosphatase and tensin homolog(PTEN)expression.However,the authors did not clearly discuss the relationships between MXS-induced hepatic steatosis reduction in the NASH model,and androgen upregulation,AMPK activation,and restoration of PTEN expression.This editorial emphasizes the reported mechanisms and explains how they act or interact with each other to reduce hepatic steatosis and inflammation in the NASH model.As a perspective,we propose additional mechanisms(such as autophagy/lipophagy activation in hepatocytes)for the clearance of LDs and suppression of hepatic steatosis by MXS in the NASH model.A proper understanding of the mechanisms of MXS-induced reduction of hepatic steatosis might help in the treatment of NASH and related diseases. 展开更多
关键词 STEATOSIS Liver Xiaoyao San Inflammation ANDROGEN Adenosine 5’-monophosphate-activated protein kinase Phosphatase and tensin homolog Autophagy Lipophagy Alpha smooth muscle actin
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New targets for cancer promotion and therapy in gliomas: Scinderin
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作者 Xi Wang Lian-Xiang Luo 《World Journal of Clinical Oncology》 2024年第6期687-690,共4页
Glioma is one of the most common primary intracranial tumors,characterized by invasive growth and poor prognosis.Actin cytoskeletal rearrangement is an essential event in tumor cell migration.Scinderin(SCIN),an actin ... Glioma is one of the most common primary intracranial tumors,characterized by invasive growth and poor prognosis.Actin cytoskeletal rearrangement is an essential event in tumor cell migration.Scinderin(SCIN),an actin severing and capping protein that regulates the actin cytoskeleton,is involved in the prolif-eration and migration of certain cancer cells.However,its biological role and molecular mechanism in glioma remain unclear.Lin et al explored the role and mechanism of SCIN in gliomas.The results showed that SCIN mechanically affected cytoskeleton remodeling and inhibited the formation of lamellipodia via RhoA/FAK signaling pathway.This study identifies the cancer-promoting role of SCIN and provides a potential therapeutic target for SCIN in glioma treatment. 展开更多
关键词 GLIOMA Scinderin Actin cytoskeleton RhoA/FAK signaling 1p/19q co-deletion
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