STAU1 promotes adipogenesis by regulating the alternative splicing of Pparγ2 mRNA.

During adipocyte differentiation, specific genes such as peroxisome proliferator-activated receptor γ (PPARγ) are transcribed and post-transcriptional pre-mRNA is processed into mature mRNA. Since Pparγ2 pre-mRNAs contain putative binding sites for STAUFEN1 (STAU1), which can affect the alternative splicing of pre-mRNA, we hypothesized that STAU1 might regulate the alternative splicing of Pparγ2 pre-mRNA. In this study, we found that STAU1 affects the differentiation of 3 T3-L1 pre-adipocytes. Through RNA-seq analysis, we confirmed that STAU1 can regulate alternative splicing events during adipocyte differentiation, mainly through exon skipping, which suggests that STAU1 is mainly involved in exon splicing. In addition, gene annotation and cluster analysis revealed that the genes affected by alternative splicing were enriched in lipid metabolism pathways. We further demonstrated that STAU1 can regulate the alternative splicing of Pparγ2 pre-mRNA and affect the splicing of exon E1 through RNA immuno-precipitation, photoactivatable ribonucleotide enhanced crosslinking and immunoprecipitation, and sucrose density gradient centrifugation assays. Finally, we confirmed that STAU1 can regulate the alternative splicing of Pparγ2 pre-mRNA in stromal vascular fraction cells. In summary, this study improves our understanding of the function of STAU1 in adipocyte differentiation and the regulatory network of adipocyte differentiation-related gene expression.

The application of medical scale in the treatment of plantar warts: analysis and prospect.

Plantar warts are common cutaneous diseases on the sole caused by the human papillomavirus, with a high annual incidence rate of 14%. It often causes pain, which impairs quality of life of patients. Numerous therapeutic options for plantar warts exist with variable success. However, all of them, including first-line treatment, have different adverse reactions or high recurrence rates. There is no one effective method for all patients. The choice of treatment method puzzles doctors. With the help of medical scales, we can analyze the patients' condition, so as to guide the choice of treatment methods, which is of great significance for the individualized treatment of patients with plantar warts. This review takes cryotherapy, intralesional injection of bleomycin and photodynamic therapy as examples to discuss the application of medical scales in the treatment of plantar warts, summarizes the scales that can be used to evaluate the status of plantar wart, adverse reactions, prognosis and patient's financial situation, and discusses their clinical and scientific value. We hope to use scales to consider the severity of plantar warts and economic level, help different patients to choose different treatment options, and make suggestions on the evaluation of the adverse reactions and treatment effect.

Staufen1 unwinds the secondary structure and facilitates the translation of fatty acid binding protein 4 mRNA during adipogenesis.

Adipogenesis is regulated by genetic interactions, in which post-transcriptional regulation plays an important role. Staufen double-stranded RNA binding protein 1 (Staufen1 or STAU1) plays diverse roles in RNA processing and adipogenesis. Previously, we found that the downregulation of STAU1 affects the expression of fatty acid-binding protein 4 (FABP4) at the protein level but not at the mRNA level. This study aimed to determine the mechanism underlying the regulation of FABP4 expression by STAU1, explaining the inconsistency between FABP4 mRNA and protein levels. We used RNA interference, photoactivatable ribonucleoside enhanced cross-linking and immunoprecipitation, and an adeno-associated virus to examine the functions of STAU1 in adipogenesis. Our results indicate that STAU1 binds to the coding sequences of FABP4, thereby regulating the translation of FABP4 mRNA by unwinding the double-stranded structure. Furthermore, STAU1 mediates adipogenesis by regulating the secretion of free fatty acids. However, STAU1 knockdown decreases the fat weight/body weight ratio but does not affect the plasma triglyceride levels. These findings describe the mechanisms involved in STAU1-mediated regulation of FABP4 expression at the translational level during adipogenesis.

The application of physical pretreatment in photodynamic therapy for skin diseases.

Photodynamic therapy (PDT) is widely used in skin diseases; the response rate of PDT treatment varies widely. The limited penetration in the tissue of photosensitizers influenced the penetration depth of PDT, which obviously impacts the therapeutic effect. The studies have improved the efficacy of PDT through various pretreatment applications; especially, the physical pretreatment had achieved significant outcomes. We will review the physical pretreatment to optimize the efficacy of PDT in skin diseases by searching the literature on this topic. The types of physical pretreatment commonly used in the clinical practice are discussed: curettage, superficial shaving, laser, surgical resection, plum-blossom needles, and microneedles. Compared with PDT alone, the physical pretreatment before PDT application was generally improved the efficacy and reduced the recurrence, especially in actinic keratoses (AK), Bowen disease (BD), basal cell carcinoma (BCC), and viral warts. The application of the physical pretreatments before PDT may improve the efficacy of PDT in various skin diseases. However, each kind of physical pretreatment has the benefit and shortcoming, and the applicable situation is different.

Assistant Diagnosis of Basal Cell Carcinoma and Seborrheic Keratosis in Chinese Population Using Convolutional Neural Network.

Objectives: To evaluate CNN models' performance of identifying the clinical images of basal cell carcinoma (BCC) and seborrheic keratosis (SK) and to compare their performance with that of dermatologists. Methods: We constructed a Chinese skin diseases dataset which includes 1456 BCC and 1843 SK clinical images and the corresponding medical history. We evaluated the performance using four mainstream CNN structures and transfer learning techniques. We explored the interpretability of the CNN model and compared its performance with that of 21 dermatologists. Results: The fine-tuned InceptionResNetV2 achieved the best performance, with an accuracy and area under the curve of 0.855 and 0.919, respectively. Further experimental results suggested that the CNN model was not only interpretable but also had a performance comparable to that of dermatologists. Conclusions: This study is the first on the assistant diagnosis of BCC and SK based on the proposed dataset. The promising results suggested that CNN model's performance was comparable to that of expert dermatologists.

A Comparative Study: Superficial Shaving Combined With Photodynamic Therapy Versus Cryotherapy in the Treatment of Recalcitrant Plantar Warts.

BACKGROUND AND OBJECTIVES: Plantar warts are a viral infectious lesion on the foot. The regression of plantar warts can be challenging despite the presence of a variety of available treatment modalities. Photodynamic therapy (PDT) has been recommended for the treatment of plantar warts. However, the effect of PDT in the treatment of plantar warts is not clear. Thus, we compared the efficacy of combining superficial shaving with PDT (SS-PDT) with that of cryotherapy in the treatment of recalcitrant plantar warts. STUDY DESIGN/MATERIALS AND METHODS: Forty-six patients with 271 warts received SS-PDT, and 26 patients with 147 warts received cryotherapy. For the SS-PDT group, the lesions were shaved in situ, and PDT was performed immediately. For the cryotherapy group, appropriate pressure was applied by freezing rod to fully freeze the lesion tissue. The overall clinical response effects, recurrence rates, adverse events, patient satisfaction and the quality of life were assessed. RESULTS: The SS-PDT group achieved a 91.3% success rate (defined as >50% on clearance) after treatment for 6 months, whereas only 23.1% of treatment in the cryotherapy group was successful. After 6 months of follow-up, the recurrence rate in the SS-PDT group was significantly lower than that in the cryotherapy group (8.7% vs. 76.9%, P < 0.001). The patients with SS-PDT were more satisfied with the treatment than the patients with cryotherapy (8.8 ± 1.4 vs. 4.9 ± 1.4, P < 0.001). Moderate pain was the main adverse event in SS-PDT, and cryotherapy may cause severe pain and blistering. CONCLUSIONS: Our results suggest that superficial shaving combined with PDT is promising as a safe and effective therapy for patients with plantar warts, especially for patients with multiple recalcitrant warts. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.

Efficacy of a New Therapeutic Option for Vulvar Intraepithelial Neoplasia: Superficial Shaving Combined With Photodynamic Therapy.

BACKGROUND AND OBJECTIVE: Vulvar intraepithelial neoplasia (VIN), a precancerous lesion, is difficult to treat by excision or ablation due to high recurrence rates. Photodynamic therapy (PDT) is a minimally invasive therapeutic procedure and is now widely used to treat non-melanoma skin diseases. However, the clinical response rates of VIN to single PDT are unstable. The reason may be the limited light penetration into deep tissues. OBJECTIVE: To retrospectively evaluate the clinical response and recurrence of VIN after combined treatment with superficial shaving and PDT. STUDY DESIGN/MATERIALS AND METHODS: Seventeen patients with VIN were enrolled. All patients had multifocal high-grade VIN that had failed to respond to various therapies. Superficial shaving was performed only once and prior to the first 5-aminolaevulinic acid (5-ALA)-PDT cycle. Generally, the procedure of 5-ALA PDT for each patient was performed in three sessions. Clinical response, recurrence, cosmetic outcomes, adverse events, patient satisfaction, quality of life, and mental health were assessed. The expression of p16 and Ki-67 in pre- and post-treatment tissue was detected. RESULTS: A clinical response of 94% was observed in 17 patients, who were administered combination therapy, over an observation period of 12 months. Approximately, 71% of patients had excellent cosmetic outcomes. All patients had satisfactory therapeutic effects and significant improvements in quality of life and mental health. Downregulation of p16 and Ki-67 may have been correlated with recurrence after 5-ALA-PDT. CONCLUSION: Combined treatment with superficial shaving and 5-ALA-PDT is a safe and effective option for VIN. In particular, combination therapy is recommended for patients with large, multifocal, high-grade lesions; repeated recurrence; and strong willingness to maintain vulvar configuration and function. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Simple shaving combined with photodynamic therapy for refractory bowen disease.

Bowen Disease (BD), also known as squamous cell carcinoma in situ, requires treatment to prevent progression to invasive cancer.. Photodynamic therapy (PDT) has been widely employed to treat BD. However, there are BD patients who undergo PDT but experience poor efficacy and recurrence. We have considered that for some, the reason is the depth of PDT penetrating tissue to be limited. Therefore, we combined simple shaving with PDT to treat 10 patients with a total of 44 advanced BD lesions. After local injection of anesthesia, the lesions were shaved once in situ, then a total of three PDT sessions were applied for each patient. At 12 weeks, all of BD lesions (100%) have shown complete clinical response. After more than 12 months follow-up, the RR was 0, and all lesions showed a good or excellent cosmetic outcome. The patient's symptoms were alleviated with improvement in the quality of life. For those with advanced BD, which are more than 3 cm in diameter, with unclear borders, ulcers, multiple occurrences and those that appear on the face and neck that are not suitable for extended resection by routine surgery, combined simple shaving with PDT is recommended.

Glucocorticoids Prevent Enterovirus 71 Capsid Protein VP1 Induced Calreticulin Surface Exposure by Alleviating Neuronal ER Stress.

Severe hand-foot-and-mouth disease (HFMD) caused by Enterovirus 71 (EV71) always accompanies with inflammation and neuronal damage in the central nervous system (CNS). During neuronal injuries, cell surface-exposed calreticulin (Ecto-CRT) is an important mediator for primary phagocytosis of viable neurons by microglia. Our data confirmed that brainstem neurons underwent neuronophagia by glia in EV71-induced death cases of HFMD. EV71 capsid proteins VP1, VP2, VP3, or VP4 did not induce apoptosis of brainstem neurons. Interestingly, we found VP1-activated endoplasmic reticulum (ER) stress and autophagy could promote Ecto-CRT upregulation, but ER stress or autophagy alone was not sufficient to induce CRT exposure. Furthermore, we demonstrated that VP1-induced autophagy activation was mediated by ER stress. Meaningfully, we found dexamethasone treatment could attenuate Ecto-CRT upregulation by alleviating VP1-induced ER stress. Altogether, these findings identify VP1-promoted Ecto-CRT upregulation as a novel mechanism of EV71-induced neuronal cell damage and highlight the potential of the use of glucocorticoids to treat severe HFMD patients with CNS complications.