Circ-sh3rf3/GATA-4/miR-29a regulatory axis in fibroblast-myofibroblast differentiation and myocardial fibrosis.

The transdifferentiation from cardiac fibroblasts to myofibroblasts is an important event in the initiation of cardiac fibrosis. However, the underlying mechanism is not fully understood. Circ-sh3rf3 (circular RNA SH3 domain containing Ring Finger 3) is a novel circular RNA which was induced in hypertrophied ventricles by isoproterenol hydrochloride, and our work has established that it is a potential regulator in cardiac hypertrophy, but whether circ-sh3rf3 plays a role in cardiac fibrosis remains unclear, especially in the conversion of cardiac fibroblasts into myofibroblasts. Here, we found that circ-sh3rf3 was down-regulated in isoproterenol-treated rat cardiac fibroblasts and cardiomyocytes as well as during fibroblast differentiation into myofibroblasts. We further confirmed that circ-sh3rf3 could interact with GATA-4 proteins and reduce the expression of GATA-4, which in turn abolishes GATA-4 repression of miR-29a expression and thus up-regulates miR-29a expression, thereby inhibiting fibroblast-myofibroblast differentiation and myocardial fibrosis. Our work has established a novel Circ-sh3rf3/GATA-4/miR-29a regulatory cascade in fibroblast-myofibroblast differentiation and myocardial fibrosis, which provides a new therapeutic target for myocardial fibrosis.

Public Interest in Cosmetic Surgical and Minimally Invasive Plastic Procedures During the COVID-19 Pandemic: Infodemiology Study of Twitter Data.

BACKGROUND: The unprecedented COVID-19 pandemic has brought drastic changes to the field of plastic surgery. It is critical for stakeholders in this field to identify the changes in public interest in plastic procedures to be adequately prepared to meet the challenges of the pandemic. OBJECTIVE: The aim of this study is to examine tweets related to the public interest in plastic procedures during the COVID-19 pandemic and to help stakeholders in the field of plastic surgery adjust their practices and sustain their operations during the current difficult situation of the pandemic. METHODS: Using a web crawler, 73,963 publicly accessible tweets about the most common cosmetic surgical and minimally invasive plastic procedures were collected. The tweets were grouped into three phases, and the tweeting frequencies and Google Trends indices were examined. Tweeting frequency, sentiment, and word frequency analyses were performed with Python modules. RESULTS: Tweeting frequency increased by 24.0% in phase 2 and decreased by 9.1% in phase 3. Tweets about breast augmentation, liposuction, and abdominoplasty ("tummy tuck") procedures consecutively increased over the three phases of the pandemic. Interest in Botox and chemical peel procedures revived first when the lockdown was lifted. The COVID-19 pandemic was associated with a negative impact on public sentiment about plastic procedures. The word frequency pattern significantly changed after phase 1 and then remained relatively stable. CONCLUSIONS: According to Twitter data, the public maintained their interest in plastic procedures during the COVID-19 pandemic. Stakeholders should consider refocusing on breast augmentation, liposuction, and abdominoplasty procedures during the current phase of the pandemic. In the case of a second wave of COVID-19, stakeholders should prepare for a temporary surge of Botox and chemical peel procedures.

miR-200b targets GATA-4 during cell growth and differentiation.

GATA-4 is an important transcription factor involved in several developmental processes of the heart, such as cardiac myocyte proliferation, differentiation and survival. The precise mechanisms underlying the regulation of GATA-4 remain unclear, this is especially true for the mechanisms that mediate the post-transcriptional regulation of GATA-4. Here, we demonstrate that miR-200b, a member of the miR-200 family, is a critical regulator of GATA-4. Overexpression of miR-200b leads to the downregulation of GATA-4 mRNA and a decrease in GATA-4 protein levels. Moreover, miR-200b not only inhibits cell growth and differentiation but also reverses the growth response mediated by GATA-4, whereas depletion of miR-200b leads to a slight reversal of the anti-growth response achieved by knocking down endogenous GATA-4. More importantly, the cell cycle-associated gene cyclin D1, which is a downstream target of GATA-4, is also regulated by miR-200b. Thus, miR-200b targets GATA-4 to downregulate the expression of cyclin D1 and myosin heavy chain (MHC), thereby regulating cell growth and differentiation.

Do entrepreneurial resources drive startup activation? Mediating effect of entrepreneurial orientation.

In order to create an entrepreneurial ecosystem at the national level, this study aims to examine the mediating role of entrepreneurial orientation between entrepreneurial resources and startup activities. Our empirical results based on samples from the Adult Population Survey (APS) and Global Entrepreneurship Monitor (GEM) data revealed that entrepreneurial resources have a positive impact on startup activation and entrepreneurial orientation plays a significant role as a mediator in the entrepreneurial resource-startup activation relationship. Our results suggest that in a business ecosystem where entrepreneurial resources persistently exist, individuals are more likely to participate in startup activation, and entrepreneurial orientation can promote startup activity not only in countries rich in entrepreneurial resources but also in emerging countries where they are scarce. Therefore, this study emphasizes the need for efforts to increase entrepreneurial orientation as well as entrepreneurial resources to create an entrepreneurial ecosystem where startups actively appear.

Efficacy and Safety of Botulinum Toxin Type A in the Treatment of Benign Parotid Hypertrophy: A Prospective Study.

BACKGROUND: Benign parotid hypertrophy makes the earlobe area appear swollen and weakens the lateral facial contour and aesthetics. Efficacious treatment for benign parotid hypertrophy is not available. The authors evaluated the efficacy and safety of botulinum toxin type A for benign parotid hypertrophy treatment. METHODS: Thirty-six participants with benign parotid hypertrophy were enrolled and treated with botulinum toxin type A injection. After 6 months of follow-up, changes in the thickness and length of the superficial lobe of the parotid gland were assessed. Analyses of patient subgroups and image analyses were also undertaken to assess improvement. RESULTS: Thirty-three participants completed this study. Superficial lobe of the parotid gland thickness was reduced significantly after botulinum toxin type A injection, but the longitudinal diameter of the parotid gland was not changed significantly ( p < 0.001 and p = 0.146, respectively). Subgroup analyses showed that the degree of parotid gland hypertrophy affected treatment efficacy and degree of improvement, but age and sex did not ( p < 0.001, p = 0.137, and p = 0.138, respectively). Image analyses showed improvement in the facial contour ( p < 0.05). Serious adverse reactions or complications were not observed. CONCLUSION: Botulinum toxin type A can be used to treat benign parotid hypertrophy, reduce parotid gland volume, and improve the facial contour. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

A GRIP-1-EZH2 switch binding to GATA-4 is linked to the genesis of rhabdomyosarcoma through miR-29a.

Terminal differentiation failure is an important cause of rhabdomyosarcoma genesis, however, little is known about the epigenetic regulation of aberrant myogenic differentiation. Here, we show that GATA-4 recruits polycomb group proteins such as EZH2 to negatively regulate miR-29a in undifferentiated C2C12 myoblast cells, whereas recruitment of GRIP-1 to GATA-4 proteins displaces EZH2, resulting in the activation of miR-29a during myogenic differentiation of C2C12 cells. Moreover, in poorly differentiated rhabdomyosarcoma cells, EZH2 still binds to the miR-29a promoter with GATA-4 to mediate transcriptional repression of miR-29a. Interestingly, once re-differentiation of rhabdomyosarcoma cells toward skeletal muscle, EZH2 was dispelled from miR-29a promoter which is similar to that in myogenic differentiation of C2C12 cells. Eventually, this expression of miR-29a results in limited rhabdomyosarcoma cell proliferation and promotes myogenic differentiation. We thus establish that GATA-4 can function as a molecular switch in the up- and downregulation of miR-29a expression. We also demonstrate that GATA-4 acts as a tumor suppressor in rhabdomyosarcoma partly via miR-29a, which thus provides a potential therapeutic target for rhabdomyosarcoma.

The effect of botulinum toxin injection dose on the appearance of surgical scar.

Early postoperative injection of botulinum toxin type A (BTxA) can reduce surgical scar hypertrophy. BTxA injection at different time points is associated with different levels of efficacy, but the efficacy of different doses of BTxA for scar management has not investigated. The purpose of this study was to investigate the effect of different doses of BTxA administered early after surgery on scar improvement through a split-scar experiment. The study included 22 patients who underwent surgery between September 2019 and October 2020. High- and low-dose BTxA was randomly administered into each half of the surgical wound closure immediately after surgery. One half of the incision was injected with a low dose (4 U) of BTxA, and the other half was injected with a high dose (8 U). The scars were then evaluated at postoperative 6 months using the modified Stony Brook Scar Evaluation Scale (mSBSES), and patient satisfaction was evaluated using the Visual Analogue Scale (VAS). The occurrence of complications or adverse events was also recorded. Twenty patients completed the study and were analyzed. Compared with the low-dose sides, the high-dose sides had significantly better mSBSES scores and significantly higher VAS scores (p < 0.01, respectively). No serious adverse reactions or post-injection complications were observed. Immediately after the operation, high-dose BTxA (that is within the therapeutic range) injection improved the appearance of postoperative scar more than low-dose injection.

Influence of the pandemic dissemination of COVID-19 on facial rejuvenation: A survey of Twitter.

BACKGROUND: With the pandemic dissemination of COVID-19, attitude and sentiment surrounding facial rejuvenation have evolved rapidly. AIMS: The purpose of this study was to understanding the impact of pandemic on the attitude of people toward facial skin rejuvenation. METHODS: Twitter data related to facial rejuvenation were collected from January 1, 2020, to April 30, 2020. Sentiment analysis, frequency analysis, and word cloud were performed to analyze the data. Statistical analysis included two-tailed t tests and chi-square tests. RESULTS: In the post-declaration, the number of tweets about facial rejuvenation increased significantly, and the search volume in Google Trends decreased. Negative public emotions increased, but positive emotions still dominate. The words frequency of "discounts" and "purchase" decreased. The dominant words in word cloud were "Botox," "facelift," "hyaluronic," and "skin." CONCLUSION: The public has a positive attitude toward facial rejuvenation during the pandemic. In particular, minimally invasive procedures dominate the mainstream, such as "Botox," "Hyaluronic acid," and "PRP." The practitioners could understand the change of the public interest in facial rejuvenation in time and decide what to focus on.

Hepatic resection for post-operative solitary liver metastasis from oesophageal squamous cell carcinoma.

BACKGROUND: Liver metastasis is common in patients with oesophageal cancer. The effect of operative intervention for post-operative solitary liver metastasis from oesophageal squamous cell carcinoma (ESCC) has not previously been examined. This research was to compare the effect of surgery and non-surgical therapy in patients with post-operative solitary liver metastasis from ESCC. METHODS: We retrospectively analysed the clinical data of 69 consecutive patients with solitary hepatic metastasis who had undergone oesophagectomy for ESCC and were subsequently referred to the First Affiliated Hospital of Zhengzhou University from January 2005 to December 2013. The survival rates of the surgical and non-surgical groups were compared. RESULTS: There were 26 patients in the surgical group and 43 patients in the non-surgical group. There was no operative death in the surgical group. Post-operative complications were observed in six patients, and all of these patients recovered after additional treatments. Patients in the surgical group had 1- and 2-year cumulative survival rates of 50.8 and 21.2%, respectively, which were significantly higher than the 31.0 and 7.1% survival rates of patients in the non-surgical group (P < 0.05). In each group, the patients with a disease-free interval (DFI) lasting >12 months had a better survival rate than those with a DFI lasting ≤12 months (all P < 0.05). CONCLUSIONS: Operative intervention is a better treatment choice for patients with post-operative solitary liver metastasis from ESCC, especially for patients with a DFI lasting >12 months. Patients selected for hepatic resection should be considered on an individual basis through a multidisciplinary team of specialists.

Which factors are associated with extremely short-term survival after surgery in patients with esophageal squamous cell carcinoma?

AIMS: Esophageal squamous cell carcinoma (ESCC) is associated with a short median survival and low cure rates. The postoperative survival time of some patients with ESCC is extremely short. It is important to understand risk factors in subsets of patients associated with extremely short-term survival. The standard factors such as T and N stage, which are predictive of actuarial survival, become less important as patients live for ≤1 year. However, the prevalence of these factors in these patient populations has not been well documented. We evaluated factors predictive of ≤1 year survival in this research. METHODS: We analyzed 1596 patients underwent esophagectomy for ESCC retrospectively. The demographic and clinicopathologic characteristics were compared between patients who died within 1 year of esophagectomy and patients who survived more than 1 year after esophagectomy. RESULTS: Univariate analysis showed significant differences between the two groups regarding gender, weight loss, comorbidity, neoadjuvant treatment, completeness of resection, pathological T stage, pathological N stage, histologic grade, the number of metastatic lymph nodes, postoperative complications, postoperative pulmonary infection and postoperative hospital stay. Based on logistic regression analysis, significant factors associated with extremely short-term survival were male gender, incomplete tumor resection, higher pathological T stage, higher pathological N stage and postoperative pulmonary infection. CONCLUSION: The independent positive predictors for extremely short-term survival are male gender, incomplete tumor resection and postoperative pulmonary infection besides higher pathological T stage and higher pathological N stage.

Transcription factor GATA-6 recruits PPARα to cooperatively activate Glut4 gene expression.

Peroxisome proliferator-activated receptor α (PPARα) is a nuclear hormone receptor that regulates energy metabolism, but its precise mechanisms remain unknown. Here, we demonstrate that the PPARα agonist fenofibrate activated expression of the glucose transporter Glut4. Moreover, PPARα was associated with the Glut4 promoter through GATA sites upon fenofibrate stimulation in cardiomyocytes. This occupancy is achieved through an interaction between amino acids 1-136 of PPARα with amino acids 276-443 of the cardiac transcription factor GATA-6. In addition, the interaction of PPARα with GATA-6 activated Glut4 gene expression, improved glucose consumption, and enhanced activity of mitochondrial citrate synthase in C2C12 myoblasts; both mutants of PPARα (1-101 aa) and GATA-6 (227-331 aa) were unable to cooperate in Glut4 activation. Thus, GATA-6 is an important component of the transcription network required for energy metabolism mediated by PPARα, and these findings provide a molecular basis for understanding the role of GATA-6 proteins in muscle development and disease.