Facial Hypertrophy as a Complication of Weight Gain in Autologous Fat Graft Patients: Considerations and Recommendations.

Fat grafting can restore facial volume for reconstructive and cosmetic indications. Common practice often involves extracting lipoaspirate from the most abundant anatomic location. However, grafted fat retains the phenotypic characteristics of its original location and can undergo exaggerated hypertrophy with patient weight fluctuations. The aim of this study was to systematically assess the literature to summarize the reported effects of postoperative weight gain on facial hypertrophy in patients after facial fat grafting and to determine potentially avoidable factors. A search through PubMed/MEDLINE was conducted on October 4, 2022, to identify relevant articles with appropriate search terms. No lower date limit was applied and all eligible nonanimal clinical articles in English were included for review. Reports were summarized and presented as descriptive statistics. The search generated 714 articles. After abstract and full-text review of the initial set of articles, 6 were included in our analysis. All articles described poor cosmetic outcomes resulting from nonanatomic hypertrophy of the grafted fat. None of the articles reported a thorough methodology for selecting the donor site to minimize fat hypertrophy with potential future weight fluctuations. Grafted facial fat is susceptible to exaggerated hypertrophy as a result of changes in patient weight. Specifically, harvesting lipoaspirate from maximally abundant areas of the body may increase this risk. Individualizing the area of fat donation may attenuate unwanted fat growth and further contribute to increased patient quality of life.

Evaluation of the Risk of Hypertrophic Scarring and Keloid Following Eyelid Procedures: A Systematic Review.

BACKGROUND: Eyelid surgeries are common operations performed for both cosmetic and functional purposes. Because the periorbital region is highly visible, it is important to avoid poor scar formation in this cosmetically sensitive region. No study to date has investigated the possible existence of keloid formation following eyelid procedures. OBJECTIVES: This study systematically reviewed the literature to identify cases of hypertrophic scar and keloid formation following cosmetic or functional (nonburn) eyelid procedures to aid surgeons when counseling patients. METHODS: A PubMed/MEDLINE search was conducted on May 17, 2022, using appropriate search terms: "blepharoplasty," "tarsorrhaphy," "canthotomy," "ptosis repair," "epicanthoplasty," "keloid," "hypertrophic scar," and related lay terms. All eligible articles in English with no lower date limit were included for analysis. Descriptive statistics, exclusion criteria, and summarized results are reported. RESULTS: The PubMed search yielded 107 abstracts/articles. Full-text review resulted in 34 articles included for analysis. Twenty manuscripts reported no occurrences of hypertrophic scars. Only 13 manuscripts reported patients with hypertrophic scarring, which equated to 36 patients out of 3650. One individual was identified in a series of 77 patients who developed a keloid after a tarsorrhaphy. No articles reported a keloid as an outcome of strictly cosmetic procedures. CONCLUSIONS: This study concludes that there are no reported instances of keloid formation following cosmetic (nonburn) eyelid procedures in the existing literature. Hypertrophic scar formation is minimally reported. The absence of keloid scar formation on the eyelid is critical knowledge for surgeons when educating patients about maladaptive scarring risks following eyelid procedures.

Gluteal Shape Framework for Augmentation Surgery: A Systematic Review of the Literature and Proposed Classification System.

BACKGROUND: Gluteal augmentation is used to improve the size and shape of the buttocks. Unlike other anatomical areas, such as the breasts, where there are classification systems for size and projection, no standardized methods for classifying gluteal size and shape exist. Patients seeking augmentation rely on photographs to communicate their desired result to surgeons. The authors' study objectively reviews this topic and proposes a novel classification system for the buttocks that can provide an organized framework for patients and providers. METHODS: A systematic of the literature was conducted on March 17, 2021, using various combinations of the following terms: "gluteal augmentation," "classification," "size," "gluteoplasty," and "Brazilian butt lift." All eligible articles were included for analysis. RESULTS: The PubMed/MEDLINE searches yielded 49 articles and abstracts. After review, eight publications were chosen for analysis. All publications were found in plastic surgery journals, with the most common journals as follows: Aesthetic Surgery Journal ( n = 4), Clinics in Plastic Surgery ( n = 2), Annals of Plastic Surgery ( n = 1), and Plastic and Reconstructive Surgery ( n = 1). There are no articles in the plastic surgery literature that provide a standardized classification system for gluteal size determination. CONCLUSIONS: The authors' study revealed the need for a standardized classification system for gluteal size and shape. Although the publications analyzed discussed various techniques for related procedures and provided ways to improve aesthetic outcomes, none presented a system for reproducibly classifying size and shape. By introducing a classification system, we hope to enable plastic surgeons to more accurately and efficiently discuss their patient's goals.

Development, implementation and outcomes of a quality assurance system for the provision of continuous renal replacement therapy in the intensive care unit.

Critically ill patients with requirement of continuous renal replacement therapy (CRRT) represent a growing intensive care unit (ICU) population. Optimal CRRT delivery demands continuous communication between stakeholders, iterative adjustment of therapy, and quality assurance systems. This Quality Improvement (QI) study reports the development, implementation and outcomes of a quality assurance system to support the provision of CRRT in the ICU. This study was carried out at the University of Kentucky Medical Center between September 2016 and June 2019. We implemented a quality assurance system using a step-wise approach based on the (a) assembly of a multidisciplinary team, (b) standardization of the CRRT protocol, (c) creation of electronic CRRT flowsheets, (d) selection, monitoring and reporting of quality metrics of CRRT deliverables, and (e) enhancement of education. We examined 34-month data comprising 1185 adult patients on CRRT (~ 7420 patient-days of CRRT) and tracked selected QI outcomes/metrics of CRRT delivery. As a result of the QI interventions, we increased the number of multidisciplinary experts in the CRRT team and ensured a continuum of education to health care professionals. We maximized to 100% the use of continuous veno-venous hemodiafiltration and doubled the percentage of patients using regional citrate anticoagulation. The delivered CRRT effluent dose (~ 30 ml/kg/h) and the delivered/prescribed effluent dose ratio (~ 0.89) remained stable within the study period. The average filter life increased from 26 to 31 h (p = 0.020), reducing the mean utilization of filters per patient from 3.56 to 2.67 (p = 0.054) despite similar CRRT duration and mortality rates. The number of CRRT access alarms per treatment day was reduced by 43%. The improvement in filter utilization translated into ~ 20,000 USD gross savings in filter cost per 100-patient receiving CRRT. We satisfactorily developed and implemented a quality assurance system for the provision of CRRT in the ICU that enabled sustainable tracking of CRRT deliverables and reduced filter resource utilization at our institution.

The COVID-19 Pandemic and Plastic Surgery: Literature Review, Ethical Analysis, and Proposed Guidelines.

BACKGROUND: Coronavirus disease 2019 (COVID-19), known as the "coronavirus," has spread to over 170 countries. In response, many organizations have spoken out and called for cancellation of all elective surgical procedures. This study aimed to provide clear recommendations for plastic surgeons to follow by addressing the following issues: (1) What defines elective surgery, and where does one draw the line between essential versus nonessential services? (2) How does this differ in the hospital versus private practice setting? (3) If called on to operate on a patient with COVID-19, how do plastic surgeons protect themselves and still provide excellent medical care? METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses systematic review of the literature on plastic surgery in the setting of a pandemic was performed on March 19, 2020. An ethical analysis was conducted using the four principles of medical ethics. RESULTS: The initial search yielded 118 articles. Eighteen articles were relevant and included for analysis. Only one editorial article was published in a plastic surgery journal. Accordingly, no peer-reviewed published COVID-19 guidelines exist for plastic surgery. Given that this pandemic may place health care systems under undue stress with an unpredictable trajectory, it is the responsibility of the plastic surgeon to assess and postpone cases whenever possible to properly contribute to adequate resource allocation and patient safety measures. CONCLUSIONS: This article fills an important gap in the literature by addressing COVID-19 and providing guidelines for upholding ethics and responsible resource allocation. By upholding these standards, plastic surgeons can do their part to help minimize the spread of this virus.

An Updated Review of Plastic Surgery-Related Hashtag Utilization on Instagram: Implications for Education and Marketing.

BACKGROUND: The popularity of social media continues to have a significant impact in the plastic surgery industry. Understanding the influence of such platforms and recognizing trends, specifically on Instagram, can reveal significant implications for education and marketing. OBJECTIVES: This study aims to gather updated information on 3 main questions: (1) what plastic surgery-related content is being posted to Instagram; (2) who is posting this content; and (3) what specific hashtags are they using? METHODS: This study analyzed 22 plastic surgery-related hashtags on Instagram. Content analysis was then used to qualitatively evaluate each of the 9 "top" posts associated with each hashtag (198). Any duplicates or posts not relevant to plastic surgery were excluded. RESULTS: A total of 11,516,969 posts utilized the 22 hashtags sampled. Of the top 198 posts, only 168 met final inclusion criteria (after duplicates and posts irrelevant to plastic surgery were excluded). Plastic surgeons eligible for membership in The Aesthetic Society accounted for only 4.17% of top posts (7 posts), whereas non-eligible physicians accounted for 20.8% (35 posts). Twenty-eight surgeons accounted for the top posts (excluding foreign surgeons); however, only 6 were board certified by either the American Board of Plastic Surgeons or The Royal College of Physicians and Surgeons of Canada. CONCLUSIONS: The Aesthetic Society eligible board-certified plastic surgeons are a minority amongst physicians posting top plastic surgery-related content on Instagram.

Making the Subjective Objective: Machine Learning and Rhinoplasty.

BACKGROUND: Machine learning represents a new frontier in surgical innovation. The ranking Convolutional Neural Network (CNN) is a novel machine learning algorithm that helps elucidate patterns and features of aging that are not always appreciable with the human eye. OBJECTIVES: The authors sought to determine the impact of aesthetic rhinoplasty on facial aging employing a multidimensional facial recognition and comparison software. METHODS: A retrospective chart review and subsequent analysis was carried out on all female patients who underwent open rhinoplasty with the senior author from 2014 through 2018 and had postoperative photos at 12 or more weeks follow-up. All photos were analyzed with Microsoft Azure Face API (Redmond, WA), which estimates patients' age by cropping the face from a photograph and then extracting a CNN-based prediction through multiple deep neural networks. RESULTS: A total of 100 patients ultimately met full inclusion criteria. The average post-surgical follow up for this cohort was 29 weeks (median, 14 weeks; range, 12-64 weeks). Patients ranged from 16 to 72 years old (mean, 32.75 years; median, 28.00 years; standard deviation, 12.79 years). The ranking CNN algorithm on average estimated patients preoperatively to be 0.03 years older than their actual age. The correlation coefficient between actual age and predicted preoperative age was r = 0.91. On average, patients were found to look younger post-open rhinoplasty (-3.10 vs 0.03 years, P < 0.0001). CONCLUSIONS: The ranking CNN algorithm is both accurate and precise in estimating human age before and after cosmetic rhinoplasty. Given the resulting data, the effects of open rhinoplasty on reversing signs of facial aging should be revisited.

The Plastic Surgery Social Media Influencer: Ethical Considerations and a Literature Review.

BACKGROUND: Social media use has become a relevant tool in plastic surgery. These platforms are utilized for many reasons, such as business promotion. Although beneficial, social media can cause ethical dilemmas if used incorrectly. OBJECTIVES: A review of the literature revealed what is understood about the implications of social media in regards to sponsorship/promotion. This paper aimed to create the foundation surrounding this topic and help facilitate future discussions on this new ethical dilemma. METHODS: A MEDLINE search with a custom publication date range and a review of the literature was conducted on June 15, 2019. RESULTS: The search yielded 139 articles and abstracts. After review, 26 publications were chosen for analysis. Articles were taken from the following journals: Plastic and Reconstructive Surgery (n = 12), Aesthetic Surgery Journal (n = 8), PRS Global Open (n = 2), Annals of Plastic Surgery (n = 1), BMJ (n = 1), AMA Journal of Ethics (n = 1), and Facial Plastic Surgery (n = 1). The 4 principles of medical ethics were analyzed in respect to promotion and sponsorship in plastic surgery. CONCLUSIONS: Social media is a novel platform that is becoming increasingly utilized in plastic surgery. Although its impact can be beneficial, it is not well understood in the context of social media sponsorship and promotion. To date, no peer-reviewed articles specifically discuss these limitations. It is critical that all plastic surgeons be cognizant of both the positive and negative aspects of social media before integrating it into their professional lives.

Correction to: Low levels of pyruvate induced by a positive feedback loop protects cholangiocarcinoma cells from apoptosis.

Following publication of the original article [1], the authors reported an error in.

The SIRT2/cMYC Pathway Inhibits Peroxidation-Related Apoptosis In Cholangiocarcinoma Through Metabolic Reprogramming.

Cholangiocarcinoma (CCA) is a malignant cancer with an unknown etiology and an unfavorable prognosis. Most patients are diagnosed at an advanced stage, thus making it essential to find novel curative targets for CCA. Metabolic reprogramming of the tumor cells includes metabolic abnormalities in glucose (known as the Warburg effect) and other substances such as amino acids and fats. Metabolic reprogramming produces anti-oxidant substances, reduces tumor oxidative stress, and finally promotes the proliferation of tumors. There is increasing evidence to imply that SIRT2, a histone deacetylase, and its downstream target cMYC, play metabolic regulatory roles in tumor cells. However, the role of the SIRT2/cMYC pathway in CCA is unclear. To assess the metabolic reprogramming function of the SIRT2/cMYC pathway in CCA and to determine the downstream targets as well as evaluate the therapeutic effect, the CCA RNA-Seq data were downloaded from the TCGA database. Differentially expressed genes were confirmed and KEGG pathway enrichment analysis was performed. Overall, 48 paired CCA samples were collected and subjected to immunohistochemical detection, and the clinical characteristics of participants were summarized. The CCA cells were suppressed or overexpressed with different downstream targets of SIRT2 and then subjected to apoptosis, immunoblotting, seahorse, and metabolites tracing analysis. In vivo experiments were also performed. We found that the SIRT2/cMYC pathway contributed to the proliferation of CCA cells and confirmed that the downstream target is PHDA1 and the serine synthesis pathway. The up-regulated SIRT2 and cMYC levels resulted in low levels of mitochondrial oxidative phosphorylation and increased conversion of glucose to serine and led to poor patient survival. The highly active SIRT2/cMYC pathway up-regulated the serine synthesis pathway pyruvate and increased antioxidant production, thus consequently protecting the CCA cells from oxidative stress-induced apoptosis. Our data revealed that the SIRT2/cMYC pathway plays a critical role in transforming glucose oxidative metabolism to serine anabolic metabolism, thus providing antioxidants for stress resistance. SIRT2/cMYC-induced metabolic reprogramming may represent a new therapeutic target for treating CCA.

[Corrigendum] Metformin facilitates BG45­induced apoptosis via an anti­Warburg effect in cholangiocarcinoma cells.

Following the publication of the article, the authors have realized that Fig. 1A contained an error (essentially, the scale bars were drawn incorrectly). The corrected version of Fig. 1 is shown below, also including a modified version of the legend for Fig. 1A. Note that these revisions do not affect the overall conclusions reported in the paper. The authors apologize to the Editor of Oncology Reports and to the readership for any inconvenience caused. [the original article was published in Oncology Reports 39: 1957­1965, 2018; DOI: 10.3892/or.2018.6275].

SIRT3 elicited an anti-Warburg effect through HIF1α/PDK1/PDHA1 to inhibit cholangiocarcinoma tumorigenesis.

Cholangiocarcinoma (CCA) is an extremely invasive malignancy with late diagnosis and unfavorable prognosis. Surgery and chemotherapy are still not effective in improving outcomes in CCA patients. It is crucial to explore a novel therapeutic target for treating CCA. An NAD-dependent deacetylase also known as Sirtuin-3 (SIRT3) has been shown to regulate cellular metabolism in various cancers dynamically. However, the biological function of SIRT3 in CCA remains unclear. In this study, bioinformatics analyses were performed to identify the differentially expressed genes and pathways enriched. CCA samples were collected for immunohistochemical analysis. Three human CCA cell lines (HuCCT1, RBE, and HCCC9810) were used to explore the molecular mechanism of SIRT3 regulation of metabolic reprogramming and malignant behavior in CCA. A CCA xenograft model was then established for further validation in vivo. The data showed that SIRT3 expression was decreased and glycolysis was enhanced in CCA. Similar metabolic reprogramming was also observed in SIRT3 knockout mice. Furthermore, we demonstrated that SIRT3 could play an anti-Warburg effect by inhibiting the hypoxia-inducible factor-1α (HIF1α)/pyruvate dehydrogenase kinase 1 (PDK1)/pyruvate dehydrogenase (PDHA1) pathway in CCA cells. CCA cell proliferation and apoptosis were regulated by SIRT3-mediated metabolic reprogramming. These findings were further confirmed in CCA clinical samples and the xenograft model. Collectively, this study suggests that in the inhibition of CCA progression, SIRT3 acts through an anti-Warburg effect on the downstream pathway HIF1α/PDK1/PDHA1.

Low levels of pyruvate induced by a positive feedback loop protects cholangiocarcinoma cells from apoptosis.

BACKGROUND: Cancer cells avidly consume glucose and convert it to lactate, resulting in a low pyruvate level. This phenomenon is known as the Warburg effect, and is important for cell proliferation. Although cMyc has often been described as an oncoprotein that preferentially contributes to the Warburg effect and tumor proliferation, mechanisms of action remain unclear. Histone deacetylase 3 (HDAC3) regulates gene expression by removing acetyl groups from lysine residues, as well as has an oncogenic role in apoptosis and contributes to the proliferation of many cancer cells including cholangiocarcinoma (CCA). HDAC inhibitors display antitumor activity in many cancer cell lines. Cancer cells maintain low levels of pyruvate to prevent inhibition of HDAC but the mechanisms remain elusive. The purpose of our study was to explore the role of cMyc in regulating pyruvate metabolism, as well as to investigate whether the inhibitory effect of pyruvate on HDAC3 could hold promise in the treatment of cancer cells. METHODS: We studied pyruvate levels in CCA cell lines using metabolite analysis, and analyzed the relationship of pyruvate levels and cell proliferation with cell viability analysis. We cultivated CCA cell lines with high or low levels of pyruvate, and then analyzed the protein levels of HDAC3 and apoptotic markers via Western Blotting. We then explored the reasons of low levels of pyruvate by using seahorse analysis and 13C6 metabolites tracing analysis, and then confirmed the results using patient tissue protein samples through Western Blotting. Bioinformatics analysis and transfection assay were used to confirm the upstream target of the low levels of pyruvate status in CCA. The regulation of cMyc by HDAC3 was studied through immunoprecipitation and Western Blotting. RESULTS: We confirmed downregulated pyruvate levels in CCA, and defined that high pyruvate levels correlated with reduced cell proliferation levels. Downregulated pyruvate levels decreased the inhibition to HDAC3 and consequently protected CCA cells from apoptosis. Synergistically upregulated LDHA, PKM2 levels resulted in low levels of pyruvate, as well as poor patient survival. We also found that low levels of pyruvate contributed to proliferation of CCA cells and confirmed that the upstream target is cMyc. Conversely, high activity of HDAC3 stabilized cMyc protein by preferential deacetylating cMyc at K323 site, which further contributed to the low pyruvate levels. Finally, this creates a positive feedback loop that maintained the low levels of pyruvate and promoted CCA proliferation. CONCLUSIONS: Collectively, our findings identify a role for promoting the low pyruvate levels regulated by c-Myc, and its dynamic acetylation in cancer cell proliferation. These targets, as markers for predicting tumor proliferation in patients undergoing clinical treatments, could pave the way towards personalized therapies.

A Quantitative Analysis of Online Plastic Surgeon Reviews for Abdominoplasty.

BACKGROUND: Online reviews increasingly influence patients' decision-making. This is the first systematic, quantitative analysis of online reviews for abdominoplasty. METHODS: Reviews for abdominoplasty were sampled from RealSelf, Yelp, and Google for six major metropolitan areas. A standard social sciences framework known as grounded theory was used to evaluate factors affecting satisfaction. The relative importance of factors was quantified using odds ratios. RESULTS: Seven hundred ninety-four reviews met inclusion criteria. There was significant geographic variation with respect to number of reviews (p < 0.01) and average rating (p = 0.014). The authors identified 10 statistically significant themes affecting satisfaction. Of these, aesthetic outcome was the most mentioned theme [n = 368 (46.3 percent)] and the most dominant driver of satisfaction. Interactions with staff had the second highest odds ratio, driven by the fact that all negative staff interactions led to negative reviews. Postoperative care had the next highest odds ratio, and was demonstrated to counteract the negative effects of poor surgical outcomes on satisfaction. The occurrence of a surgical complication and the cost of surgery were least associated with satisfaction. CONCLUSIONS: This analysis is the first to use quantitative methods to identify dominant and nondominant factors affecting patient satisfaction in cosmetic surgery. The authors found that aesthetic outcome, staff interactions, and postoperative diligence were the most critical factors affecting satisfaction in abdominoplasty, whereas postoperative complications and cost were least important. Understanding the relative importance of factors may help to improve and protect one's online reputation.

Faecalibacterium prausnitzii produces butyrate to decrease c-Myc-related metabolism and Th17 differentiation by inhibiting histone deacetylase 3.

Decreased levels of Faecalibacterium prausnitzii (F. prausnitzii), whose supernatant plays an anti-inflammatory effect, are frequently found in inflammatory bowel disease (IBD) patients. However, the anti-inflammatory products in F. prausnitzii supernatant and the mechanism have not been fully investigated. Here we found that F. prausnitzii and F. prausnitzii-derived butyrate were decreased in the intestines of IBD patients. Supplementation with F. prausnitzii supernatant and butyrate could ameliorate colitis in an animal model. Butyrate, but not other substances produced by F. prausnitzii, exerted an anti-inflammatory effect by inhibiting the differentiation of T helper 17 (Th17) cells. The mechanism underlying the anti-inflammatory effects of the butyrate produced by F. prausnitzii involved the enhancement of the acetylation-promoted degradation of c-Myc through histone deacetylase 3 (HDAC3) inhibition. In conclusion, F. prausnitzii produced butyrate to decrease Th17 differentiation and attenuate colitis through inhibiting HDAC3 and c-Myc-related metabolism in T cells. The use of F. prausnitzii may be an effective new approach to decrease the level of Th17 cells in the treatment of inflammatory diseases.

Google Ranking of Plastic Surgeons Values Social Media Presence Over Academic Pedigree and Experience.

BACKGROUND: Patients increasingly rely on online resources to make healthcare decisions. Google dominates the search engine market; first-page results receive most of the web traffic and therefore serve as an important indicator of consumer reach. OBJECTIVES: Our objective was to analyze the respective importance of physician academic pedigree, experience, and social media presence on plastic surgeon Google first-page search result placement. METHODS: A Google.com search was conducted in the top 25 United States metropolitan areas to identify the top 20 websites of board-certified plastic surgeons. Social media presence was quantified by tracking the number of followers on Facebook, Twitter, and Instagram for every surgeon as well as medical school and year of graduation. The primary outcome was website ranking in the first page of Google search results. To identify the independent predictors of presence on the front page, we performed a multivariate logistic regression. RESULTS: Total number of social medial followers was associated with Google front-page placement (P < 0.001), whereas medical school ranking and years in practice were not (P = 0.17 and 0.39, respectively). A total 19.6% of plastic surgeon practices in our study cohort still had no social media accounts whatsoever. CONCLUSIONS: For the past few decades, plastic surgery practices relied on referrals, word of mouth, and the surgeon's reputation and academic pedigree to attract new patients. It is now clear that this practice-building model is being rapidly supplanted by a new paradigm based on social media presence to reach potential patients.

Berberine promotes glucose uptake and inhibits gluconeogenesis by inhibiting deacetylase SIRT3.

OBJECTIVE: Many studies have confirmed the glucose-lowering effect of berberine in type 2 diabetes patients. Although the mechanism of action of berberine involves the improvement of insulin sensitivity, its hypoglycemic mechanism remains elusive. Here we show a new mechanism by which berberine antagonizes glucagon signaling and find that SIRT3 is involved in the hypoglycemic effect of berberine. METHODS: Gene knockout and overexpression were used to assess the inhibitory effect of berberine on SIRT3. Downstream signaling pathways and the hypoglycemic effect of SIRT3 were evaluated by immunoblotting and metabolic monitoring. RESULTS: We found that berberine led to mitochondrial dysfunction and AMP accumulation by inhibiting deacetylase SIRT3. We confirmed that AMP accumulation activated the AMPK signaling pathway and further promoted glucose uptake. Simultaneously, AMP accumulation reduced cyclic AMP (cAMP) levels and abrogated the phosphorylation of critical protein targets of protein kinase A (PKA). Furthermore, we found that phosphoenolpyruvate carboxykinase 1 (PEPCK1) is a key gluconeogenesis enzyme that can be stabilized by glucagon. Berberine caused significant PEPCK1 ubiquitination and degradation by antagonizing glucagon and was accompanied by high levels of PEPCK1 acetylation. Interestingly, berberine-induced glucagon inhibition is independent of AMPK activation. The in vivo data from sirt3 knockout mice were further confirmed by the in vitro experiments. CONCLUSIONS: Berberine promotes glucose uptake and inhibits gluconeogenesis by inhibiting SIRT3, and regulating mitochondria-related pathways may provide a novel approach to the development of antidiabetic drugs.

SIRT2 Promotes the Migration and Invasion of Gastric Cancer through RAS/ERK/JNK/MMP-9 Pathway by Increasing PEPCK1-Related Metabolism.

Metastasis is the most important feature of gastric cancer (GC) and the most widely recognized reason for GC-related deaths. Unfortunately, the underlying mechanism behind this metastasis remains unknown. Mounting evidence suggests the dynamic regulatory role of sirtuin2 (SIRT2), a histone deacetylase (HDAC), in cell migration and invasion. The present study aims to evaluate the biological function of SIRT2 in GC and identify the target of SIRT2 as well as evaluate its therapeutic efficacy. We found that SIRT2 was upregulated in GC tissues compared to adjacent normal tissues, and this was correlated with reduced patient survival. Although CCK8 and colony-formation assays showed that SIRT2 overexpression marginally promoted proliferation in GC cell lines, SIRT2 knockdown or treatment with SirReal2 decreased the migration and invasion of GC cells. We demonstrated both in vitro and in vivo that SirReal2 could inhibit the deacetylation activity of SIRT2 and its downstream target PEPCK1, which is related to mitochondrial metabolism and RAS/ERK/JNK/MMP-9 pathway. Taken together, these results demonstrate for the first time that SirReal2 selectively targets SIRT2 and decreases migration as well as invasion in human GC cells. SirReal2 therefore shows promise as a new drug candidate for GC therapy.