Nlp-dependent ER-to-Golgi transport.

The mechanism that maintains ER-to-Golgi vesicles formation and transport is complicated. As one of the adapters, Ninein-like protein (Nlp) participated in assembly and transporting of partial ER-to-Golgi vesicles that contained specific proteins, such as ß-Catenin and STING. Nlp acted as a platform to sustain the specificity and continuity of cargoes during COPII and COPI-coated vesicle transition and transportation through binding directly with SEC31A as well as Rab1B. Thus, we proposed an integrated transport model that particular adapter participated in specific cargo selection or transportation through cooperating with different membrane associated proteins to ensure the continuity of cargo trafficking. Deficiency of Nlp led to vesicle budding failure and accumulation of unprocessed proteins in ER, which further caused ER stress as well as Golgi fragmentation, and PERK-eIF2α pathway of UPR was activated to reduce the synthesis of universal proteins. In contrast, upregulation of Nlp resulted in Golgi fragmentation, which enhanced the cargo transport efficiency between ER and Golgi. Moreover, Nlp deficient mice were prone to spontaneous B cell lymphoma, since the developments and functions of lymphocytes significantly depended on secretory proteins through ER-to-Golgi vesicle trafficking, including IL-13, IL-17 and IL-21. Thus, perturbations of Nlp altered ER-to-Golgi communication and cellular homeostasis, and might contribute to the pathogenesis of B cell lymphoma.

Perfluorooctanoic acid triggers premature ovarian insufficiency by impairing NAD+ synthesis and mitochondrial function in adult zebrafish.

High-dose perfluorooctanoic acid (PFOA) impairs oocyte maturation and offspring quality. However, the physiological concentrations of PFOA in follicular fluids of patients with premature ovarian insufficiency (POI) were detected at lower levels, thus the relationship between physiological PFOA and reproductive disorders remains elusive. Here, we investigated whether physiological PFOA exposure affects gonad function in adult zebrafish. Physiological PFOA exposure resulted in POI-like phenotypes in adult females, which exhibited decreased spawning frequency, reduced number of ovulated eggs, abnormal gonadal index, and aberrant embryonic mortality. Meanwhile, oocytes from PFOA-exposed zebrafish showed mitochondrial disintegration and diminished mitochondrial membrane potential (MMP). Unlike the high-dose treated oocytes exhibiting high reactive oxygen species (ROS) levels and excessive apoptosis, physiological PFOA reduced the ROS levels and did not trigger apoptosis. Interestingly, physiological PFOA exposure would not affect testis function, indicating specific toxicity in females. Mechanistically, PFOA suppressed the NAD+ biosynthesis and impaired mitochondrial function in oocytes, thus disrupting oocyte maturation and ovarian fertility. Nicotinamide mononucleotide (NMN), a precursor for NAD+ biosynthesis, alleviated the PFOA-induced toxic effects in oocytes and improved the oocyte maturation and fertility upon PFOA exposure. Our findings discover new insights into PFOA-induced reproductive toxicity and provide NMN as a potential drug for POI therapy.

Cellular microenvironment: a key for tuning mesenchymal stem cell senescence.

Mesenchymal stem cells (MSCs) possess the ability to self-renew and differentiate into multiple cell types, making them highly suitable for use as seed cells in tissue engineering. These can be derived from various sources and have been found to play crucial roles in several physiological processes, such as tissue repair, immune regulation, and intercellular communication. However, the limited capacity for cell proliferation and the secretion of senescence-associated secreted phenotypes (SASPs) pose challenges for the clinical application of MSCs. In this review, we provide a comprehensive summary of the senescence characteristics of MSCs and examine the different features of cellular microenvironments studied thus far. Additionally, we discuss the mechanisms by which cellular microenvironments regulate the senescence process of MSCs, offering insights into preserving their functionality and enhancing their effectiveness.

Dysregulation of cholesterol metabolism in cancer progression.

Cholesterol homeostasis has been implicated in the regulation of cellular and body metabolism. Hence, deregulated cholesterol homeostasis leads to the development of many diseases such as cardiovascular diseases, and neurodegenerative diseases, among others. Recent studies have unveiled the connection between abnormal cholesterol metabolism and cancer development. Cholesterol homeostasis at the cellular level dynamically circulates between synthesis, influx, efflux, and esterification. Any dysregulation of this dynamic process disrupts cholesterol homeostasis and its derivatives, which potentially contributes to tumor progression. There is also evidence that cancer-related signals, which promote malignant progression, also regulate cholesterol metabolism. Here, we described the relationship between cholesterol metabolism and cancer hallmarks, with particular focus on the molecular mechanisms, and the anticancer drugs that target cholesterol metabolism.

VEGF signaling governs the initiation of biliary-mediated liver regeneration through the PI3K-mTORC1 axis.

Biliary epithelial cells (BECs) are a potential source to repair the damaged liver when hepatocyte proliferation is compromised. Promotion of BEC-to-hepatocyte transdifferentiation could be beneficial to the clinical therapeutics of patients with end-stage liver diseases. However, mechanisms underlying the initiation of BEC transdifferentiation remain largely unknown. Here, we show that upon extreme hepatocyte injury, vegfaa and vegfr2/kdrl are notably induced in hepatic stellate cells and BECs, respectively. Pharmacological and genetic inactivation of vascular endothelial growth factor (VEGF) signaling would disrupt BEC dedifferentiation and proliferation, thus restraining hepatocyte regeneration. Mechanically, VEGF signaling regulates the activation of the PI3K-mammalian target of rapamycin complex 1 (mTORC1) axis, which is essential for BEC-to-hepatocyte transdifferentiation. In mice, VEGF signaling exerts conserved roles in oval cell activation and BEC-to-hepatocyte differentiation. Taken together, this study shows VEGF signaling as an initiator of biliary-mediated liver regeneration through activating the PI3K-mTORC1 axis. Modulation of VEGF signaling in BECs could be a therapeutic approach for patients with end-stage liver diseases.

CDK7-YAP-LDHD axis promotes D-lactate elimination and ferroptosis defense to support cancer stem cell-like properties.

Reprogrammed cellular metabolism is essential for maintaining cancer stem cells (CSCs) state. Here, we report that mitochondrial D-lactate catabolism is a necessary initiating oncogenic event during tumorigenesis of esophageal squamous cell carcinoma (ESCC). We discover that cyclin-dependent kinase 7 (CDK7) phosphorylates nuclear Yes-associated protein 1 (YAP) at S127 and S397 sites and enhances its transcription function, which promotes D-lactate dehydrogenase (LDHD) protein expression. Moreover, LDHD is enriched significantly in ESCC-CSCs rather than differentiated tumor cells and high LDHD status is connected with poor prognosis in ESCC patients. Mechanistically, the CDK7-YAP-LDHD axis helps ESCC-CSCs escape from ferroptosis induced by D-lactate and generates pyruvate to satisfy energetic demands for their elevated self-renewal potential. Hence, we conclude that esophageal CSCs adopt a D-lactate elimination and pyruvate accumulation mode dependent on CDK7-YAP-LDHD axis, which drives stemness-associated hallmarks of ESCC-CSCs. Reasonably, targeting metabolic checkpoints may serve as an effective strategy for ESCC therapy.

TMEM92 acts as an immune-resistance and prognostic marker in pancreatic cancer from the perspective of predictive, preventive, and personalized medicine.

Background: Pancreatic cancer presents extremely poor prognosis due to the difficulty of early diagnosis, low resection rate, and high rates of recurrence and metastasis. Immune checkpoint blockades have been widely used in many cancer types but showed limited efficacy in pancreatic cancer. The current study aimed to evaluate the landscape of tumor microenvironment (TME) of pancreatic cancer and identify the potential markers of prognosis and immunotherapy efficacy which might contribute to improve the targeted therapy strategy and efficacy in pancreatic cancer in the context of predictive, preventive, and personalized medicine (PPPM). Methods: In the current study, a total of 382 pancreatic samples from the datasets of Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were selected. LM22 gene signature matrix was applied to quantify the fraction of immune cells based on "CIBERSORT" algorithm. Weighted Gene Co-expression Network Analysis (WGCNA) and Molecular Complex Detection (MCODE) algorithm was applied to confirm the hub-network of immune-resistance phenotype. A nomogram model based on COX and Logistic regression was constructed to evaluate the prognostic value and the predictive value of hub-gene in immune-response. The role of transmembrane protein 92 (TMEM92) in regulating cell proliferation was evaluated by MTS assay. Western blot and Real-time PCR were applied to assess the biological effects of PD-L1 inhibition by TMEM92. Moreover, the effect of TMEM92 in immunotherapy was evaluated with PBMC co-culture and by MTS assay. Results: Two tumor-infiltrating immune cell (TIIC) phenotypes were identified and a weighted gene co-expression network was constructed to confirm the 167 gene signatures correlated with immune-resistance TIIC subtype. TMEM92 was further identified as a core gene of 167 gene signature network based on MCODE algorithm. High TMEM92 expression was significantly correlated with unfavorable prognosis, characterizing by immune resistance. A nomogram model and external validation confirmed that TMEM92 was an independent prognostic factor in pancreatic cancer. An elevated tumor mutation burden (TMB), mostly is consistent with commonly mutations of KRAS and TP53, was found in the high TMEM92 group. The predictive role of TMEM92 in immunotherapeutic response was also confirmed by IMvigor210 datasets. In addition, the specific biological roles of TMEM92 in cancer was explored in vitro. The results showed that abnormal overexpression of TMEM92 was significantly associated with the poor survival rate of pancreatic cancer. Moreover, we demonstrated that TMEM92 inhibit tumour immune responses of the anti-PD-1 antibody with PBMC co-culture. Conclusion: The current study explored for the first time the immune-resistance phenotype of pancreatic cancer and identified TMEM92 as an innovative marker in predicting clinical outcomes and immunotherapeutic efficacy. These findings not only help to recognize high-risk and immune-resistance population which could be supplied targeted prevention, but also provide personalized medical services by intervening TMEM92 function to improve the prognosis of pancreatic cancer. In addition, the biological role of TMEM92 might reveal the potential molecular mechanisms of pancreatic cancer and lead to a novel sight for development of a PPPM approach for pancreatic cancer management. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-022-00287-0.

Progerin modulates the IGF-1R/Akt signaling involved in aging.

Progerin, a product of LMNA mutation, leads to multiple nuclear abnormalities in patients with Hutchinson-Gilford progeria syndrome (HGPS), a devastating premature aging disorder. Progerin also accumulates during physiological aging. Here, we demonstrate that impaired insulin-like growth factor 1 receptor (IGF-1R)/Akt signaling pathway results in severe growth retardation and premature aging in Zmpste24-/- mice, a mouse model of progeria. Mechanistically, progerin mislocalizes outside of the nucleus, interacts with the IGF-1R, and down-regulates its expression, leading to inhibited mitochondrial respiration, retarded cell growth, and accelerated cellular senescence. Pharmacological treatment with the PTEN (phosphatase and tensin homolog deleted on chromosome 10) inhibitor bpV (HOpic) increases Akt activity and improves multiple abnormalities in Zmpste24-deficient mice. These findings provide previously unidentified insights into the role of progerin in regulating the IGF-1R/Akt signaling in HGPS and might be useful for treating LMNA-associated progeroid disorders.

Liver tumor-initiating cells initiate the formation of a stiff cancer stem cell microenvironment niche by secreting LOX.

Accumulating evidence has shown that the traits of tumor-initiating cells (TICs) are controlled by the microenvironment niches (MENs), but the composition and remodeling mechanisms of the MENs of TICs are poorly defined. Here, we report that the voltage-gated calcium channel α2δ1 subunit-positive TICs of hepatocellular carcinoma (HCC) specifically secret lysyl oxidase (LOX), which leads to the cross-linking of collagen, forming a stiff extracellular matrix (ECM) that is sufficient to drive the formation of TICs with a stiff mechanical trait and is subsequently required for the maintenance the properties of HCC TICs. Furthermore, the cross-linked collagen results in the upregulation of integrin α7 (ITGA7), increased phosphorylation of FAK and extracellular signal-regulated kinase 1/2 (ERK1/2). Inhibition of ITGA7 abolishes all the effects of cross-linked collagen mediated by LOX. Hence, the α2δ1+ HCC TICs initiate ECM remodeling by secreting LOX to create a stiff MEN of TIC with cross-linked collagen, which drives the acquisition and subsequent maintenance of the properties of HCC TICs through ITGA7-FAK-ERK1/2 signaling pathway.

Protective roles of mesenchymal stem cells on skin photoaging: A narrative review.

Skin is a natural barrier of human body and a visual indicator of aging process. Exposure to ultraviolet (UV) radiation in the sunlight may injure the skin tissues and cause local damage. Besides, it is reported that repetitive or long-term exposure to UV radiation may reduce the collagen production, change the normal skin structure and cause premature skin aging. This is termed "photoaging". The classical symptoms of photoaging include increased roughness, wrinkle formation, mottled pigmentation or even precancerous changes. Mesenchymal stem cells (MSCs) are a kind of cells with the ability of self-renewal and multidirectional differentiation into many types of cells, like adipocytes, osteoblasts and chondrocytes. Researchers have explored diverse pharmacological actions of MSCs because of their migratory activity, paracrine actions and immunoregulation effects. In recent years, the huge potential of MSCs in preventing skin from photoaging has gained wide attention. MSCs exert their beneficial effects on skin photoaging via antioxidant effect, anti-apoptotic/anti-inflammatory effect, reduction of matrix metalloproteinases (MMPs) and activation of dermal fibroblasts proliferation. MSCs and MSC related products have demonstrated huge potential in the treatment of skin photoaging. This narrative review concisely sums up the recent research developments on the roles of MSCs in protection against photoaging and highlights the enormous potential of MSCs in skin photoaging treatment.

Immune landscape of advanced gastric cancer tumor microenvironment identifies immunotherapeutic relevant gene signature.

BACKGROUND: Advanced gastric cancer (AGC) is a disease with poor prognosis due to the current lack of effective therapeutic strategies. Immune checkpoint blockade treatments have shown effective responses in patient subgroups but biomarkers remain challenging. Traditional classification of gastric cancer (GC) is based on genomic profiling and molecular features. Therefore, it is critical to identify the immune-related subtypes and predictive markers by immuno-genomic profiling. METHODS: Single-sample gene-set enrichment analysis (ssGSEA) and ESTIMATE algorithm were used to identify the immue-related subtypes of AGC in two independent GEO datasets. Weighted gene co-expression network analysis (WGCNA) and Molecular Complex Detection (MCODE) algorithm were applied to identify hub-network of immune-related subtypes. Hub genes were confirmed by prognostic data of KMplotter and GEO datasets. The value of hub-gene in predicting immunotherapeutic response was analyzed by IMvigor210 datasets. MTT assay, Transwell migration assay and Western blotting were performed to confirm the cellular function of hub gene in vitro. RESULTS: Three immune-related subtypes (Immunity_H, Immunity_M and Immunity_L) of AGC were identified in two independent GEO datasets. Compared to Immunity_L, the Immuntiy_H subtype showed higher immune cell infiltration and immune activities with favorable prognosis. A weighted gene co-expression network was constructed based on GSE62254 dataset and identified one gene module which was significantly correlated with the Immunity_H subtype. A Hub-network which represented high immune activities was extracted based on topological features and Molecular Complex Detection (MCODE) algorithm. Furthermore, ADAM like decysin 1 (ADAMDEC1) was identified as a seed gene among hub-network genes which is highly associated with favorable prognosis in both GSE62254 and external validation datasets. In addition, high expression of ADAMDEC1 correlated with immunotherapeutic response in IMvigor210 datasets. In vitro, ADAMDEC1 was confirmed as a potential protein in regulating proliferation and migration of gastric cancer cell. Deficiency of ADAMDEC1 of gastric cancer cell also associated with high expression of PD-L1 and Jurkat T cell apoptosis. CONCLUSIONS: We identified immune-related subtypes and key tumor microenvironment marker in AGC which might facilitate the development of novel immune therapeutic targets.

Adipose-derived stem cells regulate metabolic homeostasis and delay aging by promoting mitophagy.

Tissues undergo a process of degeneration as the body ages. Mesenchymal stem cells (MSCs) have been found to have major potential in delaying the aging process in tissues and organs. However, the mechanism underlying the anti-aging effects of MSC is not clear which limits clinical applications. In this study, we used adipose-derived mesenchymal stem cells (ADSCs) to perform anti-aging treatments on senescent cells and progeroid animal models. Following intervention with ADSCs, replicative senescence was delayed and metabolic homeostasis was transformed from catabolism to anabolism. Metabolomic tests were used to analyze different metabolites. We found that ADSCs acted to accelerate mitophagy which eliminated intracellular ROS and improved the quality of mitochondria. These processes acted to regulate the cellular metabolic homeostasis and ultimately delayed the process of aging. Allogeneic stem cell therapy in a Progeria animal model (DNA polymerase gamma (POLG) knockin, mitochondrial dysfunction) also showed that ADSC therapy can improve alopecia and kyphosis by promoting mitophagy. Our research confirms for the first time that allogeneic stem cell therapy can improve aging-related symbols and phenotypes through mitochondrial quality control. These results are highly significant for the future applications of stem cells in aging-related diseases.

PolG Inhibits Gastric Cancer Glycolysis and Viability by Suppressing PKM2 Phosphorylation.

PURPOSE: Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the third leading cause of cancer-related death. There is a critical need for the development of novel therapies in GC. DNA polymerase gamma (PolG) has been implicated in mitochondrial homeostasis and affects the development of numerous types of cancer, however, its effects on GC and molecular mechanisms remain to be fully determined. The aim of the present research was to clarify the effects of PolG on GC and its possible molecular mechanism of action. METHODS: The GSE62254 dataset was used to predict the effect of PolG on prognostic value in GC patients. Lentivirus-mediated transduction was used to silence PolG expression. Western blot analysis evinced the silencing effect. Co-immunoprecipitation (Co-IP) analysis was performed to explore the potential molecular mechanism of action. Analysis of the glycolysis process in GC cells was also undertaken. Cell proliferation was determined using a CCK-8 (Cell Counting Kit-8) proliferation assay. Cell migration was detected using the Transwell device. Animal experiments were used to measure in vivo xenograft tumor growth. RESULTS: GC patients with low PolG expression have worse overall survival (OS) and progression-free survival (PFS). PolG binds to PKM2 and affects the activation of Tyr105-site phosphorylation, thus interfering with the glycolysis of GC cells. In vitro tumor formation experiments in mice also confirmed that PolG silencing of GC has a stronger proliferation ability. PolG can suppress GC cell growth both in vivo and in vitro. CONCLUSION: Our study reveals a potential molecular mechanism between PolG and the energy metabolic process of GC tumor cells for the first time, suggesting PolG as an independent novel potential therapeutic target for tumor therapy, and providing new ideas for clinical GC treatment.

The miR-204-5p/FOXC1/GDF7 axis regulates the osteogenic differentiation of human adipose-derived stem cells via the AKT and p38 signalling pathways.

BACKGROUND: Human adipose-derived stem cells (hADSCs) are stem cells with the potential to differentiate in multiple directions. miR-204-5p is expressed at low levels during the osteogenic differentiation of hADSCs, and its specific regulatory mechanism remains unclear. Here, we aimed to explore the function and possible molecular mechanism of miR-204-5p in the osteogenic differentiation of hADSCs. METHODS: The expression patterns of miR-204-5p, Runx2, alkaline phosphatase (ALP), osteocalcin (OCN), forkhead box C1 (FOXC1) and growth differentiation factor 7 (GDF7) in hADSCs during osteogenesis were detected by qRT-PCR. Then, ALP and alizarin red staining (ARS) were used to detect osteoblast activities and mineral deposition. Western blotting was conducted to confirm the protein levels. The regulatory relationship among miR-204-5p, FOXC1 and GDF7 was verified by dual-luciferase activity and chromatin immunoprecipitation (ChIP) assays. RESULTS: miR-204-5p expression was downregulated in hADSC osteogenesis, and overexpression of miR-204-5p suppressed osteogenic differentiation. Furthermore, the levels of FOXC1 and GDF7 were decreased in the miR-204-5p mimics group, which indicates that miR-204-5p overexpression suppresses the expression of FOXC1 and GDF7 by binding to their 3'-untranslated regions (UTRs). Overexpression of FOXC1 or GDF7 improved the inhibition of osteogenic differentiation of hADSCs induced by the miR-204-5p mimics. Moreover, FOXC1 was found to bind to the promoter of miR-204-5p and GDF7, promote the deacetylation of miR-204-5p and reduce the expression of miR-204-5p, thus promoting the expression of GDF7 during osteogenic differentiation. GDF7 induced hADSC osteogenesis differentiation by activating the AKT and P38 signalling pathways. CONCLUSIONS: Our results demonstrated that the miR-204-5p/FOXC1/GDF7 axis regulates the osteogenic differentiation of hADSCs via the AKT and p38 signalling pathways. This study further revealed the regulatory mechanism of hADSC differentiation from the perspective of miRNA regulation.

The Effects of Timing of Postoperative Radiotherapy on Hypertrophic Scar in a Rabbit Model.

BACKGROUND Hypertrophic scar is associated with excessive proliferation of fibroblasts, the accumulation of collagen fibers, and angiogenesis associated with chronic inflammation. Scar resection, combined with radiotherapy, is widely used in clinical practice, but timing remains controversial. This study aimed to investigate the association between the timing of postoperative radiotherapy and the effects on hypertrophic scar in a rabbit model. MATERIAL AND METHODS Forty New Zealand white rabbits, 8-12 months old, weighing 1.8-2.3 kg were used in the model of hypertrophic scar and underwent surgical resection with or without postoperative radiotherapy. The study groups included: Group 1, the non-resection group; Group 2, the resection and non-radiotherapy group; Group 3, the immediate postoperative radiotherapy group; Group 4, the 12-hour postoperative radiotherapy group; Group 5, the 24-hour postoperative radiotherapy group; Group 6, the 48-hour postoperative radiotherapy group; Group 7, the 72-hour postoperative radiotherapy group; and Group 8, the 120-hour postoperative radiotherapy group. The rabbit ear skin was observed after treatment, and the hypertrophic scar index (HI), fibroblast numerical area density (NA), and collagen fiber area density (AA) were determined. RESULTS The HI, NA, and AA were significantly lower after 48 hours of postoperative radiotherapy (P<0.05), with the effects occurring mainly within 24 hours. There was no difference in HI, NA, and AA between the radiotherapy and non-radiotherapy groups within 24 hours after surgery. CONCLUSIONS In a rabbit model of hypertrophic scar, surgical resection combined with radiotherapy resulted in an optimal effect within 24 hours after surgery.

BRAFi induced demethylation of miR-152-5p regulates phenotype switching by targeting TXNIP in cutaneous melanoma.

Treatment of advanced BRAFV600-mutant melanoma using BRAF inhibitors (BRAFi) eventually leads to drug resistance and selects for highly metastatic tumor cells. We compared the most differentially dysregulated miRNA expression profiles of vemurafenib-resistant and highly-metastatic melanoma cell lines obtained from GEO DataSets. We discovered miR-152-5p was a potential regulator mediating melanoma drug resistance and metastasis. Functionally, knockdown of miR-152-5p significantly compromised the metastatic ability of BRAFi-resistant melanoma cells and overexpression of miR-152-5p promoted the formation of slow-cycling phenotype. Furthermore, we explored the cause of how and why miR-152-5p affected metastasis in depth. Mechanistically, miR-152-5p targeted TXNIP which affected metastasis and BRAFi altered the methylation status of MIR152 promoter. Our study highlights the crucial role of miR-152-5p on melanoma metastasis after BRAFi treatment and holds significant implying that discontinuous dosing strategy may improve the benefit of advanced BRAFV600-mutant melanoma patients.

Surgical Treatment Strategy for Severe Rhinophyma With Bilateral Pedicled Nasolabial Flaps.

BACKGROUND: Rhinophyma is a rare disease characterized by chronic inflammation and hypertrophy of sebaceous glands, blood vessels, and fibrous tissue, associated with end-stage severe acne rosacea. There are multiple approaches to treatment and repair, including dermal shaving, secondary intention healing, free skin graft, and skin flaps. However, these methods have various disadvantages, such as prolonged healing, obvious scarring, and skin texture mismatch. Therefore, the authors adopted surgical excision with bilateral pedicled nasolabial flaps, which have better color, texture, thickness, and symmetry. METHODS: The authors present a case of severe nasal tip rhinophyma successfully treated by excision and repair with bilateral pedicled nasolabial flaps. This procedure combines deep excision of the focal lesion and coverage with bilateral nasolabial flaps. RESULTS: The bilateral pedicled nasolabial flaps were used for severe rhinophyma in a patient. After the operation, the flaps survived uneventfully in this study. Both functional and aesthetic results were satisfactory at 3 months. CONCLUSION: The authors offer an effective method for surgical treatment of rhinophyma. Excision of hypertrophic nasal tissue is an acknowledged effective treatment for patients with severe rhinophyma. After excision, reconstruction with nasolabial flaps results in satisfactory outcomes both functionally and aesthetically. Therefore, this approach should be considered an appropriate alternative in cases of severe rhinophyma.

Anthropometric labial analysis of Han Chinese young adults.

BACKGROUND: Facial features vary in size and proportions between different races. This study aimed to measure the anthropometric variables of the labial region in Han Chinese young adults. MATERIALS AND METHODS: A total of 900 college students (475 male and 425 female) of Chinese Han ethnicity from the northern China were included. Measurements of the labial region included 14 linear items and seven proportions. RESULTS: All the linear measurements of the males were significantly higher than those of the females (all P < 0.001). Significant gender differences were found in the philtrum morphology, philtrum width, upper vermilion-cutaneous lip, lower vermilion-cutaneous lip, and vermilion. There are significant differences in the anthropometric variables of the labial region between male and female Han Chinese young adults. CONCLUSIONS: These data may be used as a reference standard for labial reconstructive and aesthetic surgery.

CXCL11 promotes self-renewal and tumorigenicity of α2δ1+ liver tumor-initiating cells through CXCR3/ERK1/2 signaling.

Tumor-initiating cells (TICs), which are responsible for sustaining tumor growth and recurrence, rely on several regulatory factors. However, the mechanism of inflammation-related molecules in the acquisition and maintenance of TIC properties in hepatocellular carcinoma (HCC) remains elusive. We previously demonstrated that the voltage-gated calcium channel α2δ1 subunit is a functional surface marker of HCC TICs. Here, we found that the expression of an inflammation-related molecule C-X-C motif chemokine 11 (CXCL11) was significantly upregulated in α2δ1+ HCC TICs and that CXCL11 induced the expression of stem cell-related genes, such as BMI1, NANOG, MDR1, ABCG2, and CACNA2D1. Furthermore, CXCL11 could promote the acquisition and maintenance of self-renewal, tumorigenic, and chemoresistance properties of α2δ1+ HCC TICs by activating the extracellular signal-regulated kinase (ERK1/2) through its affinity receptor CXCR3. Collectively, our results suggest that CXCL11 may positively regulate the stemness of α2δ1+ HCC TICs via ERK1/2 activation through an autocrine signaling pathway.

High temperature requirement factor A1 (HTRA1) regulates the activation of latent TGF-ß1 in keloid fibroblasts.

Scar treatments are considered a major issue in the plastic surgery field. Activation of the transforming growth factor-ß (TGF-ß)-mediated signaling pathway plays a key role in the scar pathogeneses, and high temperature requirement factor A1 (HTRA1) inhibits TGF-ß1 activation in tumor cells. Our study aims to investigate the role of HTRA1 in the pathogenesis of scars. The mRNA levels of HTRA1 was evaluated by real time PCR, HTRA1 protein expression was determined using western blot and immunohistochemistry, and a luciferase assay was applied to measure dynamic changes of TGF-ß1 activity. We found that the expression of HTRA1 was significantly elevated in keloid tissues, compared to normal skin, and TGF-ß1 mRNA levels slightly increase in the keloid tissue. Furthermore, active TGF-ß1 protein levels and Smad2 phosphorylation significantly increased in the keloid tissue. Treatment with the latent TGF-ß1 or recombinant human HTRA1 (rhHTRA1), alone or in combination, increased Smad2 phosphorylation levels in keloid fibroblasts and active TGF-ß1 contents of associated supernatants. Our results suggest that HTRA1 is involved in the pathogenesis of scars through regulating activation of latent TGF-ß1 in keloid fibroblasts, and our study reveals that HTRA1 is a novel target that regulates scar formation.