The use of bone wax versus dermal regeneration matrix for the reconstruction of scalp defects.

BACKGROUND: Secondary intention healing is an alternative to consider in large tumors or tumors located in areas of limited skin mobility, such as the scalp. To promote epithelialization, we can use Dermal Regeneration Matrix (DRM) or bone wax. OBJECTIVE: This study aimed to compare the efficacy of DRM and bone wax in secondary intention healing of cutaneous scalp tumors in elderly patients with comorbidities. MATERIALS AND METHODS: The medical records of 18 patients with cutaneous scalp tumor healing by secondary intention from February 2022 to April 2023 were analyzed for demographic variables, tumor and surgical characteristics, time from withdrawal of material to complete epithelialization, and need for subsequent surgical intervention. RESULTS: Bone wax was used in 6 patients and DRM in 12. The mean patient age was 84.3 years, and the mean tumor size was 2.7 cm. There were no significant differences in demographics or postoperative complications between the groups. The median time to complete epithelization was 84.5 (60.2-108.7) days in the bone wax group and 105.0 (91.0-126.0) days in the DRM group, with no significant differences (P = 0.15). CONCLUSIONS: Bone wax is a simple and economical material that can be used for secondary intention healing of scalp tumors in elderly patients with high surgical risk.

Vascular endothelial growth factor ameliorated palmitate-induced cardiomyocyte injury via JNK pathway.

Enhanced apoptosis of cardiomyocytes in suffering overloaded saturated fatty acids (SFAs) can result in myocardial infarction and cardiac dysfunction. The function of vascular endothelial growth factor (VEGF) in cardiomyocyte protection was not clearly described. To investigate the preservative effects of VEGF sensitization on ceramide-mediated programmed cell death of cardiomyocytes, palmitate-induced injury in H9c2 cells was established as an in vitro model. Results revealed that 0.5 mM palmitate application effectively led to debased viability and activated apoptotic factors. A significant time-dependent relation between PAL and cardiomyocyte injury was observed. The apoptosis rate was increased greatly after 16 h of treatment with 0.5 mM PAL. In addition, cell viability was restored by VEGF overexpression during treatment with 0.5 mM PAL. Reduced apoptosis rate and expression of caspase 3, Bax, and NF-κB p65 were observed in this process, while boosted Bcl-2, p-JNK/JNK expression and activity of caspase 3 were checked. However, p-ERK/ERK levels did not exhibit a significant change. These findings indicated the protective effects of VEGF in confronting the ceramide-induced cardiomyocyte apoptosis, and would devote therapeutic targets for cardiovascular safeguard in dealing with fatty acid stress.

Methyl Palmitate-A suitable adjuvant for Sorafenib therapy to reduce in vivo toxicity and to enhance anti-cancer effects on hepatocellular carcinoma cells.

This study focused on evaluating the potency of Methyl Palmitate in reducing in vivo toxicity with enhancement of anti-cancer effects of Sorafenib. In vitro anti-cancer effects on human Hep-G2 cell line were analysed by MTT, Trypan blue, clonogenic, wound scratch migration and TUNEL assays. An in vivo study for anti-angiogenesis effect, toxicity and teratogenicity was analysed in Zebrafish embryos. The combination of Sorafenib (4.5 µmol/L) with Methyl Palmitate (3 mmol/L) significantly enhanced anti-cancer effects on Hep-G2 cell line by increasing cytotoxicity (P ≤ .05 in MTT assay; P ≤ .01 in Trypan blue assay), apoptosis (P ≤ .05) and decreasing the metastatic migration (P ≤ .01) than Sorafenib alone treatment. A prominent inhibition of angiogenesis in vivo was observed for combination treatment. At 5 dpf, only <20% toxicity was observed for 3 mmol/L Methyl palmitate while it was 65.75% for Sorafenib treatment which implies that it is a safer dose for in vivo treatments. A highly significant (P ≤ .001) reduction (43.20%) in toxicity was observed in combination treatment. Thus, the Sorafenib-Methyl Palmitate combination showed a promising treatment effect with significantly reduced in vivo toxicity when compared with Sorafenib alone treatment, and hence the Methyl Palmitate may serve as a good adjuvant for Sorafenib therapy.

Use of bone wax reduces blood loss and transfusion rates after total knee arthroplasty.

BACKGROUND: Unnecessary costs and complications can be reduced by minimizing blood loss and allogeneic blood transfusion in cases of total knee arthroplasty (TKA). This study evaluated the effectiveness of bone wax in reducing blood loss and transfusion rates after TKA. METHODS: A total of 674 consecutive TKAs performed for degenerative osteoarthritis were retrospectively reviewed. Propensity score-matching and inverse probability of treatment weighting analyses were performed for demographics, comorbidities, use of medications, preoperative laboratory findings and radiologic prosthetic coverage of osteotomy surface. In the bone wax group, bone wax (2.5 g) was applied to the uncovered bone section around the prostheses along with the topical administration of tranexamic acid, whereas hemostasis was achieved in the control group with the topical administration of tranexamic acid. Intergroup comparisons of estimated blood loss, decreases in hemoglobin (Hb) levels, and transfusion rates were performed. RESULTS: The mean estimated blood loss and volume of postoperative drainage were reduced in the bone wax group. The maximum decreases in Hb levels on postoperative days 1, 3, 5, and 7 were 1.8 ± 0.7 ml, 2.5 ± 0.8 ml, 2.7 ± 0.8 ml, and 2.8 ± 0.8 ml in the bone wax group and 2.1 ± 1.0 ml, 3.0 ± 1.2 ml, 3.1 ± 1.1 ml, and 3.2 ± 1.1 ml in the control group, respectively. The postoperative transfusion rates decreased markedly from 8.8% to 2.0% when bone wax was used. CONCLUSIONS: The use of bone wax significantly reduced blood loss, decreased Hb levels, and the risk of transfusion. LEVEL OF EVIDENCE: Level III, Therapeutic studies.

Punicalagin Attenuates Palmitate-Induced Lipid Droplet Content by Simultaneously Improving Autophagy in Hepatocytes.

SCOPE: Several studies show that excessive lipid intake can cause hepatic steatosis. To investigate lipotoxicity on cellular level, palmitate (PA) is often used to highly increase lipid droplets (LDs). One way to remove LDs is autophagy, while it is controversially discussed if autophagy is also affected by PA. It is aimed to investigate whether PA-induced LD accumulation can impair autophagy and punicalagin, a natural autophagy inducer from pomegranate, can improve it. METHODS AND RESULTS: To verify the role of autophagy in LD degradation, HepG2 cells are treated with PA and analyzed for LD and perilipin 2 content in presence of autophagy inducer Torin 1 and inhibitor 3-Methyladenine. PA alone seems to initially induce autophagy-related proteins but impairs autophagic-flux in a time-dependent manner, considering 6 and 24 h PA. To examine whether punicalagin can prevent autophagy impairment, cells are cotreated for 24 h with PA and punicalagin. Results show that punicalagin preserves expression of autophagy-related proteins and autophagic flux, while simultaneously decreasing LDs and perilipin 2. CONCLUSION: Data provide new insights into the role of PA-induced excessive LD content on autophagy and suggest autophagy-inducing properties of punicalagin, indicating that punicalagin can be a health-beneficial compound for future research on lipotoxicity in liver.

Fructose-palmitate based high calorie induce steatosis in HepG2 cells via mitochondrial dysfunction: An in vitro approach.

A proper in vitro model for conducting research on high energy food induced steatosis via defective energy metabolism in the liver is not visible in the literature. The present study developed an in vitro model in HepG2 cell line to mimic high energy diet induced steatosis in liver via mitochondrial dysfunction. For this, HepG2 cells were treated with fructose (100 mM) and palmitate (100 µM) for about 24 h and subjected for biochemical analysis relevant to lipogenesis and mitochondrial biology. Our findings showed that fructose-palmitate treatment caused significant lipid accumulation and rise in lipogenic proteins. Further studies showed alteration in mitochondrial integrity, dynamics and oxidative phosphorylation. Mitochondrial integrity was affected by the dissipation of trans-membrane potential, surplus mitochondrial superoxide with calcium overload. Similarly, mitochondrial dynamics were altered with up regulation of mitochondrial fission proteins: DRP1 and FIS1, cytochrome c release, caspase-3 activity and apoptosis. Various components of the electron transport chain: complex I, II, III and IV were altered with significant depletion in oxygen consumption. Overall our findings illustrate the dominant role of mitochondria in the genesis of high fructose-palmitate induced steatosis in HepG2 cells. Since continuous high energy food consumption is the main inducer of steatosis, this model is found to be an ideal one for preliminary and basic research in the area of liver disease via mitochondrial dysfunction.

Improved Healing by Adjuvant Osteoconductive Therapy Using a Novel Cotton-Like Hydroxyapatite Sheet After Median Sternotomy.

The union rate of wire fixation after median sternotomy remains unsatisfactory. We developed a novel osteoconductive sheet composed of hydrophilized hydroxyapatite and evaluated its osteogenetic effect when interposed between sternal halves in a canine model. Eighteen canines were divided equally into groups based on the hemostatic agent used: osteoconductive sheet (S), none (C), and bone wax (BW). After median sternotomy, the sternal halves were closed by wire fixation. In each group, 3 canines were euthanized at 1 month, while 3 were euthanized at 2 months. Resected sternums were mechanically assessed by the 3-point bending test, radiographically assessed by micro-CT, and pathologically assessed to quantify the osteogenesis between sternal halves. Compared with the BW group, the S group had a greater maximum stress at 1 month (S: 322.9 ± 107.7 N, C: 233.0 ± 62.7 N, BW: 124.9 ± 88.4 N; P = 0.025), and greater maximum shear force at 1 month (S: 1.92 ± 0.67 N/m2; C: 1.23 ± 0.28 N/m2; BW: 0.68 ± 0.41 N/m2; P = 0.025). Micro-CT revealed that the S group had more osteogenesis than the BW group at 1 month (25.7% ± 9.8% vs 6.9% ± 9.2%), and 2 months (34.0% ± 15.1% vs 14.8% ± 9.4%); the respective values in the C group were 17.1% ± 7.2% and 29.7% ± 9.3%. Pathologic examination revealed that the S group had the greatest osteogenetic area at 2 months (S: 38.8% ± 18.8%; C: 24.5% ± 6.9%; BW: 24.7% ± 18.6%). Adjuvant osteoconductive therapy using a cotton-like hydroxyapatite sheet in addition to wire fixation significantly improved sternal healing compared with BW. This new material also showed relatively better outcome than the C group.

Palm Oil and Beta-palmitate in Infant Formula: A Position Paper by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) Committee on Nutrition.

BACKGROUND: Palm oil (PO) is used in infant formulas in order to achieve palmitic acid (PA) levels similar to those in human milk. PA in PO is esterified predominantly at the SN-1,3 position of triacylglycerol (TAG), and infant formulas are now available in which a greater proportion of PA is in the SN-2 position (typical configuration in human milk). As there are some concerns about the use of PO, we aimed to review literature on health effects of PO and SN-2-palmitate in infant formulas. METHODS: PubMed and Cochrane Database of Systematic Reviews were systematically searched for relevant studies on possible beneficial effects or harms of either PO or SN-2-palmitate in infant formula on various health outcomes. RESULTS: We identified 12 relevant studies using PO and 21 studies using SN-2-palmitate. Published studies have variable methodology, subject characteristics, and some are underpowered for the key outcomes. PO is associated with harder stools and SN-2-palmitate use may lead to softer stool consistency. Bone effects seem to be short-lasting. For some outcomes (infant colic, faecal microbiota, lipid metabolism), the number of studies is very limited and summary evidence inconclusive. Growth of infants is not influenced. There are no studies published on the effect on markers of later diseases. CONCLUSIONS: There is insufficient evidence to suggest that PO should be avoided as a source of fat in infant formulas for health reasons. Inclusion of high SN-2-palmitate fat blend in infant formulas may have short-term effects on stool consistency but cannot be considered essential.

Dietary palmitate cooperates with Src kinase to promote prostate tumor progression.

Numerous genetic alterations have been identified during prostate cancer progression. The influence of environmental factors, particularly the diet, on the acceleration of tumor progression is largely unknown. Expression levels and/or activity of Src kinase are highly elevated in numerous cancers including advanced stages of prostate cancer. In this study, we demonstrate that high-fat diets (HFDs) promoted pathological transformation mediated by the synergy of Src and androgen receptor in vivo. Additionally, a diet high in saturated fat significantly enhanced proliferation of Src-mediated xenograft tumors in comparison with a diet high in unsaturated fat. The saturated fatty acid palmitate, a major constituent in a HFD, significantly upregulated the biosynthesis of palmitoyl-CoA in cancer cells in vitro and in xenograft tumors in vivo. The exogenous palmitate enhanced Src-dependent mitochondrial ß-oxidation. Additionally, it elevated the amount of C16-ceramide and total saturated ceramides, increased the level of Src kinase localized in the cell membrane, and Src-mediated downstream signaling, such as the activation of mitogen-activated protein kinase and focal adhesion kinase. Our results uncover how the metabolism of dietary palmitate cooperates with elevated Src kinase in the acceleration of prostate tumor progression.

Clinical evidence of the efficacy and safety of a new 3-in-1 anti-aging topical night serum-in-oil containing melatonin, bakuchiol, and ascorbyl tetraisopalmitate: 103 females treated from 28 to 84 days.

BACKGROUND: Topical melatonin is a potent antioxidant, yet there have been few clinical studies on its anti-aging effects on the skin. OBJECTIVES: To clinically assess the anti-aging efficacy and safety of a new 3-in-1 night facial serum (NFS) combining melatonin with bakuchiol, a novel retinol-like ingredient, and ascorbyl tetraisopalmitate, in all skin types. METHODS: Five clinical studies were performed, with a total of 103 subjects treated from 28 to 84 days. Under dermatologist supervision, a 3-month efficacy and safety study evaluated anti-aging properties by clinical scoring and instrumental evaluations. Two studies evaluated skin hydration properties for 12 hours after a single application of NFS. Two studies were performed in oily skin: a 1-month efficacy and safety study and a 1-month comedogenesis study. RESULTS: After 12 weeks, clinical evaluation showed a statistically significant decrease in wrinkles (11%), an increase in skin firmness (8%), a reduction in redness (70%; P < 0.01 for all), and an overall improvement in skin quality and complexion. The reduction in wrinkles and the increase in skin firmness were also supported by instrumental evaluations (Dermatop and Dynaskin). Hydration levels increased significantly from 30 minutes until 12 hours and transepidermal water loss significantly decreased after 4H and 6H. Subjects favorably evaluated the efficacy and cosmetic properties of the serum, and it was well tolerated in all skin types including oily skin. CONCLUSIONS: This 3-in-1 NFS showed significant clinical anti-aging effects when applied once daily and was well tolerated.

Management of jugular bulb injury during drilling of the internal auditory canal (ICA) for vestibular schwannoma surgery.

The retrosigmoid approach for vestibular schwannoma surgery has remained the standard approach by most neurosurgeons. Drilling the posterior wall of the internal auditory meatus (IAM) is an essential step in removing the intrameatal tumor. During IAM drilling, three anatomical structures can be encountered, including the posterior semicircular canal, vestibular aqueduct, and jugular bulb. Any of these can be injured during drilling, especially if the jugular bulb lies above the inferior edge of the IAM. Although IAM drilling is performed in most vestibular schwannoma surgeries, information on how to manage complications such as jugular bulb injury is lacking. Here we use an intraoperative video to demonstrate how to manage the inadvertent injury to the jugular bulb in order to avoid massive blood loss. We present a case of a 39-year-old woman with hearing loss, diagnosed with a cerebellopontine angle mass extending into the IAM. Surgery was required due to tumor progression. We used the retrosigmoid approach to access the tumor. During IAM drilling, the jugular bulb was injured. A thin layer of bone wax was applied under continuous suction. The margins of the wax were then gently compressed with a dissector; great care was taken to avoid pushing the wax into the jugular bulb. Excess bone wax was removed (video 1). A small diamond drill (2 mm) was used for further drilling. Our instructional video shows the surgical approach, microsurgical anatomy, and technical aspects of managing massive bleeding from jugular bulb injury. It should therefore be helpful for young neurosurgeons.

Nanoemulsions improve the efficacy of turmeric in palmitate- and high fat diet-induced cellular and animal models.

Turmeric is a well-known functional food exhibiting multiple biological activities in health and disease. However, low aqueous solubility and poor bioavailability limit its therapeutic potential. Herein, we investigated the utility of nanoemulsions as a carrier to improve the efficacy of turmeric. Compared with turmeric extract (TE), 5% TE-loaded nanoemulsion (TE-NE), which contains 20-fold lower curcumin content than TE, achieved similar inhibition of palmitate-induced lipotoxicity in HepG2 cells. Exposure of HepG2 cells to 5% TE-NE also suppressed the palmitate-induced accumulation of lipid vacuoles and reactive oxygen species comparably with TE, and was accompanied by decreased levels of sterol regulatory element-binding protein (SREBP)-1, peroxisome proliferator-activated receptor-γ2 (PPAR-γ2), cleaved caspase-3, and poly (ADP-ribose) polymerase (PARP). Consistent with these effects in HepG2 cells, oral administration of 5% TE-NE to mice fed a high fat diet (HFD) markedly suppressed lipid accumulation in liver, leading to a significant reduction in body weight and adipose tissue weight, equivalent to the effects observed with TE. Compared with TE, 5% TE-NE also equivalently inhibited the levels of SREBP-1, PPAR-γ2, cleaved caspase-3, and PARP in the liver of mice fed a HFD. Furthermore, TE and 5% TE-NE significantly improved serum lipid profiles in a similar manner. These observations indicate that nanoemulsions can improve the efficacy of turmeric, thereby eliciting more potent biological efficacy against palmitate- and high fat diet (HFD)-induced cellular damage.

Bone Wax in Neurosurgery: A Review.

It has been 125 years since the so-called initial use of bone wax (BW) by Sir Victor Horsley, and a review of this age-old hemostatic agent seems appropriate. The first use of BW for hemostasis occurred in the eighteenth century, when modeling or candle wax was used for hemostasis. Although the pioneers in the use of BW in craniofacial surgeries were Jean Louis Belloq, Khristian Khristianovich Salomon, and François Magendie, the first successful use in neurosurgery was demonstrated by Henri Ferdinand Dolbeau in 1864 after extirpation of a frontal osteoma. This technique was further popularized by Sir Victor Alexander Haden Horsley, the father of British neurosurgery, who is often incorrectly mentioned as the inventor of BW. Originally derived from beeswax, the currently available commercial preparation also contains paraffin wax and isopropyl palmitate. The main action being mechanical tamponade, BW has found several other uses in neurosurgery, other than being a hemostatic agent. Although it is cost-effective, the use of BW is associated with several complications also, including ineffective bone healing and infection. Several alternatives are being developed, but none are yet a full replacement for "Horsley's wax."

Effect of Methyl Palmitate on the Formation of Epidural Fibrosis in an Experimental Epidural Fibrosis Model.

AIM: To investigate the effects of local and systemic administration of methyl palmitate on the formation of epidural fibrosis. MATERIAL AND METHODS: Twenty-eight rats were randomly divided into four equal groups (control, Spongostan, local methyl palmitate and orally methyl palmitate) and laminectomy was performed between T11 and L1 in all rats. Local methyl palmitate (300 mg/kg) was applied with Spongostan; methyl palmitate (300 mg/kg) was given orally three times per week on different days for a total period of 4 weeks. Four weeks later, the vertebral column from T9 to L3, including the paraspinal muscles and epidural scar tissue, was removed en bloc and epidural fibrosis and arachnoidal involvement was graded and evaluated histopathologically. Kruskal-Wallis and Pearson Chi-Square test were used for statistical analysis. A statistically significant p-value was determined as p < 0.05. RESULTS: The grading of epidural fibrosis was lower at a statistically significant level in orally-administrated methyl palmitate groups compared to the control and spongostan groups (p < 0.05). CONCLUSION: The findings of this study show that oral methyl palmitate decreases the formation of epidural fibrosis and that this effect of methyl palmitate could be mediated by reducing the functions of inflammatory cells such as macrophages, neutrophils and fibroblasts, including anti-inflammatory and antioxidant effects.

Palmitate Increases ß-site AßPP-Cleavage Enzyme 1 Activity and Amyloid-ß Genesis by Evoking Endoplasmic Reticulum Stress and Subsequent C/EBP Homologous Protein Activation.

Epidemiological studies implicate diets rich in saturated free fatty acids (sFFA) as a potential risk factor for developing Alzheimer's disease (AD). In particular, high plasma levels of the sFFA palmitic acid (palmitate) were shown to inversely correlate with cognitive function. However, the cellular mechanisms by which sFFA may increase the risk for AD are not well known. Endoplasmic reticulum (ER) stress has emerged as one of the signaling pathways initiating and fostering the neurodegenerative changes in AD by increasing the aspartyl protease ß-site AßPP cleaving enzyme 1 (BACE1) and amyloid-ß (Aß) genesis. In this study, we determined the extent to which palmitate increases BACE1 and Aß levels in vitro and in vivo as well as the potential role of ER stress as cellular mechanism underlying palmitate effects. We demonstrate, in palmitate-treated SH-SY5Y neuroblastoma cells and in the hippocampi of palmitate-enriched diet-fed mice, that palmitate evokes the activation of the C/EBP Homologous Protein (CHOP), a transcription factor that is specifically responsive to ER stress. Induction of CHOP expression is associated with increased BACE1 mRNA, protein and activity levels, and subsequent enhanced amyloidogenic processing of amyloid-ß protein precursor (AßPP) that culminates in a substantial increase in Aß genesis. We further show that CHOP is an indispensable molecular mediator of palmitate-induced upregulation in BACE1 activity and Aß genesis. Indeed, we show that Chop-/- mice and CHOP knocked-down SH-SY5Y neuroblastoma cells do not exhibit the same commensurate degree of palmitate-induced increase in BACE1 expression levels and Aß genesis.

Omega-3 fatty acid EPA improves regenerative capacity of mouse skeletal muscle cells exposed to saturated fat and inflammation.

Sarcopenic obesity is characterised by high fat mass, low muscle mass and an elevated inflammatory environmental milieu. We therefore investigated the effects of elevated inflammatory cytokine TNF-α (aging/obesity) and saturated fatty acid, palmitate (obesity) on skeletal muscle cells in the presence/absence of EPA, a-3 polyunsaturated fatty acid with proposed anti-inflammatory, anti-obesity activities. In the present study we show that palmitate was lipotoxic, inducing high levels of cell death and blocking myotube formation. Cell death under these conditions was associated with increased caspase activity, suppression of differentiation, reductions in both creatine kinase activity and gene expression of myogenic factors; IGF-II, IGFBP-5, MyoD and myogenin. However, inhibition of caspase activity via administration of Z-VDVAD-FMK (caspase-2), Z-DEVD-FMK (caspase-3) and ZIETD-KMK (caspase 8) was without effect on cell death. By contrast, lipotoxicity associated with elevated palmitate was reduced with the MEK inhibitor PD98059, indicating palmitate induced cell death was MAPK mediated. These lipotoxic conditions were further exacerbated in the presence of inflammation via TNF-α co-administration. Addition of EPA under cytotoxic stress (TNF-α) was shown to partially rescue differentiation with enhanced myotube formation being associated with increased MyoD, myogenin, IGF-II and IGFBP-5 expression. EPA had little impact on the cell death phenotype observed in lipotoxic conditions but did show benefit in restoring differentiation under lipotoxic plus cytotoxic conditions. Under these conditions Id3 (inhibitor of differentiation) gene expression was inversely linked with survival rates, potentially indicating a novel role of EPA and Id3 in the regulation of apoptosis in lipotoxic/cytotoxic conditions. Additionally, signalling studies indicated the combination of lipo- and cyto-toxic effects on the muscle cells acted through ceramide, JNK and MAPK pathways and blocking these pathways using PD98059 (MEK inhibitor) and Fumonisin B1 (ceramide inhibitor) significantly reduced levels of cell death. These findings highlight novel pathways associated with in vitro models of lipotoxicity (palmitate-mediated) and cytotoxicity (inflammatory cytokine mediated) in the potential targeting of molecular modulators of sarcopenic obesity.

Oleate protects beta-cells from the toxic effect of palmitate by activating pro-survival pathways of the ER stress response.

Long-term exposure of beta cells to saturated fatty acids impairs insulin secretion and increases apoptosis. In contrast, unsaturated fatty acids protect beta-cells from the long-term negative effects of saturated fatty acids. We aimed to identify the mechanisms underlying this protective action of unsaturated fatty acids. To address the aim, insulin-secreting MIN6 cells were exposed to palmitate in the absence or presence of oleate and analyzed by using nano-LC MS/MS based proteomic approach. Important findings were validated by using alternative approaches. Proteomic analysis identified 34 proteins differentially expressed in the presence of palmitate compared to control samples. These proteins play a role in insulin processing, mitochondrial function, metabolism of biomolecules, calcium homeostasis, exocytosis, receptor signaling, ER protein folding, antioxidant activity and anti-apoptotic function. When oleate was also present during culture, expression of 15 proteins was different from the expression in the presence of palmitate alone. Most of the proteins affected by oleate are targets of the ER stress response and play a pro-survival role in beta cells such as protein folding and antioxidative defence. We conclude that restoration of pro-survival pathways of the ER stress response is a major mechanism underlying the protective effect of unsaturated fatty acids in beta-cells treated with saturated fatty acids.

Proteomic analysis of 3-MCPD and 3-MCPD dipalmitate toxicity in rat testis.

Thermal treatment of foodstuff containing fats and salt promotes the formation of 3-chloropropane-1,2-diol (3-MCPD) and its fatty acid esters. 3-MCPD-exposed rats develop testicular lesions and Leydig cell tumors. 3-MCPD and 3-MCPD ester toxicity is thought to be caused by 3-MCPD and its metabolites, since 3-MCPD esters are hydrolyzed in the gut. Inhibition of glycolysis is one of the few known molecular mechanisms of 3-MCPD toxicity. To obtain deeper insight into this process, a comparative proteomic approach was chosen, based on a 28-days repeated-dose feeding study with male Wistar rats. Animals received equimolar doses of 3-MCPD or 3-MCPD dipalmitate. A lower dose of 3-MCPD dipalmitate was also administered. Absence of histopathological changes supported an analysis of early cellular disturbance. Testes were analyzed by two-dimensional gel electrophoresis followed by mass-spectrometric protein identification. Data provide a comprehensive overview of proteomic changes induced by 3-MCPD and 3-MCPD dipalmitate in rat testis in an early phase of organ impairment. Results are compatible with known 3-MCPD effects on reproductive function, substantially extend our knowledge about cellular responses to 3-MCPD and support the hypothesis that toxicity of 3-MCPD and 3-MCPD esters is mediated via common effectors. DJ-1 was identified as a candidate marker for 3-MCPD exposure.

Non-invasive characterization of the adipogenic differentiation of human bone marrow-derived mesenchymal stromal cells by HS-SPME/GC-MS.

A non-invasive method to characterize human mesenchymal stromal cells during adipogenic differentiation was developed for the first time. Seven fatty acid methyl esters (FAMEs), including methyl laurate, methyl myristate, methyl palmitate, methyl linoleate, methyl oleate, methyl elaidate and methyl stearate, were used for characterizing adipogenic differentiation using headspace solid-phase microextraction (HS-SPME) which is a very simple and non-invasive method for the extraction of volatile compounds. Glassware was used for culturing mesenchymal stromal cells rather than the common plasticware to minimize contamination by volatile impurities. The optimal SPME fiber was selected by comparing diverse fibers containing two pure liquid polymers (PDMS and PA) and two porous solids (PDMS/DVB and CAR/PDMS). Using optimized procedures, we discovered that seven FAMEs were only detected in adipogenic differentiated mesenchymal stromal cells and not in the mesenchymal stromal cells before differentiation. These data could support the quality control of clinical mesenchymal stromal cell culture in the pharmaceutical industry in addition to the development of many clinical applications using mesenchymal stromal cells.