Gintonin-Enriched Panax ginseng Extract Fraction Sensitizes Renal Carcinoma Cells to TRAIL-Induced Apoptosis through DR4/5 Upregulation.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising chemotherapeutic agent because of its selective apoptotic action on cancer cells. However, resistance to TRAIL-induced apoptosis remains a challenge in many cancers. The gintonin-enriched Panax ginseng extract fraction (GEF) has diverse pharmacological benefits. We explored the combined efficacy of GEF and TRAIL in inducing apoptosis in human renal cell carcinoma (RCC) cells. The effect of GEF treatment on the viability, clonogenic potential, wound healing, and TRAIL-induced apoptotic signaling of RCC cells was studied in vitro. Our investigation revealed that GEF pre-treatment sensitized RCC cells to TRAIL-induced apoptosis, as evidenced by DNA fragmentation and cell proliferation, colony formation, and migration inhibition. This sensitization was linked to the upregulation of death receptors 4 and 5 and alterations in apoptotic protein expression, notably, the decreased expression of the Mu-2-related death-inducing gene, a novel anti-apoptotic protein. Our findings underscore the necessity of caspase activation for GEF/TRAIL-induced apoptosis using the pan-caspase inhibitor Z-VAD-FMK. This study demonstrates that GEF sensitizes human RCC cells to TRAIL-induced apoptosis by upregulating DR4/5 and modulating apoptotic protein expression. These findings suggest a promising strategy for overcoming TRAIL resistance in cancer therapy and highlight the potential of GEF as a valuable adjunct to TRAIL-based treatments.

Evaluating the Diverse Anticancer Effects of Laos Kaempferia parviflora (Black Ginger) on Human Melanoma Cell Lines.

Cancer has become a consistent concern globally and increasingly fatal. Malignant melanoma is a rising concern, with its increased mortality. Kaempferia parviflora Wall. ex Baker (K. parviflora (KP)), commonly known as black ginger, is well known for its medicinal contributions. For the first time, in the following study we investigated the antimelanoma potential of Laos KP extracts in human cell lines. KP extracts (KPE) in methanol, DCM, and ethyl acetate showed strong cell inhibition in both melanomas, with KPE-DCM being particularly effective in inhibiting melanoma cell migration, invasion, and proliferation by inducing cell cycle arrest and apoptosis, while KPE-Hexane exhibited a low cell inhibition rate and a more limited effect. KPE affected the increased expression of caspase-3, PARP andBax and the decreased expression of the BcL-2, Mu-2-related death-inducing gene (MUDENG, MuD) protein. Furthermore, KPE enhanced apoptotic cells in the absence and presence of the pancaspase inhibitor Z-VAD-FMK. Interestingly, these apoptotic cells were significantly suppressed by the caspase inhibitor. Moreover, elevated mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) levels, suggestive of KPE's mitochondrial-mediated apoptosis in melanoma cells, were also confirmed. KPE treatment increased MMP levels, and upregulated the generation of ROS in A375 cells but not in A2058 cells. However, pretreatment with an ROS scavenger (NAC) suppressed KPE-induced cell death and ROS generation. These results clearly pointed out KPE-induced mitochondrial-mediated apoptotic cell death as the mechanism behind the inhibition of the human melanoma cells. Future studies exploring the role of specific ROS sources and their interaction with mitochondrial dynamics could deepen the existing understanding on KPE-induced apoptosis.

Cinnamaldehyde-Rich Cinnamon Extract Induces Cell Death in Colon Cancer Cell Lines HCT 116 and HT-29.

Cinnamon is a natural spice with a wide range of pharmacological functions, including anti-microbial, antioxidant, and anti-tumor activities. The aim of this study is to investigate the effects of cinnamaldehyde-rich cinnamon extract (CRCE) on the colorectal cancer cell lines HCT 116 and HT-29. The gas chromatography mass spectrometry analysis of a lipophilic extract of cinnamon revealed the dominance of trans-cinnamaldehyde. Cells treated with CRCE (10-60 µg/mL) showed significantly decreased cell viability in a time- and dose-dependent manner. We also observed that cell proliferation and migration capacity were inhibited in CRCE-treated cells. In addition, a remarkable increase in the number of sub-G1-phase cells was observed with arrest at the G2 phase by CRCE treatment. CRCE also induced mitochondrial stress, and finally, CRCE treatment resulted in activation of apoptotic proteins Caspase-3, -9, and PARP and decreased levels of mu-2-related death-inducing gene protein expression with BH3-interacting domain death agonist (BID) activation.

Anticancer Therapeutic Effects of Green Tea Catechins (GTCs) When Integrated with Antioxidant Natural Components.

After decades of research and development concerning cancer treatment, cancer is still at large and very much a threat to the global human population. Cancer remedies have been sought from all possible directions, including chemicals, irradiation, nanomaterials, natural compounds, and the like. In this current review, we surveyed the milestones achieved by green tea catechins and what has been accomplished in cancer therapy. Specifically, we have assessed the synergistic anticarcinogenic effects when green tea catechins (GTCs) are combined with other antioxidant-rich natural compounds. Living in an age of inadequacies, combinatorial approaches are gaining momentum, and GTCs have progressed much, yet there are insufficiencies that can be improvised when combined with natural antioxidant compounds. This review highlights that there are not many reports in this specific area and encourages and recommends research attention in this direction. The antioxidant/prooxidant mechanisms of GTCs have also been highlighted. The current scenario and the future of such combinatorial approaches have been addressed, and the lacunae in this aspect have been discussed.

Consolidating the potency of matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) in viral diagnosis: Extrapolating its applicability for COVID diagnosis?

MALDI-TOF-MS has essentially delivered more than expected with respect to clinical pathogens. Viruses are the most versatile entities of clinical pathogens that have challenged well-established microbiological methodologies. This review evaluates the existing scenario with respect to MALDI TOF-MS analytical technique in the successful analysis of viral pathogens. The milestones achieved with respect to detection and identification of COVID-19 has been presented. The fact that only a handful of scattered applications for COVID-19 exist has been pointed out in the review. Further, the lapses in the utilization of the available state-of-the art MALDI-TOF-MS variants/benchmark sophistications for COVID-19 analysis, are highlighted. When the world is seeking for rapid solutions for early, sensitive, rapid COVID-19 diagnosis, maybe MALDI-TOF-MS, may be the actual 'gold standard'. Reverting to the title, this review emphasizes that there is a need for extrapolating MALDI-TOF-MS for COVID-19 analysis and this calls for urgent scientific attention.

A participatory practice study for the improvement of sub-regional health vulnerabilities: a qualitative study.

BACKGROUND: This study aimed to explore the experiences of the residents of Samho-dong with the health environment in the local community, and their in-depth opinions on health promotion using a photovoice methodology. Alternatives to improve health among the residents of Samho-dong were also discussed with the local residents, with the aim of translating suggestions from the discussion into practice. METHODS: A total of 195 photographs taken by the 15 participants over the course of 7 weeks were collected, along with 96 photovoice activity logs and transcription data from 5 rounds of focus group discussions. The photovoice activity logs consisted of the photographer's name, the dates photos were taken, and a series of responses to the following SHOWeD questions: "What do you SEE here?", "What is really HAPPENING?", "How does this situation or scenario affect OUR lives/health?", "WHY does this problem or strength Exist?", "What can we DO about it?". Direct content analysis was used for analysis. RESULTS: The analysis yielded a total of 247 semantic units, which were categorized into the themes, "the good, but insufficiency, living environment in Samho-dong," "the health environment in Samho-dong needs improvement," "small efforts to improve Samho-dong," and "points of improvement for a better Samho-dong". Samho-dong was found to have a poorer walking and transportation infrastructure than other regions, even though it was a town with a large elderly population. The dark streets in the residential complex made participants hesitate to engage in afternoon activities, and the insufficient traffic environment made it difficult to live a natural daily life by solving food, clothing, and shelter. Participants have made various attempts to solve areas that need improvement in the Samho-dong, which has led to actual improvement. It was analyzed that in order to make Samho-dong better, it was necessary to improve the perception of residents in Samho-dong and cooperate with the local community. CONCLUSIONS: This study was significant in that it enabled the in-depth exploration and identification of areas of improvement from the participants' perception of their health environment, considering that as residents, they are the direct stakeholders of the community health environment.

Mushroom Polysaccharide-Assisted Anticarcinogenic Mycotherapy: Reviewing Its Clinical Trials.

Of the biologically active components, polysaccharides play a crucial role of high medical and pharmaceutical significance. Mushrooms have existed for a long time, dating back to the time of the Ancient Egypt and continue to be well explored globally and experimented with in research as well as in national and international cuisines. Mushroom polysaccharides have slowly become valuable sources of nutraceuticals which have been able to treat various diseases and disorders in humans. The application of mushroom polysaccharides for anticancer mycotherapy is what is being reviewed herein. The widespread health benefits of mushroom polysaccharides have been highlighted and the significant inputs of mushroom-based polysaccharides in anticancer clinical trials have been presented. The challenges and limitation of mushroom polysaccharides into this application and the gaps in the current application areas that could be the future direction have been discussed.

Quercetin-3-Glucoside Extracted from Apple Pomace Induces Cell Cycle Arrest and Apoptosis by Increasing Intracellular ROS Levels.

Cervical cancer is a life-threatening disease and the fourth most common cancer among women worldwide. Apple pomace is a multifunctional phenolic compound possessing effective biological activity against cervical cancer cells. This study aimed to investigate the anticancer effects of quercetin-3-glucoside (Q3G) extracted from apple pomace in HeLa cell lines and analyze its molecular mechanisms. High-performance liquid chromatography revealed that Q3G, coumaric acid, phloridzin, quercetin, and phloretin are the major polyphenolic compounds constituting apple pomace. Among them, Q3G possessed the greatest antioxidant and anti-inflammatory effects in vitro and exhibited significant cytotoxic effects in HeLa cells in a dose-and time-dependent manner. Flow cytometric analysis indicated that Q3G induced cell cycle arrest at the S phase in a time-dependent manner by altering cyclin-dependent kinase 2. Moreover, it induced apoptosis via chromosomal DNA degradation and increased reactive oxygen species generation. Furthermore, Q3G treatment altered the apoptosis-associated protein expression in the cells by activating caspase-9/-3, downregulating anti-apoptosis protein B-cell lymphoma (Bcl)-2 expressions and up regulating the pro-apoptotic Bcl-2-associated X protein. BH3-interacting domain death agonist cleavage occurred prior to the degradation of an anti-apoptotic Mu-2-related death-inducing gene involved in cell death signaling. Consequently, apple pomace Q3G holds promise as an anti-inflammatory and anticancer agent for treating cervical cancer.

Bioinformatics for Renal and Urinary Proteomics: Call for Aggrandization.

The clinical sampling of urine is noninvasive and unrestricted, whereby huge volumes can be easily obtained. This makes urine a valuable resource for the diagnoses of diseases. Urinary and renal proteomics have resulted in considerable progress in kidney-based disease diagnosis through biomarker discovery and treatment. This review summarizes the bioinformatics tools available for this area of proteomics and the milestones reached using these tools in clinical research. The scant research publications and the even more limited bioinformatic tool options available for urinary and renal proteomics are highlighted in this review. The need for more attention and input from bioinformaticians is highlighted, so that progressive achievements and releases can be made. With just a handful of existing tools for renal and urinary proteomic research available, this review identifies a gap worth targeting by protein chemists and bioinformaticians. The probable causes for the lack of enthusiasm in this area are also speculated upon in this review. This is the first review that consolidates the bioinformatics applications specifically for renal and urinary proteomics.

The MUDENG Augmentation: A Genesis in Anti-Cancer Therapy?

Despite multitudes of reports on cancer remedies available, we are far from being able to declare that we have arrived at that defining anti-cancer therapy. In recent decades, researchers have been looking into the possibility of enhancing cell death-related signaling pathways in cancer cells using pro-apoptotic proteins. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Mu-2/AP1M2 domain containing, death-inducing (MUDENG, MuD) have been established for their ability to bring about cell death specifically in cancer cells. Targeted cell death is a very attractive term when it comes to cancer, since most therapies also affect normal cells. In this direction TRAIL has made noteworthy progress. This review briefly sums up what has been done using TRAIL in cancer therapeutics. The importance of MuD and what has been achieved thus far through MuD and the need to widen and concentrate on applicational aspects of MuD has been highlighted. This has been suggested as the future perspective of MuD towards prospective progress in cancer research.

Insights into Bioinformatic Applications for Glycosylation: Instigating an Awakening towards Applying Glycoinformatic Resources for Cancer Diagnosis and Therapy.

Glycosylation plays a crucial role in various diseases and their etiology. This has led to a clear understanding on the functions of carbohydrates in cell communication, which eventually will result in novel therapeutic approaches for treatment of various disease. Glycomics has now become one among the top ten technologies that will change the future. The direct implication of glycosylation as a hallmark of cancer and for cancer therapy is well established. As in proteomics, where bioinformatics tools have led to revolutionary achievements, bioinformatics resources for glycosylation have improved its practical implication. Bioinformatics tools, algorithms and databases are a mandatory requirement to manage and successfully analyze large amount of glycobiological data generated from glycosylation studies. This review consolidates all the available tools and their applications in glycosylation research. The achievements made through the use of bioinformatics into glycosylation studies are also presented. The importance of glycosylation in cancer diagnosis and therapy is discussed and the gap in the application of widely available glyco-informatic tools for cancer research is highlighted. This review is expected to bring an awakening amongst glyco-informaticians as well as cancer biologists to bridge this gap, to exploit the available glyco-informatic tools for cancer.

Effects of gamma-aminobutyric acid and piperine on gene regulation in pig kidney epithelial cell lines.

OBJECTIVE: Gamma-aminobutyric acid (GABA) and piperine (PIP) are both nutritional supplements with potential use in animal diets. The purpose of this study is to investigate the effect of GABA and/or PIP treatment on the gene expression pattern of a pig kidney epithelial cell line. METHODS: LLCPK1 cells were treated with GABA, PIP, or both, and then the gene expression pattern was analyzed using microarray. Gene ontology analysis was done using GeneOntology (Geneontology.org), and validation was performed using quantitative real-time polymerase chain reaction. RESULTS: Gene ontology enrichment analysis was used to identify key pathway(s) of genes whose expression levels were regulated by these treatments. Microarray results showed that GABA had a positive effect on the transcription of genes related to regulation of erythrocyte differentiation and that GABA and PIP in combination had a synergistic effect on genes related to immune systems and processes. Furthermore, we found that effects of GABA and/or PIP on these selected genes were controlled by JNK/p38 MAPK pathway. CONCLUSION: These results can improve our understanding of mechanisms involved in the effect of GABA and/or PIP treatment on pig kidney epithelial cells. They can also help us evaluate their potential as a clinical diagnosis and treatment.

Methyl lucidone induces apoptosis and G2/M phase arrest via the PI3K/Akt/NF-κB pathway in ovarian cancer cells.

Context: Methyl lucidone (ML) from the dried fruit of Lindera erythrocarpa Makino (Lauraceae) exhibits cytotoxic effects in various cancer cell lines. However, its effects on ovarian cancer cells remain unknown.Objective: This study evaluates the mechanism of ML-induced apoptosis, cell cycle distribution in ovarian cells.Materials and methods: The cytotoxic effect of ML (2.5-80 µM) on OVCAR-8 and SKOV-3 cells was evaluated by MTS assay for 24 and 48 h. Apoptosis and cell cycle arrest were analysed by flow cytometry. PCR, western blot analyses were performed to examine the related signalling pathways.Results: ML induced significant cellular morphological changes and apoptosis in ovarian cancer cells, leading to an antiproliferative effect (IC50 = 33.3-54.7 µM for OVCAR-8 and 48.8-60.7 µM for SKOV-3 cells). Treatment with ML induced cleavage of caspase-3/9 and PARP and release of cytochrome c from the mitochondria. Moreover, ML downregulated the expression of Bcl-2 and Bcl-xL and induced cell cycle arrest in the G2/M phase. Additionally, ML suppressed the expression of cyclin-A/B and promoted that of the cyclin-dependent kinase inhibitors p21 and p27. The expression of death receptors was not altered. Interestingly, ML also inhibited the activity of PI3K/Akt and NF-κB.Discussion and conclusions: ML caused G2/M phase arrest and apoptosis in ovarian cancer cells by activating intrinsic apoptotic pathways and suppressing the PI3K/Akt survival pathway. ML may be a potential anticancer agent to suppress ovarian cancer proliferation; thus, to improve the survival rate of cancer patients.

Interleukin-32θ inhibits tumor-promoting effects of macrophage-secreted CCL18 in breast cancer.

BACKGROUND: Tumor-associated macrophages can promote breast cancer metastasis by secreting cytokines and growth factors. Interleukin (IL)-32θ, a newly identified IL-32 isoform, was previously shown to down-regulate various proinflammatory factors of macrophages. Here, we report the presence of IL-32θ in breast cancer tissues and evaluate its effects on macrophage-regulated breast cancer metastasis. METHODS: RT-qPCR was used to analyze the mRNA expression of IL-32θ, Chemokine (C-C motif) ligand 18 (CCL18) in breast cancer tissues. In vitro cell-based experiments using IL-32θ-expressing MDA-MB-231 cells were conducted to examine the effects of IL-32θ on metastasis and its molecular signaling. In vivo xenograft, immunohistochemistry, and optical imaging models were generated to support in vitro and clinical findings. RESULTS: The clinical data displayed opposite expression patterns of CCL18 and IL-32θ mRNA in macrophage-infiltrated breast tumor tissues compared with those in the other tissues tested. In MDA-MB-231 cells, IL-32θ overexpression attenuated migration, invasion, tumor-promoting factors, and increased epithelial markers levels upon treatment with conditioned media from THP-1-derived macrophages. Additionally, IL-32θ expression in a xenograft model led to a remarkable decrease in tumor size and macrophage-stimulated tumor promotion. This inhibition was mediated through a direct interaction with protein kinase C-δ (PKCδ), subsequently eliminating the downstream factors STAT3 and NF-κB. Blocking CCL18 during co-culture of macrophages and breast cancer cells reduced the levels of breast cancer progression-related factors and PKCδ downstream signaling suggesting CCL18 as the main macrophage-secreted factors triggering the signaling pathway inhibited by IL-32θ. CONCLUSIONS: Our findings demonstrate a novel role of IL-32θ as an intracellular modulator to suppress macrophage-promoted breast cancer progression by targeting CCL18-dependent signaling.

Generation of single-chain Fv antibody fragments against Mu-2-related death-inducing gene in Escherichia coli.

Mu-2-related death-inducing (MuD) gene is involved in apoptosis in tumor cells. Although we have previously produced mouse monoclonal antibodies (MAbs) that specifically recognize human MuD, the application scope of MuD MAbs was restricted due to their mouse origin. Therefore, we attempted the generation of single-chain variable fragment (scFv) against MuD. The heavy- and light-chain variable region genes from two MuD hybridomas were isolated by PCR and joined by DNA encoding a (Gly4Ser1)3 linker. These scFv fragments were cloned into a phagemid vector and expressed as E-tagged fusion proteins in Escherichia coli HB2151. The reactivity of selected Abs was evaluated using ELISA. Selected MuDscFv Abs specifically recognized human MuD, retaining ~ 50% potency of the parent MAbs. MuDscFv-M3H9 recognized the middle region of MuD, while MuDscFv-C22B3 recognized a broad region. Intracellular expression of MuDscFvs-C22B3 protected cells from TRAIL-induced apoptosis. These MuDscFv Abs may help in the study of intracellular signaling pathway centered on MuD and of drug use target and points.

Epimagnolin A inhibits IL-6 production by inhibiting p38/NF-κB and AP-1 signaling pathways in PMA-stimulated THP-1 cells.

Epimagnolin A is a lignan obtained from the flower buds of Magnolia fargesii, which is traditionally used in Asian medicine for treating headache and nasal congestion. A herbal compound fargesin obtained from M. fargesii, has exerted anti-inflammatory effects in human monocytic THP-1 cells in the previous study. The anti-inflammatory effects of epimagnolin A, however, have been not elucidated yet. In this study, it was demonstrated that epimagnolin A reduced phorbol-12-myristate-13-acetate (PMA)-induced IL-6 promoter activity and IL-6 production in human monocytic THP-1 cells. Furthermore, it was investigated the modulating effects of epimagnolin A on mitogen-activated protein kinase, nuclear factor-kappa B (NF-κB), and activator protein 1 (AP-1) activities. Phosphorylation of p38 and nuclear translocation of p50 and c-Jun were down-regulated by epimagnolin A in the PMA-stimulated THP-1 cell. The results revealed that epimagnolin A attenuated the binding affinity of NF-κB and AP-1 transcription factors to IL-6 promoter and IL-6 production through p38/NF-kB and AP-1 signaling pathways in the PMA-stimulated THP-1 cells. These results suggest that epimagnolin A can be a useful drug for the treatment of inflammatory diseases.

Inhibition of IL-13 and IL-13Rα2 Expression by IL-32θ in Human Monocytic Cells Requires PKCδ and STAT3 Association.

Interleukin (IL)-32θ, a newly identified IL-32 isoform, has been reported to exert pro-inflammatory effects through the association with protein kinase C delta (PKCδ). In this study, we further examined the effects of IL-32θ on IL-13 and IL-13Rα2 expression and the related mechanism in THP-1 cells. Upon stimulating IL-32θ-expressing and non-expressing cells with phorbol 12-myristate 13-acetate (PMA), the previous microarray analysis showed that IL-13Rα2 and IL-13 mRNA expression were significantly decreased by IL-32θ. The protein expression of these factors was also confirmed to be down-regulated. The nuclear translocation of transcription factors STAT3 and STAT6, which are necessary for IL-13Rα2 and IL-13 promoter activities, was suppressed by IL-32θ. Additionally, a direct association was found between IL-32θ, PKCδ, and signal transducer and activator of transcription 3 (STAT3), but not STAT6, revealing that IL-32θ might act mainly through STAT3 and indirectly affect STAT6. Moreover, the interaction of IL-32θ with STAT3 requires PKCδ, since blocking PKCδ activity eliminated the interaction and consequently limited the inhibitory effect of IL-32θ on STAT3 activity. Interfering with STAT3 or STAT6 binding by decoy oligodeoxynucleotides (ODNs) identified that IL-32θ had additive effects with the STAT3 decoy ODN to suppress IL-13 and IL-13Rα2 mRNA expression. Taken together, our data demonstrate the intracellular interaction of IL-32θ, PKCδ, and STAT3 to regulate IL-13 and IL-13Rα2 synthesis, supporting the role of IL-32θ as an inflammatory modulator.

Recombinant human lubricin for prevention of postoperative intra-abdominal adhesions in a rat model.

BACKGROUND: Postoperative intra-abdominal adhesions are a major cause of morbidity and mortality and contribute to a heavy burden on health care resources. At present, numerous introduced adhesion prevention products have demonstrated some benefit but none are consistently effective. The aim of this study was to examine the effectiveness of recombinant human lubricin in preventing intra-abdominal adhesion formation. MATERIALS AND METHODS: A total of 62 male Wistar Albino rats were randomly assigned to the study. Six rats were used to the initial pilot study and 56 rats were randomized into four groups: (1) control cecal abrasion; (2) treatment cecal abrasion with 0.5 mg/mL lubricin solution; (3) control cecal enterotomy and primary closure; and (4) treatment cecal enterotomy and primary closure with 0.5 mg/mL lubricin solution. Rats were sacrificed at 3 d and 21 d postoperatively for the pilot and main studies, respectively. Macroscopic and microscopic adhesion severity was graded by blinded investigators. RESULTS: For the pilot study, all six rats successfully reached the end point indicating safety of the lubricin gel. In the main randomized study, adhesions in the treated cecal abrasion group were significantly reduced both macroscopically (P = 0.001) and microscopically (fibrosis P = 0.009, inflammation P < 0.0001), when compared with the control group. In the cecal enterotomy group, adhesions were reduced for the treatment group in macroscopic (P = 0.011) and microscopic grading (fibrosis P = 0.500, inflammation P = 0.206) compared with the control group. CONCLUSIONS: Recombinant human lubricin significantly reduced both macroscopic and microscopic intra-abdominal adhesions in the cecal abrasion group. The cecal enterotomy group showed modest macroscopic adhesion reduction. Future study using higher concentration of lubricin solution are needed to investigate its toxicity and more profound antiadhesion properties in significant operations.

Safety and efficacy of a laparoscopic cholecystectomy in the morbid and super obese patients.

BACKGROUND: Although a laparoscopic cholecystectomy (LC) is the gold standard treatment for symptomatic cholelithiasis, its safety and efficacy in the morbidly/super obese patients is unknown. The aim of this study was to investigate the safety and efficacy of an elective LC in the morbid/super obese patients. METHODS: A retrospective review of the hospital electronic database and medical records was conducted searching for all elective LC from 2010 to 2013. The data collected included patient demographics and body mass index (BMI), length of hospital stay (LOS), duration of surgery (DOS), intra- and post-operative complications, bile duct injuries, performance of an intra-operative cholangiogram, the incidence of open conversion and the seniority of the operator. RESULTS: A total of 799 patients (76% female) with a mean age of 46 years and BMI of 31 were included in this study. There were significant differences in the median DOS between the three BMI groups; BMI < 26 [64 min; interquartile range (IQR) 54-83]; BMI 26-40 (72 min, IQR 58-91) and BMI > 40 (82 min, IQR 63-104), P < 0.001. There were no statistically significant differences in the LOS, peri-operative complication rates, open conversions or bile duct injuries among the BMI groups. CONCLUSIONS: This study showed that LC can be performed safely in the morbid/super obese patients.

Activation of peroxisome proliferator-activated receptor δ inhibits angiotensin II-induced activation of matrix metalloproteinase-2 in vascular smooth muscle cells.

We investigated the role of peroxisome proliferator-activated receptor (PPAR) δ on angiotensin (Ang) II-induced activation of matrix metalloproteinase (MMP)-2 in vascular smooth muscle cells (VSMCs). Activation of PPARδ by GW501516, a specific ligand for PPARδ, attenuated Ang II-induced activation of MMP-2 in a concentration-dependent manner. GW501516 also inhibited the generation of reactive oxygen species in VSMCs treated with Ang II. A marked increase in the mRNA levels of tissue inhibitor of metalloproteinase (TIMP)-2 and -3, endogenous antagonists of MMPs, was also observed in GW501516-treated VSMCs. These effects were markedly reduced in the presence of siRNAs against PPARδ, indicating that the effects of GW501516 are PPARδ dependent. Among the protein kinases inhibited by GW501516, suppression of phosphatidylinositol 3-kinase/Akt signaling was shown to have the greatest effect on activation of MMP-2 in VSMCs treated with Ang II. Concomitantly, GW501516-mediated inhibition of MMP-2 activation in VSMCs treated with Ang II was associated with the suppression of cell migration to levels approaching those in cells not exposed to Ang II. Thus, activation of PPARδ confers resistance to Ang II-induced degradation of the extracellular matrix by upregulating expression of its endogenous inhibitor TIMP and thereby modulating cellular responses to Ang II in vascular cells.