Alternative Approaches to Combat Medicinally Important Biofilm-Forming Pathogens

Bacteria have developed the capability to produce structured communities (or cluster of cells) via adherence to surface to form biofilms that facilitate or prolong their survival under extreme environmental condition. Bacterial biomass adheres to inanimate and biotic surfaces in the hospital setting as well as in the environment. In the healthcare system, the biofilm formation on medical devices allows bacteria to sustain as a reservoir and becomes more resistant to antimicrobial agents. However, biofilm formation facilitates pathogens to sabotage the host defenses that are linked to long-term retention within the host cell. Therefore, in this review, we provide some steps leading to the formation of biofilm within the host and on inanimate surfaces, also emphasizing various medically significant pathogens and debate current developments on novel approaches that aimed to prevent biofilm formations and its dispersion to patients

Molecular Mechanisms of Adipogenesis: The Anti-adipogenic Role of AMP-Activated Protein Kinase

Obesity is now a widespread disorder, and its prevalence has become a critical concern worldwide, due to its association with common co-morbidities like cancer, cardiovascular diseases and diabetes. Adipose tissue is an endocrine organ and therefore plays a critical role in the survival of an individual, but its dysfunction or excess is directly linked to obesity. The journey from multipotent mesenchymal stem cells to the formation of mature adipocytes is a well-orchestrated program which requires the expression of several genes, their transcriptional factors, and signaling intermediates from numerous pathways. Understanding all the intricacies of adipogenesis is vital if we are to counter the current epidemic of obesity because the limited understanding of these intricacies is the main barrier to the development of potent therapeutic strategies against obesity. In particular, AMP-Activated Protein Kinase (AMPK) plays a crucial role in regulating adipogenesis – it is arguably the central cellular energy regulation protein of the body. Since AMPK promotes the development of brown adipose tissue over that of white adipose tissue, special attention has been given to its role in adipose tissue development in recent years. In this review, we describe the molecular mechanisms involved in adipogenesis, the role of signaling pathways and the substantial role of activated AMPK in the inhibition of adiposity, concluding with observations which will support the development of novel chemotherapies against obesity epidemics

Adipogenesis, Role of Adenosine Monophosphate-Activated Protein Kinase (AMPK) and Use of Plants Products in Combating Obesity

The increasingly widespread emergence of obesity has become a matter of critical concern around the world due to its association with common morbidities including cancer, cardiovascular diseases and diabetes. Over-nutrition and the sedentary lifestyle are considered as the most significant causes of obesity: appropriate lifestyle and behavior interventions are the corner stones of successful weight loss, but to maintain such a lifestyle is highly challenging. There is therefore an urgent need to develop innovative non- or minimally-toxic means to combat obesity. Accordingly, ample natural products from plants (either as crude extracts or purified phytochemicals) have been scrutinized for their anti-obesogenic properties because they are believed to be non-toxic and cost-effective, and frequently well-accepted by patients because of their traditional use. In this review, we will discuss adipose tissue and adipogenesis, signaling pathways involved in the regulation of adipogenesis, role of energy sensor protein of the body AMPK, and recently reported plant products in the management of obesity. We will provide a common platform for understanding obesity, and a possible mechanism of action for anti-obesogenic plant products through activated AMPK, which will be helpful in the scientific development of traditional herbal medicine

Mechanisms of action for the anti-obesogenic activities of phytochemicals

The prevalence of obesity is increasing rapidly globally and has recently reached pandemic proportions. It is a multifactorial disorder linked to a number of non-communicable diseases such as type-2 diabetes, cardiovascular disease, and cancer. Over-nutrition and a sedentary lifestyle are considered the most significant causes of obesity; a healthy lifestyle and behavioural interventions are the most powerful ways to achieve successful weight loss, but to maintain this in the long term can prove difficult for many individuals, without medical intervention. Various pharmacological anti-obesogenic drugs have been tested and marketed in the past and have been moderately successful in the management of obesity, but their adverse effects on human health often outweigh the benefits. Natural products from plants, either in the form of crude extracts or purified phytochemicals, have been shown to have anti-obesogenic properties and are generally considered as nontoxic and cost-effective compared to synthetic alternatives. These plant products combat obesity by targeting the various pathways and/or regulatory functions intricately linked to obesity. Their mechanisms of action include inhibition of pancreatic lipase activities, an increase in energy expenditure, appetite regulation, lipolytic effects, and inhibition of white adipose tissue development. In this review, we discuss the distinct anti-obesogenic properties of recently reported plant extracts and specific bioactive compounds, along with their molecular mechanisms of action. This review will provide a common platform for understanding the different causes of obesity and the possible approaches to using plant products in tackling this worldwide health issue

Anti-pancreatic lipase and anti-adipogenic effects of 5, 7, 3′,4′,5’ -pentamethoxy and 6, 2′,4′-trimethoxy flavone - An In vitro study

In this study, the anti-obesity effects of 5,7,3′,4′,5-pentamethoxyflavone (PMF) and 6,2′,4′-trimethoxyflavone (TMF) were evaluated through two distinct mechanisms of action: inhibition of crude porcine pancreatic lipase (PL), and inhibition of adipogenesis in 3T3-L1 pre-adipocytes. Both flavones show dose dependent, competitive inhibition of PL activity. Molecular docking studies revealed binding of the flavones to the active site of PL. In 3T3-L1 pre-adipocytes, both flavones reduced the accumulation of lipids and triglycerides. PMF and TMF also lowered the expression of adipogenic and lipogenic genes. They both reduced the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ), CCAAT/enhancer-binding protein α and β (C/EBP α and β), sterol regulatory element-binding protein 1 (SREBF 1), fatty acid synthase (FASN), adipocyte binding protein 2 (aP2), and leptin gene. In addition, these flavones enhanced adiponectin mRNA expression, increased lipolysis and enhanced the expression of lipolytic genes: adipose triglycerides lipase (ATGL), hormone sensitive lipase (HSL) and monoglycerides lipase (MAGL) in mature 3T3-L1 adipocytes. Overall, PMF was seen to be a more potent inhibitor of both PL activity and adipogenesis versus TMF. These results suggest that PMF and TMF possess anti-obesity activities and can be further evaluated for their anti-obesity effects

Hydroxylated polymethoxyflavones reduce the activity of pancreatic lipase, inhibit adipogenesis and enhance lipolysis in 3T3-L1 mouse embryonic fibroblast cells

Hydroxylated polymethoxyflavones (HPMFs) have been shown to possess various anti-disease effects, including against obesity. This study investigates the anti-obesity effects of HPMFs in further detail, aiming to gain un- derstanding of their mechanism of action in this context. The current study demonstrates that two HPMFs; 3′ - hydroxy-5,7,4′ ,5′-tetramethoxyflavone (3′OH-TetMF) and 4′ -hydroxy-5,7,3′ ,5′ -tetramethoxyflavone (4′OH- TetMF) possess anti-obesity effects. They both significantly reduced pancreatic lipase activity in a competitive manner as demonstrated by molecular docking and kinetic studies. In cell studies, it was revealed that both of the HPMFs suppress differentiation of 3T3-L1 mouse embryonic fibroblast cells during the early stages of adipo- genesis. They also reduced expression of key adipogenic and lipogenic marker genes, namely peroxisome proliferator-activated receptor-gamma (PPARγ), CCAAT/enhancer-binding protein α and β (C/EBP α and β), adipocyte binding protein 2 (aP2), fatty acid synthase (FASN), and sterol regulatory element-binding protein 1 (SREBF 1). They also enhanced the expression of cell cycle genes, i.e., cyclin D1 (CCND1) and C-Myc, and reduced cyclin A2 expression. When further investigated, it was also observed that these HPMFs accelerate lipid breakdown (lipolysis) and enhance lipolytic genes expression. Moreover, they also reduced the secretion of proteins (adipokines), including pro-inflammatory cytokines, from mature adipocytes. Taken together, this study concludes that these HPMFs have anti-obesity effects, which are worthy of furthe

Dependency of NELF-E-SLUG-KAT2B epigenetic axis in breast cancer carcinogenesis.

Cancer cells undergo transcriptional reprogramming to drive tumor progression and metastasis. Using cancer cell lines and patient-derived tumor organoids, we demonstrate that loss of the negative elongation factor (NELF) complex inhibits breast cancer development through downregulating epithelial-mesenchymal transition (EMT) and stemness-associated genes. Quantitative multiplexed Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins (qPLEX-RIME) further reveals a significant rewiring of NELF-E-associated chromatin partners as a function of EMT and a co-option of NELF-E with the key EMT transcription factor SLUG. Accordingly, loss of NELF-E leads to impaired SLUG binding on chromatin. Through integrative transcriptomic and genomic analyses, we identify the histone acetyltransferase, KAT2B, as a key functional target of NELF-E-SLUG. Genetic and pharmacological inactivation of KAT2B ameliorate the expression of EMT markers, phenocopying NELF ablation. Elevated expression of NELF-E and KAT2B is associated with poorer prognosis in breast cancer patients, highlighting the clinical relevance of our findings. Taken together, we uncover a crucial role of the NELF-E-SLUG-KAT2B epigenetic axis in breast cancer carcinogenesis

Murine in vitro cellular models to better understand adipogenesis and its potential applications

Adipogenesis has been extensively studied using in vitro models of cellular differentiation, enabling long-term regulation of fat cell metabolism in human adipose tissue (AT) material. Many studies promote the idea that manipulation of this process could potentially reduce the prevalence of obesity and its related diseases. It has now become essential to understand the molecular basis of fat cell development to tackle this pandemic disease, by identifying therapeutic targets and new biomarkers. This review explores murine cell models and their applications for study of the adipogenic differentiation process in vitro. We focus on the benefits and limitations of different cell line models to aid in interpreting data and selecting a good cell line model for successful understanding of adipose biology

The acquisition of the English inflectional -s Morphemes by Young L1 Chinese Speakers

This paper examines the acquisition of the inflectional –s morphemes (the plural marker, genitive marker and third person singular present tense marker) in English by eighteen young ESL learners from two Chinese primary schools. Learners were shown pictures as stimuli, and they were asked to describe the pictures in English. During these sessions, the descriptions by the learners and the conversations between the researcher and the learners were taped and later transcribed. The results of the study indicated that learners exhibited a distinct accuracy order for the morphemes. The learners also exhibited variability and produced overgeneralizations in their L2 utterances. The findings in fact suggested that the acquisition of the –s morpheme was systematic and staged. A discussion on the reasons for the phenomenon then followed and some implications were drawn for the teaching of these forms to young L1 Chinese speakers of L2 English