Leptin differentially regulate STAT3 activation in ob/ob mouse adipose mesenchymal stem cells

Background Leptin-deficient ob/ob mice exhibit adipocyte hypertrophy and hyperplasia as well as elevated adipose tissue and systemic inflammation. Multipotent stem cells isolated from adult adipose tissue can differentiate into adipocytes ex vivo and thereby contribute toward increased adipocyte cell numbers, obesity, and inflamm ation. Currently, information is lacking regarding regulation of adipose stem cell numbers as well as leptin-induced inflammation and its signaling pathway in ob/ob mice. Methods Using leptin deficient ob/ob mice, we investigated whether leptin injection into ob/ob mice increases adipose stem cell numbers and adipose tissue inflammatory marker MCP-1 mRNA and secretion levels. We also determined leptin mediated signaling pathways in the adipose stem cells. Results We report here that adipose stem cell number is significantly increased following leptin injection in ob/ob mice and with treatment of isolated stem cells with leptin in vitro. Leptin also up-regulated MCP-1 secretion in a dose- and time-dependent manner. We further showed that increased MCP-1 mRNA levels were due to increased phosphorylation of Signal Transducer and Activator of Transcription 3 (STAT3) Ser727 but not STAT3 Tyr705 phosphorylation, suggesting differential regulation of MCP-1 gene expression under basal and leptin-stimulated conditions in adipose stem cells. Conclusions Taken together, these studies demonstrate that leptin increases adipose stem cell number and differentially activates STAT3 protein resulting in up-regulation of MCP-1 gene expression. Further studies of mechanisms mediating adipose stem cell hyperplasia and leptin signaling in obesity are warranted and may help identify novel anti-obesity target strategies

A Ten-year Retrospective Study of Nasal Bone Fractures at a Tertiary Care Hospital of Nepal

 Introduction: Nasal bone fracture occurs due to its vulnerable position and reduced biomechanical resistance to traumas. If not timely treated, it can result in permanent functional and esthetic damage. Methods: A retrospective and cross-sectional study conducted on 91 patients above 17 years of age with nasal bone fractures in the Department of Otorhinolaryngology and Head and Neck surgery of a tertiary care hospital in Kavre. Results: Road traffic accident was the most common cause of fracture (45.1%) followed by fall (36.3%), violence (13.2%), sports-related accidents (4.4%) and occupational accidents (1.1%). Class I fracture was seen in 70 (76.9%), Class II in 17 (18.7%), and Class III in 4 (4.4%). A closed reduction procedure was performed in 74 (81.30%) of the cases, closed reduction with septoplasty was done in 10 (11%), closed reduction with augmentation rhinoplasty was performed for 3 (3.3%), closed reduction with inferior turbinoplasty was required in 3 (3.3%) whereas closed reduction with debridement was done in 1(1.1%). Conclusion: Nasal bone fracture is a complex clinical issue which needs to be addressed early. Violence prevention programs along with drinking and driving campaigns need to be more strengthened to decrease the alarmingly high frequency of nasal bone fracture in the current scenario

MECP2 Is a Frequently Amplified Oncogene with a Novel Epigenetic Mechanism That Mimics the Role of Activated RAS in Malignancy

An unbiased genome-scale screen for unmutated genes that drive cancer growth when overexpressed identified MECP2 as a novel oncogene. MECP2 resides in a region of the X-chromosome that is significantly amplified across 18% of cancers, and many cancer cell lines have amplified, overexpressed MECP2 and are dependent on MECP2 expression for growth. MECP2 copy number gain and RAS family member alterations are mutually exclusive in several cancer types. The MECP2 splicing isoforms activate the major growth factor pathways targeted by activated RAS, the MAPK and PI3K pathways. MECP2 rescued the growth of a KRAS(G12C)-addicted cell line after KRAS down-regulation, and activated KRAS rescues the growth of an MECP2-addicted cell line after MECP2 downregulation. MECP2 binding to the epigenetic modification 5-hydroxymethylcytosine is required for efficient transformation. These observations suggest that MECP2 is a commonly amplified oncogene with an unusual epigenetic mode of action

Leptin differentially regulate STAT3 activation in <it>ob/ob</it> mouse adipose mesenchymal stem cells

<p>Abstract</p> <p>Background</p> <p>Leptin-deficient <it>ob/ob</it> mice exhibit adipocyte hypertrophy and hyperplasia as well as elevated adipose tissue and systemic inflammation. Multipotent stem cells isolated from adult adipose tissue can differentiate into adipocytes <it>ex vivo</it> and thereby contribute toward increased adipocyte cell numbers, obesity, and inflamm ation. Currently, information is lacking regarding regulation of adipose stem cell numbers as well as leptin-induced inflammation and its signaling pathway in <it>ob/ob</it> mice.</p> <p>Methods</p> <p>Using leptin deficient <it>ob/ob</it> mice, we investigated whether leptin injection into <it>ob/ob</it> mice increases adipose stem cell numbers and adipose tissue inflammatory marker MCP-1 mRNA and secretion levels. We also determined leptin mediated signaling pathways in the adipose stem cells.</p> <p>Results</p> <p>We report here that adipose stem cell number is significantly increased following leptin injection in <it>ob/ob</it> mice and with treatment of isolated stem cells with leptin <it>in vitro</it>. Leptin also up-regulated MCP-1 secretion in a dose- and time-dependent manner. We further showed that increased MCP-1 mRNA levels were due to increased phosphorylation of Signal Transducer and Activator of Transcription 3 (STAT3) Ser727 but not STAT3 Tyr705 phosphorylation, suggesting differential regulation of MCP-1 gene expression under basal and leptin-stimulated conditions in adipose stem cells.</p> <p>Conclusions</p> <p>Taken together, these studies demonstrate that leptin increases adipose stem cell number and differentially activates STAT3 protein resulting in up-regulation of MCP-1 gene expression. Further studies of mechanisms mediating adipose stem cell hyperplasia and leptin signaling in obesity are warranted and may help identify novel anti-obesity target strategies.</p

ob/ob mouse adipose mesenchymal stem cells

Background: Leptin-deficient ob/ob mice exhibit adipocyte hypertrophy and hyperplasia as well as elevated adipose tissue and systemic inflammation. Multipotent stem cells isolated from adult adipose tissue can differentiate into adipocytes ex vivo and thereby contribute toward increased adipocyte cell numbers, obesity, and inflamm ation. Currently, information is lacking regarding regulation of adipose stem cell numbers as well as leptin-induced inflammation and its signaling pathway in ob/ob mice. Methods: Using leptin deficient ob/ob mice, we investigated whether leptin injection into ob/ob mice increases adipose stem cell numbers and adipose tissue inflammatory marker MCP-1 mRNA and secretion levels. We also determined leptin mediated signaling pathways in the adipose stem cells. Results: We report here that adipose stem cell number is significantly increased following leptin injection in ob/ob mice and with treatment of isolated stem cells with leptin in vitro. Leptin also up-regulated MCP-1 secretion in a dose- and time-dependent manner. We further showed that increased MCP-1 mRNA levels were due to increased phosphorylation of Signal Transducer and Activator of Transcription 3 (STAT3) Ser727 but not STAT3 Tyr705 phosphorylation, suggesting differential regulation of MCP-1 gene expression under basal and leptin-stimulated conditions in adipose stem cells. Conclusions: Taken together, these studies demonstrate that leptin increases adipose stem cell number and differentially activates STAT3 protein resulting in up-regulation of MCP-1 gene expression. Further studies of mechanisms mediating adipose stem cell hyperplasia and leptin signaling in obesity are warranted and may help identify novel anti-obesity target strategies

Carbon Capture: Theoretical Guidelines for Activated Carbon-Based CO2 Adsorption Material Evaluation.

Activated carbon (AC)-based materials have shown promising performance in carbon capture, offering low cost and sustainable sourcing from abundant natural resources. Despite ACs growing as a new class of materials, theoretical guidelines for evaluating their viability in carbon capture are a crucial research gap. We address this gap by developing a hierarchical guideline, based on fundamental gas-solid interaction strength, that underpins the success and scalability of AC-based materials. The most critical performance indicator is the CO2 adsorption energy, where an optimal range (-0.41 eV) ensures efficiency between adsorption and desorption. Additionally, we consider thermal stability and defect sensitivity to ensure consistent performance under varying conditions. Further, selectivity and capacity play significant roles due to external variables such as partial pressure of CO2 and other ambient air gases (N2, H2O, O2), bridging the gap between theory and reality. We provide actionable examples by narrowing our options to methylamine- and pyridine-grafted graphene

Determinants affecting utilisation of health services and treatment for children under-5 in rural Nepali health centres: a cross-sectional study

Background Large inequalities in child health remain in Nepal, with caste, ethnicity and sex being major determinants of deprivation and negative outcomes. The purpose of this study was to explore whether key demographics of under 5s were associated with health seeking behaviours, utilisation of health care, and treatment received. Methods Data came from Integrated Management of Neonatal & Childhood Illness (IMNCI) records of 23 health centres across five districts. After digitising the paper records, the data was analysed by district, caste/ethnicity, sex, and age to investigate differences in the time taken to present at a health facility after the onset of symptoms of ARI, diarrhoea and fever; accuracy of diagnosis for pneumonia; and whether the correct treatment was prescribed for pneumonia as per IMNCI guidelines. Results From 116 register books spanning 23 health centres, 30,730 child patient records were considered for analysis. The median age of attendance was 18 months (Inter-Quartile Range = 10, 32), while were more male children that attended (55.7% vs. 44.3% for females). There were statistically significant differences for the time taken to attend a health centre between different districts for ARI, diarrhoea and fever, with children in the remote Humla and Mugu districts taking significantly longer to present at a health facility after the onset of symptoms (all p  Conclusion Significant demographic differences were found based on ethnicity, sex, and district when examining health seeking behaviours for ARI, diarrhoea, and fever. Significant associations were seen for these same factors when exploring accuracy of diagnoses of pneumonia, but not for treatment. This study has emphasised the importance of a digitalised healthcare system, where inequalities can be identified without the reliance on anecdotal evidence