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Melatonin, an indole produced by pineal and extrapineal tissues, but also taken with a vegetarian diet, has strong anti-oxidant, anti-inflammatory and anti-obesogenic potentials. Non-alcoholic fatty liver disease (NAFLD) is the hepatic side of the metabolic syndrome. NAFLD is a still reversible phase but may evolve into steatohepatitis (NASH), cirrhosis and carcinoma. Currently, an effective therapy for blocking NAFLD staging is lacking. Silent information regulator 1 (SIRT1), a NAD+ dependent histone deacetylase, modulates the energetic metabolism in the liver. Micro-RNA-34a-5p, a direct inhibitor of SIRT1, is an emerging indicator of NAFLD grading. Thus, here we analyzed the effects of oral melatonin against NAFLD and underlying molecular mechanisms, focusing on steatosis, ER stress, mitochondrial shape and autophagy. Male C57BL/6J (WT) and SIRT1 heterozygous (HET) mice were placed either on a high-fat diet (58.4% energy from lard) (HFD) or on a standard maintenance diet (8.4% energy from lipids) for 16 weeks, drinking melatonin (10 mg/kg) or not. Indirect calorimetry, glucose tolerance, steatosis, inflammation, ER stress, mitochondrial changes, autophagy and microRNA-34a-5p expression were estimated. Melatonin improved hepatic metabolism and steatosis, influenced ER stress and mitochondrial shape, and promoted autophagy in WT HFD mice. Conversely, melatonin was ineffective in HET HFD mice, maintaining NASH changes. Indeed, autophagy was inconsistent in HET HFD or starved mice, as indicated by LC3II/LC3I ratio, p62/SQSTM1 and autophagosomes estimation. The beneficial role of melatonin in dietary induced NAFLD/NASH in mice was related to reduced expression of microRNA-34a-5p and sterol regulatory element-binding protein (SREBP1) but only in the presence of full SIRT1 availability.

Glioblastoma multiforme is an aggressive, invasive brain tumour with a poor survival rate. Available treatments are ineffective and some tumours remain inoperable because of their size or location. The tumours are known to invade and migrate along white matter tracts and blood vessels. Here, we exploit this characteristic of glioblastoma multiforme by engineering aligned polycaprolactone (PCL)-based nanofibres for tumour cells to invade and, hence, guide cells away from the primary tumour site to an extracortical location. This extracortial sink is a cyclopamine drug-conjugated, collagen-based hydrogel. When aligned PCL-nanofibre films in a PCL/polyurethane carrier conduit were inserted in the vicinity of an intracortical human U87MG glioblastoma xenograft, a significant number of human glioblastoma cells migrated along the aligned nanofibre films and underwent apoptosis in the extracortical hydrogel. Tumour volume in the brain was significantly lower following insertion of aligned nanofibre implants compared with the application of smooth fibres or no implants. Glioblastoma multiforme—an aggressive form of brain tumour —is known to migrate along white matter tracts and blood vessels. Now, aligned polycaprolactone nanofibres within a polymeric carrier are shown to guide tumour cells from the primary tumour site to an extracortical hydrogel ‘sink’ and hence lower tumour volume in the brain.

Bile salts are biosurfactants released into the intestinal lumen which play an important role in the solubilisation of fats and certain drugs. Their concentrations vary along the gastrointestinal tract (GIT). This is significant for implementation in physiologically based pharmacokinetic (PBPK) modelling to mechanistically capture drug absorption. The aims of this meta-analysis were to collate all appropriate data on intestinal bile salt concentrations in healthy adults across all GIT segments in fasted and fed states for the purpose of PBPK modelling. Terms relating to bile composition were searched in PubMed and Google Scholar from inception to May 2024. Selected studies included aspirated intestinal fluid collected via gastric tubes or colonoscopy. Results showed high variability across studies and a time-dependency for the fed state. Data were rich for the duodenum, which showed a two-fold increase for the fed state versus the fasted state within multiple studies. Peaks and troughs in bile salt concentrations along the GIT were observed for both fasted and fed states, likely due to segmental water absorption differences. The highest between subject variability was observed for the duodenum in the fasted and fed state and the fed proximal jejunum, distal ileum, and colon. The findings from this meta-analysis can be used for the purpose of PBPK modelling to capture segmental drug solubilisation and absorption in fasted and fed states. However, data are lacking under different fed conditions, especially following low-fat meals, so the impact of different fat content associated with different meals on bile salt concentrations cannot be discerned. Graphical Abstract Gastrointestinal bile salt concentrations in healthy subjects A meta-analysis has been conducted to collate fasted and fed gastrointestinal bile salt concentrations in healthy subjects for the purpose of physiologically-based pharmacokinetic (PBPK) modelling within the Simcyp and other PBPK simulators. Values are presented as weighted means with coefficient of variability for each segment. These data will help improve mechanistic models of oral drug absorption.

Peripheral nerve injuries cause severe disability with decreased nerve function often followed by neuropathic pain that impacts the quality of life. Even though use of autografts is the current gold standard, nerve conduits fabricated from electrospun nanofibers have shown promise to successfully bridge critical length nerve gaps. However, in depth analysis of the role of topographical cues in the context of spatio-temporal progression of the regenerative sequence has not been elucidated. Here, we explored the influence of topographical cues (aligned, random, and smooth films) on the regenerative sequence and potential to successfully support nerve regeneration in critical size gaps. A number of key findings emerged at the cellular, cytokine and molecular levels from the study. Higher quantities of IL-1α and TNF-α were detected in aligned fiber based scaffolds. Differential gene expression of BDNF, NGFR, ErbB2, and ErbB3 were observed suggesting a role for these genes in influencing Schwann cell migration, myelination, etc. that impact the regeneration in various topographies. Fibrin matrix stabilization and arrest of nerve-innervated muscle atrophy was also evident. Taken together, our data shed light on the cascade of events that favor regeneration in aligned topography and should stimulate research to further refine the strategy of nerve regeneration using topographical cues.

Background Sustainable development and urbanization are interwoven concepts that promote an eco-friendly life for all living beings, which ensures harmonious coexistence between humans and nature. Consequently, ecosystem assessments using various modi operandi are essential in evaluating urbanization’s impact and construction of the ecological civilization. This study examines microscale ornithological successional analysis, limnological parameters, and remote sensing techniques over three months (January, February, and March) in 2020 and 2023 to assess structural and temporal variations. Results The findings indicate a notable increase in avian species richness, diversity, and abundance in 2023 compared to 2020. Elevated nutrient levels in the lake water, along with an expansion in agricultural land within a 5 km radius of the lake, were identified as key drivers of increased bird diversity. Higher nutrient concentrations facilitated enhanced plant growth in the lake and surrounding agricultural areas, attracting insectivorous and omnivorous birds. These results provide valuable insights into the ecological complexity, structural changes, and dynamic transformations occurring within an urban ecosystem and their implications for local biodiversity. Conclusion This study employs an integrative approach utilizing three distinct parameters to evaluate the ecological implications of sustainable development. The findings provide a foundation for evidence-based conservation strategies and urban planning policies aimed at enhancing ecological resilience, sustainability, and coexistence. Additionally, the study underscores the need for continuous, long-term ecological monitoring to assess spatiotemporal environmental dynamics and inform future management practices. Graphical Abstract The core portion of the image is generated by Artificial Intelligence (AI) tool named “Gencraft” (Gencraft, 2023 ) with the prompt “Sustainable Indian urbanization with biodiversity having pond”