Effect of occupational exposure to lead on serum levels of lipid profile and liver enzymes: An occupational cohort study.

The present study was performed to know the effects of chronic lead exposure on serum lipids, lipoproteins, and liver enzymes in a cohort study among of lead mine workers. We followed of 200 Iranian workers for 3- years (2018-2020), 100 of them with known occupational exposure to lead thorough their work in lead mine while the others 100 were with no such exposure. Blood lead level (BLL), serum lipids, lipoproteins, and liver enzymes of the exposure group for 3- years were measured and compared with those attained in the non-exposed workers. The BLL levels of the lead-mine workers were higher than with recommended level and the non-exposed group (24.15 and 6.35 µg/dL, respectively). The findings indicated a positive and significant relationship between BLL and lactate dehydrogenase, aspartate transaminase, alkaline phosphatase, alanine transaminase, and bilirubin levels (P < 0.01). Also while we found a negative and significant correlation between BLL and triglyceride, total protein, albumin, and globulin levels (P < 0.01). This report depicted that chronic lead exposure is a risk factor for hematological, liver, and cardiovascular diseases. Despite the fact that the level of liver function parameters was in the normal range, the results of 3- years follow-up show a significant relationship between BLL and alteration of biochemical parameters levels.

Boosting 5-ALA-based photodynamic therapy by a liposomal nanomedicine through intracellular iron ion regulation.

5-Aminolevulinic acid (5-ALA) has been approved for clinical photodynamic therapy (PDT) due to its negligible photosensitive toxicity. However, the curative effect of 5-ALA is restricted by intracellular biotransformation inactivation of 5-ALA and potential DNA repair of tumor cells. Inspired by the crucial function of iron ions in 5-ALA transformation and DNA repair, a liposomal nanomedicine (MFLs@5-ALA/DFO) with intracellular iron ion regulation property was developed for boosting the PDT of 5-ALA, which was prepared by co-encapsulating 5-ALA and DFO (deferoxamine, a special iron chelator) into the membrane fusion liposomes (MFLs). MFLs@5-ALA/DFO showed an improved pharmaceutical behavior and rapidly fused with tumor cell membrane for 5-ALA and DFO co-delivery. MFLs@5-ALA/DFO could efficiently reduce iron ion, thus blocking the biotransformation of photosensitive protoporphyrin IX (PpIX) to heme, realizing significant accumulation of photosensitivity. Meanwhile, the activity of DNA repair enzyme was also inhibited with the reduction of iron ion, resulting in the aggravated DNA damage in tumor cells. Our findings showed MFLs@5-ALA/DFO had potential to be applied for enhanced PDT of 5-ALA.

Boosting 5-ALA-based photodynamic therapy by a liposomal nanomedicine through intracellular iron ion regulation

5-Aminolevulinic acid (5-ALA) has been approved for clinical photodynamic therapy (PDT) due to its negligible photosensitive toxicity. However, the curative effect of 5-ALA is restricted by intracellular biotransformation inactivation of 5-ALA and potential DNA repair of tumor cells. Inspired by the crucial function of iron ions in 5-ALA transformation and DNA repair, a liposomal nanomedicine (MFLs@5-ALA/DFO) with intracellular iron ion regulation property was developed for boosting the PDT of 5-ALA, which was prepared by co-encapsulating 5-ALA and DFO (deferoxamine, a special iron chelator) into the membrane fusion liposomes (MFLs). MFLs@5-ALA/DFO showed an improved pharmaceutical behavior and rapidly fused with tumor cell membrane for 5-ALA and DFO co-delivery. MFLs@5-ALA/DFO could efficiently reduce iron ion, thus blocking the biotransformation of photosensitive protoporphyrin IX (PpIX) to heme, realizing significant accumulation of photosensitivity. Meanwhile, the activity of DNA repair enzyme was also inhibited with the reduction of iron ion, resulting in the aggravated DNA damage in tumor cells. Our findings showed MFLs@5-ALA/DFO had potential to be applied for enhanced PDT of 5-ALA.

Biomimetic thiamine- and niacin-decorated liposomes for enhanced oral delivery of insulin.

Biomimetic nanocarriers are emerging as efficient vehicles to facilitate dietary absorption of biomacromolecules. In this study, two vitamins, thiamine and niacin, are employed to decorate liposomes loaded with insulin, thus facilitating oral absorption via vitamin ligand-receptor interactions. Both vitamins are conjugated with stearamine, which works to anchor the ligands to the surface of liposomes. Liposomes prepared under optimum conditions have a mean particle size of 125-150 nm and an insulin entrapment efficiency of approximately 30%-36%. Encapsulation into liposomes helps to stabilize insulin due to improved resistance against enzymatic disruption, with 60% and 80% of the insulin left after 4 h when incubated in simulated gastric and intestinal fluids, respectively, whereas non-encapsulated insulin is broken down completely at 0.5 h. Preservation of insulin bioactivity against preparative stresses is validated by intra-peritoneal injection of insulin after release from various liposomes using the surfactant Triton X-100. In a diabetic rat model chemically induced by streptozotocin, both thiamine- and niacin-decorated liposomes showed a comparable and sustained mild hypoglycemic effect. The superiority of decorated liposomes over conventional liposomes highlights the contribution of vitamin ligands. It is concluded that decoration of liposomes with thiamine or niacin facilitates interactions with gastrointestinal vitamin receptors and thereby facilitates oral absorption of insulin-loaded liposomes.

Biomimetic thiamine- and niacin-decorated liposomes for enhanced oral delivery of insulin

Biomimetic nanocarriers are emerging as efficient vehicles to facilitate dietary absorption of biomacromolecules. In this study, two vitamins, thiamine and niacin, are employed to decorate liposomes loaded with insulin, thus facilitating oral absorption vitamin ligand-receptor interactions. Both vitamins are conjugated with stearamine, which works to anchor the ligands to the surface of liposomes. Liposomes prepared under optimum conditions have a mean particle size of 125-150 nm and an insulin entrapment efficiency of approximately 30%-36%. Encapsulation into liposomes helps to stabilize insulin due to improved resistance against enzymatic disruption, with 60% and 80% of the insulin left after 4 h when incubated in simulated gastric and intestinal fluids, respectively, whereas non-encapsulated insulin is broken down completely at 0.5 h. Preservation of insulin bioactivity against preparative stresses is validated by intra-peritoneal injection of insulin after release from various liposomes using the surfactant Triton X-100. In a diabetic rat model chemically induced by streptozotocin, both thiamine- and niacin-decorated liposomes showed a comparable and sustained mild hypoglycemic effect. The superiority of decorated liposomes over conventional liposomes highlights the contribution of vitamin ligands. It is concluded that decoration of liposomes with thiamine or niacin facilitates interactions with gastrointestinal vitamin receptors and thereby facilitates oral absorption of insulin-loaded liposomes.

Amelioration of Metabolic Syndrome-Associated Cognitive Impairments in Mice via a Reduction in Dietary Fat Content or Infusion of Non-Diabetic Plasma.

Obesity, metabolic syndrome (MetS) and type 2 diabetes (T2D) are associated with decreased cognitive function. While weight loss and T2D remission result in improvements in metabolism and vascular function, it is less clear if these benefits extend to cognitive performance. Here, we highlight the malleable nature of MetS-associated cognitive dysfunction using a mouse model of high fat diet (HFD)-induced MetS. While learning and memory was generally unaffected in mice with type 1 diabetes (T1D), multiple cognitive impairments were associated with MetS, including deficits in novel object recognition, cued fear memory, and spatial learning and memory. However, a brief reduction in dietary fat content in chronic HFD-fed mice led to a complete rescue of cognitive function. Cerebral blood volume (CBV), a measure of vascular perfusion, was decreased during MetS, was associated with long term memory, and recovered following the intervention. Finally, repeated infusion of plasma collected from age-matched, low fat diet-fed mice improved memory in HFD mice, and was associated with a distinct metabolic profile. Thus, the cognitive dysfunction accompanying MetS appears to be amenable to treatment, related to cerebrovascular function, and mitigated by systemic factors.

Liposomes modified with cardiolipin can act as a platform to regulate the potential flux of NADP+-dependent isocitrate dehydrogenase.

Cardiolipin (CL) is a phospholipid found in the outer mitochondrial membrane (OMM) and inner mitochondrial membrane (IMM) in animal cells. Isocitrate dehydrogenase (ICDH) is an important catalytic enzyme that is localized at the cytosol and mitochondria; the metabolic pathway catalyzed by ICDH differs between the OMM and IMM. To estimate the possible role of lipid membrane in the enzymatic activity of NADP+-dependent ICDH, CL-modified liposomes were prepared using CL/1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/cholesterol (Ch), and their characteristics were analyzed based on the fluorescent probe method. The relative enzymatic activity of ICDH decreased in the presence of CL/DPPC/Ch=(30/50/20) liposome, whereas activity increased in the presence of CL/DPPC/Ch=(5/75/20) liposome. NADP+ had the greatest substrate affinity and was dominant in the regulation of ICDH activity. Analysis of membrane properties indicated that membranes in CL-modified liposomes were dehydrated by ICDH binding. Using circular dichroism analysis, CL/DPPC/Ch=(30/50/20) liposome induced a conformational change in ICDH, indicating that CL-rich membrane domains could inhibit ICDH activity. These results suggest that lipid membranes, including CL molecules, could act as a platform to regulate ICDH-related metabolic pathways such as the tricarboxylic acid cycle and lipid synthesis.