Esophageal Cancer Stem-like Cells Resist Ferroptosis-Induced Cell Death by Active Hsp27-GPX4 Pathway

Cancer stem cells (CSCs), a subpopulation of cancer cells responsible for tumor initiation and treatment failure, are more susceptible to ferroptosis-inducing agents than bulk cancer cells. However, regulatory pathways controlling ferroptosis, which can selectively induce CSC death, are not fully understood. Here, we demonstrate that the CSCs of esophageal squamous carcinoma cells enriched by spheroid culture have increased intracellular iron levels and lipid peroxidation, thereby increasing exposure to several products of lipid peroxidation, such as MDA and 4-HNE. However, CSCs do not reduce cell viability until glutathione is depleted by erastin treatment. Mechanistic studies revealed that damage from elevated lipid peroxidation is avoided through the activation of Hsp27, which upregulates GPX4 and thereby rescues CSCs from ferroptosis-induced cell death. Our results also revealed a correlation between phospho-Hsp27 and GPX4 expression levels and poor prognosis in patients with esophageal cancer. Together, these data indicate that targeting Hsp27 or GPX4 to block this intrinsic protective mechanism against ferroptosis is a potential treatment strategy for eradicating CSC in esophageal squamous cell carcinoma.

Correlation of Hemoglobin A1c Test (HbAlc) with Different Grades of Diabetic Retinopathy

Diabetic retinopathy is a disorder which generally affects the retina and disturbs the microvasculature of it and is the most dreaded complication of diabetes. This study included 50 patients with diabetic retinopathy, out of which 4% of patients infected with Non-proliferative diabetic retinopathy (NPDR), 48% with mild and 20% with very high NPDR. 8% of cases had very severe NPDR while the rest 20% had PDR. Our results which showed a higher prevalence of CSME in patients with HBA 1c of 8. 7 % and above. From the finding the elevated lipid levels in serum are associated with high risk of CSME and retinal hard exudates.

Tetrachloroaurate (III)–induced Oxidation Increases Non-thermal Plasma-induced Oxidative Stress

Non-thermal plasma (NTP) devices have been explored for medical applications. NTP devices discharge electrons, positive ions, ultraviolet, and reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as the hydroxyl radical (●OH), singlet oxygen (1O2), superoxide (O2●−), hydrogen peroxide (H2O2), ozone, and nitric oxide, at near-physiological temperature. At preclinical stages or in human clinical trials, NTP promotes blood coagulation, eradication of bacterial, viral, and biofilm-related infections, wound healing, and cancer cell death. Here, we observed that ferric, vanadium, and gold(III) ions, measured by 2-thiobarbituric acid-reactive substances (TBARS) in combination with NTP exposure, significantly elevated lipid peroxidation. Using 3,3,5,5-tetramethyl-1-pyrroline-N-oxide (M4PO) as a spin probe in electron paramagnetic resonance (EPR), we observed that tetrachloroaurate (III) yielded an M4PO-X spin adduct. Tetrachloroaurate-induced oxidation was attenuated efficiently by reduced (GSH) and oxidized glutathione (GSSG), while glycine (Gly) and L-glutamate (Glu), components of GSH, were ineffective. Furthermore, GSH and GSSG efficiently suppressed tetrachloroaurate-induced lipid peroxidation, while Gly and Glu were ineffective in suppressing TBARS elevation. These results indicate that tetrachloroaurate-induced oxidation is attenuated by GSH as well as GSSG. Further studies are warranted to elucidate the redox reactions between metal ions and biomolecules to advance the clinical application of NTP.

Mesenchymal Stem Cells Protect Against Ferroptosis via Exosome-Mediated Stabilization of Xct in Acute Liver Injury

Background: Ferroptosis, a newly recognized form of regulated cell death, was recently identified as a novel therapeutic target in tissue injury. Various studies have shown that administration of mesenchymal stem cells (MSC) is a promising therapeutic approach to repair liver injury. However, the role of ferroptosis in acute liver injury (ALI) and MSC-based therapy is unknown. Results: Here we found that CCl4 induced elevated lipid reactive oxygen species (lipid-ROS) and mRNA levels of putative molecular markers of ferroptosis such as Ptgs2 and LOX genes. CCl4 also downregulated the xCT protein levels resulting in the accumulation of lipid peroxidation and ferroptosis. MSC transplantation largely abolished CCl4-induced ferroptosis. Furthermore, the protective effects of MSC against ferroptosis were closely correlated with exosome-mediated stabilization of xCT. Administration of MSC-Exo restored the xCT protein level, decreased the elevated lipid-ROS level and Ptgs2 and LOX mRNA levels, and promoted liver restoration by inhibiting ferroptosis. Interestingly, in ALI mouse livers after MSC-Exo treatment, exosome-induced recovery of xCT protein was accompanied by upregulation of CD44 and OTUB1. The level of ubiquitinated xCT upregulated by CCl4 was significantly downregulated by OTUB1-mediated deubiquitination, and strong interactions of xCT with OTUB1 and CD44 proteins were detected. Conclusions: Taken together, our data indicate that MSC-Exo has a protective role against ferroptosis by maintaining xCT function. This provides a novel therapeutic strategy for ferroptosis-induced ALI.

Amelioration of Diabetes-Induced Nephropathy by Loranthus regularis: Implication of Oxidative Stress, Inflammation and Hyperlipidaemia

In traditional Yemeni medicine, various preparations of Loranthus regularis (L. regularis), such as powder, decoctions and infusions are commonly used to treat diabetes, kidney stone formations and inflammation. In the present study, we evaluated the antinephrotoxic effects of L. regularis extract in experimentally-induced diabetes in male Wistar rats. A single dose (60 mg/kg/day) of Streptozotocin (STZ) was used to induce type 1 diabetes. Animals were then treated for four weeks with L. regularis extract (150 or 300 mg/kg/day) by oral gavage. Renal and blood samples were subsequently harvested. Several biochemical indices, oxidative stress and inflammatory markers were assessed. Additionally, histological alterations in the renal tissue were examined. Serum glucose levels were significantly (p < 0.01) lowered while insulin levels were enhanced in L. regularis-treated diabetic animals. The increased renal markers in diabetic rats were decreased by L. regularis treatment. Serum elevated lipid profiles were markedly decreased by the plant extract. The serum and renal cytokines that were significantly increased (p < 0.001) by STZ were diminished by L. regularis treatment. Finally, renal tissue antioxidant enzymatic activity was enhanced with L. regularis treatment. Taken together, the data here indicate that L. regularis possesses therapeutic ability to reduce the development of diabetic nephropathy (DN) by minimizing oxidative injury and inflammation.

Management of Hyperlipidaemia through Ayurvedic Intervention

The potential of hyperlipidemia to engage in the pathology of atherosclerotic diseases such as coronary heart disease, which dominates the scenario of diseases causing morbidity and mortality in the world. Hyperlipidemia is defined as elevated serum levels of cholesterol, triglycerides, or both. It is characterized by abnormally elevated lipid concentrations in blood caused by impaired lipid and lipoprotein metabolism and has the potential to cause a variety of complications such as cardiovascular disease, diabetes, obesity, hypertension, atherosclerosis, and so on. Hyperlipidemia is classified as Medoroga in Ayurveda. The results obtained for the lipid profile parameter demonstrated a significant change. The difference in total serum cholesterol is 36 mg/dl, serum triglycerides is 32 mg/dl, serum LDL is 40 mg/dl, serum VLDL is 15 mg/dl and serum HDL is -3 mg/dl.

Risk of dyslipidemia among children undergoing routine medical examinations in a secondary health care facility in Benin City, Edo State

Dyslipidemias in children are a diverse group of disorders that include monogenic disorders as well as dyslipidemias caused by a variety of factors. Although cholesterol levels in healthy children differ with age, a potential link to the development of dyslipidemia may be important to determine the likelihood of an early diagnosis. In this cross-sectional study, 220 seemingly healthy children aged 1 to 12 years were studied in Benin City, Nigeria, to determine the pattern of lipid profile. An enzymatic method was used to analyze serum lipids from blood samples obtained from the participants. The level of dispersion of data needed to assess the risk of early childhood dyslipidemia was described using the 95th percentile scale. In the 1-3 years old age group, at least 95 percent of the boys had total cholesterol levels below 132 mg/dL, compared to 124 mg/dL among the girls of the same age. Similarly, total cholesterol levels in the 7-9 year old age group were 127 mg/dL in boys and 110 mg/dL in girls. These levels could serve as a guideline for children of the study’s age group who appear to be in good health. Elevated triglycerides levels were found in male children under the age of three years, as well as in the 10-12 age brackets. Increases in triglycerides in the girls, on the other hand, were not age- or time-dependent. In general, the lipid profiles shown in the results were low, particularly in the 4-6 year old age group. A significant modifiable risk factor for cardiovascular disease in children is elevated lipid levels. The results of this study demonstrate the importance of routinely screening children for dyslipidemia. Elevated lipid levels are a major modifiable risk factor for cardiovascular disease in children. The findings of this research can be used as a basis for screening children for dyslipidemia because it provides a 95th percentile in lipid profiles of seemingly healthy children.

Gut Microbiota Influence Lipid Metabolism of Skeletal Muscle in Pigs

Gut microbiota is recognized as a strong determinant of host physiology including fat metabolism and can transfer obesity-associated phenotypes from donors to recipients. However, the relationship between gut microbiota and intramuscular fat (IMF) is still largely unknown. Obese Jinhua pigs (JP) have better meat quality that is associated with higher IMF content than lean Landrace pigs (LP). The present study was conducted to test the contribution of gut microbiota to IMF properties by transplanting fecal microbiota of adult JP and LP to antibiotics-treated mice. Similar to JP donors, the mice receiving JP's microbiota (JM) had elevated lipid and triglyceride levels and the lipoprotein lipase activity, as well as reduced mRNA level of angiopoietin-like 4 (ANGPTL4) in the gastrocnemius muscles, compared to those in mice receiving LP's microbiota (LM). High-throughput 16S rRNA sequencing confirmed that transplantation of JP and LP feces differently reconstructed the gut microbiota in both jejunum and colon of mouse recipients. In colonic samples, we observed an elevated ratio of Firmicutes to Bacteroidetes and increased abundance of genus Romboutsia in JM, which were positively correlated with obesity. Furthermore, the abundance of Akkermansia decreased in JM, which is positively correlated with lean. Colonic concentrations of acetate (P = 0.047) and butyrate (P = 0.014) were significantly lower in JM than in LM, and consistently, the terminal genes for butyrate synthesis, butyryl CoA: acetate CoA transferase were less abundant in colonic microbiota of JM. Taken together, these gut microbiota of obese JP intrinsically promotes IMF accumulation and can transfer the properties to mouse recipients. Manipulation of intestinal microbiota will, therefore, have the potential to improve the meat quality and flavor of pigs and even to ameliorate the metabolic syndrome in human.