Dietary Betaine Attenuates High-Carbohydrate-Diet-Induced Oxidative Stress, Endoplasmic Reticulum Stress, and Apoptosis in Mandarin Fish (). Antioxidants (Basel, Switzerland) To investigate the impact of betaine on high-carbohydrate-diet-induced oxidative stress and endoplasmic reticulum (ER) stress, mandarin fish () (23.73 ± 0.05 g) were fed with control (NC), betaine (BET), high carbohydrate (HC), and high carbohydrate + betaine (HC + BET) diets for 8 weeks. The results showed that betaine significantly promoted the growth of mandarin fish irrespective of the dietary carbohydrate levels. The HC diet induced oxidative stress, as evidenced by significantly elevated MDA levels. The HC diet significantly stimulated the mRNA levels of genes involved in ER stress (, , , , , , ), autophagy (, , ), and apoptosis (). However, betaine mitigated HC-diet-induced oxidative stress by modulating antioxidant enzymes and alleviated ER stress by regulating the mRNA of genes in the PERK-eIF2a-ATF4 pathway. Additionally, betaine significantly reduced the mRNA levels of and , along with the apoptosis rate, indicating a mitigating effect on autophagy and apoptosis. Overall, dietary betaine improved growth, attenuated HC-diet-induced oxidative stress and ER stress, and ultimately alleviated apoptosis in mandarin fish. These findings provide evidence for the use of betaine in aquafeeds to counter disruptive effects due to diets containing high carbohydrate levels. 10.3390/antiox12101860

Chrysin-loaded PEGylated liposomes protect against alloxan-induced diabetic neuropathy in rats: the interplay between endoplasmic reticulum stress and autophagy. Biological research BACKGROUND:Diabetic neuropathy (DN) is recognized as a significant complication arising from diabetes mellitus (DM). Pathogenesis of DN is accelerated by endoplasmic reticulum (ER) stress, which inhibits autophagy and contributes to disease progression. Autophagy is a highly conserved mechanism crucial in mitigating cell death induced by ER stress. Chrysin, a naturally occurring flavonoid, can be found abundantly in honey, propolis, and various plant extracts. Despite possessing advantageous attributes such as being an antioxidant, anti-allergic, anti-inflammatory, anti-fibrotic, and anticancer agent, chrysin exhibits limited bioavailability. The current study aimed to produce a more bioavailable form of chrysin and discover how administering chrysin could alter the neuropathy induced by Alloxan in male rats. METHODS:Chrysin was formulated using PEGylated liposomes to boost its bioavailability and formulation. Chrysin PEGylated liposomes (Chr-PLs) were characterized for particle size diameter, zeta potential, polydispersity index, transmission electron microscopy, and in vitro drug release. Rats were divided into four groups: control, Alloxan, metformin, and Chr-PLs. In order to determine Chr- PLs' antidiabetic activity and, by extension, its capacity to ameliorate DN, several experiments were carried out. These included measuring acetylcholinesterase, fasting blood glucose, insulin, genes dependent on autophagy or stress in the endoplasmic reticulum, and histopathological analysis. RESULTS:According to the results, the prepared Chr-PLs exhibited an average particle size of approximately 134 nm. They displayed even distribution of particle sizes. The maximum entrapment efficiency of 90.48 ± 7.75% was achieved. Chr-PLs effectively decreased blood glucose levels by 67.7% and elevated serum acetylcholinesterase levels by 40% compared to diabetic rats. Additionally, Chr-PLs suppressed the expression of ER stress-related genes (ATF-6, CHOP, XBP-1, BiP, JNK, PI3K, Akt, and mTOR by 33%, 39.5%, 32.2%, 44.4%, 40.4%, 39.2%, 39%, and 35.9%, respectively). They also upregulated the miR-301a-5p expression levels by 513% and downregulated miR-301a-5p expression levels by 65%. They also boosted the expression of autophagic markers (AMPK, ULK1, Beclin 1, and LC3-II by 90.3%, 181%, 109%, and 78%, respectively) in the sciatic nerve. The histopathological analysis also showed that Chr-PLs inhibited sciatic nerve degeneration. CONCLUSION:The findings suggest that Chr-PLs may be helpful in the protection against DN via regulation of ER stress and autophagy. 10.1186/s40659-024-00521-1

Manganese activates autophagy and microglia M2 polarization against endoplasmic reticulum stress-induced neuroinflammation: Involvement of GSK-3β signaling. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie BACKGROUND:Endoplasmic reticulum (ER) stress-induced nerve cell damage has been known to be a hallmark feature of Mn-induced parkinsonism pathogenesis. However, several compensatory machineries, such as unfolded protein response (UPR), autophagy, and immune response, play an essential role in this damage, and the underlying molecular mechanisms are poorly understood. METHODS:Neurobehavioral impairment was assessed using catwalk gait analysis and open field test. RNA-seq analyzed the differentially expressed genes (DEGs). TUNEL staining and immunohistochemical analysis evaluated the nerve cells apoptosis and microglial cell activation. Flow cytometry assay measured microglia M1/M2 polarization. Western blotting measured protein expression. Immunofluorescence staining was used to observe the target molecules' subcellular localization. RESULTS:The study revealed that Mn caused a reduction in motor capacity, nerve cell apoptosis, and microglia activation with an imbalance in M1/M2 polarization, coupled with NF-κB signaling and PERK signaling activation. 4-PBA pretreatment could counteract these effects, while 3-MA administration exacerbated them. Additionally, autophagy could be activated by Mn. This activation could be further upregulated by 4-PBA pretreatment, whereas it was suppressed under 3-MA administration. Mn also decreased inactive GSK-3β, increased STAT3 signaling activation, and increased colocalization of GSK-3β and STAT3. These effects were strengthened by 4-PBA pretreatment, while 3-MA administration reversed them. DISCUSSION:This study suggests that autophagy and M2 microglia polarization might be protective in Mn-induced ER stress damage, possibly through GSK-3β-ULK1 autophagy signaling and STAT3 signaling activation. 10.1016/j.biopha.2023.116053