Self-Disassembling and Oxygen-Generating Porphyrin-Lipoprotein Nanoparticle for Targeted Glioblastoma Resection and Enhanced Photodynamic Therapy.

The dismal prognosis for glioblastoma multiform (GBM) patients is primarily attributed to the highly invasive tumor residual that remained after surgical intervention. The development of precise intraoperative imaging and postoperative residual removal techniques will facilitate the gross total elimination of GBM. Here, a self-disassembling porphyrin lipoprotein-coated calcium peroxide nanoparticles (PLCNP) is developed to target GBM via macropinocytosis, allowing for fluorescence-guided surgery of GBM and improving photodynamic treatment (PDT) of GBM residual by alleviating hypoxia. By reducing self-quenching and enhancing lysosome escape efficiency, the incorporation of calcium peroxide (CaO2) cores in PLCNP amplifies the fluorescence intensity of porphyrin-lipid. Furthermore, the CaO2 core has diminished tumor hypoxia and improves the PDT efficacy of PLCNP, enabling low-dose PDT and reversing tumor progression induced by hypoxia aggravation following PDT. Taken together, this self-disassembling and oxygen-generating porphyrin-lipoprotein nanoparticle may serve as a promising all-in-one nanotheranostic platform for guiding precise GBM excision and empowering post-operative PDT, providing a clinically applicable strategy to combat GBM in a safe and effective manner.

Intranasal drug delivery: The interaction between nanoparticles and the nose-to-brain pathway.

Intranasal delivery provides a direct and non-invasive method for drugs to reach the central nervous system. Nanoparticles play a crucial role as carriers in augmenting the efficacy of brain delivery. However, the interaction between nanoparticles and the nose-to-brain pathway and how the various biopharmaceutical factors affect brain delivery efficacy remains unclear. In this review, we comprehensively summarized the anatomical and physiological characteristics of the nose-to-brain pathway and the obstacles that hinder brain delivery. We then outlined the interaction between nanoparticles and this pathway and reviewed the biomedical applications of various nanoparticulate drug delivery systems for nose-to-brain drug delivery. This review aims at inspiring innovative approaches for enhancing the effectiveness of nose-to-brain drug delivery in the treatment of different brain disorders.

Extracellular vesicle therapy for obesity-induced NAFLD: a comprehensive review of current evidence.

Non-alcoholic fatty liver disease (NAFLD) as a chronic disease especially in Western countries, is still a tough question in the clinical therapy. With the rising prevalence of various chronic diseases, liver transplantation is expected to be the most common therapy after the next 10 years. However, there is still no approved drug for NAFLD, and targeted therapy for NAFLD is urgent. Exosomes as a kind of extracellular vesicle are cell-derived nanovesicles, which play an essential role in intercellular communication. Due to complex cell-cell interactions in the liver, exosomes as therapeutic drugs or drug delivery vesicles may be involved in physiological or pathological processes in NAFLD. Compared with other nanomaterials, exosomes as a cell-free therapy, are not dependent on cell number limitation, which means can be administered safely in high doses. Apart from this, exosomes with the advantages of being low-toxic, high stability, and low-immunological are chosen for targeted therapy for many diseases. In this review, firstly we introduced the extracellular vesicles, including the biogenesis, composition, isolation and characterization, and fundamental function of extracellular vesicles. And then we discussed the modification of extracellular vesicles, cargo packing, and artificial exosomes. Finally, the extracellular vesicles for the therapies of NAFLD are summarized. Moreover, we highlight therapeutic approaches using exosomes in the clinical treatment of NAFLD, which provide valuable insights into targeting NAFLD in the clinical setting.

Melatonin Alleviates Lipopolysaccharide-Induced Abnormal Pregnancy through MTNR1B Regulation of m6A.

Pregnancy is a highly intricate and delicate process, where inflammation during early stages may lead to pregnancy loss or defective implantation. Melatonin, primarily produced by the pineal gland, exerts several pharmacological effects. N6-methyladenosine (m6A) is the most prevalent mRNA modification in eukaryotes. This study aimed to investigate the association between melatonin and m6A during pregnancy and elucidate the underlying protective mechanism of melatonin. Melatonin was found to alleviate lipopolysaccharide (LPS)-induced reductions in the number of implantation sites. Additionally, it mitigated the activation of inflammation, autophagy, and apoptosis pathways, thereby protecting the pregnancy process in mice. The study also revealed that melatonin regulates uterine m6A methylation levels and counteracts abnormal changes in m6A modification of various genes following LPS stimulation. Furthermore, melatonin was shown to regulate m6A methylation through melatonin receptor 1B (MTNR1B) and subsequently modulate inflammation, autophagy, and apoptosis through m6A. In conclusion, our study demonstrates that melatonin protects pregnancy by influencing inflammation, autophagy, and apoptosis pathways in an m6A-dependent manner via MTNR1B. These findings provide valuable insights into the mechanisms underlying melatonin's protective effects during pregnancy and may have implications for potential therapeutic strategies in managing pregnancy-related complications.

Effects of monochromatic light on hepatic glycogen and lipid synthesis in broilers.

Animal growth is closely related to glycolipid metabolism, and the liver is the main organ for glycogen storage and fat synthesis in birds, but whether monochromatic light affects glycogen and lipid synthesis in the liver is unclear. Therefore, in this study, a total of 96 Arbor Acre (AA) broilers at posthatching d 0 (P0) were raised under 4 kinds of light-emitting diode (LED) lights, white light (WL), red light (RL), green light (GL), and blue light (BL), to posthatching d 21 (P21) and 35 (P35). The results showed that the liver, abdominal fat, and abdominal fat indices gradually increased with increasing age under monochromatic light treatments. The liver glycogen and triglyceride (TG) contents also showed an increasing trend. Furthermore, compared with those at P21, the mRNA levels of glycogen synthase (GS), glycogen synthase kinase-3ß (GSK-3ß), and protein kinase B (AKT1) in the liver were increased in the WL and RL groups at P35, and the mRNA levels of acetyl-CoA carboxylase (ACC) and apolipoprotein B (APOB) increased in all groups at P35. At the same time, the total antioxidant capacity (T-AOC) and liver superoxide dismutase (SOD) contents increased in all groups at P35 compared with those at P21. In addition, at P21, compared with WL, GL and BL promoted the serum glucose (GLU) and TG contents by increasing the mRNA levels of GS, GSK-3ß, glucose-6-phosphatase (G6PC), ACC, and fatty acid synthase (FAS), but no effect on the proliferative ability and damage of hepatocytes. At P35, RL promoted the hepatic glycogen and TG contents by increasing GSK-3ß, AKT1, ACC, and APOB mRNA levels, and the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were increased than in the WL group. These results suggest that the effects of light color on liver glycogen and lipid synthesis in broilers changed with age, and also provide a theoretical guidance for scientific use of color of light information to improve productive performance in broilers.

Hesperetin protects hippocampal neurons from the neurotoxicity of Aflatoxin B1 in mice.

Aflatoxin B1 (AFB1) is a major food and feed pollutant that endangers public health. Previous studies have shown that exposure to AFB1 causes neurotoxicity in the body. However, the mechanism of neurotoxicity caused by AFB1 is not well understood, and finding a workable and practical method to safeguard animals from AFB1 toxicity is essential. This study confirmed that AFB1 caused endoplasmic reticulum stress (ER stress) and apoptosis in hippocampal neurons using C57BL/6 J mice and HT22 cells as models. In vitro experiments showed that the aryl hydrocarbon receptor (AHR) plays a significant role in the cytotoxicity of AFB1. Finally, we assessed how hesperetin protecting against the neurotoxicity caused by AFB1. Our findings demonstrated that AFB1 increased the levels of BAX and Cleaved-Caspase3 proteins, while decreasing the levels of BCL2 protein in the CA1 and CA3 regions of the hippocampus. The AFB1 increased the expression of AHR and activated nuclear translocation. It also elevated the expression levels of Chop, GRP78, p-IRE1/ Xbp1s, and p-PERK/p-EIF2a. Importantly, we also discovered for the first time that blocking AHR in HT22 cells dramatically reduced the level of ER stress and apoptosis caused by AFB1. In vivo and in vitro studies, supplementation of hesperetin effectively reversed AFB1-induced cytotoxicity. We have demonstrated that hesperetin effectively restored the imbalance in the GSH/GST system in HT22 cells treated with AFB1. Furthermore, we observed that elevated GSH levels facilitated the formation of AFB1-GSH complexes, which enhanced the excretion of AFB1. Therefore, hesperetin improves ER stress-induced apoptosis by reducing AFB1 activation of AHR.

The signal pathway of melatonin mediates the monochromatic light-induced T-lymphocyte apoptosis in chicken thymus.

Our previous study revealed that under monochromatic red light (RL), the melatonin nuclear receptor reduces the proliferation activity of broiler thymic lymphocytes through the P65 signaling pathway. The main objective of this study was to investigate the signal mechanism by which RL decreases thymic lymphocyte proliferation. Initially, broilers were purchased and randomly assigned to be fed under white light (WL), red light (RL), green light (GL), and blue light (BL). Pinealectomy was performed 3 d later, and the broilers were euthanized after 14 d. The results showed that the expression of the antiapoptotic proteins Bcl-2/Bcl-xl decreased under RL, while the expression of the pro-apoptotic factor Bax/caspase-3 and the pro-inflammatory factors INF-γ/TNF-α/IL-6 increased. After pinealectomy, the expression of Bax/TNF-α/IL-6 increased in conjunction with the decrease in Bcl-2 expression. In vitro experiments demonstrated that exogenous melatonin decreased the expression of Bax/TNF-α/IL-6 in thymic lymphocytes of chicks reared under RL. This melatonin-induced effect was enhanced by SR1078 (RORα/RORγ agonist) but attenuated by SR3335 (RORα antagonist) and BAY (P65 antagonist). These findings revealed that the melatonin nuclear receptor RORα/RORγ promotes the expression of the pro-apoptotic factor Bax/caspase-3 and the pro-inflammatory factors INF-γ/TNF-α/IL-6, while inhibiting the expression of the antiapoptotic factor Bcl-2/Bcl-xl. Our research suggested the signaling pathway of monochromatic red light impacts the apoptosis of thymus lymphocytes in broiler.

ECA-TFUnet: A U-shaped CNN-Transformer network with efficient channel attention for organ segmentation in anatomical sectional images of canines.

Automated organ segmentation in anatomical sectional images of canines is crucial for clinical applications and the study of sectional anatomy. The manual delineation of organ boundaries by experts is a time-consuming and laborious task. However, semi-automatic segmentation methods have shown low segmentation accuracy. Deep learning-based CNN models lack the ability to establish long-range dependencies, leading to limited segmentation performance. Although Transformer-based models excel at establishing long-range dependencies, they face a limitation in capturing local detail information. To address these challenges, we propose a novel ECA-TFUnet model for organ segmentation in anatomical sectional images of canines. ECA-TFUnet model is a U-shaped CNN-Transformer network with Efficient Channel Attention, which fully combines the strengths of the Unet network and Transformer block. Specifically, The U-Net network is excellent at capturing detailed local information. The Transformer block is equipped in the first skip connection layer of the Unet network to effectively learn the global dependencies of different regions, which improves the representation ability of the model. Additionally, the Efficient Channel Attention Block is introduced to the Unet network to focus on more important channel information, further improving the robustness of the model. Furthermore, the mixed loss strategy is incorporated to alleviate the problem of class imbalance. Experimental results showed that the ECA-TFUnet model yielded 92.63% IoU, outperforming 11 state-of-the-art methods. To comprehensively evaluate the model performance, we also conducted experiments on a public dataset, which achieved 87.93% IoU, still superior to 11 state-of-the-art methods. Finally, we explored the use of a transfer learning strategy to provide good initialization parameters for the ECA-TFUnet model. We demonstrated that the ECA-TFUnet model exhibits superior segmentation performance on anatomical sectional images of canines, which has the potential for application in medical clinical diagnosis.

Melanopsin-mediated optical entrainment regulates circadian rhythms in vertebrates.

Melanopsin (OPN4) is a light-sensitive protein that plays a vital role in the regulation of circadian rhythms and other nonvisual functions. Current research on OPN4 has focused on mammals; more evidence is needed from non-mammalian vertebrates to fully assess the significance of the non-visual photosensitization of OPN4 for circadian rhythm regulation. There are species differences in the regulatory mechanisms of OPN4 for vertebrate circadian rhythms, which may be due to the differences in the cutting variants, tissue localization, and photosensitive activation pathway of OPN4. We here summarize the distribution of OPN4 in mammals, birds, and teleost fish, and the classical excitation mode for the non-visual photosensitive function of OPN4 in mammals is discussed. In addition, the role of OPN4-expressing cells in regulating circadian rhythm in different vertebrates is highlighted, and the potential rhythmic regulatory effects of various neuropeptides or neurotransmitters expressed in mammalian OPN4-expressing ganglion cells are summarized among them.

Melatonin Ameliorates Hepatic Ferroptosis in NAFLD by Inhibiting ER Stress via the MT2/cAMP/PKA/IRE1 Signaling Pathway.

Ferroptosis, an iron-dependent cell death form, has recently been observed in the development of non-alcoholic fatty liver disease (NAFLD). Melatonin (Mel) shows potential benefits for preventing and treating liver diseases. Whether and how Mel ameliorates hepatic ferroptosis in NAFLD is not fully understood. Here we established a mouse model of NAFLD induced by long-term high-fat diet (HFD) feeding. We found that Mel treatment ameliorated global metabolic abnormalities and inhibited the progression of NAFLD in mice. Most importantly, Mel supplementation significantly improved HFD-induced iron homeostasis disorders in the liver, including iron overload and ferritin transport disorders. For another, Mel ameliorated HFD-induced hepatic lipid peroxidation. The recuperative role of exogenous Mel on hepatocyte ferroptosis was also observed in PA- or Erastin-treated HepG2 cells. Mechanistically, MT2, but not MT1, was involved in the effect of Mel. Furthermore, Mel treatment inhibited HFD or Erastin-activated ER stress and activated the PKA/IRE1 signaling pathway. Co-expression of p-PKA and p-IRE1 was enhanced by the MT2 antagonist. Inhibitions of PKA and IRE1 respectively improved hepatocyte ferroptosis, and activations of cAMP/PKA reversed Mel's effect on ferroptosis. Collectively, these findings suggest that exogenous Mel inhibits hepatic ferroptosis in NAFLD by ameliorating ER stress through the MT2/cAMP/PKA/IRE1 pathway, proving that Mel is a promising candidate drug for the treatment of hepatic ferroptosis in NAFLD.

Chronic Stress That Changed Intestinal Permeability and Induced Inflammation Was Restored by Estrogen.

Chronic psychological stress affects the health of humans and animals (especially females or pregnant bodies). In this study, a stress-induced model was established by placing eight-week-old female and pregnant mice in centrifuge tubes for 4 h to determine whether chronic stress affects the intestinal mucosal barrier and microbiota composition of pregnant mice. Compared with the control group, we found that norepinephrine (NE), corticosterone (CORT), and estradiol (E2) in plasma increased significantly in the stress group. We then observed a decreased down-regulation of anti-inflammatory cytokines and up-regulation of pro-inflammatory cytokines, which resulted in colonic mucosal injury, including a reduced number of goblet cells, proliferating cell nuclear antigen-positive cells, caspase-3, and expression of tight junction mRNA and protein. Moreover, the diversity and richness of the colonic microbiota decreased in pregnant mice. Bacteroidetes decreased, and pernicious bacteria were markedly increased. At last, we found E2 protects the intestinal epithelial cells after H2O2 treatment. Results suggested that 25 pg/mL E2 provides better protection for intestinal barrier after chronic stress, which greatly affected the intestinal mucosal barrier and altered the colonic microbiota composition.

Roles of Rac1-Dependent Intrinsic Forgetting in Memory-Related Brain Disorders: Demon or Angel.

Animals are required to handle daily massive amounts of information in an ever-changing environment, and the resulting memories and experiences determine their survival and development, which is critical for adaptive evolution. However, intrinsic forgetting, which actively deletes irrelevant information, is equally important for memory acquisition and consolidation. Recently, it has been shown that Rac1 activity plays a key role in intrinsic forgetting, maintaining the balance of the brain's memory management system in a controlled manner. In addition, dysfunctions of Rac1-dependent intrinsic forgetting may contribute to memory deficits in neurological and neurodegenerative diseases. Here, these new findings will provide insights into the neurobiology of memory and forgetting, pathological mechanisms and potential therapies for brain disorders that alter intrinsic forgetting mechanisms.

Eucommia ulmoides polysaccharide modified nano-selenium effectively alleviated DSS-induced colitis through enhancing intestinal mucosal barrier function and antioxidant capacity.

Ulcerative colitis (UC) is currently the most common inflammatory bowel disease (IBD). Due to its diverse and complex causes, there is no cure at present, and researchers are constantly exploring new therapies. In recent years, nano-selenium particle(SeNP) has attracted wide attention due to excellent biological activities. Therefore, in this study, for the first time, we used a natural polysaccharide, Eucommia ulmoides polysaccharide (EUP), modified SeNP to get EUP-SeNP with a size of about 170 nm, and its effect on 3% dextran sulphate sodium (DSS) induced colitis was explored. Our results showed that colon intestinal histology, intestinal mucosal barrier, inflammatory cytokines and intestinal microbiome composition were changed after EUP-SeNP treatment in colitis mice. Specifically, it was also shown that oral treatment of EUP-SeNP could relieve the degree of DSS-induced colitis in mice by restoring weight loss, reducing disease activity index (DAI), enhancing colon antioxidant capacity and regulating intestinal microbiome composition. In addition, we verified the mechanism in intestinal epithelial cell lines, showing that EUP-SeNP inhibited LPS-induced activation of the TRL-4/NF-κB signaling pathway in intestinal epithelial cell lines. To some extend, our study provides therapeutic reference for the treatment of IBD.

Targeted drug delivery system inspired by macropinocytosis.

Macropinocytosis is a widely-observed and evolutionarily-conserved endocytic process found in the eukaryotic cells. In comparison to other endocytic routes, macropinocytosis allows for the internalization of greater quantities of fluid-phase drugs, making it an attractive avenue for drug delivery. Recent evidence showed that various drug delivery systems can be internalized through macropinocytosis. Utilizing macropinocytosis may therefore provide a new avenue for targeted intracellular delivery. In this review, we provide an overview into the origins and distinctive properties of macropinocytosis, summarize the roles of macropinocytosis under healthy and pathological settings. Furthermore, we highlight the biomimetic and synthetic drug delivery systems that employ macropinocytosis as the primary internalization mechanism. To facilitate the clinical applications of these drug delivery systems, additional research can be conducted to enhance the cell-type selectivity of macropinocytosis, the control of drug release at the target, and the prevention of potential toxicity. The rapidly emerging field of macropinocytosis-based targeted drug delivery and therapies holds great potential to drastically increase the efficiency and specificity of drug delivery.

Clinic-radiomics model using liver magnetic resonance imaging helps predict chronicity of drug-induced liver injury.

BACKGROUND AND AIMS: Some drug-induced liver injury (DILI) cases may become chronic, even after drug withdrawal. Radiomics can predict liver disease progression. We established and validated a predictive model incorporating the clinical characteristics and radiomics features for predicting chronic DILI. METHODS: One hundred sixty-eight DILI patients who underwent liver gadolinium-diethylenetriamine pentaacetate-enhanced magnetic resonance imaging were recruited. The patients were clinically diagnosed using the Roussel Uclaf causality assessment method. Patients who progressed to chronicity or recovery were randomly divided into the training (70%) and validation (30%) cohorts, respectively. Hepatic T1-weighted images were segmented to extract 1672 radiomics features. Least absolute shrinkage and selection operator regression was used for feature selection, and Rad-score was constructed using support vector machines. Multivariable logistic regression analysis was performed to build a clinic-radiomics model incorporating clinical characteristics and Rad-scores. The clinic-radiomics model was evaluated for its discrimination, calibration, and clinical usefulness in the independent validation set. RESULTS: Of 1672 radiomics features, 28 were selected to develop the Rad-score. Cholestatic/mixed patterns and Rad-score were independent risk factors of chronic DILI. The clinic-radiomics model, including the Rad-score and injury patterns, distinguished chronic from recovered DILI patients in the training (area under the receiver operating characteristic curve [AUROC]: 0.89, 95% confidence interval [95% CI]: 0.87-0.92) and validation (AUROC: 0.88, 95% CI: 0.83-0.91) cohorts with good calibration and great clinical utility. CONCLUSION: The clinic-radiomics model yielded sufficient accuracy for predicting chronic DILI, providing a practical and non-invasive tool for managing DILI patients.

Continuous Monochromatic Blue Light Exacerbates High-Fat Diet-Induced Kidney Injury via Corticosterone-Mediated Oxidative Stress.

Excessive illumination is one of the most severe environmental factors that impacts the organism. There is growing evidence that obesity significantly contributes to the onset of chronic kidney disease. However, the effect of continuous light on the kidney and which color can produce an apparent phenomenon remains elusive. In this study, C57BL/6 mice given either a normal diet (LD-WN) or a high-fat diet (LD-WF) were subjected to a light cycle of 12 h of illumination followed by 12 h of darkness for 12 weeks. Meanwhile, 48 high-fat diet mice were given a 24 h monochromatic light exposure of varying colors (white, LL-WF; blue, LL-BF; green, LL-GF) for 12 weeks. As expected, the LD-WF mice showed significant obesity, kidney injury, and renal dysfunction compared with the LD-WN group. LL-BF mice had worse kidney injury than LD-WF mice, including higher Kim-1 and Lcn2. The kidney of the LL-BF group showed marked glomerular and tubular injury, with decreased levels of Nephrin, Podocin, Cd2ap, and α-Actinin-4 compared to LD-WF. LL-BF also reduced the antioxidant capacity, including GSH-Px, CAT, and T-AOC, increased the production of MDA, and inhibited the activation of the NRF2/HO-1 signaling pathway. Furthermore, LL-BF upregulated the mRNA levels of the pro-inflammatory factors Tnf-α, Il-6, and Mcp-1, decreasing the inhibitory inflammatory Il-4 expression. We observed increased plasma corticosterone (CORT), renal glucocorticoid receptors (GR) expression, Hsp90, Hsp70, and P23 mRNA levels. These findings suggested that LL-BF increased CORT secretion and affected glucocorticoid receptors (GR) in comparison to the LD-WF group. Moreover, in vitro research demonstrated that CORT treatment increased oxidative stress and inflammation, which was counteracted by adding a GR inhibitor. Thus, the sustained blue light worsened kidney damage, possibly by inducing elevated CORT and increasing oxidative stress and inflammation via GR.

Interactions between gut microbes and NLRP3 inflammasome in the gut-brain axis.

The role of the gut-brain axis in maintaining the brain's and gut's homeostasis has been gradually recognized in recent years. The connection between the gut and the brain takes center stage. In this scenario, the nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome promotes inflammatory cell recruitment. It plays a crucial role in coordinating host physiology and immunity. Recent evidence shows how vital the gut-brain axis is for maintaining brain and gut homeostasis. However, more research is needed to determine the precise causal link between changed gut microbiota structure and NLRP3 activation in pathogenic circumstances. This review examines the connection between gut microbiota and the NLRP3 inflammasome. We describe how both dynamically vary in clinical cases and the external factors affecting both. Finally, we suggest that the crosstalk between the gut microbiota and NLRP3 is involved in signaling in the gut-brain axis, which may be a potential pathological mechanism for CNS diseases and intestinal disorders.

Melatonin improves skin barrier damage caused by sleep restriction through gut microbiota.

It is widely known that lack of sleep damages the skin. Therefore, it is necessary to explore the relationship between sleep deprivation and skin damage and to find effective treatments. We established a 28-day sleep restriction (SR) mice model simulating continuous long-term sleep loss. We found that SR would damage the barrier function of mice's skin, cause oxidative stress damage to the skin, weaken the oscillations of the skin's biological clock, and make the circadian rhythm of Bacteroides disappear. The circadian rhythm of short-chain fatty acids (SCFA) receptors in the skin was disordered. After melatonin supplementation, the skin damage caused by SR was improved, the oscillations of the biological clock were enhanced, the circadian rhythm of Bacteroides was restored, and the rhythm of the receptor GPR43 of propionic acid was restored. We speculated that the improving effect of melatonin may be mediated by propionic acid produced by the gut microbiota. We verified in vitro that propionic acid could improve the keratinocytes barrier function of oxidative damage. We then consumed the gut microbiota of mice through antibiotics and found that oral melatonin could not improve skin damage. Moreover, supplementing mice with propionic acid could improve skin damage. Our research showed that lack of sleep impaired skin barrier function. Oral melatonin could improve skin damage by restoring the circadian rhythm of Bacteroides and its propionic acid metabolite.

The Timing Sequence and Mechanism of Aging in Endocrine Organs.

The world is increasingly aging, and there is an urgent need to find a safe and effective way to delay the aging of the body. It is well known that the endocrine glands are one of the most important organs in the context of aging. Failure of the endocrine glands lead to an abnormal hormonal environment, which in turn leads to many age-related diseases. The aging of endocrine glands is closely linked to oxidative stress, cellular autophagy, genetic damage, and hormone secretion. The first endocrine organ to undergo aging is the pineal gland, at around 6 years old. This is followed in order by the hypothalamus, pituitary gland, adrenal glands, gonads, pancreatic islets, and thyroid gland. This paper summarises the endocrine gland aging-related genes and pathways by bioinformatics analysis. In addition, it systematically summarises the changes in the structure and function of aging endocrine glands as well as the mechanisms of aging. This study will advance research in the field of aging and help in the intervention of age-related diseases.

Microbiota-gut-adipose axis: butyrate-mediated the improvement effect on inflammatory response and fatty acid oxidation dysregulation attenuates obesity in sleep-restricted mice.

BACKGROUND: Insufficient sleep was considered as a substantial cause of obesity. The present study further explored the mechanism whereby sleep restriction (SR)-mediated intestinal dysbiosis induced metabolic disorder and ultimately lead to obesity in mice and the improvement effect of butyrate exerting on it. METHODS: A continuous 3 months SR mouse model with or without butyrate supplementation and fecal microbiota transplantation to explore the key role of intestinal microbiota in butyrate improving inflammatory response in inguinal white adipose tissue (iWAT) and fatty acid oxidation dysfunction in brown adipose tissue (BAT), further ameliorating SR-induced obesity. RESULTS: SR-mediated gut microbiota dysbiosis (down-regulation in butyrate level and up-regulation in LPS level) induced intestinal permeability increase and inflammatory response in iWAT and fatty acid oxidation dysfunction in BAT, ultimately resulting in obesity. Further, we demonstrated butyrate ameliorated gut microbiota homeostasis, suppressed inflammatory response via GPR43/LPS/TLR4/MyD88/GSK-3ß/ß-catenin loop in iWAT and restored fatty acid oxidation function via HDAC3/PPARα/PGC-1α/UCP1/Calpain1 pathway in BAT, ultimately reversing SR-induced obesity. CONCLUSIONS: We revealed that gut dysbiosis is a key factor for SR-induced obesity and provided a better understanding of the effects of butyrate. We further expected that reversing SR-induced obesity by improving microbiota-gut-adipose axis disorder could be a possible treatment for metabolic diseases.