The high expression of ADRM1 in hepatocellular carcinoma is closely related to tumor immune infiltration and is regulated by miR-891a-5p.

Liver cancer is one of the most common malignant tumors worldwide. Although some progress has been made in the diagnosis and treatment of Hepatocellular carcinoma (HCC), the diagnosis and treatment of HCC is still facing great challenges because of the high mortality rate and poor prognosis of HCC. The purpose of this study was to explore the relationship between adhesion-regulating molecule1 (ADRM1), and liver cancer, and the relationship between prognoses. ADRM1 is highly expressed in tumors and is closely associated with the prognosis of patients with liver cancer. In our previous study, we found that ADRM1 was highly expressed in HCC and was closely related to tumor immune and immune checkpoint levels in HCC. We validated the immune expression of ADRM1 in liver cancer cells using flow cytometry. In hepatocellular carcinoma tissues, miR-891a-5p regulates ADRM1. Upregulation of miR-891a-5p upregulates ADRM1, and downregulation of miR-891a-5p downregulates ADRM1. It is suggested that ADRM1 plays a key role in the occurrence and development of hepatocellular carcinoma. This study is expected to provide new ideas for the research and development of anti-HCC drugs targeting miR-891a-5p/ADRM1. However, further trials are needed to confirm these results and explore the actual results in patients with HCC.

Unveiling YWHAH: A potential therapeutic target for overcoming CD8+ T cell exhaustion in colorectal cancer.

Colorectal cancer (CRC) is a significant global health challenge, with increasing rates of incidence and mortality. Despite advancements in immunotherapy, resistance, particularly due to T cell exhaustion, remains a major hurdle. This study explores the role of YWHAH, mediated by N4-acetylcytidine (ac4C) modification, in CRC progression and its impact on CD8+ T cell exhaustion. Analysis of five paired CRC patient tissue samples using acetylated RNA immunoprecipitation and sequencing (acRIP-seq)identified ac4C-modified mRNAs. Functional assays, including cell culture, transfection, qRT-PCR, and immune assays, investigated the influence of YWHAH expression on CRC advancement. Bioinformatics analysis of TCGA data assessed the correlation between YWHAH and immune responses, as well as checkpoint inhibitors. Flow cytometry and Immunohistochemistry validated these findings, complemented by a co-culture experiment involving CD8+ T cells and CRC cell lines (LOVO and HCT116). acRIP-seq revealed YWHAH as a potential driver of CRC progression, exhibiting ac4C modification-mediated stability and upregulation. High YWHAH levels correlated with adverse outcomes and immune evasion in CRC patients, showing strong associations with immune checkpoint proteins and modest correlations with CD8+ T cell infiltration. Co-culture experiments demonstrated YWHAH-induced CD8+ T cell exhaustion, characterized by decreased proliferation and increased exhaustion markers. NAT10-mediated ac4C modification enhanced YWHAH stability in CRC. The involvement of YWHAH in CD8 + T cell exhaustion suggests its potential as a therapeutic target and prognostic marker in CRC immunotherapy, highlighting the intricate interplay between epitranscriptomic modifications, the tumor microenvironment, and immune responses in CRC progression.

Endovenous laser treatment vs conventional surgery for great saphenous vein varicosities: A propensity score matching analysis.

BACKGROUND: Varicosis is a common venous condition, which is typically treated surgically. However, selection of the optimal surgical approach can be challenging. Previous studies comparing endovenous laser treatment (EVLT) and conventional surgery were retrospective and observational in nature and the results may therefore have been influenced by selection bias and the presence of other confounding factors. In this study, we used propensity score matching to reduce selection bias when comparing EVLT and conventional surgery for the treatment of varicose great saphenous veins. AIM: To compare the perioperative and postoperative outcomes of EVLT and conventional surgery in patients with great saphenous vein varicosis. METHODS: We retrospectively reviewed the records of 1063 patients treated for primary varicosis of the great saphenous vein at the Second Affiliated Hospital of Xuzhou Medical University between January 2009 and December 2019. Among them, 56 patients were excluded owing to additional small saphenous varicose vein involvement, 81 owing to recurring varicose veins, 83 owing to complicated varicose veins (CEAP clinical classification C5-C6), and 6 owing to perioperative phlebitis. Finally, 772 patients were enrolled in this study. Standard demographic and clinicopathological data were collected from the medical records of the patients. For propensity score matching, 522 patients (261 who underwent EVLT and 261 who underwent conventional surgery) were randomly matched 1:1 by age, sex, onset time, smoking status, presence of diabetes, family history, stress therapy, C class, and the affected leg. RESULTS: Of the 772 patients included in the study, 467 underwent EVLT and 305 underwent conventional surgery. There were significant differences in age, onset time, smoking and diabetes status, and family history between the two groups. Following propensity score matching, no significant differences in patients' characteristics remained between the two groups. ELVT was associated with a shorter operation time and hospital stay than conventional surgery, both before and after propensity score matching. There were no differences in complications between the two groups after propensity score matching. Patients who underwent EVLT had a higher recurrence rate during the two-year follow-up period than those who underwent conventional surgery (33.33% vs 21.46%, χ2 = 11.506, P = 0.001), and a greater percentage of patients who underwent EVLT experienced pain one week after the procedure (39.85% vs 19.54%, P = 0.000). CONCLUSION: EVLT may not always be the best option for the treatment of great saphenous vein varicosis.

Photoelectrocatalysis Synthesis of Ammonia Based on a Ni-Doped MoS2/Si Nanowires Photocathode and Porous Water with High N2 Solubility.

The synthesis of ammonia through photocatalysis or photoelectrochemistry (PEC) and nitrogen reduction reaction (NRR) has become one of the recent research hotspots in the field, where the catalyzed materials and strategies are critical for the NRR. Herein, a Ni-doped MoS2/Si nanowires (Ni-MoS2/Si NWs) photocathode is prepared, where the Si NWs are formed on the surface of a Si slice by the metal-assisted chemical etching method, and the hydrothermally synthesized Ni-MoS2 nanosheets are then cast-coated on the Si NWs electrode. Porous water with high solubility of N2 is prepared by treating a hydrophobic porous coordination polymer with hydrophilic bovine serum albumin for subsequent aqueous dispersing. The relevant electrodes and materials are characterized by electrochemistry, UV-vis spectrophotometry, scanning electron microscopy/energy dispersive spectroscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, Brunauer-Emmett-Teller method, and zeta potential method. The uses of the Ni-MoS2/Si NWs photocathode and the porous water with high nitrogen solubility for PEC-NRR give a yield of NH3 of 12.0 mmol h-1 m-2 under optimal conditions (e.g., at 0.25 V vs RHE), and the obtained apparent Faradaic efficiency higher than 100% is discussed from the inherent photocurrent-free photocatalysis effect of the photoelectrodes and the suggested classification of three kinds of electrons in PEC, which may have some reference value in understanding and improving other PEC-based processes.

Renal Cancer Detection: Fusing Deep and Texture Features from Histopathology Images.

Histopathological images contain morphological markers of disease progression that have diagnostic and predictive values, with many computer-aided diagnosis systems using common deep learning methods that have been proposed to save time and labour. Even though deep learning methods are an end-to-end method, they perform exceptionally well given a large dataset and often show relatively inferior results for a small dataset. In contrast, traditional feature extraction methods have greater robustness and perform well with a small/medium dataset. Moreover, a texture representation-based global approach is commonly used to classify histological tissue images expect in explicit segmentation to extract the structure properties. Considering the scarcity of medical datasets and the usefulness of texture representation, we would like to integrate both the advantages of deep learning and traditional machine learning, i.e., texture representation. To accomplish this task, we proposed a classification model to detect renal cancer using a histopathology dataset by fusing the features from a deep learning model with the extracted texture feature descriptors. Here, five texture feature descriptors from three texture feature families were applied to complement Alex-Net for the extensive validation of the fusion between the deep features and texture features. The texture features are from (1) statistic feature family: histogram of gradient, gray-level cooccurrence matrix, and local binary pattern; (2) transform-based texture feature family: Gabor filters; and (3) model-based texture feature family: Markov random field. The final experimental results for classification outperformed both Alex-Net and a singular texture descriptor, showing the effectiveness of combining the deep features and texture features in renal cancer detection.

Development of a Dual ELISA for the Detection of CD2v-Unexpressed Lower-Virulence Mutational ASFV.

African swine fever virus (ASFV) is an important viral pathogen infecting pigs worldwide throughout the pig industry. CD2v (an outer-membrane glycosylated protein of ASFV)-unexpressed lower-virulence mutants have appeared in China and other countries in recent years. Using OIE-recommended quantitative PCR and ELISA methods, people can accurately judge whether pigs are infected with wild-type ASFV. However, the strategy has failed to distinguish ΔCD2v lower-virulence mutants and wild-type ASFV infection. Here, we expressed and purified the CD2v and p30 proteins via CHO cells and successfully established a dual enzyme-linked immunosorbent assay (ELISA), which can be used to differentiate pigs infected with wild-type ASFV or with CD2v-unexpressed lower-virulence mutants. The dual ELISA showed excellent specificity without cross-reactions with antibodies of PRRSV, CSFV, JEV, PRV, or PPV. The dual ELISA could detect ASFV-infected positive serum samples up to dilutions of 5120 times, possessing high sensitivity. Therefore, the application of this dual ELISA approach can play an important role in ASFV epidemiology study and fill the gaps in differential diagnosis.

Orexin-A alleviates astrocytic apoptosis and inflammation via inhibiting OX1R-mediated NF-κB and MAPK signaling pathways in cerebral ischemia/reperfusion injury.

Orexin-A (OXA) is a neuropeptide with neuroprotective effect by reducing cerebral ischemia/reperfusion injury (CIRI). Inflammation and apoptosis mediated by astrocyte activation are the key pathological mechanisms for CIRI. We thus attempted to confirm neuroprotective effects of OXA on astrocytic inflammation and apoptosis in CIRI and clarify the relative mechanisms. A middle cerebral artery occlusion and reperfusion (MCAO/R) rat model and U251 glioma cells model subjected to oxygen glucose deprivation and reperfusion (OGD/R) were established, with or without OXA treatment. Neurological deficit score was determined, and cerebral infarct volume was evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Western Blot was used to detect the expressions of NF-κB p65, p-p65, p-ERK, p-p38, GFAP, OX1R, IL-1ß, TNF-α, IL-6, iNOS, Bcl-2, Bax, CytC, cleaved caspase-9 and cleaved caspase-3 in vivo and in vitro. Pro-inflammatory cytokines in cell supernatant IL-1ß, TNF-α and IL-6 were determined by ELISA. Hoechst 33342 staining was used to detect the apoptosis of astrocyte. Immunofluorescent staining was performed to assess the nuclear translocation of p65 and the expression of GFAP. The results showed that OXA significantly improved neurological deficit score and decreased the volume of infarct area in brain. OXA decreased inflammatory mediators, inhibited astrocyte activation and nuclear translocation of NF-κB and phosphorylation of NF-κB, MAPK/ERK and MAPK/p38. Besides, OXA suppressed apoptosis via upregulating the ratio of Bcl-2/Bax and downregulating cytochrome C, cleaved-caspase-9 and cleaved caspase-3. Overall, it was concluded that OXA exerts neuroprotective effect during CIRI through attenuating astrocytes apoptosis, astrocytes activation and pro-inflammatory cytokines production, by Inhibiting OX1R-mediated NF-κB, MAPK/ERK and MAPK/p38 signaling pathways. The progress in our study is helpful to elucidate the molecular mechanisms of OXA neuroprotection, which could lead to the development of new treatment strategies for ischemic stroke.

Apelin-36 Protects HT22 Cells Against Oxygen-Glucose Deprivation/Reperfusion-Induced Oxidative Stress and Mitochondrial Dysfunction by Promoting SIRT1-Mediated PINK1/Parkin-Dependent Mitophagy.

Oxidative stress and mitochondrial dysfunction are involved in cerebral ischemia/reperfusion injury-induced neuronal apoptosis. Mitophagy is the main method to eliminate dysfunctional mitochondria. Apelin-36, a type of neuropeptide, has been reported to exert protective effects in cerebral I/R (I/R) injury, but its precise mechanisms remain to be elucidated. To study the effects of Apelin-36 on oxidative stress and mitochondrial dysfunction in cerebral I/R injury, the oxygen-glucose deprivation/reperfusion (OGD/R) model with 6 h of ischemia and 6 h of reperfusion was established in HT22 cells. Results demonstrated that Apelin-36 protected against OGD/R injury by improving cell viability, decreasing the apoptotic cells ratio and increasing the ratio of Bcl-2/Bax. In addition, Apelin-36 treatment inhibited oxidative stress by downregulating the level of reactive oxygen species (ROS) and malondialdehyde (MDA) as well as the expression of inducible nitric oxide synthase (iNOS). And Apelin-36 also activated the level of superoxide dismutase (SOD) and glutathione (GSH). Mitochondrial apoptosis was also alleviated with Apelin-36 treatment detected by the mitochondrial membrane potential (MMP) and the expression of Cytochrome c (Cyt c), Cleaved caspase-9, and Cleaved caspase-3. Furthermore, the SIRT1-mediated PINK1/Parkin-dependent mitophagy was activated by Apelin-36 treatment with the downregulation of p62 and upregulation of LC3B-II and Beclin1. Both EX527 and Cyclosporine A (CsA), which are inhibitors of SIRT1 and mitophagy, markedly alleviated the inhibition of oxidative stress and mitochondrial dysfunction caused by Apelin-36. These findings suggest that SIRT1-mediated PINK1/Parkin-dependent mitophagy is involved in the neuroprotective effects of Apelin-36 on OGD/R-induced oxidative stress and mitochondrial dysfunction.

Ghrelin protects against rotenone-induced cytotoxicity: Involvement of mitophagy and the AMPK/SIRT1/PGC1α pathway.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by the loss of dopaminergic neurons in the substantia nigra and the deposition of Lewy bodies. Mitochondrial dysfunction, oxidative stress, and autophagy dysfunction are involved in the pathogenesis of PD. Ghrelin is a brain-gut peptide that has been reported that protected against 1-methyl-4-phenyl-1,2,3,6- tetrahydropyran (MPTP)/MPP+-induced toxic effects. In the present work, human neuroblastoma SH-SY5Y cells were exposed to rotenone as a PD model to explore the underlying mechanism of ghrelin. We found that ghrelin inhibited rotenone-induced cytotoxicity, mitochondrial dysfunction, and apoptosis by improving cell viability, increasing the ratio of red/green of JC-1, inhibiting the production of reactive oxidative species (ROS), and regulating Bcl-2, Bax, Cytochrome c, caspase-9, and caspase-3 expression. Besides, ghrelin promoted mitophagy accompanied by up-regulating microtubule-associated protein 1 Light Chain 3B-II/I(LC3B-II/I) and Beclin1 but decreasing the expression of p62. Moreover, ghrelin promoted PINK1/Parkin mitochondrial translocation. Additionally, we investigated that ghrelin activated the AMPK/SIRT1/PGC1α pathway and pharmacological inhibition of AMPK and SIRT1 abolished the cytoprotection of ghrelin, decreased the level of mitophagy, and PINK1/Parkin mitochondrial translocation. Taken together, our findings suggested that mitophagy and AMPK/SIRT1/PGC1α pathways were related to the cytoprotection of ghrelin. These findings provided novel insights into the underlying mechanisms of ghrelin, further mechanistic studies on preclinical and clinical levels are required to be conducted with ghrelin to avail and foresee it as a potential agent in the treatment and management of PD.

Regulatory effects of ghrelin on endoplasmic reticulum stress, oxidative stress, and autophagy: Therapeutic potential.

Ghrelin is a regulatory peptide that is the endogenous ligand of the growth hormone secretagogue 1a (GHS-R1a) which belongs to the G protein-coupled receptor family. Ghrelin and GHS-R1a are widely expressed in the central and peripheral tissues and play therapeutic potential roles in the cytoprotection of many internal organs. Endoplasmic reticulum stress (ERS), oxidative stress, and autophagy dysfunction, which are involved in various diseases. In recent years, accumulating evidence has suggested that ghrelin exerts protective effects by regulating ERS, oxidative stress, and autophagy in diverse diseases. This review article summarizes information about the roles of the ghrelin system on ERS, oxidative stress, and autophagy in multiple diseases. It is suggested that ghrelin positively affects the treatment of diseases and may be considered as a therapeutic drug in many illnesses.

Apelin-13 inhibits apoptosis and excessive autophagy in cerebral ischemia/reperfusion injury.

Apelin-13 is a novel endogenous ligand for an angiotensin-like orphan G-protein coupled receptor, and it may be neuroprotective against cerebral ischemia injury. However, the precise mechanisms of the effects of apelin-13 remain to be elucidated. To investigate the effects of apelin-13 on apoptosis and autophagy in models of cerebral ischemia/reperfusion injury, a rat model was established by middle cerebral artery occlusion. Apelin-13 (50 µg/kg) was injected into the right ventricle as a treatment. In addition, an SH-SY5Y cell model was established by oxygen-glucose deprivation/reperfusion, with cells first cultured in sugar-free medium with 95% N2 and 5% CO2 for 4 hours and then cultured in a normal environment with sugar-containing medium for 5 hours. This SH-SY5Y cell model was treated with 10-7 M apelin-13 for 5 hours. Results showed that apelin-13 protected against cerebral ischemia/reperfusion injury. Apelin-13 treatment alleviated neuronal apoptosis by increasing the ratio of Bcl-2/Bax and significantly decreasing cleaved caspase-3 expression. In addition, apelin-13 significantly inhibited excessive autophagy by regulating the expression of LC3B, p62, and Beclin1. Furthermore, the expression of Bcl-2 and the phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway was markedly increased. Both LY294002 (20 µM) and rapamycin (500 nM), which are inhibitors of the PI3K/Akt/mTOR pathway, significantly attenuated the inhibition of autophagy and apoptosis caused by apelin-13. In conclusion, the findings of the present study suggest that Bcl-2 upregulation and mTOR signaling pathway activation lead to the inhibition of apoptosis and excessive autophagy. These effects are involved in apelin-13-induced neuroprotection against cerebral ischemia/reperfusion injury, both in vivo and in vitro. The study was approved by the Animal Ethical and Welfare Committee of Jining Medical University, China (approval No. 2018-JS-001) in February 2018.

Therapeutic Effect of C-C Chemokine Receptor Type 1 (CCR1) Antagonist BX471 on Allergic Rhinitis.

OBJECTIVE AND DESIGN: Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated inflammatory respiratory hypersensitivity characterized by elevated Th2 cytokines and infiltration of inflammatory cells to nasal tissues. BX471 is a small-molecule C-C chemokine receptor type 1 (CCR1) antagonist involved in suppression of inflammation via blocking of primary ligands. In this study, we examined the anti-inflammatory effect of BX471 on ovalbumin (OVA)-induced AR mice model. MATERIALS AND METHODS: Levels of OVA-specific IgE and Th1 cytokines were determined by enzyme-linked immunosorbent assay (ELISA). Nasal expression of proinflammatory mediators was assessed by real-time polymerase chain reaction (RT-qPCR). Nasal-cavity sections were stained with hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) to study eosinophil infiltration and goblet cell metaplasia. Relative protein levels of Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-kB), Toll-like Receptor 4 (TLR4) and Toll-like-receptor 2 (TLR2) were assessed by Western Blot. Percentage of CD4+CD25+Foxp3+ T regulatory cells (Treg) was measured by flow cytometry. RESULTS: Mice treated with BX471 showed significantly relieved sneezing and nasal-rubbing behaviors. The expression of nasal proinflammatory factors was significantly downregulated by BX471, and protein levels of tumor necrosis factor alpha (TNF- α) and NF-kB were suppressed. Blockade of CCR1 ligands inhibited eosinophil recruitment in nasal cavity. In addition, Treg cells population were upregulated in BX471-treated mice. CONCLUSION: BX471 exerts anti-inflammatory effects in a mouse model of AR by inhibiting CCR1-mediated TNF-α production, which subsequently suppresses NF-kB activation in inflammatory cells, leading to a decrease in Th2 cytokines, IL-1ß, VCAM-1, GM-CSF, RANTES, and MIP-1α expression levels, thus inhibiting eosinophil recruitment to nasal mucosa. In addition, BX-471 exhibits anti-allergic effect by increasing Treg cell population. Overall, BX471 represents a promising therapeutic strategy against AR.

Ghrelin mitigates MPP+-induced cytotoxicity: Involvement of ERK1/2-mediated Nrf2/HO-1 and endoplasmic reticulum stress PERK signaling pathway.

Parkinson's disease (PD) is a common progressive and multifactorial neurodegenerative disease. Current pharmacological therapies for PD are inadequate and often accompanied by serious side effects. In search of neuroprotective agents being considered to be beneficial to PD therapy. Ghrelin confers neuroprotective effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned PD model, but the underlying mechanism remains not fully elucidated. Here, we utilized human neuroblastoma SH-SY5Y cells exposed to MPP+ as a PD model to investigate the underlying mechanism of Ghrelin. In our present work, cell viability, cell apoptosis, oxidative stress-related indicators, and the level of Nrf2, HO-1, PERK, eIF2α, ATF4, CHOP, and ERK1/2 were examined. The results showed that Ghrelin attenuated MPP+-induced change of cell viability, apoptosis, coupled with decreased Cytochrome c, caspase-9, and caspase-3 expressions. Consistently, Ghrelin suppressed MPP+-induced oxidative stress. Moreover, Ghrelin markedly enhanced Nrf2 expression and nuclear accumulation as well as HO-1 induction. Further investigations showed that Ghrelin significantly inhibited the endoplasmic reticulum stress PERK-eIF2α-ATF4-CHOP pathway. Interestingly, we then found that Ghrelin promoted phosphorylation of ERK1/2, and pharmacological inhibition of ERK signaling abolished the cytoprotective effect of Ghrelin. Furthermore, we also found promoting the activation of the Nrf2/ HO-1 pathway and suppressing of the PERK pathway were mediated by ERK1/2. These findings provided novel insights into the underlying mechanisms of Ghrelin exerted protective effect, suggesting its potential as a novel therapeutic strategy against PD.

Ghrelin protects dopaminergic neurons against MPTP neurotoxicity through promoting autophagy and inhibiting endoplasmic reticulum mediated apoptosis.

Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder, the important pathology of PD due to the prominent loss of the dopaminergic neurodegeneration in the substantia nigra pars compacta (SNpc) and striatum (STR). Although the etiology of PD is not fully understood, aggregation of α-synuclein, impaired autophagy, and endoplasmic reticulum stress (ERS) are involved in the pathogenesis of PD. Previously it has been demonstrated that Ghrelin is a kind of peptide protected dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyran (MPTP)-induced neurotoxicity, but the detailed mechanism remains to be elucidated. In the present work, we investigated the effects of Ghrelin on autophagy and ERS-mediated apoptosis in the MPTP-lesioned PD mice model. We found that Ghrelin was neuroprotective against MPTP-induced dopaminergic neurodegeneration. Subsequently, we investigated Ghrelin inhibited the accumulation and phosphorylation of α-synuclein induced by MPTP. Moreover, Ghrelin promoted autophagy indicated by the up-regulation of microtubule-associated protein 1 Light Chain 3B-II/I (LC3B-II/I) and Beclin1, as well as decreasing the level of p62 in the SNpc and STR. Besides, the activation of the ERS-related apoptosis signaling pathway including IRE1α and Caspase-12 signaling pathway induced by MPTP was suppressed by Ghrelin treatment. Furthermore, Ghrelin also decreased Caspase-3 expression. Taken together, our results indicated that Ghrelin may exert neuroprotective effects via regulating α-synuclein activities, enhancing autophagy, and ameliorating ERS-mediated apoptosis in MPTP-lesioned mice, which provides a new target for potential pharmacologic interventions of PD treatment in the future.

Apelin-36 mediates neuroprotective effects by regulating oxidative stress, autophagy and apoptosis in MPTP-induced Parkinson's disease model mice.

Parkinson's disease (PD), a common human neurodegenerative disorder, is characterized by the presence of intraneuronal Lewy bodies composed principally of abnormal aggregated and post-translationally modified α-synuclein. In our previous research, we have demonstrated the neuroprotective effect of Apelin-36, a neuroendocrine peptide in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP)-lesioned PD model mice. Therefore, this study was designed to evaluate the neuroprotective mechanism of Apelin-36 against MPTP-induced neurotoxicity in mice. The results showed that MPTP-induced the depletion of dopamine in the striatum (STR) was partially reversed by Apelin-36. Apelin-36 also improved the activity of antioxidant system including superoxide dismutase (SOD) and glutathione (GSH), and decreased the overproduction of malondialdehyde (MDA) in the substantia nigra pars compacta (SNpc) and STR of MPTP-treated mice. Moreover, Apelin-36 downregulated inducible nitric oxide synthase (iNOS) and nitrated α-synuclein expression. Furthermore, Apelin-36 significantly promoted autophagy indicated by the up-regulation of LC3-II and Beclin1 and inhibition of p62 expression in the SNpc and STR of MPTP-treated mice. The protective effect of Apelin-36 was also associated with the inhibition of the apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal kinase (JNK) signaling pathway and inactivation of caspase-3. Taken together, our findings demonstrated that the neuroprotective mechanism of Apelin-36 against MPTP-induced neurotoxicity in mice might be related to decreasing the aggregation of nitrated α-synuclein and alleviating oxidative stress as well as promoting autophagy and inhibiting ASK1/JNK/caspase-3 apoptotic pathway, which provides a novel strategy for PD treatment.

The Role of Mitophagy in Ischemic Stroke.

Mitochondria are important places for eukaryotes to carry out energy metabolism and participate in the processes of cell differentiation, cell information transmission, and cell apoptosis. Autophagy is a programmed intracellular degradation process. Mitophagy, as a selective autophagy, is an evolutionarily conserved cellular process to eliminate dysfunctional or redundant mitochondria, thereby fine-tuning the number of mitochondria and maintaining energy metabolism. Many stimuli could activate mitophagy to regulate related physiological processes, which could ultimately reduce or aggravate the damage caused by stimulation. Stroke is a common disease that seriously affects the health and lives of people around the world, and ischemic stroke, which is caused by cerebral vascular stenosis or obstruction, accounts for the vast majority of stroke. Abnormal mitophagy is closely related to the occurrence, development and pathological mechanism of ischemic stroke. However, the exact mechanism of mitophagy involved in ischemic stroke has not been fully elucidated. In this review, we discuss the process and signal pathways of mitophagy, the potential role of mitophagy in ischemic stroke and the possible signal transduction pathways. It will help deepen the understanding of mitophagy and provide new ideas for the treatment of ischemic stroke.