PITPNA-AS1 Inhibits Cell Proliferation and Migration in Ovarian Cancer by Regulating the MIR-223-3p/RHOB Axis.

Background: Ovarian cancer is a fatal gynecologic malignancy. Long non-coding RNA (lncRNA) has been verified to serve as key regulator in ovarian cancer tumorigenesis. Objective: The aim of the study was to study the functions and mechanism of lncRNA PITPNA-AS1 in ovarian cancer cellular process. Methods: Clinical ovarian cancer samples were collected and stored at an academic medical center. Cellular fractionation assays and fluorescence in situ hybridization were conducted to locate PITPNA-AS1 in OC cells. TUNEL staining, colony-forming assays, and Transwell assays were performed for evaluating cell apoptosis as well as proliferative and migratory abilities. Western blot was conducted for quantifying protein levels of epithelialmesenchymal transition markers. The binding relation between genes was verified by RNA pulldown, RNA immunoprecipitation, and luciferase reporter assays. Gene expression levels in ovarian cancer tissues and cells were subjected to RT-qPCR. Results: PITPNA-AS1 level was downregulated in ovarian cancer samples and cells. PITPNA-AS1 overexpression contributed to the accelerated ovarian cancer cell apoptosis and inhibited cell migration, proliferation, and epithelial-mesenchymal transition process. In addition, PITPNA-AS1 interacted with miR-223-3p to regulate RHOB. RHOB knockdown partially counteracted the repressive impact of PITPNA-AS1 on ovarian cancer cell activities. Conclusion: PITPNA-AS1 inhibited ovarian cancer cellular behaviors by targeting miR-223-3p and regulating RHOB.

A review regarding the article 'Targeting inflammatory signaling pathways with SGLT2 inhibitors: Insights into cardiovascular health and cardiac cell improvement'.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have emerged as a novel category of blood glucose-lowering drugs in clinical recommendations for a wide range of diseases. SGLT2 inhibitors are promising anti-inflammatory agents by acting either indirectly via improving metabolism and reducing stress conditions or via direct modulation of inflammatory signaling pathways. The SGLT2 inhibitors empagliflozin and dapagliflozin better vascular function and avert vascular aging by decreasing the reactive oxygen species (ROS) content and increasing nitric oxide bioavailability, respectively. It was discovered that ipragliflozin has the ability to prevent dysfunction of the endothelium, and this effect was connected with oxidative stress. According to published data, SGLT2 inhibitors may delay vascular aging and arrest the development of endothelial dysfunction in animal models of type 2 diabetes (T2D) by reducing inflammation, oxidative stress, and glucose toxicity and increasing the survival of hyperglycemic endothelial cells. The adenosine monophosphate-activated protein kinase (AMPK) molecule plays a vital role in the regulation of bioenergy metabolism and is pivotal in our understanding of diabetes mellitus and other metabolic disorders. It has been hypothesized that SGLT2 inhibitors may indirectly affect AMPK to reduce mammalian target of rapamycin (mTOR) activity. Numerous studies have demonstrated that SGLT2 inhibitors can activate AMPK by restoring the AMP/ATP balance in favor of AMP, which is assumed to be the mechanism by which these medications have positive effects on the cardiac structure and microvessel.

Extreme hepatectomy with modified ALPPS in a rat model: gradual portal vein restriction associated with hepatic artery restriction.

BACKGROUND & AIM: Associating liver partition and portal vein ligation (PVL) for staged hepatectomy (ALPPS) is a creative strategy for enlarging the future liver remnant (FLR) and increasing the tumor resectability rate. However, the indications for ALPPS must have a certain limit when the FLR is too small. We aimed to establish a modified ALPPS model with more widen applicability in rats. METHODS: An extreme ALPPS model was established in rodents with only a 6.5% FLR. The portal vein (PV) was subjected to restriction to different degrees, then the portal vein pressure (PVP) was measured. Then, different modifications of ALPPS, including hepatic artery restriction (HAR), gradual portal vein restriction (GPVR), and GPVR-associated HAR (HAR+GPVR), were applied in the extreme ALPPS models. RESULTS: PVL or PVR provoked an immediate increase in the PVP. The PVP in the PVR -1.28 mm, PVR -0.81 mm, PVR -0.63 mm, and PVL groups was 11.05±1.57 cmH2O, 16.18±1.92 cmH2O, 20.66±1.99 cmH2O, and 24.10±3.33 cmH2O, respectively, and the corresponding 3-day survival rate was 100%, 90.09%, 36.33% and 0, respectively. Then, in the extreme ALPPS model, the growth ratio of the FLR in the control, HAR, GPVR, and HAR+GPVR groups was 0.43±0.21, 0.50±0.16, 4.80±0.86, and 7.40±2.56, and as a consequence, the corresponding 30-day survival rate was 9.09%, 15.38%, 84.61% and 92.90%, respectively. CONCLUSION: ALPPS itself has a limit, and high PVP after PVL contributes to postoperative death in the extreme ALPPS model. Furthermore, a modified method for extreme ALPPS is proposed, i.e., GPVR+HAR in place of PVL, which significantly improves the survival rate of extreme hepatectomy in rat models.

Extended Ligation of the Hepatic Vein May Yield a Similar Effect to Liver Venous Deprivation in a Rat Model.

AIMS: To validate the hypothesis that hepatic vein ligation (HVL) alone may produce similar results to liver venous deprivation (LVD or HVL + portal vein ligation [PVL]). METHODS: Rats were assigned to five groups, namely, the control group; the R group in which the right median hepatic vein (RMHV) was ligated; the M group in which the middle median hepatic vein (MMHV) was ligated; the RM group in which both the RMHV and MMHV were ligated (R + MMHVL, extended ligation of the hepatic veins); and the LVD group in which both the right median portal vein and the RMHV were ligated. The liver hypertrophy effect and liver enzymes were determined. Methylene blue staining and retrograde pressurized perfusion assays were performed to investigate the hemodynamic changes. RESULTS: The RM and LVD groups exhibited similar significant hypertrophy in the future liver remnants when compared to that of the control group, and almost no additional hypertrophy effect was observed in the R and M groups. There was a remarkable elevation in serum transaminase levels in both groups. The methylene blue staining experiment indicated that pressure-dependent collaterals formed between the contiguous drainage areas, and the R + MMHVL procedure blocked the outflow of the right median lobe. CONCLUSION: Extended ligation of the hepatic vein (R + MMHVL) resulted in a similar hypertrophy effect and hepatic damage to those of LVD (HVL + PVL) treatment in a rat model, and intrahepatic venovenous collaterals play key roles.

The application of nanoparticles in immunotherapy for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related deaths worldwide, however, current clinical diagnostic and treatment approaches remain relatively limited, creating an urgent need for the development of effective technologies. Immunotherapy has emerged as a powerful treatment strategy for advanced cancer. The number of clinically approved drugs for HCC immunotherapy has been increasing. However, it remains challenging to improve their transport and therapeutic efficiency, control their targeting and release, and mitigate their adverse effects. Nanotechnology has recently gained attention for improving the effectiveness of precision therapy for HCC. We summarize the key features of HCC associated with nanoparticle (NPs) targeting, release, and uptake, the roles and limitations of several major immunotherapies in HCC, the use of NPs in immunotherapy, the properties of NPs that influence their design and application, and current clinical trials of NPs in HCC, with the aim of informing the design of delivery platforms that have the potential to improve the safety and efficacy of HCC immunotherapy，and thus, ultimately improve the prognosis of HCC patients.

Co-Fermentation of Edible Mushroom By-Products with Soybeans Enhances Nutritional Values, Isoflavone Aglycones, and Antioxidant Capacity of Douchi Koji.

Douchi is a traditional salt-fermented soybean food with various bioactivities, such as anti-oxidation, anti-diabetes, and anti-hypertension, which are greatly affected by the activities of protease and ß-glucosidase during koji production. Edible mushroom by-products are ideal ingredients for enhancing food flavor and nutritional quality due to their unique nutritional characteristics of high protein, rich amino acids, and low calories. However, there is no research on the preparation of Douchi by the mixed fermentation of edible mushroom by-products and soybeans. In this study, response surface methodology (RSM) was used to optimize the fermentation conditions of edible mushroom by-product Douchi koji (EMDK) with protease and ß-glucosidase activities as indicators, and the changes in the main bioactive compounds and antioxidant activities of unfermented raw samples (URS), Douchi koji without edible mushroom by-product (DKWE), and EMDK were compared. The results of single-factor tests and RSM showed that the optimal fermentation conditions of EMDK were the Aspergillus oryzae to Mucor racemosus ratio of 1:1, inoculation amount of 6%, edible mushroom amount of 21%, and fermentation time of 63 h, and the activities of protease and ß-glucosidase under these conditions were 796.03 ± 15.01 U/g and 1175.40 ± 36.98 U/g, respectively. Additionally, compared with URS and DKWE, the contents of total isoflavones and ß-glucoside isoflavones in EMDK were notably decreased, while the contents of amino nitrogen, total phenolics, total flavonoids, and aglycone isoflavone, as well as the antioxidant capacity were significantly increased. Furthermore, significant correlations were found between the above components and antioxidant capacity. These results showed that edible mushroom by-product could be incorporated into soybeans for co-fermentation, conferring higher nutritional value to and antioxidant capacity of Douchi koji.

Tumor-Suppressive and Oncogenic Roles of microRNA-149-5p in Human Cancers.

Malignant tumors are always a critical threat to human health, with complex pathogenesis, numerous causative factors, and poor prognosis. The features of cancers, such as gene mutations, epigenetic alterations, and the activation and inhibition of signaling pathways in the organism, play important roles in tumorigenesis and prognosis. MicroRNA (miRNA) enables the control of various molecular mechanisms and plays a variety of roles in human cancers, such as radiation sensitivity and tumor immunity, through the regulation of target genes. MiR-149-5p participates in the process and is closely related to lipogenesis, the migration of vascular endothelial cells, and the expression of stem-cell-related proteins. In recent years, its role in cancer has dramatically increased. In this review, we summarize the regular physiological roles of miRNAs, specifically miR-149-5p, in the organism and discuss the tumor-suppressive or oncogenic roles of miR-149-5p in different human cancers with respect to signaling pathways involved in regulation. Possible clinical applications of miR-149-5p in future targeted therapies and prognosis improvement in oncology are suggested.

The potential role of prebiotics, probiotics, and synbiotics in adjuvant cancer therapy especially colorectal cancer.

Cancer is a global health issue that is rising swiftly with younger people and an increased number of patients. The role of human microbiota in the pathophysiology of tumors has been paid more and more attention. Microecologics including prebiotics, probiotics, and synbiotics are among the best validated/proven resources for the application of microbiological prophylaxis and therapy. There is strong evidence that microecologics have anti-cancer activity and their potential association with cancer is significant. In this review, we will focus on the role of prebiotics, probiotics, and synbiotics in tumor suppression in maintaining the colon barrier, metabolism, immune regulation, inhibition of host tumor cell proliferation, and epidemiological-based recommendations. Besides, other signs illuminate the role of microecological agents to adjunct the cancer treatment and counter the toxic side effects of cancer drugs. In addition, we will explore their role in chemotherapy, where these probiotics can be used as an adjunct to chemotherapy, counteracting the toxic side effects of chemotherapy drugs to minimize or optimize the therapeutic effect. In the treatment of cancer, we can see the role of prebiotics, probiotics, synbiotics, and their application in cancer patients, and the effectiveness effect can be considered as a clinical benefit. PRACTICAL APPLICATIONS: A large number of studies have shown that microecologics including prebiotics, probiotics, and synbiotics play an important role in regulating intestinal microecology and contribute to the prevention and treatment of cancer, indicating that prebiotics, probiotics, and synbiotics have the potential to be used as microecological modulators in the adjuvant therapy of cancer. However, it is not clear what is the anti-tumor mechanism of these microecologics and how they antagonize the side effects of cancer chemotherapy and protect normal cells. This paper reviews the role of prebiotics, probiotics, and synbiotics in tumor suppression in maintaining the colon barrier, metabolism, immune regulation, and prevention of rapid growth of host cells, as well as their potential role in cancer chemotherapy. This review helps to better understand the relationship between prebiotics, probiotics, and synbiotics with immune regulation, intestinal microecology, metabolic regulation, and cell proliferation and provides strong evidence for their potential application as microecologics in cancer adjuvant therapy.

Dietary fiber of Tartary buckwheat bran modified by steam explosion alleviates hyperglycemia and modulates gut microbiota in db/db mice.

Type 2 diabetes is a serious threat to human health. Tartary buckwheat bran dietary fiber has good hypoglycemic activity, with its modification widely studied. However, the hypoglycemic activity of steam explosion modified Tartary buckwheat bran soluble dietary fiber (SE-SDF) has not been reported. This research aimed at investigating the hypoglycemic effect with its underlying mechanism of SE-SDF on type 2 diabetic db/db mice. Results found SE-SDF decreased the levels of fasting blood glucose and glycosylated hemoglobin while improved oral glucose tolerance, insulin resistance, and injuries of liver, pancreas, and colon in diabetic db/db mice. Additionally, SE-SDF up-regulated the protein expression levels of hepatic phosphatidylinositol 3 kinase (PI3K), G protein-coupled receptor43 (GPR43), and phospho-adenosine monophosphate activated protein kinase (p-AMPK), whereas inhibited the protein expression levels of hepatic fork-head transcription factor O1 (FoxO1), phosphoenolpyruvate carboxy kinase (PEPCK) and glucose-6-phosphatase (G-6-Pase). Moreover, SE-SDF increased the production of fecal short chain fatty acids (SCFAs) and the expression of colon GPR43 and the concentration of serum glucagon like peptide-1 (GLP-1), leading to reduced ratio of Firmicutes/Bacteroidetes but increased relative abundance of Parabacteroides, norank_f_Muribaculaceae, Alloprevotella, Ruminiclostridium_9, unclassified_f_Ruminococcaceae, and Lachnospiraceae_NK4A136_group. These findings suggested that SE-SDF ameliorated type 2 diabetes via activating the liver PI3K/Akt/FoxO1 and GPR43/AMPK signaling pathways and modulating the gut microbiota-SCFAs-GPR43/GLP-1 signaling axis.

Prevention of Ulcerative Colitis in Mice by Sweet Tea (Lithocarpus litseifolius) via the Regulation of Gut Microbiota and Butyric-Acid-Mediated Anti-Inflammatory Signaling.

Sweet tea (Lithocarpus litseifolius [Hance] Chun) is a new resource for food raw materials, with plenty of health functions. This study aimed to investigate the preventive effect and potential mechanism of sweet tea extract (STE) against ulcerative colitis (UC). Briefly, BABL/c mice were treated with STE (100 and 400 mg/kg) for 2 weeks to prevent 3% dextran sulfate sodium (DSS)-induced UC. It was found that STE supplementation significantly prevented DSS-induced UC symptoms; suppressed the levels of pro-inflammatory mediators, such as myeloperoxidase and tumor necrosis factor-α; increased the levels of anti-inflammatory cytokines; and up-regulated the expression of tight junction proteins (Zonula occludens-1 and Occludin). STE also altered the gut microbiota profile of UC mice by increasing Bacteroidetes, Lactobacillus, Akkermansia, Lachnospiraceae_NK4A136_group, and Alistipes and inhibiting Firmicutes, Proteobacteria, and Helicobacter, accompanied by a significant increase in the content of butyric acid. Moreover, STE increased the expression of G-protein-coupled receptor (GPR) 43 and GPR109A and inhibited the expression of histone deacetylase 3 (HDAC3) and nuclear factor-κB p65 (NF-κB p65) in the colon. In conclusion, this study indicated that STE has a good preventive effect on UC by regulating gut microbiota to activate butyrate-GPR-mediated anti-inflammatory signaling and simultaneously inhibit HDAC3/NF-κB inflammatory signaling.

The oncogenic role of tubulin alpha-1c chain in human tumours.

Tubulin alpha-1c chain (TUBA1C), a subtype of α-tubulin, has been shown to be involved in cell proliferation and cell cycle progression in several cancers and to influence cancer development and prognosis. However, a pancancer analysis of TUBA1C to reveal its immunological and prognostic roles has not been performed. In this study, we first downloaded raw data on TUBA1C expression in cancers from The Cancer Genome Atlas (TCGA) database and multiple other databases and analysed these data with R software to investigate the prognostic and immunological value of TUBA1C in cancers. Immunohistochemical analysis was performed in gliomas to further validate our findings. Overall, TUBA1C was overexpressed in most cancers, and overexpression of TUBA1C was linked to poor prognosis and higher tumour grade in patients. In addition, TUBA1C expression was associated with tumour mutation burden (TMB), microsatellite instability (MSI), the tumour microenvironment (TME) and the infiltration of immune cells. TUBA1C was also coexpressed with most immune-related genes and influenced immune-related pathways. Immunohistochemical analysis showed that TUBA1C expression was highest in glioblastoma (GBM) tissues, second highest in low-grade glioma (LGG) tissues and lowest in normal tissues. Our study indicated that TUBA1C might be a biomarker for predicting the immune status and prognosis of cancers, offering new ideas for cancer treatment.

ROS-Related miRNAs Regulate Immune Response and Chemoradiotherapy Sensitivity in Hepatocellular Carcinoma by Comprehensive Analysis and Experiment.

Reactive oxygen species (ROS) plays an essential role in the development of cancer. Here, we chose ROS-related miRNAs for consensus clustering analysis and ROS score construction. We find that ROS is extremely associated with prognosis, tumor immune microenvironment (TIME), gene mutations, N6-methyladenosine (m6A) methylation, and chemotherapy sensitivity in hepatocellular carcinoma (HCC). Mechanistically, ROS may affect the prognosis of HCC patients in numerous ways. Moreover, miR-210-3p and miR-106a-5p significantly increased the ROS level and stagnated cell cycle at G2/M in HCC; the results were more obvious in cells after ionizing radiation (IR). Finally, the two miRNAs suppressed cell proliferation, migration, and invasion and promoted apoptosis in huh7 and smmc7721 cells. It indicated that ROS might affect the prognosis of HCC patients through immune response and increase the sensitivity of HCC patients to radiotherapy and chemotherapy.

Tubulin Alpha 1b Is Associated with the Immune Cell Infiltration and the Response of HCC Patients to Immunotherapy.

Tubulin alpha 1b (TUBA1B) is an important microtubule isoform that is involved in the formation of the cytoskeleton. The objective of our study was to explore the potential of TUBA1B in predicting the prognosis of HCC and patients' response to immunotherapy. Raw data was extracted from TCGA and GEO databases, and then HCCDB, TIMER, HPA, and GEPIA websites, as well as R software, were used to perform bioinformatics analysis to investigate the potential of TUBA1B as a prognostic and immunotherapeutic marker for hepatocellular carcinoma (HCC). We found that both TUBA1B mRNA and protein were highly expressed in HCC. TUBA1B was proved to be an independent prognostic predictor of HCC. Additionally, TUBA1B expression was associated with the infiltration of several immune cells in HCC. Moreover, TUBA1B was coexpressed with immune-related genes and immune checkpoints. Patients expressing high TUBA1B responded better to immune checkpoint inhibitor (ICI) therapy. GO and KEGG analyses revealed that TUBA1B may be involved in the processes of cell cycle, spliceosome, and DNA replication. In conclusion, TUBA1B is expected to be a prognostic and immunotherapeutic marker for HCC.

Circular RNA circStag1 promotes bone regeneration by interacting with HuR.

Postmenopausal osteoporosis is a common bone metabolic disorder characterized by deterioration of the bone microarchitecture, leading to an increased risk of fractures. Recently, circular RNAs (circRNAs) have been demonstrated to play pivotal roles in regulating bone metabolism. However, the underlying functions of circRNAs in bone metabolism in postmenopausal osteoporosis remain obscure. Here, we report that circStag1 is a critical osteoporosis-related circRNA that shows significantly downregulated expression in osteoporotic bone marrow mesenchymal stem cells (BMSCs) and clinical bone tissue samples from patients with osteoporosis. Overexpression of circStag1 significantly promoted the osteogenic capability of BMSCs. Mechanistically, we found that circStag1 interacts with human antigen R (HuR), an RNA-binding protein, and promotes the translocation of HuR into the cytoplasm. A high cytoplasmic level of HuR led to the activation of the Wnt signaling pathway by stabilizing and enhancing low-density lipoprotein receptor-related protein 5/6 (Lrp5/6) and ß-catenin expression, thereby stimulating the osteogenic differentiation of BMSCs. Furthermore, overexpression of circStag1 in vivo by circStag1-loaded adeno-associated virus (circStag1-AAV) promoted new bone formation, thereby preventing bone loss in ovariectomized rats. Collectively, we show that circStag1 plays a pivotal role in promoting the regeneration of bone tissue via HuR/Wnt signaling, which may provide new strategies to prevent bone metabolic disorders such as postmenopausal osteoporosis.

Elderberry (Sambucus nigra L.): Bioactive Compounds, Health Functions, and Applications.

Elderberry (Sambucus nigra L.) is rich in many bioactive compounds and exhibits diverse health functions, of which an understanding can be helpful for its better utilization in the food industry. This review mainly summarizes recent studies about the bioactive compounds and health functions of elderberry, highlighting the potential mechanism of action. In addition, the applications of elderberry in foods are also discussed. Elderberry contains diversely bioactive ingredients, such as (poly)phenolic compounds and terpenoid compounds. Recent studies report that some food processing methods can affect the content of bioactive compounds in elderberry. Additionally, elderberry exhibits various health functions in vitro and in vivo, including antioxidant, anti-inflammatory, anticancer, anti-influenza, antimicrobial, antidiabetic, cardiovascular protective, and neuroprotective activities, and their potential molecular mechanisms are associated with regulating some key signaling pathways and molecular targets. Up to now, there have been limited clinical trials supporting the health benefits of elderberry. Overall, elderberry is a promising dietary source of bioactive ingredients and has the potential to be developed into functional foods or nutraceuticals for preventing and treating certain chronic diseases.

Antioxidant capacity, phytochemical profiles, and phenolic metabolomics of selected edible seeds and their sprouts.

Sprouts are recognized as nutritional and functional vegetables. In this study, 17 selected seeds were germinated simultaneously. The antioxidant capacity and total phenolic content (TPC) were determined for seeds and sprouts of all species. Both seed and sprout of white radish, with the highest antioxidant capacity, and TPC among all the 17 species, were further determined for phenolic metabolomics. Four phenolic classes with 316 phenolic metabolites were identified. 198 significantly different metabolites with 146 up-regulated and 52 down-regulated were confirmed, and high amounts of phenolic acids and flavonoids were found to be accumulated in the sprout. Several metabolism and biosynthesis, including phenylpropanoid, favone and flavonol, phenylalanine, and various secondary metabolites, were significantly activated. Significant correlations were found among FRAP, DPPH, ABTS, TPC, and phenolic profiles. Therefore, white radish sprout could be served as antioxidant and could be a good source of dietary polyphenols.

RMI2 is a prognostic biomarker and promotes tumor growth in hepatocellular carcinoma.

Genomic instability is a hallmark of all cancers. RMI2 is a crucial component of the BLM-TopoIIIa-RMI1-RMI2 complex that maintains genome stability. It has been shown to accelerate tumor progression in lung cancer, cervical cancer, and prostate cancer. However, its expression and function in hepatocellular carcinoma (HCC) remain poorly defined. In this study, gene expression data and corresponding clinical information of HCC were downloaded from the TCGA, ICGC, and GEO databases. The expression level and clinical significance of RMI2 in HCC were then analyzed. In addition, cellular and molecular biology experiments were conducted to explore the effects of silencing and overexpression of RMI2 on human liver cancer cells and the associated mechanisms. The results showed that RMI2 expression was elevated in HCC tissues. High expression of RMI2 was correlated with shorter survival and poor prognosis of patients. The results of CCK-8, Edu, and clonogenic assays confirmed that RMI2 overexpression promoted the proliferation of HCC cells. Flow cytometric analysis demonstrated that RMI2 overexpression enhanced G1-S phase transition and decreased apoptosis. Moreover, the protein expression of key effector molecules in the p53 signaling pathway was reduced following RMI2 overexpression. In summary, these results indicate that RMI2 promotes the growth of HCC cells and suppresses their apoptosis by inhibiting the p53 signaling pathway. This study provides new insights into the mechanisms driving HCC tumorigenesis and new therapeutic targets.

Sodium butyrate attenuates rotenone-induced toxicity by activation of autophagy through epigenetically regulating PGC-1α expression in PC12 cells.

Short-chain fatty acids (SCFAs) are considered the key molecular link between gut microbiota and pathogenesis of Parkinson's disease (PD). However, the role of SCFAs in PD pathogenesis is controversial. Autophagy is important for the degradation of α-synuclein, which is critical to the development of PD. However, whether SCFAs can regulate autophagy in PD remains unknown. We aimed to investigate the role of SCFAs and explore the potential mechanisms in rat dopaminergic PC12 cells treated with rotenone. Expression levels of α-synuclein, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and microtubule-associated protein 1 light chain 3 beta (LC3B)-II were detected by Western blot. Histone acetylation levels at PGC-1α promoter region were measured using chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR). Among the three SCFAs, sodium butyrate (NaB) protected against rotenone-induced toxicity. NaB activated autophagy pathway and reduced rotenone-induced α-synuclein expression through the activation of autophagy. Notably, NaB activated autophagy pathway through upregulating PGC-1α expression. More importantly, NaB promoted the levels of histone 3 lysine 9 acetylation (H3K9Ac) and histone 3 lysine 27 acetylation (H3K27Ac) at PGC-1α promoter region, indicating that NaB promotes PGC-1α expression via histone acetylation modification. In conclusion, NaB can protect against rotenone-induced toxicity through activation of the autophagy pathway by upregulating PGC-1α expression via epigenetic modification.

MXD3 as an Immunological and Prognostic Factor From Pancancer Analysis.

MAX dimerization protein 3 (MXD3), a transcriptional regulator of the MXD3 superfamily, is a part of the MYC-MAX-MXD network. However, its role in tumors has been reported in several cancers, such as B-cell acute lymphoblastic leukemia, medulloblastoma, neuroblastoma, and glioblastoma. Based on TCGA and GEO data, our first pancancer study of MXD3 confirmed the high expression of MXD3 in cancer tissues. Our results revealed that patients suffering from cancers with higher MXD3 expression had poor OS, DSS, DFI, and PFI. We further explored the methylation status of the MXD3 gene body and gene promoter in cancer. Patients with a higher MXD3 gene body have better OS, while the prognosis of patients with a high MXD3 promoter is more complex. We also verified the differential expression of three clinical phenotypes of MXD3: age, sex, and tumor stage, in a variety of tumors, suggesting a correlation between MXD3 and clinical characteristics. We explored the negative relationship between MXD3 and TMB and MSI in most types of cancer, indicating the poor prognosis of patients with high MXD3 expression. We further investigated the relationship between MXD3 and immune infiltrating cells and identified the relationship between MXD3 and immune genes, immunosuppressive genes, and antigen-presenting genes. All of the above findings established a solid relationship between MXD3 and the immune environment and immune cells. These results demonstrated that MXD3 might also be a potential immune factor. We also found a higher expression of MXD3 and promoter according to the increasing glioma WHO grade or histologic types. Glioma patients with high MXD3 or MXD3 promoter expression had poor survival. Finally, we used IHC to verify the higher expression of MXD3 in glioma samples compared to normal samples. Our study shows that MXD3, as a poor prognostic factor, plays a significant role in many cancers, especially glioma. Although more clinical evidence for MXD3 as a clinical therapeutic target and an immunotherapy site is needed, MXD3 can play an important guiding role in multiple clinical treatments, including immunotherapy and demethylation therapy.

PiRNA-63049 inhibits bone formation through Wnt/ß-catenin signaling pathway.

Bone remodeling is a dynamic process between bone formation mediated by osteoblasts and bone resorption mediated by osteoclasts. Disrupted bone remodeling is a key factor in postmenopausal osteoporosis, a metabolic disorder characterized by deteriorated bone microarchitecture and increased risk of fracture. Recent studies have shown that piwi-binding RNA (piRNA) is involved in the pathogenesis of certain diseases at the post-transcriptional level. Here, we analyzed piRNA-63049 (piR-63049), which may play an essential role in bone remodeling. The expression of piR-63049 significantly increased in both bone tissues and plasma of osteoporotic rats and postmenopausal osteoporotic patients. Overexpressing piR-63049 could inhibit the osteoblastogenesis of bone marrow stromal cells (BMSCs) while knocking down piR-63049 could promote the osteoblastogenesis of BMSCs through the Wnt2b/ß-catenin signaling pathway. Moreover, knocking-down piR-63049 (piR-63049-antagonist) in vivo could attenuate the bone loss in ovariectomized rats by promoting bone formation. Taken together, the current study shows that piR-63049 inhibits bone formation through the Wnt2b/ß-catenin signaling pathway. This novel piRNA may be a potential target to increase bone formation in bone loss disorders such as postmenopausal osteoporosis.