Curcumin suppresses colorectal cancer by induction of ferroptosis via regulation of p53 and solute carrier family 7 member 11/glutathione/glutathione peroxidase 4 signaling axis.

Driven by iron-dependent lipid peroxidation, ferroptosis is regulated by p53 and solute carrier family 7 member 11 (SLC7A11)/glutathione/glutathione peroxidase 4 (GPX4) axis in colorectal cancer (CRC). This study aimed to investigate the influence of curcumin (CUR) on ferroptosis in CRC. The efficacies of CUR on the malignant phenotype of CRC cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, wound healing, and clonogenic assays. The effects of CUR on ferroptosis of CRC cells were evaluated by transmission electron microscopy, lactate dehydrogenase release assay, Fe2+ staining, and analyses of reactive oxygen species, lipid peroxide, malondialdehyde, and glutathione levels. CUR's targets in ferroptosis were predicted by network pharmacological study and molecular docking. With SW620 xenograft tumors, the efficacy of CUR on CRC was investigated, and the effects of CUR on ferroptosis were assessed by detection of Fe2+, malondialdehyde, and glutathione levels. The effects of CUR on expressions of p53, SLC7A11, and GPX4 in CRC cells and tumors were analyzed by quantitative reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry. CUR suppressed the proliferation, migration, and clonogenesis of CRC cells and xenograft tumor growth by causing ferroptosis, with enhanced lactate dehydrogenase release and Fe2+, reactive oxygen species, lipid peroxide, and malondialdehyde levels, but attenuated glutathione level in CRC. In silico study indicated that CUR may bind p53, SLC7A11, and GPX4, consolidated by that CUR heightened p53 but attenuated SLC7A11 and GPX4 mRNA and protein levels in CRC. CUR may exert an inhibitory effect on CRC by inducing ferroptosis via regulation of p53 and SLC7A11/glutathione/GPX4 axis.

Selenium Treatment Alleviates the Inhibition Caused by Nep-L Gene Knockdown in Silkworm (Bombyx mori).

Recent studies have emphasized the beneficial effects of 50 µM selenium (Se) on the growth and development of the silkworm, Bombyx mori; however, less is known about its underlying mechanism. To unravel the effect of 50 µM Se on the silkworms with neutral endopeptidase 24.11-like gene (NEP-L) knockdown, we injected small interfering RNA (siRNA) into the body cavity of silkworms. Phenotypic characteristics, mRNA expression of the Nep-L gene, and enriched Se content were evaluated in silkworms from each treatment group. After injecting Nep-L siRNA, the body weight, cocoon quality (cocoon weight, cocoon shell weight, and cocoon shell ratio), and egg production of silkworms were significantly reduced, without any significant effect on egg laying number. However, Se treatment could significantly alleviate the inhibition of body weight, and cocoon quality, without significant effects on egg laying number and production. In addition, the gene knockdown increased Se content in the B. mori. On the molecular level, the targeted Nep-L gene was inhibited significantly by siRNA interference, essentially with the strongest effect at 24 h after RNAi, followed by steady recovery. Among the three fragments, the siRNA of Nep-L-3 was the most effective in interfering with target gene expression. Nep-L gene showed the highest expression in Malpighian tubules (MTs). Both at the phenotypic and genotypic levels, our results show that Nep-L knockdown can exert a significant inhibitory effect on silkworms, and 50 µM Se can reverse the negative effect, which provides a practical prospect for strengthening the silkworm food industry.

Armeniacae semen amarum: a review on its botany, phytochemistry, pharmacology, clinical application, toxicology and pharmacokinetics.

Armeniacae semen amarum-seeds of Prunus armeniaca L. (Rosaceae) (ASA), also known as Kuxingren in Chinese, is a traditional Chinese herbal drug commonly used for lung disease and intestinal disorders. It has long been used to treat coughs and asthma, as well as to lubricate the colon and reduce constipation. ASA refers to the dried ripe seed of diverse species of Rosaceae and contains a variety of phytochemical components, including glycosides, organic acids, amino acids, flavonoids, terpenes, phytosterols, phenylpropanoids, and other components. Extensive data shows that ASA exhibits various pharmacological activities, such as anticancer activity, anti-oxidation, antimicrobial activity, anti-inflammation, protection of cardiovascular, neural, respiratory and digestive systems, antidiabetic effects, and protection of the liver and kidney, and other activities. In clinical practice, ASA can be used as a single drug or in combination with other traditional Chinese medicines, forming ASA-containing formulas, to treat various afflictions. However, it is important to consider the potential adverse reactions and pharmacokinetic properties of ASA during its clinical use. Overall, with various bioactive components, diversified pharmacological actions and potent efficacies, ASA is a promising drug that merits in-depth study on its functional mechanisms to facilitate its clinical application.

Berberine Alleviates Ischemic Brain Injury by Enhancing Autophagic Flux via Facilitation of TFEB Nuclear Translocation.

Berberine has been demonstrated to alleviate cerebral ischemia/reperfusion injury, but its neuroprotective mechanism has yet to be understood. Studies have indicated that ischemic neuronal damage was frequently driven by autophagic/lysosomal dysfunction, which could be restored by boosting transcription factor EB (TFEB) nuclear translocation. Therefore, this study investigated the pharmacological effects of berberine on TFEB-regulated autophagic/lysosomal signaling in neurons after cerebral stroke. A rat model of ischemic stroke and a neuronal ischemia model in HT22 cells were prepared using middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation (OGD), respectively. Berberine was pre-administered at a dose of 100[Formula: see text]mg/kg/d for three days in rats and 90[Formula: see text][Formula: see text]M in HT22 neurons for 12[Formula: see text]h. 24[Formula: see text]h after MCAO and 2[Formula: see text]h after OGD, the penumbral tissues and OGD neurons were obtained to detect nuclear and cytoplasmic TFEB, and the key proteins in the autophagic/lysosomal pathway were examined using western blot and immunofluorescence, respectively. Meanwhile, neuron survival, infarct volume, and neurological deficits were assessed to evaluate the therapeutic efficacy. The results showed that berberine prominently facilitated TFEB nuclear translocation, as indicated by increased nuclear expression in penumbral neurons as well as in OGD HT22 cells. Consequently, both autophagic activity and lysosomal capacity were simultaneously augmented to alleviate the ischemic injury. However, berberine-conferred neuroprotection could be greatly counteracted by lysosomal inhibitor Bafilomycin A1 (Baf-A1). Meanwhile, autophagy inhibitor 3-Methyladenine (3-MA) also slightly neutralized the pharmacological effect of berberine on ameliorating autophagic/lysosomal dysfunction. Our study suggests that berberine-induced neuroprotection against ischemic stroke is elicited by enhancing autophagic flux via facilitation of TFEB nuclear translocation in neurons.

In situ Gel Electrolytes for the Interfacial Regulation of Lithium Metal Batteries.

With the popularity and development of electronic devices, the demand for lithium batteries is increasing, which also puts high demands on the energy density, cycle life and safety of lithium batteries. Gel electrolytes achieve both of these requirements by curing the electrolytes to reduce the interfacial side reactions of lithium metal batteries. The ionic conductivity of the gel electrolytes prepared by in situ curing reach 8.0×10-4  S cm-1 , and the ionic mobility number is 0.53. Meanwhile, the gel electrolytes maintain a stable electrochemical window of 1.0-5.0 V. Benefited with the interfacial regulation of PEGDA gel electrolytes, the gel lithium metal batteries show better cycling stability, and achieved 97 % capacity retention after 200 cycles (0.2 C) with a lower increasing rate of impedance.

A new strategy for the treatment of heavily pretreated metastatic breast cancer: A case report and review of the literature.

BACKGROUND: Breast cancer is one of the most common type of cancers worldwide and remains a critical health issue. Although there are numerous treatment options for advanced metastatic breast cancer, the results are not satisfactory, particularly for triple-negative breast cancer. New treatment modalities need to be explored. CASE PRESENTATION: We present the case of a breast cancer patient with multiple metastases who achieved a good response and tolerance to the combination treatment of utidelone plus capecitabine. After being treated with 10 cycles of combined treatment, the patient is now in a good general condition with a progression-free survival time of 10 months. CONCLUSION: To our knowledge, this is the first report of utidelone plus capecitabine successfully treating a patient with heavily pretreated metastatic breast cancer. This combined treatment offers a new option for patients with multi-drug resistant breast cancer.

Qinhuo Shanggan oral solution resolves acute lung injury by down-regulating TLR4/NF-κB signaling cascade and inhibiting NLRP3 inflammasome activation.

Acute lung injury (ALI) is a common condition, particularly in the COVID-19 pandemic, which is distinguished by sudden onset of respiratory insufficiency with tachypnea, oxygen-refractory cyanosis, reduced lung compliance and diffuse infiltration of pulmonary alveoli. It is well-established that increasing activity of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling axis and the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation are associated with the pathogenesis of ALI. Since ALI poses a huge challenge to human health, it is urgent to tackle this affliction with therapeutic intervention. Qinhuo Shanggan oral solution (QHSG), a traditional Chinese herbal formula, is clinically used for effective medication of various lung diseases including ALI, with the action mechanism obscure. In the present study, with the rat model of lipopolysaccharide (LPS)-induced ALI, QHSG was unveiled to ameliorate ALI by alleviating the pathological features, reversing the alteration in white blood cell profile and impeding the production of inflammatory cytokines through down-regulation of TLR4/NF-κB signaling cascade and inhibition of NLRP3 inflammasome activation. In LPS-stimulated RAW264.7 mouse macrophages, QHSG was discovered to hinder the generation of inflammatory cytokines by lessening TLR4/NF-κB signaling pathway activity and weakening NLRP3 inflammasome activation. Taken together, QHSG may resolve acute lung injury, attributed to its anti-inflammation and immunoregulation by attenuation of TLR4/NF-κB signaling cascade and inhibition of NLRP3 inflammasome activation. Our findings provide a novel insight into the action mechanism of QHSG and lay a mechanistic foundation for therapeutic intervention in acute lung injury with QHSG in clinical practice.

Fluorinated Nonflammable In Situ Gel Polymer Electrolyte for High-Voltage Lithium Metal Batteries.

Rechargeable lithium metal batteries (LMBs) offer excellent opportunities for applications requiring high-energy-density battery systems. So far, it has received a lot of interest in pairing higher-energy-density high-voltage nickel-rich cathodes. Here, fluorinated solvents were used instead of the usual carbonate solvents to prepare gel polymer electrolytes (FGPE) by in situ polymerization of polymers introducing the fluorine-containing groups. Theoretically and experimentally, FGPE has proven to be ultra-compatible with the lithium metal anode and LiNi0.8Co0.1Mn0.1O2 cathode. A stable plating/stripping process of over 2000 h can be achieved for symmetrical lithium cells using FGPE. The Li||FGPE||NCM811 cell has a longer cycle life at a high voltage (4.5 V). In addition, the zero self-extinguishing time indicates that the FGPE has sufficient safety. In summary, the design of this electrolyte provides ideas to improve the safety and energy density of LMBs.

Exorista sorbillans (Diptera: Tachinidae) parasitism shortens host larvae growth duration by regulating ecdysone and juvenile hormone titers in Bombyx mori (Lepidoptera: Bombycidae).

The tachinid fly, Exorista sorbillans, is a notorious ovolarviparous endoparasitoid of the silkworm, Bombyx mori, causing severe damage to silkworm cocoon industry. Silkworm larvae show typically precocious wandering behavior after being parasitized by E. sorbillans; however, the underlying molecular mechanism remains unexplored. Herein, we investigated the changes in the levels of 20-hydroxyecdysone (20E) and juvenile hormone (JH) titer, and they both increased in the hemolymph of parasitized silkworms. Furthermore, we verified the expression patterns of related genes, which showed an upregulation of 20E signaling and biosynthesis genes but a significant downregulation of ecdysone oxidase (EO), a 20E inactivation enzyme, in parasitized silkworms. In addition, related genes of the JH signaling were activated in parasitized silkworms, while related genes of the JH degradation pathway were suppressed, resulting in an increase in JH titer. Notably, the precocious wandering behavior of parasitized silkworms was partly recoverable by silencing the transcriptions of BmCYP302A1 or BmCYP307A1 genes. Our findings suggest that the developmental duration of silkworm post parasitism could be shortened by regulation of 20E and JH titers, which may help silkworm to resist the E. sorbillans infestation. These findings provide a basis for deeper insight into the interplay between silkworms and E. sorbillans and may serve as a reference for the development of a novel approach to control silkworm myiasis.

Berberine is a suppressor of Hedgehog signaling cascade in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a malignant affliction that burdens people globally. Overactivated Hedgehog signal is highly implicated in CRC pathogenesis. Phytochemical berberine exerts strong potency on CRC, with molecular mechanism elusive. PURPOSE: We sought to study berberine's anti-CRC action and explore its underlying mechanism based on Hedgehog signaling cascade. METHODS: In CRC HCT116 cells and SW480 cells treated with berberine, the proliferation, migration, invasion, clonogenesis, apoptosis and cell cycle were measured, with determination of Hedgehog signaling pathway activity. Following establishment of mouse model of HCT116 xenograft tumor, the efficacies of berberine on carcinogenesis, pathological manifestation and malignant phenotypes of CRC were examined, with analysis of Hedgehog signaling axis in HCT116 xenograft tumor tissues. Additionally, toxicological study of berberine was conducted on zebrafish. RESULTS: Berberine was discovered to suppress the proliferation, migration, invasion and clonogenesis of HCT116 cells and SW480 cells. Furthermore, berberine caused cell apoptosis and blockaded cell cycle at phase G0/G1 in CRC cells, with dampened Hedgehog signaling cascade. In HCT116 xenograft tumor of nude mice, berberine inhibited tumor growth, alleviated pathological score, and promoted apoptosis and cell cycle arrest in tumor tissues, through constraining Hedgehog signaling. The toxicological study of berberine on zebrafish indicated that berberine incurred damage to the liver and heart of zebrafish at high dosage and prolonged administration. CONCLUSIONS: Taken together, berberine may inhibit the malignant phenotypes of CRC through diminishing Hedgehog signaling cascade. However, the potential adverse reactions should be taken into account upon abuse of berberine.

Ursolic Acid Suppresses Colorectal Cancer by Down-Regulation of Wnt/ß-Catenin Signaling Pathway Activity.

Overwhelming evidence points to an abnormally active Wnt/ß-catenin signaling as a key player in colorectal cancer (CRC) pathogenesis. Ursolic acid (UA) is a pentacyclic triterpenoid that has been found in a broad variety of fruits, spices, and medicinal plants. UA has been shown to have potent bioactivity against a variety of cancers, including CRC, with the action mechanism obscure. Our study tried to learn more about the efficacy of UA on CRC and its functional mechanism amid the Wnt/ß-catenin signaling cascade. We determined the efficacy of UA on CRC SW620 cells with respect to the proliferation, migration, clonality, apoptosis, cell cycle, and Wnt/ß-catenin signaling cascade, with assessment of the effect of UA on normal colonic NCM460 cells. Also, the effects of UA on the tumor development, apoptosis, cell cycle, and Wnt/ß-catenin signaling axis were evaluated after a subcutaneous SW620 xenograft tumor model was established in mice. In this work, we showed that UA drastically suppressed proliferation, migration, and clonality; induced apoptosis; and arrested the cell cycle at the G0/G1 phase of SW620 cells, without the influence on NCM460 cells, accompanied by weakened activity of the Wnt/ß-catenin signaling pathway. Besides, UA markedly deterred the growth of the xenograft tumor, ameliorated pathological features, triggered apoptosis, and arrested the cell cycle in xenograft CRC tissue, by lessening the Wnt/ß-catenin signaling cascade. Overall, UA may inhibit the malignant phenotype, induce apoptosis, and arrest the cell cycle of CRC, potentially by attenuating the Wnt/ß-catenin signaling axis, providing insights into the mechanism for the potency of UA on CRC.

Curcumin: An epigenetic regulator and its application in cancer.

Nowadays, one of the leading causes of death in humans is cancer, which is still on the rise globally and is in great need of intense study on the pathogenic mechanism and effective therapy. Epigenetics is a discipline that studies heritable changes in gene expression without alteration of DNA sequence. Epigenetic changes mainly involve DNA methylation, histone modifications and non-coding RNA (ncRNA) expression, which are interconnected to play a crucial role in the initiation and progression of various malignancies. Curcumin is a type of plant-derived polyphenolic compound with strong bioactivity against various disorders, particularly cancer. Retrieving commonly used databases such as PubMed, Google Scholar and CNKI, we summarized recent advances in the efficacy of curcumin on cancer and its epigenetic regulation in terms of DNA methylation, histone modifications and ncRNA expression. Furthermore, we also focused on improving the bioavailability of curcumin by development of novel curcumin analogs with high bioavailability, nanoparticles-loaded drug delivery system for curcumin, and combination therapy of curcumin with other agents. This review provides comprehensive insights into the molecular mechanisms, on the basis of epigenetic regulation, underlying the clinical application of curcumin in cancer.

Bone tumor necrosis rate detection in few-shot X-rays based on deep learning.

Although biopsy-based necrosis rate is a golden standard for reflecting the sensitivity of bone tumor and guiding postoperative chemotherapy, it requires biopsy which is invasive and time-consuming. In this paper, we develop a new necrosis rate detection method using time series X-ray images instead of biopsy. To overcome the limitations of few-shot samples, the proposed method utilizes a Generative Adversarial Network with Long Short-term Memory to generate time series X-ray images. For further data expansion, an image-to-image translation network is applied for producing the initial images. These augmented data are treated as the training set of a 3D-Convolutional Neural Network classification model. Our method expands the few-shot bone tumor X-rays by 10 times, and approaches the necrotic rate classification result of biopsy, which is the state-of-the-art technique in the detection of few-shot bone tumor necrosis rate. Furthermore, it provides an efficient method to investigate the bone tumor necrosis rate in few-shot samples.

Home and hub: pet trade and traditional medicine impact reptile populations in source locations and destinations.

The pet trade and Traditional Chinese Medicine (TCM) consumption are major drivers of global biodiversity loss. Tokay geckos (Gekko gecko) are among the most traded reptile species worldwide. In Hong Kong, pet and TCM markets sell tokay geckos while wild populations also persist. To clarify connections between trade sources and destinations, we compared genetics and stable isotopes of wild tokays in local and non-local populations to dried individuals from TCM markets across Hong Kong. We found that TCM tokays are likely not of local origin. Most wild tokays were related to individuals in South China, indicating a probable natural origin. However, two populations contained individuals more similar to distant populations, indicating pet trade origins. Our results highlight the complexity of wildlife trade impacts within trade hubs. Such trade dynamics complicate local legal regulation when endangered species are protected, but the same species might also be non-native and possibly damaging to the environment.

Peppermint essential oil: its phytochemistry, biological activity, pharmacological effect and application.

Mentha (also known as peppermint), a genus of plants in the taxonomic family Lamiaceae (mint family), is widely distributed throughout temperate regions of the world. Mentha contains various constituents that are classified as peppermint essential oil (PEO) and non-essential components. PEO, consisting mainly of menthol, menthone, neomenthol and iso-menthone, is a mixture of volatile metabolites with anti-inflammatory, antibacterial, antiviral, scolicidal, immunomodulatory, antitumor, neuroprotective, antifatigue and antioxidant activities. Mounting evidence indicates that PEO may pharmacologically protect gastrointestinal, liver, kidney, skin, respiratory, brain and nervous systems, and exert hypoglycemic and hypolipidemic effects. Clinically, PEO is used for gastrointestinal and dermatological diseases, postoperative adjuvant therapy and other fields. This review aims to address the advances in the extraction and isolation of PEO, its biological activities, pharmacological effects, toxicity and applications, with an emphasis on the efficacy of PEO on burn wounds and psoriasis, providing a comprehensive foundation for research, development and application of PEO in future.

Wnt signaling in colorectal cancer: pathogenic role and therapeutic target.

BACKGROUND: The Wnt signaling pathway is a complex network of protein interactions that functions most commonly in embryonic development and cancer, but is also involved in normal physiological processes in adults. The canonical Wnt signaling pathway regulates cell pluripotency and determines the differentiation fate of cells during development. The canonical Wnt signaling pathway (also known as the Wnt/ß-catenin signaling pathway) is a recognized driver of colon cancer and one of the most representative signaling pathways. As a functional effector molecule of Wnt signaling, the modification and degradation of ß-catenin are key events in the Wnt signaling pathway and the development and progression of colon cancer. Therefore, the Wnt signaling pathway plays an important role in the pathogenesis of diseases, especially the pathogenesis of colorectal cancer (CRC). OBJECTIVE: Inhibit the Wnt signaling pathway to explore the therapeutic targets of colorectal cancer. METHODS: Based on studying the Wnt pathway, master the biochemical processes related to the Wnt pathway, and analyze the relevant targets when drugs or inhibitors act on the Wnt pathway, to clarify the medication ideas of drugs or inhibitors for the treatment of diseases, especially colorectal cancer. RESULTS: Wnt signaling pathways include: Wnt/ß-catenin or canonical Wnt signaling pathway, planar cell polarity (Wnt-PCP) pathway and Wnt-Ca2+ signaling pathway. The Wnt signaling pathway is closely related to cancer cell proliferation, stemness, apoptosis, autophagy, metabolism, inflammation and immunization, microenvironment, resistance, ion channel, heterogeneity, EMT/migration/invasion/metastasis. Drugs/phytochemicals and molecular preparations for the Wnt pathway of CRC treatment have now been developed. Wnt inhibitors are also commonly used clinically for the treatment of CRC. CONCLUSION: The development of drugs/phytochemicals and molecular inhibitors targeting the Wnt pathway can effectively treat colorectal cancer clinically.

Berberine suppresses colorectal cancer by regulation of Hedgehog signaling pathway activity and gut microbiota.

BACKGROUND: A growing body of evidence reveals that dysregulation of Hedgehog signaling pathway and dysbiosis of gut microbiota are associated with the pathogenesis of colorectal cancer (CRC). Berberine, a botanical benzylisoquinoline alkaloid, possesses powerful activities against various malignancies including CRC, with the underlying mechanisms to be illuminated. PURPOSE: The present study investigated the potencies of berberine on CRC and deciphered the action mechanisms in the context of Hedgehog signaling cascade and gut microbiota. METHODS: The effects of berberine on the malignant phenotype, apoptosis, cell cycle and Hedgehog signaling of CRC cells were examined in vitro. In azoxymethane/dextran sulfate sodium-caused mouse CRC, the efficacies of berberine on the carcinogenesis, pathological profile, apoptosis, cell cycle and Hedgehog signaling were determined in vivo. Also, the influences of berberine on gut microbiota in CRC mice were assessed by high-throughput DNA sequencing analysis of 16S ribosomal RNA of fecal microbiome in CRC mice. RESULTS: In the present study, berberine was found to dampen the proliferation, migration, invasion and colony formation of CRC cells, without toxicity to normal colonic cells. Additionally, berberine induced apoptosis and arrested cell cycle at G0/G1 phase in CRC cells, accompanied by reduced Hedgehog signaling pathway activity in vitro. In mouse CRC, berberine suppressed tumor growth, ameliorated pathological manifestations, and potentially induced the apoptosis and cell cycle arrest of CRC, with lowered Hedgehog signaling cascade in vivo. Additionally, berberine decreased ß-diversity of gut microbiota in CRC mice, without influence on α-diversity. Berberine also enriched probiotic microbes and depleted pathogenic microbes, and modulated the functionality of gut microbiota in CRC mice. CONCLUSIONS: Overall, berberine may suppress colorectal cancer, orchestrated by down-regulation of Hedgehog signaling pathway activity and modulation of gut microbiota.

Ursolic acid inhibits the activation of smoothened-independent non-canonical hedgehog pathway in colorectal cancer by suppressing AKT signaling cascade.

It is being brought to light that smoothened (SMO)-independent non-canonical Hedgehog signaling is associated with the pathogenesis of various cancers. Ursolic acid (UA), a pentacyclic triterpenoid present in many medicinal herbs, manifests potent effectiveness against multiple malignancies including colorectal cancer (CRC). In our previous study, UA was found to protect against CRC in vitro by suppression of canonical Hedgehog signaling cascade. Here, the influence of UA on SMO-independent non-canonical Hedgehog signaling in CRC was investigated in the present study, which demonstrated that UA hampered the proliferation and migration, induced the apoptosis of HCT-116hSMO- cells with SMO gene knockdown, accompanied by the augmented expression of the suppressor of fused (SUFU), and lessened levels of MYC (c-Myc), glioma-associated oncogene (GLI1) and Sonic Hedgehog (SHH), and lowered phosphorylation of protein kinase B (PKB, AKT), suggesting that UA diminished non-canonical Hedgehog signal transduction in CRC. In HCT-116hSMO- xenograft tumor, UA ameliorated the symptoms, impeded the growth and caused the apoptosis of CRC, with heightened SUFU expression, and abated levels of MYC, GLI1, and SHH, and mitigated phosphorylation of AKT, indicating that UA down-regulated non-canonical Hedgehog signaling cascade in CRC. Taken together, UA may alleviate CRC by suppressing AKT signaling-dependent activation of SMO-independent non-canonical Hedgehog pathway.

Erratum: Inhibition of P-glycoprotein, multidrug resistance-associated protein 2 and cytochrome P450 3A4 improves the oral absorption of octreotide in rats with portal hypertension.

[This corrects the article DOI: 10.3892/etm.2016.3808.].

Curcumin protects against manganese-induced neurotoxicity in rat by regulating oxidative stress-related gene expression via H3K27 acetylation.

Long-term manganese exposure causes a neurodegenerative disorder referred to as manganese poisoning, but the mechanism remains unclear and no specific treatment is available. Oxidative stress is widely recognised as one of the main causes of manganese-induced neurotoxicity. In recent years, the role of histone acetylation in neurodegenerative diseases has been widely concerned. curcumin is a natural polyphenol compound extracted from the rhizome of turmeric and exhibits both antioxidant and neuroprotective properties. Therefore, we aimed to investigate whether and how curcumin protects against manganese-induced neurotoxicity from the perspective of histone acetylation, based on the reversibility of histone acetylation modification. In this study, rats were treated with or without curcumin and subjected to long-term manganese exposure. Results that treatment of manganese decreased the protein expression of H3K18 acetylation and H3K27 acetylation at the promoters of oxidative stress-related genes and inhibited the expression of these genes. Nevertheless, curcumin increased the H3K27 acetylation level at the manganese superoxide dismutase (SOD2) gene promoter and promoted the expression of SOD2 gene. Oxidative damage in the rat striatum as well as learning and memory dysfunction were ameliorated after curcumin treatment. Taken together, our results suggest that the regulation of oxidative stress by histone acetylation may be a key mechanism of manganese-induced neurotoxicity. In addition, curcumin ameliorates Mn-induced neurotoxicity may be due to alleviation of oxidative damage mediated by increased activation of H3K27 acetylation at the SOD2 gene promoter.