Luteolin, a flavone ingredient: Anticancer mechanisms, combined medication strategy, pharmacokinetics, clinical trials, and pharmaceutical researches.

Current pharmaceutical research is energetically excavating the pharmacotherapeutic role of herb-derived ingredients in multiple malignancies' targeting. Luteolin is one of the major phytochemical components that exist in various traditional Chinese medicine or medical herbs. Mounting evidence reveals that this phytoconstituent endows prominent therapeutic actions on diverse malignancies, with the underlying mechanisms, combined medication strategy, and pharmacokinetics elusive. Additionally, the clinical trial and pharmaceutical investigation of luteolin remain to be systematically delineated. The present review aimed to comprehensively summarize the updated information with regard to the anticancer mechanism, combined medication strategies, pharmacokinetics, clinical trials, and pharmaceutical researches of luteolin. The survey corroborates that luteolin executes multiple anticancer effects mainly by dampening proliferation and invasion, spurring apoptosis, intercepting cell cycle, regulating autophagy and immune, inhibiting inflammatory response, inducing ferroptosis, and pyroptosis, as well as epigenetic modification, and so on. Luteolin can be applied in combination with numerous clinical anticarcinogens and natural ingredients to synergistically enhance the therapeutic efficacy of malignancies while reducing adverse reactions. For pharmacokinetics, luteolin has an unfavorable oral bioavailability, it mainly persists in plasma as glucuronides and sulfate-conjugates after being metabolized, and is regarded as potent inhibitors of OATP1B1 and OATP2B1, which may be messed with the pharmacokinetic interactions of miscellaneous bioactive substances in vivo. Besides, pharmaceutical innovation of luteolin with leading-edge drug delivery systems such as host-guest complexes, nanoparticles, liposomes, nanoemulsion, microspheres, and hydrogels are beneficial to the exploitation of luteolin-based products. Moreover, some registered clinical trials on luteolin are being carried out, yet clinical research on anticancer effects should be continuously promoted.

Online semi-supervised learning for motor imagery EEG classification.

OBJECTIVE: Time-consuming data labeling in brain-computer interfaces (BCIs) raises many problems such as mental fatigue and is one key factor that hinders the real-world adoption of motor imagery (MI)-based BCIs. An alternative approach is to integrate readily available, as well as informative, unlabeled data online, whereas this approach is less investigated. APPROACH: We proposed an online semi-supervised learning scheme to improve the classification performance of MI-based BCI. This scheme uses regularized weighted online sequential extreme learning machine (RWOS-ELM) as the base classifier and updates its model parameters with incoming balanced data chunk-by-chunk. In the initial stage, we designed a technique that combines the synthetic minority oversampling with the edited nearest neighbor rule for data augmentation to construct more discriminative initial classifiers. When used online, the incoming chunk of data is first pseudo-labeled by RWOS-ELM as well as an auxiliary classifier, and then balanced again by the above-mentioned technique. Initial classifiers are further updated based on these class-balanced data. MAIN RESULTS: Offline experimental results on two publicly available MI datasets demonstrate the superiority of the proposed scheme over its counterparts. Further online experiments on six subjects show that their BCI performance gradually improved by learning from incoming unlabeled data. SIGNIFICANCE: Our proposed online semi-supervised learning scheme has higher computation and memory usage efficiency, which is promising for online MI-based BCIs, especially in the case of insufficient labeled training data.

Long-read sequencing reveals the landscape of aberrant alternative splicing and novel therapeutic target in colorectal cancer.

BACKGROUND: Alternative splicing complexity plays a vital role in carcinogenesis and cancer progression. Improved understanding of novel splicing events and the underlying regulatory mechanisms may contribute new insights into developing new therapeutic strategies for colorectal cancer (CRC). METHODS: Here, we combined long-read sequencing technology with short-read RNA-seq methods to investigate the transcriptome complexity in CRC. By using experiment assays, we explored the function of newly identified splicing isoform TIMP1 Δ4-5. Moreover, a CRISPR/dCasRx-based strategy to induce the TIMP1 exon 4-5 exclusion was introduced to inhibit neoplasm growth. RESULTS: A total of 90,703 transcripts were identified, of which > 62% were novel compared with current transcriptome annotations. These novel transcripts were more likely to be sample specific, expressed at relatively lower levels with more exons, and oncogenes displayed a characteristic to generate more transcripts in CRC. Clinical outcome data analysis showed that 1472 differentially expressed alternative splicing events (DEAS) were tightly associated with CRC patients' prognosis, and many novel isoforms were likely to be important determinants for patient survival. Among these, newly identified splicing isoform TIMP1 Δ4-5 was significantly downregulated in CRC. Further in vitro and in vivo assays demonstrated that ectopic expression of TIMP1 Δ4-5 significantly suppresses tumor cell growth and metastasis. Serine/arginine-rich splicing factor 1 (SRSF1) acts as a onco-splicing regulator through sustaining the inclusion of TIMP1 exon 4-5. Furthermore, CRISPR/dCasRx-based strategies designed to induce TIMP1 exon 4-5 exclusion have the potential to restrain the CRC growth. CONCLUSIONS: This data provides a rich resource for deeper studies of gastrointestinal malignancies. Newly identified splicing isoform TIMP1 Δ4-5 plays an important role in mediating CRC progression and may be a potential therapy target in CRC.

Long-term remote observations of particulate organic phosphorus concentration in eutrophic Lake Taihu based on a novel algorithm.

Monitoring the long-term spatiotemporal variations in particulate organic phosphorus concentration (CPOP) is imperative for clarifying the phosphorus cycle and its biogeochemical behavior in waters. However, little attention has been devoted to this owing to a lack of suitable bio-optical algorithms that allow the application of remote sensing data. In this study, based on Moderate Resolution Imaging Spectroradiometer (MODIS) data, a novel absorption-based algorithm of CPOP was developed for eutrophic Lake Taihu, China. The algorithm yielded a promising performance with a mean absolute percentage error of 27.75% and root mean square error of 21.09 µg/L. The long-term MODIS-derived CPOP demonstrated an overall increasing pattern over the past 19 years (2003-2021) and a significant temporal heterogeneity in Lake Taihu, with higher value in summer (81.97 ± 3.81 µg/L) and autumn (82.07 ± 3.8 µg/L), and lower CPOP in spring (79.52 ± 3.81 µg/L) and winter (78.74 ± 3.8 µg/L). Spatially, relatively higher CPOP was observed in the Zhushan Bay (85.87 ± 7.5 µg/L), whereas the lower value was observed in the Xukou Bay (78.95 ± 3.48 µg/L). In addition, significant correlations (r > 0.6, P < 0.05) were observed between CPOP and air temperature, chlorophyll-a concentration and cyanobacterial blooms areas, demonstrating that CPOP was greatly influenced by air temperature and algal metabolism. This study provides the first record of the spatial-temporal characteristics of CPOP in Lake Taihu over the past 19 years, and the CPOP results and regulatory factors analyses could provide valuable insights for aquatic ecosystem conservation.

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.

Promising Nanomedicines of Shikonin for Cancer Therapy.

Malignant tumor, the leading cause of death worldwide, poses a serious threat to human health. For decades, natural product has been proven to be an essential source for novel anticancer drug discovery. Shikonin (SHK), a natural molecule separated from the root of Lithospermum erythrorhizon, shows great potential in anticancer therapy. However, its further clinical application is significantly restricted by poor bioavailability, adverse effects, and non-selective toxicity. With the development of nanotechnology, nano drug delivery systems have emerged as promising strategies to improve bioavailability and enhance the therapeutic efficacy of drugs. To overcome the shortcoming of SHK, various nano drug delivery systems such as liposomes, polymeric micelles, nanoparticles, nanogels, and nanoemulsions, were developed to achieve efficient delivery for enhanced antitumor effects. Herein, this review summarizes the anticancer pharmacological activities and pharmacokinetics of SHK. Additionally, the latest progress of SHK nanomedicines in cancer therapy is outlined, focusing on long circulation, tumor targeting ability, tumor microenvironment responsive drug release, and nanosystem-mediated combination therapy. Finally, the challenges and prospects of SHK nanomedicines in the future clinical application are spotlighted.

The Effect of Nano-Silica Surface Infiltration on Bond Strength of a Phosphate-Monomer-containing Composite Cement to Zirconia.

PURPOSE: To evaluate the bonding receptiveness of zirconia treated with nano-silica surface infiltration and the bond strength of composite cement after aging. MATERIALS AND METHODS: Zirconia ceramic green bodies (Ceramill zolid, Amann Girbach) with dimensions of 10 x 10 x 4 mm were divided into three groups (n = 4): group C (control: no treatment after sintering), group S (sandblasted: 50-µm alumina airborne particle abrasion after sintering) and group N (nanosintered: infiltrated with nano-silica colloid, sintered, and then etched with hydrofluoric acid). Phase transformations were examined through X-ray diffraction (XRD). Composite resin (Filtek Z250, 3M Oral Care) was bonded to zirconia using the 10-MDP-containing composite cement Panavia F (Kuraray Noritake). The composite-cement/zirconia bond strength was immediately measured using the microtensile bond strength test (µTBS) as well as after three months of artificial aging in water (n = 20 microstick specimens/group). Failure mode patterns were examined using SEM. RESULTS: The specimens of groups C and S, as tested by XRD, exhibited almost full tetragonal phases, while a small extent of tetragonal-monoclinic phase transformation (t→m) was observed for group N. Group N achieved the highest bond strengths (41.5 ± 8.6 MPa), which was significantly higher than that measured for groups C and S (p < 0.05). There was a significant drop in µTBS after 90 days of water storage for groups C and S. SEM revealed a decrease in the percentage of cohesive failure in groups N and S after water storage. CONCLUSIONS: Infiltrating zirconia with nano-silica is a reliable method to establish a strong and stable bond to zirconia. The combination of surface infiltration with nano-silica and application of a phosphate monomer-containing composite cement can significantly improve the composite-cement/zirconia bond strength.

Long-term dynamics and drivers of particulate phosphorus concentration in eutrophic lake Chaohu, China.

Particulate phosphorus (PP) plays an important biological role in the eutrophication process, and is thus an important water quality parameter for assessing climatic change and anthropogenic activity factors that affect aquatic ecosystems. Here, we used 20-year Moderate Resolution Imaging Spectroradiometer (MODIS) data to explore the patterns and trends of PP concentration (CPP) in eutrophic Lake Chaohu based on a new empirical model. The validation results indicated that the developed model performed satisfactorily in estimating CPP, with a mean absolute percentage error of 31.89% and root mean square error of 0.022 mg/L. Long-term MODIS observations (2000-2019) revealed that the CPP of Lake Chaohu has experienced an overall increasing trend and distinct spatiotemporal heterogeneity. The driving factor analysis revealed that the chemical fertilizer consumption, municipal wastewater, industrial sewage, precipitation, and air temperature were the five potential driving factors and collectively explained more than 81% of the long-term variation in CPP. This study provides the long-term datasets of CPP in inland waters and new insights for future water eutrophication control and restoration efforts.

Effects of hyperbaric oxygen on Notch signaling pathway after severe carbon monoxide poisoning in mice.

Demyelination of the cerebral white matter is the most common pathological change after carbon monoxide (CO) poisoning. Notch signaling, the mechanism underlying the differentiation of astrocytes and oligodendrocytes, is critical to remyelination of the white matter after brain lesion. The purpose of this work was to determine the effects of hyperbaric oxygen (HBO) on Notch signaling pathway after CO poisoning for the explanation of the protective effects of HBO on CO-poisoning-related cerebral white matter demyelination. The male C57 BL/6 mice with severe CO poisoning were treated by HBO. And HBO therapy shortened the escape latency and improved the body mass after CO poisoning. HBO therapy also significantly suppressed protein and mRNA levels of Notch1 and Hes5 after CO poisoning. Our findings suggested that HBO could suppress the activation of Notch signaling pathway after CO poisoning, which is the mechanism underlying the neuroprotection of HBO on demyelination after severe CO poisoning.

Role of potential bioactive metabolites from traditional Chinese medicine for type 2 diabetes mellitus: An overview.

Type 2 diabetes mellitus (T2DM) is a metabolic disease with persistent hyperglycemia primarily caused by insulin resistance (IR). The number of diabetic patients globally has been rising over the past decades. Although significant progress has been made in treating diabetes mellitus (DM), existing clinical drugs for diabetes can no longer fully meet patients when they face complex and huge clinical treatment needs. As a traditional and effective medical system, traditional Chinese medicine (TCM) has a unique understanding of diabetes treatment and has developed many classic and practical prescriptions targeting DM. With modern medicine and pharmacy advancements, researchers have discovered that various bioactive metabolites isolated from TCM show therapeutic on DM. Compared with existing clinical drugs, these bioactive metabolites demonstrate promising prospects for treating DM due to their excellent biocompatibility and fewer adverse reactions. Accordingly, these valuable metabolites have attracted the interest of researchers worldwide. Despite the abundance of research works and specialized-topic reviews published over the past years, there is a lack of updated and systematic reviews concerning this fast-growing field. Therefore, in this review, we summarized the bioactive metabolites derived from TCM with the potential treatment of T2DM by searching several authoritative databases such as PubMed, Web of Science, Wiley Online Library, and Springer Link. For the convenience of readers, the content is divided into four parts according to the structural characteristics of these valuable compounds (flavonoids, terpenoids, alkaloids, and others). Meanwhile, the detailed mechanism and future directions of these promising compounds curing DM are also summarized in the related sections. We hope this review inspires increasingly valuable and significant research focusing on potential bioactive metabolites from TCM to treat DM in the future.

Polyethylene glycol-modified nanoscale conjugated polymer for the photothermal therapy of lung cancer.

Killing tumor cells efficiently with photothermal therapy remains a huge challenge. In this study, we successfully prepared a novel polymer with photothermal conversion capability via a condensation reaction, and then subjected it to Polyethylene glycol (PEG) modification and ultrasonic nanocrystalline treatment to make it suitable forin vivophotothermal therapy applications. The conjugated polymer demonstrated good biocompatibility and photothermal conversion ability and was shown in cell experiments to be effective in killing tumor cells after laser irradiation. In addition, the conjugated polymer-based photothermal therapy, guided by photoacoustic real-time imaging and mediated by laser irradiation, of a tumor-bearing mouse model could effectively inhibit the growth of tumor tissue and demonstrated goodin vivobiosafety. Thus, photothermal therapy based on the conjugated polymer synthesized in this study provides a new idea and strategy for the treatment of lung cancer.

Quality of Care in Public County Hospitals: A Cross-Sectional Study for Stroke, Pneumonia, and Heart Failure Care in Eastern China.

There are very few studies about the quality of care (QoC) in Chinese county hospitals. Using 7, 6, and 6 standard operations from clinical pathways as the process indicators, we evaluated the quality of stroke, pneumonia, and heart failure care, respectively. We also conducted chi-squared tests to detect differences of quality between selected counties or hospitals. We extracted relevant information from medical records of 421 stroke cases, 329 pneumonia cases, and 341 heart failure cases, which were sampled from 6 county hospitals in 3 counties of eastern China. The average proportion of recommended care delivered included stroke, pneumonia, and heart failure patients at 55.36%, 41.64%, and 49.56%, respectively. Great variation of QoC was detected not only across selected counties but between comprehensive county hospitals and traditional Chinese medicine county hospitals. We deny the widely-accepted assumptions that poor QoC should be blamed on defectively-equipped facilities or medicine and overwhelmed care providers. Instead, we speculate the low qualifications of medical workers, failed clinical knowledge translation, incorrect diagnosis, and a lack of electronic systems could be the reasons behind poor QoC. It is high time for China to put QoC as the national health priority.

Structural variation and spatial polysaccharide profiling of intervessel pit membranes in grapevine.

BACKGROUND AND AIMS: Intervessel pit membranes (PMs) are important cell wall structures in the vessel system that may impact a plant's water transport and its susceptibility to vascular diseases. Functional roles of intervessel PMs largely depend on their structure and polysaccharide composition, which are the targets of this study. METHODS: With grapevine used as a model plant, this study applied an immunogold-scanning electron microscopy technique to simultaneously analyse at high resolution intervessel PM structures and major pectic and hemicellulosic polysaccharides that make up intervessel PMs. KEY RESULTS: Intervessel PMs in functional xylem showed significant structural variation, with about 90 % of them being structurally intact with smooth or relatively smooth surfaces and the remaining 10 % with progressively degraded structures. The results also elucidated details of the removal process of cell wall materials from the intervessel PM surface toward its depth during its natural degradation. Four groups of pectic and hemicellulosic polysaccharides were immunolocalized in intervessel PMs and differed in their spatial distribution and abundance. Weakly methyl-esterified homogalacturonans (WMe-HGs, detected by JIM5) were abundant in the surface layer, heavily methyl-esterified homogalacturonans (HMe-HGs, detected by JIM7) and xylans detected by CCRC-M140 were mostly found in deeper layers, and fucosylated xyloglucans (F-XyGs, detected by CCRC-M1) were more uniformly distributed at different depths of the intervessel PM. CONCLUSIONS: Intervessel PMs displayed diverse structural variations in grapevine. They contained certain major groups of pectic and hemicellulosic polysaccharides with different spatial distributions and abundance. This information is crucial to reveal the polysaccharide profiling of the primary cell wall and to understand the roles of intervessel PMs in the regulation of water transport as well as in a plant's susceptibility to vascular diseases.

Study on the pore structure and radon release characteristics of coal in northern China.

Identifying the release characteristics of radon (Rn-222) in coal mines is critical preventing cancer risks for coal miners and coal fires. The present investigates the pore structure characteristics of coal samples from eleven coal mines in northern China, using low-temperature nitrogen adsorption (LTNA) test, combined with the radon exhalation rate in coal. The findings of the study reveal that the N2 adsorption isotherms of all the coal samples fall under the inverse S type, with micropores dominating in low-rank coals and mesopores dominating in the medium and high-rank coals, due to the separation of organic matter and quartz by shrinkage of micro-components and the orderly arrangement of aromatic rings as a result of ring condensation and thermal cleavage. The pore diameters of coal samples show similar distribution characteristics for sizes >2 nm, represented by a single peak near the pore diameter of 3 nm. Ash yield controls the mesopore and micropore volumes of medium and high-rank coal samples. The radon emission rate displays positive linear correlation (r2 = 0.87) with micropore volumes of analyzed coal samples due to the infillings of free radon in micropores. The radon element is derived by uranium decay, which causes a greater radon exhalation rate of coal mines in areas near the uranium mines. The results of the present study could be helpful to understand the influence mechanism of radon emission processes in coal, which provides an important basis for reducing cancer risks for coal miners and predicting coal fires.

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.

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.

SNHG1-miR-186-5p-YY1 feedback loop alleviates hepatic ischemia/reperfusion injury.

As a common cause of liver injury, hepatic ischemia/reperfusion injury (HIRI) happens in various clinical conditions including trauma, hepatectomy and liver transplantation. Since transcription factor Yin Yang 1 (YY1) was reported to be downregulated after ischemia/reperfusion (I/R) injury, we focused on YY1 to explore its function in HIRI by functional assays like Cell Counting Kit-8 (CCK-8) assays and flow cytometry assays. The RT-qPCR assay revealed that YY1 was downregulated in hepatocytes after I/R injury. The function assays disclosed that YY1 facilitated cell viability and proliferation, but hindered cell apoptosis in hepatocytes after I/R injury. Through mechanism assays including luciferase reporter assay, RIP and RNA pulldown assay, miR-186-5p was found to bind with YY1 and promote hepatocyte apoptosis by targeting YY1. Subsequently, we verified that small nucleolar RNA host gene 1 (SNHG1) could sponge miR-186-5p to upregulate YY1. Importantly, we figured out that YY1 had a positive regulation on SNHG1. Along the way, YY1 was identified as the upstream transcription factor for SNHG1. In conclusion, our study unveiled a novel competing endogenous RNA (ceRNA) pattern of SNHG1/miR-186-5p/YY1 positive feedback loop in hepatic I/R injury, which might provide new insight into prevention of HIRI during liver transplantation or hepatic surgery.

Suppression of colitis-associated colorectal cancer by scutellarin through inhibiting Hedgehog signaling pathway activity.

BACKGROUND: Colitis-associated colorectal cancer (CAC) is a specific type of colorectal cancer (CRC) and mainly develops from long-term intestinal inflammation. Mounting evidence reveals that activated Hedgehog signaling pathway plays a vital role in the pathogenesis of CRC. Scutellarin is a type of phytochemical flavonoid with a powerful efficacy on various malignancies, including CRC. AIM: Here, we studied the therapeutic effect of scutellarin on CRC and its direct regulating targets. METHODS: The CAC model in mice was established by azomethane oxide (AOM) and sodium dextran sulfate (DSS), followed by detection of the efficacies of scutellarin on the carcinogenesis, apoptosis, inflammation, Hedgehog signaling cascade and complicated inflammatory networks in CAC tissues of mice. In CRC SW480 cells, the effects of scutellarin on malignant phenotype, apoptosis and Hedgehog signaling were examined. In TNF-α-stimulated IEC-6 intestinal epithelial cells, the actions of scutellarin on inflammatory response and Hedgehog signals were assessed as well. RESULTS: Scutellarin significantly ameliorated AOM/DSS-caused CAC in mice and induced apoptosis in CAC tissues of mice, by inhibiting NF-κB (nuclear factor kappa B) -mediated inflammation and Hedgehog signaling axis. RNA-seq and transcriptome analysis indicated that scutellarin regulated complicated inflammatory networks in mouse CAC. Also, scutellarin suppressed the proliferation, migration, colony formation, and induced apoptosis of SW480 cells by down-regulation of Hedgehog signaling pathway activity. Additionally, scutellarin lessened NF-κB-mediated inflammatory response in TNF-α-stimulated IEC-6 cells, by attenuating Hedgehog signaling cascade. CONCLUSION: Scutellarin potently ameliorates CAC by suppressing Hedgehog signaling pathway activity, underpinning the promising application of scutellarin to CRC in clinical settings.

CACA Guidelines for Holistic Integrative Management of Breast Cancer.

Purpose: Breast cancer is now the most common malignant tumor worldwide. About one-fourth of female cancer patients all over the world suffer from breast cancer. And about one in six female cancer deaths worldwide is caused by breast cancer. In terms of absolute numbers of cases and deaths, China ranks first in the world. The CACA Guidelines for Holistic Integrative Management of Breast Cancer were edited to help improve the diagnosis and comprehensive treatment in China. Methods: The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to classify evidence and consensus. Results: The CACA Guidelines for Holistic Integrative Management of Breast Cancer include the epidemiology of breast cancer, breast cancer screening, breast cancer diagnosis, early breast cancer treatment, advanced breast cancer treatment, follow-up, rehabilitation, and traditional Chinese medicine treatment of breast cancer patients. Conclusion: We to standardize the diagnosis and treatment of breast cancer in China through the formulation of the CACA Guidelines.

Shikonin, a naphthalene ingredient: Therapeutic actions, pharmacokinetics, toxicology, clinical trials and pharmaceutical researches.

BACKGROUND: Shikonin is one of the major phytochemical components of Lithospermum erythrorhizon (Purple Cromwell), which is a type of medicinal herb broadly utilized in traditional Chinese medicine. It is well established that shikonin possesses remarkable therapeutic actions on various diseases, with the underlying mechanisms, pharmacokinetics and toxicological effects elusive. Also, the clinical trial and pharmaceutical study of shikonin remain to be comprehensively delineated. PURPOSE: The present review aimed to systematically summarize the updated knowledge regarding the therapeutic actions, pharmacokinetics, toxicological effects, clinical trial and pharmaceutical study of shikonin. METHODS: The information contained in this review article were retrieved from some authoritative databases including Web of Science, PubMed, Google scholar, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database and so on, till August 2021. RESULTS: Shikonin exerts multiple therapeutic efficacies, such as anti-inflammation, anti-cancer, cardiovascular protection, anti-microbiomes, analgesia, anti-obesity, brain protection, and so on, mainly by regulating the NF-κB, PI3K/Akt/MAPKs, Akt/mTOR, TGF-ß, GSK3ß, TLR4/Akt signaling pathways, NLRP3 inflammasome, reactive oxygen stress, Bax/Bcl-2, etc. In terms of pharmacokinetics, shikonin has an unfavorable oral bioavailability, 64.6% of the binding rate of plasma protein, and enhances some metabolic enzymes, particularly including cytochrome P450. In regard to the toxicological effects, shikonin may potentially cause nephrotoxicity and skin allergy. The above pharmacodynamics and pharmacokinetics of shikonin have been validated by few clinical trials. In addition, pharmaceutical innovation of shikonin with novel drug delivery system such as nanoparticles, liposomes, microemulsions, nanogel, cyclodextrin complexes, micelles and polymers are beneficial to the development of shikonin-based drugs. CONCLUSIONS: Shikonin is a promising phytochemical for drug candidates. Extensive and intensive explorations on shikonin are warranted to expedite the utilization of shikonin-based drugs in the clinical setting.