Cordycepin Enhances the Therapeutic Efficacy of Doxorubicin in Treating Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high mortality and poor prognosis. Meanwhile, doxorubicin, a chemotherapeutic agent for triple-negative breast cancer, has poor sensitivity. The objective of this study was to examine the effect of cordycepin on doxorubicin sensitivity and efficacy in the TNBC xenograft model and explore the relevant molecular pathways. The combination of the drugs in nude mice carrying MDA-MB-231 xenografts significantly reduced the volume, size, and weight of xenografts and improved the tumor inhibition rate. The drug combination was significantly more effective than cordycepin or doxorubicin alone, reflecting the fact that cordycepin enhanced the anti-tumor effects of doxorubicin in MDA-MB-231 xenografts. At the same time, the monitoring of several biological parameters failed to detect any obvious side effects associated with this treatment. After predicting the importance of the TNF pathway in inhibiting tumor growth using network pharmacology methods, we verified the expression of TNF pathway targets via immunohistochemistry and quantitative PCR. Furthermore, a TNF-α inhibitor was able to abrogate the beneficial effects of cordycepin and doxorubicin treatment in MDA-MB-231 cells. This clearly indicates the role of TNF-α, or related molecules, in mediating the therapeutic benefits of the combined treatment in animals carrying TNBC xenografts. The observations reported here may present a new direction for the clinical treatment of TNBC.

Curcumin Alleviates Osteoarthritis Through the p38MAPK Pathway: Network Pharmacological Prediction and Experimental Confirmation.

Objective: Osteoarthritis (OA) is a common degenerative disease worldwide. While curcumin has shown therapeutic effects on OA, its mechanism remains unknown. This study aimed to investigate the molecular mechanism of curcumin in treating OA through network pharmacology and both in vivo and in vitro experiments. Methods: Curcumin-related targets were obtained using the HERB and DrugBank databases. GeneCards and DisGeNET were used to build a target database for OA. The STRING database was employed to construct protein-protein interaction networks and analyze related protein interactions. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology enrichment analyses of core targets were performed using Metascape. In addition, Autodock software was utilized for molecular docking validation of curcumin and disease targets. Further validation of the main findings was conducted through in vitro and in vivo experiments. In the in vitro experiments, an inflammation model was constructed through nitric oxide donor (SNP) stimulation of chondrocytes. Subsequently, the regulatory effects of curcumin on core targets and signaling pathways were validated using Western blotting and immunofluorescence staining techniques. In the in vivo experiments, an OA model was established by performing medial meniscectomy on male Sprague-Dawley rats. The therapeutic effects were evaluated using enzyme-linked immunosorbent assays, histologic staining, and micro-computed tomography (micro-CT) techniques. Results: Core targets of curcumin relevant to OA therapy included tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, IL-6, matrix metalloproteinase 9 (MMP-9), B-cell lymphoma 2 (BCL-2), and caspase-3. The major biological processes involved oxidative stress and apoptotic processes, among others. The p38 mitogen-activated protein kinase (p38/MAPK) pathway was identified as the most likely pathway involved. In vitro experiments showed that curcumin significantly reduced oxidative stress levels, inhibited the expression of inflammatory factors IL-6 and Cyclooxygenase-2 (COX-2) and downregulated the expression of MMP-9 and MMP-1. In addition, curcumin was found to regulate the expression of BCL-2 and caspase-3 through the p38/MAPK pathway, inhibiting chondrocyte apoptosis. In vivo animal experiments demonstrated that curcumin significantly reduced the expression of OA-related factors (IL-1, IL-6, and TNF-α). Histological analysis and micro-CT results revealed that curcumin treatment significantly increased cartilage thickness, improved cartilage morphology, structure, and function, inhibited cartilage degradation, and enhanced the resorption of subchondral bone in the knee joints of rats with OA. Conclusion: Curcumin regulates oxidative stress and maintains mitochondrial function, thereby protecting chondrocyte guard. In addition, curcumin attenuates the inflammatory response of chondrocytes by inhibiting the phosphorylation of P38MAPK, slowing down the breakdown of the extrachondral matrix while preventing apoptosis of chondrocytes. Additionally curcumin attenuated cartilage degradation and bone damage while helping to boost bone density.

Clinical characteristics and phylogenetic analysis of human enteric adenovirus type 41 (HAdV-F41) from children with gastroenteritis during SARS-CoV-2 pandemic.

Human adenovirus type 41 (HAdV-F41) usually causes pediatrics gastroenteritis. However, it was reported to be associated with the outbreaks of severe acute hepatitis of unknown aetiology (SAHUA) in pediatrics during COVID-19 pandemic. In this study, we investigated the prevalence of enteric HAdV-F41 in 37,920 paediatric gastroenteritis cases from 2017 to 2022 in Guangzhou, China. All children presented were tested negative for SARS-CoV-2 during the "zero-COVID" period. The main clinical symptom of the children was diarrhea (96.5%). No fatalities nor liver abnormal symptoms was found. In 2021, one year since the pandemic of COVID-19, the prevalence of HAdV-F41 abruptly increased from 3.71% to 8.64% (P < 0.001). All of HAdV-F41 circulating worldwide were classified into eight different subtypes (G1-G8) based on the phylogenetic clustering permutation of the four capsid genes of HAdV-F41. G3 was the predominant subtype (56.2%; 77/137). CRV5 isolates from SAHUA cases belong to this subtype, in which N312D and H335D mutations in the short fiber knob were identified in both Guangzhou and CRV5 isolates, presumably changing the virus tropism by directly interacting with the heparin sulfate (HS) receptor. Additionally, a novel recombinant G6 subtype, which is unique and only circulating in China was first identified in this study. This is the first study highlighting the prevalence of HAdV-F41 in paediatric cases of gastroenteritis during COVID-19 pandemic in China. The clinical and viral evolution finding of HAdV-F41 provide insight into the clinical characteristics of children with HAdV-F41 infections as well as the uncertain role of HAdV-F41 in the cause of SAHUA.

[Clinical comparative study on resection and non-resection of the fifth metatarsal to rheumatoid forefoot deformity].

OBJECTIVE: To explore clinical effect of the fifth metatarsal head excision and non-excision in rheumatoid arthritis (RA) forefoot deformity reconstruction. METHODS: Retrospective analysis was performed on 50 patients (76 feet) with moderate to severe forefoot deformity caused by RA treated from May 2015 to January 2019. According to degeneration of the fifth metatarsophalangeal joint,the fifth metatarsal head was retained or excised by wind-like forefoot reconstruction,and divided into the fifth metatarsal head preservation group (preservation group) and the fifth metatarsal head resection group (resection group). Twenty-four female patients in preservation group,aged from 47 to 81 years old with an average of (60.37±8.60) years old;the course of disease ranged from 13 to 22 years with an average of (19.00±3.06) years;body mass index (BMI) ranged from 21 to 28 kg·m-2 with an average of (23.53±2.47) kg·m-2;six patients (6 feet) with moderate hallux valgus deformity and 18 patients (30 feet) with severe hallux valgus deformity;treated with the first metatarsophalangeal joint fusion combined with the second th the fourth metatarsophalangeal joint arthroplasty and the fifth metatarsophalangeal joint cleanup. Twenty-six female patients in resection group were female,aged from 30 to 80 years old with an average of (58.53±13.70) years old;the course of disease ranged from 8 to 25 years with an average of (17.94±3.92) years;BMI raged from 20 to 28 kg·m-2 with an average of (24.60±2.03) kg·m-2;4 patients (4 feet) with moderate bunion valgus deformity and 22 patients (36 feet) with severe bunion valgus deformity;treated by the first metatarsophalangeal joint fusion combined with the second th the fifth metatarsophalangeal joint resection of the metatarsophalangeal head. Operation time and postoperative complications between two groups were observed,hallux valgus angle (HVA),intermetatarsal angles between the first and the second metatarsals (IMAFS),intermetatarsal angles between the first and fifth metatarsals (IMAFF),Japanese Society for Surgery of Foot (JSSF) score before surgery and at the latest follow-up were compared. RESULTS: Fifty patients were followed-up from 14 to 46(25.30±8.83) months in resection group and 12 to 48 with an average of (24.30±11.12) months in preservation group,while no significant difference between two groups (P>0.05). There were no significant difference in operation time and postoperative complications between two groups (P>0.05). JSSF scores,HVA,IMAFS and IMAFF in fesection group were improved from (45.09±3.35) points,(38.90±13.67) °,(12.88±1.72) °,(32.50±2.99) ° before operation to (81.60±3.27) points,(15.40±0.90),(9.06±2.27) °,(22.20±1.98) ° at the latest follow-up (P<0.05);preservation group were improved from (47.09±3.96) points,(43.30±12.65) °,(13.99±3.13) °,(33.20±6.14) ° to (83.10±3.66) points,(15.20±1.54) °,(8.99±1.02) °,(24.70±1.88) °,respectively. There were no significant difference in JSSF score,HVA,IMAFS and IMAFF between two groups before operation and the latest follow-up (P>0.05). At the latest follow-up,there were statistically significant differences in pain and deformity in JSSF scores between two groups (P<0.05). CONCLUSION: Both rheumatoid anterior foot reconstruction and anterior foot reconstruction fifth metatarsophalangeal joint debridement showed significant improvement in clinical efficacy and imaging results. Compared with rheumatoid prefoot reconstruction,the fifth metatarsophalangeal joint reconstruction for the treatment of moderate and severe deformity of rheumatoid prefoot showed better improvement in pain,but worse improvement in deformity. For the moderate to severe deformity of the forefoot caused by rheumatoid disease,patients with mild to moderate degenerative deformity of the articular surface of the fifth metatarsal phalanges may be considered for use.

Ultrasound assisted wall-breaking extraction and primary structures, bioactivities, rheological properties of novel Exidia yadongensis polysaccharide.

New natural multifunctional polysaccharide and its innovatory extraction technology may be urgently needed for food industries. Our aims were to establish new extraction method and investigate the primary structures, bioactivities and rheological properties of novel E. yadongensis polysaccharide (EYP). Ultrasound assisted mechanical wall-breaking extraction (MAUE) was successfully established for the EYP extraction from a new E. yadongensis. Based on the MAUE with RSM, the polysaccharide yield of 17.92 ± 0.56 % with the optimal parameters of five extraction factors were obtained, and current MAUE was characterized by its high yield, low extraction temperature and short ultrasound time. After the isolation and purification, the EYP as a protein-bound polysaccharide was obtained. FT-IR and NMR analysis showed that the main backbone of the EYP comprised of (1 â†’ 4)-ß-D-glucopyranosyl and (1 â†’ 6)-ɑ-D-mannopyranosyl groups; EYP exhibited significant antioxidant, antibacterial, antitumor, antidiabetic activities, and good viscoelastic properties in low pH solutions (P < 0.05). The EYP may be used as a natural functional and cohesive agent in food industries.

The value of urinary exosomal lncRNA SNHG16 as a diagnostic biomarker for bladder cancer.

OBJECTIVE: To detect the expression level of urinary exosomal lncRNA SNHG16 in patients with bladder cancer and healthy individuals and explore its clinical application value in the diagnosis of bladder cancer. METHODS: Urine samples were collected from 42 patients with bladder cancer and 42 healthy volunteers who visited Lu'an Hospital of Anhui Medical University and the Second Hospital of Tianjin Medical University from January 2020 to December 2022. The expression levels of lncRNA SNHG16 in urinary exosomes of the two groups were detected by RT‒qPCR, and their correlation with clinical pathological parameters of bladder cancer patients was analysed. An Receiver Operating Characteristic(ROC) curve was drawn to analyse the diagnostic value of urinary exosomal lncRNA SNHG16 for bladder cancer and compared with urinary cytology. RESULTS: The expression of urinary exosomal lncRNA SNHG16 in patients with bladder cancer was significantly higher (P < 0.05), and the expression level had no correlation with the age, sex, pathological T stage, pathological grade, or tumour size of bladder cancer patients (P > 0.05). The Area Under Curve(AUC) of urinary exosomal lncRNA SNHG16 in diagnosing bladder cancer was 0.791, which was superior to that of urinary cytology (AUC = 0.597). CONCLUSION: Urinary exosomal lncRNA SNHG16 with high expression can serve as a potential diagnostic biological marker for bladder cancer.

Identification of three elevenin receptors and roles of elevenin disulfide bond and residues in receptor activation in Aplysia californica.

Neuropeptides are ubiquitous intercellular signaling molecules in the CNS and play diverse roles in modulating physiological functions by acting on specific G-protein coupled receptors (GPCRs). Among them, the elevenin signaling system is now believed to be present primarily in protostomes. Although elevenin was first identified from the L11 neuron of the abdominal ganglion in mollusc Aplysia californica, no receptors have been described in Aplysia, nor in any other molluscs. Here, using two elevenin receptors in annelid Platynereis dumerilii, we found three putative elevenin GPCRs in Aplysia. We cloned the three receptors and tentatively named them apElevR1, apElevR2, and apElevR3. Using an inositol monophosphate (IP1) accumulation assay, we demonstrated that Aplysia elevenin with the disulfide bond activated the three putative receptors with low EC50 values (ranging from 1.2 to 25 nM), supporting that they are true receptors for elevenin. In contrast, elevenin without the disulfide bond could not activate the receptors, indicating that the disulfide bond is required for receptor activity. Using alanine substitution of individual conserved residues other than the two cysteines, we showed that these residues appear to be critical to receptor activity, and the three different receptors had different sensitivities to the single residue substitution. Finally, we examined the roles of those residues outside the disulfide bond ring by removing these residues and found that they also appeared to be important to receptor activity. Thus, our study provides an important basis for further study of the functions of elevenin and its receptors in Aplysia and other molluscs.

Study on naked eye tracing of inguinal sentinel lymph nodes in penile cancer patients with carbon nanoparticle suspension injection.

Objective: Exploratory study of the effect and clinical value of carbon nanoparticle suspension injection (CNSI) as a tracer for inguinal sentinel lymph nodes in penile cancer. Method: We selected 29 patients with penile cancer in our department from January 2019 to October 2022. According to whether the CNSI tracer was injected during the pathological biopsy of the inguinal lymph nodes, the enrolled patients were assigned to the control group, the group in which CNSI was injected 12 h before the surgery (12HBS group) and the group in which CNSI was injected 0.5 h before the surgery (0.5HBS group). Evaluating the effectiveness of CNSI as a lymphatic tracer involves analyzing the following: its safety, the statistical analysis of the detection rate (DR) of different groups, the number of lymph nodes sent for each case (NOLNSFEC), the difference of positive rate of lymphatic metastasis (PROLM), and operation time (OT). Results: The lymph nodes in the 12HBS group and 0.5HBS group had an obvious black staining appearance, and no adverse reactions or surgical complications were found. Most of the black-stained areas caused by CNSI injection were removed with penile excision, which did not affect the postoperative appearance. This did not affect the pathological analysis. The DR of lymph nodes in the 12HBS group was higher (p < 0.05) than that in the control group. More lymph nodes were removed for examination (p < 0.05), which improved the efficiency of surgery. Compared with the 12HBS group, the number of lymph nodes removed in the 0.5HBS group decreased (p < 0.05). The OT was shortened (p < 0.05), but there was no significant difference in the DR and PROLM. Conclusion: CNSI was applied to the naked-eye tracing of inguinal sentinel lymph nodes in penile cancer, which is safe and efficient. Injection of CNSI 0.5 h before surgery can help identify the "foremost position" of sentinel lymph nodes and reduce surgical trauma.

Combined central retinal vascular occlusion as the presenting feature in ß-thalassemia with iron deficiency anemia.

PURPOSE: To report a case of ß-thalassemia trait (ß-TT) with iron deficiency anemia (IDA) presenting as a combined central retinal vein and artery occlusion (CCRVAO). METHODS: Case report. A 22-year-old female presented with sudden-onset blurry vision in the left eye of 3-days duration. RESULTS: Best corrected visual acuity was 20/20 and 20/1000 in right and left eyes, respectively. Fundus examination of left eye revealed optic disc edema, macular whitening with a cherry-red spot, markedly dilated and tortuous retinal veins, and hemorrhages both around the disc and extending into the macula and the periphery. Fundus fluorescein angiography (FFA) showed delayed filling of retinal vasculature, dilated and tortuous retinal veins, blocked fluorescence around and beyond the optic disc. OCT scan at presentation showed hyperreflective inner retinal layers with neurosensory detachment. OCTA showed that the vessel densities of superficial and deep capillary plexus were remarkably reduced.A diagnosis of ß-TT combined with IDA was made after hematologic work-up. The patient was treated with a course of oral iron supplements, vasodilator (Compound Xueshuantong), inhalation of a mixture of 5% carbon dioxide and 95% oxygen, and a nutritional agent (compound anisoine). By six months later, her visual acuity improved to 20/60 in the left eye with complete resolution of all clinical signs. CONCLUSION: CCRVAO is a rare emergency leading to acute vision loss and can manifest in patients with ß-TT with IDA. Prompt diagnosis and early management is important to treat underlying systemic disorders and to prevent occurrence of a similar episode in fellow eye.

Study on Transorgan Regulation of Intervertebral Disc and Extra-Skeletal Organs Through Exosomes Derived From Bone Marrow Mesenchymal Stem Cells.

Exosomes are membranous lipid vesicles fused with intracellular multicellular bodies and then released into the extracellular environment. They contain various bioactive substances, including proteins, mRNA, miRNAs, lncRNAs, circRNAs, lipids, transcription factors, and cytokine receptors. Under certain conditions, bone marrow mesenchymal stem cells (BMSCs) can differentiate into osteoblasts, chondrocytes, adipocytes, and biological functions. This study provides a theoretical basis for the application of exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) in osteology, exploring different sources of exosomes to improve bone microenvironment and resist bone metastasis. We also provided new ideas for the prevention and rehabilitation of human diseases by exosomes.

Protective effects of intravitreal administration of mesenchymal stem cell-derived exosomes in an experimental model of optic nerve injury.

Traumatic optic neuropathy results in the loss of retinal ganglion cells (RGCs), leading to unavoidable visual impairment. However, there is no effective therapy by far. Accumulated studies support the perception that mesenchymal stem cells (MSCs) secrete exosomes that serve as a protective paracrine factor. The study aimed to explore and evaluate the potential therapeutic effects of intravitreal transplantation of MSC-derived exosomes (MSC-exos) in an experimental model of optic nerve crush (ONC). Exosomes were isolated from rat MSCs and characterized by transmission electron microscope and western blotting. At the onset of ONC, a single intravitreal injection of exosomes or PBS was administered to the rats. At day 30, hematoxylin and eosin staining, immunohistochemistry, and ßIII-tubulin staining were performed to evaluate the survival of RGCs. Moreover, TUNEL assay was used to examine the apoptosis of RGCs. Inflammation-relevant factors were identified via quantitative polymerase chain reaction. The expression levels of cell apoptosis-related molecules and key members of the PI3K/AKT signaling pathway were determined via western blot analysis. We found that MSC-exos exhibited typical characteristic morphologies (cup-shaped) and sizes (peak size of 93 nm). Furthermore, they exhibited substantial expression of the exosome markers CD63 and TSG101, but lacked the expression of the cellular marker GM130. Treatment with intravitreal MSC-exos notably promoted the survival of RGCs in ONC rats. The level of pro-inflammatory cytokines, including TNF-α, IL-1ß, IL-6, IL-8, and MCP-1, were reduced, whereas those of the anti-inflammatory factor IL-10 were increased. Moreover, the apoptosis induced by ONC was decreased by the administration of MSC-exos via upregulation of the Bcl-2/Bax ratio and downregulation of caspase-3 activity. Furthermore, MSC-exos significantly stimulated AKT phosphorylation, whereas LY294002 restored the apoptosis-preventing effects of MSC-exos. The results of our results demonstrated that intravitreal administration of MSC-exos ameliorates ONC-induced injury in a rat model. These findings might aid in the development of effective exosome-based therapeutic strategies for the treatment of optic nerve degeneration.

Downregulation of high mobility group box 1 enhances the radiosensitivity of non-small cell lung cancer by acting as a crucial target of microRNA-107.

High mobility group box 1 (HMGB1) has been reported to regulate the sensitivity of several types of cancer cell to chemoradiotherapy. The present study aimed to investigate the changes in HMGB1 expression after radiotherapy, as well as its regulatory role in the radiosensitivity of non-small cell lung cancer (NSCLC) cells. The expression levels of HMGB1 in the serum of 73 patients with NSCLC were analyzed by ELISA. HMGB1 mRNA and microRNA (miR)-107 expression in NSCLC cells were assessed using reverse transcription-quantitative PCR. Receiver operating characteristic analysis was used to evaluate the diagnostic value of HMGB1. Cell counting kit-8, Transwell invasion and clonogenic assays were used to determine cellular viability, invasiveness and colony formation ability, respectively. Following radiotherapy, the levels of HMGB1 were significantly decreased in the serum of patients with NSCLC, and lower serum levels had relatively high diagnostic accuracy in radiosensitive patients. Furthermore, HMGB1-knockdown retarded cellular proliferation and invasion with or without irradiation, and enhanced NSCLC cell radiosensitivity. Furthermore, knocking down miR-107 reversed the decreases in cellular proliferation and invasiveness both with and without irradiation, and reduced the survival fractions induced by sh-HMGB1. HMGB1-knockdown leads to radiosensitivity that may result from suppression of the Toll-like receptor 4 (TLR4)/NF-κB signaling pathway. Collectively, decreased expression of HMGB1 was found to be a putative diagnostic predictor of radiosensitivity in patients with NSCLC. HMGB1-knockdown inhibited the proliferation and enhanced the radiosensitivity of NSCLC cells, which may be regulated via miR-107 by mediating the TLR4/NF-κB signaling pathway. Thus, HMGB1 may be a potential regulator of radioresistance in NSCLC, and the HMGB1/miR-107 axis may represent a promising therapeutic target.

Phlebopus roseus, a new edible bolete from China, is associated with insects and plants.

Phlebopus roseus is described as new based on collections from southwest China. Phylogenetic analyses of nuclear rDNA internal transcribed spacer region ITS1-5.8S-ITS2 (ITS) and portions of nuclear 28S rDNA (28S), translation elongation factor 1-alpha (tef1), and the largest and second largest subunits of RNA polymerase II (rpb1, rpb2) support P. roseus as a novel species in the genus Phlebopus (Boletinellaceae, Boletales). The new species resembles P. portentosus but differs from it in that mature basidiomata have a bright rose-red-colored stipe and a radiate tubular hymenophore with nested pores. Despite extensive searching, P. roseus has only been found at four sites within a 24-hectare orchard dominated by Eriobotrya japonica, which is agriculturally important given its fruit production (loquats). Therefore, this species appears to be endemic and geographically restricted. The ecology of this bolete is also unique. In line with the trophic behavior of other species in the Boletinellaceae, our observations indicate that P. roseus forms a symbiotic association with the scale insect Coccus hesperidum, identified through sequence analysis of its mitochondrial cytochrome c oxidase subunit I (COI) region, to form fungus-insect galls that develop on roots of E. japonica trees. Phlebopus roseus is an edible mushroom species and is collected from the type location by farmers and sold commercially in limited quantities at local markets alongside P. portentosus and other fungi.

Long-Term Exercise Alters the Profiles of Circulating Micro-RNAs in the Plasma of Young Women.

Objective: The objective of this paper was to study the effects of long-term exercise on circulating microRNAs (miRNAs) in human plasma. Methods: Whole blood was collected from 10 female elite athletes with at least 5 years of training experience in a Synchronized Swimming Group (S group) and 15 female college students without regular exercise training (C group). Plasma miRNAs were then isolated, sequenced, and semi-quantified by the second-generation sequencing technology, and the results were analyzed by bioinformatics methods. Results: We found 380 differentially expressed miRNAs in the S group compared with the C group, among which 238 miRNAs were upregulated and 142 were downregulated. The top five abundant miRNAs in the 380 miRNAs of the S group are hsa-miR-451a, hsa-miR-486, hsa-miR-21-5p, hsa-miR-423-5p, and hsa-let-7b-5p. Muscle-specific/enriched miRNAs were not significantly different, except for miR-206 and miR-486. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, a large proportion of the differentially expressed miRNAs are targeted in cancer-related pathways, including proteoglycans in cancer and miRNAs in cancer and basal cell carcinoma. As the levels of circulating miRNAs (ci-miRNAs) are commonly known to be significantly deregulated in cancer patients, we further compared the levels of some well-studied miRNAs in different types of cancer patients with those in the S group and found that long-term exercise regulates the level of ci-miRNAs in an opposite direction to those in cancer patients. Conclusion: Long-term exercise significantly alters the profiles of plasma miRNAs in healthy young women. It may reduce the risk of certain types of cancers by regulating plasma miRNA levels.

The choice of anti-tumor strategies based on micromolecules or drug loading function of biomaterials.

With advances in modern medicine, diverse tumor therapies have been developed. However, because of a lack of effective methods, the delivery of drugs or micromolecules in the human body has many limitations. Biomaterials are natural or synthetic functional materials that are prone to contact or interact with living systems. Therefore, the application of biomaterials provides innovative anti-tumor strategies, especially in tumor targeting, chemotherapy sensitization, tumor immunotherapy. The combination of biomaterials and drugs provides a promising strategy to overcome the biological barriers of drug delivery. Nanomaterials can target specific tumor sites to enhance the efficiency of tumor therapies and decrease the toxicity of drug through passive targeting, active targeting and direct targeting. Additionally, biomaterials can be used to enhance the sensitivity of tumor cells to chemotherapy drugs. Furthermore, modifiable biomaterials can induce effective anti-tumor immune response. Currently, the developmental trend of biomaterial for drug delivery is motivated by the combination and diversification of different therapies. With interdisciplinary development, a variety of anti-tumor strategies will emerge in an endless stream to bring great hope for tumor therapy. In this review, we will discuss the anti-tumor strategies based on nanoparticles and injectable scaffolds.

Natural cordycepin induces apoptosis and suppresses metastasis in breast cancer cells by inhibiting the Hedgehog pathway.

In the study, we investigated the role of the hedgehog (Hh) pathway in cordycepin's effects on human breast cancer cells, with respect to cell growth, apoptosis and metastasis. We found cordycepin to have low toxicity but significant anticancer effects. Cordycepin-induced apoptosis led to increased PUMA, CYTO-C, FAS, DR4/5, and cleaved caspase-3; and decreased BCL-2, XIAP and PDGFR-α. Cordycepin inhibited metastasis, which was associated with up-regulated E-cadherin, and down-regulated N-cadherin, SNAIL, SLUG and ZEB1. Cordycepin also inhibited expression of Hh pathway components and GLI transcriptional activity. Inversely, knockout of GLI blocked cordycepin-mediated effects on the apoptotic, epithelial-mesenchymal transition (EMT) and Notch pathways, which indicates that GLI is crucial for cordycepin's effects against breast cancer. Inhibition of GLI enhanced cordycepin's effect on breast cancer cell growth. To our knowledge, this is the first study of cordycepin's effect on the Hh pathway in breast cancer, and provides preliminary data for the in vivo study, and possible therapeutic use, of cordycepin.

Malignant ureteral obstruction: experience and comparative analysis of metallic versus ordinary polymer ureteral stents.

BACKGROUND: To study the outcome and experience of using metallic stents in treating patients with malignant ureteral obstruction (MUO). METHODS: Seventy-six patients with MUO were assigned to the metallic stent group (MSG) or the ordinary polymer stent group (OPSG) according to the different materials. The success rate of the operation, duration of operation, patency rate serum creatinine values ,postoperative complications and QOL scores were compared between the two groups. RESULTS: In the OPSG and MSG, the success rates of the operation were 95.5% and 96.9%, respectively, and the durations of the operation were 20.6 ± 2.2 min and 50.9 ± 10.3 min (P < 0.01), respectively. There was no significant difference between the groups in serum creatinine values at 3 days after the operation (P > 0.05); however, the creatinine values at 3 days after the operation decreased significantly compared with those before the operation (P < 0.01). In the OPSG, there was no significant difference in creatinine values between 3 days and 6 months after operation, while the creatinine values 1 year after operation were increased significantly compared to those at 3 days after the operation (P < 0.05). In the MSG, there was no significant difference among creatinine values at different intervals (P > 0.05). The total rate of post-procedural complication was lower in the MSG than that in the OPSG(P < 0.05). There was no significant difference in the QOL score between the two groups before the operation (P > 0.05); however, the QOL scores at 6 months and 1 year after the operation were higher in the MSG than that in the OPSG(P < 0.05). In the MSG, there was no significant difference in the QOL score between preoperation and 6 months after surgery. Similarly, there was also no difference in the QOL score between 6 months after surgery and 1 year after surgery(P > 0.05). On the contrary, the differences of QOL score in the OPSG group were much significant between disparate time intervals (P < 0.05). CONCLUSIONS: For patients with MUO who require long-term retention of the stent, metallic stents with longer indwelling time are superior to ordinary polymeric stents.

B7-H4 expression and its role in interleukin-2/interferon treatment of clear cell renal cell carcinoma.

The immunological mechanism mediated by T cells is the main therapeutic target in the treatment of renal cell carcinoma (RCC) with interleukin (IL)-2 and interferon (IFN)-α. The aim of the present study was to evaluate the role of B7-H4 in the IL-2, IFN-α and IFN-γ treatment of clear cell RCC (ccRCC). A total of 154 paraffin-embedded ccRCC tissues were studied using immunohistochemistry, which subsequently indicated that positive B7-H4 expression is associated with adverse clinical features in ccRCC. The effects of IL-2, IFN-α and IFN-γ on B7-H4 expression in a ccRCC cell line were evaluated at the mRNA and protein levels. In addition, the effect of B7-H4 on the killing activity of T cells was detected. B7-H4 expression was identified to be upregulated by IL-2, IFN-α and IFN-γ, of which, IFN-γ was the most capable. Additionally, blocking of B7-H4/B7-H4 ligand interactions may rescue the killing activity of T cells. Altogether, the observations of the current study showed that the immune escape pathway induced by B7-H4 may be one of the most important reasons for the low efficacy of IL-2 and IFN-α and the inability to observe the efficacy of IFN-γ in mRCC. This indicates that B7-H4 may be used as a new molecular biology marker to select treatment options for patients with ccRCC.

Roles of autophagy-related genes Beclin-1 and LC3 in the development and progression of prostate cancer and benign prostatic hyperplasia.

Prostate cancer (PCa) is common in Western populations and the second leading cause of cancer-related mortality among males in North America, with an increasing morbidity in China and other Asian countries. The aim of this study was to evaluate the protein expression of autophagy-related genes Beclin-1 and LC3 in patients with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and elucidate their association with p53 and Bcl-2. The total protein of 34 PCa and 50 BPH samples was extracted and the expression of Beclin-1 and LC3 was analyzed by western blotting assay. Subsequently, a total of 96 paraffin-embedded BPH tissue samples was subdivided into 2 groups, one group in which patients had received 5α-reductase inhibitor, due to its effect of androgen ablation, and the control group, in which patients had not received the 5α-reductase inhibitor. The samples were randomly collected and examined using immunohistochemical (IHC) analysis. The western blot analysis demonstrated that Beclin-l and LC3 expression was higher in BPH tissues compared to PCa tissues (P<0.001). There was no statistically significant difference between PCas of different Gleason scores (P>0.05). The result of IHC revealed that Beclin-l and LC3 expression in the group of patients who had received the 5α-reductase inhibitor was significantly higher compared to that in the control group; however, the expression of Bcl-2 and p53 was lower (P<0.05). Beclin-1 expression exhibited a negative correlation with Bcl-2 (r=-0.402, P<0.001), whereas LC3 expression exhibited a positive correlation with Beclin-1 (r=0.345, P=0.001) and a negative correlation with Bcl-2 (r=-0.216, P=0.035). It was suggested that autophagy-related genes Beclin-l and LC3 may be involved in the development and progression of PCa. In addition, the expression of these genes was higher in patients with BPH who had received a 5α-reductase inhibitor, due to androgen reduction. As a result, the induced autophagy may reduce the risk of PCa.

HER2 expression in renal cell carcinoma is rare and negatively correlated with that in normal renal tissue.

The aim of this study was to evaluate the status of HER2 protein expression in patients with renal cell carcinoma (RCC) and to determine its prognostic significance. A total of 42 paraffin-embedded tumor tissues and 42 additional corresponding adjacent normal tissues from RCC patients were randomly collected and studied using immunohistochemistry (IHC). Protein samples of 6 fresh specimens from tumor and adjacent normal tissues obtained during surgery were extracted and tested using western blotting to confirm the IHC results. Of the 42 tumor tissues and adjacent normal tissues tested, IHC showed that 7 tumors (16.67%) and 33 adjacent normal tissues (78.57%) expressed the HER2 protein. In addition, results of the western blotting revealed weak HER2 reactivity in primary tumor cells in two of 6 specimens obtained during surgery. All 6 normal tissues showed positive expression, which was in accordance with the outcome of IHC. In conclusion, HER2 is frequently expressed in normal renal tissues and rarely expressed in RCC tissues. Furthermore, the HER2 status of normal tissue is negatively correlated with that of the RCC tissues (r=-0.410, P=0.007) and the TNM stage (r=-0.246, P=0.027), suggesting that HER2 is involved in RCC oncogenesis.