Search

Background: Human papillomavirus (HPV) has been considered as one of the most common sexually transmitted viruses that may be linked to unexplained infertility in men. The possible mechanisms underlying correlation between HPV infection and infertility could be related to the altered sperm parameters. Current studies have investigated the effect of HPV seminal infection on sperm quality in infertile men, but have shown inconsistent results. Methods: We systematically searched PubMed, Embase, Web of Science and CNKI for studies that examined the association between HPV seminal infection and sperm progressive motility. Data were pooled using a random-effects model. Outcomes were the sperm progressive motility rate. Results are expressed as standardised mean difference (SMD) with 95% confidence interval (CI). Heterogeneity was evaluated by the I-square (I2) statistic. Results: Ten studies were identified, including 616 infertile patients with HPV seminal infection and 2029 infertile controls without HPV seminal infection. Our meta-analysis results indicated that sperm progressive motility was significantly reduced in HPV-infected semen samples compared with non-infected groups [SMD:-0.88, 95% CI:-1.17 ~ − 0.59]. There existed statistical heterogeneity (I2 value: 86%) and the subgroup analysis suggested that study region might be the causes of heterogeneity. Conclusions: HPV semen infection could significantly reduce sperm progressive motility in infertile individuals. There were some limitations in the study such as the differences in age, sample sizes and the number of HPV genotypes detected. Further evidences are needed to better elucidate the relationship between HPV seminal infection and sperm quality. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a metabolic disorder that seriously harms human health. Notoginsenoside R1 (NGR1) can be used in various diseases. We explored consequents of NGR1 on tumour necrosis factor (TNF)-α-stimulated Min6 and rat primary islets β cells. The results were that TNF-α significantly cut down cell activity, raised cell apoptosis and iNOS expression and decreased insulin secretion in Min6 and rat primary islets β cells. NGR1 alleviated TNF-α-treated cell dysfunctions. In addition, miR-29a was positively regulated by NGR1 in TNF-α-treated Min6 and rat primary islets β cells. miR-29a knockdown damaged protection roles of NGR1 through cutting down cell activity and insulin secretion, raising apoptosis and iNOS in TNF-α-treated Min6 and rat primary islets β cells. The phosphorylation of Wnt3a, β-catenin and the rate of p/t-AKT/PI3K was all increased, while p/t-GSK3β was decreased by the administration with NGR1. In conclusion, NGR1 alleviated TNF-α-stimulated Min6 and rat primary islets β cells apoptosis and worn roles via positively regulating miR-29a. This process might be through actuation of Wnt/β-catenin and PI3K/AKT/GSK3β signal ways. [ABSTRACT FROM AUTHOR]

The adaptive immune response against hepatocellular carcinoma (HCC) could be a therapeutic target to restrain HCC initiation and growth. The interactions between hepatoma cells and immune cells modify the anti‐tumor immunity to influence hepatoma cell survival. To explore the potential interplay between hepatoma cells and anti‐HCC T‐cells, we conducted a HCC induction mouse model to analyze the phenotypic and functional alterations of T‐cell subsets. We found that both hepatoma tissues and hepatoma cell lines substantially produced higher leptin, which is an adipokine usually expressed in fat tissue, than normal liver tissue or hepatocytes. We also found that regulatory T‐cells (Tregs), effector CD4+ T‐cells and CD8+ T‐cells upregulated expression of leptin receptor (LEPR) in spleens and livers after HCC induction. In vitro study showed that macrophages and dendritic cells isolated from HCC livers upregulated LEPR expression on T‐cells. Leptin inhibited Treg activation and function in vitro, demonstrated by lower expression of TGF‐β, IL‐10, CTLA4 and GITR in Tregs, as wells weaker suppression of CD8+ T‐cell proliferation and production of cytotoxic mediators. In addition, silencing LEPR in Tregs favored tumor growth in a hepatoma cell line allograft model. Taken together, our study suggests that hepatoma cells could enhance anti‐HCC immunity through secreting leptin to down‐regulate Treg activity and subsequently promote CD8+ T‐cell response. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is the most common malignant bone tumor in children and young adults, however roles of microRNAs (miRNAs) in OS is still unclear. miR-217 is recently widely studied in various cancers, but not including OS. This study is aimed to investigate the expression and cellular function of miR-217 in OS. The data showed that miR-217 expression was consistently lower in OS tissues and cell lines than the normal controls. Restoration of miR-217 expression in MG-63 and U2OS cells could inhibit cell proliferation, migration and invasion, and induced apoptosis. Bioinformatic prediction suggested that Wnt5a is a target gene of miR-217. Using luciferase assay, mRNA and protein expression analysis, it was verified that Wnt5a was a target gene of miR-217 in OS cells. Restored expression of Wnt5a weakened miR-217-mediated suppression of tumor progression. Taken together, our data indicate that miR-217 functions as a tumor suppressor in OS by suppressing Wnt5a expression. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are key regulators in the development and progression of osteosarcoma (OS). Based on our previous microarray data, we found that miR-335 expression was downregulated in OS tissue relative to normal tissue. Herein, we further found that miR-335 was downregulated in OS cell lines relative to the osteoblastic cell line hFOB 1.19. Further functional experiments found that upregulation of miR-335 suppressed the proliferation, invasion and migration of OS cells in vitro and tumor growth and lung metastasis in vivo. In addition, the expression of a total of 750 mRNAs was decreased upon the upregulation of miR-335, and SNIP1 was found to be the direct target of miR-335. Restoration of SNIP1 expression attenuated the suppressive effect of miR-335 on OS cells. Additionally, miR-335 suppressed the mRNA and protein expression of SNIP1, MMP-2, and MMP-7 in vitro and in vivo. MiR-335 also suppressed c-Myc and NFκb p65 in vitro and in vivo. In conclusion, our data suggest that miR-335 plays a significant role in the tumorigenesis and metastasis of OS and may serve as a therapeutic target for OS treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Biopsy and pathological diagnosis are the gold standard for the diagnosis of bone and soft tissue tumors. However, in the existing biopsy process, due to the heterogeneity of tumors, we find that there is still a high failure rate. As clinicians in the field of cancer, we hope to introduce the optical biopsy of bone and soft tissue tumors through the research into near-infrared fluorescence imaging in cancer. We utilize the accumulation effect of indocyanine green in tumors and use optical biopsy to further improve the success and reduce the failure rate of skeletal muscle tumor biopsy. (1) Background: Biopsies are the gold standard for the diagnosis of musculoskeletal tumors. In this study, we aimed to explore whether indocyanine green near-infrared fluorescence imaging can assist in the biopsy of bone and soft tissue tumors and improve the success rate of biopsy. (2) Method: We recruited patients with clinically considered bone and soft tissue tumors and planned biopsies. In the test group, indocyanine green (0.3 mg/kg) was injected. After identifying the lesion, a near-infrared fluorescence camera system was used to verify the ex vivo specimens of the biopsy in real time. If the biopsy specimens were not developed, we assumed that we failed to acquire lesions, so the needle track and needle position were adjusted for the supplementary biopsy, and then real-time imaging was performed again. Finally, we conducted a pathological examination. In the control group, normal biopsy was performed. (3) Results: The total diagnosis rate of musculoskeletal tumors in the test group was 94.92% (56/59) and that in the control group was 82.36% (42/51). In the test group, 14 cases were not developed, as seen from real-time fluorescence in the core biopsy, and then underwent the supplementary biopsy after changing the puncture direction and the location of the needle channel immediately, of which 7 cases showed new fluorescence. (4) Conclusions: Using the near-infrared fluorescence real-time development technique to assist the biopsy of musculoskeletal tumors may improve the accuracy of core biopsy and help to avoid missed diagnoses, especially for some selected tumors. [ABSTRACT FROM AUTHOR]

Artemisitene (ATT) activates the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) by increasing its stabilization and reducing ubiquitination. The cysteine (Cys) residues of the cytosolic Nrf2 repressor Kelch-like ECH-associated protein-1 (Keap1) function as redox sensors and may be crucial in activating Nrf2. To determine whether ATT-induced Nrf2 activation is dependent on the modification of Keap1 and to elucidate the underlying mechanism, we transfected cell lines with six different Keap1 mutant constructs, each with a Cys (−77, −151, −257, −273, −288, and −297) to Ser substitution. Only the Cys151Ser mutant prevented ATT-mediated activation of Nrf2, indicating that the Cys151 residue of Keap1 likely interacts with ATT and is essential for Nrf2 stabilization and transcription of downstream genes. Our finding provides a pharmacological basis for using artemisitene against oxidative stress-related diseases. [ABSTRACT FROM AUTHOR]

Notch-regulated ankyrin-repeat protein (NRARP) has recently been reported to be involved in a number of malignant cancers; however, its role in non-small lung cancer (NSCLC) remains unclear. The present study aimed to identify whether NRARP could be applied as a novel prognostic marker for NSCLC. A total of 108 NSCLC patients were enrolled in the present study and their lung tissues were collected. Reverse-transcription quantitative polymerase chain reaction and immunohistochemical staining were used to assess the mRNA and protein levels of NRARP. Appropriate statistical tests were performed to evaluate the associations between NRARP protein expression and clinicopathological features and prognosis in NSCLC patients. The results revealed that NRARP expression was significantly associated with tumor differentiation (P=0.001), Tumor-Node-Metastasis stage (P=0.004) and cigarette smoking (P<0.001). Furthermore, patients with higher NRARP protein expression had signifi- cantly shorter overall survival times (P<0.001). Multivariate analysis indicated that overexpression of NRARP protein could be applied as an independent prognostic biomarker for NSCLC. In summary, the present study demonstrated that NRARP protein is overexpressed in NSCLC and that high NRARP expression is correlated with tumor progression and overall survival time. These data indicated the potential value of NRARP as a novel therapeutic target for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

As an important 5-methylcytidine (m5C) methyltransferase, NOP2/Sun RNA methyltransferase family member 6 (NSUN6) has been reported to play an important role in the progression of several diseases. However, the role of NSUN6 in the progression of osteosarcoma (OS) remains unclear. This study aimed to identify the role of NSUN6 in the progression of OS and clarify the potential molecular mechanism. The present study discovered that NSUN6 was upregulated in OS and a higher NSUN6 expression was a strong indicator for poorer prognosis of patients with OS. In addition, the loss of NSUN6 led to reduced proliferation, migration and invasion of OS cells. Through bioinformatics analysis, RNA immunoprecipitation (RIP) and methylated RIP assays, eukaryotic elongation factor 1 α-2 (EEF1A2) was identified and validated as a potential target of NSUN6 in OS. Mechanistically, the expression of EEF1A2 was significantly suppressed following NSUN6 knockdown due to reduced EEF1A2 mRNA stability in an m5C-dependent manner. Meanwhile, NSUN6 deficiency inhibited m5C-dependent activation of Akt/mTOR signaling pathway. In addition, genetic overexpression of EEF1A2 or pharmacological activation of the Akt signaling pathway counteracted the suppressive effects of NSUN6 deficiency on the proliferation, invasion and migration of OS cells. The current findings suggested that NSUN6 may serve as a potential therapeutic target for OS treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] • A bilayer dressing was prepared based on the layered stacking and patterned electrospinning technique. • The mesh-like interfacial topography effectively promoted cell adhesion and proliferation. • The system with asymmetric wettability enabled directional moisture transport and deferoxamine controllable release. • This wound dressing showed a superior therapeutic effect in the diabetic wound. Diabetic wound treatment poses significant global challenges in clinical work and research, alternative treatment approaches need to be developed urgently. Exudate management and angiogenic function are critical to improve diabetic wound healing. In this work, a Janus bilayer electrospun dressing is fabricated via modified electrospinning technologies. The outer layer of dressing is hydrophilic deferoxamine (DFO)-loaded polycaprolactone (PCL) and polyethylene glycol (PEG) random nanofiber, while the inner layer is hydrophobic PCL nanofiber with mesh-like structure and patterns, and the bilayer layers are fabricated via layer-by-layer assembly. The mechanical properties, wettability, and drug release performance of the Janus dressing were studied. Difference in wettability between the two layers enables excess biological fluid to drain away from the wound, and simultaneously trigger the cascade release of DFO in the outer layer. The in vitro data evidenced that the Janus dressing had good biocompatibility. The mesh-like inner surface is considered favorable for attachment and proliferation of fibroblast, and the controlled release of DFO significantly enhanced tube formation. In vivo results from a diabetic full-thickness cutaneous wound model showed that the Janus dressing created a unique microenvironment that accelerates the wound healing process through effective biofluid draining and stimulation of angiogenesis process. The findings indicated that the Janus dressing presented a potentially valuable method for the management and treatment of diabetic wound in clinical applications. [ABSTRACT FROM AUTHOR]

Highlights: [•] Epirubicin alter the miRNA profile in osteosarcoma cells. [•] miR-302b is low-expressed in osteosarcoma and can be induced by epirubicin treatment. [•] miR-302b induces apoptosis by caspase-3 activation and regulating several proteins. [•] miR-302b arrests cell cycle at G1 phase by decreasing cyclin D1 and CDK2/4 expression. [ABSTRACT FROM AUTHOR]

Abstract: Baicalein is a bioactive flavonoid that is widely used in ancient China. However, its effects on the most common primary malignant bone tumor, osteosarcoma, remain unknown. In the present study, we investigated the effects of baicalein in osteosarcoma cells. Our results indicate baicalein might be an efficacious anti-osteosarcoma drug. We found that baicalein could inhibit cell proliferation in a time- and dose-dependent manner. Additionally, we demonstrated that baicalein promotes osteosarcoma cell apoptosis, and our mechanistic studies suggest that this is mediated by caspase activation, especially caspase-3. We also showed that the down-regulation of Bcl-2 and concurrent increase in Bax and Bim levels contribute to the apoptosis induced by baicalein. In addition, we observed that baicalein induces G1 cell cycle arrest by decreasing cyclin D1 and cyclin-dependent kinase 4 (CDK4). Furthermore, our data verifies that baicalein can reduce osteosarcoma cell adhesion, migration and invasion in vitro, which indicates its potential to inhibit osteosarcoma metastasis. The decrease in expression of matrix metalloproteinases (MMP)-2 and MMP-9 may contribute to the effects of baicalein. Taken together, our results provide evidence that baicalein plays important roles in anti-osteosarcoma therapy, and thus may serve as a novel and efficient candidate agent for osteosarcoma treatment. [Copyright &y& Elsevier]

Asthenozoospermia is considered as a common cause of male infertility and characterized by reduced sperm motility. However, the molecular mechanism that impairs sperm motility remains unknown in most cases. In the present review, we briefly reviewed the proteome of spermatozoa and seminal plasma in asthenozoospermia and considered post-translational modifications in spermatozoa of asthenozoospermia. The reduction of sperm motility in asthenozoospermic patients had been attributed to factors, for instance, energy metabolism dysfunction or structural defects in the sperm-tail protein components and the differential proteins potentially involved in sperm motility such as COX6B, ODF, TUBB2B were described. Comparative proteomic analysis open a window to discover the potential pathogenic mechanisms of asthenozoospermia and the biomarkers with clinical significance. [ABSTRACT FROM AUTHOR]