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Male hypogonadism is associated with reduced quality of life and the development of co-morbidities including obesity, diabetes mellitus, and dyslipidaemia. The mainstay of treatment for male hypogonadism is testosterone replacement therapy (TRT). However, TRT has recognised side effects including impaired spermatogenesis and there are concerns regarding its use in men with concurrent cardiovascular disease. Thus, there has been an impetus to develop novel androgen therapies for treating male hypogonadism to mitigate the side effects of TRT. This review will discuss the benefits and adverse effects of TRT, and novel therapies including nasal testosterone, aromatase inhibitors, selective oestrogen receptor modulators, and selective androgen receptor modulators.

Prostate cancer is one of the most frequently diagnosed malignancies in men worldwide and the life expectancy for men with prostate cancer is improving due to advancements in diagnostics and treatment. Male hypogonadism is associated with obesity, diabetes, and other comorbidities and also has been linked with increasing age; the primary therapy modality for this condition is testosterone replacement therapy (TRT). There are concerns that testosterone therapy may cause prostate cancer disease progression. However, contemporary evidence suggests that testosterone replacement therapy may be safe in specific groups of patients with prostate cancer. This chapter will summarise the contemporary literature regarding TRT use in hypogonadal men with prostate cancer, including limitations and future research goals.

BACKGROUND Osteoarthritis (OA) is a degenerative disease characterized by cartilage damage. We aimed to improve the understanding of the protective mechanism of synovial mesenchymal stem cell (SMSC)-derived extracellular vesicles (EVs) in cartilage damage of OA. METHODS SMSCs and SMSC-EVs were isolated from synovial biopsies of patients without OA and then identified. The pathological microenvironment of chondrocytes in OA was simulated by inducing SW1353 cells with interleukin (IL)-1β, followed by SMSC-EV treatment to assess SW1353 cell proliferation, apoptosis and inflammation. Endocytosis of Dil-labeled EVs by SW1353 cells was observed. microRNA (miR)-26a-5p expression in EVs and EV-treated SW1353 cells was assessed. The effect of miR-26a-5p was evaluated after it was down-regulated in SMSCs, followed by extraction of EVs, which acted on SW1353 cells. The target relationship of miR-26a-5p and phosphatase and tensin homologue (PTEN) was predicted and confirmed. The role of PTEN in OA was evaluated after it was overexpressed. Functional assays were implemented in vivo to certify the role of SMSC-EVs in OA. RESULTS SMSC-EVs enhanced IL-1β-induced SW1353 cell proliferation, whereas they inhibited apoptosis and inflammation. EVs were endocytosed by SW1353 cells and delivered miR-26a-5p into SW1353 cells to overexpress miR-26a-5p. Down-regulation of miR-26a-5p in EVs attenuated the protection of EVs against IL-1β-induced cell damage. miR-26a-5p targeted PTEN, for which overexpression spoiled the protection of EVs against IL-1β-induced cell damage. SMSC-EVs carrying miR-26a-5p repaired cartilage damage of OA. CONCLUSIONS SMSC-EVs carried miR-26a-5p into chondrocytes to up-regulate miR-26a-5p and inhibit PTEN, thereby inhibiting apoptosis and inflammation and ameliorating cartilage damage of OA.

Background Ex vivo and in vivo detection and imaging of adenosine triphosphate (ATP) is critically important for the diagnosis and treatment of diseases, which still remains challenges up to present. Results We herein demonstrate that ATP could be fluorescently detected and imaged ex vivo and in vivo. In particular, we fabricate a kind of fluorescent ATP probes, which are made of titanium carbide (TC) nanosheets modified with the ROX-tagged ATP-aptamer (TC/Apt). In the constructed TC/Apt, TC shows superior quenching efficiency against ROX (e.g., ~ 97%). While in the presence of ATP, ROX-tagged aptamer is released from TC surface, leading to the recovery of fluorescence of ROX under the 545-nm excitation. Consequently, a wide dynamic range from 1 μM to 1.5 mM ATP and a high sensitivity with a limit of detection (LOD) down to 0.2 μM ATP can be readily achieved by the prepared TC/Apt. We further demonstrate that the as-prepared TC/Apt probe is feasible for accurate discrimination of ATP in different samples including living cells, body fluids (e.g., mouse serum, mouse urine and human serum) and mouse tumor models. Conclusions Fluorescence detection and imaging of ATP could be readily achieved in living cells, body fluids (e.g., urine and serum), as well as mouse tumor model through a new kind of fluorescent ATP nanoprobes, offering new powerful tools for the treatment of diseases related to abnormal fluctuation of ATP concentration.

Outcomes in partial sternotomy for aortic root surgery: the new routine procedure?Running Head: Partial sternotomy for aortic root repair

MicroRNAs (miRNAs) are promising biomarkers for the early diagnosis of breast cancer. Yet, simultaneous achievement of rapid, sensitive and accurate detection of diverse miRNAs in clinical samples is still challenging due to the low abundance of miRNAs and the complex procedures of RNA extraction and separation. Herein, we develop an innovative three-dimensional (3D) surface-enhanced Raman scattering (SERS) holography sensing strategy for rapid, sensitive and multiplexed detection of human breast cancer-associated miRNAs. To establish a proof of concept, nine kinds of human breast cancer-associated miRNAs are isothermally amplified by Exonuclease (Exo) III enzyme, and the products could be spatially separated to corresponding sensing region on silicon SERS substrates. Each region has been modified with corresponding hairpin DNA probes, which are used to identify and quantify the miRNAs. Different DNA probes are labeled with different Raman reporters, which serve as “SERS tags” to incorporate spectroscopic information into computer-generated 3D SERS hologram within ~9 min. We demonstrate that 3D SERS holography chip not only achieves an ultrahigh sensitivity down to ~1 aM but also feature a high correlation with RT-qPCR in the detection of nine miRNAs in 30 clinical serum samples. This work provides a feasible tool to improve the diagnosis of breast cancer.

In this manuscript, we demonstrate that the in situ growth of fluorescent silicon (Si) nanomaterials is stimulated when organosilicane molecules interact with different green teas, producing multifunctional Si nanomaterials with controllable zero- (e.g., nanoparticles), two- (e.g., nanosheets), and three- (e.g., nanospheres) dimensional nanostructures. Such green tea-originated Si nanomaterials (GTSN) exhibit strong fluorescence (quantum yield: ∼19-30%) coupled with ultrahigh photostability, as well as intrinsic anti-cancer activity with high specificity (e.g., the GTSN can accurately kill various cancer cells, rather than normal cells). Taking advantage of these unique merits, we further performed systematic in vitro and in vivo experiments to interrogate the mechanism of the green tea- and GTSN-related cancer prevention. Typically, we found that the GTSN entered the cell nuclei and induced cell apoptosis/death of cancer cells. The prepared GTSN were observed in vivo to accumulate in the tumour tissues after 14-d post-injection, leading to an efficient inhibition of tumour growth. Our results open new avenues for designing novel multifunctional and side-effect-free Si nanomaterials with controllable structures.

Herein, we present a dual-amplification sensing strategy-based surface-enhanced Raman scattering (SERS) chip, which combines rolling circle amplification (RCA) and polyadenine (PolyA) assembly for sensitive and reproducible determination of the activity of M.SssI, a cytosine-guanine dinucleotide (CpG) methyltransferase (MTase). Typically, in the presence of M.SssI, RCA process is triggered, resulting in long, single-stranded DNA (ssDNA) fragments that are hybridized with thousands of Raman reporters of Cy3. Afterward, the resultant ssDNA fragments are conjugated to SERS-active substrates made of silver core-gold satellite nanocomposites-modified silicon wafer (Ag-Au NPs@Si), with the SERS enhancement factor of ∼5 × 106. The core-satellite nanostructures are assembled relied on the strong affinity of PolyA toward gold/silver surface. Of particular significance, the developed SERS chip displays an ultrahigh sensitivity with a low limit of detection (LOD) of 2.8 × 10-3 U/mL, which is around 2 orders of magnitude higher than most reported methods. In addition, the constructed chip features a broad detection range covering from 0.05 to 50 U/mL. Besides for the ultrahigh sensitivity and broad dynamic range, the chip also features good reproducibility (e.g., the relative standard deviation (RSD) is less than ∼12%). Taking advantages of these merits, the developed chip is feasible for accurate discrimination of M.SssI with various concentrations spiked in human serum samples with good recoveries ranging from 99.6% to 107%.