Transcriptomic characterization of interactions between sodium selenite and coenzyme Q10 on preventing cadmium-induced testicular defects.

The effect of heavy metal cadmium (Cd) on testicular function is recognized. However, the mechanism involved is not well-established. In the present study, we analyzed the testicular transcriptomic changes induced by acute Cd exposure of adult rats with and without supplementation of antioxidants selenium (Se) and/or coenzyme Q10 (CoQ). Cd significantly decreased serum testosterone and two steroidogenic proteins SCARB1 and STAR. RNA-Seq analyses of testicular RNAs revealed specific activation of oxidative stress-, inflammation-, MAPK- and NF-κB-related signaling molecules. In addition, Cd treatment down-regulated gene for I, III and IV complexes of mitochondrial electron transport chain and up-regulated genes for NADPH-oxidase, major cascade in ROS production. The decrease in steroidogenesis and increase in inflammation may result from oxidative stress since supplementation of Se and CoQ, but not with either alone, almost completely prevented these changes, including overall alterations in transcriptome. Cd exposure induced total of 1192 differentially expressed genes (DEGs), which was reduced to 29 without considering confounding factors associated with Se/CoQ, a 97.6% protection rate. In conclusion, Cd exposure inhibited Leydig cell steroidogenesis by down-regulating SCARB1 and STAR through increasing oxidative stress and inflammation, but Se plus CoQ synergistically prevented all the changes induced by the Cd exposure.

Hydrogel Combined with Phototherapy in Wound Healing.

Wound healing is a complex biological process that involves tissue regeneration. Traditional wound dressings are dry, cannot provide a moist environment for wound healing, and do not have high antibacterial properties. Hydrogels, which are capable of retaining large amounts of water, can create a moist healing environment. Currently, phototherapies have exhibited a high potential for the treatment of bacterial infections. Therefore, combining hydrogels with phototherapy can adequately overcome the shortcomings of traditional wound treatment methods and show great potential for wound healing owing to their high efficiency, low irritation, and good antibacterial performance. In this review, the application of hydrogels combined with phototherapy in wound healing is summarized. First, the basic principles of photodynamic therapy and photothermal therapy are briefly introduced. In addition, the progress of the application of hydrogel combined with phototherapy in wound healing is systematically investigated. Finally, the challenges and prospects of combining hydrogel with phototherapy in wound healing are discussed.

Low NAD+ Levels Are Associated With a Decline of Spermatogenesis in Transgenic ANDY and Aging Mice.

Advanced paternal age has increasingly been recognized as a risk factor for male fertility and progeny health. While underlying causes are not well understood, aging is associated with a continuous decline of blood and tissue NAD+ levels, as well as a decline of testicular functions. The important basic question to what extent ageing-related NAD+ decline is functionally linked to decreased male fertility has been difficult to address due to the pleiotropic effects of aging, and the lack of a suitable animal model in which NAD+ levels can be lowered experimentally in chronologically young adult males. We therefore developed a transgenic mouse model of acquired niacin dependency (ANDY), in which NAD+ levels can be experimentally lowered using a niacin-deficient, chemically defined diet. Using ANDY mice, this report demonstrates for the first time that decreasing body-wide NAD+ levels in young adult mice, including in the testes, to levels that match or exceed the natural NAD+ decline observed in old mice, results in the disruption of spermatogenesis with small testis sizes and reduced sperm counts. ANDY mice are dependent on dietary vitamin B3 (niacin) for NAD+ synthesis, similar to humans. NAD+-deficiency the animals develop on a niacin-free diet is reversed by niacin supplementation. Providing niacin to NAD+-depleted ANDY mice fully rescued spermatogenesis and restored normal testis weight in the animals. The results suggest that NAD+ is important for proper spermatogenesis and that its declining levels during aging are functionally linked to declining spermatogenesis and male fertility. Functions of NAD+ in retinoic acid synthesis, which is an essential testicular signaling pathway regulating spermatogonial proliferation and differentiation, may offer a plausible mechanism for the hypospermatogenesis observed in NAD+-deficient mice.

NIR-II Responsive Molybdenum Dioxide Nanosystem Manipulating Cellular Immunogenicity for Enhanced Tumor Photoimmunotherapy.

Photothermal therapy (PTT) in the second near-infrared (NIR-II) window has emerged as a better candidate for deep-tissue tumor elimination. More interestingly, the photothermal ablated tumor cells also manifest somewhat immunostimulation potency to elicit antitumor immunity, although most dying cells are undergoing apoptosis that is commonly considered as immunologically silent. Here, a NIR-II responsive nanosystem is established for tumor photoimmunotherapy using molybdenum dioxide (MoO2) nanodumbbells as the nanoconverter. Meanwhile, an apoptosis-blocking strategy is proposed to regulate the cell death pattern under NIR-II laser irradiation in order to improve the immunogenic cell death. The nanoformulation can efficiently block caspase 8-dependent apoptotic pathway in photothermal ablated tumor cells and transform into more immunogenic death patterns, thereby activating systemic immunity to inhibit tumor growth and metastasis. In addition, this strategy also helps enhance the body's responses to α-PD-1 immune checkpoint inhibitor, which implies a potential optimal combination for cancer immunotherapy.

Carbon Dots with Intrinsic Bioactivities for Photothermal Optical Coherence Tomography, Tumor-Specific Therapy and Postoperative Wound Management.

Carbon dots (CDs) are considered as promising candidates with superior biocompatibilities for multimodel cancer theranostics. However, incorporation of exogenous components, such as targeting molecules and chemo/photo therapeutic drugs, is often required to improve the therapeutic efficacy. Herein, an "all-in-one" CDs that exhibit intrinsic bioactivities for bioimaging, potent tumor therapy, and postoperative management is proposed. The multifunctional CDs derived from gallic acid and tyrosine (GT-CDs) consist of a graphitized carbon core and N, O-rich functional groups, which endow them with a high near-infrared (NIR) photothermal conversion efficiency of 33.9% and tumor-specific cytotoxicity, respectively. A new imaging modality, photothermal optical coherence tomography, is introduced using GT-CDs as the contrast agent, offering the micrometer-scale resolution 3D tissue morphology of tumor. For cancer therapy, GT-CDs initiate the intracellular generation of reactive oxygen species in tumor cells but not normal cells, further induce the mitochondrial collapse and subsequent tumor cellular apoptosis. Combined with NIR photothermal treatment, synergistic antitumor therapy is achieved in vitro and in vivo. GT-CDs also promote the healing process of bacteria-contaminated skin wound, demonstrating their potential to prevent postoperative infection. The integrated theranostic strategy based on versatile GT-CDs supplies an alternative easy-to-handle pattern for disease management.

A two-dimensional fingerprint nanoprobe based on black phosphorus for bio-SERS analysis and chemo-photothermal therapy.

Flake-shaped nanohybrids based on black phosphorus (BP) have been developed as multifunctional theranostic nanoplatforms for drug delivery, phototherapy and bioimaging. In this work, we report a facile strategy for fabrication of black phosphorus-Au nanoparticle hybrids (BP-AuNPs), which reveal an extraordinary near-infrared (NIR) photothermal transduction efficiency and drug delivery capacity. The applications of the nanocomposites as therapeutic agents for high-performance chemo-photothermal tumor therapy are accomplished in vitro and in vivo. BP-AuNPs also exhibit wonderful surface-enhanced Raman scattering (SERS) activity under NIR laser excitation with a low Raman background, allowing BP-AuNPs to be used as a promising two-dimensional (2D) fingerprint nanoprobe for bio-SERS analysis. The cellular component identification and label-free live-cell bioimaging based on this type of 2D SERS substrate are generally investigated, which open up promising new perspectives in nanomedicine, including diagnosis, imaging and therapy.

Nasal delivery of nerve growth factor rescue hypogonadism by up-regulating GnRH and testosterone in aging male mice.

BACKGROUND: Nerve growth factor (NGF) plays essential roles in regulating the development and maintenance of central sympathetic and sensory neurons. However, the effects of NGF on hypogonadism remain unexplored. METHODS: To assess the effects of NGF on hypogonadism, we established a convenient and noninvasive way to deliver NGF to the hypothalamus by spraying liposome-encapsulated NGF into the nasal cavity. The ten-month-old aging male senescence accelerate mouse P8 (SAMP8) mice with age-related hypogonadotrophic hypogonadism were used to study the role of NGF in hypogonadism. The age-matched accelerated senescence-resistant mouse R1 (SAMR1) served as a control. The ten-month-old SAMP8 mice were treated with NGF twice per week for 12 weeks. Sexual hormones, sexual behaviors, and fertility were analyzed after NGF treatment. And the mechanisms of NGF in sex hormones sexual function were also studied. FINDINGS: NGF could enhance the sexual function, improve the quality of the sperm, and restore the fertility of aging male SAMP8 mice with age-related hypogonadism by activating gonadotropin-releasing hormone (GnRH) neuron and regulating secretion of GnRH. And NGF regulated the GnRH release through the PKC/p-ERK1/2/p-CREB signal pathway. INTERPRETATION: These results suggest that NGF treatment could alleviate various age-related hypogonadism symptoms in male SAMP8 and may be usefulness for age-related hypogonadotrophic hypogonadism and its related subfertility. FUND: National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, the Science and Technology Plan Project of Guangzhou, Wenzhou Science & Technology Bureau, Guangdong Province Pearl River Scholar Fund, Guangdong province science and technology innovation leading Scholar Fund.

Fabrication of Graphene and AuNP Core Polyaniline Shell Nanocomposites as Multifunctional Theranostic Platforms for SERS Real-time Monitoring and Chemo-photothermal Therapy.

In this work, novel theranostic platforms based on graphene oxide and AuNP core polyaniline shell (GO-Au@PANI) nanocomposites are fabricated for simultaneous SERS imaging and chemo-photothermal therapy. PANI, a new NIR photothermal therapy agent with strong NIR absorption, outstanding stability and low cytotoxicity is decorated on AuNPs by one-pot oxidative polymerization, then the Au@PANI core-shell nanoparticles are attached to the graphene oxide (GO) sheet via π-π stacking and electrostatic interaction. The obtained GO-Au@PANI nanohybirds exhibit excellent NIR photothermal transduction efficiency and ultrahigh drug-loading capacity. The nanocomposites can also serve as novel NIR SERS probes utilizing the intense SERS signals of PANI. Rapid SERS imaging of cancer cells is achieved using this ultrasensitive nanoprobe. GO-Au@PANI also reveals good capability of drug delivery with the DOX-loading efficiency of 189.2% and sensitive NIR/pH-responsive DOX release. The intracellular real-time drug release dynamics from the nanocomposites is monitored by SERS-fluorescence dual mode imaging. Finally, chemo-photothermal ablation of cancer cells is carried out in vitro and in vivo using GO-Au@PANI as high-performance chemo-photothermal therapeutic nanoagent. The theranostic applications of GO-Au@PANI endow it with great potential for personalized and precise cancer medicine.

Vitamin E, aging and Leydig cell steroidogenesis.

Previous studies have suggested that oxidant-induced damage may play a role in the reduced ability of aged Brown Norway rat Leydig cells to produce testosterone. We reasoned that if this was the case, antioxidants such as vitamin E (VE) would be expected to have protective effects on steroidogenesis. To test this hypothesis, the effects of VE on Leydig cell steroidogenesis were examined both in vitro and in vivo. In vitro studies were conducted using Leydig cells isolated from the testes of young adult Brown Norway rats. In one experiment, isolated cells were incubated with luteinizing hormone (LH) alone or with LH plus VE (1.3-40 microg/ml). At each of 3, 5 and 7 days thereafter, the ability of the cells to produce testosterone was greater in the presence of VE than in its absence, and depended upon VE dose. Culturing the Leydig cells with the antioxidants melatonin or N-tert-butyl-alpha-phenylnitrone also protected Leydig cell steroidogenic function. Additionally, VE was found to suppress Fe2+/sodium ascorbate-induced lipid peroxidation in Leydig cells. These studies strongly supported the contention that VE has a protective effect on Leydig cell steroidogenesis. These in vitro results prompted us to ask whether, in vivo, VE also would affect steroidogenesis as Leydig cells age. To this end, rats were provided one of three diets, begun when the rats were 6 months of age and carried out through age 25 months: VE-deficient, VE-control, or VE-supplemented. The VE-deficient diet had no effect on the age-related reductions in Leydig cell testosterone production observed in VE-control rats. The VE-supplemented diet did not prevent age-related reductions in steroidogenesis, but the reductions at ages 23 and 25 months were significantly less than those seen in Leydig cells from VE-control or VE-deficient rats. Taken together, the results of the in vitro and in vivo studies reported herein are consistent with the conclusion that vitamin E exerts a protective effect on Leydig cell steroidogenesis.