Omega-3 fatty acids abrogates oxido-inflammatory and mitochondrial dysfunction-associated apoptotic responses in testis of tamoxifen-treated rats.

Background: Tamoxifen (TAM) is a widely used drug in patients with gynecomastia and breast cancer. TAM exerts its anticancer effects via its antiestrogenic activities. Unfortunately, TAM has been reported to exert gonadotoxic effects on male testes. Therefore, this study was designed to explore the possible associated mechanisms involved in TAM-induced testicular dysfunction and the possible ameliorative effects of omega-3 fatty acids (O3FA). Methodology: Animals were randomly divided into control, O3FA, TAM, and TAM + O3FA. All treatment lasted for 28 days. Results: TAM exposure impaired sperm qualities (count, motility, and normal morphology) and decreased testicular 3ß-HSD and 17ß-HSD. It was accompanied by a decline in serum testosterone and an increase in estradiol, luteinizing and follicle-stimulating hormones. These observed alterations were associated with an increase in testicular injury markers, oxido-inflammatory response, and mitochondria-mediated apoptosis. These observed alterations were ameliorated by O3FA treatments. Conclusions: O3FA ameliorated TAM-induced testicular dysfunction in male Wistar rats by modulating XO/UA and Nrf2/NF-kb signaling and cytochrome c-mediated apoptosis in TAM-treated rats.

Skoochies and its component substances induced testicular damage and impaired sperm function via increased generation of reactive oxygen species and impairment of the glutathione system in rats.

OBJECTIVE: To examine the effect of skoochies, an illicit cocktail drink, on testicular and sperm function in male rats. DESIGN: Twenty-five adult male Wistar rats were assigned randomly into five groups (n = 5) as follows: normal saline; skoochies; Cannabis sativa; codeine; and tramadol. The cocktail (skoochies) used in this study was formulated with the following composition: codeine (5 mg/kg); tramadol (20 mg/kg); and cannabis extract (2 mg/kg). These doses are as previously reported. Administration was performed once daily for 28 days. SETTING: University. ANIMAL(S): Twenty-five (25) male Wistar rats. INTERVENTION(S): Skoochies, tramadol, Codeiene, Cannabis. MAIN OUTCOME MEASURE(S): Skoochies and its components induced testicular and sperm damage via increased generation of reactive oxygen species and impairment of glutathione system in rats. RESULT(S): Skoochies increased reactive oxygen species generation and impaired the antioxidant system resulting in inflammation that eventually damaged the testicular tissue. Skoochies caused oxidoinflammatory injury to this tissue, leading to impaired testicular function. This was evident by the distorted cytoarchitecture, reduced sperm count and motility, and impaired testicular deoxyribonucleic acid integrity. CONCLUSION(S): Thus, our results infer that skoochies impaired the testicular and sperm function through the increased generation of reactive oxygen species and impairment of the glutathione system.

Wound recovery efficacy of retinol based-micellar formulations in an organotypic skin wound model.

Impairment of the skin's structural integrity initially results in acute wounds which can become chronic if timely wound closure is not achieved. Chronic wounds (CWs) affect more than 1% of the global population with increasing cases of this condition due to the ageing population. Current wound management relies on debridement, hyperbaric oxygen, antibiotics, and wound dressings, which lack early intervention and specificity. Herein, antibiotics-free retinol-based micellar formulations (RMF) were made and their wound healing efficacy were investigated in vitro. Five different formulations with retinol contents of 0.3% and 1% against a placebo were topically applied to an organotypic full-thickness skin wound model (FT-SWM, MatTek®) with a 3 mm punch wound, and maintained in an incubator for 6 days. The histological analysis of the FT-SWM was conducted at depths of 60 µm and 80 µm. It was found that all the micellar retinol formulations accelerated wound bed contraction, with 0.3% RMF demonstrating the highest efficacy. At the depths of 60 µm and 80 µm, the 0.3% RMF exhibited inner wound diameter contraction of 58% and 77%, respectively, in comparison to the placebo showing 15% and 8%. The RMF significantly accelerated wound healing and can thus be a potential early intervention for speedy wound recovery. It should be pointed out that these results were obtained based on a small sample size and a large sample size will be explored to further validate the results.

Disruptive consequences of monosodium glutamate on male reproductive function: A review.

Monosodium glutamate (MSG) is one of the most extensively used flavour enhancers worldwide. Although it is widely regarded as a safe food additive with no recommended daily dosage, its over-consumption has been associated with notably pathophysiological events in various tissues and organs of the body. Previous studies have reported of the neuro- cardio- and hepato- toxic effects of its excessive exposure. Moreover, the food additive instigates metabolic dysfunction. It has been established that MSG damages male reproductive accessory organs like prostate glands and epididymis. In addition, it impairs serum enzymatic activities and serum levels of testosterone, gonadotropin-releasing hormone, luteinizing hormone and cholesterol. Reduced sperm count, sperm motility, sperm morphology, and sperm viability, imbalances in male reproductive hormones, alongside alteration in the histoarchitecture of the testes and other male reproductive tissues have also been connected with excessive exposure to MSG. Literature reports affirm the link between the over-consumption of MSG and reproductive organ weight and male sexual behaviour. This review article addresses the multi-systemic effects of exposure to MSG and the possible mechanism of action of the compound with a focus on the negative implications of the food additive on male reproductive functions and the possible role of natural antioxidants in male reproductive functions. carefully selected keywords were used during the literature search to gather credible and up-to-date information about the subject matter.

Mechanism associated with changes in male reproductive functions during ageing process.

Ageing is a natural process with physiological changes in different body parts and has been associated with decreased reproductive capacity. Factors such as imbalance in the antioxidant defence system, vascular diseases, diabetes mellitus, accessory reproductive glands infection, obesity as well as buildup of toxic substances play a role in age-related male reproductive malfunction. Age is inversely proportional to volume of semen, sperm count, sperm progressive motility, sperm viability, normal sperm morphology. The observed negative correlation between ageing and semen indices contributes to male infertility and reproductive decline. Normal levels of ROS, plays crucial role in facilitating sperm function, such as capacitation, hyper-activation, acrosome reaction as well as sperm-oocyte fusion; however, a substantial elevation in the endogenous level of ROS, especially in reproductive tissues, usually instigates destruction of sperm cells and heightened male infertility. Contrarily, antioxidants, such as vitamins C and E, beta-carotene, and micronutrients like zinc and folate, have been found by researchers to facilitate normal semen quality and male reproductive function. Furthermore, the role of hormonal imbalance as a result of the compromised hypothalamic-pituitary-gonadal axis, Sertoli and Leydig cells disorder, and nitric oxide-medicated erectile dysfunction during ageing cannot be undermined.

Antibiotics-Free Compounds for Chronic Wound Healing.

The rapid rise in the health burden associated with chronic wounds is of great concern to policymakers, academia, and industry. This could be attributed to the devastating implications of this condition, and specifically, chronic wounds which have been linked to invasive microbial infections affecting patients' quality of life. Unfortunately, antibiotics are not always helpful due to their poor penetration of bacterial biofilms and the emergence of antimicrobial resistance. Hence, there is an urgent need to explore antibiotics-free compounds/formulations with proven or potential antimicrobial, anti-inflammatory, antioxidant, and wound healing efficacy. The mechanism of antibiotics-free compounds is thought to include the disruption of the bacteria cell structure, preventing cell division, membrane porins, motility, and the formation of a biofilm. Furthermore, some of these compounds foster tissue regeneration by modulating growth factor expression. In this review article, the focus is placed on a number of non-antibiotic compounds possessing some of the aforementioned pharmacological and physiological activities. Specific interest is given to Aloevera, curcumin, cinnamaldehyde, polyhexanide, retinoids, ascorbate, tocochromanols, and chitosan. These compounds (when alone or in formulation with other biologically active molecules) could be a dependable alternative in the management or prevention of chronic wounds.

Rohypnol-induced sexual dysfunction is via suppression of hypothalamic-pituitary-testicular axis: An experimental study in rats.

Sexual activity is an essential part of reproductive functions and needed for the maintenance of fertility. Drugs, particularly substances of abuse, impair male reproductive function either by interrupting hormonal functions or through the nonhormonal pathways. This study evaluated the impact of Rohypnol use in sexual behaviour. Materials and methods: Thirty adult male Wistar rats of comparable weights (180-200 g) were randomly allocated into three groups, the control and low-dose and high-dose Rohypnol-treated groups. The control group received 0.5 ml of distilled water, while the low- and high-dose Rohypnol-treated groups received 2 mg/kg b.w and 4 mg/kg b.w of Rohypnol via oral lavage once daily for 28 days. Rohypnol significantly increased mount latency, intromission latency, ejaculation latency and post-ejaculatory interval, as well as lowered mount frequency, intromission frequency and ejaculation frequency. Rohypnol-induced sexual dysfunction was found to be associated with significant suppression of circulatory follicle-stimulating hormone, luteinising hormone, testosterone and oestrogen. The present study reveals that Rohypnol induces sexual dysfunction through suppression of hypothalamic-pituitary-testicular axis. It also implicates Rohypnol as a potential candidate for drug-induced infertility.

Preparation of NIR absorbing axial substituted tin(iv) porphyrins and their photocytotoxic properties.

Sn(iv) porphyrins ([Sn(iv)TTP(3PyO)2] (5) and [Sn(iv)TPP(3PyO)2] (6) [tetrathienylporphyrin (TTP), tetraphenylporphyrin (TPP), and pyridyloxy (PyO)]) were prepared and characterized and their photocytotoxicity upon irradiation with 625 nm light has been studied. The presence of the 3PyO axial ligands was found to limit the aggregation and enhance the solubility of 5 and 6 in DMF/H2O (1 : 1). The photophysical properties and photodynamic therapy (PDT) activity of the meso-2-thienyl and meso-phenyl-substituted Sn(iv) porphyrins are compared. 5 and 6 were found to be photocytotoxic in MCF-7 cancer cells when irradiated with a Thorlabs M625L3 LED at 625 nm but remained nontoxic in the dark. The PDT activity of Sn(iv) meso-tetra-2-thienylporphyrin 5 was found to be significantly enhanced relative to its analogous tetraphenylporphyrin 6. There is a marked red-shift of the Q00 band of 5 into the therapeutic window due to the meso-2-thienyl rings, and 5 has an unusually high singlet oxygen quantum yield value of 0.83 in DMF. The results demonstrate that readily synthesized axially ligated Sn(iv) meso-arylporphyrins are potentially suitable for use as singlet oxygen photosensitizers in biomedical applications and merit further in depth investigation in this context.

Photophysicochemical and photodynamic therapy properties of metallophthalocyanines linked to gold speckled silica nanoparticles.

This work reports on the linkage of 2(3),9(10),16(17),23(24) tetrakis [(benzo[d]thiazol-2-yl phenoxy) phthalocyaninato] zinc(II) (1) and indium(III) chloride (2) to gold speckled silica (GSS) nanoparticles via gold to sulphur (Au-S) and gold to nitrogen (Au-N) self-assembly to form the conjugates: 1-GSS and 2-GSS. The formed conjugates were characterized using microscopic and spectroscopic techniques, and the photophysicochemical properties and photodynamic therapy (PDT) activity against human breast adenocarcinoma cell line (MCF-7 cells) were studied. The conjugates afforded decrease in fluorescence quantum yields with corresponding increase in triplet and singlet oxygen quantum yields when compared to phthalocyanines alone. Singlet oxygen is cytotoxic to cancer cells hence it is important for PDT. The in vitro dark toxicity of complex 2 and 2-GSS against MCF-7 cells showed ≥93% viable cells within concentration ranges of 10-160 µg/mL. 2-GSS showed enhanced PDT activity with less than 50% viable cells at 80 µg/mL as compared to 2 and GSS alone which showed >60% viable cells within 10-160 µg/mL. The observed improvements in the PDT activity of 2-GSS could be attributed to the high singlet oxygen generation of 2-GSS compared to 2 alone in addition to the phototoxicity of GSS.

Photodynamic therapy activity of zinc phthalocyanine linked to folic acid and magnetic nanoparticles.

In this work, the photodynamic therapy (PDT) activities (using human carcinoma adherent MCF-7 cells) of zinc phthalocyanine derivatives: complexes 1 (Zn mono cinnamic acid phthalocyanine) and 2 (zinc mono carboxyphenoxy phthalocyanine) when covalently linked to folic acid (FA) and amine functionalized magnetic nanoparticles (AMNPs) are reported. The covalent linkage of asymmetric zinc cinnamic acid Pc (1) to FA (1-FA) through an amide bond is reported for the first time. Complex 1 is insoluble in water, but upon linkage to FA, (to form 1-FA) the molecule become water soluble, hence the UV-Vis spectrum and singlet oxygen quantum yield for 1-FA were also done in water since water solubility is essential for biological applications. The reported 2-FA is also water soluble. Linking complexes 1 and 2 to FA and AMNPs decreased the dark toxicity of 1 and 2 on MCF-7 cells. Pc-FA (1-FA and 2-FA) conjugates had better singlet oxygen quantum yields (Φ∆) in DMSO as compared to Pc-AMNPs (1-AMNPs and 2-AMNPs). The water- soluble 1-FA and 2-FA also achieved a better photodynamic therapy (PDT) activity as compared to 1-AMNPs and 2-AMNPs. Folic acid targeting on the tumor cells may have also facilitated better bioavailability of 1-FA and 2-FA and improved PDT activity on MCF-7 cells over AMNPs carriers.

Photophysicochemical properties and photodynamic therapy activity of highly water-soluble Zn(II) phthalocyanines.

The syntheses of two zinc(II) phthalocyanines (ZnPcs) having either imidazole (ZnPc 1) or pyridiloxy (ZnPc 2) moieties as their macrocycle substituents are reported. Quaternization of the ZnPcs with methyl iodide afforded water soluble cationic phthalocyanines. The photophysical, photochemical properties and photodynamic therapy (PDT) activity of the ZnPcs were studied in solution. The fluorescence quantum yield and lifetime of ZnPc 1 were higher as compared to ZnPc 2. ZnPc 2 afforded higher triplet state (ΦT) and singlet oxygen quantum yields (ΦΔ) in comparison to ZnPc 1. The PDT activity of ZnPcs was investigated against human breast adenocarcinoma cells (MCF-7). The two compounds afforded a very minimal in vitro dark cytotoxicity with 85% viable cells at concentration ≤80 µM. On irradiation of the cells having the ZnPcs, ≥50% cell death was recorded for ZnPc 1 which was also evidenced by the cells photo-micrograph.

Glycosylated zinc phthalocyanine-gold nanoparticle conjugates for photodynamic therapy: Effect of nanoparticle shape.

In this work, we report on the synthesis of tris-[(2,2,7,7-tetramethyltetrahydro-3aH-bis([1,3]dioxolo)[4,5-b:4',5'-d]pyran-5-yl)methoxy)-2-(4-benzo[d]thiazol-2-ylphenoxyphthalocyaninato] zinc(II) (complex 3) and its linkage to gold nanoparticles (AuNPs) of different shapes through S-Au/N-Au self-assembly. The conjugates of complex 3 (with both gold nanorods (AuNR) and nanospheres (AuNS)), displayed decreased fluorescence quantum yield with corresponding improved triplet and singlet quantum yields compared to complex 3 alone, however 3-AuNR showed improved properties than 3-AuNS. Complex 3 showed relatively low in vitro dark cytotoxicity against the epithelial breast cancer cells with cell survival ≥ 85% at concentration ≤ 160 µg/mL but afforded reduced photodynamic therapy activity which may be due to aggregation. 3-AuNR afforded superior PDT activity with <50% viable cells at concentration ≥ 40 µg/mL in comparison to 3-AuNS with <50% viable cells at concentration ≥ 80 µg/mL. The superior activity of 3-AuNR is attributed to the photothermal therapy effect since nanorods absorb more light at 680 nm than nanospheres.

Improved Photophysical and Photochemical Properties of Thiopheneethoxy Substituted Metallophthalocyanines on Immobilization onto Gold-speckled Silica Nanoparticles.

This work reports on the synthesis of tetrakis-[(thiophineethoxy) phthalocyaninato] indium(II) chloride (3). The photophysical behavior of complex 3 was compared to that of the Zn derivative (tetrakis-[(thiophineethoxy) phthalocyaninato] zinc(II) (complex 2)). The compounds were interacted with gold-speckled silica (GSS) nanoparticles via Au-S self assembly to afford the conjugates (2-GSS and 3-GSS). The photophysicochemical behavior of the compounds and their conjugates were assessed. The conjugates afforded a decrease in fluorescence quantum yields and lifetimes with improved triplet and singlet oxygen quantum yields in comparison with complexes 2 and 3 alone. The complexes and their conjugates could serve as good candidates for photodynamic therapy.

Optical limiters with improved performance based on nanoconjugates of thiol substituted phthalocyanine with CdSe quantum dots and Ag nanoparticles.

Two alternative synthetic approaches affording a low-symmetry A3B-type phthalocyanine 1 bearing two [2'-(2''-mercaptoethoxy)ethoxy] anchoring substituents were developed. Due to the presence of thiol groups, this phthalocyanine could be conjugated with TOPO-capped (TOPO - trioctylphosphine)-capped CdSe quantum dots (CdSe-QDs) or oleylamine capped silver nanoparticles (Ag-NPs). The nonlinear optical behaviour of starting phthalocyanine, quantum dots, nanoparticles and their conjugates was studied by using an open aperture Z-scan technique, revealing that the grafting of 1 onto the nanomaterials resulted in a significant enhancement of the optical limiting of 1-Ag and 1-CdSe in comparison with the individual components. The conjugate 1-CdSe, being the first example of Pc-based thiol conjugated with quantum dots, revealed superior limiting characteristics with a limiting threshold below 0.18 J cm-2.

Characterization of phthalocyanine functionalized quantum dots by dynamic light scattering, laser Doppler, and capillary electrophoresis.

In this work, we characterized different phtalocyanine-capped core/shell/shell quantum dots (QDs) in terms of stability, ζ-potential, and size at various pH and ionic strengths, by means of capillary electrophoresis (CE), and compared these results to the ones obtained by laser Doppler electrophoresis (LDE) and dynamic light scattering (DLS). The effect of the phthalocyanine metallic center (Zn, Al, or In), the number (one or four), and nature of substituents (carboxyphenoxy- or sulfonated-) of functionalization on the phthalocyanine physicochemical properties were evaluated. Whereas QDs capped with zinc mono-carboxyphenoxy-phtalocyanine (ZnMCPPc-QDs) remained aggregated in the whole analyzed pH range, even at low ionic strength, QDs capped with zinc tetracarboxyphenoxy phtalocyanine (ZnTPPc-QDs) were easily dispersed in buffers at pH equal to or higher than 7.4. QDs capped with aluminum tetrasulfonated phthalocyanine (AlTSPPc-QDs) and indium tetracarboxyphenoxy phthalocyanines (InTCPPc-QDs) were stable in aqueous suspension only at pH higher than 9.0 due to the presence of functional groups bound to the metallic center of the phthalocyanine. The ζ-potential values determined by CE for all the samples decreased when ionic strength increased, being well correlated with the aggregation of the nanoconjugates at elevated salt concentrations. The use of electrokinetic methodologies has provided insights into the colloidal stability of the photosensitizer-functionalized QDs in physiological relevant solutions and thereby, its usefulness for improving their design and applications for photodynamic therapy. Graphical Abstract Schematic illustration of the phthalocyanine capped QDs nanoconjugates and the capillary electrophoresis methods applied for size and ζ-potential characterization.

Photophysical behavior and photodynamic therapy activity of conjugates of zinc monocarboxyphenoxy phthalocyanine with human serum albumin and chitosan.

Zinc monocarboxyphenoxy phthalocyanine (ZnMCPPc) was linked to human serum albumin (HSA) and chitosan via amide bond formation. The photophysical behavior and photodynamic therapy (PDT) activity (against human breast adenocarcinoma cell line (MCF-7 cells) of ZnMCPPc alone and its conjugates were investigated. The conjugates showed improved fluorescence, triplet and singlet oxygen quantum yields when compared to ZnMCPPc alone. The in vitro dark cytotoxicity and PDT studies were carried out at a dose of 3.6µg/mL to 57.1µg/mL. The in vitro dark cytotoxicity studies of ZnMCPPc showed cell viability <50% at 28.6µg/mL and 57.1µg/mL, while the conjugates showed > 50% in all their tested concentrations (3.6 to 57.1) µg/mL. Thus, conjugation of ZnMCPPc to HSA and chitosan improves its dark cytotoxicity, an important criteria for molecules meant for photodynamic therapy. Complex 1 showed the most efficacious PDT activity with cell viability <50% at concentration range of (14.3 to 57.1) µg/mL in comparison to the conjugates which only showed <50% cell viability at 28.6µg/mL and 57.1µg/mL for 1-HSA and 57.1µg/mL for 1-Chitosan.

First Example of Nonlinear Optical Materials Based on Nanoconjugates of Sandwich Phthalocyanines with Quantum Dots.

We report original, selective, and efficient approaches to novel nonlinear optical (NLO) materials, namely homoleptic double- and triple-decker europium(III) complexes 2 and 3 with the A3 B-type phthalocyanine ligand (2,3-bis[2'-(2''-hydroxyethoxy)ethoxy]-9,10,16,17,23,24-hexa-n-butoxyphthalocyanine 1) bearing two anchoring diethyleneglycol chains terminated with OH groups. Their covalently linked nanoconjugates with mercaptosuccinic acid-capped ternary CdSeTe/CdTeS/ZnSeS quantum dots are prepared in the presence of an ethyl(dimethylaminopropyl)carbodiimide activating agent. Optical limiting (OL) properties of the obtained low-symmetry complexes and their conjugates with quantum dots (QDs) are measured for the first time by the open-aperture Z-scan technique (532 nm laser and pulse rate of 10 ns). For comparison, symmetrical double- and triple-decker EuIII octa-n-butoxyphthalocyaninates 5 and 6 and their mixtures with trioctylphosphine oxide-capped QDs are also synthesized and studied. It is revealed that both lowering of molecular symmetry and expansion of the π-electron system upon moving from double- to triple-decker complexes significantly improves the OL characteristics, making the low-symmetry triple-decker complex 3 the most efficient optical limiter in the studied family of sandwich complexes, affording 50 % lowering of light transmittance below 0.5 J cm-2 input fluence. Conjugation (both covalent and noncovalent) with QDs affords further enhancement of the OL properties of both double- and triple-decker complexes. Altogether, the obtained results contribute to the development of novel nonlinear optical materials for future nanoelectronic and optical device applications.

Spirituality, gender and age factors in cybergossip among Nigerian adolescents.

This study investigated the patterns of spirituality, gender, and age in cybergossip practices among Nigerian adolescents. The study utilized a descriptive survey method. Five hundred thirty adolescent students, randomly selected from four major cities in Nigeria, participated in the study. Their age range was 16 to 21. General Spirituality and Gossip Purpose scales were used to collect data from the participants. Data collected were subjected to t test statistics. Findings showed that there is no significant difference in the cybergossiping practices of adolescents based on their levels of spirituality. This reveals that spirituality is not an inhibiting factor in cybergossiping practices among the adolescents. However, there is significant difference between male and female youths in their cybergossiping practices. The results showed that females are more likely than males to be involved in cybergossiping activities. There is also significant difference between early and late adolescents' cybergossiping activities. The implication is that gossip and cybergossip is a natural tendency that involves communicative expression with a pleasure-seeking purpose. It is a habit that excludes no one despite spiritual, gender, or age factors. Therefore, this behavior should be positively directed away from abusive computing and communication. This work is unique because of the need for parents, guardians, and psychologists to design measures to identify and manage various moderating variables in children's computing practices for optimal positive outcomes.