Curcumin and nano-curcumin applications in psychiatric disorders.

Psychiatric disorders cause long-lasting disabilities across different age groups. While various medications are available for mental disorders, some patients do not fully benefit from them or experience treatment resistance. The pathogenesis of psychiatric disorders involves multiple mechanisms, including an increase in the inflammatory response. Targeting inflammatory mechanisms has shown promise as a therapeutic approach for these disorders. Curcumin, known for its anti-inflammatory properties and potential neuroprotective effects, has been the subject of studies investigating its potential as a treatment option for psychiatric disorders. This review comprehensively examines the potential therapeutic role of curcumin and its nanoformulations in psychiatric conditions, including major depressive disorder (MDD), bipolar disorder, schizophrenia, and anxiety disorders. There is lack of robust clinical trials across all the studied psychiatric disorders, particularly bipolar disorder and schizophrenia. More studies have focused on MDD. Studies on depression indicate that curcumin may be effective as an antidepressant agent, either alone or as an adjunct therapy. However, inconsistencies exist among study findings, highlighting the need for further research with improved blinding, optimized dosages, and treatment durations. Limited evidence supports the use of curcumin for bipolar disorder, making its therapeutic application challenging. Well-designed clinical trials are warranted to explore its potential therapeutic benefits. Exploring various formulations and delivery strategies, such as utilizing liposomes and nanoparticles, presents intriguing avenues for future research. More extensive clinical trials are needed to assess the efficacy of curcumin as a standalone or adjunctive treatment for psychiatric disorders, focusing on optimal dosages, formulations, and treatment durations.

Antibacterial and Cellular Behaviors of Novel Zinc-Doped Hydroxyapatite/Graphene Nanocomposite for Bone Tissue Engineering.

Bacteria are one of the significant causes of infection in the body after scaffold implantation. Effective use of nanotechnology to overcome this problem is an exciting and practical solution. Nanoparticles can cause bacterial degradation by the electrostatic interaction with receptors and cell walls. Simultaneously, the incorporation of antibacterial materials such as zinc and graphene in nanoparticles can further enhance bacterial degradation. In the present study, zinc-doped hydroxyapatite/graphene was synthesized and characterized as a nanocomposite material possessing both antibacterial and bioactive properties for bone tissue engineering. After synthesizing the zinc-doped hydroxyapatite nanoparticles using a mechanochemical process, they were composited with reduced graphene oxide. The nanoparticles and nanocomposite samples were extensively investigated by transmission electron microscopy, X-ray diffraction, and Raman spectroscopy. Their antibacterial behaviors against Escherichia coli and Staphylococcus aureus were studied. The antibacterial properties of hydroxyapatite nanoparticles were found to be improved more than 2.7 and 3.4 times after zinc doping and further compositing with graphene, respectively. In vitro cell assessment was investigated by a cell viability test and alkaline phosphatase activity using mesenchymal stem cells, and the results showed that hydroxyapatite nanoparticles in the culture medium, in addition to non-toxicity, led to enhanced proliferation of bone marrow stem cells. Furthermore, zinc doping in combination with graphene significantly increased alkaline phosphatase activity and proliferation of mesenchymal stem cells. The antibacterial activity along with cell biocompatibility/bioactivity of zinc-doped hydroxyapatite/graphene nanocomposite are the highly desirable and suitable biological properties for bone tissue engineering successfully achieved in this work.

Polypropylenimine dendrimer-induced gene expression changes: the effect of complexation with DNA, dendrimer generation and cell type.

Polypropylenimine (PPI) dendrimers appear attractive non-viral vectors for the delivery of genes, antisense oligonucleotides, and small interfering RNA (siRNA). However, the effects of these synthetic gene delivery vectors on global gene expression are poorly understood. Here we have examined the toxicogenomics of generation 2 (DAB-8) and generation 3 (DAB-16) PPI dendrimers in two human cell lines. At concentrations and treatment protocols routinely used for gene and oligonucleotide transfection, PPI dendrimers alone elicited marked changes in endogenous gene expression in A431 epithelial cells. The extent of PPI-induced gene changes appeared to be dependent on the dendrimer generation as the number of genes affected was greater with G3 compared to G2 PPI dendrimers in A431 cells. The signature of DAB16-induced gene changes in A549 cells was different to those elicited in A431 cells implying a strong dependence on cell type. The DAB-16 polymer complexed with DNA (dendriplexes) also elicited marked gene expression changes in A549 cells but with a signature that was different from the polymer alone implying that dendriplexes are "recognised" by cells as chemical entities that are distinct from the polymer alone. Alterations in expression of a variety of gene ontologies were observed including those involved in defence responses, cell proliferation and apoptosis. Although there was a tendency for increased DNA damage in cells treated with DAB16 alone or its DNA dendriplexes as detected by the COMET assay, these differences were not statistically significant. These data show for the first time that PPI-dendrimers, separate from their capability as transfection reagents, can intrinsically alter the expression of many endogenous genes that could potentially lead to them exerting multiple biological effects in cells. The impact and consequences of polymer-induced gene changes should guide their rational use as delivery systems for gene-based therapeutics.

An ultra-sensitive impedimetric immunosensor for detection of the serum oncomarker CA-125 in ovarian cancer patients.

Effective treatment of ovarian cancer depends upon the early detection of the malignancy. Here, we report on the development of a new nanostructured immunosensor for early detection of cancer antigen 125 (CA-125). A gold electrode was modified with mercaptopropionic acid (MPA), and then consecutively conjugated with silica coated gold nanoparticles (AuNP@SiO2), CdSe quantum dots (QDs) and anti-CA-125 monoclonal antibody (mAb). The engineered MPA|AuNP@SiO2|QD|mAb immunosensor was characterised using transmission electron microscopy (TEM), atomic force microscopy (AFM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Successive conjugation of AuNP@SiO2, CdSe QD and anti-CA-125 mAb onto the gold electrode resulted in sensitive detection of CA-125 with a limit of detection (LOD) of 0.0016 U mL(-1) and a linear detection range (LDR) of 0-0.1 U mL(-1). Based on the high sensitivity and specificity of the immunosensor, we propose this highly stable and reproducible biosensor for the early detection of CA-125.

Preparation and evaluation of sustained release calcium alginate beads and matrix tablets of acetazolamide.

The aim of this study was to develop sustained release dosage forms of acetazolamide (ACZ) preparing its calcium alginate beads and matrix tablets. ACZ was incorporated into calcium alginate beads using microencapsulation method. Two methods were applied to prolong ACZ release rate. In the first method, the drug was incorporated into calcium alginate beads either alone or with various polymers in internal phase. The second method involved the preparation of matrix tablet from the beads benefiting direct compression method with or without various polymers in external phase. The release rate of these prepared formulations and an innovator's sustained-release capsule (Diamox®) were assessed. In-vitro dissolution studies revealed that the matrix tablets prepared by the second method containing NaCMC could sustain ACZ release properly and the drug released until 9 h. It was also found that several parameters such as concentration of sodium alginate, calcium chloride and ACZ; type and concentration of polymers; syringe needle size as well as distance between needle tip and surface of the calcium chloride could affect the properties of beads, matrix tablets and subsequently release profile. Preparation of polymer free beads, incorporation of polymers in internal phase of the beads and direct compression of the beads did not give sustained release property. Whereas, incorporation of NaCMC in the external phase of the beads in matrix tablets or in combination with alginate powder in directly compressed conventional tablets could produce dosage form with sustained release property similar to reference formulation.

Callus culture of Echium italicum L. towards production of a shikonin derivative.

Callus induction and proliferation of Echium italicum L. (Boraginaceae) were investigated using cotyledon, hypocotyl and root explants. Calli were initiated and established using B5, LS, 1/2LS and White media supplemented with different auxins, including 2,4-dichlorophenoxyacetic acid (2,4-D), indole-3-acetic acid (IAA) and 1-naphthaleneacetic acid (NAA) in combination with kinetin. The maximum pigmented callus induction (100%) was observed in the White medium. The n-hexane extract of proliferated callus tissues were analysed by TLC and HPLC. The major secondary metabolite was separated by preparative HPLC and its structure was elucidated by UV, ¹H and ¹³C-NMR spectroscopy. As a result, shikonin acetate was identified by various spectroscopic methods from callus culture of E. italicum. These findings highlight the shikonin production potential of the E. italicum callus, which may be considered as a new source for the production of shikonin and its derivatives for industrial use.

Floral nectar composition of Peganum harmala L.

Chemical composition of the floral nectar of Peganum harmala, a herbaceous medicinal perennial of the family Zygophyllaceae, was analysed using high-performance liquid chromatography technique. The nectar sugar detection experiments resulted in 33.1, 39.8 and 27.4%, respectively, for fructose, glucose and sucrose, upon which the nectar was classified as hexose rich. In addition, 11 proteinaceous amino acids were recognised and quantified in the nectar. Concentration of the insects' favoured amino acid, prolin, was markedly high. Furthermore, among four detected alkaloids, harmalol and harmine as the two beta-carboline derivatives were identified. These findings may confer a better understanding upon outcrossing processes and favour the plant-pollinator relationships.

Improved Taxol production by combination of inducing factors in suspension cell culture of Taxus baccata.

To date enormous attempts have been devoted to improve Taxol production exploiting various methodologies from bioprocess engineering to biotechnological and synthetic approaches. We have developed a 2-stage suspension cell culture of Taxus baccata L. using modified B5 medium in order to improve cell growth as well as productivity. After callus induction and cell line selection, B5 medium was supplemented with vanadyl sulfate (0.1 mg/l), silver nitrate (0.3 mg/l) and cobalt chloride (0.25 mg/l) at the first day of stage I culture to maximize cell growth. This medium was further supplemented with sucrose (1%) and ammonium citrate (50 mg/l) on day 10 and sucrose (1%) and phenylalanine (0.1 mM) on day 20 (i.e., biomass growth medium). At stage II (day 25), two different concentrations of several elicitors such as methyl jasmonate (10 or 20 mg/l), salicylic acid (50 or 100 mg/l) and fungal elicitor (25 or 50 mg/l) were added to the biomass growth medium with the aim of improving cellular productivity. For morphological analysis, microscopic inspection was carried out during cultivation. Cell-associated and extracellular amount of Taxol were detected and measured using HPLC methodology. At stage I, overall Taxol amount of biomass growth medium was 13.75 mg/l (i.e., 5.6-fold higher than that of untreated B5 control). At stage II, treated cells with methyl jasmonate (10 mg/l), salicylic acid (100 mg/l) and fungal elicitor (25 mg/l) produced the highest amount of Taxol (39.5 mg/l), which is 16-fold higher than that of untreated B5 control (2.45 mg/l). Microscopic analyses of Taxus cells in suspension cultures showed various positional auto-fluorescence showing direct correlation with Taxol production. Our studies revealed that intervallic supplementation of B5 medium with combination of biomass growth factors at stage I and mixture of elicitors at stage II could significantly increase Taxol production. Thus, we suggest that the exploitation of this methodology may improve the production of Taxol since demands for Taxol pharmaceuticals are increasingly growing and resource paucities have limited its direct harvesting from Taxus trees.