Vitamin D3 improves spatial memory and modulates cytokine levels in aged rats.

Vitamin D3 deficiency is associated with an increased risk of dementia. An association between vitamin D3 deficiency and subjective cognitive complaints in geriatric patients has been previously reported. This study aimed to evaluate the effects of two doses of vitamin D3 on spatial memory (using the Radial Maze) and cytokine levels [tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and interleukin-10 (IL-10)] on 2-, 6-, 13-, 22-, and 31-month-old male Wistar rats. Animals were supplemented with vitamin D3 at doses of 42 IU/kg and 420 IU/kg for 21 days. A radial maze test was performed to evaluate spatial memory. After the behavioral test, the frontal cortex and hippocampus were dissected for enzyme immunoassay analyses to measure the cytokine levels (TNFα, IL-1ß, IL-6, and IL-10). Our results showed that vitamin D3 supplementation reversed spatial memory impairment at the supplemented doses (42 and 420 IU/kg) in 6-, 13-, and 22-month-old animals and at a dose of 420 IU/kg in 31-month-old animals. The lower dose (42 IU/kg) regulates both pro- and anti-inflammatory cytokines mainly in the frontal cortex. Our results suggest that vitamin D3 has a modulatory action on pro- and anti-inflammatory cytokines, since older animals showed increased cytokine levels compared to 2-month-old animals, and that vitamin D3 may exert an immunomodulatory effect on aging.

Neuroprotective effects of combined therapy with memantine, donepezil, and vitamin D in ovariectomized female mice subjected to dementia model.

Women older than 60 have a higher risk of dementia, aging-related cognitive decline, and Alzheimer's Disease (AD) than the rest of the population. The main reason is hormonal senescence after menopause, a period characterized by a decline in estrogen levels. Since the effectiveness of drugs currently approved for the treatment of AD is limited, it is necessary to seek the development of new therapeutic strategies. Vitamin D deficiency is prevalent in AD patients and individuals with dementia in general. The supplementation of this vitamin in dementia patients might be an interesting approach for increasing the effectiveness of pre-existing medications for dementia treatment. Thus, the present study aims to investigate the effect of vitamin D treatment associated with memantine and donepezil in female mice submitted to ovariectomy (OVX) for five months and subjected to a dementia animal model induced by intracerebroventricular injection of aggregated amyloid ßeta (Aß1-42). For this purpose, Balb/c mice were divided into five experimental groups, which received 17 days of combined therapy with vitamin D, donepezil, and memantine. Then, animals were subjected to behavioral tests. OVX groups exhibited reduced levels of estradiol (E2) in serum, which was not altered by the combined therapy. Higher levels of vitamin D3 were found in the OVX animals submitted to the triple-association treatment. Mice exposed to both OVX and the dementia animal model presented impairment in short and long-term spatial and habituation memories. Also, female mice exposed to Aß and OVX exhibited a reduction in brain-derived neurotrophic factor (BDNF) and interleukin-4 (IL-4) levels, and an increase in tumor necrose factor-α (TNFα) levels in the hippocampus. Besides, increased levels of IL-1ß in the hippocampus and cerebral cortex were observed, as well as a significant increase in immunoreactivity for glial fibrillary acidic protein (GFAP), an astrocytes marker, in the hippocampus. Notably, triple-association treatment reversed the effects of the exposition of mice to Aß and OVX in the long-term spatial and habituation memories impairment, as well as reversed changes in TNFα, IL-1ß, IL-4, and GFAP immunoreactivity levels in the hippocampus of treated animals. Our results indicate that the therapeutic association of vitamin D, memantine, and donepezil has beneficial effects on memory performance and attenuated the neuroinflammatory response in female mice subjected to OVX associated with a dementia animal model.

Plants as Modulators of Melanogenesis: Role of Extracts, Pure Compounds and Patented Compositions in Therapy of Pigmentation Disorders.

The kingdom of plants as a "green biofabric" of valuable bioactive molecules has long been used in many ailments. Currently, extracts and pure compounds of plant origin are used to aid in pigmentation skin problems by influencing the process of melanogenesis. Melanin is a very important pigment that protects human skin against ultraviolet radiation and oxidative stress. It is produced by a complex process called melanogenesis. However, disturbances in the melanogenesis mechanism may increase or decrease the level of melanin and generate essential skin problems, such as hyperpigmentation and hypopigmentation. Accordingly, inhibitors or activators of pigment formation are desirable for medical and cosmetic industry. Such properties may be exhibited by molecules of plant origin. Therefore, that literature review presents reports on plant extracts, pure compounds and compositions that may modulate melanin production in living organisms. The potential of plants in the therapy of pigmentation disorders has been highlighted.

The Modulation of Melanogenesis in B16 Cells Upon Treatment with Plant Extracts and Isolated Plant Compounds.

Plants are a rich source of secondary metabolites that exhibit numerous desired properties. The compounds may influence the biology of melanocytes, pigment cells that produce melanin, by modulating numerous signaling pathways, including cAMP/PKA, MAPKs and PI3K/AKT. Its downstream target is microphthalmia-associated transcription factor, responsible for the expression of the tyrosinase enzyme, which plays a major role in melanogenesis. Therefore, this literature review aims to provide insights related to melanogenesis modulation mechanisms of plant extracts and isolated plant compounds in B16 cells. Database searches were conducted using online-based library search instruments from 2012 to 2022, such as NCBI-PubMed and Google Scholar. Upregulation or downregulation of signaling pathways by phytochemicals can influence skin hypo- and hyperpigmentation by changing the level of melanin production, which may pose a significant cosmetic issue. Therefore, plant extracts or isolated plant compounds may be used in the therapy of pigmentation disorders.

In vitro and In silico Studies on Leonotis nepetifolia (L.) R. Br. Root Extract against Cancer Cells.

BACKGROUND: Leonotis nepetifolia (L.) R. Br. (Lamiaceae) is a shrub traditionally used to alleviate inflammatory conditions. OBJECTIVES: The present study aimed at investigating the biological activity of methanolic nontransformed and transformed Rhizobium rhizogenes root extracts from L. nepetifolia against human melanoma cells. METHODS: Cytotoxicity and genotoxicity properties, the impact on topoisomerase I activity, and proapoptotic activity were evaluated by the MTT test, comet assay, topoisomerase I assay, and fluorescence-activated cell sorting analysis. Moreover, the expressions of p53 were examined by qPCR and Western blot analysis. Docking studies were conducted to assess the potential interactions of the identified phytochemicals with the p53 binding protein Mdm-2, and computational analyses exhibited their antioxidant potential. RESULTS: Both extracts showed cytotoxic potential against human melanoma cells, but generally the activity was more potent for transformed roots than untransformed (IC50 760 µg/mL and 980 µg/mL, respectively). A similar effect was revealed during the evaluation of genotoxic and proapoptotic properties. Moreover, the expression of p53 was also found to be increased after extract treatment. The most dominant identified compounds in both extracts were as follows: (+)- catechin, p-coumaric acid, m-coumaric acid, and (+)-rosmarinic acid. Docking studies and computational analysis showed that (+)-rosmarinic acid possesses the highest binding affinity to the p53 binding protein, Mdm-2, and exhibits the best antioxidant property from the most commonly identified phytochemicals. CONCLUSION: Our findings revealed the potential of L. nepetifolia transformed root extract as a source of bioactive compounds with cytotoxic, genotoxic, and proapoptotic activity against human melanoma cells as well as antioxidant properties.

The Modulatory Influence of Plant-Derived Compounds on Human Keratinocyte Function.

The plant kingdom is a rich source of secondary metabolites with numerous properties, including the potential to modify keratinocyte biology. Keratinocytes are important epithelial cells that play a protective role against various chemical, physical and biological stimuli, and participate in reactive oxygen scavenging and inflammation and wound healing processes. The epidermal cell response may be modulated by phytochemicals via changes in signal transduction pathways. Plant extracts and single secondary compounds can possess a high antioxidant capacity and may suppress reactive oxygen species release, inhibit pro-apoptotic proteins and apoptosis and activate antioxidant enzymes in keratinocytes. Moreover, selected plant extracts and single compounds also exhibit anti-inflammatory properties and exposure may result in limited production of adhesion molecules, pro-inflammatory cytokines and chemokines in keratinocytes. In addition, plant extracts and single compounds may promote keratinocyte motility and proliferation via the regulation of growth factor production and enhance wound healing. While such plant compounds may modulate keratinocyte functions, further in vitro and in vivo studies are needed on their mechanisms of action, and more specific toxicity and clinical studies are needed to ensure their effectiveness and safety for use on human skin.

Modern methods of treatment in palliative care.

The palliative care patient is definitely a unique type of patient. Due to the complexity of the symptoms requires a holistic therapeutic approach. Modern methods of treatment in palliative and hospice care underline an important role of physio, kinesiotherapy and pharmacological treatment coexistence. The rehabilitation reduces clinical symptoms, accompanying the basic disease and increases the quality of life of palliative patients and their families. It becomes an inseparable element of treatment, both in outpatient care as well as in stationary care and home care. Due to the high dynamics onset of cancer in the group of geriatric patients there is a need for a broader analysis of the topic. The goal of palliative care is to achieve the best possible quality of life for patients and their families.

Health-Related Quality-of-Life and Functional Outcomes in Short-Stem Versus Standard-Stem Total Hip Arthroplasty: An 18-Month Follow-Up Cohort Study.

BACKGROUND Osteoarthritis (OA) progressively produces symptoms and disability that may significantly reduce health-related quality of life (HRQoL). Total hip arthroplasty (THA) is an important treatment for symptomatic OA. An alternative to standard-stem THA for younger patients is short-stem THA. The aim of this study was to investigate potential HRQoL and functional outcome differences between these patient groups to provide additional data that will be clinically useful in the decision making between the types of prosthesis. MATERIAL AND METHODS In an 18-month follow-up longitudinal cohort study, we conducted Harris Hip Score (HHS) evaluations and SF-36 questionnaires in a study group and a control group undergoing short-stem and standard-stem THA preoperatively and during follow-up at 1, 3, 6, 12, and 18 months. Effect size was calculated to estimate the size of changes in scores during follow-up between chosen time intervals. RESULTS A total of 168 patients were included in the study. The total HHS score was significantly increased postoperatively from 46.9 to 87.0 in the standard-stem group, and from 42.7 to 85.1 in the short-stem group. All SF-36 scores improved after THA in both groups. No HRQoL or functional differences were found in the use of either surgical option in the HHS or SF-36 score results (all p>0.05). CONCLUSIONS As there were no differences in HRQoL in the two groups, we strongly recommend considering short-stem THA, especially in younger patients, due to the benefit of future revision options and a minimally invasive approach.