Flavonoids and Alzheimer's disease: reviewing the evidence for neuroprotective potential.

Neurodegeneration, which manifests as several chronic and incurable diseases, is an age-related condition that affects the central nervous system (CNS) and poses a significant threat to the public's health for the elderly. Recent decades have experienced an alarming increase in the incidence of neurodegenerative disorders (NDDs), a severe public health issue due to the ongoing development of people living in modern civilizations. Alzheimer's disease (AD) is a leading trigger of age-related dementia. Currently, there are no efficient therapeutics to delay, stop, or reverse the disease's course development. Several studies found that dietary bioactive phytochemicals, primarily flavonoids, influence the pathophysiological processes underlying AD. Flavonoids work well as a supplement to manufactured therapies for NDDs. Flavonoids are effective in complementing synthetic approaches to treat NDDs. They are biologically active phytochemicals with promising pharmacological activities, for instance, antiviral, anti-allergic, antiplatelet, anti-inflammatory, antitumor, anti-apoptotic, and antioxidant effects. The production of nitric oxide (NO), tumor necrosis factor (TNF-α), and oxidative stress (OS) are downregulated by flavonoids, which slow the course of AD. Hence, this research turned from preclinical evidence to feasible clinical applications to develop newer therapeutics, focusing on the therapeutic potential of flavonoids against AD.

A clinical study and future prospects for bioactive compounds and semi-synthetic molecules in the therapies for Huntington's disease.

A neurodegenerative disorder (ND) refers to Huntington's disease (HD) which affects memory loss, weight loss, and movement dysfunctions such as chorea and dystonia. In the striatum and brain, HD most typically impacts medium-spiny neurons. Molecular genetics, excitotoxicity, oxidative stress (OS), mitochondrial, and metabolic dysfunction are a few of the theories advanced to explicit the pathophysiology of neuronal damage and cell death. Numerous in-depth studies of the literature have supported the therapeutic advantages of natural products in HD experimental models and other treatment approaches. This article briefly discusses the neuroprotective impacts of natural compounds against HD models. The ability of the discovered natural compounds to suppress HD was tested using either in vitro or in vivo models. Many bioactive compounds considerably lessened the memory loss and motor coordination brought on by 3-nitropropionic acid (3-NP). Reduced lipid peroxidation, increased endogenous enzymatic antioxidants, reduced acetylcholinesterase activity, and enhanced mitochondrial energy generation have profoundly decreased the biochemical change. It is significant since histology showed that therapy with particular natural compounds lessened damage to the striatum caused by 3-NP. Moreover, natural products displayed varying degrees of neuroprotection in preclinical HD studies because of their antioxidant and anti-inflammatory properties, maintenance of mitochondrial function, activation of autophagy, and inhibition of apoptosis. This study highlighted about the importance of bioactive compounds and their semi-synthetic molecules in the treatment and prevention of HD.

HIV-sensitive social protection services in mitigating the challenges and vulnerability of the children affected by HIV/AIDS in Bangladesh: a qualitative study.

Children are particularly vulnerable to the consequences of HIV/AIDS. This paper reports on the challenges faced by children due to their or their parents' HIV/AIDS status and the role of HIV-sensitive social protection in mitigating these challenges. We conducted 32 semi-structured in-depth interviews - 15 with children affected by HIV/AIDS (aged 13-18 years) and 17 with parents of children aged 10-12 years. We found children face significant challenges associated with poverty, gender norms, stigma, and lack of social support which affect their rights to education, shelter, treatment, and food. HIV-sensitive social protection packages such as conditional cash transfer, counselling, and community sensitization help continuation of education, facilitate access to treatment and social protection services, reduce stigma in the community and improve wellbeing of children. Children's accessibility to these services was limited due to distance, transport expenses, poor health conditions of the parents, gender issues, and stigma. HIV-sensitive social protection is effective in improving children's wellbeing. Continuation and expansion of HIV-sensitive social protection packages including conditional cash transfer, psychosocial counselling, and community sensitization and life skills training to facilitate HIV/AIDS affected children's wellbeing and inclusion is recommended.

Nitrative DNA damage in lung epithelial cells exposed to indium nanoparticles and indium ions.

Indium compounds have been widely used in manufacturing displays of mobile phones, computers and televisions. However, inhalation exposure to indium compounds causes interstitial pneumonia in exposed workers and lung cancer in experimental animals. 8-Nitroguanine (8-nitroG) is a mutagenic DNA lesion formed under inflammatory conditions and may participate in indium-induced carcinogenesis. In this study, we examined 8-nitroG formation in A549 cultured human lung epithelial cells treated with indium compounds, including nanoparticles of indium oxide (In2O3) and indium-tin oxide (ITO), and indium chloride (InCl3). We performed fluorescent immunocytochemistry to examine 8-nitroG formation in indium-exposed A549 cells. All indium compounds significantly increased 8-nitroG formation in A549 cells at 5 ng/ml after 4 h incubation. 8-NitroG formation was largely reduced by 1400 W, methyl-ß-cyclodextrin (MBCD) and monodansylcadaverine (MDC), suggesting the involvement of nitric oxide synthase and endocytosis. 8-NitroG formation in A549 cells was also largely suppressed by small interfering RNA (siRNA) for high-mobility group box-1 (HMGB1), receptor for advanced glycation and end products (AGER, RAGE) and Toll-like receptor 9 (TLR9). These results suggest that indium compounds induce inflammation-mediated DNA damage in lung epithelial cells via the HMGB1-RAGE-TLR9 pathway. This mechanism may contribute to indium-induced genotoxicity in the respiratory system.

Nitrative DNA damage in cultured macrophages exposed to indium oxide.

OBJECTIVES: Indium compounds are used in manufacturing displays of mobile phones and televisions. However, these materials cause interstitial pneumonia in exposed workers. Animal experiments demonstrated that indium compounds caused lung cancer. Chronic inflammation is considered to play a role in lung carcinogenesis and fibrosis induced by particulate matters. 8-Nitroguanine (8-nitroG) is a mutagenic DNA lesion formed during inflammation and may participate in carcinogenesis. To clarify the mechanism of carcinogenesis, we examined 8-nitroG formation in indium-exposed cultured cells. METHODS: We treated RAW 264.7 mouse macrophages with indium oxide (In2O3) nanoparticles (primary diameter: 30-50 nm), and performed fluorescent immunocytochemistry to detect 8-nitroG. The extent of 8-nitroG formation was evaluated by quantitative image analysis. We measured the amount of nitric oxide (NO) in the culture supernatant of In2O3-treated cells by the Griess method. We also examined the effects of inhibitors of inducible NO synthase (iNOS) and endocytosis on In2O3-induced 8-nitroG formation. RESULTS: In2O3 significantly increased the intensity of 8-nitroG formation in RAW 264.7 cells in a dose-dependent manner. In2O3-induced 8-nitroG formation was observed at 2 h and further increased at 4 h, and the amount of NO released from In2O3-exposed cells was significantly increased at 2-4 h compared with the control. 8-NitroG formation was suppressed by 1400W (an iNOS inhibitor), methyl-ß-cyclodextrin and monodansylcadaverine (inhibitors of caveolae- and clathrin-mediated endocytosis, respectively). CONCLUSIONS: These results suggest that endocytosis and NO generation participate in indium-induced 8-nitroG formation. NO released from indium-exposed inflammatory cells may induce DNA damage in adjacent lung epithelial cells and contribute to carcinogenesis.

Nitrative DNA damage induced by carbon-black nanoparticles in macrophages and lung epithelial cells.

Carbon black (CB) is a nanomaterial used mainly in rubber products. Exposure to CB by inhalation causes malignant lung tumors in experimental animals. CB inhalation may cause chronic inflammation in the respiratory system, leading to carcinogenesis, but the mechanism remains unclear. Reactive oxygen and nitrogen species are generated from inflammatory and epithelial cells under inflammatory conditions, and resulting DNA damage may contribute to carcinogenesis. In this study, we performed immunocytochemistry to determine whether CB exposure induces formation of 8-nitroguanine (8-nitroG), a nitrative DNA lesion formed under inflammatory conditions, in RAW 264.7 macrophage and A549 lung epithelial cells. We compared the DNA-damaging effects of CB particles with primary diameter 56nm (CB56) and 95nm (CB95). Both types of CB induced 8-nitroG formation, mainly in the nucleus of RAW 264.7 and A549 cells, and CB95 tended to induce more 8-nitroG formation than did CB56. Flow cytometry revealed that CB95 generated larger amount of reactive oxygen species than did CB56 in RAW 264.7 cells. The Griess method showed that CB95 produced significantly larger amount of nitric oxide (NO) than did CB56. Flow cytometry showed that CB95 was more efficiently internalized into the cells than was CB56. The cellular uptake of CB and 8-nitroG formation in RAW 264.7 cells were reduced by monodansylcadaverine, an inhibitor of clathrin-mediated endocytosis, and by siRNA for Ctlc (clathrin heavy chain) gene. CB induces nitrative DNA damage in cultured cells, and clathrin-mediated endocytosis is involved, at least in part.