The Interaction Between Nutraceuticals and Gut Microbiota: a Novel Therapeutic Approach to Prevent and Treatment Parkinson's Disease.

Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons, leading to motor and non-motor symptoms. Emerging research has shed light on the role of gut microbiota in the pathogenesis and progression of PD. Nutraceuticals such as curcumin, berberine, phytoestrogens, polyphenols (e.g., resveratrol, EGCG, and fisetin), dietary fibers have been shown to influence gut microbiota composition and function, restoring microbial balance and enhancing the gut-brain axis. The mechanisms underlying these benefits involve microbial metabolite production, restoration of gut barrier integrity, and modulation of neuroinflammatory pathways. Additionally, probiotics and prebiotics have shown potential in promoting gut health, influencing the gut microbiome, and alleviating PD symptoms. They can enhance the gut's antioxidant capacity of the gut, reduce inflammation, and maintain immune homeostasis, contributing to a neuroprotective environment. This paper provides an overview of the current state of knowledge regarding the potential of nutraceuticals and gut microbiota modulation in the prevention and management of Parkinson's disease, emphasizing the need for further research and clinical trials to validate their effectiveness and safety. The findings suggest that a multifaceted approach involving nutraceuticals and gut microbiota may open new avenues for addressing the challenges of PD and improving the quality of life for affected individuals.

The stigma in patients with breast cancer: A concept analysis.

Objective: Stigma is a common problem among patients having breast cancer. However, the concept of stigma is vague and not specifically described or clearly defined in the literature. The lack of description or definition has further limited stigma research among patients having breast cancer. Therefore, this study aimed to clarify and analyze the concept of stigma in patients with breast cancer. Methods: Walker and Avant's concept analysis method was applied to analyze the connotation of stigma in patients with breast cancer. PubMed, Web of Science, PsycINFO, CNKI, Wanfang, VIP, and SinoMed databases were searched from inception until May 31, 2023. Results: Five stigma-related attributes of patients having breast cancer were identified: (1) impaired body image and physiological function; (2) negative stereotypes; (3) mixed negative feelings about developing breast cancer; (4) a feeling of avoidance; (5) experienced discrimination. Antecedents included the implementation of breast surgery and postoperative time, negative psychological factors, lack of social support, and cultural beliefs. This stigma among patients having breast cancer had significant negative effects on their quality of individual life and marriage, postoperative rehabilitation, and healthcare-seeking behavior. Conclusions: The concept analysis results clarified the concept of stigma in patients with breast cancer and provided theoretical guidance for the development of the conceptual model of stigma in these patients. What is more, it offered a theoretical basis for future studies related to the development of stigma assessment tools for breast cancer patients and for devising nursing intervention strategies.

KIF14 affects cell cycle arrest and cell viability in cervical cancer by regulating the p27Kip1 pathway.

BACKGROUND: Cervical cancer is a kind of malignant gynecological tumor. The first choice for treating cervical cancer is still a combination of surgery and chemoradiotherapy, but the 5-year survival rate remains poor. Therefore, researchers are trying to find new ways to diagnose and treat cervical cancer early. METHODS: The expression level of KIF14 in cells and tissues was determined via qRT-PCR. The ability of the cells to proliferate, migrate, and invade was examined using CCK-8 assay kits, colony formation assays, and Transwell chambers. The expression levels of Cyclin D1, Cyclin B1, p21, and p27 were also detected using western blot assays. RESULTS: The results suggested that p27 is a key regulatory factor in the KIF14-mediated regulation of the cell cycle. In addition, KIF14 knockdown promotes malignancy in cervical cancer cells by inhibiting p27 degradation, resulting in cell cycle arrest. CONCLUSIONS: KIF14 is an oncogene in cervical cancer, and knocking down KIF14 causes cell cycle arrest by inhibiting p27 degradation, thus affecting cell viability, proliferation, and migration. These results provide a potential therapeutic target for cervical cancer.

Protective effects of endotoxin tolerance on peripheral lipopolysaccharide-induced neuroinflammation and dopaminergic neuronal injury.

CONTEXT: Parkinson's disease is a common chronic neurodegenerative disease characterized by massive loss of dopaminergic neurons in the substantia nigra. Neuroinflammation has been shown to play an important role in the pathogenesis of neurodegenerative diseases such as Parkinson's disease. The role of immune tolerance in neuroinflammation and neurodegenerative diseases induced by peripheral factors is unclear. OBJECTIVE: This study established a model of endotoxin tolerance to explore the protective effect of endotoxin tolerance on Parkinson-like changes induced by repeated peripheral injections of high-dose LPS, and to explore its inflammatory mechanism. MATERIALS AND METHODS: In this study, mice were injected intraperitoneally with low dose (0.5 mg/kg) LPS for 4 days to induce endotoxin tolerance (ET). Then, high-dose (1 mg/kg) LPS was injected continuously intraperitoneally for 4 days to induce Parkinson-like changes. Cytokines were detected by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). Activation of microglial cells was detected by protein expression of CD68 and ionized calcium binding adapter molecule 1(Iba-1) by Western blotting and immunofluorescence. Hematoxylin and eosin staining and expression of tyrosine hydroxylase (TH) and dopamine (DA) were used to assess dopaminergic neuronal injury. The open field test and muscle tension test were used to assess behavioral disorders. RESULTS: As expected, compared with non-ET animals, ET preconditioning significantly reduced the production of inflammatory cytokines in the substantia nigra, inhibited microglial activation, and alleviated the pathological changes of dopaminergic neurons. CONCLUSIONS: ET may be a promising intervention method for neurodegenerative diseases.HighlightsET was successfully induced by continuous low-dose intraperitoneal LPS injection in mice.ET pretreatment inhibited neuroinflammation in the SN induced by continuous peripheral high doses of LPS.ET pretreatment inhibited continuous peripheral high-dose LPS injection-induced microglial activation in the SN.ET pretreatment decreased LPS-induced functional impairment of dopaminergic neurons.ET reversed the morphological changes of dopaminergic neurons induced by peripheral high-dose LPS.ET pretreatment improved continuous peripheral high-dose LPS injection-induced behavioral impairment.

Soybean isoflavones protect SH-SY5Y neurons from atrazine-induced toxicity by activating mitophagy through stimulation of the BEX2/BNIP3/NIX pathway.

Atrazine (ATR) is a widely used herbicide that can induce the degeneration of dopaminergic (DAergic) neurons in the substantia nigra, resulting in a Parkinson's disease-like syndrome. Despite the high risk of environmental exposure, few studies have investigated strategies for the prevention of ATR neurotoxicity. Our previous studies demonstrated that ATR can impair mitochondrial function, leading to metabolic failure. Cells maintain mitochondrial quality through selective autophagic elimination, termed mitophagy. Soybean isoflavones (SI) possess multiple beneficial bioactivities, including preservation of mitochondria function, so it was hypothesized that SI can protect neurons against ATR toxicity by promoting mitophagy. Pretreatment of SH-SY5Y neurons with SI prevented ATR-induced metabolic failure and cytotoxicity as assessed by intracellular ATP, Na+-K+-ATPase activity, mitochondrial membrane potential, and cell viability assays. The neuroprotective efficacy of SI was superior to the major individual components genistein, daidzein, and glycitein. Ultrastructural analyses revealed that ATR induced mitochondrial damage, while SI promoted the sequestration of damaged mitochondria into autophagic vesicles. Soybean isoflavones also induced mitophagy as evidenced by upregulated expression of BNIP3/NIX, BEX2, and LC3-II, while co-treatment with the mitophagy inhibitor Mdivi-1 blocked SI-mediated neuroprotection and prevented SI from reversing ATR-induced BEX2 downregulation. Furthermore, BEX2 knockdown inhibited SI-induced activation of the BNIP3/NIX pathway, mitophagy, and neuroprotection. These findings suggest that SI protects against ATR-induced mitochondrial dysfunction and neurotoxicity by activating the BEX2/BNIP3/NIX pathway.

Soybean isoflavones prevent atrazine-induced neurodegenerative damage by inducing autophagy.

Atrazine (ATR) is a widely used herbicide with documented dopaminergic (DAergic) neurotoxicity that can lead to a Parkinson's disease (PD)-like motor syndrome. However, there have been few studies on preventative interventions. The aim of the present study was to investigate the neuroprotective efficacy of soybean isoflavones (SI) and associated molecular mechanisms in a rat model of ATR-induced DAergic toxicity. Male Sprague-Dawley rats (6 weeks old) received daily intraperitoneal injection of SI (10, 50, or 100 mg/kg) or vehicle followed 1 h later by oral gavage of ATR (50 mg/kg) for 45 consecutive days. Open field and grip-strength tests indicated no differences in motor function among treatment groups. Alternatively, histopathology revealed neuronal damage in the striatum of rats receiving vehicle plus ATR that was ameliorated by SI pretreatment. SI attenuate ATR-induced oxidative stress (indicated by MDA accumulation and GSH depletion) and inflammatory damage (as evidenced by TNF-α and IL-6 elevation) in the substantia nigra. ATR increased expression of the pro-apoptotic factor Bax and reduced expression levels of the DA synthesis enzyme tyrosine hydroxylase (TH) and the anti-apoptotic factor Bcl-2 in the substantia nigra and striatum. All of these effects were reversed by SI pretreatment, suggesting that SI can inhibit ATR-induced apoptosis of DAergic neurons. ATR also inhibited autophagy in the substantial nigra as evidenced by LC3-II and Beclin-1 downregulation and increased expression of p62, whereas SI pretreatment reversed these effects, indicating autophagy induction. Furthermore, ATR increased the expression of mTOR and reduced the expression of phosphorylated S6 (p-S6) and BEX2 in the substantia nigra. Collectively, these findings suggest that SI can prevent ATR-mediated degeneration of DAergic neurons by inducing autophagy through an mTOR-dependent signaling pathway.

A retrospective study of smoking cessation intervention among university students.

This retrospective study investigated the effect of smoking cessation intervention (SCI) among university students in China.Around 192 eligible smokers among university students were included, and were assigned to an intervention group (n = 100), and a control group (n = 92). All included subjects in both groups were recommended to increase fruits and vegetables consumptions. Additionally, participants in the intervention group also underwent SCI therapy for a total of 4 weeks. The outcome measurements consisted of a number of students quit smoking, daily cigarettes, quit attempts, mean days of smoking in the past 30 days, and also stage of change.After 4-week treatment, SCI neither can decrease the number of students quit smoking (P = .21), daily cigarettes (P = .21), quit attempts (P = .07), and mean days of smoking in past 30 days (P = .77), nor can enhance the stage of change (precontemplation, P = .18; contemplation, P = .59; preparation, P = .46).The results of this study showed that after 4-week therapy, SCI may be ineffective for smokers among university students in Chinese.

Association of selenoprotein S gene polymorphism with ischemic stroke in a Chinese case-control study.

Previous studies showed that selenoprotein S (SELS) was associated with a range of inflammatory markers, and its gene expression was influenced by a polymorphism in the promoter region. The genetic basis of the ischemic stroke has now been largely determined, so the aim of the study was to examine the role of SELS genetic variants in the ischemic stroke risk in a Chinese population. We conducted a case-control study with 239 ischemic stroke patients and 240 controls. Two single-nucleotide polymorphisms (SNPs) in SELS genes were analyzed for association with the risk of ischemic stroke in the Chinese Han population. No evidence of ischemic stroke association was observed with the SNP rs34713741. Interestingly, the strongest evidence showed that SELS SNP rs4965814 was associated with ischemic stroke (P < 0.05). We found a significant association with increased ischemic stroke risk in women carrying the CC genotype of rs4965814 [hazard ratio: 2.43(1.03-5.75)]; a similar trend was also found in men carrying the TC genotype of rs4965814 [hazard ratio: 1.81(1.06-3.08)]. SNP rs4965814 of SELS may affect the susceptibility to ischemic stroke. Understanding the inflammatory mechanisms of ischemic stroke may give new therapeutic targets to pharmacologists.

[Expression profile analysis of intestinal Caco-2 cells treated with Lactobacillus acidophilus NCFM].

OBJECTIVE: Lactobacillus acidophilus NCFM is a probiotic strain that promotes human health. We evaluated the influence of Lactobacillus acidophilus NCFM on the genetic expression patterns in the Caco-2 cells. METHODS: Caco-2 cells were treated with Lactobacillus acidophilus NCFM for 2h. The total RNA of cells was extracted. Hybridization with Human Genome U133 Plus 2.0 Array was performed. The image scanning and data analysis were performed subsequently. Genes with significant expression changes were selected and analyzed. To support the microarray data, three striking difference genes were studied using Real-time RT PCR. RESULTS: Microarrays analysis showed that the expression levels of 508 genes were altered as compared with the control 473 of them were up-regulated, and 35 were down-regulated. It was supposed that many genes in Caco-2 cell were induced, so that Lactobacillus acidophilus NCFM could play a part in immune system process, antioxidant activity, biological adhesion, cholesterol absorption and so on. Three striking difference genes CCL2, PTX3 and TNFRSF9 which involved immune system process were validated by Real-time RT PCR. And the results of Real-time RT PCR showed the same expression trend as in microarray. CONCLUSION: Based on the results of gene expression alterations, the beneficial function of Lactobacillus acidophilus NCFM could be more greatly and deeply understood than ever before, and the mechanism of lactic acid bacteria would be revealed.

Local inflammation exacerbates cyclosporine a-induced gingival overgrowth in rats.

Gingival overgrowth (GO) is a common side effect of long-term cyclosporine A (CsA) treatment. The risk factors appraised include drug interactions with calcium channel blockers, age, cyclosporine dose, dental bacterial plaque, duration of treatment, and genetic predisposition. The relationship and mechanism between GO and local inflammation caused by dental bacterial plaque have not been clearly defined. This research was carried out to investigate the histomorphometrical alterations and serum levels of transforming growth factor beta1 (TGF-beta1) in CsA-induced GO with or without local inflammation. Thirty-four male Sprague-Dawley rats were divided into 4 groups: Group I (control); Group II (ligation); Group III (CsA); Group IV (ligation and CsA). After 9 weeks the rats were sacrificed. The morphological examination was made and the histological changes with hematoxylin and eosin (HE) staining were observed. TGF-beta1 levels in serum were detected by enzyme-linked immunosorbent assay (ELISA). We report here that obvious GO are found in Group III and Group IV after CsA treatment, especially those rats with existed gingivitis presented an aggravation of GO. TGF-beta1 levels in CsA-exposed groups were significantly higher than untreated groups, but ligation did not affect TGF-beta1 level. These findings suggest that CsA-induced GO can be exacerbated by local inflammation. TGF-beta1 may be a key factor for the development of GO.