Withania somnifera and Trigonella foenum-graecum as ingredients of testosterone-boosting supplements: Possible clinical implications.

This narrative review provides an overview of scientific studies on dietary supplements that may affect circulating testosterone (T) levels to explore which substances are scientifically proven to increase T concentration. We also review the scientific literature for their potential mechanisms and laboratory test changes triggered by their use. Based on the analysis of existing data on substances used to increase endogenous T levels, especially double-blind placebo-controlled randomized clinical trials, we selected 2 herbal extracts with the best documented positive effects on T levels, Withania somnifera root and root extracts/leaves and seed extracts of Trigonella foenum-graecum. Although these substances have different postulated mechanisms of action, both significantly increase T levels in men. Withania somnifera may inhibit the effects of cortisol and prolactin on the hypothalamic-pituitary-gonadal axis and directly affect the hypothalamus. Trigonella foenum-graecum seeds contain the active substance diosgenin, which is a precursor for sex hormone synthesis in gonads.

Extract from Aronia melanocarpa, Lonicera caerulea, and Vaccinium myrtillus Improves near Visual Acuity in People with Presbyopia.

Presbyopia is a global problem with an estimated 1.3 billion patients worldwide. In the area of functional food applications, dietary supplements or herbs, there are very few reports describing the positive effects of their use. In the available literature, there is a lack of studies in humans as well as on an animal model of extracts containing, simultaneously, compounds from the polyphenol group (in particular, anthocyanins) and iridoids, so we undertook a study of the effects of a preparation composed of these compounds on a condition of the organ of vision. Our previous experience on a rabbit model proved the positive effect of taking an oral extract of Cornus mas in stabilizing the intraocular pressure of the eye. The purpose of this study was to evaluate the effect of an orally administered ternary compound preparation on the status of physiological parameters of the ocular organ. The preparation contained an extract of the chokeberry Aronia melanocarpa, the honeysuckle berry Lonicera caerulea L., and the bilberry Vaccinium myrtillus (hereafter AKB) standardized for anthocyanins and iridoids, as bioactive compounds known from the literature. A randomized, double-blind, cross-over study lasting with a "wash-out" period of 17 weeks evaluated a group of 23 people over the age of 50, who were subjects with presbyopia and burdened by prolonged work in front of screen monitors. The group of volunteers was recruited from people who perform white-collar jobs on a daily basis. The effects of the test substances contained in the preparation on visual acuity for distance and near, sense of contrast for distance and near, intraocular pressure, and conjunctival lubrication, tested by Schirmer test, LIPCOF index and TBUT test, and visual field test were evaluated. Anthocyanins (including cyanidin 3-O-galactoside, delphinidin 3-O-arabinoside, cyanidin 3-O-glucoside, cyanidin 3-O-rutinoside, cyanidin 3-O-arabinoside) and iridoids (including loganin, sweroside, loganic acid) were identified as substances present in the extract obtained by HPLC-MS. The preliminary results showed that the composition of AKB applied orally does not change visual acuity in the first 6 weeks of administration. Only in the next cycle of the study was an improvement in near visual acuity observed in 92.3% of the patients. This may indicate potential to correct near vision in presbyopic patients. On the other hand, an improvement in conjunctival wetting was observed in the Schirmer test at the beginning of week 6 of administration in 80% of patients. This effect was weakened in subsequent weeks of conducting the experiment to 61.5%. The improvement in conjunctival hydration in the Schirmer test shows the potential beneficial effect of the AKB formulation in a group of patients with dry eye syndrome. This is the first study of a preparation based on natural, standardized extracts of chokeberry, honeysuckle berry, and bilberry. Preliminary studies show an improvement in near visual acuity and conjunctival hydration on the Schirmer test, but this needs to be confirmed in further studies.

RhoA/ROCK Pathway Is Upregulated in Experimental Autoimmune Myocarditis and Is Inhibited by Simvastatin at the Stage of Myosin Light Chain Phosphorylation.

Many studies have proven the involvement of the RhoA/ROCK pathway in autoimmune and cardiovascular diseases and the beneficial effects of its downregulation. Here, we examined whether the effect of simvastatin on experimental autoimmune myocarditis (EAM) may be through targeting the Ras homolog family member A/Rho-associated coiled-coil containing kinases (RhoA/ROCK) pathway and whether previously shown downregulation of metalloproteinase 9 (MMP-9) could be associated with MLC phosphorylation. Two doses of simvastatin were administered to experimental rats with autoimmune myocarditis by gastric gavage for 3 weeks, at the stage of development of the inflammatory process. Immunohistochemical staining for RhoA and ROCK1 was evaluated semi-quantitatively with H-score. The RhoA staining showed no significant differences in expression between the groups, but the ROCK1 expression was significantly upregulated in the hearts of the EAM group and was not downregulated by simvastatin. The Western blotting analysis of the last downstream product of the RhoA/ROCK axis, phosphorylated myosin light chain (phospho-MYL9), revealed that protein content increased in EAM hearts and it was prevented by the highest dose of simvastatin. Our findings suggest that the RhoA/ROCK pathway is upregulated in EAM, and simvastatin in EAM settings inhibits the RhoA/ROCK pathway at the stage of phosphorylation of myosin light chains and provides a new insight into the molecular pathology of autoimmune myocarditis.

Cornelian Cherry (Cornus mas L.) Fruit Extract Lowers SREBP-1c and C/EBPα in Liver and Alters Various PPAR-α, PPAR-γ, LXR-α Target Genes in Cholesterol-Rich Diet Rabbit Model.

Cornelian cherry (Cornus mas L.) fruits, abundant in iridoids and anthocyanins, are natural products with proven beneficial impacts on the functions of the cardiovascular system and the liver. This study aims to assess and compare whether and to what extent two different doses of resin-purified cornelian cherry extract (10 mg/kg b.w. or 50 mg/kg b.w.) applied in a cholesterol-rich diet rabbit model affect the levels of sterol regulatory element-binding protein 1c (SREBP-1c) and CCAAT/enhancer binding protein α (C/EBPα), and various liver X receptor-α (LXR-α), peroxisome proliferator-activated receptor-α (PPAR-α), and peroxisome proliferator-activated receptor-γ (PPAR-γ) target genes. Moreover, the aim is to evaluate the resistive index (RI) of common carotid arteries (CCAs) and aortas, and histopathological changes in CCAs. For this purpose, the levels of SREBP-1c, C/EBPα, ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), fatty acid synthase (FAS), endothelial lipase (LIPG), carnitine palmitoyltransferase 1A (CPT1A), and adiponectin receptor 2 (AdipoR2) in liver tissue were measured. Also, the levels of lipoprotein lipase (LPL), visceral adipose tissue-derived serine protease inhibitor (Vaspin), and retinol-binding protein 4 (RBP4) in visceral adipose tissue were measured. The RI of CCAs and aortas, and histopathological changes in CCAs, were indicated. The oral administration of the cornelian cherry extract decreased the SREBP-1c and C/EBPα in both doses. The dose of 10 mg/kg b.w. increased ABCA1 and decreased FAS, CPT1A, and RBP4, and the dose of 50 mg/kg b.w. enhanced ABCG1 and AdipoR2. Mitigations in atheromatous changes in rabbits' CCAs were also observed. The obtained outcomes were compared to the results of our previous works. The beneficial results confirm that cornelian cherry fruit extract may constitute a potentially effective product in the prevention and treatment of obesity-related disorders.

Does a pickle a day keep Alzheimer's away? Fermented food in Alzheimer's disease: A review.

Fermented food is commonly viewed as healthy, mostly due to its probiotic and digestion-enhancing properties and recently it has been examined with regard to the development of new therapeutic and preventive measures for Alzheimer's disease. Fermented food has been shown to have anti-inflammatory and antioxidant properties and to alter the gut microbiota. However, the exact pathogenesis of Alzheimer's disease is still unknown and its connections to systemic inflammation and gut dysbiosis, as potential targets of fermented food, require further investigation. Therefore, to sum up the current knowledge, this article reviews recent research on the pathogenesis of Alzheimer's disease with emphasis on the role of the gut-brain axis and studies examining the use of fermented foods. The analysis of the fermented food research includes clinical and preclinical in vivo and in vitro studies. The fermented food studies have shown promising effects on amyloid-ß metabolism, inflammation, and cognitive impairment in animals and humans. Fermented food has great potential in developing new approaches to Alzheimer's disease treatment.

Imatinib-Functionalized Galactose Hydrogels Loaded with Nanohydroxyapatite as a Drug Delivery System for Osteosarcoma: In Vitro Studies.

This study reports an impact of structure (XRPD, FT-IR) and surface morphology (SEM-EDS) of imatinib-functionalized galactose hydrogels, loaded and unloaded with nHAp, on osteosarcoma cell (Saos-2 and U-2OS) viability, levels of free oxygen radicals, and nitric oxide, levels of BCL-2, p53, and caspase 3 and 9, as well as glycoprotein-P activity. It was investigated how the rough surface of the crystalline hydroxyapatite-modified hydrogel affected amorphous imatinib (IM) release. The imatinib drug effect on cell cultures has been demonstrated in different forms of administration-directly to the culture or the hydrogels. Administration of IM and hydrogel composites could be expected to reduce the risk of multidrug resistance development by inhibiting Pgp.

The Hypothalamic-Pituitary-Gonadal Axis in Men with Schizophrenia.

Schizophrenia is a severe mental disorder with a chronic, progressive course. The etiology of this condition is linked to the interactions of multiple genes and environmental factors. The earlier age of onset of schizophrenia, the higher frequency of negative symptoms in the clinical presentation, and the poorer response to antipsychotic treatment in men compared to women suggests the involvement of sex hormones in these processes. This article aims to draw attention to the possible relationship between testosterone and some clinical features in male schizophrenic patients and discuss the complex nature of these phenomena based on data from the literature. PubMed, Web of Science, and Google Scholar databases were searched to select the papers without limiting the time of the publications. Hormone levels in the body are regulated by many organs and systems, and take place through the neuroendocrine, hormonal, neural, and metabolic pathways. Sex hormones play an important role in the development and function of the organism. Besides their impact on secondary sex characteristics, they influence brain development and function, mood, and cognition. In men with schizophrenia, altered testosterone levels were noted. In many cases, evidence from available single studies gave contradictory results. However, it seems that the testosterone level in men affected by schizophrenia may differ depending on the phase of the disease, types of clinical symptoms, and administered therapy. The etiology of testosterone level disturbances may be very complex. Besides the impact of the illness (schizophrenia), stress, and antipsychotic drug-induced hyperprolactinemia, testosterone levels may be influenced by, i.a., obesity, substances of abuse (e.g., ethanol), or liver damage.

Cornus mas L. Extract Targets the Specific Molecules of the Th17/Treg Developmental Pathway in TNBS-Induced Experimental Colitis in Rats.

Given that one of the crucial events in the pathogenesis of inflammatory bowel disease is the loss of homeostasis between Th17 and Treg cells, targeting the specific molecules of the Th17/Treg axis developmental pathway is a promising strategy for inflammatory bowel disease prevention and treatment. The current study aimed to assess the impact of cornelian cherry (Cornus mas L.) extract, rich in iridoids and polyphenols known for their potential anti-inflammatory activity, at two doses (20 or 100 mg/kg) on the crucial factors for Th17/Treg cell differentiation in the course of experimental colitis and compare this action with that of sulfasalazine. This study was conducted on the biobank colon tissue samples collected during the previous original experiment, in which colitis in rats was induced by trinitrobenzenesulfonic acid (TNBS). The levels of IL-6, RORγt, total STAT3, p-STAT3, and Foxp3 were determined by ELISA. The expression of PIAS3 mRNA was quantified by qPCR. Cornelian cherry extract at a dose of 100 mg/kg counteracted the TNBS-induced elevation of IL-6, RORγt, and p-STAT3 levels and a decrease in Foxp3 level and PIAS3 mRNA expression, while given concomitantly with sulfasalazine was more effective than sulfasalazine alone in reversing the TNBS-induced changes in IL-6, RORγt, total STAT3, p-STAT3, Foxp3 levels, and PIAS3 mRNA expression. The beneficial effect of cornelian cherry extract on experimental colitis may be due to its immunomodulatory activity reflected by the influence on factors regulating the Th17/Treg axis.

Does Inflammation Play a Major Role in the Pathogenesis of Alzheimer's Disease?

Alzheimer's disease (AD) is a neurodegenerative disease leading to dementia for which no effective medicine exists. Currently, the goal of therapy is only to slow down the inevitable progression of the disease and reduce some symptoms. AD causes the accumulation of proteins with the pathological structure of Aß and tau and the induction of inflammation of nerves in the brain, which lead to the death of neurons. The activated microglial cells produce pro-inflammatory cytokines that induce a chronic inflammatory response and mediate synapse damage and the neuronal death. Neuroinflammation has been an often ignored aspect of ongoing AD research. There are more and more scientific papers taking into account the aspect of neuroinflammation in the pathogenesis of AD, although there are no unambiguous results regarding the impact of comorbidities or gender differences. This publication concerns a critical look at the role of inflammation in the progression of AD, based on the results of our own in vitro studies using model cell cultures and other researchers.

Do Medical Universities Students Use Cognitive Enhancers while Learning?-Conclusions from the Study in Poland.

BACKGROUND: Stress and everyday problems may impact memory and cognition. Therefore, many people use cognitive enhancers (CEs), sold for prescription, as over-the-counter drugs, or dietary supplements, believing they may help with everyday functioning. Our study was designed to answer whether taking CEs is common among Medical University students and to identify which substances are mainly used. METHODS AND RESULTS: An anonymous online questionnaire was answered by 479 students of Medical (88%) and Dentistry (12%) Faculties in Poland. Women constituted the majority of respondents (63%). CEs were used by 53% of respondents, with the most frequent being caffeine, ginseng, nicotine, theanine, ginkgo, and lecithin. Some persons used CEs that are available only with a prescription. The most important reasons for the use of CEs were to increase arousal and improve concentration (mentioned by 81% and 73%, respectively). Over 65% of students experienced some undesired/adverse effects after taking CEs, with tachycardia being the most common, followed by sleep disturbances (reported by 51% and 40%, respectively). CONCLUSIONS: More than half of the respondents from the Medical and Dentistry Faculties reported using CEs, despite their unproven efficacy and not-well-established safety. This raises significant concern about the knowledge of young persons regarding CEs and should encourage universities to undertake educational actions.

Search for immunomodulatory compounds with antiproliferative activity against melanoma.

BACKGROUND: Melanoma is a highly aggressive neoplasm with a high degree of malignancy and rapid acquisition of resistance by cancer cells. METHODS: Biological studies of a series of isoxazole compounds with immunomodulatory properties were preceded by in silico analysis. The assay evaluated the viability of NHDF and A375 cell cultures after the administration of isoxazole compounds after a 24-hour incubation period in the MTT test. Analyzes of ROS and NO scavenging, P-glycoprotein activity, and properties were performed. The levels of Caspase 3 and Caspase 9 were measured using ELISA to assess which pathways induced apoptosis by the tested compounds. On the chip, the synergistic effect of doxorubicin and the most active compound from the MM9 series on cells of the A375 melanoma line was determined. RESULTS: All tested N'-substituted derivatives of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide with immunomodulatory activity show multidirectional antitumor activity on A375 melanoma lines with an affinity for P-glycoprotein, induction of free radical formation and generation of DNA damage leading to the death of cancer cells, as well as formation of complexes with DNA Topoisomerase II. Most of the tested compounds show pro-apoptotic activity. The most active compound in the series induces apoptosis in three distinct pathways and acts synergistically with doxorubicin. CONCLUSIONS: The most active compound with immunomodulatory properties showed multidirectional antitumor activity against cells of the A375 melanoma line and also had a synergistic pro-apoptotic effect with doxorubicin, which may result in a reduction of this cytostatic dose with increased effectiveness.

Cornelian Cherry (Cornus mas L.) Iridoid and Anthocyanin-Rich Extract Reduces Various Oxidation, Inflammation, and Adhesion Markers in a Cholesterol-Rich Diet Rabbit Model.

Atherogenesis leads to the development of atherosclerosis, a progressive chronic disease characterized by subendothelial lipoprotein retention and endothelial impairment in the arterial wall. It develops mainly as a result of inflammation and also many other complex processes, which arise from, among others, oxidation and adhesion. Cornelian cherry (Cornus mas L.) fruits are abundant in iridoids and anthocyanins-compounds with potent antioxidant and anti-inflammatory activity. This study aimed to determine the effect of two different doses (10 mg and 50 mg per kg of body weight, respectively) of iridoid and anthocyanin-rich resin-purified Cornelian cherry extract on the markers that are important in the progress of inflammation, cell proliferation and adhesion, immune system cell infiltration, and atherosclerotic lesion development in a cholesterol-rich diet rabbit model. We used biobank blood and liver samples that were collected during the previous original experiment. We assessed the mRNA expression of MMP-1, MMP-9, IL-6, NOX, and VCAM-1 in the aorta, and the serum levels of VCAM-1, ICAM-1, CRP, PON-1, MCP-1, and PCT. The application of the Cornelian cherry extract at a dose of 50 mg/kg bw resulted in a significant reduction in MMP-1, IL-6, and NOX mRNA expression in the aorta and a decrease in VCAM-1, ICAM-1, PON-1, and PCT serum levels. The administration of a 10 mg/kg bw dose caused a significant decrease in serum ICAM-1, PON-1, and MCP-1. The results indicate the potential usefulness of the Cornelian cherry extract in the prevention or treatment of atherogenesis-related cardiovascular diseases, such as atherosclerosis or metabolic syndrome.

The Proton Pump Inhibitors Use and COVID-19 from Prior to Vaccination Perspective: A Review.

BACKGROUND: The coronavirus infectious disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has been a huge challenge, affecting directly or indirectly the human race worldwide. Many COVID-19-related risk factors have been identified. Various drugs, including proton pump inhibitors (PPIs), have been claimed to increase the risk of acquiring or affecting the outcome of COVID-19 prior to the availability of vaccines. The aim of this review was to summarize the uncertain role of PPI use on the SARS-CoV-2 infection and COVID-19 clinical course, including both some well-established and presumptive indications to these potent inhibitors of gastric acid secretion, before vaccinations against COVID-19 were implemented on a massive scale. SUMMARY: Although iatrogenic hypochlorhydria alters human microbiota and impairs the nonspecific innate immunity, increasing the likelihood of gastrointestinal and pulmonary infections, published data on the relationship between SARS-CoV-2 positivity and clinical manifestations of COVID-19 are quite inconclusive. On the contrary, the beneficial role of PPI use in the prevention of the upper gastrointestinal bleeding, particularly in at-risk patients receiving dual antiplatelet treatment and/or concomitant anticoagulation, constituting a significant proportion of COVID-19 patients, has been well-documented. Furthermore, PPIs have been marked as a potential antiviral remedy, just like many already existing repurposed drugs, that merit further studies in search of successful anti-CO-VID-19 pharmacotherapy. KEY MESSAGES: The controversial role of PPIs on the SARS-CoV-2 infection and COVID-19 severity propounded in the past should not prevent the use of these potent inhibitors of gastric acid secretion in well-established clinical indications.

The Protective Effect of Simvastatin on the Systolic Function of the Heart in the Model of Acute Ischemia and Reperfusion Is Due to Inhibition of the RhoA Pathway and Independent of Reduction of MMP-2 Activity.

The present study investigated whether Rho-associated protein kinase (RhoA/ROCK) signaling pathway inhibitor simvastatin inhibits matrix metalloproteinase 2 (MMP-2) activity in a rat ischemia-reperfusion injury (I/Ri) model by inhibiting the RhoA/ROCK pathway and reducing MMP-2 mRNA levels. Isolated rat hearts were subjected to aerobic perfusion or I/Ri control. The effect of simvastatin was assessed in hearts subjected to I/Ri. We determined cardiac mechanical function, the content of RhoA, phosphorylated myosin light chain subunit 1 (phospho-MYL9), troponin I, MMP-2, and MMP-2 mRNA in the heart homogenates, as well as MMP-2 activity in heart tissue. We showed that treatment with simvastatin caused improvement in the contractile function of the heart subjected to I/Ri which was accompanied by a decrease of MMP-2 activity in heart tissue along with inhibition of RhoA pathway, expressed in a reduction in both RhoA and its downstream product-phosphorylated myosin light chain (phospho-MYL9) in hearts treated with simvastatin. MMP-2 inactivation is not due to inhibition of MMP-2 m-RNA synthesis caused by inhibition of RhoA/ROCK pathway and is due, at least in part, to the direct drug action. The protective effect of simvastatin on systolic function in the acute ischemia-reperfusion model does not appear to be related to reduced MMP-2 activation, but other mechanisms related with the inhibition RhoA/ROCK pathway.

Effect of tricyclic 1,2-thiazine derivatives in neuroinflammation induced by preincubation with lipopolysaccharide or coculturing with microglia-like cells.

BACKGROUND: Alzheimer's disease (AD) is considered the most common cause of dementia among the elderly. One of the modifiable causes of AD is neuroinflammation. The current study aimed to investigate the influence of new tricyclic 1,2-thiazine derivatives on in vitro model of neuroinflammation and their ability to cross the blood-brain barrier (BBB). METHODS: The potential anti-inflammatory effect of new tricyclic 1,2-thiazine derivatives (TP1, TP4, TP5, TP6, TP7, TP8, TP9, TP10) was assessed in SH-SY5Y cells differentiated to the neuron-like phenotype incubated with bacterial lipopolysaccharide (5 or 50 µg/ml) or THP-1 microglial cell culture supernatant using MTT, DCF-DA, Griess, and fast halo (FHA) assays. Additionally, for cultures preincubated with 50 µg/ml lipopolysaccharide (LPS), a cyclooxygenase (COX) activity assay was performed. Finally, the potential ability of tested compounds to cross the BBB was evaluated by computational studies. Molecular docking was performed with the TLR4/MD-2 complex to assess the possibility of binding the tested compounds in the LPS binding pocket. Prediction of ADMET parameters (absorption, distribution, metabolism, excretion and toxicity) was also conducted. RESULTS: The unfavorable effect of LPS and co-culture with THP-1 cells on neuronal cell viability was counteracted with TP1 and TP4 in all tested concentrations. Tested compounds reduced the oxidative and nitrosative stress induced by both LPS and microglia activation and also reduced DNA damage. Furthermore, new derivatives inhibited total COX activity. Additionally, new compounds would cross the BBB with high probability and reach concentrations in the brain not lower than in the serum. The binding affinity at the TLR4/MD-2 complex binding site of TP4 and TP8 compounds is similar to that of the drug donepezil used in Alzheimer's disease. The ADMET analysis showed that the tested compounds should not be toxic and should show high intestinal absorption. CONCLUSIONS: New tricyclic 1,2-thiazine derivatives exert a neuroregenerative effect in the neuroinflammation model, presumably via their inhibitory influence on COX activity and reduction of oxidative and nitrosative stress.

Targeting Lineage-Specific Transcription Factors and Cytokines of the Th17/Treg Axis by Novel 1,3,4-Oxadiazole Derivatives of Pyrrolo[3,4-d]pyridazinone Attenuates TNBS-Induced Experimental Colitis.

The pharmacotherapy of inflammatory bowel disease (IBD) is still not fully effective and safe. Attempts to search for new IBD drugs remain an incessant research aim. One of the novel approaches is targeting the developmental pathway molecules and effector cytokines of Th17/Treg axis. This study aimed to elucidate the impact of new pyrrolo[3,4-d]pyridazinone derivatives, compounds 7b, 10b, or 13b, on the course of experimental colitis in rats and to assess whether these new compounds may influence Th17/Treg axis. Rats were pretreated with studied compounds intragastrically before intrarectal administration of 2,4,6-trinitrobenzenesulfonic acid used for colitis induction. Body weight loss, disease activity index, colon index, and colon tissue damage were analyzed to evaluate the severity of colitis. The colonic levels of RORγt, STAT3, CCR6, Foxp3, IL-6, IL-10, IL-17, TNF-α, IL-23, and PGE2 were assessed. Pretreatment with compounds 7b and 13b alleviated the severity of colitis and concomitantly counteracted the increased levels of RORγt, STAT3, CCR6, IL-6, IL-17, IL-23, TNF-α, and PGE2. The beneficial effect of compounds 7b and 13b may be due to the decrease in the levels of Th17-specific transcription factors and cytokines. The studied compounds might therefore constitute a promising therapeutic strategy in Th17/Treg imbalance-driven inflammatory conditions such as IBD.

The Risk of Developing Alzheimer's Disease and Parkinson's Disease in Patients with Inflammatory Bowel Disease: A Meta-Analysis.

Recently, a growing body of research has linked gut microbiota dysbiosis to central nervous system diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), and has suggested that AD and PD pathology may take its origin from chronic inflammation in the gastrointestinal tract. Thus, this study aimed to elucidate whether inflammatory bowel disease (IBD) is associated with a higher risk of developing AD and PD as compared to the non-IBD population by conducting a meta-analysis. A thorough search of Pubmed and Embase databases was performed to identify all relevant articles. The quality of included studies was assessed using the Newcastle-Ottawa Scale. The odds ratios (ORs) with 95% confidence intervals (CIs) were analyzed using a fixed-effect model. To assess publication bias and heterogeneity among the studies, Egger's test and L'Abbé plots were used, respectively. A total of eight eligible studies were included in this meta-analysis. No significant heterogeneity or significant publication bias was detected. The risk of developing AD in IBD patients was higher than in non-IBD patients (OR = 0.37; 95% CI = 0.14−1.00; p = 0.05), and there was a relationship between the occurrence of AD and Crohn's disease or ulcerative colitis (OR = 0.11; 95% CI = 0.04−0.30; p < 0.0001, OR = 0.14; 95% CI = 0.04−0.49; p = 0.0024, respectively). The risk of developing both of the most common neurodegenerative diseases, AD and PD, was also significantly higher in patients diagnosed with Crohn's disease or ulcerative colitis (OR = 0.21; 95% CI = 0.09−0.49; p = 0.0003, OR = 0.25; 95% CI = 0.13−0.51; p = 0.0001, respectively). This meta-analysis revealed a higher risk of AD and PD among CD and UC patients compared to the general population. It may suggest a key role for the gut microbiota in the pathogenesis of not only Crohn's disease and ulcerative colitis but also AD and PD. The identification of this potential risk may provide earlier preventive measures to be implemented to reduce comorbidity and mortality rate.

Factors That Influence the Use of Dietary Supplements among the Students of Wroclaw Medical University in Poland during the COVID-19 Pandemic.

BACKGROUND AND AIM: The use of dietary supplements (DS) and over-the-counter (OTC) drugs is increasing every year. The COVID-19 pandemic might additionally influence the use of such preparations. The study aimed to investigate factors influencing the use of dietary supplements (DS), including stress-relieving supplements, by the students. METHODS: In the cross-sectional study, 624 students of the Wroclaw Medical University in Poland, from the second to the last year of studies, completed the anonymous questionnaire, consisting of 22 items, about the use of DS/OTC drugs during the academic year 2020/2021. Obtained data were analyzed using Pearson's chi-square test, the U-Mann Whitney test, the Kruskal-Wallis test with the post-hoc analysis, and with logistic regression. RESULTS: About 70% of students declared the use of any DS, 33% used DS for stress, anxiety, depression, or sleeping problems, and 59% used other DS. The most important factors influencing the decision to take any kind of DS were Division (p = 0.0001, odds ratio [OR]: 0.35, and confidence interval [CI]: 0.21-0.59), a self-estimated level of stress (p = 0.014, OR: 1.13, CI: 1.03-1.25), and self-estimated level of knowledge about DS (p = 0.0000, OR: 1.31, CI: 1.19-1.36). In the case of students taking DS for stress, anxiety, depression, or sleeping problems, the level of stress and the declared knowledge had the greatest impact on the decision for such a use of DS (p = 0.0001, OD: 1.24, CI: 1.11-1.39 and p = 0.0000, OD: 1.35, CI: 1.22-1.5, respectively). The COVID-19 pandemic did not change the pattern of DS/OTC drug usage in about 33% of students. Those who started taking DS during the pandemic accounted for 19% of all students. CONCLUSIONS: The use of DS is common among Wroclaw Medical University students with some differences between subgroups of respondents. Additionally, despite declared good knowledge about DS, most students declare the need to learn more about them.

The Role of the Microbiota-Gut-Brain Axis in the Development of Alzheimer's Disease.

Along with the increase in life expectancy in the populations of developed and developing countries resulting from better access and improved health care, the number of patients with dementia, including Alzheimer's disease (AD), is growing. The disease was first diagnosed and described at the beginning of the 20th century. However, to this day, there is no effective causal therapy, and symptomatic treatment often improves patients' quality of life only for a short time. The current pharmacological therapies are based mainly on the oldest hypotheses of the disease-cholinergic (drugs affecting the cholinergic system are available), the hypothesis of amyloid-ß aggregation (an anti-amyloid drug was conditionally approved by the FDA in 2020), and one drug is an N-methyl-D-aspartate receptor (NMDAR) antagonist (memantine). Hypotheses about AD pathogenesis focus on the nervous system and the brain. As research progresses, it has become known that AD can be caused by diseases that have been experienced over the course of a lifetime, which could also affect other organs. In this review, we focus on the potential association of AD with the digestive system, primarily the gut microbiota. The role of diet quality in preventing and alleviating Alzheimer's disease is also discussed. The problem of neuroinflammation, which may be the result of microbiota disorders, is also described. An important aspect of the work is the chapter on the treatment strategies for changing the microbiota, potentially protecting against the disease and alleviating its course in the initial stages.

Influence of 40 Hz and 100 Hz Vibration on SH-SY5Y Cells Growth and Differentiation-A Preliminary Study.

(1) Background: A novel bioreactor platform of neuronal cell cultures using low-magnitude, low-frequency (LMLF) vibrational stimulation was designed to discover vibration influence and mimic the dynamic environment of the in vivo state. To better understand the impact of 40 Hz and 100 Hz vibration on cell differentiation, we join biotechnology and advanced medical technology to design the nano-vibration system. The influence of vibration on the development of nervous tissue on the selected cell line SH-SY5Y (experimental research model in Alzheimer's and Parkinson's) was investigated. (2) Methods: The vibration stimulation of cell differentiation and elongation of their neuritis were monitored. We measured how vibrations affect the morphology and differentiation of nerve cells in vitro. (3) Results: The highest average length of neurites was observed in response to the 40 Hz vibration on the collagen surface in the differentiating medium, but cells response did not increase with vibration frequency. Also, vibrations at a frequency of 40 Hz or 100 Hz did not affect the average density of neurites. 100 Hz vibration increased the neurites density significantly with time for cultures on collagen and non-collagen surfaces. The exposure of neuronal cells to 40 Hz and 100 Hz vibration enhanced cell differentiation. The 40 Hz vibration has the best impact on neuronal-like cell growth and differentiation. (4) Conclusions: The data demonstrated that exposure to neuronal cells to 40 Hz and 100 Hz vibration enhanced cell differentiation and proliferation. This positive impact of vibration can be used in tissue engineering and regenerative medicine. It is planned to optimize the processes and study its molecular mechanisms concerning carrying out the research.