Berberine for prevention of dementia associated with diabetes and its comorbidities: A systematic review

Background A growing number of epidemiological studies indicate that metabolic syndrome (MetS) and its associated features play a key role in the development of certain degenerative brain disorders, including Alzheimer’s disease and vascular dementia. Produced by several different medicinal plants, berberine is a bioactive alkaloid with a wide range of pharmacological effects, including antidiabetic effects. However, it is not clear whether berberine could prevent the development of dementia in association with diabetes. Objective To give an overview of the therapeutic potential of berberine as a treatment for dementia associated with diabetes. Search strategy Database searches A and B were conducted using PubMed and ScienceDirect. In search A, studies on berberine’s antidementia activities were identified using “berberine” and “dementia” as search terms. In search B, recent studies on berberine’s effects on diabetes were surveyed using “berberine” and “diabetes” as search terms. Inclusion criteria Clinical and preclinical studies that investigated berberine’s effects associated with MetS and cognitive dysfunction were included. Data extraction and analysis Data from studies were extracted by one author, and checked by a second; quality assessments were performed independently by two authors. Results In search A, 61 articles were identified, and 22 original research articles were selected. In search B, 458 articles were identified, of which 101 were deemed relevant and selected. Three duplicates were removed, and a total of 120 articles were reviewed for this study. The results demonstrate that berberine exerts beneficial effects directly in the brain: enhancing cholinergic neurotransmission, improving cerebral blood flow, protecting neurons from inflammation, limiting hyperphosphorylation of tau and facilitating β-amyloid peptide clearance. In addition, evidence is growing that berberine is effective against diabetes and associated disorders, such as atherosclerosis, cardiomyopathy, hypertension, hepatic steatosis, diabetic nephropathy, gut dysbiosis, retinopathy and neuropathy, suggesting indirect benefits for the prevention of dementia. Conclusion Berberine could impede the development of dementia via multiple mechanisms: preventing brain damages and enhancing cognition directly in the brain, and indirectly through alleviating risk factors such as metabolic dysfunction, and cardiovascular, kidney and liver diseases. This study provided evidence to support the value of berberine in the prevention of dementia associated with MetS

The Mid-term Effect of Bare Metal Suprarenal Fixation on Renal Function Following Endovascular Abdominal Aortic Aneurysm Repair

ObjectiveThe aim of this study was to assess the mid term effect of proximal bare metal fixation design on renal function in patients undergoing endovascular repair (EVR) of abdominal aortic aneurysm (AAA).MethodsConsecutive EVR patients for AAA from December 1995-2001 were included and grouped to either infrarenal (Group 1) or uncovered suprarenal (Group 2) fixation. Peri-operative renal function and at 6, 12 and 24 months was determined by serum creatinine (sCr mmoll−1) and Cockroft-Gault creatinine clearance (CrC mlmin−1). Changes in renal function were compared using non-parametric analysis.ResultsOf the 179 EVR procedures during this six-year period, paired renal data was available for 135 patients at a minimal follow-up of 6 months (Gp1, n=63; Gp2, n=72). Median pre-EVR sCr and CrC were 113, 57 in Group 1 and 108, 58 in Group 2, p=NS. There was no significant deterioration in renal function within or between either group at 2 years post-EVR: median sCr, CrC values were 118, 56 (Group 1) and 111, 56 (Group 2), all p=NS.ConclusionThis study suggests mid-term renal function remains unaffected following EVR of AAA, irrespective of proximal fixation type. Designs to improve stent durability and EVR applicability do not appear to compromise renal function

Psoas major cross-sectional area: A potential marker of cardiorespiratory fitness

Background and Aim: Cardiorespiratory fitness is an important marker for overall health that significantly correlates with obesity-associated morbidities and mortality. Maximal oxygen uptake (VO2max) recorded during an incremental exercise test is the gold standard assessment for aerobic fitness. However, its cost, chronic illness, and frailty often preclude its application. The cross-sectional area (CSA) of the abdominal psoas major muscle is a predictor of sarcopenia and surgery outcomes and represents a promising biomarker for cardiorespiratory health. Therefore, in the present study, we have planned to assess the relationship between psoas major CSA, anthropometry, and body composition in a UK-based cohort of 210 men and women. Methods: Body mass (kg), height (cm), waist circumference (cm), VO2max, and blood pressure were measured in each participant. The CSA of psoas major, rectus abdominus, and another abdominal muscle of the core muscle group were assessed. Results: Following adjustment for height, psoas major CSA was found to be a significant predictor of percentage body fat (P = 0.02) in men, and body mass index (BMI) in both men (P = 0.015) and women (P = 0.004). We found psoas major CSA correlated more strongly with VO2max (r = 0.74, P < 0.01) than any other study outcome, including age and BMI. Conclusion: Psoas major muscle CSA represents an accurate, reproducible, and time-efficient surrogate for cardiorespiratory fitness and body composition

Metabolic dysfunction following weight cycling in male mice

Background: Combatting over-weight or obesity can lead to large fluctuations in an individual‟s body weight, often referred to as weight cycling or “yo-yo” dieting. Current evidence regarding the potentially damaging effects of these changes is conflicting. Methods: Here, we assess the metabolic effects of weight cycling in a murine model, comprising three dietary switches to normal or high fat diets at 6 week intervals; male C57BL/6 mice were fed either a control (C) or high fat (F) diet for 6 weeks (n=140/group). C and F groups were then either maintained on their initial diet (CC and FF respectively) or switched to a high fat (CF) or control (FC) diet (n=35/group). For the final 6 week interval, CC and CF groups were returned to the control diet (CCC and CFC groups) while FC and FF groups were placed on a high fat diet (FCF and FFF) (n=28/group). Results: For the majority of metabolic outcomes changes aligned with dietary switches; however assessment of neuropeptides and receptors involved in appetite regulation and reward signalling pathways reveal variable patterns of expression. Furthermore, we demonstrate that multiple cycling events leads to a significant increase in internal fat deposition, even when compared to animals maintained on a high fat diet (Internal Fat: FCF: 7.4 ± 0.2g vs. FFF: 5.6 ± 0.2g; p<0.01). Conclusions: Increased internal adipose tissue is strongly linked to the development of metabolic syndrome associated conditions such as type 2 diabetes, cardiovascular disease and hypertension. While further work will be required to elucidate the mechanisms underlying the neuronal control of energy homeostasis, these studies provide a causative link between weight cycling and adverse health

Cannabidiol modulates mitochondrial redox and dynamics in MCF7 cancer cells: a study using fluorescence lifetime imaging microscopy of NAD(P)H

The cannabinoid, cannabidiol (CBD), is part of the plant's natural defence system that when given to animals has many useful medicinal properties, including activity against cancer cells, modulation of the immune system, and efficacy in epilepsy. Although there is no consensus on its precise mode of action as it affects many cellular targets, CBD does appear to influence mitochondrial function. This would suggest that there is a cross-kingdom ability to modulate stress resistance systems that enhance homeostasis. As NAD(P)H autofluorescence can be used as both a metabolic sensor and mitochondrial imaging modality, we assessed the potential of this technique to study the in vitro effects of CBD using 2-photon excitation and fluorescence lifetime imaging microscopy (2P-FLIM) of NAD(P)H against more traditional markers of mitochondrial morphology and cellular stress in MCF7 breast cancer cells. 2P-FLIM analysis revealed that the addition of CBD induced a dose-dependent decrease in bound NAD(P)H, with 20 µM treatments significantly decreasing the contribution of bound NAD(P)H by 14.6% relative to control (p<0.001). CBD also increased mitochondrial concentrations of reactive oxygen species (ROS) (160 ± 53 vs. 97.6 ± 4.8%, 20 µM CBD vs. control, respectively, p<0.001) and Ca2+ (187 ± 78 vs. 105 ± 10%, 20 µM CBD vs. control, respectively, p<0.001); this was associated with significantly decreased mitochondrial branch length and increased fission. These are all suggestive of mitochondrial stress. Our results support the use of NAD(P)H autofluorescence as an investigative tool and provide further evidence that CBD can modulate mitochondrial function and morphology in a dose dependent manner, with clear evidence of it inducing oxidative stress at higher concentrations. This continues to support emerging data in the literature and may provide further insight into its overall mode of action, not only in cancer, but potentially its function in the plant and why it can act as a medicine

Machine Learning Prediction of Susceptibility to Visceral Fat Associated Diseases

Classifying subjects into risk categories is a common challenge in medical research. Machine Learning (ML) methods are widely used in the areas of risk prediction and classification. The primary objective of such algorithms is to use several features to predict dichotomous responses (e.g., healthy/at risk). Similar to statistical inference modelling, ML modelling is subject to the problem of class imbalance and is affected by the majority class, increasing the false-negative rate. In this study, we built and evaluated thirty-six ML models to classify approximately 4300 female and 4100 male participants from the UK Biobank into three categorical risk statuses based on discretised visceral adipose tissue (VAT) measurements from magnetic resonance imaging. We also examined the effect of sampling techniques on the models when dealing with class imbalance. The sampling techniques used had a significant impact on the classification and resulted in an improvement in risk status prediction by facilitating an increase in the information contained within each variable. Based on domain expert criteria the best three classification models for the female and male cohort visceral fat prediction were identified. The Area Under Receiver Operator Characteristic curve of the models tested (with external data) was 0.78 to 0.89 for females and 0.75 to 0.86 for males. These encouraging results will be used to guide further development of models to enable prediction of VAT value. This will be useful to identify individuals with excess VAT volume who are at risk of developing metabolic disease ensuring relevant lifestyle interventions can be appropriately targeted

Cationic lipid-based nanoparticles mediate functional delivery of acetate to tumor cells in vivo leading to significant anticancer effects

Metabolic reengineering using nanoparticle delivery represents an innovative therapeutic approach to normalizing the deregulation of cellular metabolism underlying many diseases, including cancer. Here, we demonstrated a unique and novel application to the treatment of malignancy using a short-chain fatty acid (SCFA)-encapsulated lipid-based delivery system – liposome-encapsulated acetate nanoparticles for cancer applications (LITA-CAN). We assessed chronic in vivo administration of our nanoparticle in three separate murine models of colorectal cancer. We demonstrated a substantial reduction in tumor growth in the xenograft model of colorectal cancer cell lines HT-29, HCT-116 p53+/+ and HCT-116 p53-/-. Nanoparticle-induced reductions in histone deacetylase gene expression indicated a potential mechanism for these anti-proliferative effects. Together, these results indicated that LITA-CAN could be used as an effective direct or adjunct therapy to treat malignant transformation in vivo

Thermodynamics of the Anisotropic Spin-1/2 Heisenberg Chain and Related Quantum Chains

The free energy and correlation lengths of the spin-1/2 $XYZ$ chain are studied at finite temperature. We use the quantum transfer matrix approach and derive non-linear integral equations for all eigenvalues. Analytic results are presented for the low-temperature asymptotics, in particular for the critical $XXZ$ chain in an external magnetic field. These results are compared to predictions by conformal field theory. The integral equations are solved numerically for the non-critical $XXZ$ chain and the related spin-1 biquadratic chain at arbitrary temperature.Comment: 31 pages, LATEX, 5 PostScript figures appended, preprint cologne-93-471

Two-magnon Raman scattering in insulating cuprates: Modifications of the effective Raman operator

Calculations of Raman scattering intensities in spin 1/2 square-lattice Heisenberg model, using the Fleury-Loudon-Elliott theory, have so far been unable to describe the broad line shape and asymmetry of the two magnon peak found experimentally in the cuprate materials. Even more notably, the polarization selection rules are violated with respect to the Fleury-Loudon-Elliott theory. There is comparable scattering in $B_{1g}$ and $A_{1g}$ geometries, whereas the theory would predict scattering in only $B_{1g}$ geometry. We review various suggestions for this discrepency and suggest that at least part of the problem can be addressed by modifying the effective Raman Hamiltonian, allowing for two-magnon states with arbitrary total momentum. Such an approach based on the Sawatzsky-Lorenzana theory of optical absorption assumes an important role of phonons as momentum sinks. It leaves the low energy physics of the Heisenberg model unchanged but substantially alters the Raman line-shape and selection rules, bringing the results closer to experiments.Comment: 7 pages, 6 figures, revtex. Contains some minor revisions from previous versio

Equation of state for Universe from similarity symmetries

In this paper we proposed to use the group of analysis of symmetries of the dynamical system to describe the evolution of the Universe. This methods is used in searching for the unknown equation of state. It is shown that group of symmetries enforce the form of the equation of state for noninteracting scaling multifluids. We showed that symmetries give rise the equation of state in the form $p=-\Lambda+w_{1}\rho(a)+w_{2}a^{\beta}+0$ and energy density $\rho=\Lambda+\rho_{01}a^{-3(1+w)}+\rho_{02}a^{\beta}+\rho_{03}a^{-3}$, which is commonly used in cosmology. The FRW model filled with scaling fluid (called homological) is confronted with the observations of distant type Ia supernovae. We found the class of model parameters admissible by the statistical analysis of SNIa data. We showed that the model with scaling fluid fits well to supernovae data. We found that $\Omega_{\text{m},0} \simeq 0.4$ and $n \simeq -1$ ($\beta = -3n$), which can correspond to (hyper) phantom fluid, and to a high density universe. However if we assume prior that $\Omega_{\text{m},0}=0.3$ then the favoured model is close to concordance $\Lambda$CDM model. Our results predict that in the considered model with scaling fluids distant type Ia supernovae should be brighter than in $\Lambda$CDM model, while intermediate distant SNIa should be fainter than in $\Lambda$CDM model. We also investigate whether the model with scaling fluid is actually preferred by data over $\Lambda$CDM model. As a result we find from the Akaike model selection criterion prefers the model with noninteracting scaling fluid.Comment: accepted for publication versio