Comparison of heat shock response in Brucella abortus and Brucella melitensis

Heat shock protein (hsp) is highly conserved, that serves a wide range of function in protein folding and transport. It protect from various type of stress including heat shocks. However, it is well known that the virulence of B. melitensis is more than B. abortus, but there is not any strong evidence to verify it. For this purpose, in refer to potent antigenicity of hsps in various infectious as well as some hsp molecules act as potent activator of macrophage (danger signal), we hypothesized that difference in virulence between B. abortus and B. melitensis may be originated from difference in pattern of response to heat shock induced by high degree of fever that usually present in brucellosis. To this end, five B. abortus and five B. melitensis strains isolated from cows and human, were subjected to 39, 40 and 42°C heat shocks. The bacterial whole cell proteins were extracted and resolved by SDS-PAGE. Western blotting was used to detect antibody production against the extracted bacterial proteins especially hsp60 in both control and patient sera. SDS-PAGE gels revealed protein bands mainly in the range of 10-100 kDa. The amounts of a 60 kDa protein band (hsp60) was significantly enhanced following heat shock at 42°C in relation to the unheated cells in both bacterial species. The heat shock responses in B. abortus and B. melitensis point to the higher production of a 60 kDa protein (hsp60) in both bacterial species, especially in B. abortus. It seems that, lower hsp60 production by B. melitensis would induce a relatively much lower immune response against the bacterium leading to its greater virulence potentials; the sera from Brucellosis patients reacted with several of these cell derived protein bands in western blots, none of which were reactive with sera from healthy individuals. The western blot protein bands showed striking differences. This observation points to the immunogenic properties of hsps, specially the overwhelming response to hsp-60. Therefore, hsp-60 can be a good antigenic candidate for engineering subumt vaccine against Brucella, as well as for ELISA test development. © 2008 Asian Network for Scientific Information

Estrogenic Plant Extracts Reverse Weight Gain and Fat Accumulation without Causing Mammary Gland or Uterine Proliferation

Long-term estrogen deficiency increases the risk of obesity, diabetes and metabolic syndrome in postmenopausal women. Menopausal hormone therapy containing estrogens might prevent these conditions, but its prolonged use increases the risk of breast cancer, as wells as endometrial cancer if used without progestins. Animal studies indicate that beneficial effects of estrogens in adipose tissue and adverse effects on mammary gland and uterus are mediated by estrogen receptor alpha (ERα). One strategy to improve the safety of estrogens to prevent/treat obesity, diabetes and metabolic syndrome is to develop estrogens that act as agonists in adipose tissue, but not in mammary gland and uterus. We considered plant extracts, which have been the source of many pharmaceuticals, as a source of tissue selective estrogens. Extracts from two plants, Glycyrrhiza uralensis (RG) and Pueraria montana var. lobata (RP) bound to ERα, activated ERα responsive reporters, and reversed weight gain and fat accumulation comparable to estradiol in ovariectomized obese mice maintained on a high fat diet. Unlike estradiol, RG and RP did not induce proliferative effects on mammary gland and uterus. Gene expression profiling demonstrated that RG and RP induced estradiol-like regulation of genes in abdominal fat, but not in mammary gland and uterus. The compounds in extracts from RG and RP might constitute a new class of tissue selective estrogens to reverse weight gain, fat accumulation and metabolic syndrome in postmenopausal women

Ellagic acid ameliorates cuprizone-induced acute CNS inflammation via restriction of microgliosis and down-regulation of CCL2 and CCL3 pro-inflammatory chemokines

Ellagic acid (EA) is a natural phenol antioxidant with various therapeutic activities. However, the efficacy of EA has not been examined in neuro-inflammatory conditions. Microglia making the innate immune system of the central nervous system (CNS) and are imperative cellular mediators of neuro-inflammatory processes. In this study, neuro-protective effects of EA on cuprizone (Cup)-induced acute CNS inflammation evaluated. C57BL/6J mice were fed with chow containing 0.2 Cup for 3 weeks to induce acute neuro-inflammation predominantly in the corpus callosum (CC). EA was administered at different doses (40 or 80 mg/kg body weight/day/i.p) from the first day of the Cup diet. Microglia activation (microgliosis) and expression of microglia related chemokines during Cup challenge were examined. Results shows that EA significantly decreased the number of activated microglia cells (Iba-1+ cells) and also restricted proliferation of these cell population (Iba-1+/Ki67+ cells) in dose dependent manner. Consequently, concentration of microglial pro-inflammatory chemokines including monocyte chemoattractant protein-1/Chemokine (C-C motif) ligand 2 (MCP-1/CCL2), and macrophage inflammatory protein 1-alpha/Chemokine (C-C motif) ligand 3 (MIP-1-a/CCL3) dramatically reduced in CC after EA treatment. According to this results, we conclude that EA is a suitable therapeutic agent for moderation brain damages in neuro-inflammatory diseases. © 2016 by the C.M.B. Association. All rights reserved

Low, but not high, dose triptolide controls neuroinflammation and improves behavioral deficits in toxic model of multiple sclerosis by dampening of NF-κB activation and acceleration of intrinsic myelin repair

Cuprizone (Cup) is a copper chelating agent frequently used to study factors that affect oligodendrocytes (OLGs) death and acute demyelination. Triptolide (TP), a nuclear factor-kappaB (NF-κB) blocker, is a major bioactive component of Tripterygium wilfordii Hook f. (TWHf) with various therapeutic activities. In this study, we examined the effects of TP on neuroglia activation, inflammation, apoptosis, demyelination, and behavioral deficits in the Cup-induced toxic model of multiple sclerosis (MS). C57BL/6 J mice were fed with chow containing 0.2 Cup for 6 weeks to induce detectable neuroinflammation and myelin loss. TP was administered intraperitoneally at different doses (125, 250 or 500 μg/kg/day) during the last week of the Cup challenge. Although TP substantially decreased Cup-induced NF-κB extra activation, TNF-α and IL-1 over expression, and gliosis in a dose-dependent manner, only low dose of TP (TP-125) was able to raise the number of OLGs precursor cells (NG-2+/O4+), reduce Bax/Bcl-2 ratio and improve behavioral deficits. In addition, TP-125 decreased NF-κB activation on GFAP+ astrocytes more than MAC-3+ microglial and MOG+ oligodendrocytes which suggested the possibility of specific dampening of NF-κB signaling in reactive astrocytes. Behavioral assessments by open-field and rota-rod tests showed that only TP-125 notably improved motor function and motor coordination compared to the Cup group. These findings highlight the pivotal role of NF-κB signaling in the oligodendrogenesis and lesion reduction in demyelination diseases such as MS. © 2018 Elsevier Inc

Low, but not high, dose triptolide controls neuroinflammation and improves behavioral deficits in toxic model of multiple sclerosis by dampening of NF-κB activation and acceleration of intrinsic myelin repair

Cuprizone (Cup) is a copper chelating agent frequently used to study factors that affect oligodendrocytes (OLGs) death and acute demyelination. Triptolide (TP), a nuclear factor-kappaB (NF-κB) blocker, is a major bioactive component of Tripterygium wilfordii Hook f. (TWHf) with various therapeutic activities. In this study, we examined the effects of TP on neuroglia activation, inflammation, apoptosis, demyelination, and behavioral deficits in the Cup-induced toxic model of multiple sclerosis (MS). C57BL/6 J mice were fed with chow containing 0.2 Cup for 6 weeks to induce detectable neuroinflammation and myelin loss. TP was administered intraperitoneally at different doses (125, 250 or 500 μg/kg/day) during the last week of the Cup challenge. Although TP substantially decreased Cup-induced NF-κB extra activation, TNF-α and IL-1 over expression, and gliosis in a dose-dependent manner, only low dose of TP (TP-125) was able to raise the number of OLGs precursor cells (NG-2+/O4+), reduce Bax/Bcl-2 ratio and improve behavioral deficits. In addition, TP-125 decreased NF-κB activation on GFAP+ astrocytes more than MAC-3+ microglial and MOG+ oligodendrocytes which suggested the possibility of specific dampening of NF-κB signaling in reactive astrocytes. Behavioral assessments by open-field and rota-rod tests showed that only TP-125 notably improved motor function and motor coordination compared to the Cup group. These findings highlight the pivotal role of NF-κB signaling in the oligodendrogenesis and lesion reduction in demyelination diseases such as MS. © 2018 Elsevier Inc

Reduced serum immunoglobulin G concentrations in multiple sclerosis: prevalence and association with disease-modifying therapy and disease course

Background: In multiple sclerosis (MS), the frequency of hypogammaglobulinemia is unknown. We aimed to evaluate the frequency of reduced immunoglobulin (Ig) concentrations and its association with immunotherapy and disease course in two independent MS cohorts. Methods: In our retrospective cross-sectional study, MS patients and control patients with head or neck pain from Bern University Hospital (Bern, Switzerland) and Eginition University Hospital (Athens, Greece) were included. The lower limits of normal (LLN) for serum Ig concentration were IgG < 700 mg/dl, IgM < 40 mg/dl, and IgA < 70 mg/dl. Mann–Whitney U test, analysis of variance test, and multiple linear regression analysis were employed. Results: In total, 327 MS patients were retrospectively identified (Bern/Athens: n = 226/101). Serum IgG concentrations were frequently under LLN in both MS cohorts (Bern/Athens: 15.5%/14.9%), even when considering only untreated patients (Bern/Athens: 7.9%/8.6%). MS patients (n = 327) were significantly more likely to have IgG concentrations below LLN and below 600 mg/dl in comparison with controls (n = 58) (p = 0.015 and 0.047, respectively). Between both patient groups, no significant differences were found in frequencies of IgA and IgM concentrations under LLN [n (MS patients/controls): IgA 203/30, IgM 224/24]. Independently of age, secondary progressive MS patients had lower IgG concentrations than relapsing–remitting and primary progressive patients (both: p ⩽ 0.01). After adjusting for sex, age, and disease course, IgG concentrations were lower in patients treated with rituximab (p = 0.001; n = 42/327), intravenous corticosteroids (p < 0.001; n = 16/327), natalizumab (p < 0.001; n = 48/327), and fingolimod (p = 0.003; n = 6/327). Conclusion: Our study demonstrated high prevalence rates of reduced serum IgG concentrations in MS patients with and without disease-modifying treatments. The significance of lower IgG concentrations at the levels noted is unclear considering that infections or interference with antibody production generally occur when IgG levels are much lower, at or below 400 mg/dl. However, the information is useful to monitor IgG levels especially with anti-B-cell therapies and consider IgG substitution when levels drop below 400 mg/dl. © The Author(s), 2019

Understanding the global hydrological droughts of 2003–2016 and their relationships with teleconnections

Droughts often evolve gradually and cover large areas, and therefore, affect many people and activities. This motivates developing techniques to integrate different satellite observations, to cover large areas, and understand spatial and temporal variability of droughts. In this study, we apply probabilistic techniques to generate satellite derived meteorological, hydrological, and hydro-meteorological drought indices for the world's 156 major river basins covering 2003–2016. The data includes Terrestrial Water Storage (TWS) estimates from the Gravity Recovery And Climate Experiment (GRACE) mission, along with soil moisture, precipitation, and evapotranspiration reanalysis. Different drought characteristics of trends, occurrences, areal-extent, and frequencies corresponding to 3-, 6-, 12-, and 24-month timescales are extracted from these indices. Drought evolution within selected basins of Africa, America, and Asia is interpreted. Canonical Correlation Analysis (CCA) is then applied to find the relationship between global hydro-meteorological droughts and satellite derived Sea Surface Temperature (SST) changes. This relationship is then used to extract regions, where droughts and teleconnections are strongly interrelated. Our numerical results indicate that the 3- to 6-month hydrological droughts occur more frequently than the other timescales. Longer memory of water storage changes (than water fluxes) has found to be the reason of detecting extended hydrological droughts in regions such as the Middle East and Northern Africa. Through CCA, we show that the El Niño Southern Oscillation (ENSO) has major impact on the magnitude and evolution of hydrological droughts in regions such as the northern parts of Asia and most parts of the Australian continent between 2006 and 2011, as well as droughts in the Amazon basin, South Asia, and North Africa between 2010 and 2012. The Indian ocean Dipole (IOD) and North Atlantic Oscillation (NAO) are found to have regional influence on the evolution of hydrological droughts