Glucosamine prevents in vitro collagen degradation in chondrocytes by inhibiting advanced lipoxidation reactions and protein oxidation

Osteoarthritis (OA) affects a large segment of the aging population and is a major cause of pain and disability. At present, there is no specific treatment available to prevent or retard the cartilage destruction that occurs in OA. Recently, glucosamine sulfate has received attention as a putative agent that may retard cartilage degradation in OA. The precise mechanism of action of glucosamine is not known. We investigated the effect of glucosamine in an in vitro model of cartilage collagen degradation in which collagen degradation induced by activated chondrocytes is mediated by lipid peroxidation reaction. Lipid peroxidation in chondrocytes was measured by conjugated diene formation. Protein oxidation and aldehydic adduct formation were studied by immunoblot assays. Antioxidant effect of glucosamine was also tested on malondialdehyde (thiobarbituric acid-reactive substances [TBARS]) formation on purified lipoprotein oxidation for comparison. Glucosamine sulfate and glucosamine hydrochloride in millimolar (0.1 to 50) concentrations specifically and significantly inhibited collagen degradation induced by calcium ionophore-activated chondrocytes. Glucosamine hydrochloride did not inhibit lipid peroxidation reaction in either activated chondrocytes or in copper-induced oxidation of purified lipoproteins as measured by conjugated diene formation. Glucosamine hydrochloride, in a dose-dependent manner, inhibited malondialdehyde (TBARS) formation by oxidized lipoproteins. Moreover, we show that glucosamine hydrochloride prevents lipoprotein protein oxidation and inhibits malondialdehyde adduct formation in chondrocyte cell matrix, suggesting that it inhibits advanced lipoxidation reactions. Together, the data suggest that the mechanism of decreasing collagen degradation in this in vitro model system by glucosamine may be mediated by the inhibition of advanced lipoxidation reaction, preventing the oxidation and loss of collagen matrix from labeled chondrocyte matrix. Further studies are needed to relate these in vitro findings to the retardation of cartilage degradation reported in OA trials investigating glucosamine

Interplay of magnetic order and Jahn-Teller distortion in a model with strongly correlated electron system

The Hubbard model has been employed successfully to understand many aspects of correlation driven physical properties, in particular, the magnetic order in itenerant electron systems. In some systems such as Heusler alloys, manganites etc., it is known that, in addition to magnetic order, distortion induced by Jahn-Teller(J-T) effect also exists. In this paper, based on two-fold degenerate Hubbard model, the influence of magnetic order on J-T distortion is investigated. The electron correlation is treated using a spectral density approach and J-T interaction is added to the model. We find that magnetic order and structural distortion coexist at low temperature $T$ for a certain range of electron correlation strength $U$, J-T coupling strength $G$ and band occupation $n$. At T=0, for a given $n$ and $U$, magnetic order is present but distortion appears only for a $G$ larger than a critical value. We also studied the temperature dependence of lattice strain and magnetization choosing a $G$ close to the critical value.Comment: 12 pages, 5 Figures. Physica- B 405 1701-1705 (2010

A rapid review of differences in cerebrospinal neurofilament light levels in clinical subtypes of progressive multiple sclerosis

BackgroundMultiple sclerosis (MS) is divided into three clinical phenotypes: relapsing–remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS). It is unknown to what extent SPMS and PPMS pathophysiology share inflammatory or neurodegenerative pathological processes. Cerebrospinal (CSF) neurofilament light (NfL) has been broadly studied in different MS phenotypes and is a candidate biomarker for comparing MS subtypes.Research questionAre CSF NfL levels different among clinical subtypes of progressive MS?MethodsA search strategy identifying original research investigating fluid neurodegenerative biomarkers in progressive forms of MS between 2010 and 2022 was applied to Medline. Identified articles underwent title and abstract screen and full text review against pre-specified criteria. Data abstraction was limited to studies that measured NfL levels in the CSF. Reported statistical comparisons of NfL levels between clinical phenotypes were abstracted qualitatively.Results18 studies that focused on investigating direct comparisons of CSF NfL from people with MS were included in the final report. We found NfL levels were typically reported to be higher in relapsing and progressive MS compared to healthy controls. Notably, higher NfL levels were not clearly associated with progressive MS subtypes when compared to relapsing MS, and there was no observed difference in NfL levels between PPMS and SPMS in articles that separately assessed these phenotypes.ConclusionCSF NfL levels distinguish individuals with MS from healthy controls but do not differentiate MS subtypes. Broad biological phenotyping is needed to overcome limitations of current clinical phenotyping and improve biomarker translatability to decision-making in the clinic

Dietary iron intake in the first 4 months of infancy and the development of type 1 diabetes: a pilot study

<p>Abstract</p> <p>Aims</p> <p>To investigate the impact of iron intake on the development of type 1 diabetes (T1DM).</p> <p>Methods</p> <p>Case-control study with self-administered questionnaire among families of children with T1DM who were less than 10 years old at the time of the survey and developed diabetes between age 1 and 6 years. Data on the types of infant feeding in the first 4 months of life was collected from parents of children with T1DM (n = 128) and controls (n = 67) <10 years old. Because some cases had sibling controls, we used conditional logistic regression models to analyze the data in two ways. First we performed a case-control analysis of all 128 cases and 67 controls. Next, we performed a case-control analysis restricted to cases (n = 59) that had a sibling without diabetes (n = 59). Total iron intake was modeled as one standard deviation (SD) increase in iron intake. The SD for iron intake was 540 mg in the total sample and 539 mg in the restricted sample as defined above.</p> <p>Results</p> <p>The median (min, max) total iron intake in the first 4 months of life was 1159 (50, 2399) mg in T1DM cases and 466 (50, 1224) mg among controls (<it>P </it>< 0.001). For each one standard deviation increase in iron intake, the odds ratio (95% confidence interval) for type 1 diabetes was 2.01 (1.183, 3.41) among all participants (128 cases and 67 controls) while it was 2.26 (1.27, 4.03) in a restricted sample of T1 D cases with a control sibling (59 cases and 59 controls) in models adjusted for birth weight, age at the time of the survey, and birth order.</p> <p>Conclusion</p> <p>In this pilot study, high iron intake in the first 4 months of infancy is associated with T1DM. Whether iron intake is causal or a marker of another risk factor warrants further investigation.</p

Characterization of Oxidative Guanine Damage and Repair in Mammalian Telomeres

8-oxo-7,8-dihydroguanine (8-oxoG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) are among the most common oxidative DNA lesions and are substrates for 8-oxoguanine DNA glycosylase (OGG1)–initiated DNA base excision repair (BER). Mammalian telomeres consist of triple guanine repeats and are subject to oxidative guanine damage. Here, we investigated the impact of oxidative guanine damage and its repair by OGG1 on telomere integrity in mice. The mouse cells were analyzed for telomere integrity by telomere quantitative fluorescence in situ hybridization (telomere–FISH), by chromosome orientation–FISH (CO–FISH), and by indirect immunofluorescence in combination with telomere–FISH and for oxidative base lesions by Fpg-incision/Southern blot assay. In comparison to the wild type, telomere lengthening was observed in Ogg1 null (Ogg1−/−) mouse tissues and primary embryonic fibroblasts (MEFs) cultivated in hypoxia condition (3% oxygen), whereas telomere shortening was detected in Ogg1−/− mouse hematopoietic cells and primary MEFs cultivated in normoxia condition (20% oxygen) or in the presence of an oxidant. In addition, telomere length abnormalities were accompanied by altered telomere sister chromatid exchanges, increased telomere single- and double-strand breaks, and preferential telomere lagging- or G-strand losses in Ogg1−/− mouse cells. Oxidative guanine lesions were increased in telomeres in Ogg1−/− mice with aging and primary MEFs cultivated in 20% oxygen. Furthermore, oxidative guanine lesions persisted at high level in Ogg1−/− MEFs after acute exposure to hydrogen peroxide, while they rapidly returned to basal level in wild-type MEFs. These findings indicate that oxidative guanine damage can arise in telomeres where it affects length homeostasis, recombination, DNA replication, and DNA breakage repair. Our studies demonstrate that BER pathway is required in repairing oxidative guanine damage in telomeres and maintaining telomere integrity in mammals

The Effect of Iron Limitation on the Transcriptome and Proteome of Pseudomonas fluorescens Pf-5

One of the most important micronutrients for bacterial growth is iron, whose bioavailability in soil is limited. Consequently, rhizospheric bacteria such as Pseudomonas fluorescens employ a range of mechanisms to acquire or compete for iron. We investigated the transcriptomic and proteomic effects of iron limitation on P. fluorescens Pf-5 by employing microarray and iTRAQ techniques, respectively. Analysis of this data revealed that genes encoding functions related to iron homeostasis, including pyoverdine and enantio-pyochelin biosynthesis, a number of TonB-dependent receptor systems, as well as some inner-membrane transporters, were significantly up-regulated in response to iron limitation. Transcription of a ribosomal protein L36-encoding gene was also highly up-regulated during iron limitation. Certain genes or proteins involved in biosynthesis of secondary metabolites such as 2,4-diacetylphloroglucinol (DAPG), orfamide A and pyrrolnitrin, as well as a chitinase, were over-expressed under iron-limited conditions. In contrast, we observed that expression of genes involved in hydrogen cyanide production and flagellar biosynthesis were down-regulated in an iron-depleted culture medium. Phenotypic tests revealed that Pf-5 had reduced swarming motility on semi-solid agar in response to iron limitation. Comparison of the transcriptomic data with the proteomic data suggested that iron acquisition is regulated at both the transcriptional and post-transcriptional levels

TNFR2 Signaling Regulates the Immunomodulatory Function of Oligodendrocyte Precursor Cells

Multiple sclerosis (MS) is a neuroimmune disorder characterized by inflammation, CNS demyelination, and progressive neurodegeneration. Chronic MS patients exhibit impaired remyelination capacity, partly due to the changes that oligodendrocyte precursor cells (OPCs) undergo in response to the MS lesion environment. The cytokine tumor necrosis factor (TNF) is present in the MS-affected CNS and has been implicated in disease pathophysiology. Of the two active forms of TNF, transmembrane (tmTNF) and soluble (solTNF), tmTNF signals via TNFR2 mediating protective and reparative effects, including remyelination, whereas solTNF signals predominantly via TNFR1 promoting neurotoxicity. To better understand the mechanisms underlying repair failure in MS, we investigated the cellular responses of OPCs to inflammatory exposure and the specific role of TNFR2 signaling in their modulation. Following treatment of cultured OPCs with IFNγ, IL1β, and TNF, we observed, by RNA sequencing, marked inflammatory and immune activation of OPCs, accompanied by metabolic changes and dysregulation of their proliferation and differentiation programming. We also established the high likelihood of cell–cell interaction between OPCs and microglia in neuroinflammatory conditions, with OPCs able to produce chemokines that can recruit and activate microglia. Importantly, we showed that these functions are exacerbated when TNFR2 is ablated. Together, our data indicate that neuroinflammation leads OPCs to shift towards an immunomodulatory phenotype while diminishing their capacity to proliferate and differentiate, thus impairing their repair function. Furthermore, we demonstrated that TNFR2 plays a key role in this process, suggesting that boosting TNFR2 activation or its downstream signals could be an effective strategy to restore OPC reparative capacity in demyelinating disease

Burden of excessive gestational weight gain and postpartum weight retention among Indian women - A systematic review and meta-analysis

Background: Excessive weight gain during pregnancy and weight retention in the postpartum period may lead to obesity, diabetes mellitus, and cardiovascular events among women in later life, as well as adverse perinatal outcomes, and long-term offspring health outcomes during the current and subsequent pregnancies. However, most studies of gestational weight gain (GWG) and postpartum weight retention (PPWR) are in western and developed countries. Therefore, this paper aimed to determine the burden of gestational weight gain and postpartum weight retention among Indian women. Materials &amp; methods: Three electronic database- Medline, Google Scholar, and Cochrane library were searched for studies up until March 31, 2022. Studies on GWG and PPWR from India were included in the review. Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) checklist was used for reporting the current review. Online platform Rayyan was used to screen and select the studies. Data were extracted from the 13 selected articles and pooled estimates, proportion and mean of GWG &amp; PPWR along with 95% CI were estimated. Results: Overall 271 articles were identified after the initial search and 13 articles were included (n = 6656) in the review. Nine studies reported proportion of women with excessive GWG, seven studies reported mean GWG and three studies described weight retention among postpartum mothers. The pooled proportion of Indian pregnant women with excessive GWG was found to be 16.48% (95% CI: 11.52, 21.43) and the pooled mean of GWG was 10.08 kg (95% CI: 7.81–12.34). The highest pooled proportion of women with excessive GWG was reported in the North region with 22.57% and the lowest in the East region with 9.15%. The highest pooled mean of GWG was reported in the East region with 12.90 kg and the lowest in the North region with 6.40 kg. Findings from three studies were systematically reviewed and summarized for postpartum weight retention among Indian women. Conclusion: Although majority of Indian women achieved GWG less than the recommendations, there is a need for larger population based surveys among Indian women to obtain adequate, appropriate and complete health related information about weight changes during and after pregnancy

Dynamic Responses of Microglia in Animal Models of Multiple Sclerosis

Microglia play an essential role in maintaining central nervous system (CNS) homeostasis, as well as responding to injury and disease. Most neurological disorders feature microglial activation, a process whereby microglia undergo profound morphological and transcriptional changes aimed at containing CNS damage and promoting repair, but often resulting in overt inflammation that sustains and propagates the neurodegenerative process. This is especially evident in multiple sclerosis (MS), were microglial activation and microglia-driven neuroinflammation are considered key events in the onset, progression, and resolution of the disease. Our understanding of microglial functions in MS has widened exponentially in the last decade by way of new tools and markers to discriminate microglia from other myeloid populations. Consequently, the complex functional and phenotypical diversity of microglia can now be appreciated. This, in combination with a variety of animal models that mimic specific features and processes of MS, has contributed to filling the gap of knowledge in the cascade of events underlying MS pathophysiology. The purpose of this review is to present the most up to date knowledge of the dynamic responses of microglia in the commonly used animal models of MS, specifically the immune-mediated experimental autoimmune encephalomyelitis (EAE) model, and the chemically-induced cuprizone and lysolecithin models. Elucidating the spectrum of microglial functions in these models, from detrimental to protective, is essential to identify emerging targets for therapy and guide drug discovery efforts

Performance of Pigeonpea Varieties against Sterility Mosaic Disease (SMD) for Rainfed Regions of Prakasam District, Andhra Pradesh, India

Pigeonpea is one of India's most important grain legumes, accounting for 90 per cent of global production. It is primarily farmed and consumed in poor nations, with India being a major producer. The area under Red gram crop in Prakasam district is about 1,00,000 hectares, which is under Rainfed cultivation during Kharif season, as a sole crop. The occurrence of Sterility Mosaic Disease (SMD) has resulted in significant yield loss over the last three years in Prakasam District. As a result, the current study was done to investigate the performance of seven varieties for the disease incidence and yield attributes that are suitable for rainfed region of Prakasam district were evaluated. Among the varieties evaluated, no disease incidence was observed in BSMR 736 (842 kg/ha), ICPL87119 (816 kg/ha) followed by TRG 59 with disease incidence of 8.67 per cent and yield of 756 kg/ha. The variety GRG 152 recorded disease incidence of 4.47 per cent and yield of 610 kg/ha. The variety LRG 105 recorded disease incidence of 26.33 per cent and yield of 546 kg/ha which was found to be moderately resistant. These findings are important for choosing resistant genotypes and can be used to validate and generate more SMD resistant pigeonpea genotypes in the future