ABSTRACT
Silicon (Si), a newer trace element, is believed to be important for healthy bone formation and to decrease bone resorption, improving the quality of bone by manipulating several hormones and enzymes. Therefore, the current investigation was conducted to determine the impact of Si supplementation on growth, immunity, antioxidant, hormonal profile and biomarkers of bone health in pre-ruminant crossbred calves. Twenty-four crossbred calves (5-7 days) were selected on the basis of their body weight (BW 31.65 ± 0.46 kg) and divided into 4 groups (n = 6) and fed as per ICAR (2013) feeding standards except that these were additionally supplemented with 0 (Si0), 50 (Si50), 100 (Si100) and 150 (Si150) mg of Si/kg dry matter (DM) in four respective groups for 90 days. Every month, peripheral blood samples were drawn (0, 30, 60 and 90 days post supplementing with Si) and analysed for antioxidant status, hormonal profile and bone health biomarkers. It is reported that dietary Si supplementation improved (P < 0.05) net body weight gain (kg), average daily gain (g) and average dry matter intake (kg), whereas feed intake (kg/100 kg BW), was not altered due to Si supplementation. Structural growth measurements were significantly higher (P < 0.05) in Si100 and Si150 groups as compared to Si50 and control groups. However, immune response (humoral as well as cell-mediated immunity), erythrocytic antioxidant enzymes (superoxide dismutase, SOD, glutathione peroxidase, GPx and catalase), plasma ferric reducing total antioxidant power (FRAP) activity and the plasma concentration of total immunoglobulins (TIg) remained unaffected by Si supplementation. Silicon increased (P < 0.05) the concentration of plasma growth hormone (GH), vitamin D3, bone alkaline phosphatase (BALP) and osteocalcin (OCN) in Si100 and Si150 groups, but the levels of calcitonin, parathyroid hormone (PTH) and hydroxyproline (HYP) remained similar among all the groups. As a result of the current investigation, it can be inferred that the inclusion of 100 and 150 mg of Si/kg DM was effective in improving the growth performance, growth hormone, vitamin D3 and bone health status in pre-ruminant calves. However, supplementation of 150 mg of Si/kg DM had no additional benefit; therefore 100 mg of Si/kg DM is the optimum level of Si supplementation in pre-ruminant calves.
ABSTRACT
Gold nanoparticles (AuNPs) have been reported to modulate bone tissue regeneration and are being extensively utilized in biomedical implementations attributable to their low cytotoxicity, biocompatibility and simplicity of functionalization. Lately, biologically synthesized nanoparticles have acquired popularity because of their environmentally acceptable alternatives for diverse applications. Here we report the green synthesis of AuNPs by taking the biopolymer Carboxymethyl Tamarind (CMT) as a unique reducing as well as a stabilizing agent. The synthesized CMT-AuNPs were analyzed by UV-vis spectrophotometer, DLS, FTIR, XRD, TGA, SEM and TEM. These results suggest that CMT-AuNPs possess an average size of 19.93 ± 8.52 nm and have long-term stability. Further, these CMT-AuNPs promote the proliferation together with the differentiation and mineralization of osteoblast cells in a "dose-dependent" manner. Additionally, CMT-AuNPs are non-toxic to SD rats when applied externally. We suggest that the CMT-AuNPs have the potential to be a suitable and non-toxic agent for differentiation and mineralization of osteoblast cells in vitro and this can be tested in vivo as well.
Subject(s)
Metal Nanoparticles , Tamarindus , Rats , Animals , Gold/pharmacology , Calcium , Biomineralization , Rats, Sprague-Dawley , Plant ExtractsABSTRACT
In leishmaniasis, the protective immunity is largely mediated by proinflammatory cytokine producing abilities of T cells and an efficient parasite killing by phagocytic cells. Notwithstanding a substantial progress that has been made during last decades, the mechanisms or factors involved in establishing protective immunity against Leishmania are not identified. In ancient Indian literature, metallic "bhasma," particularly that of "swarna" or gold (fine gold particles), is indicated as one of the most prominent metal-based therapeutic medicine, which is known to impart protective and curative properties in various health issues. In this work, we elucidated the potential of swarna bhasma (SB) on the effector properties of phagocytes and antigen-activated CD4+ T cells in augmenting the immunogenicity of L. donovani antigens. The characterization of SB revealing its shape, size, composition, and measurement of cytotoxicity established the physiochemical potential for its utilization as an immunomodulator. The activation of macrophages with SB enhanced their capacity to produce nitric oxide and proinflammatory cytokines, which eventually resulted in reduced uptake of parasites and their proliferation in infected cells. Further, in Leishmania-infected animals, SB administration reduced the generation of IL-10, an anti-inflammatory cytokine, and enhanced pro-inflammatory cytokine generation by antigen activated CD4+ T cells with increased frequency of double (IFNγ+/TNFα+) and triple (IFNγ+TNFα+IL-2+) positive cells and abrogated disease pathogeneses at the early days of infection. Our results also suggested that cow-ghee (A2) emulsified preparation of SB, either alone or with yashtimadhu, a known natural immune modulator which enhances the SB's potential in enhancing the immunogenicity of parasitic antigens. These findings suggested a definite potential of SB in enhancing the effector functions of phagocytes and CD4+ T cells against L. donovani antigens. Therefore, more studies are needed to elucidate the mechanistic details of SB and its potential in enhancing vaccine-induced immunity.
Subject(s)
Antigen Presentation , Antigens, Protozoan , CD4-Positive T-Lymphocytes , Calotropis , Gold , Latex , Leishmania donovani , Macrophages , Medicine, Ayurvedic , Th1 Cells , Arsenic , Drug Combinations , Gold/administration & dosage , Gold/pharmacology , Latex/administration & dosage , Latex/pharmacology , Lead , Macrophages/drug effects , Macrophages/immunology , CD4-Positive T-Lymphocytes/immunology , Phagocytes/drug effects , Phagocytes/immunology , Leishmaniasis/immunology , Leishmaniasis/parasitology , Leishmania donovani/drug effects , Leishmania donovani/growth & development , Leishmania donovani/immunology , Antigens, Protozoan/immunology , Th1 Cells/immunology , Animals , Mice , RAW 264.7 Cells , Female , Mice, Inbred BALB CABSTRACT
The coronavirus (COVID-19) pandemic is claiming millions of lives and creating an additional burden on health care, which is already affected by the rise of non-communicable diseases (NCDs). The scientific community, on the other side, is enormously engaged with studies to best identify the characteristics of the virus and minimize its effect while supporting the fight to contain NCDs, mainly cardiovascular diseases (CVDs), which are contributing hugely to the global death toll. Hence, the roles of vitamin D in COVID-19 immunity and cardiovascular health are gaining traction recently. This literature review will mainly focus on summarizing pertinent studies and scientific publications which highlight the association of vitamin D levels with the various outcomes of COVID-19 and CVDs. It will also address how low vitamin D correlates with the epidemiology of CVDs and the inflammatory mechanisms attributed to COVID-19 severity. We believe that our review may open up hindsight perspectives and further discussions among the physicians in tapping the potential of vitamin D supplementation to tackle the morbidity, mortality, and health care cost of the two deadly diseases, COVID-19 and CVDs.
ABSTRACT
BACKGROUND: Despite the low prevalence of help-seeking behavior among victims of intimate partner violence (IPV) in India, quantitative evidence on risk factors, is limited. We use a previously validated exploratory approach, to examine correlates of help-seeking from anyone (e.g. family, friends, police, doctor etc.), as well as help-seeking from any formal sources. METHODS: We used data from a nationally-representative health survey conducted in 2015-16 in India, and included all variables in the dataset (~6000 variables) as independent variables. Two machine learning (ML) models were used- L-1, and L-2 regularized logistic regression models. The results from these models were qualitatively coded by researchers to identify broad themes associated with help-seeking behavior. This process of implementing ML models followed by qualitative coding was repeated until pre-specified criteria were met. RESULTS: Identified themes associated with help-seeking behavior included experience of injury from violence, husband's controlling behavior, husband's consumption of alcohol, and being currently separated from husband. Themes related to women's access to social and economic resources, such as women's employment, and receipt of maternal and reproductive health services were also noted to be related factors. We observed similarity in correlates for seeking help from anyone, vs from formal sources, with a greater focus on women being separated for help-seeking from formal sources. CONCLUSION: Findings highlight the need for community programs to reach out to women trapped in abusive relationships, as well as the importance of women's social and economic connectedness; future work should consider holistic interventions that integrate IPV screening and support services with women's health related services.
Subject(s)
Help-Seeking BehaviorABSTRACT
CONTEXT: Fisetin as a caloric restriction mimetic (CRM) exerts numerous beneficial effects on different aging model systems. The effect of fisetin on erythrocyte membrane functions against induced aging is not very clear. OBJECTIVES: The potential role of fisetin in the modulation of erythrocytes membrane-bound transporters during natural and induced aging in rats was assessed. MATERIALS AND METHODS: Male Wistar rats were used for natural and D-galactose (D-gal) induced aging model. After supplementation with fisetin, the activities of different membrane transporters and biomarkers of oxidative stress were evaluated. RESULTS: Fisetin modulated membrane transporters such as calcium-ATPase, sodium potassium-ATPase and sodium hydrogen exchanger during senescence-induced as well as in natural aging. Fisetin also protected oxidative modifications in rat aging. DISCUSSION AND CONCLUSION: Fisetin supplementation improves the ionic homeostasis, a factor that is involved in the aetiology of several age-associated diseases, in naturally old as well as D-gal induced aged rats.
Subject(s)
Caloric Restriction , Flavonols , Animals , Homeostasis , Male , Oxidative Stress , Rats , Rats, WistarABSTRACT
Multiple sclerosis (MS) is an autoimmune disease affecting a large number of people every year. The exact causal factor for this disease is unclear, but it commonly affects middle-aged women, with known triggers like stress, childbirth, infections, poor diet, lack of sleep, etc. Many epidemiological studies have indicated that various genetic abnormalities are also critical drivers of the onset of MS. The major risk factors of MS identified include hypovitaminosis D while environmental protective factors include allele HLA DRB1 1501, obesity, Epstein-Barr virus infection, sexual hormones, and smoking. Our article explores the correlation between the deficiency of vitamin D and the onset and progression of MS. The study uses a systematic review methodology by researching and reviewing scholarly articles exploring the topic. We conducted online searches of literature on Google Scholar and PubMed using the keywords "vitamin D deficiency" and "multiple sclerosis" and accessed the relevant secondary literature sources for review. The variables under study included vitamin D insufficiency as the dependent variable while MS was the independent variable. Causal variables included environmental, genetic, and protective factors. We hypothesized that there is indeed a correlation between vitamin D deficiency and MS. The findings from our review indicate a strong correlation between the insufficiency of vitamin D and the onset and progression of MS. These results are essential in devising interventions to accomplish primary and secondary prevention of MS, as well as integrating vitamin D supplementation in current treatment protocols for MS.
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Obesity has become a worldwide health problem. It triggers additional co-morbidities like cardiovascular diseases, cancer, depression, sleep disorders, gastrointestinal problems and many more. Excess accumulation of fat in obesity could be caused by many factors like sedentary lifestyle, consumption of high-fat diet, genetic predisposition, etc. Imbalanced energy metabolism i.e., greater energy consumption than utilisation, invariably underlies obesity. Considering the high prevalence and continuous, uncontrolled increase of this major public health issue, there is an urgent need to find appropriate therapeutic agents with minimal or no side effects. The high prevalence of obesity in recent years has led to a surge in the number of drugs available in the market that claim to control obesity. Although there is a long list of medicines and management strategies that are available, selecting the right therapeutic intervention and feasible management of obesity is a challenge. Several phytochemicals like hydroxycitric acid, flavonoids, tannins, anthocyanins, phytohaemagglutinin, thymoquinone and epigallocatechin gallate have been shown to possess promising anti-obesity properties. However, studies providing information on how various phytochemicals exert their anti-obesity effects are inadequate. This calls for more experimentation in this less explored area of research. Additionally, the complication of obesity arises when it is a result of multiple factors and associated with a number of co-morbidities. In order to handle such complexities, combinatorial therapeutic interventions become effective. In this review, we have described the medicinal chemistry of different highly effective phytochemicals which can be used in the effective treatment and management of obesity.
Subject(s)
Anti-Obesity Agents/chemistry , Enzyme Inhibitors/chemistry , Obesity/drug therapy , Phytochemicals/chemistry , Plant Extracts/chemistry , Plants/chemistry , Adipokines/chemistry , Animals , Anthocyanins/chemistry , Anti-Obesity Agents/pharmacology , Benzoquinones/chemistry , Catechin/analogs & derivatives , Catechin/chemistry , Citrates/chemistry , Drug Discovery , Drug Therapy, Combination , Energy Metabolism/drug effects , Enzyme Inhibitors/pharmacology , Flavonoids/chemistry , Humans , Lipids/chemistry , Phytochemicals/pharmacology , Phytohemagglutinins/chemistry , Plant Extracts/pharmacology , Signal Transduction , Tannins/chemistryABSTRACT
INTRODUCTION: Boron (B) is thought to play key role in proper bone growth and development as well as have some role in regulation of minerals such as calcium (Ca), phosphorus (P) and magnesium (Mg) which act synergistically with vitamin D. OBJECTIVE: Present study was planned in two phases to assess the effect of optimum and supranutritional levels of (B) in the form of boric acid (BA) supplementation on bone health of growing cross bred calves. METHOD: During Phase-1, twenty four male crossbred calves were blocked into four groups (nâ¯=â¯6) on the basis of their body weight (154.83⯱â¯8.5â¯kg), age (7-9 months) and were supplemented with 0 (C), 2.6 (T-1), 5.4 (T-2) and 10.7 (T-3) g BA for appropriate B (0.175 adjustment factor to calculate B form BA) consumption i.e. 0, 100, 200 and 400â¯ppm in each group respectively, for 90 days. During phase 2, twenty-one male crossbred calves were divided into 3 groups (nâ¯=â¯7) on the basis of their body weight (103.76⯱â¯4.34â¯kg) and age (5-8 months). All the groups were on similar dietary regimen with additional supplementation of boric acid as 0â¯g (control); 3.6â¯g (200â¯ppm B; T-1) and 10.8â¯g (600â¯ppm B; T-2), respectively for a period of 120 d. RESULTS: From the first experiment it is reported that plasma levels of bovine alkaline phosphatase (BALP), type I collagen cross-linked N-telopeptide (NTx) and Ca were significantly (Pâ¯<â¯0.05) affected in T-2 and T-3 groups as compared to T-1 and control groups. Whereas, plasma osteocalcin (OCN) concentration was found to be higher in T-2 and T-3 groups as compared to control group. However, plasma concentrations (ng/mL) of tartrate resistant acid phosphatase (TRAP) remained unaltered due to dietary treatments. Based on the results, another experiment was conducted to validate the above findings and further to determine the effect of still higher i.e supranutritional levels of BA supplementation on bone health of calves. Results revealed that supplementation of BA in T-2â¯group had no beneficial effect on bone health as the plasma concentration of BALP, OCN, NTx, 25 (OH) vitamin D and Ca as compared to T-1â¯group in phase 2. Other possible attributes of bone health i.e. plasma concentration of Mg, P, parathyroid hormone (PTH), and calcitonin were not affected by BA supplementation at any levels. CONCLUSION: Overall from present study it can be concluded that supplementation of boric acid 3.6â¯g/d (equivalent to 200â¯ppm B) in the diet of growing animals has positive effect on bone health related biomarkers (OCN, NTx and BALP) and supplementation of supranutritional level of BA i.e. 10.8â¯g (equivalent to 600â¯ppm B) level had neither additional beneficial nor harmful effect on bone health of calves.
Subject(s)
Bone and Bones/drug effects , Boric Acids/pharmacology , Animals , Biomarkers/blood , Body Weight/drug effects , Bone Density/drug effects , Bone and Bones/metabolism , Boric Acids/administration & dosage , Cattle , Dietary Supplements , Male , Tropical ClimateABSTRACT
Evidence on the impact of the quality of prenatal care on childhood mortality is limited in developing countries, including India. Therefore, using nationally representative data from the latest round of the National Family Health Survey (2015-16), this study examined the impact of the quality of prenatal care on neonatal and infant mortality in India using a multivariable binary logistic regression model. The effect of the essential components of prenatal care services on neonatal and infant mortality were also investigated. The results indicate that improvement in the quality of prenatal care is associated with a decrease in neonatal (OR: 0.93, 95% CI: 0.91-0.97) and infant (OR: 0.94, 95% CI: 0.92-0.96) mortality in India. Tetanus toxoid vaccination, consumption of iron-folic acid tablets during pregnancy and having been weighed during pregnancy were statistically associated with a lower risk of neonatal and infant mortality. Educating women on pregnancy complications was also associated with a lower risk of neonatal mortality. No effect of blood pressure examination, blood test and examination of the abdomen during pregnancy were found on either of the two indicators of childhood mortality. Although the coverage of prenatal care has increased dramatically in India, the quality of prenatal care is still an area of concern. There is therefore a need to ensure high-quality prenatal care in India.
Subject(s)
Infant Mortality , Pregnancy Complications/prevention & control , Prenatal Care/methods , Quality of Health Care , Adolescent , Adult , Cross-Sectional Studies , Dietary Supplements , Female , Health Surveys , Humans , India , Infant , Infant, Newborn , Logistic Models , Middle Aged , Pregnancy , Sampling Studies , Tetanus/mortality , Tetanus/prevention & control , Tetanus Toxoid/therapeutic use , Vaccination , Young AdultABSTRACT
Alzheimer's disease (AD) is the most common progressive neurodegenerative disease mainly associated with cognition impairment. Studies in last more than six decades have suggested that the disease pathology primarily includes the depleted cholinergic neurons, accumulation of amyloid beta plaques and hyper phosphorylation of tau proteins. However, the disease etiology remains enigmatic and no therapy is available to modify the disease status. Studies in experimental models and in post mortem brain of AD patients have suggested the involvement of oxidative stress, inflammatory responses, unfolded protein responses and apoptosis in disease pathology, yet the information is deficit to develop the disease modifying therapeutics. Owing to the need of novel effective treatment, chronic consumption of medicines with minimum side effects, recently the researchers turned towards the traditional medicines. This review is mainly focusing on the traditional herbs which have been suggested to contain disease related antidote activities and may be utilized for the effective treatment of AD patients.
Subject(s)
Alzheimer Disease/drug therapy , Brain/drug effects , Neurons/drug effects , Plants, Medicinal , Alzheimer Disease/metabolism , Animals , Brain/metabolism , Humans , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/metabolism , Neurons/metabolism , Oxidative Stress/drug effectsABSTRACT
Aging is associated with decreased cellular cysteine uptake, which acts as a precursor for glutathione biosynthesis. Whey protein, a liquid aspect of milk, is an effective cysteine delivery system. The study was undertaken to evaluate the potential role of whey protein concentrate (WPC) on the redox biomarkers during aging. Male Wistar rats were divided into following four groups: young control (4 months old); young treated with WPC (300 mg/kg b.w./day orally); old (24 months old) control; old treated with WPC for 28 days. After treatment, changes in body weight, lipid profile and levels of redox biomarkers were determined. A marked decrease in prooxidants such as reactive oxygen species, lipid peroxidation and protein carbonyl and significant (p ≤ 0.05) increase in antioxidants such as reduced glutathione and GST levels were observed after WPC supplementation in old age rats. We also found marked decrease in the level of sialic acid and AGEs after WPC supplementation. In conclusion, WPC provides protection against age-dependent redox imbalance which might be attributed to its antioxidant activity.
Subject(s)
Aging/drug effects , Erythrocytes/drug effects , Oxidative Stress/drug effects , Whey Proteins/therapeutic use , Aging/metabolism , Animals , Biomarkers/metabolism , Cysteine/metabolism , Drug Evaluation, Preclinical , Erythrocytes/metabolism , Glycation End Products, Advanced/metabolism , Lipid Metabolism/drug effects , Male , Rats, Wistar , Reactive Oxygen Species/metabolism , Tryptophan/blood , Tyrosine/analogs & derivatives , Tyrosine/blood , Whey Proteins/pharmacologyABSTRACT
Lipid structure critically dictates the molecular interactions of drugs with membranes influencing passive diffusion, drug partitioning and accumulation, thereby underpinning a lipid-composition specific interplay. Spurring selective passive drug diffusion and uptake through membranes is an obvious solution to combat growing antibiotic resistance with minimized toxicities. However, the spectrum of complex mycobacterial lipids and lack thereof of suitable membrane platforms limits the understanding of mechanisms underlying drug-membrane interactions in tuberculosis. Herein, we developed membrane scaffolds specific to mycobacterial outer membrane and demonstrate them as improvised research platforms for investigating anti-tubercular drug interactions. Combined spectroscopy and microscopy results reveal an enhanced partitioning of model drug Rifabutin in trehalose dimycolate-containing mycobacterial membrane systems. These effects are apportioned to specific changes in membrane structure, order and fluidity leading to enhanced drug interaction. These findings on the membrane biophysical consequences of drug interactions will offer valuable insights for guiding the design of more effective antibiotic drugs coupled with tuned toxicity profiles.
Subject(s)
Antitubercular Agents/pharmacology , Lipid Bilayers/metabolism , Models, Biological , Mycobacterium/metabolism , Rifabutin/pharmacology , Biophysical Phenomena , Drug Evaluation, Preclinical , Membrane Fluidity , Mycobacterium/drug effects , TemperatureABSTRACT
The noradrenaline (NA) level in the brain is reduced during rapid eye movement sleep (REMS). However, upon REMS deprivation (REMSD) its level is elevated, which induces apoptosis and the degeneration of neurons in the brain. In contrast, isolated studies have reported that NA possesses an anti-oxidant property, while REMSD reduces lipid peroxidation (LP) and reactive oxygen species (ROS). We argued that an optimum level of NA is likely to play a physiologically beneficial role. To resolve the contradiction and for a better understanding of the role of NA in the brain, we estimated LP and ROS levels in synaptosomes prepared from the brains of control and REMS deprived rats with or without in vivo treatment with either α1-adrenoceptor (AR) antagonist, prazosin (PRZ) or α2-AR agonist, clonidine (CLN). REMSD significantly reduced LP and ROS in synaptosomes; while the effect on LP was ameliorated by both PRZ and CLN; ROS was prevented by CLN only. Thereafter, we evaluated in vitro the effects of NA, vitamin E (Vit E), vitamin C (Vit C), and desferrioxamine (DFX, iron chelator) in modulating hydrogen peroxide (H2O2)-induced LP and ROS in rat brain synaptosomes, Neuro2a, and C6 cells. We observed that NA prevented ROS generation by chelating iron (inhibiting a Fenton reaction). Also, interestingly, a lower dose of NA protected the neurons and glia, while a higher dose damaged the neurons and glia. These in vitro and in vivo results are complementary and support our contention. Based on the findings, we propose that REMS maintains an optimum level of NA in the brain (an antioxidant compromised organ) to protect the latter from continuous oxidative onslaught.
ABSTRACT
Extract of Ulmus wallichiana is being used as traditional medicine used for the treatment of fractured bones however the effect of its individual flavonols is not known. The present study was conducted to investigate the effect of its novel flavonol, (2S, 3S)-(+)-30, 40, 5, 7-tetrahydroxydihydroflavonol-6-C-b-d-glucopyranoside named as Ulmoside A (UA), on lipopolysaccharides (LPS) treated neurons. LPS treatment to neuronal cells caused significant cytotoxicity, reactive oxygen species generation, depletion in glutathione and mitochondrial impairment which were significantly inhibited with UA treatment. LPS treatment also caused significant translocation of cytochrome-c, decreased level of Bcl2, increased level of Bax and cleaved caspase-3 in neuronal cells reflecting the involvement of intrinsic apoptotic pathway in neuronal death which was attenuated with UA treatment. Since LPS is a well known pro-inflammatory agent it also offered the significant increase in proinflammatory cytokines (tumor necrosis factors-α & interleukin 1-beta) however, UA treatment did not exhibit significant inhibition against LPS induced inflammatory response. LPS also caused the augmented level of inducible nitric oxide synthase (iNOS) which was also not inhibited with co treatment of UA. We have also observed the significant DNA fragmentation and augmented level of cleaved Poly (ADP-Ribose) polymerase 1 after LPS treatment which was significantly reverted with UA treatment. Findings suggested that UA acts through mitochondria and exhibited its anti-oxidative and anti-apoptotic activities in neuronal cells while no significant anti-inflammatory activity and effect on iNOS were observed.
Subject(s)
Antioxidants/pharmacology , Apoptosis/drug effects , Flavonoids/pharmacology , Glycosides/pharmacology , Neurons/drug effects , Neuroprotective Agents/pharmacology , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Ulmus , Animals , Antioxidants/isolation & purification , Apoptosis Regulatory Proteins/metabolism , Cell Line, Tumor , Cytokines/metabolism , Flavonoids/isolation & purification , Glutathione/metabolism , Glycosides/isolation & purification , Inflammation Mediators/metabolism , Lipopolysaccharides/toxicity , Membrane Potential, Mitochondrial/drug effects , Mice , Mitochondria/drug effects , Mitochondria/metabolism , Mitochondria/pathology , Neurons/metabolism , Neurons/pathology , Neuroprotective Agents/isolation & purification , Nitric Oxide Synthase Type II/metabolism , Signal Transduction , Ulmus/chemistryABSTRACT
N-acetyl-l-cysteine (NAC) is a precursor of cysteine, which is known to increase the level of glutathione (GSH) in the brain. Several neurodegenerative changes linked to oxidative stress take place in the aging brain. This study aimed to assess the neuroprotective effect of NAC supplementation on age-dependent neurodegeneration in the rat brain. Young (4 months) and old (24 months) Wistar rats (n = 6 rats/group) were supplemented with NAC (100 mg/kg b.w. orally) for 14 days. Enzymatic and nonenzymatic antioxidants such as superoxide dismutase and catalase, and GSH and total thiol respectively, prooxidants such as protein carbonyl, advanced oxidation protein products, reactive oxygen species, and malondialdehyde were assessed in the brain homogenates. Furthermore, nitric oxide level, acetylcholinesterase activity, and Na+/K+-ATPase activity were measured and gene expression studies were also performed. The results indicated that NAC augmented the level of enzymatic and nonenzymatic antioxidants with a significant reduction in prooxidant levels in old rats. NAC supplementation also downregulated the expression of inflammatory markers (TNF-α, IL-1ß, IL-6) and upregulated the expression of marker genes associated with aging (sirtuin-1) and neurodegeneration (neuron-specific enolase, neuroglobin, synapsin-I, myelin basic protein 2) in old rats. The present findings support a neuroprotective role of NAC which has therapeutic implication in controlling age-related neurological disorders.
Subject(s)
Acetylcysteine/pharmacology , Aging/drug effects , Brain/drug effects , Neurodegenerative Diseases/drug therapy , Oxidative Stress/drug effects , Acetylcholinesterase/metabolism , Aging/metabolism , Animals , Antioxidants/pharmacology , Biomarkers/metabolism , Brain/metabolism , Disease Models, Animal , Down-Regulation/drug effects , Inflammation/metabolism , Male , Neurodegenerative Diseases/metabolism , Nitric Oxide/metabolism , Rats , Rats, Wistar , Sodium-Potassium-Exchanging ATPase/metabolism , Up-Regulation/drug effectsABSTRACT
Whey protein concentrate (WPC) is a rich source of sulfur-containing amino acids and is consumed as a functional food, incorporating a wide range of nutritional attributes. The purpose of this study is to evaluate the neuroprotective effect of WPC on rat brain during aging. Young (4 months) and old (24 months) male Wistar rats were supplemented with WPC (300 mg/kg body weight) for 28 days. Biomarkers of oxidative stress and antioxidant capacity in terms of ferric reducing antioxidant potential (FRAP), lipid hydroperoxide (LHP), total thiol (T-SH), protein carbonyl (PC), reactive oxygen species (ROS), nitric oxide (NO), and acetylcholinesterase (AChE) activity were measured in brain of control and experimental (WPC supplemented) groups. In addition, gene expression and histopathological studies were also performed. The results indicate that WPC augmented the level of FRAP, T-SH, and AChE in old rats as compared with the old control. Furthermore, WPC-treated groups exhibited significant reduction in LHP, PC, ROS, and NO levels in aged rats. WPC supplementation also downregulated the expression of inflammatory markers (tumor necrosis factor alpha, interleukin (IL)-1ß, IL-6), and upregulated the expression of marker genes associated with autophagy (Atg3, Beclin-1, LC3B) and neurodegeneration (neuron specific enolase, Synapsin-I, MBP-2). The findings suggested WPC to be a potential functional nutritional food supplement that prevents the progression of age-related oxidative damage in Wistar rats.
Subject(s)
Aging/drug effects , Brain/drug effects , Neurodegenerative Diseases/drug therapy , Oxidative Stress/drug effects , Whey Proteins/pharmacology , Acetylcholinesterase/metabolism , Animals , Autophagy/drug effects , Autophagy-Related Proteins/genetics , Autophagy-Related Proteins/metabolism , Beclin-1/genetics , Beclin-1/metabolism , Biomarkers/blood , Brain/metabolism , Dietary Supplements , Gene Expression Regulation , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Lipid Peroxidation/drug effects , Male , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Nitric Oxide/metabolism , Peptide Synthases/genetics , Peptide Synthases/metabolism , Protein Carbonylation , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism , Sulfhydryl Compounds/metabolism , Synapsins/genetics , Synapsins/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
The effective long-term cryopreservation of human mesenchymal stem cells (MSCs) is an essential prerequisite step and represents a critical approach for their sustained supply in basic research, regenerative medicine, and tissue engineering applications. Therefore, attempts have been made in the present investigation to formulate a freezing solution consisting of a combination of Selaginella bryopteris water-soluble extract with and without dimethyl sulfoxide (Me2SO) for the efficient long-term storage of human umbilical cord blood- (hUCB-) derived MSCs. The cryopreservation experiment using the formulated freezing solution was further performed with hUCB MSCs in a controlled rate freezer. A significant increase in postthaw cell viability and cell attachment of MSCs was achieved with freezing medium containing Selaginella bryopteris water extract along with 10% Me2SO as compared to the freezing medium containing Me2SO (10% v/v) alone. Furthermore, the decreasing apoptotic events and reactive oxygen species production along with increasing expression of heat shock proteins also confirmed the beneficial effect of Selaginella bryopteris water extract. The beneficial effect of Selaginella bryopteris water extract was validated by its ability to render postpreservation high cell viability. In conclusion, the formulated freezing solution has been demonstrated to be effective for the standardization of cryopreservation protocol for hMSCs.
Subject(s)
Apoptosis/drug effects , Cryopreservation/methods , Plant Extracts/pharmacology , Selaginellaceae/chemistry , Actin Cytoskeleton/drug effects , Cell Adhesion/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Dimethyl Sulfoxide/chemistry , Fetal Blood/cytology , Freezing , Heat-Shock Proteins/metabolism , Humans , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Microscopy, Confocal , Plant Extracts/chemistry , Reactive Oxygen Species/metabolism , Selaginellaceae/metabolism , Water/chemistryABSTRACT
We report the fluorination of electrically insulating hexagonal boron nitride (h-BN) and the subsequent modification of its electronic band structure to a wide bandgap semiconductor via introduction of defect levels. The electrophilic nature of fluorine causes changes in the charge distribution around neighboring nitrogen atoms in h-BN, leading to room temperature weak ferromagnetism. The observations are further supported by theoretical calculations considering various possible configurations of fluorinated h-BN structure and their energy states. This unconventional magnetic semiconductor material could spur studies of stable two-dimensional magnetic semiconductors. Although the high thermal and chemical stability of h-BN have found a variety of uses, this chemical functionalization approach expands its functionality to electronic and magnetic devices.
ABSTRACT
Metformin, a biguanide, is a widely used antidiabetic drug, which inhibits gluconeogenesis and is used to treat hyperglycemia in type 2 diabetes. Through activation of AMPK (AMP-activated protein kinase) pathway, metformin also mimics caloric restriction health benefits. Aging causes substantial molecular to morphological changes in brain, the brain cells being more susceptible toward oxidative stress mediated damages due to the presence of high lipid content and higher oxygen consumption. Wistar rats (naturally aged and d-galactose induced rat model) were supplemented with metformin (300 mg/kg b.w. orally) for 6 weeks. The biomarkers of oxidative stress such as antioxidant capacity (ferric reducing antioxidant potential [FRAP]), malondialdehyde (MDA), reduced glutathione (GSH), protein carbonyl (PCO), reactive oxygen species (ROS), acetylcholinesterase (AChE) activity, and nitric oxide (NO) were measured in brain tissues of control and experimental groups. The results indicate that metformin treatment augmented the levels of FRAP and GSH in naturally aged, and d-gal induced aging model groups compared to the respective controls. In contrast, metformin treated groups exhibited significant reduction in MDA, PCO, ROS, and NO levels and a significant increase in AChE activity in induced aging rats. The administration of d-galactose upregulated the expression of sirtuin-2, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) and downregulated the expression of Beclin-1. Metformin supplementation downregulated the d-galactose induced expressions of sirtuin-2, IL-6, and TNF-α expression, whereas upregulated the Beclin-1 expression. Our data confirm that metformin restores the antioxidant status and improves healthy brain aging through the activation of autophagy and reduction in inflammation.