Targeted inhibition of osteoclastogenesis reveals the pathogenesis and therapeutics of bone loss under sympathetic neurostress.

Sympathetic cues via the adrenergic signaling critically regulate bone homeostasis and contribute to neurostress-induced bone loss, but the mechanisms and therapeutics remain incompletely elucidated. Here, we reveal an osteoclastogenesis-centered functionally important osteopenic pathogenesis under sympatho-adrenergic activation with characterized microRNA response and efficient therapeutics. We discovered that osteoclastic miR-21 was tightly regulated by sympatho-adrenergic cues downstream the ß2-adrenergic receptor (ß2AR) signaling, critically modulated osteoclastogenesis in vivo by inhibiting programmed cell death 4 (Pdcd4), and mediated detrimental effects of both isoproterenol (ISO) and chronic variable stress (CVS) on bone. Intriguingly, without affecting osteoblastic bone formation, bone protection against ISO and CVS was sufficiently achieved by a (D-Asp8)-lipid nanoparticle-mediated targeted inhibition of osteoclastic miR-21 or by clinically relevant drugs to suppress osteoclastogenesis. Collectively, these results unravel a previously underdetermined molecular and functional paradigm that osteoclastogenesis crucially contributes to sympatho-adrenergic regulation of bone and establish multiple targeted therapeutic strategies to counteract osteopenias under stresses.

Sympathetic Neurostress Drives Osteoblastic Exosomal MiR-21 Transfer to Disrupt Bone Homeostasis and Promote Osteopenia.

Innervation and extracellular vesicle secretion co-exist in the local tissue microenvironment for message transfer, but whether they are interconnected to regulate organ homeostasis remains unknown. Sympatho-adrenergic activation is implicated in stress-induced depression and leads to bone loss, but the mechanisms and therapeutics are incompletely elucidated. Here, it is revealed that sympathetic neurostress through the ß1/2 -adrenergic receptor (ß1/2-AR) signaling triggers the transcription response of a microRNA, miR-21, in osteoblasts, which is transferred to osteoclast progenitors via exosomes for dictating osteoclastogenesis. After confirming that miR-21 deficiency retards the ß1/2-AR agonist isoproterenol (ISO)-induced osteopenia, it is shown that the pharmacological inhibition of exosome release by two clinically-relevant drugs, dimethyl amiloride and omeprazole, suppresses osteoblastic miR-21 transfer and ameliorates bone loss under both ISO and chronic variable stress (CVS)-induced depression conditions. A targeted delivery approach to specifically silence osteoblastic miR-21 is further applied, which is effective in rescuing the bone remodeling balance and ameliorating ISO- and CVS-induced osteopenias. These results decipher a previously unrecognized paradigm that neural cues drive exosomal microRNA communication to regulate organ homeostasis and help to establish feasible strategies to counteract bone loss under psychological stresses.

Higher intakes of dietary caffeine are associated with 25-hydroxyvitamin D deficiency.

Low serum 25-hydroxyvitamin D [25(OH)D] levels remain a challenge worldwide. While some in vitro studies show a caffeine-induced decrease in vitamin D receptor expression, there is a paucity of research to define the extent of caffeine intake and effects on 25(OH)D levels. Therefore, we aimed to associate dietary caffeine intake with 25(OH)D deficiency through a recognized dataset. Using data collected from the 2005-2006 National Health and Nutrition Examination Survey (NHANES), 25(OH)D levels and dietary caffeine intake were extracted from 13134 individuals (30-47 years, interquartile range). We used one-way ANOVA and chi-square tests for quantitative and qualitative variables, respectively, and performed multivariate logistic regression for four models to assess the odds ratio (OR) of 25(OH)D deficiency (<20 ng/ml or <50 nmol/L) based on quartiles of dietary caffeine intake. Both crude and multivariable models detected higher OR for 25(OH)D deficiency according to the highest intakes of caffeine (15.8±9.5, 51.9±11.9, and 177±156 mg/d) when compared to the reference category (2.19±1.04 mg/d), in which the OR in the highest category of caffeine intake was 1.24 (95% CI: 1.12 to 1.37) and 1.48 (95% CI: 1.16 to 1.78) for the crude model and the most complete multivariable analysis (adjustment for age, sex, race, body mass index, smoking, physical activity, occupation, energy intake, protein intake, and fat intake), respectively. In conclusion, higher dietary intakes of caffeine were associated with 25(OH)D deficiency in a representative sample of the American population, but further investigation is warranted to determine causation.

APOE2 promotes the development and progression of subretinal neovascularization in age-related macular degeneration via MAPKs signaling pathway.

BACKGROUND: Neovascular age-related macular degeneration (nvAMD) is one of the main pathological features of wet AMD. Apolipoprotein E2 is involved in the formation of nvAMD but the molecular mechanism has not been reported. METHODS: The APOE alleles in AMD patients were detected by genotyping. Mouse models were divided into 4 groups according to transfection different gene segments and laser-induced treatment. APOE2, VEGF, PDGF-BB, b-FGF and inflammatory cytokines (including p-NF-κB, TNF-α, IL-1ß and IL-6) were tested by ELISA in mice retinal lysate. The formation of nvAMD in the indicated treatment groups at 3rd, 7th and 14th day after laser-induced damage were detected by FFA. Besides, qRT-PCR was used to determine the mRNA levels of p38, JNK and ERK in ARPE-19 cells. Finally, the inflammatory cytokines and MAPK proteins (including P38, p-P38, JNK, p-JNK, ERK and p-ERK) were detected by western blot. RESULTS: The statistics of APOE alleles showed that APOE2 allele carriers were more likely to nvAMD. VEGF, PDGF-BB, b-FGF and related inflammatory cytokines were up-regulated significantly after treatment with APOE2, which were reduced after silencing the MAPK family genes, however. Further, the expression levels of neovascular growth factors and inflammatory cytokines were highly consistent between mouse models and ARPE-19 cells. Besides, the phosphorylation levels of p38, JNK and ERK were affected by APOE2. CONCLUSION: nvAMD was affected directly by the overexpression of VEGF, PDGF-BB and b-FGF, which were regulated by APOE2 through activating MAPKs pathway.

Exploring the beneficial role of telmisartan in sepsis-induced myocardial injury through inhibition of high-mobility group box 1 and glycogen synthase kinase-3ß/nuclear factor-κB pathway.

In the present experimental study, cecal ligation and puncture significantly increased the myocardial injury assessed in terms of excess release of creative kinase-MB (CK-MB), cardiac troponin I (cTnI), interleukin (IL)-6 and decrease of IL-10 in the blood following 12 h of laparotomy procedure as compared to normal control. Also, a significant increase in protein expression levels of high-mobility group box 1 (HMGB1) and decreased phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) was observed in the myocardial tissue as compared to normal control. A single independent administration of telmisartan (2 and 4 mg/kg) and AR-A014418 (1 and 2 mg/kg) substantially reduced sepsis-induced myocardial injury in terms of decrease levels of CK-MB, cTnI and IL-6, HMGB1, GSK-3ß and increase in IL-10 and p-GSK-3ß in the blood in sepsis- subjected rats. The effects of telmisartan at dose 4 mg/kg and AR-A014418 at a dose of 2 mg/kg were significantly higher than the telmisartan at a dose of 2 mg/kg and AR-A014418 1 mg/kg respectively. Further, no significant effects on different parameters were observed in the sham control group in comparison to normal. Therefore it is plausible to suggest that sepsis may increase the levels of angiotensin II to trigger GSK-3ß-dependent signaling to activate the HMGB1/receptors for advanced glycation end products, which may promote inflammation and myocardial injury in sepsis-subjected rats.

Effects of walnut intake on anthropometric characteristics: A systematic review and dose-response meta-analysis of randomized controlled trials.

BACKGROUND & OBJECTIVE: Effects of walnut intake on anthropometric measurements have been inconsistent among clinical studies. Thus, we conducted a meta-analysis of randomized clinical trials (RCTs) to evaluate and quantify the effects of walnut intake on anthropometric characteristics. METHODS: We carried out a systematic search of all available RCTs up to June 2019 in the following electronic databases: PubMed, Scopus, Web of Science and Google Scholar. Pooled weight mean difference (WMD) of the included studies was estimated using random-effects model. RESULTS: A total of 27 articles were included in this meta-analysis, with walnuts dosage ranging from 15 to 108 g/d for 2 wk to 2 y. Overall, interventions with walnut intake did not alter waist circumference (WC) (WMD: -0.193 cm, 95 % CI: -1.03, 0.64, p = 0.651), body weight (BW) (0.083 kg, 95 % CI: -0.032, 0.198, p = 0.159), body mass index (BMI) (WMD: -0.40 kg/m,295 % CI: -0.244, 0.164, p = 0.703), and fat mass (FM) (WMD: 0.28 %, 95 % CI: -0.49, 1.06, p = 0.476). Following dose-response evaluation, reduced BW (Coef.= -1.62, p = 0.001), BMI (Coef.= -1.24, p = 0.041) and WC (Coef.= -5.39, p = 0.038) were significantly observed through walnut intake up to 35 g/day. However, the number of studies can be limited as to the individual analysis of the measures through the dose-response fashion. CONCLUSIONS: Overall, results from this meta-analysis suggest that interventions with walnut intake does not alter BW, BMI, FM, and WC. To date, there is no discernible evidence to support walnut intake for improving anthropometric indicators of weight loss.

Ajmalicine and its Analogues Against AChE and BuChE for the Management of Alzheimer's Disease: An In-silico Study.

BACKGROUND: Alzheimer's disease (AD) is the most well-known reason for disability in persons aged greater than 65 years worldwide. AD influences the part of the brain that controls cognitive and non-cognitive functions. OBJECTIVE: The study focuses on the screening of natural compounds for the inhibition of AChE and BuChE using a computational methodology. METHODS: We performed a docking-based virtual screening utilizing the 3D structure of AChE and BuChE to search for potential inhibitors for AD. In this work, a screened inhibitor Ajmalicine similarity search was carried out against a natural products database (Super Natural II). Lipinski rule of five was carried out and docking studies were performed between ligands and enzyme using 'Autodock4.2'. RESULTS: Two phytochemical compounds SN00288228 and SN00226692 were predicted for the inhibition of AChE and BuChE, respectively. The docking results revealed Ajmalicine, a prominent natural alkaloid, showing promising inhibitory potential against AChE and BuChE with the binding energy of -9.02 and -8.89 kcal/mole, respectively. However, SN00288228- AChE, and SN00226692-BuChE were found to have binding energy -9.88 and -9.54 kcal/mole, respectively. These selected phytochemical compounds showed better interactions in comparison to Ajmalicine with the target molecule. CONCLUSION: The current study verifies that SN00288228 and SN00226692 are more capable inhibitors of human AChE and BuChE as compared to Ajmalicine with reference to ΔG values.

Sustained delivery of prilocaine and lidocaine using depot microemulsion system: in vitro, ex vivo and in vivo animal studies.

Topical drug delivery for local anesthetics has been an interesting area of research for formulators considering the resistance and barrier properties of skin and high clearance rate of drugs like prilocaine and lidocaine (duration of action < 2.5 h). In this study, efforts have been made to sustain the release of prilocaine and lidocaine by using depot microemulsion system. Drug loaded microemulsions were formulated using Capmul MCM, Pluronic F127, polyethylene glycol 200 (PEG 200) and water from pseudo-ternary diagrams. The Smix at 1:4 ratio showed larger microemulsion area in comparison to 1:2 ratio. The ex-vivo studies indicate sustained release of prilocaine and lidocaine from the microemulsion up to 8 h, in comparison to 4 h with ointments. Skin irritation study on rabbits confirmed the safety of drug loaded microemulsions for local drug delivery. The improved ex vivo data is reflected in the in vivo studies, were radiant heat tail-flick test and sciatic nerve model showed prolong duration of action for both prilocaine and lidocaine microemulsions in comparison to ointment. The in vitro and in vivo efficacy of prilocaine and lidocaine was non-significant. The improved efficacy was due to high penetration of microemulsion and depot effect due to local precipitation (destabilization of microemulsion) of drug in the skin layer. The sustained local anesthetic effect is highly desirable for the treatment of skin irritation due to skin burns and pre- and post-operative pain.

Novel Polyvinyl Pyrrolidone-Loaded Olopatadine HCl-Laden Doughnut Contact Lens to Treat Allergic Conjunctivitis.

Olopatadine HCl is an antiallergic drug used for the management of allergic conjunctivitis. Currently, it is delivered via eye drop solution, which is highly inefficient due to low bioavailability. Silicone contact lenses can be used to sustain the release of ophthalmic drugs. However, the presence of drug alters the optical transmittance and physical properties of the contact lens. The objective was to design a novel polyvinyl pyrrolidone (PVP)-coated olopatadine-ethyl cellulose microparticles-laden doughnut contact lens to sustained ocular delivery with limited alteration to the optical and swelling properties of the contact lens. The doughnut was implanted within the periphery of the lens using modified casting technique. Olopatadine HCl was loaded by soaking (SM-OL), direct loading (DL-OL), and doughnut casting method (DNT-OL). PVP (comfort agent) was loaded on the surface of contact lens for all the batches via novel curing technique. The in vitro olopatadine HCl release data of SM-OL (up to 48-72 h) and DL-OL batches (up to 72 h) showed high burst release, whereas DNT-OL batch showed sustained release up to 120 h without significant (p > 0.05) alteration in the optical and swelling properties of contact lens. All the batches showed sustained release of PVP up to 120 h. The in vivo studies in the rabbit tear fluid showed improvement in the olopatadine HCl and PVP retention time in comparison to eye drop solution. The PVP-loaded DNT-OL-500 lens showed tear stabilization (comfort wear) in Schirmer strip test (rabbits) with no protein adherence in comparison to DNT-OL-500 lens without PVP. The study demonstrated the successful delivery of olopatadine HCl and PVP-K30 from the doughnut contact lens for the extended period with limited alteration to the optical and swelling properties of contact lens.

The effect of psyllium consumption on weight, body mass index, lipid profile, and glucose metabolism in diabetic patients: A systematic review and dose-response meta-analysis of randomized controlled trials.

Water-soluble dietary fibers have been shown to improve lipid profile and glucose metabolism in diabetes. The aim of this study was to review the effects of psyllium consumption on weight, body mass index, lipid profiles, and glucose metabolism in diabetic patients in randomized controlled trials. A comprehensive systematic search was performed in PubMed/MEDLINE, Web of Sciences, Cochrane, and Scopus by two independent researchers up to August 2019 without any time and language restrictions. The DerSimonian and Laird random-effects model method performed to calculate the pooled results. Inclusion criteria were randomized controlled trial design, adult subjects, and studies reporting the mean differences with the 95% confidence interval for outcome. Eight studies containing nine arms with 395 participants were identified and included in final analysis. Combined results found a significant reduction in triglycerides, low-density lipoprotein, fasting blood sugar, and hemoglobin A1c following psyllium consumption (weighted mean differences [WMD]: -19.18 mg/dl, 95% CI [-31.76, -6.60], I2 = 98%), (WMD: -8.96 mg/dl, 95% CI [-13.39, -4.52], I2 = 97%), (WMD: -31.71 ml/dl, 95% CI [-50.04, -13.38], I2 = 97%), and (WMD: -0.91%, 95% CI [-1.31, -0.51], I2 = 99%), respectively. There was no significant change in high-density lipoprotein, body mass index, cholesterol, and weight. In conclusion, the results demonstrated a significant reduction in triglycerides, low-density lipoprotein, fasting blood sugar, and hemoglobin A1c by psyllium intervention among diabetic patients.

Association of aspirin therapy with risk of hepatocellular carcinoma: A systematic review and dose-response analysis of cohort studies with 2.5 million participants.

Although aspirin is commonly used for the prevention of cardiovascular disease, evidence from research has shown that these beneficial effects might extend to hepatocellular carcinoma (HCC). This dose-response analysis was performed to investigate the association between aspirin use and risk of HCC. A systematic search was conducted in MEDLINE/PubMed, SCOPUS, Cochrane, and Web of Science databases from inception up to 29th October 2019. DerSimonian and Laird Random-effects model was used to estimate pooled hazard ratios (HRs) from included studies. Overall, eight studies containing 2,604,319 participants evaluating the association between aspirin use and risk of HCC were uncovered and included in the present meta-analysis. Pooled results of included studies showed a significant reduction in risk of HCC in participants who used aspirin (HR 0.59, 95 % CI 0.47-0.75, Pheterogeneity = 0.001, I2 = 90 %). In total, 13,636 cases of HCC detected during the follow-up period of these studies. Furthermore, linear dose-response model showed an significant inverse association between aspirin dose and risk of HCC (exp (b) = 0.994, p < 0.001), while non-linear dose-response analysis revealed an even more robust association (Coef1=-0.008, p1 = 0.04, Coef2 = 0.033, p2 = 0.13). This systematic review and dose-response analysis identified significant inverse relation between aspirin and risk of HCC using both linear and non-linear models.

Gold nanoparticles synthesized from Euphorbia fischeriana root by green route method alleviates the isoprenaline hydrochloride induced myocardial infarction in rats.

The procurance of gold nanoparticles in the plant extracts is an excellent way to attain nanomaterials natural and eco-friendly nanomaterials. The Dehydrated roots of Chinese Euphorbia fischeriana flowering plant are called "Lang-Du". In this study, the retrieving of gold nanoparticles from Euphorbia fischeriana root was amalgamated by standard procedure. Fabricated gold nanoparticles were portrayed through the investigations of ultraviolet and visible spectrophotometry (UV-Vis), Fourier transform infrared spectroscopy (FTIR), High resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD). The UV-Vis and FTIR results explicated the obtained particles were sphere-shaped and the terpenoids of Euphorbia fischeriana had strong communications with gold surface. The HRTEM and XRD images exposed the produced gold nanoparticles had an extreme composition of crystal arrangement and excellent uniformed size of particles. In our study, the Isoprenaline induced myocardial damage established the elevation in TBARS, LOOH of heart tissues and notable decline in antioxidant enzymes SOD, CAT, GPx, and GSH. This biochemical result was additionally proved by histopathological assessment. Remarkably, the pretreatment with EF-AuNps(50 mg/kg b.w) illustrated stabilized levels of serum creatine and cardiotropins in myocardial infarcted animals. And further we understood the essential function of NF-ƙB, TNF-α, IL-6 signaling molecules and its way progression in the development of vascular tenderness.

Galectin-3 is associated with severe heart failure and death: A hospital-based study in Chinese patients.

Heart failure (HF) is a serious disease syndrome characterized by elevated pro-inflammatory cytokines and inflammatory mediators presume to have significant contribution on disease progression. Galectins are carbohydrate-binding proteins responsible of various physiological functions. Role of galectins in heart failure has been ill-defined. In the present case-controls study, 136 patients clinically diagnosed with heart failure and 125 healthy Chinese controls were recruited. Levels of galectins (Gal-1, 3 and 9) and cytokines (IFN-γ, IL-17A, IL-4 and TGF-ß) were quantified by ELISA. Increased levels of galectin-1 and 3 was observed in HF patients and associated with clinical severity. In addition, pro-inflammatory cytokines such as IFN-γ and IL-17A were increased in patients whereas, anti-inflammatory TGFß was decreased. Galectin-3 was positively correlated with IFN-γ, IL-17A and inversely with TGF-ß. Furthermore, ROC curve analysis suggested galectin-3 as a promising biomarker for diagnosis and HF and clinical severity. Interestingly, a two-year follow-up indicated significant association of elevated galectin-3 with mortality due to HF. In conclusion, galectin-3 associated with HF and clinical manifestations possibly by inducing pro-inflammatory cytokines and could be a possible biomarker of HF and severe clinical conditions.

Increased susceptibility of mice obtained from in vitro fertilization to global cerebral ischemia-reperfusion injury: possible role of hydrogen sulphide and its biosynthetic enzymes.

Aim of the Study: This study was designed to explore the relative susceptibility of in vitro fertilization (IVF)-conceived mice to global cerebral ischemic injury with the possible role of hydrogen sulphide and enzymes responsible for its production.Materials and Methods: IVF was carried to obtain pups, which were allowed to grow to the age of eight weeks. Thereafter, male mice were subjected to 20 min of global ischemia and 24 h of reperfusion. The mice obtained from other groups including normal mating, superovulation but normal mating and normal mating but embryo implantation were also subjected to global ischemia-reperfusion (I/R) injury.Results: IVF-derived mice exhibited significant more injury in response to I/R injury in comparison to other groups assessed in terms of impairment in locomotor activity, development of motor in coordination, neurological severity score, cerebral infarction and apoptosis markers (caspase-3 activity and Bcl-2 expression). Moreover, there was a relative decrease in the brain levels of hydrogen sulphide (H2S) and its biosynthetic enzymes viz. cystathionine-ß-synthase and cystathionine-γ-lyase. Interestingly, the levels of H2S and cystathionine-γ-lyase were significantly low in IVF-derived mice in basal conditions also, i.e. before subjecting to I/R injury and these biochemical alterations were associated with the behavioural deficits in mice, even before subjecting to I/R injury.Conclusion: It is concluded that in vitro fertilization-derived mice are more susceptible to global cerebral I/R injury, which may be possibly due to decreased levels of hydrogen sulphide and its biosynthetic enzymes viz., cystathionine-ß-synthase and cystathionine-γ-lyase.

Nrf2/HO-1 Mediated Protective Activity of Genistein Against Doxorubicin-Induced Cardiac Toxicity.

The current study evaluated the cardioprotective activity of genistein in cases of doxorubicin-(Dox) induced cardiac toxicity and a probable mechanism underlying this protection, such as an antioxidant pathway in cardiac tissues. Animals used in this study were categorized into four groups. The first group was treated with sodium carboxymethylcellulose (0.3%; CMC-Na) solution. The second group received Dox (3.0 mg/kg, i.p.) on days 6, 12, 18, and 24. The third and fourth groups received Dox (3 mg/kg, i.p.) on days 6, 12, 18, and 24 and received protective doses of genistein (100 [group 3] and 200 [group 4] mg/kg/day, p.o.) for 30 days. Treatment with genistein significantly improved the altered cardiac function markers and oxidative stress markers. This was coupled with significant improvement in cardiac histopathological features. Genistein enhanced the Nrf2 and HO-1 expression, which showed protection against oxidative insult induced by Dox. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed substantial inhibition of apoptosis by genistein in myocardia. The study showed that genistein has a strong reactive oxygen species scavenging property and potentially (P ≤ .001) decreases the lipid peroxidation as well as inhibits DNA damage in cardiac toxicity induced by Dox. In conclusion, the potential antioxidant effect of genistein may be because of its modulatory effect on Nrf2/HO-1 signalling pathway and by this means exhibits cardioprotective effects from Dox-induced oxidative injury.

Assessment of the Therapeutic Effects of Fucoxanthin by Attenuating Inflammation in Ovalbumin-Induced Asthma in an Experimental Animal Model.

Asthma has affected more than 300 million people worldwide and is considered one of the most debilitating global public health problems based on a recent statistical report from the Global Initiative for Asthma. Inflammation of the airways leads to the various interrelated mechanisms of innate and adaptive immunity acting mutually with the epithelium of the respiratory organ. Fucoxanthin is an orange or brown pigment which is naturally found in various seaweeds. To the best of our knowledge, there are no scientific claims or evidence of the curative effects of fucoxanthin against asthma. Hence, this present research was designed to investigate the curative activity of fucoxanthin against ovalbumin-induced asthma in a mouse model. Fucoxanthin (50 mg/kg) showed significant (P < 0.001) antiasthma activity. It effectively decreased intracellular secretion of reactive oxygen species and increased antioxidant enzyme activity. Fucoxanthin also decreased inflammatory cytokine markers in bronchoalveolar lavage fluid. Because fucoxanthin showed effective antiasthma activity against ovalbumin-induced asthma in experimental animals, further research on this natural antioxidant could lead to development of a novel drug for the treatment of asthma in humans.

Activation of Nrf2 signaling by sitagliptin and quercetin combination against ß-amyloid induced Alzheimer's disease in rats.

The objective of this study was to evaluate the neuroprotective effect of sitagliptin (Sita), quercetin (QCR) and its combination in ß-amyloid (Aß) induced Alzheimer's disease (AD). Male Sprague-Dawley rats, weighing between 220 and 280 g were used for experiment. Rats were divided into 5 groups (n = 10) and the groups were as follows: (a) Sham control; (b) Aß injected; (c) Aß injected + Sita 100; (d) Aß injected + QCR 100; and (e) Aß injected + Sita 100 + QCR 100. Cognitive performance was observed by the Morris water maze (MWM), biochemical markers, for example, MDA, SOD, CAT, GSH, Aß1-42 level, Nrf2/HO-1 expression and histopathological study of rat brain were estimated. Pretreatment with Sita, QCR and their combination showed a significant increase in escape latency in particular MWM cognitive model. Further co-administration of sita and QCR significantly reduced Aß1-42 level when compared with individual treatment. Biochemical markers, for example, increased SOD, CAT and GSH, decreased MDA were seen, and histopathological studies revealed the reversal of neuronal damage in the treatment group. Additionally, Nrf2/HO-1 pathway in rat's brain was significantly increased by Sita, QCR and their combination. Pretreatment with QCR potentiates the action of Sita in Aß induced AD in rats. The improved cognitive memory could be because of the synergistic effect of the drugs by decreasing Aß1-42 level, antioxidant activity and increased expression of Nrf2/HO-1 in rat brain.

Rabdosia rubescens Linn: green synthesis of gold nanoparticles and their anticancer effects against human lung cancer cells A549.

Nanomedicine is a rapidly emerging field and is reported to be a promising tool for treating various diseases. Green synthesized nanoparticles are documented to possess a potent anticancer effect. Rabdosia rubescens is a Chinese plant which is also one of the components of PC-SPES and used to treat prostate cancer. In the present study, we synthesized the gold nanoparticles from R. rubescens (RR-AuNP) and analyzed its anticancer activity against the lung carcinoma A549 cell lines. Since lung cancer is reported to be with increased morbidity and decreased survival rate. The biosynthesized RR-AuNP were confirmed using UV-Visible spectrophotometer, size and shape of RR-AuNP were assessed by DLS, TEM and EDX. The biomolecules present in RR-AuNP and its topographical structure were detected using FTIR, SAED and AFM analysis. MTT assay was performed to detect the IC50 dose of RR-AuNP and its apoptotic effect was assessed by detecting the caspases activation, ROS generation. The anticancer effect of RR-AuNP was confirmed by DAPI staining, TUNEL assay and its molecular mechanism were confirmed by assessing the apoptotic signalling molecules protein expression. Our results illustrate that RR-AuNP showed a strong absorption peak at 550 nm and the RRAuNP were polydispersed nanospheres with size of 130 nm. RR-AuNP IC50 dose against A549 lung carcinoma cell line was detected to be at 25 µg/ml. The results of DAPI staining, TUNEL and immunoblotting analysis confirms both the 25 µg/ml and 50 µg/ml of RR-AuNP possess potent anticancer and apoptotic effect, suggesting that RR-AuNP that it may be a persuasive molecule to treat lung cancer.

Biomimetic hydroxyapatite/poly xylitol sebacic adibate/vitamin K nanocomposite for enhancing bone regeneration.

Hydroxyapatite (HAP) is a significant bone mineral that establishes bone strength. HAP composites in combination with biodegradable and bioactive polymer poly xylitol sebacic adipate (PXSA) would result in a constant release at target sites. Numerous studies have shown that vitamin K (VK) might possess a vital function in bone metabolism. The purpose of the present study was to inspect the synthesized composite HAP/PXSA/VK in developing polymeric biomaterials composite for the application of bone tissue regeneration. FTIR, X-ray diffraction, SEM and TEM techniques were applied to characterize the prepared composites. The release of VK from the HAP/PXSA/VK composite was evidenced through UV-Vis spectroscopy. In vitro studies proved that the HAP/PXSA/VK composite is appropriate for mesenchymal stem cell culture. Compared to pure HAP prepared following the same method, HAP/PXSA/VK composite provided favourable microstructures and good biodegradation distinctiveness for the application of tissue engineering, as well as tissue in-growth characteristics and improved scaffold cell penetration. This work reveals that the HAP/PXSA/VK composites have the potential for applications in bone tissue engineering.

Evaluation of wound healing activity of plumbagin in diabetic rats.

This study was performed to evaluate the antidiabetic and wound healing activity of plumbagin in diabetic rats by macroscopical, biochemical, histological, immunohistochemical and molecular methods. Percentage of wound closure and contraction was delayed in diabetic rats when compared to non-diabetic group. There was significant reduction in period of epithelialization, collagen and protein content. Serum insulin level was significantly lowered together with increase in glucose level in diabetic rats. Lipid levels were increased significantly with concomitant decrease in HDL level. The mRNA levels of Nrf2, collagen-1, TGF-ß and α-SMA were significantly lowered whereas Keap-1 levels were increased in diabetic rats. The level of lipid peroxides was increased while the levels of antioxidants were lowered significantly. ELISA results reveal upregulated levels of inflammatory markers. Western blot result shows upregulated levels of CD68 and CD163 proteins in wound area of diabetic rats. Histopathological observation revealed increased inflammatory cells infiltration in diabetic control. Immunofluorescent staining and immunohistochemical analysis also displayed delayed wound healing in diabetic groups. Diabetic rats treated with 10% and 20% plumbagin showed increased epithelialization, collagen deposition, increased serum insulin level and increased antioxidant status. Lipid peroxides and lipid levels were lowered significantly with increase in HDL level. Inflammatory markers were lowered, and growth factors expressions were increased markedly. Thus, the results of the study indicated that plumbagin administration could improve wound healing activity and could serve as a potent antidiabetic and anti-inflammatory agent.