A Modified Tongue Crib Appliance for Correction of Tongue Thrusting.

Digit sucking and tongue thrusting are parafunctional habits that are commonly observed and are recognized as major etiological factors in the development of dental malocclusion. Treatment for these oral habits typically involves removal of the etiology, retraining exercises, and use of mechanical restraining appliances. A 13-year-old male patient reported a complaint of forwardly placed upper front teeth. The extraoral examination of the patient showed a convex profile, good facial symmetry, acute nasolabial angle, incompetent lips at rest, and a shallow mentolabial sulcus. Intraoral examination showed class I molar and canine relations on either side, a mild open bite tendency, a midline diastema, proclined upper and lower anteriors, an increased overjet, and tongue thrusting habit. A modification to the tongue crib was made by adding an acrylic bead in the center of the crib. The patient was trained to roll the bead posteriorly with the aim of retraining the tongue to posture away from the front teeth. Harmful forces of the tongue can result in excessive posterior teeth eruption, open bite, and increased overjet. Duration of appliance wear and type of appliance used are important considerations in treating patients with tongue thrust or open bite. A modified tongue crib was used for six months resulting in significant improvement in maxillary anterior dentition position, lip competence, arch forms, overbite, and midline diastema closure. A tongue crib is a useful tool for addressing tongue thrusting and digit-sucking behaviors by retraining the related muscles, providing physical restraint, and serving as a reminder to break the habit. It can be used in conjunction with a fixed appliance to improve its effectiveness.

Increased health risk assessment in different vegetables grown under untreated sewerage irrigation regime due to higher heavy metals accumulation.

Heavy metals are environmental pollutants and carcinogenic for human health if ingested. In developing countries, including Pakistan, untreated sewerage water is one of the major sources of irrigation for vegetable production in the vicinities of urban areas which might be toxic to human health due to heavy metals contamination. The present study was conducted to investigate the uptake of heavy metals by sewage water application and its impact on human health. The experiment consisted of five vegetable crops (Raphanus sativus L, Daucus carota, Brassica rapa, Spinacia oleracea, and Trigonella foenum-graecum L.) and two irrigation sources (clean water irrigation and sewage water irrigation). Each treatment was three time replicated for all five vegetables, and standard agronomic practices were applied. The results demonstrated that shoot and root growth in radish, carrot, turnip, spinach, and fenugreek was enhanced significantly with sewerage water, probably due to enhanced organic matter. However, pithiness was observed in the root of radish under sewerage water treatment. Very high concentrations of Cd, up to 7.08 ppm in turnip roots while up to 5.10 ppm in fenugreek shoot, were observed, and other vegetables also contained higher concentrations of Cd. Zn concentrations in the edible parts of carrot (control (C) = 129.17 ppm, sewerage (S) = 164.10 ppm), radish (C = 173.73 ppm, S = 253.03), turnip (C = 109.77 ppm, S = 149.67 ppm), and fenugreek (C = 131.87 ppm, S = 186.36 ppm) were increased by sewerage water treatment but a decrease in Zn concentration in spinach (C = 262.17 ppm, S = 226.97 ppm) was observed. Fe concentration in edible parts of carrot (C = 888.00 ppm, S = 524.80 ppm), radish (C = 139.69 ppm, S = 123.60 ppm), turnip (C = 195.00 ppm, S = 121.37 ppm), and fenugreek (C = 1054.93 ppm, S = 461.77 ppm) were also decreased by sewerage water treatment while spinach leaves had accumulated higher Fe (C = 1560.33 ppm, S = 1682.67 ppm) in sewerage water treatment. The highest bioaccumulation factor value was 4.17 for Cd in carrots irrigated with sewerage water. The maximum value of bioconcentration factor was 3.11 for Cd in turnip under control, and the highest value of translocation factor was 4.82 in fenugreek irrigated with sewerage water. Daily intake of metals and health risk index (HRI) calculation indicated that HRI for Cd was more than 1, suggesting toxicity in these vegetables while HRI for Fe and Zn is still under safe limit. Correlation analysis among different traits of all vegetables under both treatments revealed valuable information for selecting traits in the next crop breeding programs. It is concluded that untreated sewerage-irrigated vegetables, highly contaminated with Cd, are potentially toxic for human consumption and should be banned in Pakistan. Furthermore, it is suggested that the sewerage water should be treated to eliminate toxic compounds, particularly Cd, before irrigation usage and non-edible/phytoremediation crops might be grown in contaminated soils.

Lagenaria siceraria fruit: A review of its phytochemistry, pharmacology, and promising traditional uses.

Since ancient times, the Cucurbitaceae family is used as a therapeutic option in human medicine. This family has around 130 genera and 800 species. Researchers have studied the various plants of this family including Lagenaria siceraria due to their medicinal potential. Various properties are beneficial for human health, that have been attributed to L. siceraria like antioxidant, hypolipidemic, diuretic, laxative, hepatoprotective, analgesic, antihypertensive, cardioprotective, central nervous system stimulant, anthelmintic, free radical scavenging, immunosuppressive, and adaptogenic. The fruit of this plant is commonly used as a vegetable that has a low-calorie value. The species possess a diverse set of biological compounds like flavonoids, sterols, saponins, and terpenoids. Vitamins, choline, flavonoids, minerals, proteins, terpenoids, and other phytochemicals are also found in the edible parts of this plant. Besides 17 different amino acids, many minerals are reported to be present in the seeds of L. siceraria. According to the USDA nutritional database per 100 g of L. siceraria contains 14 Kcal energy, 3.39 g carbohydrates, 0.62 g protein, 0.2 g fat, and 0.5 g fiber. L. siceraria performs a wide range of pharmacological and physiological actions. The literature reviewed from various sources including PubMed, Science Direct, Google scholar, etc. shows the remarkable potential to treat various human and animal illnesses due to its' potent bioactive chemicals. The key objective of this thorough analysis is to present a summary of the data about the beneficial and harmful effects of L. siceraria intake on human health, as well as in veterinary fields.

Comparative Study of Antimicrobial and Antioxidant Potential of Olea ferruginea Fruit Extract and Its Mediated Selenium Nanoparticles.

Nanotechnology, the science of the recent era, has diverse applications in agriculture. Selenium (Se) is a non-metal and an essential micronutrient for animals and humans. In this study, selenium nanoparticles (SeNPs) were biosynthesized by using Olea ferruginea fruit extracts. The size, shape, chemical nature, and identification of functional groups involved in the synthesis of SeNPs were studied by UV-visible spectroscopy, Scanning Electron Microscope (SEM), and Fourier Transform Infra-Red (FTIR) spectrometry. SeNP synthesis was confirmed by an absorption peak at 258 nm by UV-visible spectroscopy. SEM showed that SeNPs were spherical, smooth, and between 60 and 80 nm in size. FTIR spectrometry confirmed the presence of terpenes, alcohols, ketones, aldehydes, and esters as well as phyto-constituents, such as alkaloids and flavonoids, that possibly act as reducing or capping agents of SeNPs in an aqueous solution of Olea ferruginea. Antimicrobial activity was examined against bacterial pathogens, such as Klebsiella pneumonia, Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermitis, as well as fungal pathogens, such as Aspergillus niger and Fusarium oxysporum, by using the well-diffusion method. Antioxidant activity was observed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, ABTs assay, and reducing power assay. At a higher concentration of 400 ppm, biosynthesized SeNPs showed an inhibition zone of 20.5 mm, 20 mm, 21 mm, and 18.5 mm against Klebsiella pneumonia, Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermitis, respectively. Similarly, SeNPs also demonstrated a zone of inhibition against Aspergillus niger and Fusarium oxysporum of 17.5 and 21 mm, respectively. In contrast to Olea ferruginea fruit extracts, Olea ferruginea-mediated SeNPs demonstrated strong antimicrobial activity. By performing the DPPH, ABTs, and reducing power assay, SeNPs showed 85.2 ± 0.009, 81.12 ± 0.007, and 80.37 ± 0.0035% radical scavenging potential, respectively. The present study could contribute to the drug development and nutraceutical industries.

Phytochemical Screening, Anti-Inflammatory, and Antidiabetic Activities of Different Extracts from Caralluma edulis Plant.

The plant Caralluma edulis is traditionally used against diabetes and inflammatory conditions in Pakistan. This study was designed to provide scientific validation of the traditional use of Caralluma edulis. Phytochemicals were extracted from the plant by different solvents (distilled water, methanol, ethanol, and acetone) using the Soxhlet's extraction method. Bioactive compounds were detected by gas chromatography-mass spectrometry (GC-MS). The in vitro anti-inflammatory activities (albumin denaturation, membrane stabilization, and proteinase inhibition) and antioxidant capacity (DPPH scavenging activity, FRAP reducing activity) of different extracts from Caralluma edulis were assessed. The antidiabetic potential of Caralluma edulis plant extracts was determined in acute and subacute diabetic rabbit models. Oxidative stress and enzymatic antioxidant status were also estimated in MDA, CAT, and SOD levels. Results showed that the methanol extract yielded the highest contents of phenolics, flavonoids, alkaloids, and terpenoids. The in vitro anti-inflammatory activity and antioxidant potential of the methanol extract were the highest among the tested solvents. The tested extracts did not show any remarkable antidiabetic activity in the acute diabetic model. However, all tested extracts demonstrated antidiabetic potential in the subacute diabetic model. No adverse effect was observed at the tested dose (200 mg/kg) of Caralluma edulis extracts in experimental animals. It is concluded that methanol is the key solvent for extracting bioactive compounds from Caralluma edulis. The plant can be used against inflammatory disorders and may prove a potential candidate for drug development. Long-term use of Caralluma edulis at the tested dose (200 mg/kg) showed antidiabetic properties in the animal model.

Extracellular vesicles and exosome: insight from physiological regulatory perspectives

The current study highlights prospective mechanisms of biogenesis of extracellular vesicles (EVs) and potential involvement in cellular signaling and transport with great emphasis to illustrate their role as biomarkers in certain pathologies. The current review highlights EVs, the heterogeneous entities secreted by cells in highly conserved manner. A series of consensus terminologies for various types is yet to be organized. Exosomes, microvesicles and apoptotic bodies are major populations among EVs. EVs are key regulators in cellular physiological homeostasis, disease progression and evolve either from plasma membrane (microvesicles) or fusion of endosomes with exosomes. However, how vesicular inclusions elicit a plethora of biological responses is still not much clear. However, how these vesicular inclusions get packaged and delivered by these EVs shows great involvement in inter- and intracellular cellular signaling and channeling of multiple proteins, variety of RNAs and certain fat molecules. It’s worth to mention that EVs carry small non-coding RNAs (snRNAs) which are involved in multiple cellular molecular events at targeted sites. Moreover, snRNA trafficking through exosomes and microvesicles depicts remarkable potential as non-invasive biomarkers in different clinical disorders especially immune system pathologies, cardiovascular issues, and metabolic syndromes. (AU)

Evaluation of the hepatoprotective activity of hydroalcoholic extract of Alhagi camelorum against valproic acid-induced hepatotoxicity in rats.

BACKGROUND AND PURPOSE: Despite many liver disorders, clinically useful drugs are scarce. Moreover, the available therapies are facing the challenges of efficacy and safety. Alhagi camelorum has been used in folk medicine globally for millennia to treat several ailments. Alhagi camelorum (Ac) is an old plant with a significant therapeutic value throughout Africa, Asia, and Latin America. Our goal was to determine the hepatoprotective activity of Alhagi camelorum against valproic acid induced hepatotoxicity using an animal model. EXPERIMENTAL APPROACH: The animals were segregated in 4-groups (6 male rats each) weighing 250-290 g. Group-1 animals were treated with normal saline, Group-2 animals were treated with VPA at the dose of 500 mg/kg i.p for 14 days consecutively, while Group-3 and 4 were treated with valproic acid (VPA) at the dose of 500 mg/kg i.p for 14 days along with 400 mg/kg and 600 mg/kg of Ac hydroalcoholic extract respectively. Subsequently, blood serum samples and liver tissues were collected for biochemical and histopathological analysis. Phytochemical screening was carried out to screen for phytochemical classes and HPLC analysis was conducted to screen polyphenols. The antioxidant activity was carried by different assays such as DPPH, SOD, NO etc. KEY RESULTS: The administration of Ac showed hepatoprotection at the doses of 400 and 600 mg/kg. Ac significantly reduces the elevated serum levels of liver biomarkers compared to the valproic acid-induced hepatotoxic group. These findings were confirmed with histopathological changes where Ac was capable of reversing the toxic effects of valproic acid on liver cells CONCLUSION: It is concluded that Ac showed significant hepatoprotective effects at different doses in the animal model used in this study.

Nephroprotective Effects of Alhagi camelorum against Cisplatin-Induced Nephrotoxicity in Albino Wistar Rats.

Alhagi camelorum (AC) is an old plant with a significant therapeutic value throughout Africa, Asia, and Latin America. The overuse of cisplatin (Cis > 50 mg/m2) is associated with observed nephrotoxicity, ototoxicity, gastrotoxicity, myelosuppression, and allergic reactions. Remedial measures are needed for the protection of nephrotoxicity against cisplatin. Thus, we investigated the nephroprotective effects of AC plant extract to prevent cisplatin-induced nephrotoxicity in albino Wistar rats. The presence of polyphenols, phenolic compounds, tannins, and saponins was revealed during phytochemical investigation, and a significantly intense antioxidant activity was recorded. There were no toxicological symptoms in the treated rats, and no anatomical, physiological, or histological abnormalities were found compared to the control rats. The results of correcting cisplatin-induced nephrotoxicity revealed that the extract has a significant ability to treat kidney damage, with most parameters returning to normal after only three weeks of therapy. It is concluded that co-administration of cisplatin with AC extract showed exceptional nephroprotective effects at a dose of 600 mg/kg for Cis-induced nephrotoxicity.

Extracellular vesicles and exosome: insight from physiological regulatory perspectives.

The current study highlights prospective mechanisms of biogenesis of extracellular vesicles (EVs) and potential involvement in cellular signaling and transport with great emphasis to illustrate their role as biomarkers in certain pathologies. The current review highlights EVs, the heterogeneous entities secreted by cells in highly conserved manner. A series of consensus terminologies for various types is yet to be organized. Exosomes, microvesicles and apoptotic bodies are major populations among EVs. EVs are key regulators in cellular physiological homeostasis, disease progression and evolve either from plasma membrane (microvesicles) or fusion of endosomes with exosomes. However, how vesicular inclusions elicit a plethora of biological responses is still not much clear. However, how these vesicular inclusions get packaged and delivered by these EVs shows great involvement in inter- and intracellular cellular signaling and channeling of multiple proteins, variety of RNAs and certain fat molecules. It's worth to mention that EVs carry small non-coding RNAs (snRNAs) which are involved in multiple cellular molecular events at targeted sites. Moreover, snRNA trafficking through exosomes and microvesicles depicts remarkable potential as non-invasive biomarkers in different clinical disorders especially immune system pathologies, cardiovascular issues, and metabolic syndromes.

Comparison of the protective antigen variabilities of prevalent Newcastle disease viruses in response to homologous/heterologous genotype vaccines.

The genotype VII Newcastle disease virus (NDV) vaccine has begun to replace the traditional genotype II NDV vaccine and is widely used in the commercial poultry of China. However, the effect of homologous and heterogeneous anti-NDV serum on the evolution of prevalent NDV is unknown. To understand the effect of genotype II and VII anti-NDV serum on the evolution of genotype VII NDV strains, ZJ1 (waterfowl origin) and CH/SD/2008/128 (ND128; chicken origin) were used for serial passage of 30 generations in DF-1 cells without anti-NDV serum or with genotype II and VII anti-NDV serum independently. The F and HN genes of the 2 viruses were amplified for the 10th, 20th, and 30th generations of each serial passage group and compared with their respective original viruses. We found that there was only one mutation at position 248 in the F gene of ZJ1 due to the serum pressure of genotype VII anti-NDV. Similarly, mutations at residue 527 of the F gene, and position 9 and 319 of the HN gene of ND128 were noted in both anti-NDV serum groups. The results show that the nonsynonymous (NS)-to-synonymous (S) ratio of the F gene of ZJ1 virus was 1.6, and for the HN gene, it was 2.5 in the anti-II serum group. In the anti-VII serum group, the NS/S ratio for the F gene was 2.1, and for the HN gene, it was 2.5. The NS/S ratio of the F gene of the ND128 virus was 0.8, and for the HN gene, it was 3 in the anti-II serum group. Furthermore, the NS/S ratio of the F gene was 0.8, and the HN gene was 2.3 in the anti-VII group. Taken together, our findings highlight that there was no significant difference in the variation of protective antigens in genotype VII NDV under the selection pressure of homologous and heterogeneous genotype NDV inactivated vaccines.

Phenotypic characterization of exotic tomato germplasm: An excellent breeding resource.

Tomato production in Pakistan faces significant problems of low yields due to various biotic and abiotic stresses primarily because of a narrow genetic base of the cultivars being used. Therefore, Introduction and evaluation of the exotic tomato germplasm has become necessary to acquire elite material to develop future breeding programs. To this end, the present study was conducted for the phenotypic characterization of twenty exotic tomato genotypes along with two locally grown cultivars in semi-arid subtropical climate. Data were collected for morphological, fruit quality and fruit yield traits. A significant (p<0.05) phenotypic variation was observed for all the studied traits. Maximum yield was obtained from "Rober" i.e., 1508.31 g per plant. The maximum shelf life was observed in the Cromco, with the least weight loss (2.45%) and loss in the firmness of fruit (22.61%) in 4 days. Correlation analyses revealed a strong genetic association among morphological and yield related traits. High estimates of the heritability (ranged from 79.77% to 95.01% for different traits), along with a high genetic advance (up to 34%) showed the potential usefulness of these traits and genotypes to develop breeding programs to improve the tomato yield and fruit quality.

Newcastle Disease Virus Induced Pathologies Severely Affect the Exocrine and Endocrine Functions of the Pancreas in Chickens.

Newcastle disease virus (NDV) causes a highly contagious and devastating disease in poultry. ND causes heavy economic losses to the global poultry industry by decreasing the growth rate, decrease in egg production high morbidity and mortality. Although significant advances have been made in the vaccine development, outbreaks are reported in vaccinated birds. In this study, we report the damage caused by NDV infection in the pancreatic tissues of vaccinated and specific-pathogen-free chickens. The histopathological examination of the pancreas showed severe damage in the form of partial depletion of zymogen granules, acinar cell vacuolization, necrosis, apoptosis, congestion in the large and small vessels, sloughing of epithelial cells of the pancreatic duct, and mild perivascular edema. Increased plasma levels of corticosterone and somatostatin were observed in NDV-infected chicken at three- and five- days post infection (DPI). A slight decrease in the plasma concentrations of insulin was noticed at 5 DPI. Significant changes were not observed in the plasma levels of glucagon. Furthermore, NDV infection decreased the activity and mRNA expression of amylase, lipase, and trypsin from the pancreas. Taken together, our findings highlight that NDV induces extensive tissue damage in the pancreas, decreases the activity and expression of pancreatic enzymes, and increases plasma corticosterone and somatostatin. These findings provide new insights that a defective pancreas may be one of the reasons for decreased growth performance after NDV infection in chickens.

3-Hydroxy-4,7-megastigmadien-9-one, isolated from Ulva pertusa, attenuates TLR9-mediated inflammatory response by down-regulating mitogen-activated protein kinase and NF-κB pathways.

CONTEXT: Seaweeds are rich in bioactive compounds in the form of vitamins, phycobilins, polyphenols, carotenoids, phycocyanins and polysaccharides; many of these are known to have advantageous applications in human health. 3-Hydroxy-4,7-megastigmadien-9-one (comp) was isolated from Ulva pertusa (U. pertusa) Kjellman (Ulvaceae), which is a familiar edible green seaweed. OBJECTIVE: This study evaluates the anti-inflammatory activity of comp in CpG DNA-stimulated bone marrow-derived dendritic cells (BMDCs). MATERIALS AND METHODS: For evaluating the effect of comp on cytokines production, BMDCs were treated with doses of comp (0, 0.5, 1, 2, 5, 10, 25 and 50 µM) for 1 h before stimulation with CpG DNA (1 µM). Cytokine production was measured by ELISA. Western blotting was conducted for evaluating effect of comp (50 µM) on MAPKs and NF-κB pathways. Luciferase reporter gene assay was conducted for effect of comp (0, 5, 10 and 25 µM) on transcriptional activity of AP-1 and NF-κB. RESULTS: Comp exhibited strong inhibition of interleukin (IL)-12 p40, IL-6 and TNF-α cytokine production with IC50 values of 6.02 ± 0.35, 27.14 ± 0.73, and 7.56 ± 0.21 µM, respectively. It blocked MAPKs and NF-κB pathways by inhibiting the phosphorylation of ERK1/2, JNK1/2, p38 and IκBα. In addition, it strongly inhibited the transcriptional activity of AP-1 and NF-κB with IC50 values of 8.74 ± 0.31 and 12.08 ± 0.24 µM, respectively. DISCUSSION AND CONCLUSION: Taken together, these data suggest that comp has a significant anti-inflammatory property and warrants further studies concerning the potential of comp for medicinal use.

A new saponin from Acanthopanax koreanum with anti-inflammatory activity.

Twelve saponins were isolated from the leaves of Acanthopanax koreanum, including one new lupane-type triterpene glycoside, named acankoreoside R (1), together with 11 known triterpenoid saponins (2-12). Their structures were elucidated by 1D and 2D nuclear magnetic resonance (NMR), mass spectroscopic data (MS). All of the fractions and isolated saponins were evaluated for anti-inflammatory activities in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) by ELISA. Among them, compounds 1-5, 7, 10, and 12 showed strong inhibitions towards interleukin-12 (IL-12) production with IC50 values ranging from 1.59 to 5.46 µM. Other compounds were weak or inactive toward IL-12 p40 production.

Monoolein, isolated from Ishige sinicola, inhibits lipopolysaccharide-induced inflammatory response by attenuating mitogen-activated protein kinase and NF-κB pathways.

Ishige sinicola (I. sinicola) is an edible brown alga native to South Korea. In the present study, we screened the anti-inflammatory activity of monoolein isolated from I. sinicola. Monoolein pretreatment in lipopolysaccharide (LPS)-stimulated primary murine bone marrow-derived dendritic cells (BMDCs) showed strong dose-dependent inhibition of interleukin (IL)-12 p40, IL-6, and TNF-α cytokine production with IC50 values of 1.69±0.02, 6.87±0.37, and 5.19±0.56 µM, respectively. Pretreatment of monoolein attenuated the activation of MAPK and NF-κB pathways in the LPS-stimulated BMDCs by inhibiting the phosphorylation of p38, ERK1/2, JNK1/2, and IκBα. Furthermore, monoolein inhibited the production of NO and iNOS in RAW264.7 cells. Overall, our findings indicate that monoolein has a significant anti-inflammatory activity, and further studies regarding the potential of monoolein for medicinal use is warranted.

Anti-inflammatory Flavonoid C-Glycosides from Piper aduncum Leaves.

Four new compounds, acacetin 8-C-[ß-D-apiofuranosyl-(1 → 2)-ß-D-glucopyranoside] (1), 7-methoxyacacetin 8-C-[ß-D-apiofuranosyl-(1 → 3)-ß-D-glucopyranoside] (2), 7-methoxyacacetin 8-C-[ß-D-glucopyranosyl-(1 → 2)-ß-D-glucopyranoside] (3), and 4‴-O-acetylacacetin 8-C-[α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranoside] (4), along with ten known compounds (5-14), were isolated from Piper aduncum leaves. The effects of these compounds on lipopolysaccharide-induced expression of the proinflammatory cytokines IL-12 p40, IL-6, and TNF-α in bone marrow-derived dendritic cells were evaluated. Compounds 2, 3, 6, 8, 9, and 11-13 inhibited the production of both IL-12 p40 and IL-6, with IC50 values ranging from 0.35 ± 0.01 to 1.40 ± 0.04 µM and 1.22 ± 0.02 to 3.79 ± 0.10 µM, respectively. Compounds 5 and 10 only showed strong inhibition effects on the production of IL-12 p40, with IC50 values of 2.76 ± 0.08 and 0.39 ± 0.05 µM, respectively. However, all compounds showed weak activity or no activity on TNF-α production at the tested concentrations.

4-Hydroxy-2,3-Dimethyl-2-Nonen-4-Olide Has an Inhibitory Effect on Pro-Inflammatory Cytokine Production in CpG-Stimulated Bone Marrow-Derived Dendritic Cells.

This study was intended to assess the anti-inflammatory properties of 4-hydroxy-2,3-dimethyl-2-nonen-4-olide (Comp) isolated from Ulva pertusa Kjellman on production of pro-inflammatory cytokines. Comp revealed remarkable inhibitory effects on production of pro-inflammatory cytokines in bone marrow-derived dendritic cells (BMDCs). Comp pre-treatment in the CpG DNA-stimulated BMDCs exhibited strong inhibition of interleukin (IL)-12 p40 and IL-6 production with IC50 values ranging from 7.57 ± 0.2 to 10.83 ± 0.3, respectively. It revealed an inhibitory effect on the phosphorylation of ERK1/2, JNK1/2, and p38, and on activator protein (AP)-1 reporter activity. Comp displayed noteworthy inhibitory effects on phosphorylation and degradation of IκBα, and on NF-κB reporter activity. In summary, these data propose that Comp has substantial anti-inflammatory properties and warrants further study concerning its potential use as a therapeutic agent for inflammation-associated maladies.

Soluble DPP-4 up-regulates toll-like receptors and augments inflammatory reactions, which are ameliorated by vildagliptin or mannose-6-phosphate.

OBJECTIVE: Studies have shown that dipeptidyl peptidase-4 (DPP-4) inhibitors have anti-inflammatory effects. Soluble DPP-4 (sDPP-4) has been considered as an adipokine of which actions need to be further characterized. METHODS: We investigated the pro-inflammatory actions of sDPP-4 and the anti-inflammatory effects of DPP-4 inhibition, using vildagliptin, as an enzymatic inhibitor, and mannose-6-phosphate (M6P) as a competitive binding inhibitor. RESULTS: In lipopolysaccharide (LPS)-stimulated RAW264.7 cells, vildagliptin suppressed the increased expression of inducible nitric oxide synthase (iNOS) and phosphorylated JNK (pJNK), activation of the NF-κB pathway, and the resultant NO and proinflammatory cytokine production. Although sDPP-4 alone did not affect the protein level of iNOS or pJNK or the production of NO in RAW264.7 cells, it did amplify iNOS expression, NO responses, and proinflammatory cytokine production in LPS-stimulated RAW264 cells. As a probable mechanism, we found that sDPP-4 caused dose-dependent increases in the expression levels of toll-like receptor 4 (TLR4) and TLR2 in RAW264.7 cells, and that these alterations were inhibited by vildagliptin, M6P, or bisindolylmaleimide II, a protein kinase C inhibitor. Either vildagliptin or M6P suppressed iNOS expression and NO and cytokine production in LPS+DPP-4-co-stimulated macrophages, while combined treatment of the co-stimulated cells with both agents had increased anti-inflammatory effects compared with either treatment alone. Intravenous injection of sDPP-4 to C57BL/6J mice increased the expression of both TLRs in kidney and white adipose tissues. CONCLUSION: Our findings suggest that sDPP-4 enhances inflammatory actions via TLR pathway, while DPP-4 inhibition with either an enzymatic or binding inhibitor has anti-inflammatory effects.

Status of oxidant, antioxidantand serum enzymes in thalassaemic children receiving multiple blood transfusions.

OBJECTIVE: To determine the levels of oxidant, antioxidant and serum enzymes in thalassaemic children receiving multiple blood transfusions. METHODS: The case-control study was done from February to August 2012, and comprised thalassaemic children receiving multiple blood transfusions at Allied Hospital, Ali Zeb Foundation, and the Thalassaemia Centre in Hilal-e-Ahmar Hospital, Faisalabad, Pakistan. Healthy subjects were also screened for any related disease condition that could prejudice the results. Blood samples were analysed for the values of total oxidant status, total antioxidant capacity, serum malondialdehyde, catalase, paraoxonase, arylesterase, glutathione peroxidase and ceruloplasmin. RESULTS: There were 180 children in the study; 90(50%) cases and 90(50%) controls. Of the cases, 48(53.3%) were under-weight while the weight of 42(46.7%) was in the normal range. The values of total oxidant status and total antioxidant capacity were significantly (p<0.01) higher in thalassaemic children compared to normal values. Serum malondialdehyde and catalase levels were also considerably elevated (p<0.05), suggesting the increased activity of these enzymes. However, the concentrations of serum paraoxonase, arylesterase, glutathione peroxidase were significantly (p<0.01) lower in cases than the controls, displaying diminished activities during multiple blood transfusions in these patients. CONCLUSIONS: Multiple blood transfusions disconcert the levels of oxidants, antioxidants and serum enzymes of thalassaemic children. Oxidative damage is seen because of the increased iron overload in these patients. Hence, regular evaluation of oxidant and antioxidant status should be monitored in thalassaemic patients during initial few years of life.

Dermatological evaluation of counter irritant potential of human urine in rabbits.

OBJECTIVE: To confirm the effect of human urine in the treatment of wounds, burns and irritation. METHODS: The study was conducted at Bahauddin Zakariya University, Multan, in November 2013 and comprised 15 rabbits of either gender. Irritation was induced by clockwise frictional movement of fine sandpaper to the ear of the rabbits. The counter-irritant activity was determined by calculating the mean decrease in redness and erythema. A group of 3 rabbits each was used while experimenting with the main assay every time the concentration of irritants was increased. The ear treated with distilled water was used as a control. Sodium lauryl sulfate irritation model was also applied and the counter-irritant activity was evaluated. One-way analysis of variance followed by Bonferroni test were used for statistical analysis. RESULTS: The mean weight of the 15 rabbits was 1.5+/-SD kg. Urine (50 and 100µl) showed excellent counter-irritant activity when compared with control and standard dexamethasone. Both the doses showed counter-irritant activity, ranging between 76.84% and 95.68% in the sandpaper model, and 68.90% and 93.68% in the sodium lauryl sulfate model. CONCLUSION: Human urine countered the effect of irritation in experimental animals and can be an alternative way of countering irritation.