Acrosorium polyneurum Extract Inhibits the LPS-Induced Inflammatory Response by Impairing the MAPK and NF-κB Pathways

Marine algae exhibit broad spectrum anti-bacterial and anti-inflammatory activities. Acrosorium polyneurum (A. polyneurum) is a marine red alga and belongs to the family Delesseriaceae. The present research evaluates the antiinflammatory effects of A. polyneurum extract (APE) on pro-inflammatory cytokine production. APE demonstrated substantial inhibitory effects on production of pro-inflammatory cytokine in bone marrow-derived macrophages (BMDMs). APE pre-treatment in the lipopolysaccharide (LPS)-stimulated BMDMs exhibited a robust inhibitory effect on production of interleukin (IL)-12, IL-6 and tumor necrosis factor (TNF)-α. It revealed a robust inhibitory effect on phosphorylation of ERK1/2, JNK1/2 and p38. APE also showed remarkable inhibitory effect on phosphorylation and degradation of IκBα. Furthermore, APE pre-treatment demonstrated substantial inhibition of LPS-induced production of nitric oxide and inducible nitric oxide synthase. Collectively, these data suggest that APE has a noteworthy anti-inflammatory property and deserve further studies concerning its potential use as a medicinal agent for inflammation-related disorders.

An Update on Gut Microbiota and Infant's Health

Childhood malnutrition is a global problem and one of the leading cause of stunted growth, and responsible for the death of millions of children every year. Although extensive efforts have been made to promote healthy growth but results are not satisfactory and infant's health remains a challenge. Previously, it was demonstrated that undernourished children have disrupted normal pattern of intestinal microbiota and led to a proposal that it might be involved in impaired postnatal growth. Recently, various research groups focused on Malawian population and proved the role of intestinal microbiota in the stunted growth of children. In addition, one group showed the role of sialylated bovine milk oligosaccharides in promoting microbiota-dependent growth in malnourished children. Moreover, it was also revealed that Clostridium symbiosum and Ruminococcus gnavus might be used as therapeutic agent for ameliorating growth abnormalities in malnourished children. The current article summarizes the recent advancement in identifying interventions regarding health promotion of malnourished children.

3-Hydroxy-4,7-megastigmadien-9-one, Isolated from Ulva pertusa Kjellman, Inhibits LPS-Induced Inflammatory Response by Down-Regulating Mitogen-Activated Protein Kinase and NF-κB Pathways

In the present study we evaluated the anti-inflammatory potential of 3-hydroxy-4,7-megastigmadien-9-one (Comp) isolated from Ulva pertusa Kjellman, in LPS-stimulated bone marrow-derived dendritic cells (BMDCs). Comp treatment exhibited strong dose dependent inhibition of IL-12 p40 and IL-6 cytokine production with IC₅₀ values of 7.85 ± 0.32 and 7.86 ± 0.18, respectively in LPS-stimulated BMDCs. Treatment of Comp inhibited MAPKs and NF-κB pathways in LPS-stimulated BMDCs by inhibiting the phosphorylation of ERK1/2, JNK1/2, p38 and IκB. Thus, these results suggest that Comp have a significant anti-inflammatory property and affirm further studies concerning the potentials of Comp for medicinal use.

Dermatological evaluation of counter irritant potential of human urine in rabbits

To confirm the effect of human urine in the treatment of wounds, burns and irritation. 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. The mean weight of the 15 rabbits was 1.5 +/- SD kg. Urine [50 and 100microl] 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. Human urine countered the effect of irritation in experimental animals and can be an alternative way of countering irritation

A20 Protects Against Arthritis by Regulation of the NLRP3 Inflammasome

Rheumatoid arthritis is an autoinflammatory disease that primarily affects joints and is characterized by pervasive joint inflammation. A20/Tumor necrosis factor, alpha-induced protein 3 (Tnfaip3) inhibits activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) and has been associated with rheumatoid arthritis. However, the precise role of A20 in rheumatoid arthritis remains unclear. Deletion of A20/Tnfaip3 gene in mice elicits impulsive erosive polyarthritis that is similar to rheumatoid arthritis in patients. Recently, it has been shown that A20 protects against arthritis by regulating the NLRP3 inflammasome.

Prevalence of Ascaridia galli in white leghorn layers and Fayoumi-Rhode Island red crossbred flock at government poultry farm Dina, Punjab, Pakistan

Poultry farming not only provides high nutritious food but also creates employment opportunity for rural masses. Documented evidences elaborates that helminth parasitism is most deciduous problem of chickens especially in developing world. Ascaridia (A.) galli, a nematode of small intestine, has been considered as the most common and important parasite of chicken. The present study was carried out to investigate prevalence and severity of A. galli in White Leghorn layers (housing type: battery cage and deep litter, 50 each) and Fayoumi-Rhode Island Red crossbred (male and female: 50 each) flock rearing at Government Poultry Farm, Dina, Punjab, Pakistan. Two hundred faecal samples were examined by using standard parasitological and McMaster egg counting technique. The overall prevalence was 24.5% at farm, 13% in White leghorn layer (battery cage=2%, deep litter=24%) and 36% in Fayoumi-Rhode Island Red (male=34%, female=38%). It was also observed that White leghorn layer rearing in deep litter had more severe infection (EPG=1920) of A. galli compare with battery cages birds (EPG=500). Parasite prevalence was significantly related with sex (P<0.05) in Fayoumi-Rhode Island Red and male birds had less number of average parasites (0.34±0.47) as compared to females (0.38±0.490). Additionally, female birds were under serious threat of infection (EPG=2270) compared with its counterpart (EPG=1250). Given the high infection rates, particular attention should be paid to management and provision of feed supplement to White leghorn layer housing in deep litter and female bird of Fayoumi-Rhode Island Red crossbred.

Serum ferritin level in thalassemic patients of 10-15 years and its relationship with thyroid function tests

To determine the prevalence of hypothyroidism and to evaluate any possible correlation between serum ferritin level and thyroid function tests in transfusion dependent beta-thalassemic patients. An observational and correlation study. This study was conducted at DHQ hospital, Hilal-e-Ahmar hospital and Ali Zaib Foundation hospital Faisalabad from 15[th] of May 2011 to 15[th] of Jan 2012. A total number of 90 thalassemia major patients, of 10-15 years of age, were included in this study. Serum levels of thyroxine, tri-iodothyronine, thyroid stimulating hormone were determined and correlated with serum ferritin level. Five milliliters of blood was drawn from each subject and thyroid profile [T[3], T[4] and TSH] and serum ferritin were determined. Pearson correlation coefficient test was applied to determine any correlation between serum ferritin level and other parameters. There was a weak negative correlation of Serum Ferritin with both Triiodothyronine and Thyroxine, but both correlations were statistically insignificant [p-value= 0.294 and 0.189 respectively]. Serum Ferritin had a weak positive, but insignificant correlation with TSH. Hypothyroidism was detected in 15 patients [16.67%]. Out of these 8 [8.89%] were having subclinical hypothyroidism, 5 [5.56%] mild hypothyroidism, 1 [1.11%] overt hypothyroidism and 1[1.11%] patient having secondary hypothyroidism. High prevalence of hypothyroidism warrants regular screening of thyroid functions in thalassemic patients irrespective of their serum ferritin levels

Mitogen-activated Protein Kinase Signaling in Inflammation-related Carcinogenesis

The role of mitogen-activated protein kinases (MAPKs) in regulation of inflammation is well known. MAPK family is activated by various stimuli and involved in transmitting extracellular signals to nucleus leading to gene regulation. Inflammation is primary defensive response of host against microbes. Controlled inflammation is helpful and indispensable for host defense. However, uncontrolled inflammatory response leads to various inflammatory diseases and cancer. Persistent inflammation leads to cell proliferation and survival that plays crucial role in tumorigenesis. In this review, we recapitulate the recent knowledge of MAPK signaling and its roles in inflammation-associated carcinogenesis.

Anti-inflammatory Effect of Plocamium telfairiae Extract in LPS-stimulated Bone Marrow-derived Macrophages and Dendritic Cells

Marine algae are rich sources of various biologically active compounds with potential pharmaceutical properties. In the present study, we investigated the inhibitory effects of Plocamium telfairiae extract (PTE) on proinflammatory cytokine production in bone marrow-derived macrophage (BMDMs) and dendritic cells (BMDCs). PTE pre-treatment in LPS-stimulated BMDMs and BMDCs showed a strong inhibition on interleukin (IL)-12 p40, IL-6, and tumor necrosis factor (TNF)-alpha production as compared to non-treated controls. PTE pre-treatment showed significant inhibition on phosphorylation of mitogen-activated protein kinases and degradation of inhibitor of kappa B (IkappaBalpha). Taken together, these results suggest that PTE may have potential anti-inflammatory property and hence, warrant further studies concerning the potentials of PTE for medicinal purpose.

cGAS-cGAMP Signaling and Antiviral Defense

Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that plays an important role in innate immunity. Transfection of DNA or DNA virus infection results in the induction of type I interferon production in fibroblasts, macrophages, and dendritic cells which is dependent on cGAS. Recently, cGas (-/-) mice have been reported to be more vulnerable to fatal infection with herpes simplex virus 1 (HSV1) as compared to wild-type mice.

PKR as a Regulator of Inflammasome Activation

Detection of pathogen by pattern recognition receptors leads to activation of inflammasome which plays a crucial role in immune system. The inflammasome regulates the release of cytokines, such as interleukin (IL)-1beta, IL-18 and high-mobility group box 1 (HMGB1). Double-stranded RNA-dependent protein kinase (PKR) is a critical component of an inflammatory complex. Recently, the critical role of PKR was reported in regulation of multiple inflammasomes.

NLRP6 as a Negative Regulator of Innate Immunity

Nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) play important role in immune responses by regulating nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB), type I interferon and inflammasomes. Nod-like receptor pyrin domain-containing protein 6 (NLRP6) is vital for protection of mice from colitis and colorectal tumorigenesis. However, the role of NLRP6 in microbial infection remains unclear. NLRP6 was recently reported as negative regulator of inflammatory signaling and demonstrated that how it hinders clearance of bacterial pathogens.

Bacterial 23S Ribosomal RNA, a Ligand for Toll-like Receptor 13

Toll-like receptors are required for detection of pathogen-associated molecular patterns and play critical roles in protection of host from infection. Murine TLR13 was recently reported to be involved in recognition of bacterial 23S ribosomal RNA sequence that is the binding site of different antibiotics.

Mitogen-activated Protein Kinases in Inflammation

Mitogen-activated protein kinases (MAPKs) play critical regulatory roles in the production of the pro-inflammatory cytokines and downstream signaling events which lead to inflammation. Inflammation is a primarily localized and protective response of host against microbial infection. Controlled inflammation is beneficial and necessary for host defense while uncontrolled inflammatory response results in inflammatory diseases such as septic shock, rheumatoid arthritis and cancer. The MAPK family consists of three subfamilies; the extracellular signal-regulated kinases (ERKs), the c-Jun N-terminal kinases (JNKs), and the p38 MAPKs. MAPKs are involved in transmitting extracellular signals to nucleus which leads to gene regulation. In this review, we summarize the current knowledge of ERK1/2, JNKs, and p38 MAPK members and their roles in inflammation.

Caspase-11, the Main Executioner in Non-canonical Inflammasome

Murine caspase-11 is orthologus to human caspase-4 and caspase-5, and is required for the response to cholera toxin B and infection with Escherichia coli, Citrobacter rodentium or Vibrio cholerae. Caspase-11 rather than caspase-1 is the main offender involved in sepsis. Hence, caspase-11 plays an essential pro-inflammatory role in innate immune response to bacterial infections.