Chemicals from Cimicifuga dahurica and Their Inhibitory Effects on Pro-inflammatory Cytokine Production by LPS-stimulated Bone Marrow-derived Dendritic Cells

Inflammation is a biological response caused by overactivation of the immune system and is controlled by immune cells via a variety of cytokines. The overproduction of pro-inflammatory cytokines enhances abnormal host immunity, resulting in diseases such as rheumatoid arthritis, cardiovascular disease, Alzheimer's disease, and cancer. Inhibiting the production of pro-inflammatory cytokines such as interleukin (IL)-12p40, IL-6, and tumor necrosis factor (TNF)-α might be one way to treat these conditions. Here, we investigated the anti-inflammatory activity of compounds isolated from Cimicifuga dahurica (Turcz.) Maxim., which is traditionally used as an antipyretic and analgesic in Korea. In primary cell culture assays, 12 compounds were found to inhibit the production of pro-inflammatory cytokines (IL-12p40, IL-6, and TNF-α) in vitro in bone marrow-derived dendritic cells stimulated with LPS.

NLRC3 Attenuates Colon Cancer by Down-Regulating PI3K-mTOR Signaling

The nucleotide-binding oligomerization domain-like receptors (NOD-like receptors, NLRs) are intracellular sensors. Most of them positively affect inflammatory responses, particularly the inflammasome forming NLRs. On the other hand, several studies on gene-deficient mice have revealed that several NLRs negatively influence innate immune responses. Some recent studies have identified a novel sub-group of non-inflammasome forming NLRs that negatively influence different pathways related to inflammation and carcinogenesis. Cytosolic pattern recognition receptor NRLC3 is a negative regulator of innate immune response. In this review we will discuss finding related with NLRC3 and its mechanism by which it alter cancer pathogenesis. Recently, it has been found that mice deficient in Nlrc3 are hyper-susceptible to colitis and colitis-associated colon carcinogenesis. Oncogenic inhibitory effect of NLRC3 is more dominant in epithelial compartment than hematopoietic compartment. It down regulates mTOR signaling and reduce cell proliferation. NLRC3 interact with PI3Ks and suppress activation of PI3K dependent kinase AKT. Understanding the role of NLRC3 in cancer may facilitate the recognition of new therapeutic strategies.

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.

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.

Suppression of Antimicrobial Defense and Stabilization of STAT3 by IRAK-M Expression in Tumor Cells Promotes Colorectal Carcinogenesis

Different environmental and genetic factors have been attributed to the etiology of colorectal cancer. Dysbiotic gut microbiota is associated with initiation and progression of colon carcinogenesis. Hyperactivation of STAT3 promotes carcinogenesis by upregulating cell proliferation, survival, tumor-induced immunosupression and angiogenesis. IRAK-M is a negative regulator of toll-like receptor signaling and inhibits innate immune response. The cancer cell may exploit this property of IRAK-M and evade host immune surveillance. Recently, it has been found that IRAK-M provide controlled feed back to bacteria involved in colorectal cancer by reducing antibacterial response in mice. Furthermore, IRAK-M increased the stability of STAT3 in tumor cells that support tumor promotion by upregulating cell proliferation and survival. Thus, it is suggested that IRAK-M promotes colitis associated colon cancer by enhancing bacterial colonization and stabilization of STAT3.

High-fat-diet-modulated Gut Microbiota Promotes Intestinal Carcinogenesis

Gut microbiota play a critical role in the development of intestinal cancer. Dietary changes cause dysbiosis of gut microbiota that mediates production of dietary factors triggering intestinal cancer. Genetic and dietary factors work in different combinatorial ways in initiation and progression of intestinal cancer, one of which is changes in gut microbiota. Recently, it has been found that high-fat-diet promote intestinal tumorigenesis in a genetically susceptible K-ras(G12Dint) mice without induction of obesity. High-fat-diet along with oncogene activation dampened paneth-cell mediated immunity and thus shift bacterial communities in such a way that promotes intestinal cancer.

profile of plasma concentration of adiponectin in primary school children in Dera Ismail Khan

The objective of the present study was to determine the plasma Adiponectin concentration in primary school children 6-11 years and to evaluate negative association of Adiponectin in obese children. This cross sectional study was carried out in the Department of Chemistry, Gomal University, Dera Ismail Khan from June 2007 to August 2010. A total number of 1336 primary school children were examined in the Municipality area of Dera Ismail Khan and excluding those suffering from chronic health problems. Height [m], weight [kg] of each child was taken and BMI was calculated according to Quatelet's Index. Body mass Status was also calculated through CDCs' Growth Charts 2002, 2-20years for children to have percentile for each school child. School children with >/= 5[th] percentile were declared normal weight and the ones having >/= 95[th] percentile as obese. 83 school children were randomly selected among 1336 children with 23 [27.71%] normal weight and 60 [72.28%] as obese ones. Gender wise distribution of the sample was 48 [57.83%] boys and 35 [42.16%] as girls. Fasting plasma adiponectin concentration was determined by ELIZA method. Mean plasma adiponectin concentration in normal weight children was noted as 21.38micro g/ml [P = 0.013] and 20.89micro g/ml [P = 0.011] in boys and girls respectively. The observed, mean plasma adiponectin level in obese children was 20.38micro g/ml [P =0.0130] and 25.56micro g/ml [P = 0.0016] in boys and girls respectively. Significant difference in plasma adiponectin concentration was observed between normal weight and obese girls

Efficacy of piroxicam in osteoarthritis

To evaluate the therapeutic efficacy of this most important nonsteroidal anti-inflammatory drug by using series of 60 patients with osteoarthritis. Cross sectional study. The prospecting study was undertaken from amongst patients visiting the outpatient orthopedic department of District Head Quarter Hospital Charsadda of Khyber Pakhtunkhwa [KPK] for the period of six months from 1[st] January 2011 to 30[th] June 2011. This study was conducted on a mixed population of patients presenting with symptomatic osteoarthritis, which is relatively a common disease. Studies have shown that, the age of 40, 0% of all persons developed from mild clinical symptoms to degenerative changes in their weight bearing joints. indicates a significant therapeutic efficacy as compared to placebo, both at the 2[nd] and 4[th] week of treatment, table 3 represent the comparison of Piroxicam with placebo in the reduction of mean walking pain [hip] 2[nd] and 4[th] week of treatment on the basis of four point scale. The present study revealed sustained and significant improvement in the osteoarthritis of the knee or hip joint with Piroxicam treatment resulting in marked reduction in night-pain mean walking pain, and improved objective assessment in the functions of affected joints as compared to the findings emerging out of the use of the naproxen, aspirin and placebo

possible role of selenium concentration in hepatitis B and C patients

The compelling evidence reported that selenium is an essential trace mineral for human beings. Selenium plays a pivotal role in the restoration of immune functions. High rates of hepatitis B and C are present in Pakistan. Epidemiologic surveys demonstrated an inverse association between selenium [Se] level and regional cancer incidence, as well as viral infection. The present study was designed to evaluate the concentration of selenium in the serum of patients suffering from hepatitis B and C. In this cross-sectional descriptive analytical study, serum selenium concentration of 150 patients suffering from hepatitis B and C, along with 26 healthy controls, was determined by atomic absorption spectrophotometer equipped with hydride generation system, model Analytic Jena [Vario III]. The mean and standard deviation of serum selenium concentration observed in male and female patients with hepatitis C were 101.60 +/- 0.55 and 77.43 +/- 0.47 microg/L, respectively, whereas the mean and standard deviation of serum selenium concentration observed in male and female patients with hepatitis B were 107.58 +/- 0.44 and 137.8 +/- 036 microg/L. Analysis of t test showed significant difference between C and B [P<0.001] patients in serum selenium concentration, when compared with the control. The obtained results indicate that serum selenium concentration of hepatitis B and C patients is less than serum selenium concentration of healthy individuals. However, serum selenium decline is relative to severity of disease. Based on findings of this study, it is proposed that selenium should be supplemented in such patients in order to optimize nutritional support and to get better treatment response

Factors affecting serum ferritin level in school going children of district Bannu

To investigate the factors affecting serum ferritin level in school going healthy children in Distt Bannu, Khyber Pakhtunkhwa and to know the potential risk in children associated with hypoferritinemia, leading to microcytic hypochromic anemia in our population. This cross sectional study was carried out at Institute of Kidney Diseases [IKD] Hayatabad Medical Complex Peshawar in one year time from March 2010- March 2011. A total of 113 healthy children of both genders were selected with no history of bleeding, blood transfusion, any extensive surgery or infections. 05cc blood sample was taken from each child. Out of which, 03cc were used for ferritin estimation by using the Roche Elecsys 2010 Immunoassay Analyzer, while 02cc were used for basic hematological examination, using Sysmex k-1000. There was no significant relationship between serum ferritin of boys and girls [p>0.05].However boys had high ferritin level as compared to girls. While comparing serum ferritin in rural and urban areas it has been observed that serum ferritin was high in rural areas. Moreover serum ferritin was positively correlated with hygienic conditions [p=0.01] and dietary intake [p=0.00]. The finding of our study reveals that serum ferritin level is quite low in female population in both urban and rural areas, hence anemia and low iron status are more prevalent in female population. Environmental conditions, socioeconomic factors and diet habits are the main factors, which affect ferritin level in children

Prevalence of sub clinical hypothyroidism in school children [6-11 years] of Dera Ismail Khan

To determine the prevalence of sub clinical hypothyroidism [hyperthyrotropinemia] in obese school children. This cross-sectional study was carried out in Department of Chemistry, Gomal university, Dera Ismail Khan, from June 2007 to August 2010 including eight primary schools of Dera Ismail Khan having mixed population with some of the wards belonging to high socioeconomic group. Thorough clinical examination excluded those suffering from chronic health problems. Height and weight of each child was taken according to standard anthropometric procedures. Body mass index and body mass status of each study subject was calculated according to Quetelet's Index and WHO criteria respectively. a total of 83 school children [6-11 years] were randomly selected among 1336 children. The sample included 23 [27.71%] normal weight children and 60 [72.28%] obese. Gender wise distribution of the sample was 48 [57.83%] boys and 35 [42.16%] girls. Free Thyroxin [FT] and Thyroid Stimulating Hormone [TSH] were measured using radioimmunoassay. Hyperthyrotropinemia was the most commonly observed thyroid hormone dysfunction [8.43%] in the whole sample [n=83] and 8.33% in obese children compared with 3-8% in general population of the United States. Sub clinical hypothyroidism is the most common finding in the childhood obesity. The prevalence of sub clinical hypothyroidism in the present study is 8.43% in the whole sample [n=83] compared with 3-8% in general population of the United States. It is suggested that all the obese children expressing minimum organ abnormalities be investigated to prevent the irreversible problems over the course of many years

In vitro screening of Circium arvense for potential antibacterial and antifungal activities

The antimicrobial activities of Circium arvense extracts were evaluated against two human gram positive [Staphylococcus aureus, Micrococcus luteus] and four gram negative pathogen [Escherichia coli, pseudomonas aeruginosa, Enterobacter, Klebsiella pneumoniae]. The Methanol extracts of Circium arvense were used to obtain various fractions [XI] n-hexane, [X2] chloroform, [X3] ethyl acetate and [X4] n-butanol. The agar well diffusion assay and agar dilution susceptibility testing were carried out to determine the zone of inhibitions and the minimum inhibitory concentration respectively. Antifungal activity was employed by agar well diffusion method. The Ampicilline, Ofloxacine and Itraconazole were used as standard agents. Almost all fractions exhibited more or less antimicrobial activity. The X2 [Chloroform] fraction was reported as highly active fraction with good antimicrobial activity MIC 0.312 mg/ml against Staphylococcus areous. The MBC values of fraction X2 [chloroform] was 2 times the MIC. Similarly all fractions exhibited good inhibitory activities against Aspergillus niger. The fraction Xl [n-hexane] was found highly active 6[ +/- 0.11], followed by X2 [chloform] fraction 5 [ +/- 0.17]. Present study provides a base to explore the antimicrobial potential of Circium arvense. It is concluded that the Circium arvense having potential antibacterial and antifungal activities, irrespective of fact that the MIC values reported were high. Further investigations are recommended to exploit the hidden medicinal value of plant

Waist circumference and lipid profile among primary school children

To explore the association of lipids and lipoprotein levels with large waist circumference in obese primary school children of Dera Ismaii Khan. This study explores the frequency of adverse level of waist circumference in primary school children and associated high serum concentration of lipids and lipoproteins to identify children at risk for cardiovascular disease. The study involved 86 primary school children, [Obese: 61 [70.93%], Normal weight: 25 [29.06%]]. Adverse level of waist circumference [WC] was observed in 32% normal weight and 78.69% in obese children. Gender difference for higher level of WC, was observed in obese children [boys = 42%, girls = 36 .68%]. Higher level of lipids [Triglyceride and Total Cholesterol] and lipoproteins [High Density Lipoprotein Cholesterol and Low Density Lipoprotein Cholesterol] was noted in children with higher WC [Normal weight 6 [24%], Obese 48 [80%]] compared with children having low level of WC [normal weight <61cms and obese <71cm]. The adverse level of waist circumference was observed in most of the obese children and a higher level of lipids and lipoproteins was also noted in children with adverse level of waist circumference

Iron deficiency anemia significance of serum ferritin in diagnosis in pregnant females of Pakistan

Anemia is very common especially in developing countries and in Pakistan 70-80% of pregnant population is suffering from iron deficiency anemia. Ferritin is intracellular globular iron storage protein. The low level of ferritin indicates lack of iron that may lead to anemia and its high values may indicate iron overload. To determine the incidence of anemia on the basis of ferritin in three socioeconomic groups i.e. poor, middle and upper class and in three trimesters of pregnancy. Total 45 pregnant females were selected and divided in three categories of poor, middle, and upper class based on their socioeconomic status. Serum ferritin levels were measured by ELISA method. Total mean serum ferritin [ng/ml] level were found to be 18.5 +/- 3.5, 14.6 +/- 3.0, 14.7 +/- 3.6 in first, second and third trimesters respectively. Serum ferritin was very low in all three socioeconomic groups and it was lowest in poor class as compare to middle and upper class. It was concluded that serum ferritin is a good and reliable marker for detection of iron deficiency anemia during pregnancy as compared to hemoglobin

Relationship between blood groups and male infertility

Blood is man's complete and unchangeable identity. The ABO and Rh groups are recognised as major and clinically significant blood groups. Blood group antigens are not only important in relation to blood transfusion and organ transplantation, but also have been utilised in genetic research, anthropology and tracing ancestral relation of humans. The objective the present study is to examine the blood group antigens in infertile men for assessing the relationship to male infertility and to know the frequency of various blood groups among infertile males in our population. A total of 1,521 patients along with 460 proven fathers as controls were recruited for the present study from both rural and urban areas of Pakistan and referred to Department of Reproductive Physiology/Health, Public Health Divisions, NIH, Islamabad, during 2002 to 2006. Blood grouping [ABO] and Rhesus factors [Rh] was done by the antigen antibody agglutination test. Overall distribution of blood groups in the studied population of 1,521 subjects was 35.50%, 28.27%, 26.89% and 9.34% for blood groups O, B, A and AB respectively. The ratio of control to patient was 1:3.3. The present preliminary study revealed that in our population the prevalence of male infertility in blood group O is invariably higher than in all other ABO blood groups, showing a strong relationship between blood group O and male infertility

Platelet screening tests in patients with hepatic cirrhosis

This is the largest report to investigate the importance of platelet screening tests in patients with hepatic cirrhosis. One hundred eighty seven patients were examined in this study. On an appropriate clinical historic back ground, biochemical results and biopsy - proven cirrhotic patients were investigated. An abnormal bleeding time was found in 78 patients. There were significant differences between the group of patients with an abnormal bleeding time and the group with a normal bleeding time with respect to platelet count, prothrombin time and serum bilirubin concentrations [all p < 0.05]. We recommend to measure the bleeding time in patients with raised bilirubin concentrations or poor hepatic function, even if platelet counts and prothrombin time are with in [safe limits], before making a decision about potentially dangerous therapeutic measures, such as surgery

Glucose tolerance and insulin response in myocardial infarction patients in type 2 diabetes mellitus

To investigate glucose tolerance and insulin response in myocardial infarction patients in type-2 diabetic population, normoglycemic FDRs or type-2 DM patients and MI with out DM and having no history of type-2 DM in family. Sixty five MI patients and twenty two healthy controls were selected for study. Subjects were divided in to four groups. The study was conducted for the period of 9 months in cardiology ward of various hospitals. Fasting plasma glucose levels in diabetic patients were abnormally higher as compared to other groups. Mean insulin level of FDRs and diabetic MI patients were significantly higher than controls and non diabetics. When viewed with higher fasting glucose level in groups, indicates considerable resistance. Higher insulin levels of FDRs may indicate start of insulin resistance at normoglycemic control. Finally we conclude that insulin resistance appears to be risk factors in diabetics and FDRs MI groups, while in non diabetics, non FDRs, MI patients these risk factors does not seem to play major role

Circulating leukocytes; relation with acute mental stress and coronary artery disease

Evaluating circulating leukocytes in acute mental stress and relation with coronary artery disease. Descriptive study Muhammad Medical College Mirpurkhas, from March 2007 to August 2007. Two hundred young healthy adults were studied for stress experiment. Venous blood samples were drawn before and after stress for estimation of leukocyte counts. Values were presented as mean +/- standard error of mean [SEM]. The difference in Pre and during stress results of variables were TLC =-4630.85 +/- 140.65, N% =-11.8 +/- 0.36, L% =4.03 +/- 0.14, M% =5.48 +/- 0.37, E% = 1.18 +/- 0.07, B% = 1.11 +/- 0.022. Highly significant p-values [

HBV vaccination; status in health care workers

The study was conducted to determine the HBV vaccination status in health care workers of Muhammad Medical College Mirpurkhas. This was a descriptive study carried out at Muhammad Medical College Mirpurkhas, From December 2007 to February 2008. Total 480 health care workers were included; both male and female. Vaccination status and other data were filled on preformed Questionnaire proforma, if vaccinated or not. And if vaccinated either complete or incomplete. Total 480 health care workers were studied, including 300 [62.5%] male and 180 [37.5%] females. The mean age was 34 +/- 8.7 and 36 +/- 9.3 years in vaccinated and non-vaccinated subjects respectively. A total of 255 [53.15%] were vaccinated, including 215 males and 40 females. A 225 [44.875%] patients were non-vaccinated including 85 males and 140 females. The prevaccination HBsAg status was checked and found negative in all the subjects. The frequency of vaccination was highest among house officer 55 [91.66%] and lowest in the sanitary workers 3 [11.5%]. The most common reason of not being vaccinated was non-affordability [high cost of vaccine]. We conclude that a substantial number of health care workers are not vaccinated. So it demands a need for a more aggressive approach to be vaccinated and vaccine must be cost effective