Bovine Meissner-like corpuscle and evolutionary ecology of mammalian somatosensory acuity.

The mammalian snout has Meissner's corpuscles (MCs), which transmit epicritic sensations as the animal explores its surroundings. To comprehend the somatosensory acuity in mammals, we examined the structural organization and density of bovine Meissner-like corpuscles (BMLCs) at various ages and compared the changes with other mammalian MCs. The skin from the snout of cows or oxen (2-11 years old) was obtained and processed through routine histological technique. Five-µm thick sections were prepared, silver stained according to the Bielschowsky technique as modified by Winkelman and Schmidt (Mayo Clinic Proceedings, 1957, 217), and observed under a compound light microscope quantitatively and qualitatively. The glabrous skin of the cow snout consisted of two types of BMLCs: One was a cylindrical or elongated structure found in the dermal papillae. The other type was spherical and developed in the superficial layers of the epidermis. BMLCs consisted of both coarse and fine nerve fibres. In the young, the corpuscle comprised thin nerve fibres with indistinct cell outlines. In adults, nerve fibres in the corpuscles were closely packed, and networks, varicosities and end bulbs were well developed. With advancing age, the MCs attenuated into a disorganized mass of nerve fibres. The bovine snout is a highly evolved somatosensory organ due to its rich nerve supply and functionally resembles the anthropoid fingertip. Somatosensory acuity will be lower in the glabrous bovine skin than in primate glabrous skin of the fingertip, as the nerve terminals within the BMLCs are less elaborate in content and structural complexity.

Epidemiological and Molecular Characterization of Echinococcus granulosus Isolated from Small Ruminants in Kashmir Valley, India.

BACKGROUND: Cystic Echinococcosis (CE) is an emergent or re-emergent zoonosis and remains a public health and economic problem all over the world. METHODS: The present study was carried on the prevalence and genotypes of Echinococcus present in small ruminants in Kashmir valley. A total of 2100, sheep (2052) and goats (48), slaughtered or spontaneously dead, from various areas of Kashmir valley were screened for the presence of hydatidosis. In case of goat none of the cases were found positive for hydatidosis, whereas, all the positive cases (85) were recorded in sheep only. The overall prevalence of hydatidosis was 4.04%. The prevalence was higher in female sheep (5.46%) compared to males (2.83%). Season-wise highest prevalence was in summer (4.55%), followed by autumn (4.1%), spring (3.89%) and winter (2.5%).The liver was observed to be the most frequently infected organ with relative prevalence of 61.17% followed by lungs (38.82%).The rDNA-ITS1 fragment of positive samples was amplified with BD1 / 4S primers. RESULTS: The length of amplified fragment for all isolated samples was 1000bps. The products obtained on PCR were digested with four restriction enzymes (Rsa 1, Alu 1, Msp 1 and Taq1). Rsa 1, Alu 1, Msp 1 yielded identical fragments, 300 and 700 bp in sheep. TaqI restriction enzyme had no effect on PCR product and after digestion; intact 1000bps fragment was seen. CONCLUSION: Phylogenetic analysis of ITS1 gene revealed that the common sheep strain (G1) is the predominant genotype in sheep in Kashmir valley.

Transformation and evaluation of Broad-Spectrum insect and weedicide resistant genes in Gossypium arboreum (Desi Cotton).

Gossypium arboreum (Desi Cotton) holds a special place in cotton industry because of its inherent ability to withstand drought, salinity, and remarkable resistance to sucking pests and cotton leaf curl virus. However, it suffers yield losses due to weeds and bollworm infestation. Genetic modification of G. arboreum variety FBD-1 was attempted in the current study to combat insect and weedicide resistance by incorporating cry1Ac, cry2A and cp4-EPSPS genes under control of 35S promoter in two different cassettes using kanamycin and GUS as markers through Agrobacterium-mediated shoot apex cut method of cotton transformation. The efficiency of transformation was found to be 1.57%. Amplification of 1700 bp for cry1Ac, 167 bp for cry2A and 111 bp for cp4-EPSPS confirmed the presence of transgenes in cotton plants. The maximum mRNA expression of cry1Ac and cp4-EPSPS was observed in transgenic cotton line L3 while minimum in transgenic cotton line L1. The maximum protein concentrations of Cry1Ac, Cry2A and Cp4-EPSPS of 3.534 µg g-1, 2.534 µg g-1 and 3.58 µg-g-1 respectively were observed for transgenic cotton line L3 as compared to control cotton line. On leaf-feed-based insect bioassay, almost 99% mortality was observed for Helicoverpa armigera on the transgenic cotton plant (L3). It completely survived the 1900 ml hectare-1 glyphosate spray assay as compared to non-transgenic cotton plants. The necrotic spots appeared on the third day, leading to the complete death of control plants on the fifth day of assay. The successful multiple gene-stacking in G. arboreum FBD-1 variety could be further used for qualitative improvement of cotton fiber through plant breeding techniques.

Alteration of adipose tissue immune cell milieu towards the suppression of inflammation in high fat diet fed mice by flaxseed oil supplementation.

The present study evaluates the effect of flaxseed oil (FXO) supplementation on adipose tissue macrophages (ATM's), E and D series resolvin (Rv) levels and adipose tissue inflammation. Male C57BL/6J mice were divided into five groups (n = 5): lean group (given standard chow diet), HFD group given high fat diet (approx. 18 weeks) till they developed insulin resistance and 4, 8 or 16 mg/kg group (HFD group later orally supplemented with 4, 8 or 16 mg/kg body weight flaxseed oil) for 4 weeks.The present study showed that FXO supplementation led to enhanced DHA, EPA, RvE1-E2, RvD2, RvD5- D6, IL-4, IL-10 and arginase 1 levels in ATMs together with altered immune cell infiltration and reduced NF-κB expression. The FXO supplementation suppresses immune cell infiltration into adipose tissue and alters adipose tissue macrophage phenotype towards the anti-inflammatory state via enhancement of E and D series resolvins, arginase 1 expression and anti-inflammatory cytokines level (IL-4 and IL-10.) leading to amelioration of insulin resistance in flaxseed oil supplemented HFD mice.

Pigments from Soil Bacteria and Their Therapeutic Properties: A Mini Review.

Advancement in research on dyes obtained from natural sources e.g., plants, animals, insects and micro-organisms is widening the application of natural dyes in various fields. The natural dyes substituted their synthetic analogs at the beginning of twentieth century due to their improved quality, value, ease of production, ease of dyeing and some other factors. This era of dominance ended soon when toxic effects of synthetic dyes were reported. In the last few decades, pigments from micro-organisms especially soil derived bacteria is replacing dyes from other natural sources because of the increasing demand for safe, non-toxic, and biodegradable natural product. Apart from application in agriculture practices, cosmetics, textile, food and paper industries, bacterial pigments have additional biological activities e.g., anti-tumor, anti-fungal, anti-bacterial, immunosuppressive anti-viral, and many more which make them a potential candidate for pharmaceutical industry. Optimization of culture conditions and fermentation medium is the key strategies for large scale production of these natural dyes. An effort has been done to give an overview of pigments obtained from bacteria of soil origin, their dominance over dyes from other sources (natural and synthetic) and applications in the medical world in the underlying study.

Therapeutic applications of bacterial pigments: a review of current status and future opportunities.

Non-toxicity, biodegradability and non-carcinogenicity of the natural pigments, dyes and colorants make them an attractive source for human use. Bacterial pigments are colored metabolites secreted by bacteria under stress. The industrial uses of bacterial pigments have increased many folds because of several advantages over the synthetic pigments. Among natural resources, bacterial pigments are mostly preferred because of simple culturing and pigment extraction techniques, scaling up and being time economical. Generally, the bacterial pigments are safe for human use and therefore have a wide range of applications in pharmaceutical, textile, cosmetics and food industries. Therapeutic nature of the bacterial pigments is revealed because of their antimicrobial, anticancer, cytotoxic and remarkable antioxidant properties. Owing to the importance of bacterial pigments it was considered important to produce a comprehensive review of literature on the therapeutic and industrial potential of bacterial pigments. Extensive literature has been reviewed on the biomedical application of bacterial pigments while further opportunities and future challenges have been discussed.

Plant growth promoting bacteria as an alternative strategy for salt tolerance in plants: A review.

Approximately 5.2 billion hectare agriculture land are affected by erosion, salinity and soil degradation. Salinity stress has significantly affecting the fertile lands, and therefore possesses a huge impact on the agriculture and economy of a country. Salt stress has severe effects on the growth and development of plants as well as reducing its yield. Plants are inherently equipped with stress tolerance ability to responds the specific type of stress. Plants retained specific mechanisms for salt stress mitigation, such as hormonal stimulation, ion exchange, antioxidant enzymes and activation of signaling cascades on their metabolic and genetic frontiers that sooth the stressed condition. Additional to the plant inherent mechanisms, certain plant growth promoting bacteria (PGPB) also have specialized mechanism that play key role for salt stress tolerance and plant growth promotion. These bacteria triggers plants to produce different plant growth hormones like auxin, cytokinine and gibberellin as well as volatile organic compounds. These bacteria also produces growth regulators like siderophore, which fix nitrogen, solubilize organic and inorganic phosphate. Considering the importance of PGPB in compensation of salt tolerance in plants, the present study has reviewed the different aspect and mechanism of bacteria that play key role in promoting plants growth and yield. It can be concluded that PGPB can be used as a cost effective and economical tool for salinity tolerance and growth promotion in plants.

Gross and histopathological alterations associated with cystic echinococcosis in small ruminants.

Hydatidosis, an important parasitic zoonoses is a major public health as well as economic concern throughout the world. A total of 2100, sheep (2052) and goats (48), slaughtered or spontaneously dead, from various areas of Kashmir valley were screened for the presence of hydatidosis. Out of 2100 cases, 85 were positive for hydatidosis. The frequently infected organs were lungs and liver. The liver was observed to be the most frequently infected organ with relative prevalence of 61.17% followed by lungs (38.82%). The pulmonary cysts were more fertile (55%) compared to hepatic cysts (45%). Histopathologicallly, the cyst wall consisted of the inner germinal, middle lamellated/laminated, and outer fibrous layer. Inflammatory reaction around the cyst was variable and was characterized by an inner zone of loosely arranged fibroblasts infiltrated with mononuclear cells, followed by densely arranged fibroblasts along with mononuclear cells; and an outer layer of fibrous connective tissue. Fibroplasia and calcification were noted at places. In liver besides the cellular reaction against the expanding cyst, hepatocellular degeneration and cirrhosis were observed, the severity of which was inversely related to the distance from the cyst. The structural details of the protoscolices were clearly discernable.

Inhibition of Src homology 2 domain containing protein tyrosine phosphatase as the possible mechanism of metformin-assisted amelioration of obesity induced insulin resistance in high fat diet fed C57BL/6J mice.

SHP-1 (Src homology 2 domain containing protein tyrosine phosphatase) is a known negative regulator of insulin signaling and inflammation. To date, the molecular mechanism of metformin in modulating SHP-1 expression has remained elusive. In the present study, we have investigated the role of SHP-1 in relation to anti-hyperglycemic and anti-inflammatory actions of metformin in an obese phenotype mouse model. We observed that metformin treatment significantly reduced SHP-1 activity in obese mice, leading to improved insulin sensitivity. Additionally, metformin down regulated inflammatory markers like TLR2, TLR4, CD80, CD86, NF-κB, STAT1 and suppressed adipose tissue inflammation by efficiently polarizing adipose tissue macrophages toward anti-inflammatory state by way of indirect inhibition of SHP-1 mRNA and protein expressions. Our study suggests that metformin exerts its insulin sensitizing effects via inhibition of SHP-1 activity and expression.

Amelioration of obesity-associated inflammation and insulin resistance in c57bl/6 mice via macrophage polarization by fish oil supplementation.

Enormous phenotypic plasticity makes macrophages the target cells in obesity-associated inflammatory diseases. Thus, nutritional components that polarize macrophages toward antiinflammatory phenotype can partially reverse inflammatory diseases like insulin resistance. In the present study, macrophage-polarizing and insulin-sensitizing properties of fish oil (FO) were evaluated in obese insulin-resistant c57bl/6 mice fed high-fat diet (HFD-IR) after oral supplementation with FO (4, 8 or 16mg/kg body weight) and compared to lean and HFD-IR mice. FO-supplemented HFD-IR mice exhibited reduced adiposity index, serum cholesterol and triglycerides and increased insulin sensitization and showed improved adipose tissue physiology under light and transmission electron microscopy. NF-κB/P65 expression showed a downward shift on FO supplementation. The surface marker of M1 macrophages (CD-86) and the TLR-4 expression reduced with the increased supplementation of FO. Expression of arginase 1, an important marker of M2 macrophages, increased in a dose-dependent manner in response to FO dosage, which was observed at protein level by the western blotting and at mRNA level by real-time PCR. The cytokine profile of adipose tissue macrophages showed a steep shift toward antiinflammatory ones (IL-4 and IL-10) from the inflammatory TNF-α, IFN-γ, IL-2 and IL-1ß. Thus, macrophage polarization seems to be the plausible mechanism via which FO alleviates obesity-induced inflammation and insulin resistance.

Protein tyrosine phosphatase SHP-1: resurgence as new drug target for human autoimmune disorders.

Recognition of self-antigen and its destruction by the immune system is the hallmark of autoimmune diseases. During the developmental stages, immune cells are introduced to the self-antigen, for which tolerance develops. The inflammatory insults that break the immune tolerance provoke immune system against self-antigen, progressively leading to autoimmune diseases. SH2 domain containing protein tyrosine phosphatase (PTP), SHP-1, was identified as hematopoietic cell-specific PTP that regulates immune function from developing immune tolerance to mediating cell signaling post-immunoreceptor activation. The extensive research on SHP-1-deficient mice elucidated the diversified role of SHP-1 in immune regulation, and inflammatory process and related disorders such as cancer, autoimmunity, and neurodegenerative diseases. The present review focalizes upon the implication of SHP-1 in the pathogenesis of autoimmune disorders, such as allergic asthma, neutrophilic dermatosis, atopic dermatitis, rheumatoid arthritis, and multiple sclerosis, so as to lay the background in pursuance of developing therapeutic strategies targeting SHP-1. Also, new SHP-1 molecular targets have been suggested like SIRP-α, PIPKIγ, and RIP-1 that may prove to be the focal point for the development of therapeutic strategies.

Implication of protein tyrosine phosphatase SHP-1 in cancer-related signaling pathways.

The altered expression of SHP-1 (SH2 domain-containing protein tyrosine phosphatase) as a consequence of promoter hypermethylation or mutations has evidently been linked to cancer development. The notion of being a cancer drug target is conceivable as SHP-1 negatively regulates cell cycle and inflammatory pathways which are an inevitable part of oncogenic transformation. In the present review, we try to critically analyze the role of SHP-1 in cancer progression via regulating the above mentioned pathways with the major emphasis on cell cycle components and JAK/STAT pathway, commencing with the SHP-1 biology in immune cell signaling. Lastly, we have provided the future directions for researchers to encourage SHP-1 as a prognostic marker and curative target for this debilitating disease called as cancer.

Balanced TH1 and TH2 immunopotentiating effects of silicates partly containing nanoparticles present in calcined serpentine.

Calcined Serpentine (CS) is used in various formulations of alternative systems of medicine as a tonic to vital organs and as an anti-inflammatory agent. The process of calcination or incineration is believed to render non-toxic, gently absorbable, adaptable and digestible properties to the mineral compounds. The present study characterized CS and also evaluated its immunostimulatory potential. CS was characterized by using transmission electron microscopy (TEM), X-ray powder diffraction, atomic absorption spectroscopy and CHNS analysis. The characterized CS was further evaluated for its immunomodulatory potential in Swiss mice. X-Ray diffraction analysis revealed that the CS contained silicates of magnesium, calcium and iron as major minerals. Elemental composition and heavy metal analyses showed a presence of various inorganic elements/heavy metals, albeit at levels well below daily permissive intake values. TEM analysis of the test CS revealed a presence of nano particles with an average size of 10-20 nm (≈ 26% of total material). Oral administration of CS to mice at 50, 75, 100 or 200 µg/kg body weight for 10 days led to enhanced levels of total IgG, IgG1, IgG2a and IgG2b in ovalbumin-immunized mice as well as ex vivo lymphocyte proliferation and levels of TH1 (IL-2, IFNγ) and TH2 (IL-4, IL-10) cytokines produced by their cultured splenocytes. Similarly, CS treatment resulted in enhanced delayed-type hypersensitivity responses in GRBC-primed hosts. CS also activated host peritoneal macrophages, as indicated by increases in phagocytic activity and in TLR-2, CD80 and CD86 expression. The CS did not affect liver, kidney and spleen histology. Taken together, the results indicated that absorbed CS was stimulatory of host cell-mediated immune responses. It is hypothesized for now that the immunomodulatory effect of CS may have been due, in part, to a presence of nanoparticles on the CS; further study is required to validate this viewpoint.

Macrophage polarization: the link between inflammation and related diseases.

OBJECTIVE: In the present review, we try to critically evaluate the two faces of the macrophages and their roles in relation to gene alteration in some inflammatory conditions. The pros- and cons of each type of macrophage in immunologic outcomes are discussed. INTRODUCTION: If ''Diversity is the rule of nature'', macrophages have proven to be its obedient followers. A cell type that was classically considered to be activated by Interferon-c, under the influence of T(H)-1 type of response and a well-accepted warrior of cellular immunity to the intracellular pathogens is not as simple as once considered. Past decade has revolutionized this notion with the advent of T(H)-2 influenced alternatively activated macrophages, now established as wound repairing and tissue regenerating. METHODS: Literature survey was done to present a detailed study on this macrophage dichotomy and its relevance to immune disorders via expression of some critical genes, nuclear factor kappa-light-chain-enhancer of activated B cells, peroxisome proliferator-activated receptors and SH2-containing inositol-50-phosphatase 1, highly implicated in a myriad of immunological emergencies like inflammation, insulin resistance, wound healing, cancer, etc. CONCLUSION: The evaluation of macrophage dichotomy in these disorders may prove to be the first step towards the formulation of innovative therapeutic approaches.

Partial Reversal of Obesity-Induced Insulin Resistance Owing to Anti-Inflammatory Immunomodulatory Potential of Flaxseed Oil.

The present study was designed to assess the potential of supplementation of diet with Flaxseed (Linum usitatissimum, L.) oil (FXO), on obesity-related inflammation and reversal of obesity-induced insulin resistance. Swiss Albino mice, C57bl/6 mice and co-culture of 3T3-L1 adipocytes - RAW 264.7 macrophages to mimick obese adipose tissue environment were used for the study. Oral gavage of FXO at concentrations of 4, 8 or 16 mg/kg body weight (bwt) for 4 weeks or high-fat diet (HFD, 60% energy as fat) supplemented with dietary FXO (4, 8 or 16 mg/kg bwt) was given to the mice. FXO was characterised using gas chromatography - mass spectrometry. FXO supplemented HFD-fed mice (4 mg/kg bwt exhibited reduced adiposity index, serum glucose levels and triglycerides (8 and 16 mg/kg bwt) and improvement in insulin sensitisation (4, 8 and 16 mg/kg bwt) when compared with HFD mice. The co-culture showed a dose-dependent shift in cytokines towards anti-inflammatory (IL-4) state, with a decrease in pro-inflammatory TNF-α (p < 0.05). For immunomodulatory studies a dose-dependent increase (p < 0.05) was observed in antigen-specific levels of Th2 (IL-4) cytokine, serum anti-ova IgG1 and IgE levels. Suppression in anti-ova IgG2a, IgG2b, and IgG3 and antigen-specific Th1 cytokines like TNF-α and IFN-γ significantly (p < 0.05) was observed at 16 mg/kg bwt dosage. The results indicate that FXO exhibits an anti-inflammatory immunomodulatory potential and may partially relieve symptoms of obesity-associated insulin resistance.

Mineral pitch stimulates humoral, cellular and innate immune responses in mice.

CONTEXT: Mineral pitch (MP), a traditional medicine, is proposed to boost immunity in conditions that suppress Th1 cytokines such as AIDS/HIV, tuberculosis, leishmaniasis and cancer. OBJECTIVE: This study investigates the immunoregulatory mechanisms of MP in innate, humoral and cell-mediated immunity. MATERIALS AND METHODS: Mice given MP (100, 200, 300 or 400 mg/kg, orally) for 10 consecutive days were immunized intravenously with goat RBC or ovalbumin, and investigated for plaque-forming cells (PFC), hemagglutination titer, hypersensitivity response, lymphocyte proliferation and macrophage function. RESULTS: MP increased PFC (330.2 versus 182.2/106 splenocytes) in mice immunized with goat RBC and elicited ovalbumin-specific IgG titer at 400 mg/kg. Increase in Th1 immunity was correlated with the increased level of IFN-γ (724 versus 470 pg/ml) and decreased IL-4 (96 versus 178 pg/ml). CD4⁺/CD3⁺ ratio and delayed-type hypersensitivity response also increased to, respectively, 20.62 ± 0.59 (versus 16.47 ± 0.72) and 1.59 ± 0.12 (versus 0.87 ± 0.10 mm) in MP-treated mice. MP increased lymphocyte proliferation (11.14 ± 0.60 versus 5.81 ± 0.40 SI) and macrophage phagocyte response (0.24 ± 0.02 versus 0.15 ± 0.009), expressed as absorbance at 570 nm, but decreased nitrite production (17.4 ± 1.10 versus 24.3 ± 1.30 µM/106 cells). We also observed an increased bone marrow cellularity (24.5 ± 1.10 versus 17.10 ± 0.70 cells/femur) and WBC count (12 667 ± 377 versus 9178 ± 213 cells/mm³) following MP treatment. There was no sign of toxicity at 400 mg/kg, 1/12th of reported LD50. CONCLUSION: MP elicits a dose-dependent Th1 immune response.

ACE I/D Polymorphism in Hypertensive Patients of Kashmiri Population.

BACKGROUND: The angiotensin-converting enzyme (ACE) gene in humans has an insertion-deletion (I/D) polymorphic state in intron 16 on chromosome 17q23. This polymorphism has been widely investigated in different diseases. In this study we aimed to investigate the ACE I/D genotype frequency in hypertensive cases in Kashmiri population. MATERIALS AND METHODS: We designed a case control study, where 52 hypertensive cases were studied for ACE I/D polymorphism against 150 age/sex matched controls taken from general population. The polymorphisms of ACE gene were investigated using polymerase chain reaction for detection of ACE I/D genotype. Fisher's Chi square test was used for calculation of P value and OR. RESULTS: We found the frequency of ACE DD genotype to be 46.15% (24/52), II 23.07% (12/52) and DI 30.77% (16/52) in 52 hypertensive cases. CONCLUSIONS: The ACE I/D genotype is positively associated with hypertension in our population.