Aqeel Javeed

Ecotoxicological risks associated with tannery effluent wastewater.

The problem of water pollution acquires greater relevance in the context of a developing agrarian economy like Pakistan. Even though, the leather industry is a leading economic sector in Pakistan, there is an increasing environmental concern regarding tanneries because they produce large amounts of potentially toxic wastewater containing both trivalent and hexavalent chromium, which are equally hazardous for human population, aquaculture and agricultural activities in the area. Therefore, we defined the scope of the present study as to employ different bioassays to determine the eco-toxic potential of tannery effluent wastewater (TW) and its chromium based components, i.e., potassium dichromate (K(2)Cr(2)O(7)) and chromium sulfate Cr(2)(SO(4))(3). Particle-induced X-ray emission (PIXE) analysis of TW was carried out to determine the concentration of chromium in TW and then equal concentrations of hexavalent (K(2)Cr(2)O(7)) and trivalent chromium Cr(2)(SO(4))(3) were obtained for this study. Cytotoxicity assay, artemia bioassay and phytotoxicity assay was utilized to investigate the eco-toxicological potential of different concentrations of TW, K(2)Cr(2)O(7) and Cr(2)(SO(4))(3). All the dilutions of TW, K(2)Cr(2)O(7) and Cr(2)(SO(4))(3) presented concentration dependent cytotoxic effects in these assays. The data clearly represents that among all three tested materials, different dilutions of K(2)Cr(2)O(7) caused significantly more damage (P<0.001) to vero cell, brine shrimp and germination of maize seeds. Interestingly, the overall toxicity effects of TW treated groups were subsequent to K(2)Cr(2)O(7) treated group. Based on biological evidences presented in this article, it is concluded that hexavalent chromium (K(2)Cr(2)O(7)) and TW has got significant eco-damaging potential clearly elaborating that environmental burden in district Kasur is numerous and high levels of chromium is posing a considerable risk to the human population, aquaculture and agricultural industry that can obliterate ecosystem surrounding the tanneries.

Macrophage-migration inhibitory factor: role in inflammatory diseases and graft rejection

Abstract.Macrophage migration inhibitory factor (MIF) functions as a pleiotropic protein, participating in inflammatory and immune responses. MIF was originally discovered as a lymphokine involved in delayed hypersensitivity and various macrophage functions, including production of proinflammatory cytokines, glucocorticoid-induced immunomodulator, and natural killer cell inhibitory factor (NKIF), regulation of toll-like receptor expression, adherence and phagocytosis of macrophages, as well as induction of metalloproteinase. Therefore MIF is considered as a potential target protein in many pathophysiological states. In this review, considering the protein structure and the acting mechanisms of MIF, we mainly discuss the important role of MIF in pathogenesis of inflammatory diseases and graft rejection.

Non-steroidal anti-inflammatory drugs, tumour immunity and immunotherapy

Non-steroidal anti-inflammatory drugs (NSAIDs) have received considerable importance in cancer chemoprevention over the last few years. They are now being considered as prospective candidates in cancer immunotherapy because of their striking immune-enhancing impact on various effector elements of anti-tumour immunity on one hand, and to augment the efficacy of different anti-cancer immunotherapeutic strategies on the other. This review specifically discusses the role of NSAIDs in anti-tumour immunity by describing their immunomodulatory effects on different immune cells including tumour-associated macrophages (TAM), dendritic cells (DC), natural killer (NK) cells, T effector cells, and T regulatory cells (Treg). Secondly, the therapeutic perspective of NSAIDs in combination with different anti-cancer immunotherapeutic approaches, in particular the cancer vaccines, tumour-specific monoclonal antibodies, and cytokine-based therapy, has been outlined. At the end, the impact of anti-inflammatories other than NSAIDs on tumour immunity and immunotherapy, and the immunopharmacological potential of selective E-prostanoid (EP) receptor antagonists with respect to cancer immunity have also been discussed briefly.

Transforming Growth Factor–β–Induced Differentiation of Airway Smooth Muscle Cells Is Inhibited by Fibroblast Growth Factor–2

In asthma, basic fibroblast growth factor (FGF-2) plays an important (patho)physiological role. This study examines the effects of FGF-2 on the transforming growth factor-β (TGF-β)-stimulated differentiation of airway smooth muscle (ASM) cells in vitro. The differentiation of human ASM cells after incubation with TGF-β (100 pM) and/or FGF-2 (300 pM) for 48 hours was assessed by increases in contractile protein expression, actin-cytoskeleton reorganization, enhancements in cell stiffness, and collagen remodeling. FGF-2 inhibited TGF-β-stimulated increases in transgelin (SM22) and calponin gene expression (n = 15, P < 0.01) in an extracellular signal-regulated kinase 1/2 (ERK1/2) signal transduction-dependent manner. The abundance of ordered α-smooth muscle actin (α-SMA) filaments formed in the presence of TGF-β were also reduced by FGF-2, as was the ratio of F-actin to G-actin (n = 8, P < 0.01). Furthermore, FGF-2 attenuated TGF-β-stimulated increases in ASM cell stiffness and the ASM-mediated contraction of lattices, composed of collagen fibrils (n = 5, P < 0.01). However, the TGF-β-stimulated production of IL-6 was not influenced by FGF-2 (n = 4, P > 0.05), suggesting that FGF-2 antagonism is selective for the regulation of ASM cell contractile protein expression, organization, and function. Another mitogen, thrombin (0.3 U ml(-1)), exerted no effect on TGF-β-regulated contractile protein expression (n = 8, P > 0.05), α-SMA organization, or the ratio of F-actin to G-actin (n = 4, P > 0.05), suggesting that the inhibitory effect of FGF-2 is dissociated from its mitogenic actions. The addition of FGF-2, 24 hours after TGF-β treatment, still reduced contractile protein expression, even when the TGF-β-receptor kinase inhibitor, SB431542 (10 μM), was added 1 hour before FGF-2. We conclude that the ASM cell differentiation promoted by TGF-β is antagonized by FGF-2. A better understanding of the mechanism of action for FGF-2 is necessary to develop a strategy for therapeutic exploitation in the treatment of asthma.

Aspirin and immune system

The time-tested gradual exploration of aspirins diverse pharmacological properties has made it the most reliable therapeutic agent worldwide. In addition to its well-argued anti-inflammatory effects, many new and exciting data have emerged regarding the role of aspirin in cells of the immune system and certain immunopathological states. For instance, aspirin induces tolerogenic activity in dendritic cells and determines the fate of naive T cells to regulatory phenotypes, which suggests its immunoregulatory potential in relevance to immune tolerance. It also displays some intriguing traits to modulate the innate and adaptive immune responses. In this article, the immunomodulatory relation of aspirin to different immune cells, such as neutrophils, macrophages, dendritic cells (DCs), natural killer (NK) cells, and the T and B lymphocytes has been highlighted. Moreover, the clinical prospects of aspirin in terms of autoimmunity, allograft rejection and immune tolerance have also been outlined.

Artemisinins and immune system.

Artemisinins in combination with other antimalarial drugs remain the mainstay of current antimalarial armamentarium. It is interesting to note that many traditional drugs with antiprotozoal background can wield immunomodulation on the recipients immune system in a positive or negative direction. Artemisinins also attribute immunomodulatory distensions. For instance, they demonstrate predominant immunosuppressive traits toward different immune components by particularly regulating the cellular proliferation and cytokine release, which indicates that they possess some additional mechanisms and features demanding deliberate attentions. This article reviews the data-based immunomodulatory effects of artemisinins on different immune cells including neutrophils, macrophages, splenocytes, T and B cells in conjunction with their therapeutic prospective with regard to inflammation, autoimmunity and delayed-type hypersensitivity.

The brain interstitial system: Anatomy, modeling, in vivo measurement, and applications

HIGHLIGHTSAn overview of the brain interstitial space (ISS), with a comprehensive consideration of neurobiology, biophysics, therapeutics, neuroimaging, image analysis and processing technologies.Detailed discussion of a novel tracer‐based MRI method that can image brain ISF flow in deep nuclei and the recent discovery of brain ISS divisions using this method.Insights into the impacts of brain ISS knowledge on understanding brain structure, function, and mechanisms as well as improving therapeutics for brain disorders. ABSTRACT Although neurons attract the most attention in neurobiology, our current knowledge of neural circuit can only partially explain the neurological and psychiatric conditions of the brain. Thus, it is also important to consider the influence of brain interstitial system (ISS), which refers to the space among neural cells and capillaries. The ISS is the major compartment of the brain microenvironment that provides the immediate accommodation space for neural cells, and it occupies 15% to 20% of the total brain volume. The brain ISS is a dynamic and complex space connecting the vascular system and neural networks and it plays crucial roles in substance transport and signal transmission among neurons. Investigation of the brain ISS can provide new perspectives for understanding brain architecture and function and for exploring new strategies to treat brain disorders. This review discussed the anatomy of the brain ISS under both physiological and pathological conditions, biophysical modeling of the brain ISS and in vivo measurement and imaging techniques, including recent findings on brain ISS divisions. Moreover, the implications of ISS knowledge for basic neuroscience and clinical applications are addressed.

The significantly enhanced frequency of functional CD4+CD25+Foxp3+ T regulatory cells in therapeutic dose aspirin-treated mice ☆

CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells, produced in the thymus or periphery as a functionally mature T cell subpopulation, play pivotal roles in maintenance of self-tolerance and negative regulation of immune responses. Aspirin (ASA) is widely used to reduce pain, the risk of cardiovascular diseases and allo-graft rejection. However, the effect of ASA on CD4(+)CD25(+)Foxp3(+) Treg cells has yet to be determined. The frequency, phenotype and immunosuppressive function of CD4(+)CD25(+)Foxp3(+) Treg cells were detected in BALB/c mice treated with low or high doses of ASA for 4 weeks. ASA significantly decreased the percentage and number of CD4(+) T cells in the periphery, while ASA remarkably increased the percentage of CD4(+)CD25(+)Foxp3(+) Treg cells in CD4(+)T cells. The total cell numbers of thymocytes were significantly decreased in ASA-treated mice, but the number of CD4(+) CD25(+)Fxop3(+) cells and its ratio in CD4(+)CD8(-) thymocytes were markedly enhanced in the thymi of ASA-treated mice. The phenotype of CD4(+)CD25(+) Treg cells, including the expressions of CD44, CD45RB, CD62L, CD69, GITR and CTLA-4, did not show detectable changes in ASA-treated mice. CD4(+)CD25(+) Treg cells in ASA-treated mice exhibited unimpaired immunosuppressive function on CD4(+)CD25(-) T effector cells. ASA significantly enhanced the frequency of functional CD4(+)CD25(+)Foxp3(+) Treg cells in mice in a therapeutic dose range. The different effects of ASA on CD4(+)CD25(+)Foxp3(+) Treg cells and CD4(+)CD25(-) T cells may potentially make hosts susceptible to tolerance induction which would be beneficial for tolerance induction in patients with autoimmune diseases or allo-grafts. This study may have potential impacts in the clinical application of ASA.

Prevalence of Neospora caninum Antibodies in Sheep and Goats in Pakistan

abstract:  The purpose of the present study was to obtain seroepidemiological information on the Neospora caninum infection status of sheep and goats in different areas of Punjab Province and Azad Kashmir (Pakistan). A cross-sectional study, with the use of a competitive ELISA, showed an overall 27.7% (35 of 128) (95% confidence interval [CI] ± 7.7%) and 8.6% (13 of 142) (95% CI ± 4.6%) seroprevalence of N. caninum antibodies in sheep and goats, respectively. The difference in seroprevalence between sheep and goat populations was statistically significant (P < 0.05). The highest prevalence (37.4% ± 13.2%) was recorded in the tailless breed of sheep.

Characterization of tannery effluent wastewater by proton-induced X-ray emission (PIXE) analysis to investigate their role in water pollution.

IntroductionOver the last few decades, the chromium-based tanning industry has shown rapid growth in Pakistan. However, the rules and regulations promulgated by the government are not strictly followed for processing the effluent discharge from the tanneries. Consequently, tannery effluents have become a great source of water pollution in surrounding areas.Materials and methodsIn this case study, characterization of tannery effluent wastewater (TW), shallow groundwater (SW), and deep groundwater (DW) samples was carried out to determine the source of water pollution in the district of Kasur, Pakistan.ResultsThe concentrations of calcium (Ca), chlorine (Cl), chromium (Cr), iron (Fe), potassium (K), Mg, sulfur (S), silicon (Si), and Sr in TW were significantly higher than SW and DW, which also exceeded the international limits. In addition, increased concentrations of major toxic elements (Cl, Cr, Fe, K, Ni, and Si) were also observed in SW, which were higher in comparison to DW. Strikingly, the concentrations of Cr and Si in various DW samples were also beyond World Health Organization (WHO) safe limit, which reinforced the trend that water pollution in the area is directly linked to the distance from the source (TW). The particle-induced X-ray emission (PIXE) indices also suggested that TW is a main contributory source of water-based pollution in the area, which is imposing great threat to local inhabitants due to known hazardous and carcinogenic potential of these elements.ConclusionProtecting the water resources will be a formidable challenge in the study area, which requires modernization of tannery industry, thereby improving the recovery and recycling of TW. Moreover, PIXE analysis presented here as a successful tool, could serve as landmark for the contemporary research in environmental toxicology.