Trypanosoma cruzi (T. cruzi), the causative agent of Chagas disease, has infected 6 million people, putting 70 million people at risk worldwide. Presently, very limited drugs are available, and these have severe side effects. Hence, there is an urgency to delve into other pathways and targets for novel drugs. Trypanosoma cruzi (T. cruzi) expresses a number of different cyclic AMP (cAMP)-specific phosphodiesterases (PDEs). cAMP is one of the key regulators of mammalian cell proliferation and differentiation, and it also plays an important role in T. cruzi growth. Very few studies have demonstrated the important role of cyclic nucleotide-specific PDEs in T. cruzi’s survival. T. cruzi phosphodiesterase C (TcrPDEC) has been proposed as a potential new drug target for treating Chagas disease. In the current study, we screen several analogs of xanthine for potency against trypomastigote and amastigote growth in vitro using three different strains of T. cruzi (Tulahuen, Y and CA-1/CL72). One of the potent analogs, GVK14, has been shown to inhibit all three strains of amastigotes in host cells as well as axenic cultures. In conclusion, xanthine analogs that inhibit T. cruzi PDE may provide novel alternative therapeutic options for Chagas disease.
Claudin-4 is part of the Claudin family of transmembrane tight junction (TJ) proteins found in almost all tissues and, together with adherens junctions and desmosomes, forms epithelial and endothelial junctional complexes. Although the distribution of Claudin-4 occurs in many cell types, the level of expression is cell-specific. Claudin proteins regulate cell proliferation and differentiation by binding cell-signaling ligands, and its expression is upregulated in several cancers. As a result, alterations in Claudin expression patterns or distribution are vital in the pathology of cancer. Profiling the genetic expression of Claudin-4 showed that Claudin-4 is also a receptor for the clostridium perfringens enterotoxin (CPE) and that Claudin-4 has a high sequence similarity with CPE’s high-affinity receptor. CPE is cytolytic due to its ability to form pores in cellular membranes, and CPE treatment in breast cancer cells have shown promising results due to the high expression of Claudin-4. The C-terminal fragment of CPE (c-CPE) provides a less toxic alternative for drug delivery into breast cancer cells, particularly metastatic tumors in the brain, especially as Claudin-4 expression in the central nervous system (CNS) is low. Therefore, c-CPE provides a unique avenue for the treatment of breast–brain metastatic tumors.
Sugarcane is one of the main crops worldwide, and it has an important impact on environmental issues. Sugarcane is used in daily routine life in many ways like as vinegar, jiggery, juices etc. In India sugarcane crop is best cultivated in the west U.P. Sugarcane original vinegar drink with high nutritional quality was produced from fresh sugarcane juice using the yeast culture and acetic acid bacteria by fermentation techniques such as submerged alcoholic fermentation followed by acetic fermentation at room temperature. Refined sugarcane is the primary product of sugarcane juice, during its processing, various other valuable products are also obtained in an unrefined form such as brown sugar, molasses, jaggery and vinegar. Sugarcane juice is widely used in the treatment of jaundice, hemorrhage, dysuria, and other urinary disease. Nowadays sugarcane vinegar is also used in Indian kitchens commonly in pickles, salads, etc. Vinegar is extremely useful for human health including antimicrobial activity, blood pressure reduction, antioxidant activity, reduction in the effects of diabetes, and prevention of cardiovascular disease. Phenolic acid in vinegar can scavenge superoxide anion and free radicals in vivo resulting in a potent antioxidant activity.
Huge quantities of agricultural residues are generated every year but it is neither converted into energy nor allowed to go back to the soil and sometimes burnt that leads to air pollution and loss of soil biology and fertility. Cellulolytic microfungi secrete extracellular enzymes that degrade lignocellulosic biomass in nature and this ability of microbes may be exploited to enhance the rates of degradation of agriculture residues to recycle carbon, nitrogen and minerals in the soil. This study aimed to find out the effect(s) of co-cultivation of high cellulolytic microfungi in various combinations on rice straw under field conditions to enhance its microbial decomposition to discourage the farmers from burning it in the fields. The effectiveness of five fungal cultures in different combinations was tested for efficient degradation of rice straw. Five dominant species of fungi that have been earlier shown to secrete high amounts of cellulases in our own laboratories, were cultured on medium containing yeast powder (2g/L), jaggery (5g/L) and urea (1g/L) at room temperature. Release of reducing sugars from 1 g of rice straw treated with 10IU/mL of fungal extracellular enzymes showed that Penicillium chrysogenum released highest amount of mono and oligomers (96 mg/g) followed by Aspergillus flavus (80 mg/g) and A. oryzae (78 mg/g), A. fumigatus (72 mg/g) and Trichoderma viride (70 mg/g) within 24 h that increased with increasing temperature and increasing period of incubation. Treatment of rice straw with fungal cultures of Penicillium chrysogenum, Aspergillus flavus and A. oryzae revealed that the co-inoculation of all these species decomposed approximately 75% of the total rice straw as assessed by weight loss method. The application extracellular secretory enzymes on rice straw, though, revealed to release of reducing sugars, but the rate of reducing sugars was not sufficient enough to be used for degradation of rice straw under field conditions, hence, the used of mixed cultures of microfungi was planned and tested experimentally, which allowed the decomposition of rice straw much faster than control which were treated with heat-killed dead cultures of test microfungi. Hence, it is recommended that additional spray of mixed cultures of microfungi on rice straw may facilitate its degradation under field conditions.
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