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•History of cisplatin motivates researcher about explanation of negative observation.•Knowledge of synthesis and purification of cisplatin are useful for medical purposes.•Knowledge ...of mechanism action and resistance may improve delivery of anticancer drugs.•Uses and side effects are useful for cancer patients to understand precautions.•Combination therapies and development strategies help to build more effective drugs.•Understanding of nanoconjugated platinum drugs help to deliver drugs more easily.
Cisplatin or (SP-4-2)-diamminedichloridoplatinum(II) is one of the most potential and widely used drugs for the treatment of various solid cancers such as testicular, ovarian, head and neck, bladder, lung, cervical cancer, melanoma, lymphomas and several others. Cisplatin exerts anticancer activity via multiple mechanisms but its most acceptable mechanism involves generation of DNA lesions by interacting with purine bases on DNA followed by activation of several signal transduction pathways which finally lead to apoptosis. However, side effects and drug resistance are the two inherent challenges of cisplatin which limit its application and effectiveness. Reduction of drug accumulation inside cancer cells, inactivation of drug by reacting with glutathione and metallothioneins and faster repairing of DNA lesions are responsible for cisplatin resistance. To minimize cisplatin side effects and resistance, combination therapies are used and have proven more effective to defect cancers. This article highlights a systematic description on cisplatin which includes a brief history, synthesis, action mechanism, resistance, uses, side effects and modulation of side effects. It also briefly describes development of platinum drugs from very small cisplatin complex to very large next generation nanocarriers conjugated platinum complexes.
Cytochrome P450 monooxygenases (P450s) represent the largest enzyme family of the plant metabolism. Plants typically devote about 1% of the protein-coding genes for the P450s to execute primary ...metabolism and also to perform species-specific specialized functions including metabolism of the triterpenes, isoprene-derived 30-carbon compounds. Triterpenes constitute a large and structurally diverse class of natural products with various industrial and pharmaceutical applications. P450-catalyzed structural modification is crucial for the diversification and functionalization of the triterpene scaffolds. In recent times, a remarkable progress has been made in understanding the function of the P450s in plant triterpene metabolism. So far, ∼80 P450s are assigned biochemical functions related to the plant triterpene metabolism. The members of the subfamilies CYP51G, CYP85A, CYP90B-D, CYP710A, CYP724B, and CYP734A are generally conserved across the plant kingdom to take part in plant primary metabolism related to the biosynthesis of essential sterols and steroid hormones. However, the members of the subfamilies CYP51H, CYP71A,D, CYP72A, CYP81Q, CYP87D, CYP88D,L, CYP93E, CYP705A, CYP708A, and CYP716A,C,E,S,U,Y are required for the metabolism of the specialized triterpenes that might perform species-specific functions including chemical defense toward specialized pathogens. Moreover, a recent advancement in high-throughput sequencing of the transcriptomes and genomes has resulted in identification of a large number of candidate P450s from diverse plant species. Assigning biochemical functions to these P450s will be of interest to extend our knowledge on triterpene metabolism in diverse plant species and also for the sustainable production of valuable phytochemicals.
Electrochemical synthesis offers a mild, simple, and efficient tool for the preparation of interesting and useful molecules, thus eluding severe chemical oxidizing and reducing agents used in ...conventional synthetic methods. In particular, electrochemical C−H activation is expected to play an important role in the direct functionalization of heterocyclic compounds. Over the past few decades, the research interest in imidazopyridine and indazole has increased significantly due to their multipurpose uses in medicinal and industrial chemistry. Therefore, structural modification of these heterocycles using electro‐oxidation has become one of the important research topics among synthetic organic chemistry in recent time. This review provides a comprehensive discussion of electrochemical functionalization of indazoles and imidazopyridines published so far. A summary of the current challenges and the future direction for the development of efficient and green electrochemical methods for functionalization of these heterocycles is also presented.
Aim of the present study is to investigate the effect of deformation temperature and cooling rate on microstructural features and mechanical properties of Nb–Ti stabilized microalloyed steel. Rolling ...schedule in 3 different phase regimes (γ-recrystallization region at Tnr+50°C, γ-nonrecrystallization region at Tnr−50°C and (α+γ) region) was designed on the basis of critical temperatures, Ar3 and Ar1 (obtained from dilatometric study, Gleeble-3800), and Tnr (determined from Boratto equation). The combination of high yield strength (YS) and ductility of the forced air-cooled (FAC) and quenched specimens rolled in (α+γ) region is attributed to the high misorientation angles of matrix, formation of subgrain ferrite (~2µm)+larger ferrite (~35µm) and precipitation of NbC (<10nm). Whereas, the good combination of YS, ductility and high impact energy of the forced air cooled samples deformed at 1050°C is endorsed to the high fraction of acicular ferrite (76%), formation of degenerate pearlite and precipitation of nanosize TiC. TEM investigation substantiated the formation of shear bands and nanosize carbide precipitates; whereas, EBSD analysis confirmed subgrain formation and misorientation angles of matrix grains.
A mild, efficient, and one-pot protocol for three-component carbosilylation of alkenes with imidazoheterocycle and silanes has been developed by merging iron(II) and visible-light photocatalysis. ...This C–C and C–Si bond-forming method provides functionalized organosilicon derivatives having imidazoheterocycles moieties in good yields. The reaction possibly proceeds through a radical pathway.
The association of colonial power with turban has not been made since the beginning of British rule in India. This link has been developed through various setbacks. The Britishers' perceptions about ...the dress of the native employees was not as same in the 1880s-90s as it was in the 1800s. As the time progressed, the body-politics related to colonizer's sartorial manners in India matured. By attaching the tag of "civilized" to own sartorial etiquette, the Britishers made their social etiquette inaccessible to the natives for power's sake. It was from this mentality that the Britishers created an English-educated class in Indian Native society, who used to consider following many indigenous customs and manners tantamount to their backwardness. Wearing a turban was among one of them. Based on the turban, the sphere of symbolic power that was constituted in colonial India until the end of the nineteenth century will be discussed in this article.
Plant often responds to fungal pathogens by expressing a group of proteins known as pathogenesis-related proteins (PRs). The expression of PR is mediated through pathogen-induced signal-transduction ...pathways that are fine-tuned by phytohormones such as methyl jasmonate (MeJA). Here, we report functional characterization of an Ocimum basilicum PR5 family member (ObTLP1) that was identified from a MeJA-responsive expression sequence tag collection. ObTLP1 encodes a 226 amino acid polypeptide that showed sequence and structural similarities with a sweet-tasting protein thaumatin of Thaumatococcus danielli and also with a stress-responsive protein osmotin of Nicotiana tabacum. The expression of ObTLP1 in O. basilicum was found to be organ-preferential under unstressed condition, and responsive to biotic and abiotic stresses, and multiple phytohormone elicitations. Bacterially-expressed recombinant ObTLP1 inhibited mycelial growth of the phytopathogenic fungi, Scleretonia sclerotiorum and Botrytis cinerea; thereby, suggesting its antifungal activity. Ectopic expression of ObTLP1 in Arabidopsis led to enhanced tolerance to S. sclerotiorum and B. cinerea infections, and also to dehydration and salt stress. Moreover, induced expression of the defense marker genes suggested up-regulation of the defense-response pathways in ObTLP1-expressing Arabidopsis upon fungal challenge. Thus, ObTLP1 might be useful for providing tolerance to the fungal pathogens and abiotic stresses in crops.
A
bstract
Compared to other neutrino sources, the huge anti-neutrino fluxes at nuclear reactor based experiments empower us to derive stronger bounds on non-standard interactions of neutrinos with ...electrons mediated by light scalar/vector mediators. At neutrino energy around 200 keV reactor anti-neutrino flux is at least an order of magnitude larger compared to the solar flux. The atomic and crystal form factors of the detector materials related to the details of the atomic structure becomes relevant at this energy scale as the momentum transfers would be small. Non-standard neutrino-electron interaction mediated by light scalar/vector mediator arises naturally in many low-scale models. We also propose one such new model with a light scalar mediator. Here, we investigate the parameter space of such low-scale models in reactor based neutrino experiments with low threshold Ge and Si detectors, and find the prospect of probing/ruling out the relevant parameter space by finding the projected sensitivity at 90% confidence level by performing a
χ
2
-analysis. We find that a detector capable of discriminating between electron recoil and nuclear recoil signal down to a very low threshold such as 5 eV placed in reactor based experiment would be able to probe a larger region in parameter space compared to the previously explored region. A Ge (Si) detector with 10 kg-yr exposure and 1 MW reactor anti-neutrino flux would be able to probe the scalar and vector mediators with masses below 1 keV for coupling products
g
ν
g
e
∼ 1
×
10
−
6
(9
.
5
×
10
−
7
) and 1
×
10
−
7
(8
×
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−
8
), respectively.
Oxidative insult, inflammation, apoptosis and autophagy play a pivotal role in the etiology of diabetic nephropathy, a global health concern. Ferulic acid, a phytochemical, is reported to protect ...against varied diseased conditions. However, the ameliorative role and mechanisms of ferulic acid in averting STZ-mediated nephrotoxicity largely remains unknown. For
study, a single intraperitoneal injection of streptozotocin (50 mg kg
body wt.) was administered in experimental rats to induce diabetes. The diabetic rats exhibited a rise in blood glucose level as well as kidney to body weight ratio, a decrease in serum insulin level, severe kidney tissue damage and dysfunction. Elevation of intracellular ROS level, altered mitochondrial membrane potential and cellular redox balance impairment shown the participation of oxidative stress in hyperglycemia-triggered renal injury. Treatment with ferulic acid (50 mg kg
body wt., orally for 8 weeks), post-diabetic induction, could markedly ameliorate kidney injury, renal cell apoptosis, inflammation and defective autophagy in the kidneys. The underlying mechanism for such protection involved the modulation of AGEs, MAPKs (p38, JNK, and ERK 1/2), NF-κB mediated inflammatory pathways, mitochondria-dependent and -independent apoptosis as well as autophagy induction. In cultured NRK-52E cells, ferulic acid (at an optimum dose of 75 μM) could counter excessive ROS generation, induce autophagy and inhibit apoptotic death of cells under high glucose environment. Blockade of autophagy could significantly eradicate the protective effect of ferulic acid in high glucose-mediated cell death. Together, the study confirmed that ferulic acid, exhibiting hypoglycemic, antioxidant, anti-inflammatory, anti-apoptotic activities and role in autophagy, could circumvent oxidative stress-mediated renal cell damage.
We consider searches for the inelastic scattering of low-mass dark matter at direct detection experiments, using the Migdal effect. We find that there are degeneracies between the dark matter mass ...and the mass splitting that are difficult to break. Using XENON1T data we set bounds on a previously unexplored region of the inelastic dark matter parameter space. For the case of exothermic scattering, we find that the Migdal effect allows xenon-based detectors to have sensitivity to dark matter with O(MeV) mass, far beyond what can be obtained with nuclear recoils alone.
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