Recent advances of benzimidazole as anticancer agents.

Cancer is the second leading cause of death globally, with 9.6 million deaths yearly. As a life-threatening disease, it necessitates the emergence of new therapies. Resistance to current chemotherapies drives scientists to develop new medications that will eventually be accessible. Because heterocycles are so common in biological substances, compounds play a big part in the variety of medications that have been developed. The "Master Key" is the benzimidazole nucleus, which consists of a six-membered benzene ring fused with a five-membered imidazole/imidazoline ring, which is an azapyrrole. One of the five-membered aromatic nitrogen heterocycles identified in American therapies that have been approved by the Food and Drug Administration (FDA). Our results show that benzimidazole's broad therapeutic spectrum is due to its structural isosteres with purine, which improves hydrogen bonding, electrostatic interactions with topoisomerase complexes, intercalation with DNA, and other functions. It also enhances protein and nucleic acid inhibition, tubulin microtubule degeneration, apoptosis, DNA fragmentation, and other functions. Additionally, readers for designing the more recent benzimidazole analogues as prospective cancer treatments.

Multi-omics assisted breeding for biotic stress resistance in soybean.

Biotic stress is a critical factor limiting soybean growth and development. Soybean responses to biotic stresses such as insects, nematodes, fungal, bacterial, and viral pathogens are governed by complex regulatory and defense mechanisms. Next-generation sequencing has availed research techniques and strategies in genomics and post-genomics. This review summarizes the available information on marker resources, quantitative trait loci, and marker-trait associations involved in regulating biotic stress responses in soybean. We discuss the differential expression of related genes and proteins reported in different transcriptomics and proteomics studies and the role of signaling pathways and metabolites reported in metabolomic studies. Recent advances in omics technologies offer opportunities to reshape and improve biotic stress resistance in soybean by altering gene regulation and/or other regulatory networks. We suggest using 'integrated omics' to precisely understand how soybean responds to different biotic stresses. We also discuss the potential challenges of integrating multi-omics for the functional analysis of genes and their regulatory networks and the development of biotic stress-resistant cultivars. This review will help direct soybean breeding programs to develop resistance against different biotic stresses.

Recent Developments in the Synthesis and Anticancer Activity of Indole and Its Derivatives.

Heterocyclic compounds are a class of compounds that is deeply intertwined with biological processes and is found in about 90% of commercially available medicines. They serve a critical function in medicinal chemistry and are focused in the field of medication development for their intensive research due to their broad variety of biological effects because of their intriguing molecular architecture, such as indoles are good candidates for drug development. It is a bicyclic structure consisting of a six-membered benzene ring fused to a five-membered pyrrole ring with several pharmacophores that yield a library of different lead compounds. Human cancer cells have been demonstrated to be inhibited by indoles in the development of new anticancer medicines. This is the first comprehensive review to focus on current methodologies for incorporating indole moiety, with their mechanistic targets as anticancer drugs, in order to shed light on the logical development of indole-based anticancer treatment options with high efficacy. This compiled data may serve as a benchmark for modifying existing ligands in order to design novel potent molecules through excellent yield synthesis techniques.

Sulphur Containing Heterocyclic Compounds as Anticancer Agents.

After cardiovascular disease, cancer is the most common cause of death worldwide. Due to their versatility, heterocyclic compounds play an important role in drug discovery. Medical remedies are constantly being discovered, especially for catastrophic disorders such as cancer. Here, this review is focused on sulphur containing heterocyclic compounds as anticancer agents. Sulphur is found in a variety of vitamin cofactors, sugars, and nucleic acids, and it also plays a function in controlling translation by sulphurating transfer RNA. Sulphur has obtained a lot of interest in the anticancer research medicinal fields. Thiophene derivatives were tested for anti-proliferative activity against breast cancer cells in a recent screening study, and the bulk of chemicals exhibited potent inhibitory effects. In recent years, azoles such as thiazole and thiadiazole structures have gained prominence in cancer research.

A Review on Modern Approaches to Benzimidazole Synthesis.

Cancer is the second most source of cessation of life globally, with 9.6 million expirations at each stage around the globe. The resistance to the current chemotherapies urges researchers to develop new drugs to be available in the market. Among the wide range of drugs synthesized, heterocyclic compounds play a major role due to the abundance of heterocyclic rings in biological substances. In medicinal chemistry, benzimidazole is an important pharmacophore and a privileged structure. This bicyclic compound is made up of the fusion of a six-membered benzene ring and a five-membered imidazole ring with two nitrogen atoms at 1,3-positions. The benzimidazole ring has a great deal of stability. Many strong acids and alkalis do not affect benzimidazoles. The benzene ring of benzimidazole cleaves only under extreme conditions. Except in certain circumstances, the benzimidazole ring is also quite resistant to reduction. It is the most popular nucleus to study because of its wide range of biological functions. The recently developed methods for preparing benzimidazoles, such as condensation of o-phenylene diamines (OPDs) with aldehydes and many others using a wide range of nano, metal-based catalysts under solventfree conditions, are discussed in detail in the current studies.

OMICS in Fodder Crops: Applications, Challenges, and Prospects.

Biomass yield and quality are the primary targets in forage crop improvement programs worldwide. Low-quality fodder reduces the quality of dairy products and affects cattle's health. In multipurpose crops, such as maize, sorghum, cowpea, alfalfa, and oat, a plethora of morphological and biochemical/nutritional quality studies have been conducted. However, the overall growth in fodder quality improvement is not on par with cereals or major food crops. The use of advanced technologies, such as multi-omics, has increased crop improvement programs manyfold. Traits such as stay-green, the number of tillers per plant, total biomass, and tolerance to biotic and/or abiotic stresses can be targeted in fodder crop improvement programs. Omic technologies, namely genomics, transcriptomics, proteomics, metabolomics, and phenomics, provide an efficient way to develop better cultivars. There is an abundance of scope for fodder quality improvement by improving the forage nutrition quality, edible quality, and digestibility. The present review includes a brief description of the established omics technologies for five major fodder crops, i.e., sorghum, cowpea, maize, oats, and alfalfa. Additionally, current improvements and future perspectives have been highlighted.

Tetrazole: A privileged scaffold for the discovery of anticancer agents.

Carcinoma, characterized by abnormal growth of cells and tissue, is a ubiquitously leading cause of mortality across the globe due to some carcinogenic factors. Currently, several anticancer agents are commercially available in the global market. However, due to their resistance and cost, researchers are gaining more interest in developing newer novel potential anticancer agents. In the search for new drugs for clinical use, the tetrazole ring system has emerged as an exciting prospect in the optimization studies of promising lead molecules. Among the various heterocyclic agents, tetrazole-containing compounds have shown significant promise in the treatment of a wide range of diseases, particularly cancer. Here, in this review, we focused on several synthetic approaches for the synthesis of tetrazole analogs, their targets for treating cancer along with the biological activity of some of the recently reported tetrazole-containing anticancer agents.

Omics for the Improvement of Abiotic, Biotic, and Agronomic Traits in Major Cereal Crops: Applications, Challenges, and Prospects.

Omics technologies, namely genomics, transcriptomics, proteomics, metabolomics, and phenomics, are becoming an integral part of virtually every commercial cereal crop breeding program, as they provide substantial dividends per unit time in both pre-breeding and breeding phases. Continuous advances in omics assure time efficiency and cost benefits to improve cereal crops. This review provides a comprehensive overview of the established omics methods in five major cereals, namely rice, sorghum, maize, barley, and bread wheat. We cover the evolution of technologies in each omics section independently and concentrate on their use to improve economically important agronomic as well as biotic and abiotic stress-related traits. Advancements in the (1) identification, mapping, and sequencing of molecular/structural variants; (2) high-density transcriptomics data to study gene expression patterns; (3) global and targeted proteome profiling to study protein structure and interaction; (4) metabolomic profiling to quantify organ-level, small-density metabolites, and their composition; and (5) high-resolution, high-throughput, image-based phenomics approaches are surveyed in this review.

Silver or gold? A comparison of nanoparticle modified electrochemical genosensors based on cobalt porphyrin-DNA.

We applied a cobalt-porphyrin modified DNA as electrochemical marker, which was attached to nanoparticles, to detect specific DNA sequences. We compare the performance of gold and silver NPs in oligonucleotide sensors to determine if a change in metal will lead to either higher sensitivity or different selectivity, based on the redox behaviour of silver vs. gold. Surprisingly, we find that using either gold or silver NPs yields very similar overall performance. The electrochemical measurements of both types of sensors show the same redox behaviour which is dominated by the cobalt porphyrin, indicating that the electron pathway does not include the NP, but there is direct electron transfer between the porphyrin and the electrode. Both sensors show a linear response in the range of 5 × 10-17-1 × 10-16 M; the limit of detection (LOD) is 3.8 × 10-18 M for the AuNP sensor, and 5.0 × 10-18 M for the AgNP sensor, respectively, which corresponds to the detection of about 20-50 DNA molecules in the analyte. Overall, the silver system results in a better DNA economy and using cheaper starting materials for the NPs, thus shows better cost-effectivness and could be more suitable for the mass-production of highly sensitive DNA sensors.

Inexpensive, Three-Dimensional, Open-Cell, Fluid-Permeable, Noble-Metal Electrodes for Electroanalysis and Electrocatalysis.

This study describes the fabrication of three-dimensional, open-cell, noble-metal (Au, Ag, and Pt) electrodes that have a complex geometry, i.e., wire mesh, metallic foam, "origami" wire mesh, and helix wire mesh. The electrodes were fabricated using an ultrasonication-assisted electroplating method that deposits a thin, continuous, and defect-free layer of noble metal (i.e., Au, Ag, or Pt) on an inexpensive copper substrate that has the desired geometry. The method is inexpensive, easy to use, and capable of fabricating noble-metal electrodes of complex geometries that cannot be fabricated using established techniques like screen printing or physical vapor deposition. By minimizing the amount of the pure noble metal in the electrodes, their cost drops significantly and could become low enough even for single-use applications; for example, the cost of metal in a Au wire-mesh electrode is $0.007/cm2 of exposed area that is about 400 times lower than that of a wire-mesh electrode composed entirely of Au. The electrodes exhibit an almost identical electrochemical performance to noble-metal electrodes of similar shape composed of bulk noble metal; therefore, these electrodes could replace two-dimensional noble-metal electrodes (e.g., rods, disks, foils) in numerous electroanalytical and electrocatalytical systems or even allow the use of noble-metal electrodes in new applications such as flow-based electrochemical systems. In this study, wire-mesh and metallic foam noble-metal electrodes have been successfully used as working electrodes for the electrocatalytical oxidation of methanol and for the electrochemical detection of redox mediators, lead ions, and nitrobenzene using various electroanalytical techniques.

Electrochemical Strategies for Adulterated Heroin Samples.

Electrochemical strategies to selectively detect heroin in street samples without the use of complicated electrode modifications were developed for the first time. For this purpose, heroin, mixing agents (adulterants, cutting agent, and impurities), and their binary mixtures were subjected to square wave voltammetry measurements at bare graphite electrodes at pH 7.0 and pH 12.0, in order to elucidate the unique electrochemical fingerprint of heroin and mixing agents as well as possible interferences or reciprocal influences. Adjusting the pH from pH 7.0 to pH 12.0 allowed a more accurate detection of heroin in the presence of most common mixing agents. Furthermore, the benefit of introducing a preconditioning step prior to running square wave voltammetry on the electrochemical fingerprint enrichment was explored. Mixtures of heroin with other drugs (cocaine, 3,4-methylenedioxymethamphetamine, and morphine) were also tested to explore the possibility of their discrimination and simultaneous detection. The feasibility of the proposed electrochemical strategies was tested on realistic heroin street samples from forensic cases, showing promising results for fast, on-site detection tools of drugs of abuse.

Determination of norfloxacin in urine and pharmaceutical samples using terbium doped zinc sulphide nanomaterials-sensitized fluorescence method.

Highly crystalline polyethylene glycol (PEG) coated Tb3+ doped ZnS nanoparticles have been synthesized and successfully used for norfloxacin sensing. The crystallographic and morphological analyses of PEG coated Tb3+ doped ZnS nanoparticles were performed by X-ray diffraction and Transmission electron microscopy, respectively. The confirmation of Tb3+ doping in ZnS host matrix was done by emission spectroscopy and energy dispersive X-ray spectroscopy. Further, the interaction of norfloxacin with PEG coated Tb3+ doped ZnS nanomaterials was confirmed by optical analysis: spectrophotometrically and spectrofluorimetrically. Norfloxacin sensing was measured by luminescence intensity which increased with increase in concentration of norfloxacin in range from 2.0 × 10-9-8.0 × 10-7 mol L-1, with its correlation coefficient 0.9991. The detection limit of proposed method was 0.05 × 10-9 mol L-1. The developed luminescence method was successfully applied for the determination of norfloxacin using PEG coated Tb3+ doped ZnS nanoparticles in urine and pharmaceutical samples.

Electrochemical Sensor Platforms Based on Nanostructured Metal Oxides, and Zeolite-Based Materials.

Electrochemical sensors have drawn significant attention over the last couple of decades because of their ability to improve detection of organic and inorganic analytes found in the field of biotechnology, environmental sciences, medicine, and food quality control. This personal account summarizes the state-of-art research carried out in the construction and evaluation of nanostructured metal oxides and zeolite based electrochemical sensors. Metal oxides and zeolite-based nanomaterials have many unique and extraordinary properties such as tunable redox activity, surface functionalization ability, optimum conductivity, large surface area, biocompatibility and so forth. In this personal account, the current advances in electrochemical sensor applications of metal oxides, zeolite-based nanomaterials, and their nanocomposites are described for the single and simultaneous determination of organic & inorganic contaminants present in water bodies, physiological bio-molecules present in human blood & urine samples, and organic contaminants present in food materials.Moreover, concluding section focuses discussion on the future developments and applications of these materials in various emerging technologies.

Approaching single DNA molecule detection with an ultrasensitive electrochemical genosensor based on gold nanoparticles and cobalt-porphyrin DNA conjugates.

We describe an ultrasensitive electrochemical genosensor based on gold nanoparticles and cobalt-porphyrin functionalised ssDNA probes. The sensitivity at the attomolar concentration level arises from an increased density of redox labels on the electrode surface compared to sensors without NP modification. The electrode detects as few as 23 DNA molecules, approaching single molecule detection.

From Point-of-Care Testing to eHealth Diagnostic Devices (eDiagnostics).

Point-of-care devices were originally designed to allow medical testing at or near the point of care by health-care professionals. Some point-of-care devices allow medical self-testing at home but cannot fully cover the growing diagnostic needs of eHealth systems that are under development in many countries. A number of easy-to-use, network-connected diagnostic devices for self-testing are needed to allow remote monitoring of patients' health. This Outlook highlights the essential characteristics of diagnostic devices for eHealth settings and indicates point-of-care technologies that may lead to the development of new devices. It also describes the most representative examples of simple-to-use, point-of-care devices that have been used for analysis of untreated biological samples.

Highly Sensitive Electrochemical Sensor for the Detection of Anions in Water Based on a Redox-Active Monolayer Incorporating an Anion Receptor.

In the present work, gold electrodes were modified using a redox-active layer based on dipyrromethene complexes with Cu(II) or Co(II) and a dipodal anion receptor functionalized with dipyrromethene. These modified gold electrodes were then applied for the electrochemical detection of anions (Cl-, SO42-, and Br-) in a highly diluted water solution (in the picomolar range). The results showed that both systems, incorporating Cu(II) as well as Co(II) redox centers, exhibited highest sensitivity toward Cl-. The selectivity sequence found for both systems was Cl- > SO42- > Br-. The high selectivity of Cl- anions can be attributed to the higher binding constant of Cl- with the anion receptor and the stronger electronic effect between the central metal and anion in the complex. The detection limit for the determination of Cl- was found at the 1.0 pM level for both sensing systems. The electrodes based on Co(II) redox centers displayed better selectivity toward Cl- anion detection than those based on Cu(II) centers which can be attributed to the stronger electronic interaction between the receptor-target anion complex and the Co(II)/Co(III) redox centers in comparison to the Cu(II)/Cu(I) system. Applicability of gold electrodes modified with DPM-Co(II)-DPM-AR for the electrochemical determination of Cl- anions was demonstrated using the artificial matrix mimicking human serum.

Cytosolic phospholipase A2 (cPLA2) IVA as a potential signature molecule in cigarette smoke condensate induced pathologies in alveolar epithelial lineages.

BACKGROUND: Smoking is one of the leading causes of millions of deaths worldwide. During cigarette smoking, most affected and highly exposed cells are the alveolar epithelium and generated oxidative stress in these cells leads to death and damage. Several studies suggested that oxidative stress causes membrane remodeling via Phospholipase A2s but in the case of cigarette smokers, mechanistically study is not yet fully defined. In view of present perspective, we evaluated the involvement of cytosolic phospholipase A2 (cPLA2) IVA as therapeutic target in cigarette smoke induced pathologies in transformed type I and type II alveolar epithelial cells. METHODS: Transformed type I (WI26) and type II (A549) alveolar epithelial cells were used for the present study. Cigarette smoke condensate (CSC) was prepared from most commonly used cigarette (Gold Flake with filter) by the Indian population. CSC-induced molecular changes were evaluated through cell viability using MTT assay, reactive oxygen species (ROS) measurement using 2,7 dichlorodihydrofluorescin diacetate (DCFH-DA), cell membrane integrity using fluorescein diacetate (FDA) and ethidium bromide (EtBr) staining, super oxide dismutase (SOD) levels, cPLA2 activity and molecular involvement of specific cPLA2s at selected 24 h time period. RESULTS: CSC-induced response on both type of epithelial cells shown significantly reduction in cell viability, declined membrane integrity, with differential escalation of ROS levels in the range of 1.5-15 folds and pointedly increased cPLA2 activity (p < 0.05). Likewise, we observed distinction antioxidant potential in these two types of lineages as type I cells had considerably higher SOD levels when compared to type II cells (p < 0.05). Further molecular expression of all cPLA2s increased significantly in a dose dependent manner, specifically cytosolic phospholipase A2 IVA with maximum manifestation of 3.8 folds. Interestingly, CSC-induced ROS levels and cPLA2s expression were relatively higher in A549 cells as compared to WI26 cells. CONCLUSIONS: The present study indicates that among all cPLA2s, specific cPLA2 IVA are the main enzymes involved in cigarette smoke induced anomalies in type I and type II lung epithelial cells and targeting them holds tremendous possibilities in cigarette smoke induced lung pathologies.

Biomineralization of hydroxyapatite in silver ion-exchanged nanocrystalline ZSM-5 zeolite using simulated body fluid.

Silver ion-exchanged nanocrystalline zeolite (Ag-Nano-ZSM-5) and silver ion-exchanged conventional zeolite (Ag-ZSM-5) were synthesized. Zeolites were incubated in simulated body fluid at 310K for different time periods to grow hydroxyapatite in their matrixes. Significant large amount of hydroxyapatite was grown in Ag-Nano-ZSM-5 matrix after incubation in simulated body fluid when compared to Ag-ZSM-5. The resultant material was characterized using X-ray diffraction, N2-adsorption, scanning/transmission electron microscopy, energy dispersive X-ray, and inductively coupled plasma analysis. Mechanical properties such as compressive modulus, compressive strength, and strain at failure of the parent materials were evaluated. Biocompatibility assays suggested that Ag-Nano-ZSM-5 and hydroxyapatite grown in Ag-Nano-ZSM-5 were compatible and did not impose any toxicity to RAW 264.7 cells macrophase and Caco2 cells suggesting considerable potential for biomedical applications such as bone implants.

Endometrial evaluation by ultrasonography, hysteroscopy and histopathology in cases of breast carcinoma on Tamoxifen therapy.

INTRODUCTION: Tamoxifen, a nonsteroidal antiestrogenic agent, is used widely as adjunctive therapy for women with breast cancer. Most studies have found that the increased relative risk of developing endometrial cancer for women taking Tamoxifen is two to three times higher than that of an age-matched population. So we designed this study to assess the endometrial status in patients taking Tamoxifen for breast carcinoma. MATERIAL AND METHODS: The study was conducted at Govt. Medical College and Rajindra Hospital, Patiala, India. A total of 50 patients of Ca Breast taking Tamoxifen were selected as per study criterion and TVS performed. If endometrial thickness was more than 5 mm hysteroscopy and endometrial HPE was done and data analysed. RESULTS: On ultrasonography 35 patients (70%) had an endometrial thickness up to 5 mm. 15 patients (30%) had an endometrial thickness more than 5mm. Out of these, 11 patients, i.e. 22% of total, had an endometrial thickness of 5.1 to 10 mm and 2 patients, i.e. 4% of total had an endometrial thickness of more than 20 mm. Hysteroscopy was done on 11 patients. Out of these 8 patients had a normal hysteroscopic appearance whereas 3 patients had an abnormal hysteroscopic picture. Endometrial HPE of these 11 patients revealed 2 patients had secretory changes, 1 had polyp change, 1 had atrophic endometrium, 3 had simple endometrial hyperplasia, 1 had endometrial adenocarcinoma and 4 patients were reported to have scanty curetting. CONCLUSION: The duration of Tamoxifen therapy turned out to have a relationship with the incidence of endometrial carcinoma (P < 0.0001). Also, a relationship was observed between the duration of Tamoxifen therapy and symptom status of the patients (P < 0.0001). This correlation did not extend to duration of Tamoxifen therapy and endometrial thickness. (P = 0.190). This correlation did not extend to duration of Tamoxifen therapy and endometrial thickness. (P = 0.190).

Isolation and immobilization of alkaline protease on mesoporous silica and mesoporous ZSM-5 zeolite materials for improved catalytic properties.

Alkaline protease from brinjal leaf (Solanum melongena) having milk clotting activity has been purified to 9.44 fold to a final specific activity of 45.71 U/mg. SDS-PAGE of the final preparation revealed a single protein band of approx 14 kDa. Purified enzyme was characterized and was successfully immobilized into the amorphous mesoporous silica (SBA-15) and crystalline mesoporous zeolite (Nano-ZSM-5) using entrapment method. Maximum immobilization of 63.5% and 79.77% was obtained with SBA-15 and Nano-ZSM-5, respectively. This protocol serves as a novel approach for bioprocesses, mainly as milk coagulant for local dairy products and particularly, cheese making, and opens the new dimension of further research and other innovation.