Plant-based natural products in cancer therapeutics.

Various cells in our body regularly divide to replace old cells and dead cells. For a living cell to be growing, cell division and differentiation is highly essential. Cancer is characterised by uncontrollable cell division and invasion of other tissues due to dysregulation in the cell cycle. An accumulation of genetic changes or mutations develops through different physical (UV and other radiations), chemical (chewing and smoking of tobacco, chemical pollutants/mutagens), biological (viruses) and hereditary factors that can lead to cancer. Now, cancer is considered as a major death-causing factor worldwide. Due to advancements in technology, treatment like chemotherapy, radiation therapy, bone marrow transplant, immunotherapy, hormone therapy and many more in the rows. Although, it also has some side effects like fatigue, hair fall, anaemia, nausea and vomiting, constipation. Modern improved drug therapies come with severe side effects. There is need for safer, more effective, low-cost treatment with lesser side-effects. Biologically active natural products derived from plants are the emerging strategy to deal with cancer proliferation. Moreover, they possess anti-carcinogenic, anti-proliferative and anti-mutagenic properties with reduced side effects. They also detoxify and remove reactive substances formed by carcinogenic agents. In this article, we discuss different plant-based products and their mechanism of action against cancer.

CuAs2O4: Design, Hydrothermal Synthesis, Crystal Structure, Photocatalytic Dye Degradation, Hydrogen Evolution Reaction, Knoevenagel Condensation Reaction, and Thermal Studies.

CuAs2O4 has been explored as a heterogeneous catalyst in the fields of photocatalysis, electrocatalysis, and solvent-free organic transformation reactions. The homogeneity has been successfully attained for the first time by designing a pH-assisted hydrothermal synthesis technique. Single-crystal X-ray diffraction studies reveal that no phase transition has been observed by lowering the temperature up to 103 K with no existence of satellite reflections. The crystal structure exhibits tetragonal symmetry with space group P42/mbc and consists of [CuO6] octahedra and [AsO3E] tetrahedra (E represents the stereochemically active lone pair). Structural investigation shows a cylindrical void inside the structure, which could lead to interesting physical and chemical properties. The photocatalytic dye degradation efficiency with methylene blue (MB) showed ∼100% degradation, though the degradation efficiency increased by 2-fold with the addition of 6% H2O2. The reusability of the catalyst up to the 10th cycle with ∼35% MB dye degradation has been established. It can exhibit HER activity with a low overpotential of 165 mV with respect to RHE to attain the current density of j = 10 mA cm-2. SEM and TEM revealed rod-shaped particles, which supported the large number of catalytic active sites. The structural consistency of the catalyst after photodegradation and HER studies is confirmed by the PXRD pattern. XPS confirms the oxidation state of Cu and As in the compound. The catalytic activity toward the Knoevenagel condensation reaction at moderate temperature under solvent-free condition is also studied. TG-DTA shows an endothermic minimum (Tmin) at 436 °C due to the mass loss of As2O3.

Topological reorganization and functional alteration of distinct genomic components in gallbladder cancer.

Altered three-dimensional architecture of chromatin influences various genomic regulators and subsequent gene expression in human cancer. However, knowledge of the topological rearrangement of genomic hierarchical layers in cancer is largely limited. Here, by taking advantage of in situ Hi-C, RNA-sequencing, and chromatin immunoprecipitation sequencing (ChIP-seq), we investigated structural reorganization and functional changes in chromosomal compartments, topologically associated domains (TADs), and CCCTC binding factor (CTCF)-mediated loops in gallbladder cancer (GBC) tissues and cell lines. We observed that the chromosomal compartment A/B switch was correlated with CTCF binding levels and gene expression changes. Increased inter-TAD interactions with weaker TAD boundaries were identified in cancer cell lines relative to normal controls. Furthermore, the chromatin short loops and cancer unique loops associated with chromatin remodeling and epithelial-mesenchymal transition activation were enriched in cancer compared with their control counterparts. Cancer-specific enhancer-promoter loops, which contain multiple transcription factor binding motifs, acted as a central element to regulate aberrant gene expression. Depletion of individual enhancers in each loop anchor that connects with promoters led to the inhibition of their corresponding gene expressions. Collectively, our data offer the landscape of hierarchical layers of cancer genome and functional alterations that contribute to the development of GBC.

Oligonucleotide nanoassemblies with allyl bromide scaffold-based small molecules.

The development of oligonucleotide nanoassemblies with small molecules has shown great potential in bio-medical applications. However, the interaction of negatively charged oligonucleotides with halogenated small molecules represents a scientific challenge. Here, we introduced a distinct allyl bromide halogenated scaffold, which exhibits specific interaction with adenine nucleic bases of the oligonucleotides, thus leading to the formation of self-assembled nanostructures.

Zn3Sb4O6F6 and KI-Doped Zn3Sb4O6F6: A Metal Oxyfluoride System for Photocatalytic Activity, Knoevenagel Condensation, and Bacterial Disinfection.

Zn3Sb4O6F6 crystallites were synthesized by a pH-regulated hydrothermal synthetic approach, while doping on Zn3Sb4O6F6 by KI was performed by the "incipient wetness impregnation technique." The effect of KI in Zn3Sb4O6F6 is found with the changes in morphology in the doped compound, i.e., needle-shaped particles with respect to the irregular cuboid and granular shaped in the pure compound. Closer inspection of the powder diffraction pattern of doped compounds also reveals the shifting of Braggs' peaks toward a lower angle and the difference in cell parameters compared to the pure compound. Both metal oxyfluoride comprising lone pair elements and their doped compounds have been successfully applied as photocatalysts for methylene blue dye degradation. Knoevenagel condensation reactions were performed using Zn3Sb4O6F6 as the catalyst and confirmed 99% yield even at 60 °C temperature under solvent-free conditions. Both pure and KI-doped compounds were tested against several standard bacterial strains, i.e., Enterobacter sp., Escherichia coli, Staphylococcus sp., Salmonella sp., Bacillus sp., Proteous sp., Pseudomonas sp., and Klebsiella sp. by the "disk diffusion method" and their antimicrobial activities were confirmed.

An Overview of Epigenetic Methylation in Pancreatic Cancer Progression.

Over the past decades, the aberrant epigenetic modification, apart from genetic alteration, has emerged as dispensable events mediating the transformation of pancreatic cancer (PC). However, the understanding of molecular mechanisms of methylation modifications, the most abundant epigenetic modifications, remains superficial. In this review, we focused on the mechanistic insights of DNA, histone, and RNA methylation that regulate the progression of PC. The methylation regulators including writer, eraser and reader participate in the modification of gene expression associated with cell proliferation, invasion and apoptosis. Some of recent clinical trials on methylation drug targeting were also discussed. Understanding the novel regulatory mechanisms in the methylation modification may offer alternative opportunities to improve therapeutic efficacy to fight against this dismal disease.

Molecular Engineering of Aptamer Self-Assemblies Increases in Vivo Stability and Targeted Recognition.

Functionally modified aptamer conjugates are promising tools for targeted imaging or treatment of various diseases. However, broad applications of aptamer molecules are limited by their in vivo instability. To overcome this challenge, current strategies mostly rely on covalent chemical modification of aptamers, a complicated process that requires case-by-case sequence design, multiple-step synthesis, and purification. Herein, we report a covalent modification-free strategy to enhance the in vivo stability of aptamers. This strategy simply utilizes one-step molecular engineering of aptamers with gold nanoclusters (GNCs) to form GNCs@aptamer self-assemblies. Using Sgc8 as a representative aptamer, the resulting GNCs@Sgc8 assemblies enhance cancer-cell-specific binding and sequential internalization by a receptor-mediated endocytosis pathway. Importantly, the GNCs@aptamer self-assemblies resist nuclease degradation for as long as 48 h, compared to the degradation of aptamer alone at 3 h. In parallel, the tumor-targeted recognition and retention of GNCs@aptamer self-assemblies are dramatically enhanced, indicated by a 9-fold signal increase inside the tumor compared to the aptamer alone. This strategy is to avoid complicated chemical modification of aptamers and can be extended to all aptamers. Our work provides a simple, effective, and universal strategy for enhancing the in vivo stability of any aptamer or its conjugates, thus expanding their imaging and therapeutic applications.

Assessment of Likelihood Ratio for Four Contact Dermatitis Symptoms of Vinca Minor.

BACKGROUND: Contact dermatitis (CD) is a frequently occurring medical condition, for which Vinca minor (VM) is one of the recommended homeopathic medicines. However, the symptoms indicating this medicine have not yet been assessed systematically. Likelihood ratio (LR), based on Bayesian statistics, may yield better estimation of a medicine's indication than the existing method of entry of symptoms into materia medica and repertories. METHODS: We investigated LRs of four CD symptoms of VM: (1) great sensitiveness of skin, with redness and soreness from slightest rubbing; (2) weeping eczema with foul, thick crusts; (3) itching amelioration in open air; and (4) CD of scalp. An observational, prospective, patient-outcome study was conducted in five different practice settings on 390 CD patients over 18 months using three outcomes-Glasgow Homeopathic Hospital Outcome Scale (GHHOS), Scoring Atopic Dermatitis (SCORAD), and Dermatology Life Quality Index (DLQI), assessed at baseline, after 3 and 6 months. The LR of each of the four symptoms was estimated as per the patient-rated outcomes on GHHOS. RESULTS: Seventy-four VM and 316 non-VM cases were analyzed. Estimated LRs were as follows: symptom 1, 1.29 (95% confidence interval [CI]: 0.65 to 2.60); symptom 2, 1.48 (95% CI: 0.80 to 2.74); symptom 3, 1.70 (95% CI: 0.94 to 3.07); symptom 4, 1.36 (95% CI: 0.74 to 2.51). There were statistically significant reductions in SCORAD and DLQI scores over 3 and 6 months. CONCLUSION: There was insufficient evidence to attribute any of the four assessed symptoms clearly to VM. Though non-significant, a high LR was observed for "itching amelioration in open air" (symptom 3). Symptoms in the homeopathic materia medica for VM are perhaps over-represented. More research of this nature is warranted.