Assessment of herbaceous community structure for identifying metal-tolerant species at different land uses in and around Varanasi city.

Plant community structure under different land uses provides an important understanding of vegetation dynamics to safeguard future restoration programmes and balance ecosystem services. Therefore, this study was carried out to estimate the alterations in soil properties and contamination by potentially toxic metals at different land uses (industrial, brick kiln, highway, and residential areas) compared to the reference (botanical garden area) site coupled with their subsequent influence on herbaceous community structure, bioconcentration, translocation, and extraction amount of metals in different plant species. Most of the total and phytoavailable metals (Co, Cr, Cd, Cu, Ni, Pb, Mn, and Zn) were higher at the contaminated sites compared to the reference site. The number of herbaceous species was highest at the reference site and minimum at the industrial site. Dominant and tolerant species were Cyanodon dactylon, Croton bonaplandianus, Achyranthus aspera, Malvestrum coromendelianum, Dicanthium annulatum, Nicotiana hindostana, Sporobolus virginicus, and Parthenium hysterophorus, found at the industrial, brick kiln, and highway sites. Based on transfer coefficients, C. bonaplandianus, D. annulatum, and Eleusine indica were recognized as potential accumulators, whereas C. dactylon, Commelina benghalensis, A. aspera, Amaranthus sessilis, and M. coromendelianum were found as excluder species for different metals. The identified tolerant herbaceous species could be used for future phytoremediation strategies and the prevention of hazardous risks to living components of contaminated sites.

Ecological and health risk assessment of different land uses along with seasonal variation in toxic metal contamination around Varanasi city situated in Indo-Gangetic Plain.

Metal pollution load in soil environment has been enhanced during last few decades due to increasing industrialization and wide application of metals in all sectors. Due to the persistent and hazardous nature of metals, it can accumulate in the living system and cause severe risks to the ecosystem. The abundance of metals in soils from 5 different land use systems (industrial, industrial highway, brick kiln production area, residential highways and botanical gardens) in the Indo-Gangetic Plain region of India was analysed for three consecutive years (2018-2020) to evaluate the effects of metal load on soil properties and ecosystem health. Soil enzymatic activities, moisture, porosity, total nitrogen, and organic carbon were least at the industrial area of Ramnagar site and highest at Botanical garden area of BHU. Geochemical indices were calculated to compare the background status of metals in the soil where Cd, Cu, Cr, Co, Ni, Mn and Zn were increased in recent times. Contamination, enrichment and potential ecological risk factors with respect to Cu and Cd contents in soil were significantly higher at industrial area of Ramnagar and highway near industrial area. Maximum lifetime non-cancer and cancer health hazards were observed for Cd and Ni, respectively. The study clearly indicates that Cd, Cu and Ni are capable of posing health risk and cause imbalance in ecological functioning of soil due to chronic exposure of the potential toxic metals generated through change in land uses in sub-urban areas of Indo-Gangetic Plain region.

Diverse functions of long noncoding RNAs in acute myeloid leukemia: emerging roles in pathophysiology, prognosis, and treatment resistance.

PURPOSE OF REVIEW: Advancements in the next-generation sequencing technologies have identified rare transcripts of long noncoding RNAs (lncRNAs) in the genome of cancers, including in acute myeloid leukemia (AML). The purpose of this review is to highlight the contribution of lncRNAs in AML pathogenesis, prognosis, and chemoresistance. RECENT FINDINGS: Several studies have recently reported that deregulated lncRNAs are novel key players in the development of AML and are associated with AML pathophysiology and may serve as prognostic indicators. A few aberrantly expressed lncRNAs that correlated with the recurrent genetic mutations in AML such as NPM1 and RUNX1 have recently been characterized. Moreover, a few lncRNAs in MLL-rearranged leukemia have been described. Additionally, the involvement of lncRNAs in AML chemoresistance has been postulated. SUMMARY: Investigating the functional roles of the noncoding regions including lncRNAs, may provide novel insights into the pathophysiology, refine the prognostic schema, and provide novel therapeutic treatment strategies in AML.

Wilms Tumor 1 Mutations Are Independent Poor Prognostic Factors in Pediatric Acute Myeloid Leukemia.

The prognostic impact of Wilms tumor 1 (WT1) mutations remains controversial for patients with acute myeloid leukemia (AML). Here, we aimed to determine the clinical implication of WT1 mutations in a large cohort of pediatric AML. The clinical data of 870 pediatric patients with AML were downloaded from the therapeutically applicable research to generate effective treatment (TARGET) dataset. We analyzed the prevalence, clinical profile, and prognosis of AML patients with WT1 mutations in this cohort. Our results showed that 6.7% of total patients harbored WT1 mutations. These WT1 mutations were closely associated with normal cytogenetics (P<0.001), FMS-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD) mutations (P<0.001), and low complete remission induction rates (P<0.01). Compared to the patients without WT1 mutations, patients with WT1 mutations had a worse 5-year event-free survival (21.7 ± 5.5% vs 48.9 ± 1.8%, P<0.001) and a worse overall survival (41.4 ± 6.6% vs 64.3 ± 1.7%, P<0.001). Moreover, patients with both WT1 and FLT3/ITD mutations had a dismal prognosis. Compared to chemotherapy alone, hematopoietic stem cell transplantation tended to improve the prognoses of WT1-mutated patients. Multivariate analysis demonstrated that WT1 mutations conferred an independent adverse impact on event-free survival (hazard ratio 1.910, P = 0.001) and overall survival (hazard ratio 1.709, P = 0.020). In conclusion, our findings have demonstrated that WT1 mutations are independent poor prognostic factors in pediatric AML.

Identification of a novel 1,2 oxazine that can induce apoptosis by targeting NF-κB in hepatocellular carcinoma cells.

Constitutive activation of NF-κB is associated with proinflammatory diseases and suppression of the NF-κB signaling pathway has been considered as an effective therapeutic strategy in the treatment of various cancers including hepatocellular carcinoma (HCC). Herein, we report the synthesis of 1,2 oxazines and their anticancer potential. The antiproliferative studies presented 3-((4-(1H-benzo[d]imidazol-2-yl)piperidin-1-yl)methyl)-4-phenyl-4,4a,5,6,7,7a-hexahydrocyclopenta [e][1,2]oxazine(3i) as a lead cytotoxic agent against HCC cells. Flow cytometric analysis showed that 3i caused a substantial increase in the subG1 cell population. Annexin-V-FITC-PI staining showed a significant increase in the percentage of apoptotic cells on treatment with 3i. Transfection with p65 siRNA significantly reduced the 3i induced DNA fragmentation indicating that 3i may primarily mediate its proapoptotic effects by abrogating the NF-κB signaling. In addition, treatment of HCC cells with 3i decreased the DNA binding ability of NF-κB and NF-κB-dependent luciferase expression. Taken together, this report introduces 1,2-oxazine that potently targets the NF-κB signaling pathway in HCC cells.

Molecular Targets Modulated by Fangchinoline in Tumor Cells and Preclinical Models.

Despite tremendous progress made during the last few decades in the treatment options for cancer, compounds isolated from Mother Nature remain the mainstay for therapy of various malignancies. Fangchinoline, initially isolated from the dried root of Stephaniae tetrandrine, has been found to exhibit diverse pharmacological effects including significant anticancer activities both in tumor cell lines and selected preclinical models. This alkaloid appears to act by modulating the activation of various important oncogenic molecules involved in tumorigenesis leading to a significant decrease in aberrant proliferation, survival and metastasis of tumor cells. This mini-review briefly describes the potential effects of fangchinoline on important hallmarks of cancer and highlights the molecular targets modulated by this alkaloid in various tumor cell lines and preclinical models.

Atomistic simulation study of influence of Al2O3-Al interface on dislocation interaction and prismatic loop formation during nano-indentation on Al2O3-coated aluminum.

A large-scale molecular dynamics (MD) simulation of nano-indentation was carried out to provide insight into the influence of the Al-Al2O3 interface on dislocation evolution and deformation behavior of Al substrate coated with Al2O3 thin film. Adaptive common neighbor analysis (a-CNA), centro-symmetry parameter (CSP) estimation, and dislocation extraction algorithm (DXA) were implemented to represent structural evolution during nano-indentation deformation. The absence of elastic regime was observed in the P-h curve for this simulated nano-indentation test of Al2O3 thin film coated Al specimen. The displacement of oxygen atoms from Al2O3 to Al partly through the interface greatly influences the plastic deformation behavior of the specimen during nano-indentation. Prismatic dislocation loops, which are formed due to pinning of Shockley partials (1/6 < 112>) by Stair-rod (1/6 < 110>) and Hirth dislocation (1/3 < 001>), were observed in all cases studied in this work. Pile-up of atoms was also observed and the extent of the pile-up was found to vary with the test temperature. A distorted stacking fault tetrahedron (SFT) is formed when a nano-indentation test is carried out at 100 K. The presence of a prismatic dislocation loop, SFT and dislocation forest caused strain hardening and, consequently, there is an increase in hardness as indentation depth increases. Graphical abstract Figure illustrates nano-indentation model set up along with load vs. depth curve and distorted stacking fault tetrahedron.

Possible use of Punica granatum (Pomegranate) in cancer therapy.

The intake of fruits has proven to reduce the risk and incidence of cancer worldwide and plays a crucial role in cancer prevention. Pomegranate (Punica granatum), which belongs to the Punicaceae family, is one such plant that contains beneficial nutrients as well as many bioactive components and important phytochemicals that can be attributed to cancer-related therapeutic purposes. Pomegranate possesses antioxidant, anti-inflammatory, anti-proliferative, anti-angiogenic, anti-invasive, and anti-metastatic properties, and induces apoptosis. It also down-regulates various signaling pathways such as NF-κB, PI3K/AKT/mTOR, and Wnt, and down-regulates the expression of genes that are responsible in cancer development, such as anti-apoptotic genes, MMPs, VEGF, c-met, cyclins, Cdks, and pro-inflammatory cytokines. Therefore, inclusion of the fruit in one's diet would assist in a healthy life protected from cancer and also act as an effective chemotherapeutic with no toxic side effects.

Novel 1,3,4-Oxadiazole Induces Anticancer Activity by Targeting NF-κB in Hepatocellular Carcinoma Cells.

Aberrant activation of NF-κB is linked with the progression of human malignancies including hepatocellular carcinoma (HCC), and blockade of NF-κB signaling could be a potential target in the treatment of several cancers. Therefore, designing of novel small molecule inhibitors that target NF-κB activation is of prime importance in the treatment of several cancers. In the present work, we report the synthesis of series of 1,3,4-oxadiazoles, investigated their anticancer potential against HCC cells, and identified 2-(3-chlorobenzo[b]thiophen-2-yl)-5-(3-methoxyphenyl)-1,3,4-oxadiazole (CMO) as the lead compound. Further, we examined the effect of CMO on cell cycle distribution (flow cytometry), apoptosis (annexin V-propidium iodide-FITC staining), and phosphorylation of NF-κB signaling pathway proteins (IκB and p65) in HCC cells. We found that CMO induced antiproliferative effect in dose- and time-dependent manner. Also, CMO significantly increased the percentage of sub-G1 cell population and induced apoptosis. Furthermore, CMO found to decrease the phosphorylation of IκB (Ser 32) in the cytoplasmic extract and p65 (Ser 536) in the nuclear extract of HCC cells. It also abrogated the DNA binding ability and transcriptional activity of NF-κB. CMO induced the cleavage of PARP and caspase-3 in a time-dependent manner. In addition, transfection with p65 small interfering RNA blocks CMO-induced caspase-3/7 activation. Molecular docking analysis revealed that CMO interacts with the hydrophobic region of p65 protein. Thus, we are reporting CMO as an inhibitor of NF-κB signaling pathway.

The Application of Embelin for Cancer Prevention and Therapy.

Embelin is a naturally-occurring benzoquinone compound that has been shown to possess many biological properties relevant to human cancer prevention and treatment, and increasing evidence indicates that embelin may modulate various characteristic hallmarks of tumor cells. This review summarizes the information related to the various oncogenic pathways that mediate embelin-induced cell death in multiple cancer cells. The mechanisms of the action of embelin are numerous, and most of them induce apoptotic cell death that may be intrinsic or extrinsic, and modulate the NF-κB, p53, PI3K/AKT, and STAT3 signaling pathways. Embelin also induces autophagy in cancer cells; however, these autophagic cell-death mechanisms of embelin have been less reported than the apoptotic ones. Recently, several autophagy-inducing agents have been used in the treatment of different human cancers, although they require further exploration before being transferred from the bench to the clinic. Therefore, embelin could be used as a potential agent for cancer therapy.

Therapeutic potential of gambogic acid, a caged xanthone, to target cancer.

Natural compounds have enormous biological and clinical activity against dreadful diseases such as cancer, as well as cardiovascular and neurodegenerative disorders. In spite of the widespread research carried out in the field of cancer therapeutics, cancer is one of the most prevalent diseases with no perfect treatment till date. Adverse side effects and the development of chemoresistance are the imperative limiting factors associated with conventional chemotherapeutics. For this reason, there is an urgent need to find compounds that are highly safe and efficacious for the prevention and treatment of cancer. Gambogic acid (GA) is a xanthone structure extracted from the dry, brownish gamboge resin secreted from the Garcinia hanburyi tree in Southeast Asia and has inherent anti-cancer properties. In this review, the molecular mechanisms underlying the targets of GA that are liable for its effective anti-cancer activity are discussed that reveal the potential of GA as a pertinent candidate that can be appropriately developed and designed into a capable anti-cancer drug.

Molecular Targets of Ascochlorin and Its Derivatives for Cancer Therapy.

Cancer is an extremely complex disease comprising of a multitude of characteristic hallmarks that continue to evolve with time. At the genomic level, random mutations leading to deregulation of diverse oncogenic signal transduction cascades and polymorphisms coupled with environmental as well as life style-related factors are major causative agent contributing to chemoresistance and the failure of conventional therapies as well as molecular targeted agents. Hence, there is an urgent need to identify novel alternative therapies based on alternative medicines to combat this dreaded disease. Ascochlorin (ASC), an isoprenoid antibiotic isolated initially from the fermented broth of Ascochyta viciae, and its synthetic derivatives have recently demonstrated substantial antineoplastic effects in a variety of tumor cell lines and mouse models. The major focus of this review article is to briefly analyze the chemopreventive as well as therapeutic properties of ASC and its derivatives and to identify the multiple molecular targets modulated by this novel class of anticancer agent.

Butein in health and disease: A comprehensive review.

BACKGROUND: The risk of suffering from many chronic diseases seems to have made no improvement despite the advancement in medications available in the modern world. Moreover, the use of synthetic chemicals as medications has proved to worsen the scenario due to the various adverse side effects associated with them. PURPOSE: Extensive research on natural medicines provides ample evidence on the safety and efficacy of phytochemicals and nutraceuticals against diverse chronic ailments. Therefore, it is advisable to use natural products in the management of such diseases. This article aims to present a comprehensive and critical review of known pharmacological and biological effects of butein, an important chalcone polyphenol first isolated from Rhus verniciflua Stokes, implicated in the prevention and treatment of various chronic disease conditions. METHODS: An extensive literature search was conducted using PubMed, ScienceDirect, Scopus and Web of ScienceTM core collections using key words followed by evaluation of the bibliographies of relevant articles. RESULTS: Butein has been preclinically proven to be effective against several chronic diseases because it possesses a wide range of biological properties, including antioxidant, anti-inflammatory, anticancer, antidiabetic, hypotensive and neuroprotective effects. Furthermore, it has been shown to affect multiple molecular targets, including the master transcription factor nuclear factor-κB and its downstream molecules. Moreover, since it acts on multiple pathways, the chances of non-responsiveness and resistance development is reduced, supporting the use of butein as a preferred treatment option. CONCLUSION: Based on numerous preclinical studies, butein shows significant therapeutic potential against various diseases. Nevertheless, well-designed clinical studies are urgently needed to validate the preclinical findings.

The potential role of boswellic acids in cancer prevention and treatment.

Despite the extensive research carried out in the field of cancer therapeutics, cancer is one of the most dreadful diseases in the world with no definitive treatment to date. The key attributes responsible for this are the various limiting factors associated with conventional chemotherapeutics that primarily include adverse side-effects and development of chemoresistance. Hence, there is an utter need to find compounds that are highly safe and efficacious for the prevention and treatment of cancer. Boswellic acid, a group of pentacyclic compounds, seems to be promising enough due to its inherent anti-cancerous properties. Considering this perspective, the present review highlights the established studies related to the anti-cancer potential of boswellic acid against different cancer types. The molecular mechanisms underlying the targets of boswellic acid that are accountable for its potent anti-cancer effect are also discussed. Overall, this review projects the pieces of evidence that reveal the potential of boswellic acid as a suitable candidate that can be appropriately developed and designed into a promising anti-cancer drug.