Ethnomedicinal values of L. as a panacea against multiple human ailments: a state of art review.

Therapeutic botanicals (plants and derivatives) are in use since antiquity for various health ailments. The ethnic community is the repository of the information, the multifactorial therapeutic applications of which may often need scientific validation. The spreading hogweed or L.

Computational Approach to Combat COVID-19 Infection: Emerging Tools for Accelerating Drug Research.

Background: The process of drug discovery and development is expensive, complex, timeconsuming, and risky. There are different techniques involved in the process of drug development, including random screening, computational approaches, molecular manipulation, and serendipitous research. Among these methods, the computational approach is considered an efficient strategy to accelerate and economize the drug discovery process.

Natural therapeutics for urinary tract infections-a review.

Background: The recurrence of the urinary tract infections (UTI), following the antibiotic treatments suggests the pathogen's resistance to conventional antibiotics. This calls for the exploration of an alternative therapy.

Main Body: The anti-uropathogenic and bactericidal activity of many plant extracts was reported by many researchers, which involves only preliminary antibacterial studies using different basic techniques like disk diffusion, agar well diffusion, or minimum inhibitory concentration (MIC) of the crude plant extracts, but reports on the specific action of the phytoconstituents against uropathogens are limited.

Nanoquinacrine sensitizes 5-FU-resistant cervical cancer stem-like cells by down-regulating Nectin-4 via ADAM-17 mediated NOTCH deregulation.

Purpose: Cervical cancer is a major cause of cancer-related death in women world-wide. Although the anti-metabolite 5-FU is widely used for its treatment, its clinical utility is limited due to the frequent occurrence of drug resistance during metastasis. Cancer stem-like cells (CSCs), present in the heterogeneous population of CC cells, are thought to contribute to this resistance.

The soluble nectin-4 ecto-domain promotes breast cancer induced angiogenesis via endothelial Integrin-β4.

Cancer stem cells secrete diffusible factors into the microenvironment that bind to specific endothelial cell receptors and initiate an angiogenesis cascade. Tumor-induced angiogenesis is an important parameter of tumorigenesis and is critical for tumor growth and metastasis. A pvrl-4 encoded gene, NECTIN-4, has potential roles in cancer cell growth and aggressiveness, and it is only expressed in cancer cells.

Metallic gold and bioactive quinacrine hybrid nanoparticles inhibit oral cancer stem cell and angiogenesis by deregulating inflammatory cytokines in p53 dependent manner.

Complete eradication of aggressive oral cancer remains a challenge due to the presence of CSCs. They resist conventional chemotherapeutic agents due to their self-renewal, drug efflux, and efficient DNA repair capacity. Here, we formulated a hybrid-nanoparticle (QAuNP) using quinacrine and gold and characterized/investigated its anti-angiogenic and anti-metastatic effect on OSCC-CSCs.

Enzyme-linked immunosorbent assay for group A Streptococcal anti-DNase B in human sera, using recombinant proteins - Comparison to the DNA methyl green micromethod.

Among the four known Streptococcal nucleases comprising of DNase A, B, C and D; DNase B is the most common, and determination of the levels of antibody to DNase B (ADB) is often used to confirm a clinical diagnosis of Streptococcus pyogenes/group A Streptococcal (GAS) infection. The commonly used assays for antibodies that neutralize DNase B or streptolysin O activity use partially purified antigens that often fail to detect antibody changes subsequent to culture documented infections. Therefore, an enzyme-linked immunosorbent assay (ELISA) was developed employing his-tagged recombinant DNase B as plate antigen for comparison to the commonly used DNA methyl green micromethod (DMGM).

TRAIL enhances quinacrine-mediated apoptosis in breast cancer cells through induction of autophagy via modulation of p21 and DR5 interactions.

Purpose: Previously, we reported that quinacrine (QC) may cause apoptosis in breast and colon cancer cells by activating the death receptor 5 (DR5), resulting in autophagic cell death through p21 modulation. Here, we systematically evaluated the combined role of p21 and DR5 and their crosstalk in QC-mediated autophagy and apoptosis in breast cancer cells using in vitro and in vivo models.

Methods: Multiple breast cancer-derived cell lines (MCF-7, ZR-75-1, T47D, MDA-MB-231 and MCF-10A-Tr) and a mouse xenograft model were used.

Mild cold induced thermogenesis: are BAT and skeletal muscle synergistic partners?

There are two well-described thermogenic sites; brown adipose tissue (BAT) and skeletal muscle, which utilize distinct mechanisms of heat production. In BAT, mitochondrial metabolism is the molecular basis of heat generation, while it serves only a secondary role in supplying energy for thermogenesis in muscle. Here, we wanted to document changes in mitochondrial ultrastructure in these two tissue types based upon adaptation to mild (16°C) and severe (4°C) cold in mice.

Nanoquinacrine caused apoptosis in oral cancer stem cells by disrupting the interaction between GLI1 and β catenin through activation of GSK3β.

Presences of cancer stem cells (CSCs) in a bulk of cancer cells are responsible for tumor relapse, metastasis and drug resistance in oral cancer. Due to high drug efflux, DNA repair and self-renewable capacity of CSCs, the conventional chemotherapeutic agents are unable to kill the CSCs. CSCs utilizes Hedgehog (HH-GLI), WNT-β catenin signalling for its growth and development.

Etoposide and doxorubicin enhance the sensitivity of triple negative breast cancers through modulation of TRAIL-DR5 axis.

Death receptor 5 (DR5) is an important target for development of anticancer agents against triple-negative breast cancer (TNBC). Recently, we reported the molecular level details for the modulation of TRAIL-DR5 axis by quinacrine (QC) in breast cancer cells. In this work, the DR5 mediated anticancer potential of topoisomerase inhibitor etoposide (ET) and doxorubicin (DOX) against TNBC has been evaluated.

Nectin-4 is a breast cancer stem cell marker that induces WNT/β-catenin signaling via Pi3k/Akt axis.

Nectin-4 is well known as a junction protein. Recent reports have implicated it in cancer, but there has been little exploration of its functional significance in metastasis and cancer stem cells. Here, using the breast cancer metastasis model system, we report Nectin-4 is a marker for breast cancer stem cells (BCSCs) and provide experimental evidence suggesting that it utilizes WNT/β-Catenin signaling via Pi3k/Akt axis for self renewal of BCSCs.

Scaffold-Hopping of Aurones: 2-Arylideneimidazo[1,2-]pyridinones as Topoisomerase IIα-Inhibiting Anticancer Agents.

Scaffold-hopping of bioactive natural product aurones has been studied for the first time. 2-Arylideneimidazo[1,2-]pyridinones as potential topoisomerase IIα (hTopoIIα)-targeting anticancer compounds were considered. A multifunctional activator, polyphosphoric acid, enabled to realize a cascade reaction of 2-aminopyridine with 2,3-epoxyesters toward synthesis of 2-arylideneimidazo[1,2-]pyridinones.

Quinacrine induces apoptosis in cancer cells by forming a functional bridge between TRAIL-DR5 complex and modulating the mitochondrial intrinsic cascade.

Death Receptor 5 (DR5) is known to be an important anti-cancer drug target. TRAIL is a natural ligand of DR5, but its drug action is limited because of several factors. A few agonistic ligands were identified as TRAIL-DR5 axis modulators, which enhance the cellular apoptosis.

SURVIVIN as a marker for quiescent-breast cancer stem cells-An intermediate, adherent, pre-requisite phase of breast cancer metastasis.

Cancer stem cells drive the metastatic cascade by undergoing epithelial to mesenchymal transition (EMT) and again mesenchymal to epithelial transition (MET). Using multiple breast cancer cell lines including cigarette smoke induced breast cancer cells and tumor derived primary cells from patient sample; we developed a breast cancer metastasis model and reported the existence of an adherent, distinct pre-metastatic phase, quiescent-breast cancer stem cells (Q-BCSCs) prior to attaining an EMT. SURVIVIN was found to be expressed in Q-BCSCs.

ABT-888 and quinacrine induced apoptosis in metastatic breast cancer stem cells by inhibiting base excision repair via adenomatous polyposis coli.

PARP inhibitors in combination with other agents are in clinical trial against cancer, but its effect on cancer stem cells (CSCs) is limited. CSCs are responsible for drug resistance, metastasis and cancer relapse due to high DNA repair capacity. Here, we present preclinical effects of Quinacrine (QC) with ABT-888, a PARP inhibitor, on highly metastatic breast cancer stem cells (mBCSCs).

Chk1 inhibitor synergizes quinacrine mediated apoptosis in breast cancer cells by compromising the base excision repair cascade.

Quinacrine (QC) causes apoptosis in breast cancer cells by induction of DNA damage, arrest of cells in S-phase, and by topoisomerase inhibition. Here, we show that QC-mediated apoptosis is not only due to increased DNA damage but also by compromising cell cycle checkpoints and base excision repair (BER) capacity in breast cancer cells. QC decreased CHK1, CDKs (CDC2, MDM2, CDC6), cyclins (B1, E1) and CDC25-A in a dose dependent manner.

Anti-malarials are anti-cancers and vice versa - one arrow two sparrows.

Repurposing is the novel means of drug discovery in modern science due to its affordability, safety and availability. Here, we systematically discussed the efficacy and mode of action of multiple bioactive, synthetic compounds and their potential derivatives which are used to treat/prevent malaria and cancer. We have also discussed the detailed molecular pathway involved in anti-cancer potentiality of an anti-malarial drug and vice versa.

The bioactive and therapeutic potential of Hemidesmus indicus R. Br. (Indian Sarsaparilla) root.

The root of Hemidesmus indicus R. Br., commonly known as Indian Sarsaparilla, is used traditionally to treat a wide variety of illnesses including rheumatism, leprosy, impotence, urinary tract and skin infections.

Effect of Hemidesmus indicus R.Br. root extract against Salmonella enterica serovar Typhimurium-induced apoptosis in murine macrophage cell line (P388D1).

Background & Objective: Previous studies on natural products had mainly dealt with their antimicrobial activity and studies on the interference of these bioactive compounds with host-bacterial interaction is limited. The present study was undertaken to investigate the effect of the sterols and fatty acids present in the chloroform fraction of crude methanol extract of Hemidesmus indicus root (CHI) on Salmonella enterica serovar Typhimurium (S. Typhimurium) mediated apoptosis in a murine macrophage cell line (P388D1).

Protective role of Hemidesmus indicus R. Br. root extract against Salmonella typhimurium-induced cytotoxicity in Int 407 cell line.

The present investigation deals with the effect of the chloroform fraction composed of sterols and fatty acids isolated from Hemidesmus indicus root extract (CHI) on Salmonella enterica serovar Typhimurium (S. typhimurium)-induced cytotoxicity in a human intestinal epithelial cell line (Int 407). The optimum dose was fixed as 100 microg/mL for CHI against S.

Glycosides derived from Hemidesmus indicus R. Br. root inhibit adherence of Salmonella typhimurium to host cells: receptor mimicry.

For centuries, indigenous plants have been used against enteritis but their molecular targets and mode of action remain obscure. The present study was carried out to elucidate the protective and therapeutic role, if any, of glycosides from Hemidesmus indicus against S. typhimurium-induced pathogenesis.

Antienterobacterial activity of Hemidesmus indicus R. Br. root extract.

The antienterobacterial activity of the chloroform and methanol extracts of Hemidesmus indicus root was demonstrated using a variety of methods and different enterobacterial strains. Although the constituents were similar in the chloroform extract (CHI) and the fatty substance separated (ME1) from the methanol extract (MHI), ME1 was found to be more effective than CHI as evident from the disc diffusion method. ME1 was found to be more active than MHI, followed by CHI.

Antidiarrhoeal effects of methanolic root extract of Hemidesmus indicus (Indian sarsaparilla)--an in vitro and in vivo study.

Methanolic extract of H. indicus root (MHI) was screened for its antimicrobial activity against S. typhimurium, E.