Revisiting the ethnomedicinal, ethnopharmacological, phytoconstituents and phytoremediation of the plant Solanum viarum Dunal.

Solanum viarum, a perennial shrub, belongs to the family Solanaceae known for its therapeutic value worldwide. As a beneficial remedial plant, it is used for treating several disorders like dysentery, diabetes, inflammation, and respiratory disorders. Phytochemistry studies of this plant have shown the presence of steroidal glycoside alkaloids, including solasonine, solasodine, and solamargine. It also has flavonoids, saponins, minerals, and other substances. S. viarum extracts and compounds possess a variety of pharmacological effects, including antipyretic, antioxidant, antibacterial, insecticidal, analgesic, and anticancer activity. Most of the heavy metals accumulate in the aerial sections of the plant which is considered a potential phytoremediation, a highly effective method for the treatment of metal-polluted soils. We emphasize the forgoing outline of S. viarum, as well as its ethnomedicinal and ethnopharmacological applications, the chemistry of its secondary metabolites, and heavy metal toxicity. In addition to describing the antitumor activity of compounds and their mechanisms of action isolated from S. viarum, liabilities are also explained and illustrated, including any significant chemical or metabolic stability and toxicity risks. A comprehensive list of information was compiled from Science Direct, PubMed, Google Scholar, and Web of Science using different key phrases (traditional use, ethnomedicinal plants, western Himalaya, Himachal Pradesh, S viarum, and biological activity). According to the findings of this study, we hope that this review will inspire further studies along the drug discovery pathway of the chemicals extracted from the plant of S. viarum. Further, this review shows that ethnopharmacological information from ethnomedicinal plants can be a promising approach to drug discovery for cancer and diabetes.

Highly sensitive plasmonic paper substrate fabricated via amphiphilic polymer self-assembly in microdroplet for detection of emerging pharmaceutical pollutants.

We report an innovative and facile approach to fabricating an ultrasensitive plasmonic paper substrate for surface-enhanced Raman spectroscopy (SERS). The approach exploits the self-assembling capability of poly(styrene-b-2-vinyl pyridine) block copolymers to form a thin film at the air-liquid interface within the single microdroplet scale for the first time and the subsequent in situ growth of silver nanoparticles (AgNPs). The concentration of the block copolymer was found to play an essential role in stabilizing the droplets during the mass transfer phase and formation of silver nanoparticles, thus influencing the SERS signals. SEM analysis of the morphology of the plasmonic paper substrates revealed the formation of spherical AgNPs evenly distributed across the surface of the formed copolymer film with a size distribution of 47.5 nm. The resultant enhancement factor was calculated to be 1.2 × 107, and the detection limit of rhodamine 6G was as low as 48.9 pM. The nanohybridized plasmonic paper was successfully applied to detect two emerging pollutants-sildenafil and flibanserin-with LODs as low as 1.48 nM and 3.45 nM, respectively. Thus, this study offers new prospects for designing an affordable and readily available, yet highly sensitive, paper-based SERS substrate with the potential for development as a lab-on-a-chip device.

Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease.

The mammalian target of rapamycin (mTOR) is a protein kinase that controls cellular metabolism, catabolism, immune responses, autophagy, survival, proliferation, and migration, to maintain cellular homeostasis. The mTOR signaling cascade consists of two distinct multi-subunit complexes named mTOR complex 1/2 (mTORC1/2). mTOR catalyzes the phosphorylation of several critical proteins like AKT, protein kinase C, insulin growth factor receptor (IGF-1R), 4E binding protein 1 (4E-BP1), ribosomal protein S6 kinase (S6K), transcription factor EB (TFEB), sterol-responsive element-binding proteins (SREBPs), Lipin-1, and Unc-51-like autophagy-activating kinases. mTOR signaling plays a central role in regulating translation, lipid synthesis, nucleotide synthesis, biogenesis of lysosomes, nutrient sensing, and growth factor signaling. The emerging pieces of evidence have revealed that the constitutive activation of the mTOR pathway due to mutations/amplification/deletion in either mTOR and its complexes (mTORC1 and mTORC2) or upstream targets is responsible for aging, neurological diseases, and human malignancies. Here, we provide the detailed structure of mTOR, its complexes, and the comprehensive role of upstream regulators, as well as downstream effectors of mTOR signaling cascades in the metabolism, biogenesis of biomolecules, immune responses, and autophagy. Additionally, we summarize the potential of long noncoding RNAs (lncRNAs) as an important modulator of mTOR signaling. Importantly, we have highlighted the potential of mTOR signaling in aging, neurological disorders, human cancers, cancer stem cells, and drug resistance. Here, we discuss the developments for the therapeutic targeting of mTOR signaling with improved anticancer efficacy for the benefit of cancer patients in clinics.

Advances in Nanotechnology for Biofilm Inhibition.

Biofilm-associated infections have emerged as a significant public health challenge due to their persistent nature and increased resistance to conventional treatment methods. The indiscriminate usage of antibiotics has made us susceptible to a range of multidrug-resistant pathogens. These pathogens show reduced susceptibility to antibiotics and increased intracellular survival. However, current methods for treating biofilms, such as smart materials and targeted drug delivery systems, have not been found effective in preventing biofilm formation. To address this challenge, nanotechnology has provided innovative solutions for preventing and treating biofilm formation by clinically relevant pathogens. Recent advances in nanotechnological strategies, including metallic nanoparticles, functionalized metallic nanoparticles, dendrimers, polymeric nanoparticles, cyclodextrin-based delivery, solid lipid nanoparticles, polymer drug conjugates, and liposomes, may provide valuable technological solutions against infectious diseases. Therefore, it is imperative to conduct a comprehensive review to summarize the recent advancements and limitations of advanced nanotechnologies. The present Review encompasses a summary of infectious agents, the mechanisms that lead to biofilm formation, and the impact of pathogens on human health. In a nutshell, this Review offers a comprehensive survey of the advanced nanotechnological solutions for managing infections. A detailed presentation has been made as to how these strategies may improve biofilm control and prevent infections. The key objective of this Review is to summarize the mechanisms, applications, and prospects of advanced nanotechnologies to provide a better understanding of their impact on biofilm formation by clinically relevant pathogens.

Value Addition Employing Waste Bio-Materials in Environmental Remedies and Food Sector.

Overall, combating food waste necessitates a multifaceted approach that includes education, infrastructure, and policy change. By working together to implement these strategies, we can help reduce the negative impacts of food waste and create a more sustainable and equitable food system. The sustained supply of nutrient-rich agrifood commodities is seriously threatened by inefficiencies caused by agricultural losses, which must be addressed. As per the statistical data given by the Food and Agriculture Organisation (FAO) of the United Nations, nearly 33.33% of the food that is produced for utilization is wasted and frittered away on a global level, which can be estimated as a loss of 1.3 billion metric tons per annum, which includes 30% cereals, 20% dairy products 35% seafood and fish, 45% fruits and vegetables, and 20% of meat. This review summarizes the various types of waste originating from various segments of the food industry, such as fruits and vegetables, dairy, marine, and brewery, also focusing on their potential for developing commercially available value-added products such as bioplastics, bio-fertilizers, food additives, antioxidants, antibiotics, biochar, organic acids, and enzymes. The paramount highlights include food waste valorization, which is a sustainable yet profitable alternative to waste management, and harnessing Machine Learning and Artificial Intelligence technology to minimize food waste. Detail of sustainability and feasibility of food waste-derived metabolic chemical compounds, along with the market outlook and recycling of food wastes, have been elucidated in this review.

Identification and exploration of quinazoline-1,2,3-triazole inhibitors targeting EGFR in lung cancer.

Epidermal growth factor receptor (EGFR) enhances lung cancer development, due to their inability to permeate the cell membrane, secreted growth factors work through specialized signal transduction pathways. The purpose of this study is to find out a novel anticancer agent that inhibits EGFR and reduces the chances of lung cancer. A series of triazole-substituted quinazoline hybrid compounds were designed by Chemdraw software and docked against five different crystallographic EGFR tyrosine kinase domain (TKD). For docking and visualization PyRx, Autodock vina, and Discovery studio visualizer were used. Molecule-14, Molecule-16, Molecule-19, Molecule-20, and Molecule-38 showed significant affinity but Molecule-19 showed excellent binding affinity (-12.4 kcal/mol) with crystallographic EGFR tyrosine kinase. The superimposition of the co-crystalized ligand with the hit compound shows similar conformation at the active site of EGFR (PDB ID: 4HJO) indicating excellent coupling and pharmaceutically active. The hit compound showed a good bioavailability score (0.55) with no sign of carcinogenesis, mutagenesis, or reproductive toxicity properties. MD simulation and MMGBSA represent good stability and binding free energy demonstrating that the hit (Molecule-19) may be used as a lead compound. Molecule-19 also showed good ADME properties, bioavailability scores, and synthetic accessibility with fewer signs of toxicity. It was observed that Molecule-19 may be a novel and potential inhibitor against EGFR with fewer side effects than the reference molecule. Additionally, the molecular dynamics simulation revealed the stable nature of protein-ligand interaction and provided information about the amino acid residues involved in binding. Overall, this study led to the identification of potential EGFR inhibitors with favorable pharmacokinetic properties. We believe that the outcome of this study can help to develop more potent drug-like molecules to tackle human lung cancer.

A delve into the pharmacological targets and biological mechanisms of Paederia foetida Linn.: a rather invaluable traditional medicinal plant.

Drug development from herbal medicines or botanical sources is believed to have a prominent role in the exploration of novel counteractive drugs that has sparked much interest in recent times. Paederia foetida is one such medicinal plant used in both traditional and folkloric medicine. Several parts of the herb are locally utilised as a natural curative agent for several ailments since time immemorial. Paederia foetida indeed possesses anti-diabetic, anti-hyperlipidaemic, antioxidant, nephro-protective, anti-inflammatory, antinociceptive, antitussive, thrombolytic, anti-diarrhoeal, sedative-anxiolytic, anti-ulcer, hepatoprotective activity, anthelmintic and anti-diarrhoeal activity. Furthermore, growing evidence shows many of its active constituents to be effective in cancer, inflammatory diseases, wound healing and spermatogenesis as well. These investigations shed light on possible pharmacological targets and attempts to establish a mechanism of action for these pharmacological effects. These findings contrast the significance of this medicinal plant for further research and for the exploration of novel counteractive drugs to establish a mechanism of action before being employed to healthcare. Pharmacological activities of Paederia foetida and their mechanism of action.

Role and Recent Advancements of Ionic Liquids in Drug Delivery Systems.

Advancements in the fields of ionic liquids (ILs) broaden its applications not only in traditional use but also in different pharmaceutical and biomedical fields. Ionic liquids "Solutions for Your Success" have received a lot of interest from scientists due to a myriad of applications in the pharmaceutical industry for drug delivery systems as well as targeting different diseases. Solubility is a critical physicochemical property that determines the drug's fate at the target site. Many promising drug candidates fail in various phases of drug research due to poor solubility. In this context, ionic liquids are regarded as effective drug delivery systems for poorly soluble medicines. ILs are also able to combine different anions/cations with other cations/anions to produce salts that satisfy the concept behind the ILs. The important characteristics of ionic liquids are the modularity of their physicochemical properties depending on the application. The review highlights the recent advancement and further applications of ionic liquids to deliver drugs in the pharmaceutical and biomedical fields.

Polymer-Based Hybrid Nanoarchitectures for Cancer Therapy Applications.

Globally, cancer is affecting societies and is becoming an important cause of death. Chemotherapy can be highly effective, but it is associated with certain problems, such as undesired targeting and multidrug resistance. The other advanced therapies, such as gene therapy and peptide therapy, do not prove to be effective without a proper delivery medium. Polymer-based hybrid nanoarchitectures have enormous potential in drug delivery. The polymers used in these nanohybrids (NHs)provide them with their distinct properties and also enable the controlled release of the drugs. This review features the recent use of polymers in the preparation of different nanohybrids for cancer therapy published since 2015 in some reputed journals. The polymeric nanohybrids provide an advantage in drug delivery with the controlled and targeted delivery of a payload and the irradiation of cancer by chemotherapeutical and photodynamic therapy.

Solvent-resistant microfluidic paper-based analytical device/spray mass spectrometry for quantitative analysis of C18 -ceramide biomarker.

We developed a highly efficient and low-cost organic solvents-resistant microfluidic paper-based analytical device (µPAD) coupled with paper spray mass spectrometry (PS-MS) for quantitative determination of C18 -ceramide as a prognostic biomarker for several diseases. Several models of µPAD patterns have been examined to select the most resistant and efficient microchannel barriers, which can provide continuous spray at ionization zone and prevent "coffee ring" effect. Moreover, the developed µPAD has enabled the analysis of low concentration of C18 -ceramide because of the maximum supply of deposited analyte through microchannel. The MS results confirmed the formation of doubly and singly charged metal ion complexes between ceramide and different metal ions. Notably, the complexation that occurs between lithium ions and C18 -ceramide showed a high relative abundance compared with other formed complexes. Taking into account the relative abundance of complex [Cer + Li]+ at 572.8 m/z, it can be considered as a stable ion and therefore be used for the analysis of C18 -ceramide at low concentrations. Complexation of C18 -ceramide and lithium confirmed with quantum chemical calculations. The proposed method represents good linearity with a regression coefficient of 0.9956 for the analysis of C18 -ceramide and reaches a limit of detection to 0.84 nM. It has been adapted successfully for practical application in human serum samples with high recovery values in range of 92%-105%. The developed µPAD-MS technique provides clear advantages by reducing the experimental steps and simplifying the operation process and enables to identify subnanomolar concentration of C18 -ceramide in human serum samples.

Dual emission nonionic molecular imprinting conjugated polythiophenes-based paper devices and their nanofibers for point-of-care biomarkers detection.

Enzyme-based assays have been extensively used for the early diagnosis of disease-related biomarkers. However, these assays are time-consuming, resource-intensive, and infrastructure-dependent, which renders them unsuitable and impractical for use in resource-constrained areas. Thus, there is a strong demand for a biocompatible and potentially generalizable sensor that can rapidly detect cancer biomarkers at ultralow concentration. Herein, an enzyme-free, cost-efficient, and easy-to-use assay based on a novel approach that entails fluorescent molecularly imprinting conjugated polythiophenes (FMICPs) for cancer biomarkers detection is developed. The promising conjugated polythiophenes structure, with a PLQY as high as 55%, provides a straightforward, and affordable method for free-enzyme signal generation. More importantly, the feasibility of integrating printed-paper technology with a sensitive and cost-effective smartphone and portable prototype testing device that could be utilized for rapid point-of-care (POC) cancer diagnostics is successfully introduced. Significantly, the unique structure of FMICP nanofibers (FMICP NFs) displays superior performance with enhanced sensitivity that is 80 times higher than that of pristine FMICP. This assay could lower the limits of detection to 15 fg mL-1 and 3.5 fg mL-1 for α-fetoprotein (AFP) and carcinoembryonic antigen (CEA), respectively, which are three orders of magnitude exceeding that of the standard enzyme-based assay. Moreover, the developed sensors are successfully applied to the fast diagnosis of AFP in liver cancer patients and the FMICP and FMICP NFs results are in excellent agreement with those of clinical ELISA.

Recent Advances in Nanomicelles Delivery Systems.

The efficient and selective delivery of therapeutic drugs to the target site remains the main obstacle in the development of new drugs and therapeutic interventions. Up until today, nanomicelles have shown their prospective as nanocarriers for drug delivery owing to their small size, good biocompatibility, and capacity to effectively entrap lipophilic drugs in their core. Nanomicelles are formed via self-assembly in aqueous media of amphiphilic molecules into well-organized supramolecular structures. Molecular weights and structure of the core and corona forming blocks are important properties that will determine the size of nanomicelles and their shape. Selective delivery is achieved via novel design of various stimuli-responsive nanomicelles that release drugs based on endogenous or exogenous stimulations such as pH, temperature, ultrasound, light, redox potential, and others. This review summarizes the emerging micellar nanocarriers developed with various designs, their outstanding properties, and underlying principles that grant targeted and continuous drug delivery. Finally, future perspectives, and challenges for nanomicelles are discussed based on the current achievements and remaining issues.