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The present review article thoroughly analyses natural products and their derived phytoconstituents as a rich source of plausible anticancer drugs. The study thoroughly explores the chemical components derived from various natural sources, thus emphasizing their unique structural characteristics and therapeutic potential as an anticancer agent. The review contains the critical chemical constituents' in‐depth molecular mechanisms, their source's chemical structures and the categories. The review also comprises an exhaustive and comprehensive analysis of different chemical spacing parameters of the anticancer agents derived from natural products. It compares them with USFDA‐approved synthetic anticancer drugs up to 2020, thus providing a meaningful understanding of the relationship between natural and synthetic compounds portraying the anticancer assets. The review also delves more deeply into the chemical analysis of the heterocyclic moieties from the natural product arena, illustrating the anticancer mechanisms. The present article is, therefore, expected to serve as a valuable resource for natural product and medicinal chemists, encouraging and promoting an integrated approach to exploit the potential of natural products in drug discovery development and translational research, which have a prerequisite of bench to bedside approach. The work could guide researchers toward innovative approaches for the ever‐evolving field of anticancer drug discovery. [ABSTRACT FROM AUTHOR]

Summary: Newly arising variants of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) are now a threat to global public health and are creating COVID‐19 surges in different countries. At the same time, there is limited knowledge about these emerging variants. Even if research data are available, it is varyingly scattered. In this review, we have discussed the appearance of significant alarming SARS‐CoV‐2 variants in the entire world. The study also discusses the properties of the substantial variant of concern (VOC) variants such as B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.427 (Epsilon) and B.1.429 (Epsilon). At the same time, the characteristic properties of some significant variant of interest (VOI) variants like B.1.525 (Eta), B.1.526 (Iota) (sublineage B.1.526.1), B.1.617 (sublineages B.1.617.1 (Kappa), B.1.617.2 (Delta) and B.1.617.3), P.2 (Zeta), P.3 (Theta), B.1.616 and B.1.427 have also been discussed. Here, we have explained some essential mutations for the VOC and VOI variants such as K417T/N, L452R, E484K, N501Y, D614G and P681R. Consecutively, we also highlighted the crucial clinical characteristics of the variants, such as transmissibility, infectivity, re‐infectivity, immune escape, vaccine activity and vaccine escape. Our comprehensive review will provide updated information on the newly appearing variants of SARS‐CoV‐2 and help the researchers to formulate strategies to curtail the COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

In this study, a real‐time empirical mode decomposition (RT‐EMD) based control technique is adopted for effective mitigation of system harmonics under ideal and non‐ideal supply voltage conditions. The proposed control algorithm takes the active component of load current samples and the positive sequence voltage component for generating the desired reference. The fundamental component of load current is found by employing RT‐EMD, which decomposes the distorted non‐linear sample into a finite number of fine‐scale signals termed as intrinsic mode function (IMF). Each IMF is extracted adopting continuous calculation of upper and lower envelopes using a series pipeline structure which decreases the computational complexity. The proposed control algorithm takes the positive sequence voltage component for generating the desired reference so that the system can operate in non‐sinusoidal grid voltage conditions. The proposed control algorithm adopts carrier‐based modulation scheme for switching of the inverter module. The effectiveness of the proposed control approach is investigated in MATLAB‐Simulink environment with balanced and unbalanced loading condition and its experimental validation is carried out by a hardware prototype model using a Spartan 6 FPGA controller. [ABSTRACT FROM AUTHOR]

COVID‐19 leads to mortality of several patients and the cytokine storm is reportedly critical in the patients. To reduce the cytokine storm, we would like to propose the interleukin (IL) 6 receptor (IL‐6R) antagonist therapy for the COVID‐19 patients. Two humanized monoclonal antibodies are in clinical trial following IL‐6R antagonist therapies namely tocilizumab and sarilumab. However, researchers and physicians should look for more IL‐6R antagonists for the therapy of cytokine storm syndrome severe acute respiratory syndrome coronavirus 2 infected persons to enhance the therapeutic options for cytokine storm. Highlights: Cytokine storm syndrome or cytokine release syndrome (CRS) is often observed in severe COVID‐19 patients.CRS may be the leading cause of the deaths of severe COVID‐19 patients.IL6 receptor antagonist molecules may be helpful for the therapy for containing CRS.Two humanized monoclonal antibodies (IL6 receptor antagonists), namely, tocilizumab and sarilumab, are in the clinical trials for the treatment of CRS of COVID‐19 patients. [ABSTRACT FROM AUTHOR]

Due to an increase in traffic collisions, the demand for prehospital medical services is on the rise, even in low-resource countries where emergency ambulance services have not been previously provided. To build a sustainable and continuous prehospital ambulance operation model, it is necessary to consider the medical system and economic conditions of the corresponding country. In an attempt to construct a prehospital ambulance operation model that ensures continuous operation, a pilot “emergency patient transporting service from field to hospital” operation was established for approximately three months in Kinshasa, the capital of the DR Congo. To construct a continuously operating model even after the pilot operation, willingness to pay (WTP) by type of emergency medical and transport service was investigated by implementing the contingent valuation method (CVM). Using CVM, the WTP for prehospital emergency services targeting ambulance services personnel, patients, policemen, and hospital staff participating in the pilot operation was calculated. The results of the pilot operation revealed that there were a total of 212 patients with a mean patient number of 2.4 per day. A total of 155 patients used the services for hospital transport, while 121 patients used the services for traffic collisions. Traffic collisions were the category in which ambulance services were most frequently needed (66.2%). Pay services were most frequently utilized in the home-visit services category (40.9%). Based on these results, eight independently operated ambulance operation models and sixteen models that utilize hospital medical personnel and policemen already belonging to existing institutions were proposed. In an effort to implement emergency medical ambulance services in the DR Congo, medical staff receiving pay for performance (incentive pay) should be deployed in the field and on call. Accordingly, with respect to sustainable development goals, various pay-for-service models should be used. [ABSTRACT FROM AUTHOR]

Periprosthetic osteolysis remains the leading obstacle for total joint replacements. Primarily, it was thought that aseptic loosening is mainly caused by macrophage mediated inflammatory process arising from production of wear debris. The role of osteoclasts and its sequential bone resorption ability has been extensively studied, but little is known about impaired osteogenesis during osteolysis. In the current study, we have tried to delineate the regulatory mechanism of osteogenic signals by Ti particles in osteoprogenitor cells as well its participatory role in wear debris induced osteolysis. Implantation of Ti particles on mice calvaria induced pro-inflammatory response, elevated expression of COX2 and reduced the expression of Osterix. Treatment of Ti particles to MC3T3 E-1 cells displayed decreased osteogenic activity including ALP activity, mineralization and mRNA levels several osteogenic genes. Moreover, the basal activity of WNT and BMP signaling pathways was suppressed in MC3T3 E-1 cells treated with Ti particles. As an early response to Ti particles, MC3T3 E-1 cells showed activation of ERK and JNK. Co-inhibition of ERK and JNK with their specific inhibitors resulted in partial recovery of WNT and BMP signaling activity as well as ALP activity and collagen synthesis. Finally, LiCl mediated activation of WNT signaling pathway demonstrated rescue of Ti particle facilitated suppression of Osterix expression in mice calvaria. Our results provide evidences that WNT signaling pathway is regulated by ERK, JNK, and BMP signaling pathway during wear debris induced inflammatory osteolysis and may be considered as suitable therapeutic targets for the treatment. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 912-926, 2017. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an inflammatory disease that primarily affects joints. This autoimmune disease pathogenesis is related to cytokine signaling. In this review, we have described the existence of various microRNAs (miRNAs) involved in regulation of major protein cascades of cytokine signaling associated with RA. Moreover, we have tried to portray the role of various miRNAs in different cytokines such as TNF-α, IL-1, IL-6, IL-10, IL-17, IL-18, IL-21, and granulocyte macrophage colony-stimulating factor (GMCSF). Along with this, we have also discussed the miRNA regulation in T cells and synovial tissue. From the analyzed data, we suggest that miR-146a and miR-155 might be the potential therapeutic target for treating RA. The insight illustrated in this review will offer a better understanding of the role of miRNA in cytokine signaling pathways and inflammation during RA and could project them as diagnostic or therapeutic agents in near future. [ABSTRACT FROM AUTHOR]

The Wnt signaling pathway is mediated by a family of secreted glycoproteins through canonical and noncanonical mechanism. The signaling pathways are regulated by various modulators, which are classified into two classes on the basis of their interaction with either Wnt or its receptors. Secreted frizzled-related proteins (sFRPs) are the member of class that binds to Wnt protein and antagonizes Wnt signaling pathway. The other class consists of Dickkopf (DKK) proteins family that binds to Wnt receptor complex. The present review discusses the disease related association of various polymorphisms in Wnt signaling modulators. Furthermore, this review also highlights that some of the sFRPs and DKKs are unable to act as an antagonist for Wnt signaling pathway and thus their function needs to be explored more extensively. [ABSTRACT FROM AUTHOR]

In human, Wnt/β-catenin signaling pathway plays a significant role in cell growth, cell development, and disease pathogenesis. Four human (Rspo)s are known to activate canonicalWnt/β-catenin signaling pathway. Presently, (Rspo)s serve as therapeutic target for several human diseases. Henceforth, basic understanding about themolecular properties of (Rspo)s is essential. We approached this issue by interpreting the biochemical and biophysical properties alongwithmolecular evolution of (Rspo)s thorough computational algorithm methods. Our analysis shows that signal peptide length is roughly similar in (Rspo)s family along with similarity in aa distribution pattern. In Rspo3, four N-glycosylation sites were noted. All members are hydrophilic in nature and showed alike GRAVY values, approximately. Conversely, Rspo3 contains the maximum positively charged residues while Rspo4 includes the lowest. Four highly aligned blocks were recorded through Gblocks. Phylogenetic analysis shows Rspo4 is being rooted with Rspo2 and similarly Rspo3 and Rspo1 have the common point of origin. Through phylogenomics study, we developed a phylogenetic tree of sixty proteins (n= 60) with the orthologs and paralogs seed sequences. Protein-protein network was also illustrated. Results demonstrated in our study may help the future researchers to unfold significant physiological and therapeutic properties of (Rspo)s in various disease models. [ABSTRACT FROM AUTHOR]

Advancement in the gene delivery system have resulted in clinical successes in gene therapy for patients with several genetic diseases, such as immunodeficiency diseases, X-linked adrenoleukodystrophy (X-ALD) blindness, thalassemia, and many more. Among various delivery systems, liposomal mediated gene delivery route is offering great promises for gene therapy. This review is an attempt to depict a portrait about the polymer based liposomal gene delivery systems and their future applications. Herein, we have discussed in detail the characteristics of liposome, importance of polymer for liposome formulation, gene delivery, and future direction of liposome based gene delivery as a whole. [ABSTRACT FROM AUTHOR]

Proteins and genes of therapeutic interests in conjunction with different delivery systems are growing towards new heights. "Next generation delivery systems" may providemore efficient platformfor delivery of proteins and genes. In the present review, snapshots about the benefits of proteins or gene therapy, general procedures for therapeutic protein or gene delivery system, and different next generation delivery system such as liposome, PEGylation, HESylation, and nanoparticle based delivery have been depicted with their detailed explanation. [ABSTRACT FROM AUTHOR]

Summary: This paper describes an empirical mode decomposition control algorithm to extract the fundamental component and set the reference for harmonic extraction in a cascaded multilevel inverter–based shunt active filter. The proposed technique is fully reliant on the data samples that are decomposed instantaneously and does not require any weighing factor. The fundamental component of load current is found by applying a novel empirical mode decomposition algorithm from the nonlinear load current samples. Spline interpolation is used to extract the intrinsic mode function. For online implementation, the maxima and minima points of load current are stored using a modified field programming gate array (FPGA)‐based circular buffer circuit. Finally, the proposed cascaded multilevel inverter–based shunt active filter is investigated both by simulation and hardware implementation. The results obtained validates the performance of the proposed control technique under balanced and unbalanced loading conditions. [ABSTRACT FROM AUTHOR]

Summary: The paper describes the design aspect and control logic of a cascaded multilevel inverter‐based shunt active filter by employing single‐phase toroidal core transformers in cascaded manner which enable to operate with a single DC‐link capacitor. The presented topology uses a single DC‐link capacitor, thus minimizing the number of sensors and controller for voltage balancing. The induction of cascaded toroidal core transformer makes the system highly reliable as it minimizes the failure possibility of the DC‐link capacitor. For reference current generation, a perfect harmonic cancelation (PHC) control technique is implemented which is insensitive to distorted input condition and frequency deviation. To verify the effectiveness of the PHC controller, it is compared with a well‐known id‐iq control technique under ideal and non‐ideal supply main conditions. Furthermore, the developed topology is validated through MATLAB simulation and its prototype along with a well‐known DSP‐based FPGA controller. [ABSTRACT FROM AUTHOR]

Mer-tyrosine kinase (MERTK), a member of the AXL, TYRO3, and MERTK (TAM) family, is one of the promising targets for cancer treatment. It plays a key role in cancer cell survival and proliferation and regulates immune responses in cancer. The study aimed to rationally design and develop molecules considering the pharmacophoric requirements of MERTK using a multi-synthetic approach followed by the hybridization of individual pharmacophores. A hybrid drug design approach was employed by hybridization of pyrrolo[2,1-f][1,2,4]triazine and 1-(methylpiperidin-4-yl)aniline pharmacophoric systems to develop novel leads (1K1-1K5). The molecules were synthesized via a multi-step synthetic approach. The synthesized molecules were assessed for their pharmacological potential via cell viability, drug metabolism and pharmacokinetics (DMPK), and MERTK inhibition studies corroborated by in silico studies. IK5 was found to have an IC 50 value of 0.36 μM towards A549, followed by 0.42 μM and 0.80 μM against MCF-7 and MDA-MB-231 cells, respectively. Further, the molecules were also analyzed for their microsomal stability and were found to be stable with better intrinsic clearance profiles. The molecules thus pave a strategy for developing novel MERTK inhibitors and their advance in vitro and in vivo assessment in the future., (© 2024 The Author(s). Chemical Biology & Drug Design published by John Wiley & Sons Ltd.)