A cub and sushi domain-containing protein with esterase-like activity confers insecticide resistance in the Indian malaria vector Anopheles stephensi.

Chemical insecticides (organophosphates and pyrethroids) in the form of IRS (Indoor Residual Sprays) and LLINs (Long Lasting Insecticidal Nets) are the cornerstone for vector control, globally. However, their incessant use has resulted in widespread development of resistance in mosquito vectors, warranting continuous monitoring and investigation of the underlying mechanisms of resistance. Here, we identified a previously uncharacterized- Cub and Sushi Domain containing Insecticide Resistance (CSDIR) protein and generated evidence for its role in mediating insecticide resistance in the Anopheles stephensi. A strong binding affinity of the CSDIR protein towards different classes of insecticide molecules-malathion (KD 6.43 µM) and deltamethrin (KD 46.7 µM) were demonstrated using MD simulation studies and Surface Plasmon Resonance (SPR) experiments. Further, the recombinant CSDIR913-1190 protein exhibited potent esterase-like activity (α-naphthyl acetate (α-NA)- 1.356 ± 0.262 mM/min/mg and ß-naphthyl acetate (ß -NA)- 1.777 ± 0.220 mM/min/mg). Interestingly, dsRNA-mediated gene silencing of the CSDIR transcripts caused >60% mortality in resistant An. stephensi upon 1-h exposure to deltamethrin and malathion insecticides, compared to the control group. A significant reduction in the esterase-like activity was also observed against α-NA (p = 0.004) and ß-NA (p = 0.025) in CSDIR silenced mosquitoes compared to the control group. Using computational analysis and experimental data, our results provided significant evidence of the involvement of the CSDIR protein in mediating insecticide resistance in Anopheles mosquitoes. Thereby making the CSDIR protein, a novel candidate for exploration of novel insecticide molecules. These data would also be helpful in further understanding the development of metabolic resistance by the Anopheles vector.

konnect2prot: a web application to explore the protein properties in a functional protein-protein interaction network.

MOTIVATION: The regulation of proteins governs the biological processes and functions and, therefore, the organisms' phenotype. So there is an unmet need for a systematic tool for identifying the proteins that play a crucial role in information processing in a protein-protein interaction (PPI) network. However, the current protein databases and web servers still lag behind to provide an end-to-end pipeline that can leverage the topological understanding of a context-specific PPI network to identify the influential spreaders. Addressing this, we developed a web application, 'konnect2prot' (k2p), which can generate context-specific directional PPI network from the input proteins and detect their biological and topological importance in the network. RESULTS: We pooled together a large amount of ontological knowledge, parsed it down into a functional network, and gained insight into the molecular underpinnings of the disease development by creating a one-stop junction for PPI data. k2p contains both local and global information about a protein, such as protein class, disease mutations, ligands and PDB structure, enriched processes and pathways, multi-disease interactome and hubs and bottlenecks in the directional network. It also identifies spreaders in the network and maps them to disease hallmarks to determine whether they can affect the disease state or not. AVAILABILITY AND IMPLEMENTATION: konnect2prot is freely accessible using the link https://konnect2prot.thsti.in. The code repository is https://github.com/samrat-lab/k2p_bioinfo-2022.

Expanding the Role of Chiral Drugs and Chiral Nanomaterials as a Potential Therapeutic Tool.

Chirality, the property of molecules having mirror-image forms, plays a crucial role in pharmaceutical and biomedical research. This review highlights its growing importance, emphasizing how chiral drugs and nanomaterials impact drug effectiveness, safety, and diagnostics. Chiral molecules serve as precise diagnostic tools, aiding in accurate disease detection through unique biomolecule interactions. The article extensively covers chiral drug applications in treating cardiovascular diseases, CNS disorders, local anesthesia, anti-inflammatories, antimicrobials, and anticancer drugs. Additionally, it explores the emerging field of chiral nanomaterials, highlighting their suitability for biomedical applications in diagnostics and therapeutics, enhancing medical treatments.

An Overview of the Anticancer Potential of Silver Nanostructures against Cervical Cancer.

Women are impacted by the extremely common cancer known as cervical cancer worldwide. Although preventive vaccines for cervical cancer are successful, treatment of cervical cancer is far less satisfactory because of multidrug resistance and side effects. There is an increasing need for alternative treatment modalities due to the rather aggressive and non-specific nature of conventional chemotherapeutics. With the advent of new technologies, scientists are working harder to create novel drug delivery strategies for chemotherapy of cervical cancer. Metal nanoparticles, and particularly silver nanoparticles, are a relatively new class with a lot of promise in the field of cancer biology. Nanoparticle therapeutics are attractive platforms for clinically relevant drug development because of their powerful anti-cancer properties, correspondingly attenuated side effects, and cancer-specific targeting. In this review, we provide an overview of the most recent uses of nanotechnology, particularly silver nanostructures, in the diagnosis and treatment of cervical cancer. The salient features of silver nanoparticle-based therapeutic concepts that are novel, viable, and attainable are emphasized in this review, along with those that pose a significant obstacle to their progress toward clinical application.

Exploration of functional relations among differentially co-expressed genes identifies regulators in glioblastoma.

The conventional computational approaches to investigating a disease confront inherent constraints as they often need to improve in delving beyond protein functional associations and grasping their deeper contextual significance within the disease framework. Such context-specificity can be explored using clinical data by evaluating the change in interaction between the biological entities in different conditions by investigating the differential co-expression relationships. We believe that the integration and analysis of differential co-expression and the functional relationships, primarily focusing on the source nodes, will open novel insights about disease progression as the source proteins could trigger signaling cascades, mostly because they are transcription factors, cell surface receptors, or enzymes that respond instantly to a particular stimulus. A thorough contextual investigation of these nodes could lead to a helpful beginning point for identifying potential causal linkages and guiding subsequent scientific investigations to uncover mechanisms underlying observed associations. Our methodology includes functional protein-protein Interaction (PPI) data and co-expression information and filters functional linkages through a series of critical steps, culminating in the identification of a robust set of regulators. Our analysis identified eleven key regulators-AKT1, BRCA1, CAMK2G, CUL1, FGFR3, KIF3A, NUP210, PRKACB, RAB8A, RPS6KA2 and TGFB3-in glioblastoma. These regulators play a pivotal role in disease classification, cell growth control, and patient survivability and exhibit associations with immune infiltrations and disease hallmarks. This underscores the importance of assessing correlation towards causality in unraveling complex biological insights.

A Comprehensive Review: Pharmacogenomics and Personalized Medicine Customizing Drug Therapy Based on Individual Genetics Profiles.

Numerous factors, such as genetics, environmental factors, and illness determinants, might contribute to an unpleasant pharmaceutical response. In an effort to increase efficacy and safety, as well as to gain a better understanding of drug disposition and clinical consequences, researchers in the two quickly emerging fields of pharmacogenetics (which focuses on single genes) and pharmacogenomics (which focuses on many genes) have studied the genetic personalization of drug response. This is due to the fact that a large number of pharmacological responses seem to be genetically based, and the relationship between medication response and genotype may be important for diagnosis. We now have a better understanding of the genetic basis of individual medication responses because to research on pharmaceuticals and genes. Pharmacogenomics aims to improve patient outcomes by developing personalized medicine by using the diversity of the human genome and how it affects medication response. Translational in nature, pharmacogenomics research encompasses everything from the discovery of genotype-phenotype associations to clinical investigations that might show therapeutic relevance. Though the conversion of pharmacogenomics research findings into clinical practice has been sluggish, advances in the field offer considerable potential for future therapeutic applications in specific people.

Caspase inhibitors: a review on recently patented compounds (2016-2023).

INTRODUCTION: Caspases are a family of protease enzymes that play a crucial role in apoptosis. Dysregulation of caspase activity has been implicated in various pathological conditions, making caspases an important focus of research in understanding cell death mechanisms and developing therapeutic strategies for diseases associated with abnormal apoptosis. AREAS COVERED: It is a comprehensive review of caspase inhibitors that have been comprising recently granted patents from 2016 to 2023. It includes peptide and non-peptide caspase inhibitors with their application for different diseases. EXPERT OPINION: This review categorizes and analyses recently patented caspase inhibitors on various diseases. Diseases linked to caspase dysregulation, including neurodegenerative disorders, and autoimmune conditions, are highlighted to accentuate the therapeutic relevance of the patented caspase inhibitors. This paper serves as a valuable resource for researchers, clinicians, and pharmaceutical developers seeking an up-to-date understanding of recently patented caspase inhibitors. The integration of recent patented compounds, structural insights, and mechanistic details provides a holistic view of the progress in caspase inhibitor research and its potential impact on addressing various diseases.

Geometric Shape Recognition with an Ultra-High Density Perovskite Nanowire Array-Based Artificial Vision System.

Artificial vision systems (AVS) have potential applications in visual prosthetics and artificially intelligent robotics, and they require a preprocessor and a processor to mimic human vision. Halide perovskite (HP) is a promising preprocessor and processor due to its excellent photoresponse, ubiquitous charge migration pathways, and innate hysteresis. However, the material instability associated with HP thin films hinders their utilization in physical AVSs. Herein, we have developed ultrahigh-density arrays of robust HP nanowires (NWs) rooted in a porous alumina membrane (PAM) as the active layer for an AVS. The NW devices exhibit gradual photocurrent change, responding to changes in light pulse duration, intensity, and number, and allow contrast enhancement of visual inputs with a device lifetime of over 5 months. The NW-based processor possesses temporally stable conductance states with retention >105 s and jitter <10%. The physical AVS demonstrated 100% accuracy in recognizing different shapes, establishing HP as a reliable material for neuromorphic vision systems.

An ultrawide field-of-view pinhole compound eye using hemispherical nanowire array for robot vision.

Garnering inspiration from biological compound eyes, artificial vision systems boasting a vivid range of diverse visual functional traits have come to the fore recently. However, most of these artificial systems rely on transformable electronics, which suffer from the complexity and constrained geometry of global deformation, as well as potential mismatches between optical and detector units. Here, we present a unique pinhole compound eye that combines a three-dimensionally printed honeycomb optical structure with a hemispherical, all-solid-state, high-density perovskite nanowire photodetector array. The lens-free pinhole structure can be designed and fabricated with an arbitrary layout to match the underlying image sensor. Optical simulations and imaging results matched well with each other and substantiated the key characteristics and capabilities of our system, which include an ultrawide field of view, accurate target positioning, and motion tracking function. We further demonstrate the potential of our unique compound eye for advanced robotic vision by successfully completing a moving target tracking mission.

L-theanine attenuates LPS-induced motor deficit in experimental rat model of Parkinson's disease: emphasis on mitochondrial activity, neuroinflammation, and neurotransmitters.

RATIONALE: Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons. The pathogenesis of PD includes oxidative stress, mitochondrial dysfunction, neuroinflammation, and neurotransmitter dysregulation. L-theanine is found in green tea and has antioxidant, anti-inflammatory, and neuroprotective effects with a high blood brain barrier permeability. OBJECTIVE: The objective of this study was to investigate the possible neuroprotective effect of L-theanine in lipopolysaccharide (LPS) induced motor deficits and striatal neurotoxicity in a rat model of PD. METHODS: LPS was infused at a dose of 5 µg/5 µl PBS stereotaxically into SNpc of rats. Treatment with L-theanine (50 and 100 mg/kg; po) and Sinemet (36 mg/kg; po) was given from day 7 to 21 in of LPS injected rat. On a weekly basis all behavioral parameters were assessed, and animals were sacrificed on day 22. The striatum tissue of brain was isolated for biochemicals (Nitrite, GSH, catalase, SOD, mitochondrial complexes I and IV), neuroinflammatory markers, and neurotransmitters (serotonin, dopamine, norepinephrine, GABA, and glutamate) estimations. RESULTS: Results revealed that L-theanine dose-dependently and significantly reversed motor deficits, assessed through locomotor and rotarod activity. Moreover, L-theanine attenuated biochemical markers, reduced oxidative stress, and neurotransmitters dysbalance in the brain. L-theanine treatment at 100 mg/kg; po substantially reduced these pathogenic events by increasing mitochondrial activity, restoring neurotransmitter levels, and inhibiting neuroinflammation. CONCLUSIONS: These data suggest that the positive effects of L-theanine on motor coordination may be mediated by the suppression of NF-κB induced by LPS. Therefore, L-theanine would have a new therapeutic potential for PD.

Tremor and Rigidity in Patients with Parkinson's Disease: Emphasis on Epidemiology, Pathophysiology and Contributing Factors.

Parkinson's disease (PD) is the second most prominent neurodegenerative movement disorder after Alzheimer's disease, involving 2-3% of the population aged above 65 years. This is mainly triggered by the depletion of dopaminergic neurons located in substantia nigra pars compacta (SNpc) in the region of basal ganglia. At present, diagnosis for symptoms of PD is clinical, contextual, unspecified and therapeutically incomprehensive. Analysis of various causes of PD is essential for an accurate examination of the disease. Among the different causes, such as tremors and rigidity, unresponsiveness to the current treatment approach contributes to mortality. In the present review article, we describe various key factors of pathogenesis and physiology associated with tremors and rigidity necessary for the treatment of PI (postural instability) in patients with PD. Additionally, several reports showing early tremor and rigidity causes, particularly age, cortex lesions, basal ganglia lesions, genetic abnormalities, weakened reflexes, nutrition, fear of fall, and altered biomechanics, have been explored. By summarizing the factors that contribute to the disease, histopathological studies can assess rigidity and tremor in PD. With a clear understanding of the contributing factors, various prospective studies can be done to assess the incidence of rigidity and tremors.

Role of vitamin D in targeting cancer and cancer stem cell populations and its therapeutic implications.

Cancer is recognized globally as the second-most dominating and leading cause of morbidities. Fighting the global health epidemic threat posed by cancer requires progress and improvements in imaging techniques, surgical techniques, radiotherapy, and chemotherapy. The existence of a small subpopulation of undifferentiated cells known as cancer stem cells has been supported by accumulating evidence and ongoing research. According to clinical data, cancer recurrence, tumor development, and metastasis are thought to be caused by CSCs. Nutritional or dietary supplements can help you to fight against cancer and cope with the treatment side effects. Vitamin D, sometimes known as the sunshine vitamin, is produced in the skin in reaction to sunlight. Vitamin D deficiency is hazardous to any degree, increasing the risk of diseases such as cancer and disorders like osteoporosis. Bioactive vitamin D, or calcitriol, regulates several biological pathways. Many modes of action of Vitamin D might be helpful in protecting somatic stem cells (e.g., DNA damage repair and oxidative stress protection) or restricting cancer stem cell growth (e.g., cell cycle arrest, cell apoptosis). Researchers have recently begun to investigate the inhibitory effects of dietary vitamin D on cancer stem cells. In this review, we investigated the therapeutic impact of vitamin D and its molecular processes to target cancer and cancer stem cells as well.

A proposal for a quality system for herbal products.

Today, there is an increasing worldwide demand for botanicals. Developing countries heavily rely on plant-derived medicines for their primary healthcare. One reason amongst many is the relatively inexpensive process economics and the lack of stringent product governance associated with the exploitation of traditional plant medicines compared with modern medicine. Developed countries impose stringent good manufacturing practices and quality control measures on drug products derived from any manufacturing process, regardless of the primary raw material. However, several factors hamper the full-scale application of traditional plant medicines: lack of implementation of effective quality assurance in the manufacturing process; lack of traceability in the supply chain and associated value additions; and inefficient identification of molecular species that affect the therapeutic efficacy of the final product. There lacks an assessable, causative, and prognostic relationship between the raw materials, the manufacturing process and the final product quality. This article suggests some solutions that may be adopted by the phytodrug industry to widen its global reach and retain its credibility. Primarily among them is the implementation of hazards analysis and critical control point in the manufacturing process and employment of process analytical technology for ensuring minimal deviation from the manufacturing process of phytotherapeutics.