In silico design and evaluation of a multiepitope vaccine targeting the nucleoprotein of Puumala orthohantavirus.

The Puumala orthohantavirus is present in the body of the bank vole (Myodes glareolus). Humans infected with this virus may develop hemorrhagic fever accompanying renal syndrome. In addition, the infection may further lead to the failure of an immune system completely. The present study aimed to propose a possible vaccine by employing bioinformatics techniques to identify B and T-cell antigens. The best multi-epitope of potential immunogenicity was generated by combining epitopes. Additionally, the linkers EAAAK, AAY, and GPGPG were utilized in order to link the epitopes successfully. Further, C-ImmSim was used to perform in silico immunological simulations upon the vaccine. For the purpose of conducting expression tests in Escherichia coli, the chimeric protein construct was cloned using Snapgene into the pET-9c vector. The designed vaccine showed adequate results, evidenced by the global population coverage and favorable immune response. The developed vaccine was found to be highly effective and to have excellent population coverage in a number of computer-based assessments. This work is fully dependent on the development of nucleoprotein-based vaccines, which would constitute a significant step forward if our findings were used in developing a global vaccination to combat the Puumala virus.

Twenty-eight days of repeated dose sub-acute toxicological evaluation of polyherbal Ayurvedic medicine BPGrit in Sprague-Dawley rats.

A pre-clinical toxicological evaluation of herbal medicines is necessary to identify any underlying health-associated side effects, if any. BPGrit is an Ayurveda-based medicine prescribed for treating hypertensive conditions. High-performance liquid chromatography-based analysis revealed the presence of gallic acid, ellagic acid, coumarin, cinnamic acid, guggulsterone E, and guggulsterone Z in BPGrit. For sub-acute toxicity analysis of BPGrit, male and female Sprague-Dawley rats were given repeated oral gavage at 100, 300, and 1000 mg/kg body weight/day dosages for 28 days, followed by a 14-day recovery phase. No incidences of mortality, morbidity, or abnormal clinical signs were observed in BPGrit-treated rats throughout the study period. Also, the body weight and food consumption habits of the experimental animals did not change during the study duration. Hematological, biochemical, and histopathological analysis did not indicate any abnormal changes occurring in the BPGrit-treated rats up to the highest tested dose of 1000 mg/kg body weight/day. Finally, the study established the "no-observed-adverse-effect level" for BPGrit at >1000 mg/kg body weight/day in Sprague-Dawley rats.

Livogrit prevents Amiodarone-induced toxicity in experimental model of human liver (HepG2) cells and Caenorhabditis elegans by regulating redox homeostasis.

Treatment with cationic amphiphilic drugs like Amiodarone leads to development of phospholipidosis, a type of lysosomal storage disorder characterized by excessive deposition of phospholipids. Such disorder in liver enhances accumulation of drugs and its metabolites, and dysregulates lipid profiles, which subsequently leads to hepatotoxicity. In the present study, we assessed pharmacological effects of herbal medicine, Livogrit, against hepatic phospholipidosis-induced toxicity. Human liver (HepG2) cells and in vivo model of Caenorhabditis elegans (N2 and CF1553 strains) were used to study effect of Livogrit on Amiodarone-induced phospholipidosis. In HepG2 cells, Livogrit treatment displayed enhanced uptake of acidic pH-based stains and reduced phospholipid accumulation, oxidative stress, AST, ALT, cholesterol levels, and gene expression of SCD-1 and LSS. Protein levels of LPLA2 were also normalized. Livogrit treatment restored Pgp functionality which led to decreased cellular accumulation of Amiodarone as observed by UHPLC analysis. In C. elegans, Livogrit prevented ROS generation, fat-6/7 gene overexpression, and lysosomal trapping of Amiodarone in N2 strain. SOD-3::GFP expression in CF1553 strain normalized by Livogrit treatment. Livogrit regulates phospholipidosis by regulation of redox homeostasis, phospholipid anabolism, and Pgp functionality hindered by lysosomal trapping of Amiodarone. Livogrit could be a potential therapeutic intervention for amelioration of drug-induced phospholipidosis and prevent hepatotoxicity.

Dynamics of hierarchical weighted networks of van der Pol oscillators.

We investigate the dynamics of regular fractal-like networks of hierarchically coupled van der Pol oscillators. The hierarchy is imposed in terms of the coupling strengths or link weights. We study the low frequency modes, as well as frequency and phase synchronization, in the network by a process of repeated coarse-graining of oscillator units. At any given stage of this process, we sum over the signals from the oscillator units of a clique to obtain a new oscillating unit. The frequencies and the phases for the coarse-grained oscillators are found to progressively synchronize with the number of coarse-graining steps. Furthermore, the characteristic frequency is found to decrease and finally stabilize to a value that can be tuned via the parameters of the system. We compare our numerical results with those of an approximate analytic solution and find good qualitative agreement. Our study on this idealized model shows how oscillations with a precise frequency can be obtained in systems with heterogeneous couplings. It also demonstrates the effect of imposing a hierarchy in terms of link weights instead of one that is solely topological, where the connectivity between oscillators would be the determining factor, as is usually the case.

Tri-Herbal Medicine Divya Sarva-Kalp-Kwath (Livogrit) Regulates Fatty Acid-Induced Steatosis in Human HepG2 Cells through Inhibition of Intracellular Triglycerides and Extracellular Glycerol Levels.

Steatosis is characterized by excessive triglycerides accumulation in liver cells. Recently, application of herbal formulations has gained importance in treating complex diseases. Therefore, this study explores the efficacy of tri-herbal medicine Divya Sarva-Kalp-Kwath (SKK; brand name, Livogrit) in treating free fatty acid (FFA)-induced steatosis in human liver (HepG2) cells and rat primary hepatocytes. Previously, we demonstrated that cytosafe SKK ameliorated CCl4-induced hepatotoxicity. In this study, we evaluated the role of SKK in reducing FFA-induced cell-death, and steatosis in HepG2 through analysis of cell viability, intracellular lipid and triglyceride accumulation, extracellular free glycerol levels, and mRNA expression changes. Plant metabolic components fingerprinting in SKK was performed via High Performance Thin Layer Chromatography (HPTLC). Treatment with SKK significantly reduced the loss of cell viability induced by 2 mM-FFA in a dose-dependent manner. SKK also reduced intracellular lipid, triglyceride accumulation, secreted AST levels, and increased extracellular free glycerol presence in the FFA-exposed cells. SKK normalized the FFA-stimulated overexpression of SREBP1c, FAS, C/EBPα, and CPT1A genes associated with the induction of steatosis. In addition, treatment of rat primary hepatocytes with FFA and SKK concurrently, reduced intracellular lipid accumulation. Thus, SKK showed efficacy in reducing intracellular triglyceride accumulation and increasing extracellular glycerol release, along with downregulation of related key genetic factors for FFA-associated steatosis.

Tracking urban human activity from mobile phone calling patterns.

Timings of human activities are marked by circadian clocks which in turn are entrained to different environmental signals. In an urban environment the presence of artificial lighting and various social cues tend to disrupt the natural entrainment with the sunlight. However, it is not completely understood to what extent this is the case. Here we exploit the large-scale data analysis techniques to study the mobile phone calling activity of people in large cities to infer the dynamics of urban daily rhythms. From the calling patterns of about 1,000,000 users spread over different cities but lying inside the same time-zone, we show that the onset and termination of the calling activity synchronizes with the east-west progression of the sun. We also find that the onset and termination of the calling activity of users follows a yearly dynamics, varying across seasons, and that its timings are entrained to solar midnight. Furthermore, we show that the average mid-sleep time of people living in urban areas depends on the age and gender of each cohort as a result of biological and social factors.

Attenuation of Pseudomonas aeruginosa quorum sensing, virulence and biofilm formation by extracts of Andrographis paniculata.

Quorum-sensing (QS) is known to play an essential role in regulation of virulence factors and toxins during Pseudomonas aeruginosa infection which may frequently cause antibiotic resistance and hostile outcomes of inflammatory injury. Therefore, it is an urgent need to search for a novel agent with low risk of resistance development that can target QS and inflammatory damage prevention as well. Andrographis paniculata, a herbaceous plant under the family Acanthaceae, native to Asian countries and also cultivated in Scandinavia and some parts of Europe, has a strong traditional usage with its known antibacterial, anti-inflammatory, antipyretic, antiviral and antioxidant properties. In this study, three different solvent extracts (viz., chloroform, methanol and aqueous) of A. paniculata were examined for their anti-QS and anti-inflammatory activities. Study was carried out to assess the effect on some selected QS-regulatory genes at transcriptional level using Real Time-PCR. In addition, ability to attenuate MAPK pathways upon P. aeruginosa infection was performed to check its potential anti-inflammatory activity. Chloroform and methanol extracts showed significant reduction (p < 0.05) of the QS-controlled extracellular virulence factors in P. aeruginosa including the expression of pyocyanin, elastase, total protease, rhamnolipid and hemolysin without affecting bacterial viability. They also significantly (p < 0.05) reduced swarming motility and biofilm formation of P. aeruginosa. The chloroform extract, which was found to be more effective, decreased expression of lasI, lasR, rhlI and rhlR by 61%, 75%, 41%, and 44%, respectively. Moreover, chloroform extract decreased activation of p-p38 and p-ERK1/2 expression levels in MAPK signal pathways in P. aeruginosa infected macrophage cells. As the present study demonstrates that A. paniculata extracts inhibit QS in P. aeruginosa and exhibit anti-inflammatory activities, therefore it represents itself as a prospective therapeutic agent against P. aeruginosa infection.

Nanodrugs to target articular cartilage: An emerging platform for osteoarthritis therapy.

Cartilage undergoes drastic structural changes during the development of osteoarthritis and cannot heal itself due to a defective chondrocyte response. Thus, much effort has been invested in the development of disease modifying drugs able to block key mediators within the cartilage matrix and biochemical pathways inside chondrocytes. However, the delivery of therapeutic agents into cartilage is ineffective. This has led to the use of cartilage-targeted nanodrugs to accumulate therapeutic agents into specific cartilage sub-compartments. This review will describe the nanodrugs targeted to specific components of cartilage matrix to generate drug reservoirs within the cartilage. The nanodrugs used as chondrocyte-specific gene delivery systems are also described. Although the use of cartilage-targeted nanodrugs in osteoarthritis is still in its infancy, these studies lay the foundation for the development of novel approaches for preventing the progression of cartilage breakdown and improving the quality of life of patients with osteoarthritis. FROM THE CLINICAL EDITOR: Osteoarthritis is a degeneration of joint cartilage, which affects a large number of aging people. Current therapy for disease modification is often suboptimal. Recent research in nanomedicine has led to the design and use of nanodrugs with the aim to help reverse the disease process. In this comprehensive review, the authors described and discussed various nanodrugs in the hope that newer drugs could be discovered in the future.

Biological interactions of carbon-based nanomaterials: From coronation to degradation.

Carbon-based nanomaterials including carbon nanotubes, graphene oxide, fullerenes and nanodiamonds are potential candidates for various applications in medicine such as drug delivery and imaging. However, the successful translation of nanomaterials for biomedical applications is predicated on a detailed understanding of the biological interactions of these materials. Indeed, the potential impact of the so-called bio-corona of proteins, lipids, and other biomolecules on the fate of nanomaterials in the body should not be ignored. Enzymatic degradation of carbon-based nanomaterials by immune-competent cells serves as a special case of bio-corona interactions with important implications for the medical use of such nanomaterials. In the present review, we highlight emerging biomedical applications of carbon-based nanomaterials. We also discuss recent studies on nanomaterial 'coronation' and how this impacts on biodistribution and targeting along with studies on the enzymatic degradation of carbon-based nanomaterials, and the role of surface modification of nanomaterials for these biological interactions. FROM THE CLINICAL EDITOR: Advances in technology have produced many carbon-based nanomaterials. These are increasingly being investigated for the use in diagnostics and therapeutics. Nonetheless, there remains a knowledge gap in terms of the understanding of the biological interactions of these materials. In this paper, the authors provided a comprehensive review on the recent biomedical applications and the interactions of various carbon-based nanomaterials.

Keeping it real: The importance of material characterization in nanotoxicology.

Nanomaterials are small and the small size and corresponding large surface area of nanomaterials confers specific properties, making these materials desirable for various applications, not least in medicine. However, it is pertinent to ask whether size is the only property that matters for the desirable or detrimental effects of nanomaterials? Indeed, it is important to know not only what the material looks like, but also what it is made of, as well as how the material interacts with its biological surroundings. It has been suggested that guidelines should be implemented on the types of information required in terms of physicochemical characterization of nanomaterials for toxicological studies in order to improve the quality and relevance of the published results. This is certainly a key issue, but it is important to keep in mind that material characterization should be fit-for-purpose, that is, the information gathered should be relevant for the end-points being studied.

Dual effects of ß-cyclodextrin-stabilised silver nanoparticles: enhanced biofilm inhibition and reduced cytotoxicity.

The composition and mode of synthesis of nanoparticles (NPs) can affect interaction with bacterial and human cells differently. The present work describes the ability of ß-cyclodextrin (ß-CD) capped silver nanoparticles (AgNPs) to inhibit biofilm growth and reduce cytotoxicity. Biofilm formation of Staphylococcus epidermidis CSF 41498 was quantified by a crystal violet assay in the presence of native and capped AgNPs (Ag-10CD and Ag-20CD), and the morphology of the biofilm was observed by scanning electron microscope. The cytotoxicity of the AgNPs against HaCat cells was determined by measuring the increase in intracellular reactive oxygen species and change in mitochondrial membrane potential (ΔΨm). Results indicated that capping AgNPs with ß-CD improved their efficacy against S. epidermidis CSF 41498, reduced biofilm formation and their cytotoxicity. The study concluded that ß-CD is an effective capping and stabilising agent that reduces toxicity of AgNPs against the mammalian cell while enhancing their antibiofilm activity.

Assessing the potential of Psidium guajava derived phytoconstituents as anticholinesterase inhibitor to combat Alzheimer's disease: an in-silico and in-vitro approach.

Acetylcholinesterase (AChE) inhibitors play a crucial role in the treatment of Alzheimer's disease. These drugs increase acetylcholine levels by inhibiting the enzyme responsible for its degradation, which is a vital neurotransmitter involved in memory and cognition. This intervention intermittently improves cognitive symptoms and augments neurotransmission. This study investigates the potential of Psidium guajava fruit extract as an acetylcholinesterase (AChE) inhibitor for Alzheimer's disease treatment. Molecular characteristics and drug-likeness were analyzed after HR-LCMS revealed phytocompounds in an ethanolic extract of Psidium guajava fruit. Selected phytocompounds were subjected to molecular docking against AChE, with the best-docked compound then undergoing MD simulation, MMGBSA, DCCM, FEL, and PCA investigations to evaluate the complex stability. The hit compound's potential toxicity and further pharmacokinetic features were also predicted. Anticholinesterase activity was also studied using in vitro assay. The HR-LCMS uncovered 68 compounds. Based on computational analysis, Fluspirilene was determined to have the highest potential to inhibit AChE. It was discovered that the Fluspirilene-AChE complex is stable and that Fluspirilene has a high binding affinity for AChE. Extract of Psidium guajava fruit significantly inhibits AChE (88.37% at 200 µg/ml). It is comparable to the standard AChE inhibitor Galantamine. Fluspirilene exhibited remarkable binding to AChE. Psidium guajava fruit extract demonstrated substantial AChE inhibitory activity, indicating its potential for Alzheimer's treatment. The study underscores natural sources' significance in drug discovery.Communicated by Ramaswamy H. Sarma.

Neuroprotection by Polyherbal Medicine Divya-Medha-Vati Against Scopolamine-Induced Cognitive Impairment Through Modulation of Oxidative Stress, Acetylcholine Activity, and Cell Signaling.

Alzheimer disease is associated with cognitive impairments and neuronal damages. In this study, Scopolamine, a model drug used for the generation of Alzheimer-like symptoms induced cognitive dysfunction in C57BL/6 mice. It also elevated acetylcholine esterase (AcHE) activity, and reduced antioxidant (superoxide dismutase and catalase) activity in cortex tissue. Scop reduced neuronal density and increased pyknotic neurons in hippocampus tissue. In mouse neuroblastoma (Neuro2a) cells, Scop triggered a dose-dependent loss of cell viability and neurite outgrowth reduction. Scop-treated Neuro2a cells showed oxidative stress and reduction in mRNA expression for brain-derived neurotrophic factor (BDNF), nerve growth factor-1 (NGF-1), and Synapsin-1 (SYN-1) genes. Mice treated with Divya-Medha-Vati (DMV), an Ayurvedic polyherbal medicine showed protection against Scop-induced cognitive impairment (Morris Water Maze Escape Latency, and Elevated Plus Maze Transfer Latency). DMV protected against Scop-induced AcHE activity, and loss of antioxidant activities in the mice brain cortex while sustaining neuronal density in the hippocampus region. In the Neuro2a cells, DMV reduced Scop-induced loss of cell viability and neurite outgrowth loss. DMV protected the cells against induction of oxidative stress and promoted mRNA expression of BDNF, NGF-1, and SYN-1 genes. Phytochemical profiling of DMV showed the presence of Withanolide A, Withanolide B, Bacopaside II, Jujubogenin, Apigenin, Gallic acid, Caffeic acid, and Quercetin that are associated with antioxidant and neurostimulatory activities. In conclusion, the study showed that Divya-Medha-Vati was capable of promoting neuronal health and inhibiting Alzheimer-like cognitive dysfunction through enhanced antioxidant activities and modulation of neuronal activities.

Advancements in Nano-Mandoor Bhasma: Unravelling the Particle Size-Ascorbic Acid Synergy for Enhanced Iron Bioavailability for Anemia Treatment.

Mandoor Bhasma (MB) medicine, based on classical Indian Ayurveda, was size- and surface-modified to improve its therapeutic efficiency for treating iron-deficient anemia. Physical grinding reduced the size of MB to the nanoparticle (nano-MB) range without changing its chemical composition, as measured by particle size distribution. The surface of nano-MB was modified with ascorbic acid (nano-AA-MB) and confirmed using scanning electron microscopy and Fourier transformed infrared spectroscopy. Enhanced iron dissolution from the surface-modified nano-AA-MB under neutral-to-alkaline pH conditions, and in the intestinal region of the simulated gastrointestinal tract (GIT) digestion model was determined using inductively coupled plasma mass spectroscopy. GIT digestae of MB microparticles and nano-AA-MB were found to be biocompatible in human colon epithelial (Caco-2) cells, with the latter showing threefold higher iron uptake. Subsequently, a dose-dependent increase in cellular ferritin protein was observed in the nano-AA-MB digestae-treated Caco-2 cells, indicating the enhanced bioavailability and storage of dissolved iron. Overall, the study showed that reducing the size of centuries-old traditional Mandoor Bhasma medicine to nanoscale, and its surface-modification with ascorbic acid would help in enhancing its therapeutic abilities for treating iron-deficient anemia.

Multifaceted targets of cannabidiol in epilepsy: Modulating glutamate signaling and beyond.

Cannabidiol has been reported to interact with broad-spectrum biological targets with pleiotropic pharmacology including epilepsy although a cohesive mechanism is yet to be determined. Even though some studies propose that cannabidiol may manipulate glutamatergic signals, there is insufficient evidence to support cannabidiol direct effect on glutamate signaling, which is important in intervening epilepsy. Therefore, the present study aimed to analyze the epilepsy-related targets for cannabidiol, assess the differentially expressed genes with its treatment, and identify the possible glutamatergic signaling target. In this study, the epileptic protein targets of cannabidiol were identified using the Tanimoto coefficient and similarity index-based targets fishing which were later overlapped with the altered expression, epileptic biomarkers, and genetically altered proteins in epilepsy. The common proteins were then screened for possible glutamatergic signaling targets with differentially expressed genes. Later, molecular docking and simulation were performed using AutoDock Vina and GROMACS to evaluate binding affinity, ligand-protein stability, hydrophilic interaction, protein compactness, etc. Cannabidiol identified 30 different epilepsy-related targets of multiple protein classes including G-protein coupled receptors, enzymes, ion channels, etc. Glutamate receptor 2 was identified to be genetically varied in epilepsy which was targeted by cannabidiol and its expression was increased with its treatment. More importantly, cannabidiol showed a direct binding affinity with Glutamate receptor 2 forming a stable hydrophilic interaction and comparatively lower root mean squared deviation and residual fluctuations, increasing protein compactness with broad conformational changes. Based on the cheminformatic target fishing, evaluation of differentially expressed genes, molecular docking, and simulations, it can be hypothesized that cannabidiol may possess glutamate receptor 2-mediated anti-epileptic activities.

Netting into the Sophoretin pool: An approach to trace GSTP1 inhibitors for reversing chemoresistance.

Chemoresistance, a significant challenge in cancer treatment, is often associated with the cellular glutathione-related detoxification system. The GSTP1 isoenzyme (glutathione S-transferases) plays a critical role in the cytoplasmic inactivation of anticancer drugs. This suggests the identification of GSTP1 inhibitors to combat chemoresistance. We screened Sophoretin (also called quercetin) derivatives for molecular properties, pharmacokinetics, and toxicity profiles. Following that, we conducted molecular docking and simulations between selected derivatives and GSTP1. The best-docked complex, GSTP1-quercetin 7-O-ß-D-glucoside, exhibited a binding affinity of -8.1 kcal/mol, with no predicted toxicity and good pharmacokinetic properties. Molecular dynamics simulations confirmed the stability of this complex. Quercetin 7-O-ß-D-glucoside shows promise as a lead candidate for addressing chemoresistance in cancer patients, although further experimental studies are needed to validate its efficacy and therapeutic potential.

Exploring the globoid cell leukodystrophy protein network and therapeutic interventions.

Globoid cell leukodystrophy is a severe rare disorder characterized by white matter degradation, resulting in a progressive loss of physical and mental abilities and has extremely limited therapeutic interventions. Therefore, this study aimed to delve into the Globoid cell leukodystrophy associated intricate network of differentially expressed genes (p < 0.05, |Fc|> 1) to identify potential druggable targets and possible therapeutic interventions using small molecules. The disease-associated neuronal protein circuit was constructed and analyzed, identifying 53 nodes (minimum edge cutoff 1), among which five (FOS, FOSB, GDNF, GFRA1, and JUN) were discerned as potential core protein nodes. Although our research enumerates the potential small molecules to target various protein nodes in the proposed disease network, we particularly underscore T-5224 to inhibit c-Jun activity as JUN was identified as one of the pivotal elements within the disease-associated neuronal protein circuit. The evaluation of T-5224 binding energy (- 11.0 kcal/mol) from docking study revealed that the compound to exhibit a notable affinity towards Jun/CRE complex. Moreover, the structural integrity of complex was affirmed through comprehensive molecular dynamics simulations, indicating a stable hydrophilic interaction between T-5224 and the Jun/CRE complex, thereby enhancing protein compactness and reducing solvent accessibility. This binding energy was further substantiated by free binding analysis, revealing a substantial thermodynamics complex state (- 448.00 ± 41.73 kJ/mol). Given that this investigation is confined to a computational framework, we additionally propose a hypothetical framework to ascertain the feasibility of inhibiting the Jun/CRE complex with T-5224 against Globoid cell leukodystrophy, employing a combination of in vitro and in vivo methodologies as a prospective avenue of this study.

Computational pharmacology profiling of borapetoside C against melanoma.

Melanoma,also known as a 'black tumor', begins in the melanocytes when cells (that produce pigment) grows out of control. Immunological dysregulation, which raises the risk for multiple illnesses, including melanoma, may be influenced by stress tiggered through viral infection, long term effects of ultraviolet radiation, environmental pollutants etc. Borapetoside C is one of the phytoconstituents from Tinospora crispa, and its biological source has been reported for its antistress property. Network pharmacology and KEGG pathway analysis of borapetoside C-regulated proteins were conducted to identify the hub genes involved in melanoma development. Further, a molecular docking was performed between borapetoside C and targets involved in melanoma. Further, the top 3 complexes were selected based on the binding energy to conduct molecular dynamics simulations to evaluate the stability of ligand-protein complex followed by principal component analysis and dynamic cross-correlation matrix. In addition, borapetoside C was also screened for its pharmacokinetics and toxicity profile. Network Pharmacology studies and KEGG pathway analysis revealed 8 targets involved in melanoma. Molecular docking between borapetoside C and targets involved in melanoma identified 3 complexes with minimum binding i.e. borapetoside C- MAP2K1, MMP9, and EGFR. Further, molecular dynamics simulations showed a stable complex of borapetoside C with MMP9 and EGFR. The present study suggested that borapetoside C may target MMP9 and EGFR to possess an anti-melanoma property. This finding can be useful in developing a novel therapeutic agent against melanoma from a natural source.Communicated by Ramaswamy H. Sarma.

Integration of network pharmacology, molecular docking, and simulations to evaluate phytochemicals from Drymaria cordata against cervical cancer.

Introduction: Cervical cancer is prevalent among women worldwide. It is a type of cancer that occurs in the cells of the cervix, the lower part of the uterus. Mostly, it is observed in developing nations due to limited access to screening tools. Natural products with anticancer properties and fewer side effects have gained attention. Therefore, this study evaluates the potential of Drymaria cordata as a natural source for treating cervical cancer. Methodology: Phytocompounds present in Drymaria cordata were screened for their molecular properties and drug-likeness. The selected compounds were studied using systems biology tools such as network pharmacology, molecular docking, and molecular dynamics simulations, including MMGBSA studies. Results: Through network pharmacology, molecular docking, and molecular dynamics simulations, quercetin 3-O-ß-d-glucopyranosyl-(1→2)-rhamnopyranoside was identified as a hit compound targeting HRAS and VEGFA proteins. These proteins were found to be responsible for the maximum number of pathway modulations in cervical cancer. Conclusion: Drymaria cordata exhibits potential for treating cervical cancer due to the presence of quercetin 3-O-ß-d-glucopyranosyl-(1→2)-rhamnopyranoside. Further validation of these findings through in vitro and in vivo studies is required.

Cellular senescence in lung cancer: Molecular mechanisms and therapeutic interventions.

Lung cancer stands as the primary contributor to cancer-related fatalities worldwide, affecting both genders. Two primary types exist where non-small cell lung cancer (NSCLC), accounts for 80-85% and SCLC accounts for 10-15% of cases. NSCLC subtypes include adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Smoking, second-hand smoke, radon gas, asbestos, and other pollutants, genetic predisposition, and COPD are lung cancer risk factors. On the other hand, stresses such as DNA damage, telomere shortening, and oncogene activation cause a prolonged cell cycle halt, known as senescence. Despite its initial role as a tumor-suppressing mechanism that slows cell growth, excessive or improper control of this process can cause age-related diseases, including cancer. Cellular senescence has two purposes in lung cancer. Researchers report that senescence slows tumor growth by constraining multiplication of impaired cells. However, senescent cells also demonstrate the pro-inflammatory senescence-associated secretory phenotype (SASP), which is widely reported to promote cancer. This review will look at the role of cellular senescence in lung cancer, describe its diagnostic markers, ask about current treatments to control it, look at case studies and clinical trials that show how senescence-targeting therapies can be used in lung cancer, and talk about problems currently being faced, and possible solutions for the same in the future.