Synthesis of novel (R)-carvone-tagged thiazolidinone as anticancer leads: characterization, in vitro antiproliferative evaluation and in silico studies.

This work describes the successful synthesis of a series of three novel thiazolidinone-carvone-O-alkyl hybrids through a two-step approach involving heterocyclization and O-alkylation reactions. Comprehensive structural characterization of the obtained products was achieved using NMR and HRMS spectroscopic techniques. This study assessed in vitro antiproliferative activity of synthesized thiazolidinone-carvone-O-alkyl hybrids (5a-c) against various human cancer cell lines, viz. HT-1080 (fibrosarcoma), A-549 (lung cancer), MCF-7 (breast cancer) and MDA-MB-231 (breast cancer). MTT assay revealed promising results for compounds 5b and 5c, demonstrating good antiproliferative activity against A-549 and MCF-7 cell lines comparable to the positive control, Doxorubicin. Compound 5a, harbouring an O-acetoxy group, displayed limited anticancer activity against MCF-7 and MDA-MB-231 cells, with IC50 values of 69.33 ± 0.42 µM and >100 µM, respectively. Docking results confirmed that the compounds 5a-c binds at the active site of p21 with docking scores -2.0, -4.8, and -7.0 kcal/mol, respectively. Compound 5a-c also showed good binding potential against Bcl2 protein with docking score of -4.9, -6.0, -5.5 kcal/mol, respectively. Furthermore, binding energy analysis and dynamics simulation studies of compounds towards p21 and Bcl2 yielded promising results. In PAK4 assay, compound 5c showed comparable potency (IC50 6.76 µM) with the standard control UC2288 (IC50 6.40 µM), while in BCL-2 TR-FRET assay, 5c exhibited good inhibition (IC50 1.78 µM) as compared to Venetoclax (IC50 0.016 µM). In conclusion, compounds 5a-c could be used as a structural framework for the discovery of novel therapeutics to combat different types of cancer.Communicated by Ramaswamy H. Sarma.

Adjuvant Novel Nanocarrier-Based Targeted Therapy for Lung Cancer.

Lung cancer has the lowest survival rate due to its late-stage diagnosis, poor prognosis, and intra-tumoral heterogeneity. These factors decrease the effectiveness of treatment. They release chemokines and cytokines from the tumor microenvironment (TME). To improve the effectiveness of treatment, researchers emphasize personalized adjuvant therapies along with conventional ones. Targeted chemotherapeutic drug delivery systems and specific pathway-blocking agents using nanocarriers are a few of them. This study explored the nanocarrier roles and strategies to improve the treatment profile's effectiveness by striving for TME. A biofunctionalized nanocarrier stimulates biosystem interaction, cellular uptake, immune system escape, and vascular changes for penetration into the TME. Inorganic metal compounds scavenge reactive oxygen species (ROS) through their photothermal effect. Stroma, hypoxia, pH, and immunity-modulating agents conjugated or modified nanocarriers co-administered with pathway-blocking or condition-modulating agents can regulate extracellular matrix (ECM), Cancer-associated fibroblasts (CAF),Tyro3, Axl, and Mertk receptors (TAM) regulation, regulatory T-cell (Treg) inhibition, and myeloid-derived suppressor cells (MDSC) inhibition. Again, biomimetic conjugation or the surface modification of nanocarriers using ligands can enhance active targeting efficacy by bypassing the TME. A carrier system with biofunctionalized inorganic metal compounds and organic compound complex-loaded drugs is convenient for NSCLC-targeted therapy.

Design, synthesis, molecular docking, and in vitro studies of 2-mercaptoquinazolin-4(3H)-ones as potential anti-breast cancer agents.

Triple-negative breast cancer (TNBC) comprises 10 % to 20 % of breast cancer, however, it is more dangerous than other types of breast cancer, because it lacks druggable targets, such as the estrogen receptors (ER) and the progesterone receptor (PR), and has under expressed receptor tyrosine kinase, ErbB2. Present targeted therapies are not very effective and other choices include invasive procedures like surgery or less invasive ones like radiotherapy and chemotherapy. This study investigated the potential anticancer activity of some novel quinazolinone derivatives that were designed on the structural framework of two approved anticancer drugs, Ispinesib (KSP inhibitor) and Idelalisib (PI3Kδ inhibitor), to find out solutions for TNBC. All the designed derivatives (3a-l) were subjected to extra precision molecular docking and were synthesized and spectrally characterized. In vitro enzyme inhibition assay of compounds (3a, 3b, 3e, 3 g and 3 h) revealed their nanomolar inhibitory potential against the anticancer targets, KSP and PI3Kδ. Using MTT assay, the cytotoxic potential of compounds 3a, 3b and 3e were found highest against MDA-MB-231 cells with an IC50 of 14.51 µM, 16.27 µM, and 9.97 µM, respectively. Remarkably, these compounds were recorded safe against the oral epithelial normal cells with an IC50 values of 293.60 µM, 261.43 µM, and 222 µM, respectively. The anticancer potential of these compounds against MDA-MB-231 cells was revealed to be associated with their apoptotic activity. This was established by examination with the inverted microscope that revealed the appearance of various apoptotic features like cell shrinkage, apoptotic bodies, and membrane blebbing. Using flow cytometry, the Annexin V/PI-stained cancer cells showed an increase in early and late apoptotic cells. In addition, DNA fragmentation was revealed to occur after treatment with the tested compounds by gel electrophoresis. The relative gene expression of pro-apoptotic and anti-apoptotic genes revealed an overexpression of the P53 and BAX genes and a downregulation of the BCL-2 gene by real-time PCR. So, this work proved that compounds 3a, 3b, and 3e could be developed as anticancer candidates, via their P53-dependent apoptotic activity.

Unraveling NEAT1's complex role in lung cancer biology: a comprehensive review.

This review delves into the pivotal role of the long non-coding RNA NEAT1 in cancer biology, particularly in lung cancer (LC). It emphasizes NEAT1's unique subcellular localization and active involvement in gene regulation and chromatin remodeling. The review highlights NEAT1's impact on LC development and progression, including cell processes such as proliferation, migration, invasion, and resistance to therapy, positioning it as a potential diagnostic marker and therapeutic target. The complex web of NEAT1's regulatory interactions with proteins and microRNAs is explored, alongside challenges in targeting it therapeutically. The review concludes optimistically, suggesting future avenues for research and personalized LC therapies, shedding light on NEAT1's crucial role in LC. See also the Graphical abstract(Fig. 1).

Volatile Oil Containing Plants as Phytopharmaceuticals to Treat Psoriasis: A Review.

INTRODUCTION: Psoriasis is a chronic skin condition caused by an autoimmune response that accelerates the life cycle of skin cells, resulting in the characteristic symptoms of scaling, inflammation, and itching. METHODS: Palliative treatment options for psoriasis often prioritize the use of volatile oils. These oils contain monoterpenes, sesquiterpenes, and phenylpropanoids that are intricately linked to the molecular cascades involved in the pathogenesis and symptoms of psoriasis. To evaluate the antipsoriatic efficacy of volatile oils and their components, we conducted a systematic review of scientific studies. Our literature search encompassed various online databases, including PubMed, BIREME, SCIELO, Open Grey, Scopus, and ScienceDirect. The selected studies included experimental in vitro/in vivo assessments as well as clinical studies that examined the potential of volatile oils and their extracts as antipsoriatic agents. We excluded conference proceedings, case reports, editorials, and abstracts. Ultimately, we identified and evaluated a total of 12 studies for inclusion in our analysis. RESULTS: The data collected, compiled, and analyzed strongly support the interaction between volatile oils and their constituents with the key molecular pathways involved in the pathogenesis of psoriasis and the development of its symptoms. Volatile oils play a significant role in the palliative treatment of psoriasis, while their chemical constituents have the potential to reduce the symptoms and recurrence of this condition. CONCLUSION: The current review highlights that the constituents found in volatile oils offer distinct chemical frameworks that can be regarded as promising starting points for the exploration and development of innovative antipsoriatic agents.

MALAT1: A key regulator in lung cancer pathogenesis and therapeutic targeting.

Lung cancer remains a formidable global health burden, necessitating a comprehensive understanding of the underlying molecular mechanisms driving its progression. Recently, lncRNAs have become necessary controllers of various biological functions, including cancer development. MALAT1 has garnered significant attention due to its multifaceted role in lung cancer progression. Lung cancer, among other malignancies, upregulates MALAT1. Its overexpression has been associated with aggressive tumor behavior and poor patient prognosis. MALAT1 promotes cellular proliferation, epithelial-mesenchymal transition (EMT), and angiogenesis in lung cancer, collectively facilitating tumor growth and metastasis. Additionally, MALAT1 enhances cancer cell invasion by interacting with numerous signaling pathways. Furthermore, MALAT1 has been implicated in mediating drug resistance in lung cancer, contributing to the limited efficacy of conventional therapies. Recent advancements in molecular biology and high-throughput sequencing technologies have offered fresh perspectives into the regulatory networks of MALAT1 in lung cancer. It exerts its oncogenic effects by acting as a ceRNA to sponge microRNAs, thereby relieving their inhibitory effects on target genes. Moreover, MALAT1 also influences chromatin remodeling and post-translational modifications to modulate gene expression, further expanding its regulatory capabilities. This review sheds light on the multifaceted roles of MALAT1 in lung cancer progression, underscoring its potential as an innovative therapeutic target and diagnostic biomarker. Targeting MALAT1 alone or combined with existing therapies holds promise to mitigate lung cancer progression and improve patient outcomes.

From LncRNA to metastasis: The MALAT1-EMT axis in cancer progression.

Cancer is a complex disease that causes abnormal genetic changes and unchecked cellular growth. It also causes a disruption in the normal regulatory processes that leads to the creation of malignant tissue. The complex interplay of genetic, environmental, and epigenetic variables influences its etiology. Long non-coding RNAs (LncRNAs) have emerged as pivotal contributors within the intricate landscape of cancer biology, orchestrating an array of multifaceted cellular processes that substantiate the processes of carcinogenesis and metastasis. Metastasis is a crucial driver of cancer mortality. Among these, MALAT1 (Metastasis-Associated Lung Adenocarcinoma Transcript 1) has drawn a lot of interest for its function in encouraging metastasis via controlling the Epithelial-Mesenchymal Transition (EMT) procedure. MALAT1 exerts a pivotal influence on the process of EMT, thereby promoting metastasis to distant organs. The mechanistic underpinning of this phenomenon involves the orchestration of an intricate regulatory network encompassing transcription factors, signalling cascades, and genes intricately associated with the EMT process by MALAT1. Its crucial function in transforming tumor cells into an aggressive phenotype is highlighted by its capacity to influence the expression of essential EMT effectors such as N-cadherin, E-cadherin, and Snail. An understanding of the MALAT1-EMT axis provides potential therapeutic approaches for cancer intervention. Targeting MALAT1 or its downstream EMT effectors may reduce the spread of metastatic disease and improve the effectiveness of already available therapies. Understanding the MALAT1-EMT axis holds significant clinical implications. Therefore, directing attention towards MALAT1 or its downstream mediators could present innovative therapeutic strategies for mitigating metastasis and improving patient prognosis. This study highlights the importance of MALAT1 in cancer biology and its potential for cutting back on metastatic disease with novel treatment strategies.

New horizons in lung cancer management through ATR/CHK1 pathway modulation.

Lung cancer is the leading cause of cancer-related deaths worldwide. Molecular profiling has contributed to a new classification of lung cancer, driving advancements in research and therapy. The ataxia telangiectasia and rad3/checkpoint kinase 1 (ATR/CHK1) pathway plays a crucial role in maintaining genomic stability, and its activation has been linked to the development of lung cancer, drug resistance and poor prognosis. Clinical and preclinical studies have demonstrated promising results in targeting this pathway. ATR and CHK1 are proteins that collaborate to repair DNA damage caused by radiation or chemotherapy. ATR/CHK1 inhibitors are currently under investigation in preclinical and clinical trials. This article explores the ATR/CHK1 pathway and its potential for treating lung cancer.

Design-of-Experiment-Assisted Fabrication of Biodegradable Polymeric Nanoparticles: In Vitro Characterization, Biological Activity, and In Vivo Assessment.

Berberine (BER) is an alkaloid obtained from berberis plant having broad biological activities including anticancer. BER-encapsulated alginate (ALG)/chitosan (CHS) nanoparticles (BER-ALG/CHS-NPs) were developed for long-acting improved treatment in breast cancer. The surface of the NPs was activated by a conjugation reaction, and thereafter, the BER-ALG/CHS-NP surface was grafted with folic acid (BER-ALG/CHS-NPs-F) for specific targeting in breast cancer. BER-ALG/CHS-NPs-F was optimized by applying the Box-Behnken design using Expert design software. Moreover, formulations are extensively evaluated in vitro for biopharmaceutical performances and tested for cell viability, cellular uptake, and antioxidant activity. The comparative pharmacokinetic study of formulation and free BER was carried out in animals for estimation of bioavailability. The particle size recorded for the diluted sample using a Malvern Zetasizer was 240 ± 5.6 nm. The ζ-potential and the predicted % entrapment efficiency versus (vs) observed were +18 mV and 83.25 ± 2.3% vs 85 ± 3.5%. The high % drug release from the NPs was recorded. The analytical studies executed using infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction expressed safe combinations of the components in the formulation and physical state of the drug revealed to be amorphous in the formulation. Cytotoxicity testing demonstrated that the formulation effectively lowered the cell viability and IC50 of the tested cell line in comparison to a raw drug. The cellular uptake of BER-ALG/CHS-NPs-F was 5.5-fold higher than that of BER-suspension. The antioxidant capacities of BER-ALG/CHS-NPs-F vs BER-suspension by the DPPH assay were measured to be 62.3 ± 2.5% vs 30 ± 6%, indicating good radical scavenging power of folate-conjugated NPs. The developed formulation showed a 4.4-fold improved oral bioavailability compared to BER-suspension. The hemolytic assay intimated <2% destruction of erythrocytes by the developed formulation. The observed experimental characterization results such as cytotoxicity, cellular uptake, antioxidant activity, and improved absorption suggested the effectiveness of BER-ALG/CHS-NPs-F toward breast cancer.

Bedaquiline-Loaded Solid Lipid Nanoparticles Drug Delivery in the Management of Non-Small-Cell Lung Cancer (NSCLC).

Non-small-cell lung cancer (NSCLC) mortality and new case rates are both on the rise. Most patients have fewer treatment options accessible due to side effects from drugs and the emergence of drug resistance. Bedaquiline (BQ), a drug licensed by the FDA to treat tuberculosis (TB), has demonstrated highly effective anti-cancer properties in the past. However, it is difficult to transport the biological barriers because of their limited solubility in water. Our study developed a UPLC method whose calibration curves showed linearity in the range of 5 ng/mL to 500 ng/mL. The UPLC method was developed with a retention time of 1.42 and high accuracy and precision. Its LOQ and LOD were observed to be 10 ng/mL and 5 ng/mL, respectively, whereas in the formulation, capmul MCM C10, Poloxamer 188, and PL90G were selected as solid lipids, surfactants, and co-surfactants, respectively, in the development of SLN. To combat NSCLC, we developed solid lipid nanoparticles (SLNs) loaded with BQ, whereas BQ suspension is prepared by the trituration method using acacia powder, hydroxypropyl methylcellulose, polyvinyl acrylic acid, and BQ. The developed and optimized BQ-SLN3 has a particle size of 144 nm and a zeta potential of (-) 16.3 mV. whereas BQ-loaded SLN3 has observed entrapment efficiency (EE) and loading capacity (LC) of 92.05% and 13.33%, respectively. Further, BQ-loaded suspension revealed a particle size of 1180 nm, a PDI of 0.25, and a zeta potential of -0.0668. whereas the EE and LC of BQ-loaded suspension were revealed to be 88.89% and 11.43%, respectively. The BQ-SLN3 exhibited insignificant variation in particle size, homogeneous dispersion, zeta potential, EE, and LC and remained stable over 90 days of storage at 25 °C/60% RH, whereas at 40 °C/75% RH, BQ-SLN3 observed significant variation in the above-mentioned parameters and remained unstable over 90 days of storage. Meanwhile, the BQ suspension at both 25 °C (60% RH) and 40 °C (75% RH) was found to be stable up to 90 days. The optimized BQ-SLN3 and BQ-suspension were in vitro gastrointestinally stable at pH 1.2 and 6.8, respectively. The in vitro drug release of BQ-SLN3 showed 98.19% up to 12 h at pH 7.2 whereas BQ suspensions observed only 40% drug release up to 4 h at pH 7.2 and maximum drug release of >99% within 4 h at pH 4.0. The mathematical modeling of BQ-SLN3 followed first-order release kinetics followed by a non-Fickian diffusion mechanism. After 24 to 72 h, the IC50 value of BQ-SLN3 was 3.46-fold lower than that of the BQ suspension, whereas the blank SLN observed cell viability of 98.01% and an IC50 of 120 g/mL at the end of 72 h. The bioavailability and higher biodistribution of BQ-SLN3 in the lung tumor were also shown to be greater than those of the BQ suspension. The effects of BQ-SLN3 on antioxidant enzymes, including MDA, SOD, CAT, GSH, and GR, in the treated group were significantly improved and reached the level nearest to that of the control group of rats over the cancer group of rats and the BQ suspension-treated group of rats. Moreover, the pharmacodynamic activity resulted in greater tumor volume and tumor weight reduction by BQ-SLN3 over the BQ suspension-treated group. As far as we are aware, this is the first research to look at the potential of SLN as a repurposed oral drug delivery, and the results suggest that BQ-loaded SLN3 is a better approach for NSCLC due to its better action potential.

Emergence of Nano-Based Formulations for Effective Delivery of Flavonoids against Topical Infectious Disorders.

Flavonoids are hydroxylated phenolic substances in vegetables, fruits, flowers, seeds, wine, tea, nuts, propolis, and honey. They belong to a versatile category of natural polyphenolic compounds. Their biological function depends on various factors such as their chemical structure, degree of hydroxylation, degree of polymerization conjugation, and substitutions. Flavonoids have gained considerable attention among researchers, as they show a wide range of pharmacological activities, including coronary heart disease prevention, antioxidative, hepatoprotective, anti-inflammatory, free-radical scavenging, anticancer, and anti-atherosclerotic activities. Plants synthesize flavonoid compounds in response to pathogen attacks, and these compounds exhibit potent antimicrobial (antibacterial, antifungal, and antiviral) activity against a wide range of pathogenic microorganisms. However, certain antibacterial flavonoids have the ability to selectively target the cell wall of bacteria and inhibit virulence factors, including biofilm formation. Moreover, some flavonoids are known to reverse antibiotic resistance and enhance the efficacy of existing antibiotic drugs. However, due to their poor solubility in water, flavonoids have limited oral bioavailability. They are quickly metabolized in the gastrointestinal region, which limits their ability to prevent and treat various disorders. The integration of flavonoids into nanomedicine constitutes a viable strategy for achieving efficient cutaneous delivery owing to their favorable encapsulation capacity and diminished toxicity. The utilization of nanoparticles or nanoformulations facilitates drug delivery by targeting the drug to the specific site of action and exhibits excellent physicochemical stability.

Synthesis and Anticancer Evaluation of 4-Chloro-2-((5-aryl-1,3,4-oxadiazol-2-yl)amino)phenol Analogues: An Insight into Experimental and Theoretical Studies.

We report herein the synthesis, docking studies and biological evaluation of a series of new 4-chloro-2-((5-aryl-1,3,4-oxadiazol-2-yl)amino)phenol analogues (6a-h). The new compounds were designed based on the oxadiazole-linked aryl core of tubulin inhibitors of IMC-038525 and IMC-094332, prepared in five steps and further characterized via spectral analyses. The anticancer activity of the compounds was assessed against several cancer cell lines belonging to nine different panels as per National Cancer Institute (NCI US) protocol. 4-Chloro-2-((5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazol-2-yl)amino)phenol (6h) demonstrated significant anticancer activity against SNB-19 (PGI = 65.12), NCI-H460 (PGI = 55.61), and SNB-75 (PGI = 54.68) at 10 µM. The compounds were subjected to molecular docking studies against the active site of the tubulin-combretastatin A4 complex (PDB ID: 5LYJ); they displayed efficient binding and ligand 4h (with docking score = -8.030 kcal/mol) lay within the hydrophobic cavity surrounded by important residues Leu252, Ala250, Leu248, Leu242, Cys241, Val238, Ile318, Ala317, and Ala316. Furthermore, the antibacterial activity of some of the compounds was found to be promising. 4-Chloro-2-((5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl)amino)phenol (6c) displayed the most promising antibacterial activity against both Gram-negative as well as Gram-positive bacteria with MICs of 8 µg/mL and a zone of inhibition ranging from 17.0 ± 0.40 to 17.0 ± 0.15 mm at 200 µg/mL; however, the standard drug ciprofloxacin exhibited antibacterial activity with MIC values of 4 µg/mL.

Unveiling the connection: Long-chain non-coding RNAs and critical signaling pathways in breast cancer.

Breast cancer is a complex and diverse condition that disrupts multiple signaling pathways essential for cell proliferation, survival, and differentiation. Recently, the significant involvement of long-chain non-coding RNAs (lncRNAs) in controlling key signaling pathways associated with breast cancer development has been discovered. This review aims to explore the interaction between lncRNAs and various pathways, including the AKT/PI3K/mTOR, Wnt/ß-catenin, Notch, DNA damage response, TGF-ß, Hedgehog, and NF-κB signaling pathways, to gain a comprehensive understanding of their roles in breast cancer. The AKT/PI3K/mTOR pathway regulates cell growth, survival, and metabolic function. Recent data suggests that specific lncRNAs can influence the functioning of this pathway, acting as either oncogenes or tumor suppressors. Dysregulation of this pathway is commonly observed in breast cancer cases. Moreover, breast cancer development has been associated with other pathways such as Wnt/ß-catenin, Notch, TGF-ß, Hedgehog, and NF-κB. Emerging studies have identified lncRNAs that modulate breast cancer's growth, progression, and metastasis by interacting with these pathways. To advance the development of innovative diagnostic tools and targeted treatment options, it is crucial to comprehend the intricate relationship between lncRNAs and vital signaling pathways in breast cancer. By fully harnessing the therapeutic potential of lncRNAs, there is a possibility of developing more effective and personalized therapy choices for breast cancer patients. Further investigation is necessary to comprehensively understand the role of lncRNAs within breast cancer signaling pathways and fully exploit their therapeutic potential.

Design, Synthesis, ADME, and Anticancer Studies of Newer N-Aryl-5-(3,4,5-Trifluorophenyl)-1,3,4-Oxadiazol-2-Amines: An Insight into Experimental and Theoretical Investigations.

In continuance of our investigation into the anticancer activity of oxadiazoles, we report here the preparation of 10 new 1,3,4-oxadiazole analogues using the scaffold hopping technique. We have prepared the oxadiazoles having a common pharmacophoric structure (oxadiazole linked aryl nucleus) as seen in the reported anticancer agents IMC-038525 (tubulin inhibitor), IMC-094332 (tubulin inhibitor), and FATB (isosteric replacement of the S of thiadiazole with the O of oxadiazole). All of the oxadiazole analogues were predicted for their absorption, distribution, metabolism, and excretion (ADME) profiles and toxicity studies. All of the compounds were found to follow Lipinski's rule of 5 with a safe toxicity profile (Class IV compound) against immunotoxicity, mutagenicity, and toxicity. All of the compounds were synthesized and characterized using spectral data, followed by their anticancer activity tested in a single-dose assay at 10 µM as reported by the National Cancer Institute (NCI US) Protocol against nearly 59 cancer cell lines obtained from nine panels, including non-small-cell lung, ovarian, breast, central nervous system (CNS), colon, leukemia, prostate, and cancer melanoma. N-(2,4-Dimethylphenyl)-5-(3,4,5-trifluorophenyl)-1,3,4-oxadiazol-2-amine (6h) displayed significant anticancer activity against SNB-19, OVCAR-8, and NCI-H40 with percent growth inhibitions (PGIs) of 86.61, 85.26, and 75.99 and moderate anticancer activity against HOP-92, SNB-75, ACHN, NCI/ADR-RES, 786-O, A549/ATCC, HCT-116, MDA-MB-231, and SF-295 with PGIs of 67.55, 65.46, 59.09, 59.02, 57.88, 56.88, 56.53, 56.4, and 51.88, respectively. The compound 6h also registered better anticancer activity than Imatinib against CNS, ovarian, renal, breast, prostate, and melanoma cancers with average PGIs of 56.18, 40.41, 36.36, 27.61, 22.61, and 10.33, respectively. Molecular docking against tubulin, one of the appealing cancer targets, demonstrated an efficient binding within the binding site of combretastatin A4. The ligand 6h (docking score = -8.144 kcal/mol) interacted π-cationically with the residue Lys352 (with the oxadiazole ring). Furthermore, molecular dynamic (MD) simulation studies in complex with the tubulin-combretastatin A4 protein and ligand 6h were performed to examine the dynamic stability and conformational behavior.

Long non-coding RNAs in lung cancer: Unraveling the molecular modulators of MAPK signaling.

Lung cancer (LC) continues to pose a significant global medical burden, necessitating a comprehensive understanding of its molecular foundations to establish effective treatment strategies. The mitogen-activated protein kinase (MAPK) signaling system has been scientifically associated with LC growth; however, the intricate regulatory mechanisms governing this system remain unknown. Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of diverse cellular activities, including cancer growth. LncRNAs have been implicated in LC, which can function as oncogenes or tumor suppressors, and their dysregulation has been linked to cancer cell death, metastasis, spread, and proliferation. Due to their involvement in critical pathophysiological processes, lncRNAs are gaining attention as potential candidates for anti-cancer treatments. This article aims to elucidate the regulatory role of lncRNAs in MAPK signaling in LC. We provide a comprehensive review of the key components of the MAPK pathway and their relevance in LC, focusing on aberrant signaling processes associated with disease progression. By examining recent research and experimental findings, this article examines the molecular mechanisms through which lncRNAs influence MAPK signaling in lung cancer, ultimately contributing to tumor development.

Exploring Nanocarriers as Treatment Modalities for Skin Cancer.

Cancer is a progressive disease of multi-factorial origin that has risen worldwide, probably due to changes in lifestyle, food intake, and environmental changes as some of the reasons. Skin cancer can be classified into melanomas from melanocytes and nonmelanoma skin cancer (NMSC) from the epidermally-derived cell. Together it constitutes about 95% of skin cancer. Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC) are creditworthy of 99% of NMSC due to the limited accessibility of conventional formulations in skin cancer cells of having multiple obstacles in treatment reply to this therapeutic regime. Despite this, it often encounters erratic bioavailability and absorption to the target. Nanoparticles developed through nanotechnology platforms could be the better topical skin cancer therapy option. To improve the topical delivery, the nano-sized delivery system is appropriate as it fuses with the cutaneous layer and fluidized membrane; thus, the deeper penetration of therapeutics could be possible to reach the target spot. This review briefly outlooks the various nanoparticle preparations, i.e., liposomes, niosomes, ethosomes, transferosomes, transethosomes, nanoemulsions, and nanoparticles technologies tested into skin cancer and impede their progress tend to concentrate in the skin layers. Nanocarriers have proved that they can considerably boost medication bioavailability, lowering the frequency of dosage and reducing the toxicity associated with high doses of the medication.

Amelioration of Cancer Employing Chitosan, Its Derivatives, and Chitosan-Based Nanoparticles: Recent Updates.

The limitations associated with the conventional treatment of cancer have necessitated the design and development of novel drug delivery systems based mainly on nanotechnology. These novel drug delivery systems include various kinds of nanoparticles, such as polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, hydrogels, and polymeric micelles. Among the various kinds of novel drug delivery systems, chitosan-based nanoparticles have attracted the attention of researchers to treat cancer. Chitosan is a polycationic polymer generated from chitin with various characteristics such as biocompatibility, biodegradability, non-toxicity, and mucoadhesiveness, making it an ideal polymer to fabricate drug delivery systems. However, chitosan is poorly soluble in water and soluble in acidic aqueous solutions. Furthermore, owing to the presence of reactive amino groups, chitosan can be chemically modified to improve its physiochemical properties. Chitosan and its modified derivatives can be employed to fabricate nanoparticles, which are used most frequently in the pharmaceutical sector due to their possession of various characteristics such as nanosize, appropriate pharmacokinetic and pharmacodynamic properties, non-immunogenicity, improved stability, and improved drug loading capacity. Furthermore, it is capable of delivering nucleic acids, chemotherapeutic medicines, and bioactives using modified chitosan. Chitosan and its modified derivative-based nanoparticles can be targeted to specific cancer sites via active and passive mechanisms. Based on chitosan drug delivery systems, many anticancer drugs now have better effectiveness, potency, cytotoxicity, or biocompatibility. The characteristics of chitosan and its chemically tailored derivatives, as well as their use in cancer therapy, will be examined in this review.

The pyroptotic role of Caspase-3/GSDME signalling pathway among various cancer: A Review.

Cytotoxic drugs have long been recognised to kill cancer cells through apoptosis. According to a current study, pyroptosis inhibits cell proliferation and shrinks tumors. Pyroptosis and apoptosis are caspase-dependent programmed cell death (PCD) processes. Inflammasomes activate caspase-1 and latent cytokines, including IL-1ß and IL-18, to cleave gasdermin E (GSDME) and induce pyroptosis. Gasdermin proteins activate caspase-3 to induce pyroptosis, which is associated with tumour genesis, development, and therapy response. These proteins may serve as therapeutic biomarkers for cancer detection, and their antagonists may be a new target. Caspase-3, a crucial protein in both pyroptosis and apoptosis, governs tumour cytotoxicity when activated, and GSDME expression modulates this. Once active caspase-3 cleaves GSDME, its N-terminal domain punches holes in the cell membrane, causing it to expand, burst, and die. To understand the cellular and molecular mechanisms of PCD mediated by caspase-3 and GSDME, we focused on pyroptosis. Hence, caspase-3 and GSDME may be promising targets for cancer treatment.

Barbigerone prevents scopolamine-induced memory impairment in rats by inhibiting oxidative stress and acetylcholinesterase levels.

The current study was designed for the evaluation of barbigerone on memory loss. In this experimental study, 24 Wistar rats (n = 6) were used. Control rats and scopolamine (SCOP)-treated control group rats were orally administered with 3 ml of 0.5% sodium carboxymethyl cellulose (vehicle), whereas barbigerone was (10 and 20 mg kg-1) administered orally to the rats from the test group. During the 14-day treatment, control group rats were given 3 ml kg-1 day-1 saline, and all other groups were administered SCOP (1 mg kg-1 day-1, i.p.) 1 h after barbigerone p.o. treatment. The spontaneous alternation activities, learning capacities of a rat's memory were tested with Morris water maze and Y-maze. Reduced glutathione, malondialdehyde, acetylcholine esterase (AChE) and catalase (CAT) levels were measured in rat brain tissue as oxidative stress/antioxidant markers. Moreover, the levels of tumour necrosis factor, interleukin-6 (IL-6) and IL-1ß were also estimated. Treatment with barbigerone in SCOP-administered rats dramatically reduced SCOP-induced neurobehavioural deficits, oxidative stress and neuroinflammatory markers, improved endogenous antioxidants, and restored AChE activity. By improving cholinergic function and reducing oxidative damage, barbigerone could mitigate the effects of SCOP-induced changes in the brain.

Galangin as an inflammatory response modulator: An updated overview and therapeutic potential.

Numerous chronic diseases, such as cancer, diabetes, rheumatoid arthritis, cardiovascular disease, and gastrointestinal disorders, all have an inflammation-based etiology. In cellular and animal models of inflammation, flavonols were used to show potent anti-inflammatory activity. The flavonols enhanced the synthesis of the anti-inflammatory cytokines transforming growth factor and interleukin-10 (IL-10) and reduced the synthesis of the prostaglandins IL-6, tumor necrosis factor-alpha (TNF-α), and prostaglandin E2 (PGE2), IL-1. Galangin (GAL), a natural flavonol, has a strong ability to control apoptosis and inflammation. GAL was discovered to suppress extracellular signal-regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)p65 phosphorylation, which results in anti-inflammatory actions. Arthritis, inflammatory bronchitis, stroke, and cognitive dysfunction have all been treated with GAL. The current review aimed to demonstrate the anti-inflammatory properties of GAL and their protective effects in treating various chronic illnesses, including those of the heart, brain, skin, lungs, liver, and inflammatory bowel diseases.