Peptide spiders are emerging as novel therapeutic interventions for nucleic acid delivery.

The FDA has approved many nucleic acid (NA)-based products. The presence of charges and biological barriers however affect stability and restrict widespread use. The emergence of three parts in one system, i.e., electrostatic complexation of peptide with PEG-NAs via nonreducible and reducible agents. The reducible linkage made detachment of siRNA from PEG easy compared with a nonreducible linkage. A peptide spider produces a small hydrodynamic particle size, which can improve drug release and pharmacokinetics. Several examples of peptide spiders that enhance stability, protection and transfection efficiency are discussed. Moreover, this review also covers the challenges, future perspectives and unmet needs of peptide spiders.

Kaempferol: Paving the path for advanced treatments in aging-related diseases.

Aging-related diseases (ARDs) are a major global health concern, and the development of effective therapies is urgently needed. Kaempferol, a flavonoid found in several plants, has emerged as a promising candidate for ameliorating ARDs. This comprehensive review examines Kaempferol's chemical properties, safety profile, and pharmacokinetics, and highlights its potential therapeutic utility against ARDs. Kaempferol's therapeutic potential is underpinned by its distinctive chemical structure, which confers antioxidative and anti-inflammatory properties. Kaempferol counteracts reactive oxygen species (ROS) and modulates crucial cellular pathways, thereby combating oxidative stress and inflammation, hallmarks of ARDs. Kaempferol's low toxicity and wide safety margins, as demonstrated by preclinical and clinical studies, further substantiate its therapeutic potential. Compelling evidence supports Kaempferol's substantial potential in addressing ARDs through several mechanisms, notably anti-inflammatory, antioxidant, and anti-apoptotic actions. Kaempferol exhibits a versatile neuroprotective effect by modulating various proinflammatory signaling pathways, including NF-kB, p38MAPK, AKT, and the ß-catenin cascade. Additionally, it hinders the formation and aggregation of beta-amyloid protein and regulates brain-derived neurotrophic factors. In terms of its anticancer potential, kaempferol acts through diverse pathways, inducing apoptosis, arresting the cell cycle at the G2/M phase, suppressing epithelial-mesenchymal transition (EMT)-related markers, and affecting the phosphoinositide 3-kinase/protein kinase B signaling pathways. Subsequent studies should focus on refining dosage regimens, exploring innovative delivery systems, and conducting comprehensive clinical trials to translate these findings into effective therapeutic applications.

Unraveling the impact of miR-21 on apoptosis regulation in glioblastoma.

Glioblastoma is a prevalent form of carcinoma that exhibits a greater incidence rate across diverse demographics globally. Despite extensive global efforts, GBM continues to be a highly lethal disease that is characterized by a grim prognosis. There is a wealth of evidence suggesting that the pathophysiology of GBM is associated with the dysregulation of numerous cellular and molecular processes. The etiology of GBM may involve various cellular and molecular pathways, including EGFR, PDCD4, NF-κB, MAPK, matrix metalloproteinases, STAT, and Akt. MicroRNAs, short non-coding RNA molecules, regulate gene expression and mRNA translation after transcription but before translation to exert control over a wide range of biological functions. Extensive research has consistently demonstrated the upregulation of miRNA-21 in glioma, indicating its involvement in diverse biological pathways that facilitate tumor cell survival. By explaining the intricate interplay between miR-21 and the regulation of apoptosis in GBM, this review has the potential to significantly enhance our comprehension of the illness and provide potential targets for therapeutic intervention.

The emerging role of non-coding RNAs in the Wnt/ß-catenin signaling pathway in Prostate Cancer.

Prostate cancer (PCa) is an important worldwide medical concern, necessitating a greater understanding of the molecular processes driving its development. The Wnt/-catenin signaling cascade is established as a central player in PCa pathogenesis, and recent research emphasizes the critical involvement of non-coding RNAs (ncRNAs) in this scenario. This in-depth study seeks to give a thorough examination of the complex relationship between ncRNAs and the Wnt/ß-catenin system in PCa. NcRNAs, such as circular RNAs (circRNAs), long ncRNAs (lncRNAs), and microRNAs (miRNAs), have been recognized as essential regulators that modulate numerous facets of the Wnt/ß-catenin network. MiRNAs have been recognized as targeting vital elements of the process, either enhancing or inhibiting signaling, depending on their specific roles and targets. LncRNAs participate in fine-tuning the Wnt/ß-catenin network as a result of complicated interplay with both upstream and downstream elements. CircRNAs, despite being a relatively recent addition to the ncRNA family, have been implicated in PCa, influencing the Wnt/ß-catenin cascade through diverse mechanisms. This article encompasses recent advances in our comprehension of specific ncRNAs that participate in the Wnt/ß-catenin network, their functional roles, and clinical relevance in PCa. We investigate their use as screening and predictive indicators, and targets for treatment. Additionally, we delve into the interplay between Wnt/ß-catenin and other signaling networks in PCa and the role of ncRNAs within this complex network. As we unveil the intricate regulatory functions of ncRNAs in the Wnt/ß-catenin cascade in PCa, we gain valuable insights into the disease's pathogenesis. The implementation of these discoveries in practical applications holds promise for more precise diagnosis, prognosis, and targeted therapeutic approaches, ultimately enhancing the care of PCa patients. This comprehensive review underscores the evolving landscape of ncRNA research in PCa and the potential for innovative interventions in the battle against this formidable malignancy.

Anaesthesia-induced Changes in Genomic Expression Leading to Neurodegeneration.

General anaesthetics (GA) have been in continuous clinical use for more than 170 years, with millions of young and elderly populations exposed to GA to relieve perioperative discomfort and carry out invasive examinations. Preclinical studies have shown that neonatal rodents with acute and chronic exposure to GA suffer from memory and learning deficits, likely due to an imbalance between excitatory and inhibitory neurotransmitters, which has been linked to neurodevelopmental disorders. However, the mechanisms behind anaesthesia-induced alterations in late postnatal mice have yet to be established. In this narrative review, we present the current state of knowledge on early life anaesthesia exposure-mediated alterations of genetic expression, focusing on insights gathered on propofol, ketamine, and isoflurane, as well as the relationship between network effects and subsequent biochemical changes that lead to long-term neurocognitive abnormalities. Our review provides strong evidence and a clear picture of anaesthetic agents' pathological events and associated transcriptional changes, which will provide new insights for researchers to elucidate the core ideas and gain an in-depth understanding of molecular and genetic mechanisms. These findings are also helpful in generating more evidence for understanding the exacerbated neuropathology, impaired cognition, and LTP due to acute and chronic exposure to anaesthetics, which will be beneficial for the prevention and treatment of many diseases, such as Alzheimer's disease. Given the many procedures in medical practice that require continuous or multiple exposures to anaesthetics, our review will provide great insight into the possible adverse impact of these substances on the human brain and cognition.

Non-coding RNAs: Emerging biomarkers and therapeutic targets in ulcerative colitis.

Ulcerative colitis (UC) is a persistent inflammatory condition affecting the colon's mucosal lining, leading to chronic bowel inflammation. Despite extensive research, the precise molecular mechanisms underlying UC pathogenesis remain elusive. NcRNAs form a category of functional RNA molecules devoid of protein-coding capacity. They have recently surfaced as pivotal modulators of gene expression and integral participants in various pathological processes, particularly those related to inflammatory disorders. The diverse classes of ncRNAs, encompassing miRNAs, circRNAs, and lncRNAs, have been implicated in UC. It highlights their involvement in key UC-related processes, such as immune cell activation, epithelial barrier integrity, and the production of pro-inflammatory mediators. ncRNAs have been identified as potential biomarkers for UC diagnosis and monitoring disease progression, offering promising avenues for personalized medicine. This approach may pave the way for novel, more specific treatments with reduced side effects, addressing the current limitations of conventional therapies. A comprehensive understanding of the interplay between ncRNAs and UC will advance our knowledge of the disease, potentially leading to more effective and personalized treatments for patients suffering from this debilitating condition. This review explores the pivotal role of ncRNAs in the context of UC, shedding light on their possible targets for diagnosis, prognosis, and therapeutic interventions.

Synthesis, Anticancer Activity, and In Silico Studies of 5-(3-Bromophenyl)-N-aryl-4H-1,2,4-triazol-3-amine Analogs.

In the current study, we described the synthesis of ten new 5-(3-Bromophenyl)-N-aryl-4H-1,2,4-triazol-3-amine analogs (4a-j), as well as their characterization, anticancer activity, molecular docking studies, ADME, and toxicity prediction. The title compounds (4a-j) were prepared in three steps, starting from substituted anilines in a satisfactory yield, followed by their characterization via spectroscopic techniques. The National Cancer Institute (NCI US) protocol was followed to test the compounds' (4a-j) anticancer activity against nine panels of 58 cancer cell lines at a concentration of 10-5 M, and growth percent (GP) as well as percent growth inhibition (PGI) were calculated. Some of the compounds demonstrated significant anticancer activity against a few cancer cell lines. The CNS cancer cell line SNB-75, which showed a PGI of 41.25 percent, was discovered to be the most sensitive cancer cell line to the tested compound 4e. The mean GP of compound 4i was found to be the most promising among the series of compounds. The five cancer cell lines that were found to be the most susceptible to compound 4i were SNB-75, UO-31, CCRF-CEM, EKVX, and OVCAR-5; these five cell lines showed PGIs of 38.94, 30.14, 26.92, 26.61, and 23.12 percent, respectively, at 10-5 M. The inhibition of tubulin is one of the primary molecular targets of many anticancer agents; hence, the compounds (4a-j) were further subjected to molecular docking studies looking at the tubulin-combretastatin A-4 binding site (PDB ID: 5LYJ) of tubulin. The binding affinities were found to be efficient, ranging from -6.502 to -8.341 kcal/mol, with two major electrostatic interactions observed: H-bond and halogen bond. Ligand 4i had a binding affinity of -8.149 kcal/mol with the tubulin-combretastatin A-4 binding site and displayed a H-bond interaction with the residue Asn258. The ADME and toxicity prediction studies for each compound were carried out using SwissADME and ProTox-II software. None of the compounds' ADME predictions showed that they violated Lipinski's rule of five. All of the compounds were also predicted to have LD50 values between 440 and 500 mg/kg, putting them all in class IV toxicity, according to the toxicity prediction. The current discovery could potentially open up the opportunity for further developments in cancer.

Ameliorative Effect of Ethanolic Extract of Moringa oleifera Leaves in Combination with Curcumin against PTZ-Induced Kindled Epilepsy in Rats: In Vivo and In Silico.

The ameliorative effect of ethanolic extract of M. oleifera (MOEE) leaves in combination with curcumin against seizures, cognitive impairment, and oxidative stress in the molecular docking of PTZ-induced kindled rats was performed to predict the potential phytochemical effects of MOEE and curcumin against epilepsy. The effect of pretreatment with leaves of M. oleifera ethanolic extracts (MOEE) (250 mg/kg and 500 mg/kg, orally), curcumin (200 mg/kg and 300 mg/kg, orally), valproic acid used as a standard (100 mg/kg), and the combined effect of MOEE (250 mg/kg) and curcumin (200 mg/kg) at a low dose on Pentylenetetrazole was used for (PTZ)-induced kindling For the development of kindling, individual Wistar rats (male) were injected with pentyletetrazole (40 mg/kg, i.p.) on every alternate day. Molecular docking was performed by the Auto Dock 4.2 tool to merge the ligand orientations in the binding cavity. From the RCSB website, the crystal structure of human glutathione reductase (PDB ID: 3DK9) was obtained. Curcumin and M. oleifera ethanolic extracts (MOEE) showed dose-dependent effects. The combined effects of MOEE and curcumin leaves significantly improved the seizure score and decreased the number of myoclonic jerks compared with a standard dose of valproic acid. PTZ kindling induced significant oxidative stress and cognitive impairment, which was reversed by pretreatment with MOEE and curcumin. Glutathione reductase (GR) is an enzyme that plays a key role in the cellular control of reactive oxygen species (ROS). Therefore, activating GR can uplift antioxidant properties, which leads to the inhibition of ROS-induced cell death in the brain. The combination of the ethanolic extract of M. oleifera (MOEE) leaves and curcumin has shown better results than any other combination for antiepileptic effects by virtue of antioxidant effects. As per the docking study, chlorogenic acid and quercetin treated with acombination of curcumin have much more potential.

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.

A comprehensive review on the emerging role of long non-coding RNAs in the regulation of NF-κB signaling in inflammatory lung diseases.

Public health globally faces significant risks from conditions like acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and various inflammatory lung disorders. The NF-κB signaling system partially controls lung inflammation, immunological responses, and remodeling. Non-coding RNAs (lncRNAs) are crucial in regulating gene expression. They are increasingly recognized for their involvement in NF-κB signaling and the development of inflammatory lung diseases. Disruption of lncRNA-NF-κB interactions is a potential cause and resolution factor for inflammatory respiratory conditions. This study explores the therapeutic potential of targeting lncRNAs and NF-κB signaling to alleviate inflammation and restore lung function. Understanding the intricate relationship between lncRNAs and NF-κB signaling could offer novel insights into disease mechanisms and identify therapeutic targets. Regulation of lncRNAs and NF-κB signaling holds promise as an effective approach for managing inflammatory lung disorders. This review aims to comprehensively analyze the interaction between lncRNAs and the NF-κB signaling pathway in the context of inflammatory lung diseases. It investigates the functional roles of lncRNAs in modulating NF-κB activity and the resulting inflammatory responses in lung cells, focusing on molecular mechanisms involving upstream regulators, inhibitory proteins, and downstream effectors.

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.

Natural Oils Enhance the Topical Delivery of Ketoconazole by Nanoemulgel for Fungal Infections.

Nanoemulgel (NEG) pharmaceutical formulations are gaining popularity because of their ability to serve both as a nanoemulsion and as a gel. These products are well-known for their ease of use, spreadability, controlled release, and ability to hydrate dry skin. Natural essential oils have been shown to promote the cutaneous permeability of topical formulations, enhancing medication safety and efficacy. Herein, we developed NEG for the enhanced permeation of ketoconazole against candidiasis using clove oil (clove-oil-NEG) or eucalyptus oil (eucalyptus-oil-NEG), using the gelling agents carbopol 943 and hydroxypropyl methylcellulose (HPMC). We tested various excipients to increase the solubility of ketoconazole and formulate a nanoemulsion (NE). We measured the NE droplet particle size, shape, entrapment efficiency, and drug release. Furthermore, the physicochemical properties of the optimized nanoemulsion formulation were characterized by techniques such as Fourier transform infrared (FT-IR) spectroscopy and X-ray diffraction (XRD) analysis. The NEs were loaded into gels to form NEGs. NEGs were characterized for drug content, homogeneity, rheology, spreadability, and antifungal activity against Candida albicans, both in vitro and in vivo. Optimized ketoconazole NEG preparations consisted of either 15% clove oil or 20% eucalyptus oil. Droplet sizes in the optimized NEs were <100 nm, and the polydispersity indexes were 0.24 and 0.26. The percentages of ketoconazole released after 24 h from the clove-oil-NEG and eucalyptus-oil-NEGs were 91 ± 4.5 and 89 ± 7%, respectively. Scanning electron microscopy (SEM) showed that the NEGs had a smooth, uniform, and consistent shape and internal structural organization. The drug contents in the clove-oil-NEG and eucalyptus-oil-NEG were 98.5 ± 2.2 and 98.8 ± 3.4%, respectively. Permeation values of ketoconazole from clove-oil-NEG and eucalyptus-oil-NEG were 117 ± 7 and 108.34 ± 6 µg cm-2, respectively. The ketoconazole NEG formulations also had higher levels of fungal growth inhibition than a marketed formulation. Finally, in vivo studies showed that the NEGs do not irritate the skin. Ketoconazole NEG with either 15% clove oil or 20% eucalyptus oil is stable with better efficacy than ketoconazole alone due to excellent dispersion, drug dissolution, and permeability and thus might be recommended for the effective and safe treatment of candidiasis.

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.

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.

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.

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.

Probing the links: Long non-coding RNAs and NF-κB signalling in atherosclerosis.

Atherosclerosis is a chronic inflammatory disease that involves the accumulation of lipids and immune cells in the arterial wall. NF-kB signaling is a key regulator of inflammation and is known to play a critical role in atherosclerosis. Recent studies have shown that lncRNAs can regulate NF-kB and contribute to the development and progression of atherosclerosis. Preliminary findings reveal significant alterations in the expression of specific lncRNAs in atherosclerotic lesions compared to healthy arterial tissue. Experimental evidence suggests that these dysregulated lncRNAs can influence the NF-kB pathway. By unravelling the crosstalk between lncRNAs and NF-kB signaling, this review aims to enhance our understanding of the molecular mechanisms underlying atherosclerosis. Identifying novel therapeutic targets and diagnostic markers may lead to developing interventions and management strategies for this prevalent cardiovascular disease. This review summarizes the current knowledge on the role of lncRNAs in NF-kB signaling in atherosclerosis and highlights their potential as therapeutic targets for this disease.

Nanomedicine in the Management of Alzheimer's Disease: State-of-the-Art.

Alzheimer's disease (AD) is a deadly, progressive, and irreversible brain condition that impairs cognitive abilities. Globally, it affects 32.6 million individuals, and if no viable therapies are available by 2050, that figure might rise to 139 million. The current course of treatment enhances cognitive abilities and temporarily relieves symptoms, but it does not halt or slow the disease's development. Additionally, treatments are primarily offered in conventional oral dosage forms, and conventional oral treatments lack brain specialization and cause adverse effects, resulting in poor patient compliance. A potential nanotechnology-based strategy can improve the bioavailability and specificity of the drug targeting in the brain. Furthermore, this review extensively summarizes the applications of nanomedicines for the effective delivery of drugs used in the management of AD. In addition, the clinical progress of nanomedicines in AD is also discussed, and the challenges facing the clinical development of nanomedicines are addressed in this article.

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.

Preferential Solvation Study of Rosuvastatin in the {PEG400 (1) + Water (2)} Cosolvent Mixture and GastroPlus Software-Based In Vivo Predictions.

Rosuvastatin (RST) is a poorly water-soluble drug responsible for limited in vivo dissolution and subsequently low oral systemic absorption (poor bioavailability). The mole fraction solubility values of RST in various ratios of binary mixtures "{PEG400 (1) + water (2)}" at 298.15 K were employed to investigate the preferential solvation (PS) of RST (3) by the binary components. Moreover, the GastroPlus program predicted the drug dissolution/absorption rates, plasma drug concentration, and compartmental regional drug absorbed from a conventional tablet as compared to the RST-loaded (PEG400 + water) mixture (at x 1 = 0.5) in healthy subjects (considering the fast condition). Fedors' method was adopted to estimate the values of molar volume (314.8 cm3·mol-1) and Hildebrand solubility parameter (28.08 MPa1/2) of RST. The results of inverse Kirkwood-Buff integrals showed the PS of RST by PEG400 as observed in all studied ratios of the binary mixture. The highest PS value (δx 1,3 = 1.65 × 10-2) for RST by PEG400 was attained at x 1 = 0.5. Finally, the GastroPlus program predicted the maximum dissolution rate [20 mg within 15 min as compared to pure RST (1.5 mg within 15 min)]. Moreover, the program predicted increased in vivo oral absorption (1.2 µg/mL) and enhanced regional absorption (95.3%) of RST from upper segments of the gastrointestinal tract for the RST-loaded PEG400 + water mixture in humans as compared to conventional tablets (87.5% as total regional absorption and 0.88 µg/mL as in vivo absorption). Hence, the present binary system ferrying RST can be a promising strategy to control systemic dyslipidemia after oral or subcutaneous administration.